Accelerometer as a tool to assess sedentarity and adherence to physical activity recommendations after cardiac rehabilitation program.

PURPOSE: To objectively assess, in stable cardiac patients, the adherence to physical activity (PA) recommendations using an accelerometer at 2 or 12 months after the discharge of cardiac rehabilitation program (CRP). METHODS: Eighty cardiac patients wore an accelerometer at 2 months (group 1, short-term adherence, n = 41) or one-year (group 2, long-term adherence, n = 39) after a CRP including therapeutic education about regular PA. PA was classified as "light" (1.8-2.9 Metabolic Equivalent of Task [METs]), "moderate" (3-5.9 METs), or "intense" (>6 METs). Energy expenditure (EE, in Kcal) and time (min) spent in these three different levels were measured during a one-week period with the MyWellness Key actimeter (MWK). Motivational readiness for change was also assessed at the end of CRP. Patients were considered as physically active when a minimum of 150 min of moderate PA during the one-week period was achieved. RESULTS: Both groups were comparable, except for exercise capacity at the end of the CRP which was slightly higher in group 1 (167.5 ± 42.3 versus 140.7 ± 46.1 W, P < 0.01). The total weekly active EE averaged 676.7 ± 353.2 kcal and 609.5 ± 433.5 kcal in group 1 and 2, respectively. The time spent within the light-intensity range PA was 319.4 ± 170.9 and 310.9 ± 160.6 min, and the time spent within the moderate-intensity range averaged 157.4 ± 115.4 and 165 ± 77.2 min per week for group 1 and 2, respectively. Fifty-three percent and 41% of patients remained active in both groups respectively. CONCLUSION: About half of the patients are non-adherent to PA after CRP and do not reach target levels recommended by physicians. The first 2 months following the discharge of CRP seem to be of outmost importance for lifestyle modifications maintenance, and further study monitoring more closely PA decrease could help to clarify the optimal follow-up options.

Attributes of response in depressed patients switched to treatment with duloxetine.

BACKGROUND: This study was designed to assess clinical and functional outcomes associated with switching to duloxetine treatment in patients with major depressive disorder (MDD) experiencing emotional and painful physical symptoms in their current episode. METHODS: In this 8-week, multinational, multicentre, single-arm, open-label clinical trial, 242 MDD patients were switched to duloxetine 60 mg/day after selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI) treatment. The primary analysis compared mean change from baseline in Brief Pain Inventory-Modified Short Form (BPI-SF) interference score between initial responders [≥ 50% reduction from baseline on the 17-item Hamilton Depression Rating Scale (HAMD(17)) Maier subscale] and initial non-responders after 4 weeks. Initial responders continued with duloxetine 60 mg/day. Initial non-responders received duloxetine 120 mg/day for the remaining 4 weeks. Depression, pain, anxiety and functional outcomes were also compared after 8 weeks. RESULTS: BPI-SF interference decreased from baseline in initial responders (n = 108) and initial non-responders (n = 85) after 4 weeks of duloxetine treatment, with greater reductions in initial responders [BPI-SF mean difference in reduction: 1.01 (95% CI 0.42-1.61); p < 0.001]. Reductions in pain interference favouring initial responders were also apparent after 8 weeks [0.68 (95% CI: 0.03-1.33); p = 0.042]. Depression, pain, anxiety and function improved over 8 weeks across patient groups. CONCLUSIONS: Elements of core mood and pain are important residual symptoms following poor treatment response in MDD. Early improvement in these symptoms after switching to duloxetine indicated an increased chance of functional recovery.

Association between painful physical symptoms and clinical outcomes in East Asian patients with major depressive disorder: a 3-month prospective observational study.

AIMS: Reports from non-Asian populations indicate that painful physical symptoms (PPS) are associated with poorer clinical and functional outcomes in major depressive disorder (MDD). The purpose of this study is to report comparative changes in disease severity, treatment patterns and quality of life observed in East Asian patients with MDD, with and without PPS, as assessed prospectively over a 3-month observation period. METHODS: This observational study enrolled 909 patients with MDD in psychiatric care settings in China, Hong Kong, Korea, Malaysia, Singapore and Taiwan. Patients were classified as PPS positive (PPS+) or negative (PPS-) based on mean modified Somatic Symptom Inventory scores of >or= 2 or < 2 respectively. The Clinical Global Impression of Severity (CGI-S) and 17-item Hamilton Depression Rating Scale (HAMD(17)) determined depression severity; a visual analogue scale (VAS) determined pain severity; and the EuroQoL (EQ-5D) assessed well-being after 3 months observation. RESULTS: Of the 909 enrollees, 355/471 (75.4%) of PPS+ patients and 363/438 (82.9%) of PPS- patients completed the study (p = 0.006). PPS+ patients improved less than PPS- patients on depression, pain and quality of life measures during the study (HAMD(17) p < 0.001, CGI-S p < 0.001, VAS p = 0.008 and EQ-5D p = 0.004). Fewer PPS+ patients (46.5%) achieved remission compared with PPS- patients (69.4%, p < 0.001). CONCLUSION: As the presence of PPS is associated with poorer outcomes in East Asian MDD patients, clinical management should aim to address both the mental and PPS associated with MDD.

