Advancing youth tobacco surveillance with novel methods.

Tobacco surveillance in the United States is robust but cannot be quickly modified to capture newly identified tobacco products or behaviors. We present an example of a rapidly deployed nonprobability survey using social media recruitment that collected data on rapidly changing tobacco use behaviors. We recruited 15- to 17-year old current vapers from NY, USA, using targeted social media advertisements to complete the New York Adolescent Vaping Survey (NY AVS), which asked about vaping behaviors not addressed in existing probability surveillance surveys. We used the New York Youth Risk Behavior Survey (NY YRBS) to apply calibration weights to ensure that the distribution of the demographic characteristics accurately reflected the population distribution. We found systematic differences in demographic variable distributions between the probability-based NY YRBS and the convenience sample of the NY AVS that were reconciled in the weighting calibration. We found no statistically significant differences between the NY YRBS and NY AVS estimates after calibration for two outcome variables of interest. Recruiting a sample of adolescents using social media advertising to conduct a rapid survey on vaping provided valuable data that complemented traditional surveillance surveys; this approach could be used to fill future knowledge gaps in youth tobacco surveillance.

The role of motivation on physical activity and screen time behaviors among parent-adolescent dyads: The FLASHE study.

Behavioral theories inform the development of lifestyle interventions to address low participation in physical activity (PA); however, relatively little is known about the value of self-determination theory (SDT) for explaining screen time (ST) behaviors or in extending SDT into a dyadic context. Actor-partner (i.e., parent-adolescent) interdependence models (APIMs) allow for examination of these interpersonal relationships. The purpose of this study was to examine PA and ST among parent-adolescent dyads using the cross-sectional Family Life, Activity, Sun, Health, and Eating (FLASHE) Study. Parent-adolescent dyads provided responses to online surveys addressing PA (n = 1177 dyads) and ST (n = 1489 dyads) behaviors. We examined the influence of SDT-based constructs (perceived competence and motivation) on PA and ST behaviors. Structural equations were used to estimate APIMs in STATA 15.1. Full models provided a good fit to the data. For both PA and ST, perceived competence was more strongly associated with motivation among adolescents compared with parents (PA: ß = 0.72 vs. 0.58, ST: ß = 0.34 vs. 0.22, p's < 0.001). Parental motivation was associated with parental PA and both adolescent motivation for PA and ST (p's < 0.001). Parental motivation was not associated with adolescent ST-behavior. Adolescent motivation was only associated with parent motivation for PA. In the FLASHE study, SDT constructs extend acceptably to the dyadic setting, with PA models providing a slightly better fit to the data than ST models. Longitudinal studies that target perceived competence and the self-regulation of motivation in parents and their adolescents are a next logical step to understanding both PA and ST behaviors.

Variability in sleep disturbance, physical activity and quality of life by level of depressive symptoms in women with Type 2 diabetes.

AIMS: To examine (1) the prevalence of depressive symptoms in women with Type 2 diabetes, (2) the associations between depressive symptoms and the following dependent variables: sleep disturbance; physical activity; physical health-related; and global quality of life, and (3) the potential moderating effects of antidepressants and optimism on the relationship between depressive symptoms and dependent variables. METHODS: Participants in the Women's Health Initiative who had Type 2 diabetes and data on depressive symptoms (N=8895) were included in the analyses. In multivariable linear regression models controlling for sociodemographic, medical and psychosocial covariates, we examined the main effect of depressive symptoms, as well as the interactions between depressive symptoms and antidepressant use, and between depressive symptoms and optimism, on sleep disturbance, physical activity, physical health-related quality of life; and global quality of life. RESULTS: In all, 16% of women with Type 2 diabetes reported elevated depressive symptoms. In multivariable analyses, women with depressive symptoms had greater sleep disturbance (P<0.0001) and lower global quality of life (P<.0001). We found evidence of significant statistical interaction in the models for quality-of-life outcomes: the increased risk of poor physical health-related quality of life associated with antidepressant use was stronger in women without vs with depressive symptoms, and the association between greater optimism and higher global quality of life was stronger in women with vs without depressive symptoms. CONCLUSIONS: To improve health behaviours and quality of life in women with Type 2 diabetes, sociodemographic and medical characteristics may identify at-risk populations, while psychosocial factors including depression and optimism may be important targets for non-pharmacological intervention.

