Trang Quynh Nguyen

Role of CaVβ Subunits, and Lack of Functional Reserve, in Protein Kinase A Modulation of Cardiac CaV1.2 Channels

Protein kinase A (PKA)-mediated enhancement of L-type calcium currents (ICa,L) is essential for sympathetic regulation of the heartbeat and is the classic example of channel regulation by phosphorylation, and its loss is a common hallmark of heart failure. Mechanistic understanding of how distinct CaV channel subunits contribute to PKA modulation of ICa,L has been intensely pursued yet remains elusive. Moreover, critical features of this regulation such as its functional reserve (the surplus capacity available for modulation) in the heart are unknown. Here, we use an overexpression paradigm in heart cells to simultaneously identify the impact of auxiliary CaV&bgr;s on PKA modulation of ICa,L and to gauge the functional reserve of this regulation in the heart. CaV1.2 channels containing wild-type &bgr;2a or a phosphorylation-deficient mutant (&bgr;2a,AAA) were equally upregulated by PKA, discounting a necessary role for &bgr; phosphorylation. Nevertheless, channels reconstituted with &bgr;2a displayed a significantly diminished PKA response compared with other &bgr; isoforms, an effect explainable by a uniquely higher basal Po of &bgr;2a channels. Overexpression of all &bgr;s increased basal current density, accompanied by a concomitant decrease in the magnitude of PKA regulation. Scatter plots of fold increase in current against basal current density revealed an inverse relationship that was conserved across species and conformed to a model in which a large fraction of channels remained unmodified after PKA activation. These results redefine the role of &bgr; subunits in PKA modulation of CaV1.2 channels and uncover a new design principle of this phenomenon in the heart, vis à vis a limited functional reserve.

Solitary vertebral metastasis.

As survival time increases for many cancers, it is likely that the incidence and prevalence of spinal metastases will increase also. Given that most patients first present with solitary lesions in the spine, proper initial diagnosis and management are of paramount importance in minimizing pain, improving neurologic function, and potentially lengthening survival. Although pain control and standard radiation are still used, spinal stereotactic radiosurgery, vertebroplasty and kyphoplasty, and spinal cord decompression and fusion are now consistently used in aggressive management and offer exciting preliminary results.

Stereotactic Radiosurgery for Spine Tumors: Review of Current Literature

Stereotactic radiosurgery (SR) is increasingly utilized for the treatment of intracranial and extracranial pathology. It is considered an important adjuvant to surgery, chemotherapy or fractionated radiotherapy, and the role of SR as a primary treatment modality continues to be explored. Although SR for spinal lesions is in its infancy, there is a growing body of literature supporting its efficacy. The purpose of this review is to summarize the pertinent literature regarding the use of SR for lesions of the spine and spinal cord. Particular emphasis will be placed on large clinical series of both primary and secondary spine tumors.

Syringe Exchange in the United States: A National Level Economic Evaluation of Hypothetical Increases in Investment

Abstract To examine whether increasing investment in needle/syringe exchange programs (NSPs) in the US would be cost-effective for HIV prevention, we modeled HIV incidence in hypothetical cases with higher NSP syringe supply than current levels, and estimated number of infections averted, cost per infection averted, treatment costs saved, and financial return on investment. We modified Pinkerton’s model, which was an adaptation of Kaplan’s simplified needle circulation theory model, to compare different syringe supply levels, account for syringes from non-NSP sources, and reflect reduction in syringe sharing and contamination. With an annual

Negative Family Treatment of Sexual Minority Women and Transmen in Vietnam: Latent Classes and Their Predictors

10 to

Pain Symptoms Associated with Opioid Use among Vulnerable Persons with HIV: An exploratory study with implications for palliative care and opioid abuse prevention.

50 million funding increase, 194–816 HIV infections would be averted (cost per infection averted

Homosexuality Tolerance Among Male and Female Vietnamese Youth: An Examination of Traditional Sexual Values, Self-Esteem, and Demographic/Contextual Characteristics

51,601–

Application of the Consolidated Framework for Implementation Research to assess factors that may influence implementation of tobacco use treatment guidelines in the Viet Nam public health care delivery system

61,302). Contrasted with HIV treatment cost savings alone, the rate of financial return on investment would be 7.58–6.38. Main and sensitivity analyses strongly suggest that it would be cost-saving for the US to invest in syringe exchange expansion.

Causal Mediation Analysis With a Binary Outcome and Multiple Continuous or Ordinal Mediators: Simulations and Application to an Alcohol Intervention

Quantitative research on parental/family disapproval and rejection of sexual/gender minority persons has often measured family rejection as one binary/continuous variable, or using several variables representing specific behaviors or dimensions of behaviors. Absent from this literature is analysis using a person-oriented approach, examining heterogeneity across individuals in the types of family treatment experience. Using data from 2,664 adult sexual minority women and transmen in Vietnam, latent class analysis was conducted on 19 items representing negative family behaviors. The six-class solution best fit the data, including one non-negative class (peace, 36.7% of the sample) and five negative classes (pressure, 34.0%; aggressive to respondent and girlfriend, 10.3%; aggressive to respondent, 8.1%; severe, 6.0%; and extreme, 4.7%). Class membership was regressed on individual, family, and contextual variables. Overall, younger age, transman identity, religious affiliation, and parent awareness predicted being in worse family treatment classes. Further research is needed to separate cohort and age effects and to examine developmental trajectories of family behavior. Findings suggested that it may be general conservativeness rather than a specific religious doctrine that predicts negative family treatment and revealed that nonparent family members’ role in family response to sexual/gender nonconformity may be significant.

Sensitivity analysis for an unobserved moderator in RCT-to-target-population generalization of treatment effects

Current or former injection drug users with human immunodeficiency virus (HIV) are at high risk for pain, which adversely affects their quality of life and may increase their risk for illicit drug use or relapse. We explored associations between pain symptoms and substance use among injection-drug-using study participants with HIV who had histories of heroin use. Using generalized estimating equations and controlling for prior substance use, we found that pain in each six-month period was associated with the use of heroin and prescription opioids, but not the use of nonopioid drugs or alcohol. Routine clinical assessment and improved management of pain symptoms may be needed for persons with HIV and a history of injection drug use, particularly those with chronic pain, for whom there is increased risk for heroin use.