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Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy

Wed, 09/28/2016 - 12:24pm

PURPOSE: To provide an initial assessment of the safety of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in adults and children with retinal degeneration caused by RPE65 mutations.

DESIGN: Nonrandomized, multicenter clinical trial.

PARTICIPANTS: Eight adults and 4 children, 6 to 39 years of age, with Leber congenital amaurosis (LCA) or severe early-childhood-onset retinal degeneration (SECORD).

METHODS: Patients received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of 2 dose levels, and were followed up for 2 years after treatment.

MAIN OUTCOME MEASURES: The primary safety measures were ocular and nonocular adverse events. Exploratory efficacy measures included changes in best-corrected visual acuity (BCVA), static perimetry central 30 degrees visual field hill of vision (V30) and total visual field hill of vision (VTOT), kinetic perimetry visual field area, and responses to a quality-of-life questionnaire.

RESULTS: All patients tolerated subretinal injections and there were no treatment-related serious adverse events. Common adverse events were those associated with the surgical procedure and included subconjunctival hemorrhage in 8 patients and ocular hyperemia in 5 patients. In the treated eye, BCVA increased in 5 patients, V30 increased in 6 patients, VTOT increased in 5 patients, and kinetic visual field area improved in 3 patients. One subject showed a decrease in BCVA and 2 patients showed a decrease in kinetic visual field area.

CONCLUSIONS: Treatment with rAAV2-CB-hRPE65 was not associated with serious adverse events, and improvement in 1 or more measures of visual function was observed in 9 of 12 patients. The greatest improvements in visual acuity were observed in younger patients with better baseline visual acuity. Evaluation of more patients and a longer duration of follow-up will be needed to determine the rate of uncommon or rare side effects or safety concerns.

A Single Injection of Recombinant Adeno-Associated Virus into the Lumbar Cistern Delivers Transgene Expression Throughout the Whole Spinal Cord

Wed, 09/28/2016 - 12:24pm

The lack of methods to deliver transgene expression in spinal cord has hampered investigation of gene function and therapeutic targets for spinal cord diseases. Here, we report that a single intrathecal injection of recombinant adeno-associated virus rhesus-10 (rAAVrh10) into the lumbar cistern led to transgene expression in 60 to 90 % of the cells in the spinal cord. The transgene was expressed in all cell types, including neurons, glia, ependymal cells, and endothelial cells. Additionally, the transgene was expressed in some brain areas up to the frontal cortex and the olfactory bulb. The rAAV was distributed predominantly in the spinal cord, where its genome copy was over ten times that of the peripheral organs. Compared with intravenous injection, another method for rAAV delivery to the broad central nervous system (CNS), the intrathecal injection reduced the dosage of rAAV required to achieve similar or higher levels of transgene expression in the CNS by ~100-fold. Finally, the transduced areas were co-localized with the perivascular spaces of Virchow-Robin, from which the rAAV spreads further into the CNS parenchyma, thus suggesting that rAAV penetrated the CNS parenchyma through this pathway. Taken together, we have defined a fast and efficient method to deliver widespread transgene expression in mature spinal cord in mice. This method can be applied to stably overexpress or silence gene expression in the spinal cord to investigate gene functions in mammalian CNS. Additionally, this method can be applied to validate therapeutic targets for spinal cord diseases.

Epstein-Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation

Wed, 09/28/2016 - 12:24pm

Whether the human tumor virus, Epstein-Barr Virus (EBV), promotes breast cancer remains controversial and a potential mechanism has remained elusive. Here we show that EBV can infect primary mammary epithelial cells (MECs) that express the receptor CD21. EBV infection leads to the expansion of early MEC progenitor cells with a stem cell phenotype, activates MET signaling and enforces a differentiation block. When MECs were implanted as xenografts, EBV infection cooperated with activated Ras and accelerated the formation of breast cancer. Infection in EBV-related tumors was of a latency type II pattern, similar to nasopharyngeal carcinoma (NPC). A human gene expression signature for MECs infected with EBV, termed EBVness, was associated with high grade, estrogen-receptor-negative status, p53 mutation and poor survival. In 11/33 EBVness-positive tumors, EBV-DNA was detected by fluorescent in situ hybridization for the viral LMP1 and BXLF2 genes. In an analysis of the TCGA breast cancer data EBVness correlated with the presence of the APOBEC mutational signature. We conclude that a contribution of EBV to breast cancer etiology is plausible, through a mechanism in which EBV infection predisposes mammary epithelial cells to malignant transformation, but is no longer required once malignant transformation has occurred.

