Faculty Bibliography

Introduction: Sleep may play a role in AD pathogenesis, but the timing, role, and extent to which sleep disturbances in late-life are associated with increasing burden of AD neuropathology remains unclear. Sleep spindles have been implicated in sleep quality. Wakefulness is mediated by an arousal system beginning in the brainstem and continuing on to the diencephalon and innervating the thalamus, the region where sleep spindle oscillations are generated. In AD pathology, hyperphosphorylated tau (P-Tau) protein accumulates in the brainstem, from where it spreads to the entorhinal cortices, hippocampi and other brain regions. These tau aggregates may interfere with the sleep-wake cycle resulting in down-regulation of sleep spindles and associated sleep disruption. Increased CSF P-tau and T-tau levels are likely related to the formation of neurofibrillary tangles in the brainstem and limbic system (Braak stages I-IV). Methods: 49 cognitively normal (CDR=0) elderly (66.95 +/- 7.76 years) subjects completed a structural MRI, lumbar puncture (LP) and nocturnal polysomnography (NPSG) within 4.65 +/- 6.81 months of the LP. From the NPSG, spindle frequency and density were analyzed for stages NREM1, NREM2 and NREM3, using an automated optimization algorithm which decomposes the EEG as a sum of transient and oscillatory components. This was used to detect the spindles and a Fourier analysis was performed to evaluate the spindle frequency in Hz. Results: Spindle frequency and density in NREM2 sleep were inversely associated with CSF P-tau (r= -0.355, p<0.05; r=-0.476, p<0.05) and CSF T-tau (r=-0.405, p<.05; r=-0.542, p<.05) using partial correlation controlling for age and ApoE4 allele. There were no associations between spindle frequency or density and CSF P-tau or CSF T-tau in stages NREM1, NREM3. Conclusion: The association of spindle frequency and density in NREM2 to CSF P-tau and CSF T-tau in cognitively normal elderly suggest either that tau pathology may produce an early downstream effect on sleep spindles, or that changes in sleep spindles can identify a process relating to tau pathology. Whether the association of tau to spindles is a non-specific effect of tau on increasing sleep fragmentation in general remains an area of active investigation

The study evaluated the acceptability of text message- and voice-based ecological momentary assessment (EMA) methods among a sample (n=74) of young men who have sex with men (MSM). We assessed the acceptability of text message- and voice-based EMA methods. Almost all participants (96%) reported that they would be willing to accept texts on their smartphone to answer questions about their current mood, surroundings, or feelings. A large majority (89%) also reported being willing to accept phone calls to answer these questions. This work suggests that different EMA methods are acceptable for use among young MSM.

Parental mental health may be a critical component in understanding the overlapping health burdens of mental health symptomatology and drug use in young men who have sex with men (YMSM), yet studies of YMSM have not fully examined these associations. To understand these relationships, data drawn from a study of gay, bisexual, and other YMSM were used examine associations between perceived parental psychopathology and the mental health symptomatology and drug use of YMSM. Findings suggest that YMSM reporting at least one parent with perceived depression, manic depression, schizophrenia, or antisocial behavior anytime during their childhoods were more likely to report higher levels of both depressive symptomatology and post-traumatic stress disorder (PTSD) than those reporting no perception of any of these psychopathologies in their parents. Number of different drugs uses in one's were higher among participants who perceived at least one parent as depressed. Mediation analyses indicated that the relationship between perceived parental depression and lifetime drug use of YMSM was mediated both by YMSM depression and YMSM PTSD. These results suggest that parental psychopathology plays an important role in the health of sexual minority men, a population with elevated levels of mental health burden and drug use across the lifespan.

INTRODUCTION/BACKGROUND:Approximately 70,000 adolescent and young adults (AYA) are diagnosed with cancer each year. While advancements in treatment have led to improved prognosis and survival for patients, these same treatments can adversely affect AYA reproductive capacity. Localized treatments such as surgery and radiation therapy may affect fertility by removing or damaging reproductive organs, and systemic therapies such as chemotherapy can be toxic to gonads, (ovaries and testicles), thus affecting fertility and/or endocrine function. This can be traumatic for AYA with cancer as survivors often express desire to have genetic children and report feelings of regret or depression as a result of infertility caused by cancer treatments. AREAS COVERED/UNASSIGNED:Emerging technologies in the field of assisted reproductive technology offer new promise for preserving the reproductive capacity of AYA cancer patients prior to treatment as well as providing alternatives for survivors. The following review revisits contemporary approaches to fertility preservation as well newly developing technologies. EXPERT COMMENTARY/UNASSIGNED:There are several advances in ART that hold promise for patients and survivors. However there are challenges that inhibit uptake including poor communication between providers and patients about risks and fertility preservation options; high costs; and lack of insurance coverage for fertility preservation services.