The inverse relationship between number of steps per day and obesity in a population-based sample: the AusDiab study.

BACKGROUND: Physical activity (PA) is inversely associated with obesity but the effect has been difficult to quantify using questionnaires. In particular, the shape of the association has not yet been well described. Pedometers provide an opportunity to better characterize the association. METHODS: Residents of households over the age of 25 years in randomly selected census districts in Tasmania were eligible to participate in the AusDiab cross-sectional survey conducted in 1999-2000. 1848 completed the AusDiab survey and 1126 of these (609 women and 517 men) wore a pedometer for 2-weekdays. Questionnaire data on recent PA, TV time and other factors were obtained. The outcomes were waist circumference (in cm) and body mass index (BMI) (kg/m(2)). RESULTS: Increasing daily steps were associated with a decline in the obesity measures. The logarithmic nature of the associations was indicated by a sharper decline for those with lower daily steps. For example, an additional 2000 steps for those taking only 2000 steps per day was associated with a reduction of 2.8 (95% confidence interval (CI): 2.1,4.4) cm in waist circumference among men (for women; 2.2 (95% CI: 0.6, 3.9 cm)) with a baseline of only 2000, steps compared to a 0.7 (95% CI 0.3, 1.1) cm reduction (for women; 0.6 (95% CI: 0.2, 1.0)) for those already walking 10,000 steps daily. In the multivariable analysis, clearer associations were detected for PA and these obesity measures using daily step number rather than PA time by questionnaire. INTERPRETATION: Pedometer measures of activity indicate that the inverse association between recent PA and obesity is logarithmic in form with the greatest impact for a given arithmetic step number increase seen at lower levels of baseline activity. The findings from this study need to be examined in prospective settings.

Injectable vaccines for preventing pneumococcal infection in patients with chronic obstructive pulmonary disease.

BACKGROUND: As chronic obstructive pulmonary disease (COPD) progresses, exacerbations can occur with increasing frequency. One goal of therapy in COPD is to try and prevent these exacerbations, thereby reducing disease morbidity and associated healthcare costs. Pneumococcal vaccinations are considered to be one strategy for reducing the risk of infective exacerbations. OBJECTIVES: To determine the safety and efficacy of pneumococcal vaccination in COPD. The primary outcome assessed was acute exacerbations. Secondary outcomes of interest included episodes of pneumonia, hospital admissions, adverse events related to treatment, disability, change in lung function, mortality, and cost effectiveness. SEARCH STRATEGY: We searched the Cochrane Airways Group COPD trials register using pre-specified terms. We also conducted additional handsearches of conference abstracts. The last round of searches were performed in April 2006. SELECTION CRITERIA: Only randomised controlled trials assessing the effects of injectable pneumococcal vaccine in people with COPD were included. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and three review authors independently assessed trial quality. MAIN RESULTS: Although 10 studies cited in 11 publications were identified that met the inclusion criteria for this review, only four of these provided data on participants with COPD. The studies which did provide data for this review consisted of two trials using a 14-valent vaccine, and two using a 23-valent injectable vaccine. Data for the primary outcome, acute exacerbation of COPD, was available from only one of the four studies. The odds ratio of 1.43 (95% confidence interval (CI) 0.31 to 6.69) between interventions was not statistically significant. Of the secondary outcomes for which data were available and could be extracted, none reached statistical significance. Three studies provided dichotomous data for persons who developed pneumonia (OR 0.89, 95% CI 0.58 to 1.37, n = 748). Rates of hospital admissions and emergency department visits came from a single study. There was no significant reduction in the odds of all-cause mortality 1 to 48 months post-vaccination (Peto odds ratio 0.94, 95% CI 0.67 to 1.33, n = 888), or for death from cardiorespiratory causes (OR 1.07, 95% CI 0.69 to 1.66). AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled trials that injectable pneumococcal vaccination in persons with COPD has a significant impact on morbidity or mortality. Further large randomised controlled trials would be needed to ascertain if the small benefits suggested by individual studies are real.

Climate change, flow regulation and land-use effects on the hydrology of the Peace-Athabasca-Slave System; findings from the Northern Rivers Ecosystem Initiative.