Using Best-Worst Scaling to Understand Patient Priorities: A Case Example of Papanicolaou Tests for Homeless Women

Wed, 09/28/2016 - 12:24pm

PURPOSE: Best-worst scaling (BWS) is a survey method for assessing individuals' priorities. It identifies the extremes-best and worst items, most and least important factors, biggest and smallest influences-among sets. In this article, we demonstrate an application of BWS in a primary care setting to illustrate its use in identifying patient priorities for services.

METHODS: We conducted a BWS survey in 2014 in Boston, Massachusetts, to assess the relative importance of 10 previously identified attributes of Papanicolaou (Pap) testing services among women experiencing homelessness. Women were asked to evaluate 11 sets of 5 attributes of Pap services, and identify which attribute among each set would have the biggest and smallest influence on promoting uptake. We show how frequency analysis can be used to analyze results.

RESULTS: In all, 165 women participated, a response rate of 72%. We identified the most and least salient influences on encouraging Pap screening based on their frequency of report among our sample, with possible standardized scores ranging from+1.0 (biggest influence) to -1.0 (smallest influence). Most important was the availability of support for issues beyond health (+0.39), while least important was the availability of accommodations for personal hygiene (-0.27).

CONCLUSIONS: BWS quantifies patient priorities in a manner that is transparent and accessible. It is easily comprehendible by patients and relatively easy to administer. Our application illustrates its use in a vulnerable population, showing that factors beyond those typically provided in health care settings are highly important to women in seeking Pap screening. This approach can be applied to other health care services where prioritization is helpful to guide decisions.

Twenty-Five Year Secular Trends in Lipids and Modifiable Risk Factors in a Population-Based Biracial Cohort: The Coronary Artery Risk Development in Young Adults (CARDIA) Study, 1985-2011

Wed, 09/28/2016 - 12:24pm

BACKGROUND: Cross-sectional analyses suggest that total and low-density lipoprotein cholesterol (LDL-c) trends that had been declining are now reversing. We examined longitudinal data from the Coronary Artery Risk Development in Young Adults (CARDIA) study to examine secular trends in total cholesterol, LDL-c, high-density lipoprotein cholesterol (HDL-c), and triglycerides over 25 years. We also assessed whether modifiable lifestyle factors (body mass index, physical activity, alcohol consumption, smoking, and lipid-lowering medications) are associated with these trends.

METHODS AND RESULTS: CARDIA recruited 5115 black and white men and women ages 18 to 30 years from 4 US communities in 1985-1986, and re-examined them 5, 10, 15, 20, and 25 years later. Secular trends, modeled as age-matched time trends, were estimated using repeated-measures regression stratified on race and sex. Total cholesterol and LDL-c initially decreased approximately 5 to 8 mg/dL between visits before plateauing and moving toward adverse trends in all groups, except black women, by year 25. HDL-c showed an upward secular trend of 1 to 3 mg/dL between visits starting at year 15 in all groups; triglyceride trends were largely flat. Obesity and use of lipid-lowering medications, which both increased over follow-up, had strong independent, but opposite, associations with lipid trends over time. In aggregate, associations of modifiable lifestyle factors counterbalanced one another, minimally influencing secular trends.

CONCLUSIONS: Over 25 years, initially favorable trends in total cholesterol and LDL-c have leveled off and may be reversing, persisting after control for modifiable risk factors. Factors such as dietary changes over 25 years and poor adherence to medications are candidates for additional investigation.