In Vitro Induction of Human Regulatory T Cells Using Conditions of Low Tryptophan Plus Kynurenines.

Thymic regulatory T cells (tTregs) and induced regulatory T cells (iTregs) suppress murine acute graft-versus-host disease (GVHD). Previously, we demonstrated that the plasmacytoid dendritic cell indoleamine 2,3-dioxygenase (IDO) fosters the in vitro development of human iTregs via tryptophan depletion and kynurenine (Kyn) metabolites. We now show that stimulation of naïve CD4+ T cells in low tryptophan (low Trp) plus Kyn supports human iTreg generation. In vitro, low Trp + Kyn iTregs and tTregs potently suppress T effector cell proliferation equivalently but are phenotypically distinct. Compared with tTregs or T effector cells, bioenergetics profiling reveals that low Trp + Kyn iTregs have increased basal glycolysis and oxidative phosphorylation and use glutaminolysis as an energy source. Low Trp + Kyn iTreg viability was reliant on interleukin (IL)-2 in vitro. Although in vivo IL-2 administration increased low Trp + Kyn iTreg persistence on adoptive transfer into immunodeficient mice given peripheral blood mononuclear cells to induce GVHD, IL-2-supported iTregs did not improve recipient survival. We conclude that low Trp + Kyn create suppressive iTregs that have high metabolic needs that will need to be addressed before clinical translation.

Child Psychiatric Emergencies: Updates on Trends, Clinical Care, and Practice Challenges.

Over the past 15 years, the number of pediatric patients presenting to the emergency room in psychiatric crisis has nearly doubled. Suicidality and aggression are among the most common presenting problems, making it important for providers to have up-to-date knowledge about the assessment and management of these frequently encountered clinical issues. Psychometrically sound suicide risk assessment tools are available for use in the emergency room setting, which can be administered efficiently with minimal provider training. Rates of off-label medication use in the pediatric population continue to increase and are often used in the management of acute agitation in the pediatric population. The current literature will be reviewed and summarized for application in emergent treatment settings. Overall, evidence to inform best practice is limited, leading to opportunities for innovation in health care delivery, the development of new research aims, and discussion of challenging clinical dilemmas.

Cardiovascular response to exercise training in the systemic right ventricle of adults with transposition of the great arteries.

KEY POINTS: Patients with transposition of the great arteries (TGA) and systemic right ventricles have premature congestive heart failure; there is also a growing concern that athletes who perform extraordinary endurance exercise may injure the right ventricle. Therefore we felt it essential to determine whether exercise training might injure a systemic right ventricle which is loaded with every heartbeat. Previous studies have shown that short term exercise training is feasible in TGA patients, but its effect on ventricular function is unclear. We demonstrate that systemic right ventricular function is preserved (and may be improved) in TGA patients with exercise training programmes that are typical of recreational and sports participation, with no evidence of injury on biomarker assessment. Stroke volume reserve during exercise correlates with exercise training response in our TGA patients, identifying this as a marker of a systemic right ventricle (SRV) that may most tolerate (and possibly even be improved by) exercise training. ABSTRACT: We aimed to assess the haemodynamic effects of exercise training in transposition of the great arteries (TGA) patients with systemic right ventricles (SRVs). TGA patients have limited exercise tolerance and early mortality due to systemic (right) ventricular failure. Whether exercise training enhances or injures the SRV is unclear. Fourteen asymptomatic patients (34 ± 10 years) with TGA and SRV were enrolled in a 12 week exercise training programme (moderate and high-intensity workouts). Controls were matched on age, gender, BMI and physical activity. Exercise testing pre- and post- training included: (a) submaximal and peak; (b) prolonged (60 min) submaximal endurance and (c) high-intensity intervals. Oxygen uptake (V̇O2; Douglas bag technique), cardiac output (Q̇c, foreign-gas rebreathing), ventricular function (echocardiography and cardiac MRI) and serum biomarkers were assessed. TGA patients had lower peak V̇O2, Q̇c, and stroke volume (SV), a blunted Q̇c/V̇O2 slope, and diminished SV response to exercise (SV increase from rest: TGA = 15.2%, controls = 68.9%, P < 0.001) compared with controls. After training, TGA patients increased peak V̇O2 by 6 ± 8.5%, similar to controls (interaction P = 0.24). The magnitude of SV reserve on initial testing correlated with Q̇c training response (r = 0.58, P = 0.047), though overall, no change in peak Q̇c was observed. High-sensitivity troponin T (hs-TnT) and N-terminal prohormone of brain naturetic peptide (NT pro-BNP) were low and did not change with acute exercise or after training. Our data show that TGA patients with SRVs in this study safely participated in exercise training and improved peak V̇O2. Neither prolonged submaximal exercise, nor high-intensity intervals, nor short-term exercise training seem to injure the systemic right ventricle.

