Mechanistic insights into robust cardiac I potassium channel activation by aromatic polyunsaturated fatty acid analogues.

Voltage-gated potassium (K) channels are important regulators of cellular excitability and control action potential repolarization in the heart and brain. K channel mutations lead to disordered cellular excitability. Loss-of-function mutations, for example, result in membrane hyperexcitability, a characteristic of epilepsy and cardiac arrhythmias.

Mechanistic insights into robust cardiac I potassium channel activation by aromatic polyunsaturated fatty acid analogues.

Voltage-gated potassium (K ) channels are important regulators of cellular excitability and control action potential repolarization in the heart and brain. K channel mutations lead to disordered cellular excitability. Loss-of-function mutations, for example, result in membrane hyperexcitability, a characteristic of epilepsy and cardiac arrhythmias.

Polyunsaturated fatty acid analogues differentially affect cardiac Na, Ca, and K channels through unique mechanisms.

The cardiac ventricular action potential depends on several voltage-gated ion channels, including Na, Ca, and K channels. Mutations in these channels can cause Long QT Syndrome (LQTS) which increases the risk for ventricular fibrillation and sudden cardiac death. Polyunsaturated fatty acids (PUFAs) have emerged as potential therapeutics for LQTS because they are modulators of voltage-gated ion channels.

Polyunsaturated fatty acids produce a range of activators for heterogeneous IKs channel dysfunction.

Repolarization and termination of the ventricular cardiac action potential is highly dependent on the activation of the slow delayed-rectifier potassium IKs channel. Disruption of the IKs current leads to the most common form of congenital long QT syndrome (LQTS), a disease that predisposes patients to ventricular arrhythmias and sudden cardiac death. We previously demonstrated that polyunsaturated fatty acid (PUFA) analogues increase outward K+ current in wild type and LQTS-causing mutant IKs channels.

ω-6 and ω-9 polyunsaturated fatty acids with double bonds near the carboxyl head have the highest affinity and largest effects on the cardiac I potassium channel.

Aim: The I channel is important for termination of the cardiac action potential. Hundreds of loss-of-function mutations in the I channel reduce the K current and, thereby, delay the repolarization of the action potential, causing Long QT Syndrome. Long QT predisposes individuals to Torsades de Pointes which can lead to ventricular fibrillation and sudden death.

Meningococcal Conjugate and Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccination Among HIV-infected Youth.

Background: The meningococcal conjugate vaccine (MCV4) and the tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) were first recommended for adolescents in the US in 2005. The goal of our study was to determine MCV4 and Tdap vaccines coverage among perinatally and behaviorally HIV-infected adolescents in 2006 and to compare coverage estimates in our study population to similarly aged healthy youth in 2006.

Methods: Longitudinal Epidemiologic Study to Gain Insight into HIV/AIDS in Children and Youth (LEGACY) is a retrospective cohort study of HIV-infected youth in 22 HIV specialty clinics across the US.

Perinatal HIV Prevention Outcomes in U.S.-Born Versus Foreign-Born Blacks, PSD Cohort, 1995-2004.

We examined differences in HIV-infected U.S.-born and foreign-born black mothers who delivered perinatally HIV-exposed and -infected children during 1995-2004 in the Pediatric Spectrum of HIV Disease Project, a longitudinal cohort study.

Prevalence and outcomes of recycling NNRTIs despite documented NNRTI resistance in HIV-infected children and youth.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are commonly used in pediatric patients; however, rapid development of resistance, due to non-adherence and cross-resistance, results in their discontinuation and limits their recycling. We evaluated the clinical experience of recycling NNRTIs despite documented NNRTI resistance (NNRTI-R), and examined virologic and CD4 cell count outcomes among participants enrolled in Longitudinal Epidemiologic Study to Gain Insight into HIV/AIDS in Children and Youth (LEGACY), a national HIV-infected pediatric cohort. We conducted a retrospective analysis of LEGACY participants with major NNRTI-R.

Incidence of opportunistic illness before and after initiation of highly active antiretroviral therapy in children.

Background: Little is known about immune reconstitution inflammatory syndrome in children in the United States.

Methods: LEGACY is a longitudinal cohort study of HIV-infected participants 0-24 years at enrollment during 2005 to 2007 from 22 US clinics. For this analysis, we included participants with complete medical record abstraction from birth or time of HIV diagnosis through 2006.

Use of nucleoside reverse transcriptase inhibitor-only regimens in HIV-infected children and adolescents.

Objective: In adults, nucleoside reverse transcriptase inhibitor-only antiretroviral regimens (NOARs) with ≥3 nucleoside reverse transcriptase inhibitors are less potent than highly active antiretroviral therapy (HAART). Published pediatric experience with NOARs is limited; thus, we wished to better define the virological, immunological and toxicological effects of NOARs in children and adolescents.