Impaired neurodevelopment by the low complexity domain of CPEB4 reveals a convergent pathway with neurodegeneration

Wed, 09/28/2016 - 12:24pm

CPEB4 is an RNA binding protein expressed in neuronal tissues including brain and spinal cord. CPEB4 has two domains: one that is structured for RNA binding and one that is unstructured and low complexity that has no known function. Unstructured low complexity domains (LCDs) in proteins are often found in RNA-binding proteins and have been implicated in motor neuron degenerative diseases such as amyotrophic lateral sclerosis, indicating that these regions mediate normal RNA processing as well as pathological events. While CPEB4 null knockout mice are normal, animals expressing only the CPEB4 LCD are neonatal lethal with impaired mobility that display defects in neuronal development such as reduced motor axon branching and abnormal neuromuscular junction formation. Although full-length CPEB4 is nearly exclusively cytoplasmic, the CPEB4 LCD forms nucleolar aggregates and CPEB4 LCD-expressing animals have altered ribosomal RNA biogenesis, ribosomal protein gene expression, and elevated levels of stress response genes such as the actin-bundling protein DRR1, which impedes neurite outgrowth. Some of these features share similarities with other LCD-related neurodegenerative disease. Most strikingly, DRR1 appears to be a common focus of several neurodevelopmental and neurodegenerative disorders. Our study reveals a possible molecular convergence between a neurodevelopmental defect and neurodegeneration mediated by LCDs.

Workforce Innovation and Opportunity Act (WIOA) and its Application to Youth and Young Adults with Serious Mental Health Conditions (SMHC)

Tue, 09/20/2016 - 10:44am

Many sections of the Workforce Innovation and Opportunity Act are specific to students and to youth with disabilities. Though none pertain specifically to youth with significant psychiatric disabilities there are many areas that providers, advocates, family, members, and youth themselves should be aware of as avenues for possible employment related services and interventions. This brief will highlight some of the key topics to consider.

Molecular and Dynamic Mechanism Underlying Drug Resistance in Genotype 3 Hepatitis C NS3/4A Protease

Mon, 09/19/2016 - 9:02am

Hepatitis C virus (HCV), affecting an estimated 150 million people worldwide, is the leading cause of viral hepatitis, cirrhosis and hepatocellular carcinoma. HCV is genetically diverse with six genotypes (GTs) and multiple subtypes of different global distribution and prevalence. Recent development of direct-acting antivirals against HCV including NS3/4A protease inhibitors (PIs) has greatly improved treatment outcomes for GT-1. However, all current PIs exhibit significantly lower potency against GT-3. Lack of structural data on GT-3 protease has limited our ability to understand PI failure in GT-3. In this study the molecular basis for reduced potency of current inhibitors against GT-3 NS3/4A protease is elucidated with structure determination, molecular dynamics simulations and inhibition assays. A chimeric GT-1a3a NS3/4A protease amenable to crystallization was engineered to recapitulate decreased sensitivity of GT-3 protease to PIs. High-resolution crystal structures of this GT-1a3a bound to 3 PIs, asunaprevir, danoprevir and vaniprevir, had only subtle differences relative to GT-1 despite orders of magnitude loss in affinity. In contrast, hydrogen-bonding interactions within and with the protease active site and dynamic fluctuations of the PIs were drastically altered. The correlation between loss of intermolecular dynamics and inhibitor potency suggests a mechanism where polymorphisms between genotypes (or selected mutations) in the drug target confer resistance through altering the intermolecular dynamics of the protein-inhibitor complex.

From Plan to Action: Successful Data Management Plan Implementation in a Multidisciplinary Project

Fri, 09/16/2016 - 9:56am

Objective and Setting: While data management planning becomes more commonplace, moving from planning into implementation remains a hurdle for many researchers. With little specific guidance from funding agencies and libraries in the early stages of developing services to assist researchers, insights into what contributes to successful data management are sorely needed. The objective of this study was to document how a multidisciplinary research team, after consultation with the University of Illinois Library, took steps to implement a data management plan.

Design and Methods: A case study was designed to gather insights from the research group through semi-structured interviews. Questions focused on which of the recommended data management strategies were adopted and how those strategies affected the project in terms of cost, time, effectiveness, and long-term data use.

Results: From these interviews five major themes emerged as important: intentional staffing, addressing essential data management elements, iterative improvement, training and mentorship, and increased efficiency and peace of mind.

Conclusions: Despite the initial investment that data management requires, researchers report significant benefits.