Theta oscillations orchestrate medial temporal lobe and neocortex in remembering autobiographical memories.

Remembering autobiographical events can be associated with detailed visual imagery. The medial temporal lobe (MTL), precuneus and prefrontal cortex are held to jointly enable such vivid retrieval, but how these regions are orchestrated remains unclear. An influential prediction from animal physiology is that neural oscillations in theta frequency may be important. In this experiment, participants prospectively collected audio recordings describing personal autobiographical episodes or semantic knowledge over 2 to 7 months. These were replayed as memory retrieval cues while recording brain activity with magnetoencephalography (MEG). We identified a peak of theta power within a left MTL region of interest during both autobiographical and General Semantic retrieval. This MTL region was selectively phase-synchronized with theta oscillations in precuneus and medial prefrontal cortex, and this synchrony was higher during autobiographical as compared to General Semantic knowledge retrieval. Higher synchrony also predicted more detailed visual imagery during retrieval. Thus, theta phase-synchrony orchestrates in humans the MTL with a distributed neocortical memory network when vividly remembering autobiographical experiences.

Deletion variant in the ADRA2B gene increases coupling between emotional responses at encoding and later retrieval of emotional memories.

A deletion variant of the ADRA2B gene that codes for the α2b adrenoceptor has been linked to greater susceptibility to traumatic memory as well as attentional biases in perceptual encoding of negatively valenced stimuli. The goal of the present study was to examine whether emotional enhancements of memory associated with the ADRA2B deletion variant were predicted by encoding, as indexed by the subjectively perceived emotional salience (i.e., arousal) of events at the time of encoding. Genotyping was performed on 186 healthy young adults who rated positive, negative, and neutral scenes for level of emotional arousal and subsequently performed a surprise recognition memory task 1 week later. Experience of childhood trauma was also measured, as well as additional genetic variations associated with emotional biases and episodic memory. Results showed that subjective arousal was linked to memory accuracy and confidence for ADRA2B deletion carriers but not for non-carriers. Our results suggest that carrying the ADRA2B deletion variant enhances the relationship between arousal at encoding and subsequent memory for moderately arousing events.

Psychosis and seizure disorder: challenges in diagnosis and treatment.

Psychosis temporally related to seizure episodes has been a recognized entity with much clinical attention, yet there are less clear guidelines for treatment. Presence of perceptual disturbances and cognitive impairment symptoms make the differentiation between primary psychoses and seizure- related psychoses blurred. Moreover, there are only a few reported cases describing clinical presentation, diagnostic dilemma and treatment challenges when these two entities are present at the same time, with overlapping symptomatology. We describe such a case where the presence of these two problems complicated the diagnoses and the patient's subsequent management required a very intricate collaboration between psychiatry and neurology. In addition, we review available published articles including case reports, studies, and review articles regarding the diagnosis and treatment of this complicated clinical presentation. Some of the analyses were reviewed in detail and resulting outcomes are discussed. Finally, we review the diagnostic and treatment guidelines in the context of the presenting case.

White matter integrity in physically fit older adults.