Methods: We analyzed data from NOAR-treated participants in LEGACY, a multicenter observational cohort study of HIV-infected children and adolescents.

Methicillin-Resistant Staphylococcus aureus Infections in Human Immunodeficiency Virus-Infected Children and Adolescents.

Background. Methicillin-resistant Staphylococcus aureus (MRSA) infection incidence has increased in healthy US children. Our objective was to evaluate MRSA incidence and correlates in HIV-infected youth.

Cervical pap screening cytological abnormalities among HIV-infected adolescents in the LEGACY cohort.

Objectives: To determine the prevalence of cervical Pap screening (CPAP-S), identify factors associated with CPAP-S, and explore risk factors for abnormal cervical cytology in female adolescents with perinatally and behaviorally acquired HIV infection.

Design: Cross-sectional.

Setting: LEGACY is a national observational cohort chart review study of 1478 HIV-infected persons ( View Article and Find Full Text PDF

Correlates of sexual activity and sexually transmitted infections among human immunodeficiency virus-infected youth in the LEGACY cohort, United States, 2006.

Background: To determine the prevalence and correlates of sexual activity and sexually transmitted infections (STIs) among human immunodeficiency virus (HIV)-infected youth.

Methods: The Longitudinal Epidemiologic Study to Gain Insight into HIV/AIDS in Children and Youth (LEGACY) is an observational medical record study of perinatally and behaviorally HIV-infected (PHIV and BHIV) youth followed at 22 US HIV clinics. PHIV youth were HIV infected at birth or by breast-feeding.

Associations of medically documented psychiatric diagnoses and risky health behaviors in highly active antiretroviral therapy-experienced perinatally HIV-infected youth.

The Longitudinal Epidemiologic Study to Gain Insight into HIV/AIDS in Children and Youth (LEGACY) study is a prospective, multisite, longitudinal cohort of U.S. HIV-infected youth.

Antiretroviral therapy and preterm delivery-a pooled analysis of data from the United States and Europe.

Objective:  To investigate reported differences in the association between highly active antiretroviral therapy (HAART) in pregnancy and the risk of preterm delivery among HIV-infected women.

Design:   Combined analysis of data from three observational studies.

Setting:  USA and Europe.

Effect of the photoreaction solvent on surface and bulk properties of poly(lactic acid) and poly(hydroxyalkanoate) films.

The major objective of this research was to modify the surface properties of poly(lactic acid) (PLA) and poly(hydroxyalkanoate) (PHA) films by using a sequential two-step photografting approach. In step 1, benzophenone was photografted on the film surface and in step 2, hydrophilic monomers acrylamide and acrylic acid were photopolymerized from the film surfaces. Another objective was to study the effect of the reaction solvent in step 2 on surface and bulk properties of these films.

Declines in low birth weight and preterm birth among infants who were born to HIV-infected women during an era of increased use of maternal antiretroviral drugs: Pediatric Spectrum of HIV Disease, 1989-2004.

Objective: Our goal was to determine trends in low birth weight and preterm birth among US infants born to HIV-infected women.

Methods: We used data from the longitudinal Pediatric Spectrum of HIV Disease, a large HIV cohort, to assess trends in low birth weight and preterm birth from 1989 to 2004 among 11,321 study infants. Among women with prenatal care, we also assessed risk factors, including maternal antiretroviral therapy during pregnancy, that were predictive of low birth weight and preterm birth using univariate and multivariate logistic regression models.

Updated estimates of healthcare utilization and costs among perinatally HIV-infected children.

Objectives: This study examined changes in healthcare use among perinatally HIV-infected children and developed new estimates of expected lifetime treatment costs.

Methods: The study analyzed longitudinal medical record data from the Pediatric Spectrum of Disease study on perinatally HIV-infected children enrolled in 6 US sites during 1995 and 2001 for enrollee characteristics including healthcare utilization. For the year 2001, costs were assigned to hospitalization, HIV-related drug usage, and laboratory testing.

Incidence of presumed cytomegalovirus retinitis in HIV-infected pediatric patients.

Introduction: Large population studies of adult patients suggest an incidence of cytomegalovirus (CMV) retinitis as high as 19% to 20% as a late complication of adult HIV infection. We conducted this prospective study of a large cohort of HIV-infected children to determine the incidence of CMV retinitis in HIV-infected children.

Methods: From January 1984 to August 1997, 173 HIV-infected children were followed up for an average of 55.

Adequacy of prenatal care and prescription of zidovudine to prevent perinatal HIV transmission.

In 1994, data were published on the effectiveness of zidovudine in preventing perinatal transmission of HIV infection. Using data from surveillance projects in San Antonio, Dallas, and Houston, Texas, U.S.