Safety of Striatal Infusion of siRNA in a Transgenic Huntington's Disease Mouse Model

Wed, 09/14/2016 - 9:48am

BACKGROUND: The immune system In Huntington's disease (HD) is activated and may overreact to some therapies. RNA interference using siRNA lowers mutant huntingtin (mHTT) protein but could increase immune responses.

OBJECTIVE: To examine the innate immune response following siRNA infusion into the striatum of wild-type (WT) and HD transgenic (YAC128) mice.

METHODS: siRNAs (2'-O-methyl phosphorothioated) were infused unilaterally into striatum of four month-old WT and YAC128 mice for 28 days. Microglia number and morphology (resting (normal), activated, dystrophic), cytokine levels, and DARPP32-positive neurons were measured in striatum immediately or 14 days post-infusion. Controls included contralateral untreated striatum, and PBS and sham treated striata.

RESULTS: The striata of untreated YAC128 mice had significantly fewer resting microglia and more dystrophic microglia than WT mice, but no difference from WT in the proportion of activated microglia or total number of microglia. siRNA infusion increased the total number of microglia in YAC128 mice compared to PBS treated and untreated striata and increased the proportion of activated microglia in WT and YAC128 mice compared to untreated striata and sham treated groups. Cytokine levels were low and siRNA infusion resulted in only modest changes in those levels. siRNA infusion did not change the number of DARPP32-positive neurons.

CONCLUSION: Findings suggest that siRNA infusion may be a safe method for lowering mHTT levels in the striatum in young animals, since treatment does not produce a robust cytokine response or cause neurotoxicity. The potential long-term effects of a sustained increase in total and activated microglia after siRNA infusion in HD mice need to be explored.

Evaluating Academic Scientists Collaborating in Team-Based Research: A Proposed Framework

Wed, 09/14/2016 - 9:47am

Criteria for evaluating faculty are traditionally based on a triad of scholarship, teaching, and service. Research scholarship is often measured by first or senior authorship on peer-reviewed scientific publications and being principal investigator on extramural grants. Yet scientific innovation increasingly requires collective rather than individual creativity, which traditional measures of achievement were not designed to capture and, thus, devalue. The authors propose a simple, flexible framework for evaluating team scientists that includes both quantitative and qualitative assessments. An approach for documenting contributions of team scientists in team-based scholarship, nontraditional education, and specialized service activities is also outlined. Although biostatisticians are used for illustration, the approach is generalizable to team scientists in other disciplines.The authors offer three key recommendations to members of institutional promotion committees, department chairs, and others evaluating team scientists. First, contributions to team-based scholarship and specialized contributions to education and service need to be assessed and given appropriate and substantial weight. Second, evaluations must be founded on well-articulated criteria for assessing the stature and accomplishments of team scientists. Finally, mechanisms for collecting evaluative data must be developed and implemented at the institutional level. Without these three essentials, contributions of team scientists will continue to be undervalued in the academic environment.

Association of Lipid-Related Genetic Variants with the Incidence of Atrial Fibrillation: The AFGen Consortium

Wed, 09/14/2016 - 9:47am

BACKGROUND: Several studies have shown associations between blood lipid levels and the risk of atrial fibrillation (AF). To test the potential effect of blood lipids with AF risk, we assessed whether previously developed lipid gene scores, used as instrumental variables, are associated with the incidence of AF in 7 large cohorts.

METHODS: We analyzed 64,901 individuals of European ancestry without previous AF at baseline and with lipid gene scores. Lipid-specific gene scores, based on loci significantly associated with lipid levels, were calculated. Additionally, non-pleiotropic gene scores for high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were calculated using SNPs that were only associated with the specific lipid fraction. Cox models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of AF per 1-standard deviation (SD) increase of each lipid gene score.

RESULTS: During a mean follow-up of 12.0 years, 5434 (8.4%) incident AF cases were identified. After meta-analysis, the HDLc, LDLc, total cholesterol, and triglyceride gene scores were not associated with incidence of AF. Multivariable-adjusted HR (95% CI) were 1.01 (0.98-1.03); 0.98 (0.96-1.01); 0.98 (0.95-1.02); 0.99 (0.97-1.02), respectively. Similarly, non-pleiotropic HDLc and LDLc gene scores showed no association with incident AF: HR (95% CI) = 1.00 (0.97-1.03); 1.01 (0.99-1.04).