BACKGROUND: White matter (WM) integrity declines with normal aging. Physical activity may attenuate age-related WM integrity changes and improve cognitive function. This study examined brain WM integrity in Masters athletes who have engaged in life-long aerobic exercise training. We tested the hypothesis that life-long aerobic training is associated with improved brain WM integrity in older adults. METHODS: Ten Masters athletes (3 females, age=72.2 ± 5.3 years, endurance training >15 years) and 10 sedentary older adults similar in age and educational level (2 females, age=74.5 ± 4.3 years) participated. MRI fluid-attenuated-inversion-recovery (FLAIR) images were acquired to assess white matter hyperintensities (WMH) volume. Diffusion tensor imaging (DTI) was performed to evaluate the WM microstructural integrity with a DTI-derived metric, fractional anisotropy (FA) and mean diffusivity (MD). RESULTS: After normalization to whole-brain volume, Masters athletes showed an 83% reduction in deep WMH volume relative to their sedentary counterparts (0.05 ± 0.05% vs. 0.29 ± 0.29%, p<0.05). In addition, we found an inverse relationship between aerobic fitness (VO2max) and deep WMH volume (r=-0.78, p<0.001). Using TBSS, Masters athletes showed higher FA values in the right superior corona radiata (SCR), both sides of superior longitudinal fasciculus (SLF), right inferior fronto-occipital fasciculus (IFO), and left inferior longitudinal fasciculus (ILF). In addition, Masters athletes also showed lower MD values in the left posterior thalamic radiation (PTR) and left cingulum hippocampus. CONCLUSIONS: These findings suggest that life-long exercise is associated with reduced WMH and may preserve WM fiber microstructural integrity related to motor control and coordination in older adults.

Bronchoscopic lung-volume reduction with Exhale airway stents for emphysema (EASE trial): randomised, sham-controlled, multicentre trial.

BACKGROUND: Airway bypass is a bronchoscopic lung-volume reduction procedure for emphysema whereby transbronchial passages into the lung are created to release trapped air, supported with paclitaxel-coated stents to ease the mechanics of breathing. The aim of the EASE (Exhale airway stents for emphysema) trial was to evaluate safety and efficacy of airway bypass in people with severe homogeneous emphysema. METHODS: We undertook a randomised, double-blind, sham-controlled study in 38 specialist respiratory centres worldwide. We recruited 315 patients who had severe hyperinflation (ratio of residual volume [RV] to total lung capacity of ≥0·65). By computer using a random number generator, we randomly allocated participants (in a 2:1 ratio) to either airway bypass (n=208) or sham control (107). We divided investigators into team A (masked), who completed pre-procedure and post-procedure assessments, and team B (unmasked), who only did bronchoscopies without further interaction with patients. Participants were followed up for 12 months. The 6-month co-primary efficacy endpoint required 12% or greater improvement in forced vital capacity (FVC) and 1 point or greater decrease in the modified Medical Research Council dyspnoea score from baseline. The composite primary safety endpoint incorporated five severe adverse events. We did Bayesian analysis to show the posterior probability that airway bypass was superior to sham control (success threshold, 0·965). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00391612. FINDINGS: All recruited patients were included in the analysis. At 6 months, no difference between treatment arms was noted with respect to the co-primary efficacy endpoint (30 of 208 for airway bypass vs 12 of 107 for sham control; posterior probability 0·749, below the Bayesian success threshold of 0·965). The 6-month composite primary safety endpoint was 14·4% (30 of 208) for airway bypass versus 11·2% (12 of 107) for sham control (judged non-inferior, with a posterior probability of 1·00 [Bayesian success threshold >0·95]). INTERPRETATION: Although our findings showed safety and transient improvements, no sustainable benefit was recorded with airway bypass in patients with severe homogeneous emphysema. FUNDING: Broncus Technologies.

Lesion Explorer: a comprehensive segmentation and parcellation package to obtain regional volumetrics for subcortical hyperintensities and intracranial tissue.