BACKGROUND:Arteriovenous accesses (AVA) in patients performing hemodialysis (HD) are labeled "permanent" for AV fistulas (AVF) or grafts (AVG) and "temporary" for tunneled central venous catheters (TCVC). Durability and outcomes of permanent vascular accesses based on the sequence in which they were placed or used receives little attention. This study analyzed longitudinal transitions between TCVC-based and AVA-based HD outcomes according to the order of placement. METHODS:All 391 patients initiating chronic HD via a TCVC between 2012 and 2013 at 12 outpatient academic dialysis units were included in this study. Chronological distributions of HD vascular accesses were recorded over a mean (SD) of 2.8 (0.9) years and sequentially grouped into periods for TCVC-delivered and AVA-delivered (AVF or AVG) HD. Primary AVA failure and cumulative access survival were evaluated based on access placement sequence and type, adjusting for age. RESULTS:In total, 92.3% (361/391) of patients underwent 497 AVA placement surgeries. Analyzing the initial 3 surgeries, primary AVF failure rates increased with each successive fistula placement (p = 0.008). Among the 82.9% (324/391) of TCVC patients successfully converted to an AVA, 30.9% returned to a TCVC, followed by a 58.0% conversion rate to another AVA. Annual per-patient vascular access transition rates were 2.02 (0.09) HD periods using a TCVC and 0.54 (0.03) HD periods using an AVA. Comparing the first AVA used with the second, cumulative access survivals were 701.0 (370.0) vs. 426.5 (275.0) days, respectively. Excluding those never converting to an AVF or AVG, 169 (52.2%) subsequently converted from a TCVC to a permanent access and received HD via AVA for ≥80% of treatments. CONCLUSIONS:HD vascular access outcomes differ based on the sequence of placement. In spite of frequent AVA placements, only half of patients effectively achieved a "permanent" vascular access and used an AVA for the majority of HD treatments.

Antibiotic therapy against non-tuberculous mycobacteria (NTM) is prolonged and can be associated with toxicity. We sought to evaluate whether chest physical therapy (PT) was associated with clinical improvement in patients with NTM not receiving anti-mycobacterial pharmacotherapy. A retrospective review of 77 subjects that were followed from June 2006 to September 2014 was performed. Baseline time point was defined as the first positive sputum culture for NTM; symptoms, pulmonary function, and radiology reports were studied. Subjects were followed for up to 24 months and results analyzed at specified time points. Half of the subjects received chest PT at baseline. Cough improved at 12 (p = 0.001) and 24 months (p = 0.003) in the overall cohort when compared with baseline, despite lack of NTM antibiotic treatment. Cough decreased at 6 (p = 0.01), 9 (p = 0.02), 12 (p = 0.02) and 24 months (p = 0.002) in subjects that received chest PT. Sputum production also improved at 24 months in the overall cohort (p = 0.01). There was an increase in the percent change of total lung capacity in subjects that received chest PT (p = 0.005). Select patients with NTM may have clinical improvement with chest PT, without being subjected to prolonged antibiotic therapy. Future studies are warranted to prospectively evaluate outcomes in the setting of non-pharmacologic treatment and aid with the decision of antibiotic initiation.

The current study examines the additive and joint roles of chronic poverty-related adversity and three candidate neurocognitive processes of emotion regulation (ER)-including: (i) attention bias to threat (ABT); (ii) accuracy of facial emotion appraisal (FEA); and (iii) negative affect (NA)-for low-income, ethnic minority children's internalizing problems (N = 338). Children were enrolled in the current study from publicly funded preschools, with poverty-related adversity assessed at multiple time points from early to middle childhood. Field-based administration of neurocognitively-informed assessments of ABT, FEA and NA as well as parental report of internalizing symptoms were collected when children were ages 8-11, 6 years after baseline. Results suggest that chronic exposure to poverty-related adversity from early to middle childhood predicted higher levels of internalizing symptomatology when children are ages 8-11, even after controlling for initial poverty status and early internalizing symptoms in preschool. Moreover, each of the 3 hypothesized components of ER played an independent and statistically significant role in predicting children's parent-reported internalizing symptoms at the 6-year follow-up, even after controlling for early and chronic poverty-related adversity.