CONCLUSIONS: In this large cohort study of individuals of European ancestry, gene scores for lipid fractions were not associated with incident AF.

Collective-Intelligence Recommender Systems: Advancing Computer Tailoring for Health Behavior Change Into the 21st Century

Wed, 09/14/2016 - 9:47am

BACKGROUND: What is the next frontier for computer-tailored health communication (CTHC) research? In current CTHC systems, study designers who have expertise in behavioral theory and mapping theory into CTHC systems select the variables and develop the rules that specify how the content should be tailored, based on their knowledge of the targeted population, the literature, and health behavior theories. In collective-intelligence recommender systems (hereafter recommender systems) used by Web 2.0 companies (eg, Netflix and Amazon), machine learning algorithms combine user profiles and continuous feedback ratings of content (from themselves and other users) to empirically tailor content. Augmenting current theory-based CTHC with empirical recommender systems could be evaluated as the next frontier for CTHC.

OBJECTIVE: The objective of our study was to uncover barriers and challenges to using recommender systems in health promotion.

METHODS: We conducted a focused literature review, interviewed subject experts (n=8), and synthesized the results.

RESULTS: We describe (1) limitations of current CTHC systems, (2) advantages of incorporating recommender systems to move CTHC forward, and (3) challenges to incorporating recommender systems into CTHC. Based on the evidence presented, we propose a future research agenda for CTHC systems.

CONCLUSIONS: We promote discussion of ways to move CTHC into the 21st century by incorporation of recommender systems.

Relation of Atrial Fibrillation in Acute Myocardial Infarction to In-Hospital Complications and Early Hospital Readmission

Wed, 09/14/2016 - 9:47am

Atrial fibrillation (AF) is a common complication of acute myocardial infarction (AMI) and contributes to high rates of in-hospital adverse events. However, there are few contemporary studies examining rates of AF in the contemporary era of AMI or the impact of new-onset AF on key in-hospital and postdischarge outcomes. We examined trends in AF in 6,384 residents of Worcester, Massachusetts, who were hospitalized with confirmed AMI during 7 biennial periods between 1999 and 2011. Multivariate logistic regression analysis was used to examine associations between occurrence of AF and various in-hospital and postdischarge complications. The overall incidence of AF complicating AMI was 10.8%. Rates of new-onset AF increased from 1999 to 2003 (9.8% to 13.2%), and decreased thereafter. In multivariable adjusted models, patients developing new-onset AF after AMI were at a higher risk for in-hospital stroke (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.6 to 4.1), heart failure (OR 2.0, 95% CI 1.7 to 2.4), cardiogenic shock (OR 3.7, 95% CI 2.8 to 4.9), and death (OR 2.3, 95% CI 1.9 to 3.0) than patients without AF. Development of AF during hospitalization for AMI was associated with higher rates of readmission within 30 days after discharge (21.7% vs 16.0%), but no significant difference was noted in early postdischarge 30-day all-cause mortality rates (8.3% vs 5.1%). In conclusion, new-onset AF after AMI is strongly related to in-hospital complications of AMI and higher short-term readmission rates.

Physical impairment and body weight history in postmenopausal women: the Women's Health Initiative

Wed, 09/14/2016 - 9:47am

OBJECTIVE: To examine whether weight history and weight transitions over adult lifespan contribute to physical impairment among postmenopausal women.

DESIGN: BMI categories were calculated among postmenopausal women who reported their weight and height at age 18 years. Multiple-variable logistic regression was used to determine the association between BMI at age 18 years and BMI transitions over adulthood on severe physical impairment (SPI), defined as scoring < 60 on the Physical Functioning subscale of the Rand thirty-six-item Short-Form Health Survey.

SETTING: Participants were part of the Women's Health Initiative Observational Study (WHI OS), where participants' health was followed over time via questionnaires and clinical assessments.

SUBJECTS: Postmenopausal women (n 76 016; mean age 63.5 (sd 7.3) years).