Subcortical hyperintensities (SH) are a commonly observed phenomenon on MRI of the aging brain (Kertesz et al., 1988). Conflicting behavioral, cognitive and pathological associations reported in the literature underline the need to develop an intracranial volumetric analysis technique to elucidate pathophysiological origins of SH in Alzheimer's disease (AD), vascular cognitive impairment (VCI) and normal aging (De Leeuw et al., 2001; Mayer and Kier, 1991; Pantoni and Garcia, 1997; Sachdev et al., 2008). The challenge is to develop processing tools that effectively and reliably quantify subcortical small vessel disease in the context of brain tissue compartments. Segmentation and brain region parcellation should account for SH subtypes which are often classified as: periventricular (pvSH) and deep white (dwSH), incidental white matter disease or lacunar infarcts and Virchow-Robin spaces. Lesion Explorer (LE) was developed as the final component of a comprehensive volumetric segmentation and parcellation image processing stream built upon previously published methods (Dade et al., 2004; Kovacevic et al., 2002). Inter-rater and inter-method reliability was accomplished both globally and regionally. Volumetric analysis showed high inter-rater reliability both globally (ICC=.99) and regionally (ICC=.98). Pixel-wise spatial congruence was also high (SI=.97). Whole brain pvSH volumes yielded high inter-rater reliability (ICC=.99). Volumetric analysis against an alternative kNN segmentation revealed high inter-method reliability (ICC=.97). Comparison with visual rating scales showed high significant correlations (ARWMC: r=.86; CHIPS: r=.87). The pipeline yields a comprehensive and reliable individualized volumetric profile for subcortical vasculopathy that includes regionalized (26 brain regions) measures for: GM, WM, sCSF, vCSF, lacunar and non-lacunar pvSH and dwSH.

Impaired event memory and recollection in a case of developmental amnesia.

A current debate in the literature is whether all declarative memories and associated memory processes rely on the same neural substrate. Here, we show that H.C., a developmental amnesic person with selective bilateral hippocampal volume loss, has a mild deficit in personal episodic memory, and a more pronounced deficit in public event memory; semantic memory for personal and general knowledge was unimpaired. This was accompanied by a subtle difference in impairment between recollection and familiarity on lab-based tests of recognition memory. Strikingly, H.C.'s recognition did not benefit from a levels-of-processing manipulation. Thus, not all types of declarative memory and related processes can exist independently of the hippocampus even if it is damaged early in life.

Some sex hormone profiles are consistent over time in normal menstruating women: implications for sports injury epidemiology.

PURPOSE: It is unclear whether sex hormone profiles obtained in two consecutive months are consistent within women. Month-to-month consistency in daily, nadir, peak and mean hormone concentrations during the early follicular and luteal phases in recreationally active, young eumenorrheic women was prospectively examined. METHODS: 60 healthy, non-smoking women who reported normal and consistent menstrual cycles lasting 26-32 days for the past 6 months were followed prospectively to obtain serum samples for the first 6 days of menses and for 8 days after a positive ovulation test over two consecutive months. Month-to-month consistency of daily concentrations of oestradiol (pg/ml), progesterone (ng/ml), testosterone (ng/dl), sex hormone-binding globulin (nmol/l) and free androgen index were determined using linear mixed models. Month-to-month consistency in nadir, peak and mean concentrations were then assessed using intraclass correlation coefficients and SEM to more precisely examine intraindividual consistency. RESULTS: Linear mixed models revealed stable hormone concentrations across cycles and cycles by day. Reliability estimates for nadir, peak, mean menses and mean postovulatory concentrations range from 0.56 to 0.86 for oestradiol, 0.44 to 0.91 for progesterone, 0.60 to 0.86 for testosterone, 0.88 to 0.97 for sex hormone-binding globulin and 0.78 to 0.91 for free androgen index. CONCLUSIONS: Hormone profiles were reproducible over two consecutive months. To reduce month-to-month intraindividual variations and improve measurement consistency, it is recommended that multiple samples be taken over consecutive days as opposed to a single sample.

Regulated expression of telomerase activity in human T lymphocyte development and activation.