RESULTS: Women with overweight (BMI=25.0-29.9 kg/m2) or obesity (BMI > /=30.0 kg/m2) at 18 years had greater odds (OR (95 % CI)) of SPI (1.51 (1.35, 1.69) and 2.14 (1.72, 2.65), respectively) than normal-weight (BMI=18.5-24.9 kg/m2) counterparts. Transitions from normal weight to overweight/obese or to underweight (BMI < 18.5 kg/m2) were associated with greater odds of SPI (1.97 (1.84, 2.11) and 1.35 (1.06, 1.71), respectively) compared with weight stability. Shifting from underweight to overweight/obese also had increased odds of SPI (1.52 (1.11, 2.09)). Overweight/obese to normal BMI transitions resulted in a reduced SPI odds (0.52 (0.39, 0.71)).

CONCLUSIONS: Higher weight history and transitions into higher weight classes were associated with higher likelihood of SPI, while transitioning into lower weight classes for those with overweight/obesity was protective among postmenopausal women.

Atrial fibrillation without comorbidities: Prevalence, incidence and prognosis (from the Framingham Heart Study)

Wed, 09/14/2016 - 9:47am

BACKGROUND: The epidemiology of atrial fibrillation (AF) without comorbidities, known as 'lone AF', is uncertain. Although it has been considered a benign condition, we hypothesized that it confers a worse prognosis compared with a matched sample without AF.

METHODS: We described the proportion of AF without comorbidities (clinical, subclinical cardiovascular disease and triggers) among the entire AF sample in Framingham Heart Study (FHS). We compared AF without comorbidities with typical AF, and age-, sex- and cohort-matched individuals without AF, using Cox proportional hazards analysis in relation to combined cardiovascular events (stroke, heart failure, myocardial infarction), and mortality.

RESULTS: Of 10,311 FHS participants, 1,961 were diagnosed with incident AF, among which 173 individuals had AF without comorbidities (47% women, mean age 71+/-12 years). AF without comorbidities had a prevalence of 1.7% of the entire cohort, and an annual incidence of 0.5 per 1000 person-years. During a median follow-up of 9.7 years after initial AF, 137 individuals with AF without comorbidities (79.2%) died and 141 individuals developed cardiovascular events (81.5%). AF without comorbidities had significantly lower mortality (HR 0.67, 95%CI 0.55-0.81, P < .001) and total cardiovascular events (HR 0.66, 95% CI 0.55-0.80, P < .001) compared with typical AF. However, mortality (HR1.43, 95% CI 1.18-1.75, P < .001) and risk of total cardiovascular events (HR 1.73, 95% CI 1.39-2.16, P < .001) were higher than age-, sex-, and cohort-matched individuals without AF.

CONCLUSIONS: The risk of cardiovascular outcomes and mortality among individuals with AF without comorbidities is lower than typical AF, but is significantly elevated compared with matched individuals without AF.

Ages at menarche and menopause and reproductive lifespan as predictors of exceptional longevity in women: the Women's Health Initiative

Wed, 09/14/2016 - 9:47am

OBJECTIVE: The aim of the present study was to investigate associations between reproductive factors and survival to age 90 years.

METHODS: This was a prospective study of postmenopausal women from the Women's Health Initiative recruited from 1993 to 1998 and followed until the last outcomes evaluation on August 29, 2014. Participants included 16,251 women born on or before August 29, 1924 for whom survival to age 90 during follow-up was ascertained. Women were classified as having survived to age 90 (exceptional longevity) or died before age 90. Multivariable logistic regression models were used to evaluate associations of ages at menarche and menopause (natural or surgical) and reproductive lifespan with longevity, adjusting for demographic, lifestyle, and reproductive characteristics.

RESULTS: Participants were on average aged 74.7 years (range, 69-81 y) at baseline. Of 16,251 women, 8,892 (55%) survived to age 90. Women aged at least 12 years at menarche had modestly increased odds of longevity (odds ratio [OR], 1.09; 95% CI, 1.00-1.19). There was a significant trend toward increased longevity for later age at menopause (natural or surgical; Ptrend = 0.01), with ORs (95% CIs) of 1.19 (1.04-1.36) and 1.18 (1.02-1.36) for 50 to 54 and at least 55 compared with less than 40 years, respectively. Later age at natural menopause as a separate exposure was also significantly associated with increased longevity (Ptrend = 0.02). Longer reproductive lifespan was significantly associated with increased longevity (Ptrend = 0.008). The odds of longevity were 13% (OR 1.13; 95% CI, 1.03-1.25) higher in women with more than 40 compared with less than 33 reproductive years.

CONCLUSIONS: Reproductive characteristics were associated with late-age survival in older women.

Peripartum neuroactive steroid and gamma-aminobutyric acid profiles in women at-risk for postpartum depression

Wed, 09/14/2016 - 9:47am

Neuroactive steroids (NAS) are allosteric modulators of the gamma-aminobutyric acid (GABA) system. NAS and GABA are implicated in depression. The peripartum period involves physiologic changes in NAS which may be associated with peripartum depression and anxiety. We measured peripartum plasma NAS and GABA in healthy comparison subjects (HCS) and those at-risk for postpartum depression (AR-PPD) due to current mild depressive or anxiety symptoms or a history of depression. We evaluated 56 peripartum medication-free subjects. We measured symptoms with the Hamilton Depression Rating Scale (HAM-D17), Hamilton Anxiety Rating Scale (HAM-A) and Spielberger State-Trait Anxiety Inventory-State (STAI-S). Plasma NAS and GABA were quantified by liquid chromatography-mass spectrometry. We examined the associations between longitudinal changes in NAS, GABA and depressive and anxiety symptoms using generalized estimating equation methods. Peripartum GABA concentration was 1.9+/-0.7ng/mL (p=0.004) lower and progesterone and pregnanolone were 15.8+/-7.5 (p=0.04) and 1.5+/-0.7ng/mL (p=0.03) higher in AR-PPD versus HCS, respectively. HAM-D17 was negatively associated with GABA (beta=-0.14+/-0.05, p=0.01) and positively associated with pregnanolone (beta=0.16+/-0.06, p=0.01). STAI-S was positively associated with pregnanolone (beta=0.11+/-0.04, p=0.004), allopregnanolone (beta=0.13+/-0.05, p=0.006) and pregnenolone (beta=0.02+/-0.01, p=0.04). HAM-A was negatively associated with GABA (beta=-0.12+/-0.04, p=0.004) and positively associated with pregnanolone (beta=0.11+/-0.05, p=0.05). Altered peripartum NAS and GABA profiles in AR-PPD women suggest that their interaction may play an important role in the pathophysiology of peripartum depression and anxiety.

What is a 504 Plan and How Can it Help My Teen?

Mon, 09/12/2016 - 6:31pm

In this tip sheet, we offer parents and guardians some information on 504 plans based on Section 504 of the Rehabilitation Act of 1973.

A randomized controlled trial of a videoconferencing smoking cessation intervention for Korean American women: preliminary findings

Sun, 09/11/2016 - 9:17pm

Introduction: Korean women are reluctant to pursue in-person smoking cessation treatment due to stigma attached to women smokers and prefer treatment such as telephone and online smoking cessation programs that they can access secretively at home. However, there is some evidence that face-to-face interaction is the most helpful intervention component for them to quit smoking.

Methods: This study is a pilot clinical trial that examined the acceptability and feasibility of a videoconferencing smoking cessation intervention for Korean American women and compared its preliminary efficacy with a telephone-based intervention. Women of Korean ethnicity were recruited nationwide in the United States and randomly assigned at a ratio of 1:1 to either a video arm or a telephone arm. Both arms received eight 30-minute weekly individualized counseling sessions of a deep cultural smoking cessation intervention and nicotine patches for 8 weeks. Participants were followed over 3 months from the quit day.

Results: The videoconferencing intervention was acceptable and feasible for Korean women aged <50 years, whereas it was not for older women. Self-reported abstinence was high at 67% and 48% for the video and telephone arm at 1 month post-quit, respectively. The rates declined to 33% for the video arm and 28% for the telephone arm at 3 months post-quit when salivary cotinine test was performed.

Conclusion: Findings support that both videoconferencing and telephone counseling can be effective, and personal preference is likely an important factor in treatment matching. The deep cultural smoking cessation intervention may account for the outcomes of telephone counseling being better than prior studies in the literature for Korean women.