Telomerase, a ribonucleoprotein that is capable of synthesizing telomeric repeats, is expressed in germline and malignant cells, and is absent in most normal human somatic cells. The selective expression of telomerase has thus been proposed to be a basis for the immortality of the germline and of malignant cells. In the present study, telomerase activity was analyzed in normal human T lymphocytes. It was found that telomerase is expressed at a high level in thymocyte subpopulations, at an intermediate level in tonsil T lymphocytes, and at a low to undetectable level in peripheral blood T lymphocytes. Moreover, telomerase activity is highly inducible in peripheral T lymphocytes by activation through CD3 with or without CD28 costimulation, or by stimulation with phorbol myristate acetate (PMA)/ionomycin. The induction of telomerase by anti-CD3 plus anti-CD28 (anti-CD3/CD28) stimulation required RNA and protein synthesis, and was blocked by herbimycin A, an inhibitor of S pi protein tyrosine kinases. The immunosuppressive drug cyclosporin A selectively inhibited telomerase induction by PMA/ionomycin and by anti-CD3, but not by anti-CD3/CD28. Although telomerase activity in peripheral T lymphocytes was activation dependent and correlated with cell proliferation, it was not cell cycle phase restricted. These results indicate that the expression of telomerase in normal human T lymphocytes is both developmentally regulated and activation induced. Telomerase may thus play a permissive role in T cell development and in determining the capacity of lymphoid cells for cell division and clonal expansion.

Mechanisms underlying binding of immune complexes to macrophages.

The mechanism of binding of immune complexes to macrophages was investigated using purified antibody and haptens of different valences. Antibody alone bound to macrophages; enhancement of binding occurred when polyvalent and divalent haptens were present at equivalence but did not occur in great antigen excess. Monovalent hapten did not increase the binding of antibody at any concentration ratio tried, though it inhibited the enhancement due to oligovalent hapten. Ultracentrifuged normal rabbit globulin also inhibited the binding of complexes indicating the presence of exposed binding sites on the uncomplexed molecules. Complexes bound more strongly than antibody alone as determined from elution studies. These results support the hypothesis that the enhancement of antibody binding to macrophages in the presence of antigen is due to increased energy of binding resulting from summation of individual binding sites already exposed on the antibody molecules. It was also possible, by saturating the macrophages with gamma globulin, to estimate the number of binding sites per cell; this was calculated to be approximately 2 million per alveolar macrophage.

H-2-linked genetic control of immune responsiveness to ovalbumin and ovomucoid.

Immune responsiveness of inbred mice to low doses of ovalbumin or ovomucoid is under control of single dominant genes closely linked to alleles of the H-2 locus. High responsiveness to ovomucoid is linked with the H-2(a) and H-2(k) alleles, and to ovalbumin with the H-2(b), H-2(d), and H-2(q) alleles.

Telomere length, telomerase activity, and replicative potential in HIV infection: analysis of CD4+ and CD8+ T cells from HIV-discordant monozygotic twins.

To address the possible role of replicative senescence in human immunodeficiency virus (HIV) infection, telomere length, telomerase activity, and in vitro replicative capacity were assessed in peripheral blood T cells from HIV+ and HIV- donors. Genetic and age-specific effects on these parameters were controlled by studying HIV-discordant pairs of monozygotic twins. Telomere terminal restriction fragment (TRF) lengths from CD4+ T cells of HIV+ donors were significantly greater than those from HIV- twins. In contrast, telomere lengths in CD8+ T cells from HIV+ donors were shorter than in HIV- donors. The in vitro replicative capacity of CD4+ cells from HIV+ donors was equivalent to that of HIV- donors in response to stimulation through T cell receptor CD3 and CD28. Little or no telomerase activity was detected in freshly isolated CD4+ or CD8+ lymphocytes from HIV+ or HIV- donors, but was induced by in vitro stimulation of both HIV+ and HIV- donor cells. These results suggest that HIV infection is associated with alterations in the population dynamics of both CD4+ and CD8+ T cells, but fail to provide evidence for clonal exhaustion or replicative senescence as a mechanism underlying the decline in CD4+ T cells of HIV-infected donors.

Immune responses of inbred mice to repeated low doses of antigen: relationship to histocompatibility (H-2) type.

Immunization of inbred strains of mice with repeated minute doses (0.1 to 1.0 microgram) of hapten-protein conjugates demonstrated wide differences in the magnitude of their antibody responses, which were related to the histocompatibility (H-2) type of the strains. Immunization with a single high dose (100 micrograms) of antigen failed to demonstrate these differences.