The Northern Rivers Ecosystem Initiative (NREI) was established in the late 1990s to address important science questions resulting from previous studies undertaken by the Northern Rivers Basin Study (NRBS). This manuscript summarizes the results from a number of reports on hydrologic research conducted on the Peace-Athabasca-Slave river and lake systems. Specific concerns expressed by the NRBS and subsequent NREI focused on how these systems were being affected by climate change, flow regulation and land-use changes. Issues addressed in this report include: the fate of aquatic perched basins within the Peace-Athabasca Delta under historical and future climate trends; the sources of major floods that replenish these basins and how the frequency, magnitude and source areas of such events have changed over time; the synoptic weather patterns and atmospheric teleconnections that are responsible for the generation of major snowmelt runoff that drive major floods; the potential effect that climate and land-use changes might have on basin runoff and delta lake levels; the specific hydro-climatic conditions required to produce major ice-jam floods on the Peace River and how these may be altered by climate change; remote-sensing methods to document delta flooding and vegetation change; and the dual effect of climate and flow regulation on the water levels of Great Slave Lake and how these may affect other nearshore processes, particularly wind seiches, that influence flooding of the Slave River Delta. A review of the major findings and recommendations for future research concludes the report.

Derivation and analysis of basic computational operations of thalamocortical circuits.

Shared anatomical and physiological features of primary, secondary, tertiary, polysensory, and associational neocortical areas are used to formulate a novel extended hypothesis of thalamocortical circuit operation. A simplified anatomically based model of topographically and nontopographically projecting ("core" and "matrix") thalamic nuclei, and their differential connections with superficial, middle, and deep neocortical laminae, is described. Synapses in the model are activated and potentiated according to physiologically based rules. Features incorporated into the models include differential time courses of excitatory versus inhibitory postsynaptic potentials, differential axonal arborization of pyramidal cells versus interneurons, and different laminar afferent and projection patterns. Observation of the model's responses to static and time-varying inputs indicates that topographic "core" circuits operate to organize stored memories into natural similarity-based hierarchies, whereas diffuse "matrix" circuits give rise to efficient storage of time-varying input into retrievable sequence chains. Examination of these operations shows their relationships with well-studied algorithms for related functions, including categorization via hierarchical clustering, and sequential storage via hash- or scatter-storage. Analysis demonstrates that the derived thalamocortical algorithms exhibit desirable efficiency, scaling, and space and time cost characteristics. Implications of the hypotheses for central issues of perceptual reaction times and memory capacity are discussed. It is conjectured that the derived functions are fundamental building blocks recurrent throughout the neocortex, which, through combination, gives rise to powerful perceptual, motor, and cognitive mechanisms.

Work-based antipoverty programs for parents can enhance the school performance and social behavior of children.

We assess the impact of the New Hope Project, an antipoverty program tested in a random assignment experimental design, on family functioning and developmental outcomes for preschool- and school-aged children (N = 913). New Hope offered wage supplements sufficient to raise family income above the poverty threshold and subsidies for child care and health insurance to adults who worked full-time. New Hope had strong positive effects on boys' academic achievement, classroom behavior skills, positive social behavior, and problem behaviors, as reported by teachers, and on boys' own expectations for advanced education and occupational aspirations. There were not corresponding program effects for girls. The child outcomes may have resulted from a combination of the following: Children in New Hope families spent more time in formal child care programs and other structured activities away from home than did children in control families. New Hope parents were employed more, had more material resources, reported more social support, and expressed less stress and more optimism about achieving their goals than did parents in the control sample. The results suggest that an anti-poverty program that provides support for combining work and family responsibilities can have beneficial effects on the development of school-age children.

Intraoperative decrease in pulse oximeter readings following injection of isosulfan blue.

PURPOSE: Sentinel lymph node mapping, involving injection of isosulfan blue dye around a tumour, is beginning to be used in patients with carcinoma of the breast. Absorption of the dye into the circulation may interfere with pulse oximetry, causing falsely low readings. This report describes changes in pulse oximeter readings following injection of isosulfan blue for sentinel lymph node mapping in a patient with carcinoma of the breast. CLINICAL FEATURES: An 83-yr-old female patient underwent sentinel node biopsy of the axilla followed by partial mastectomy for carcinoma of the left breast. Isosulfan blue was injected in the area of the tumour in the left breast. The SpO2 began to decrease 15 min after dye injection, reaching a nadir of 89-90% 30 min after injection. Arterial blood gas analysis showed normal arterial partial pressure of oxygen. Pulse oximeter readings did not return to normal until more than six hours after dye injection. CONCLUSION: Review of the literature reveals a small number of case reports of similar occurrences of low pulse oximeter readings following injection of isosulfan blue or patent blue dye for lymphatic mapping. Data from these reports and the case described here suggest that the latency, magnitude and duration of effect on pulse oximeter readings following injection of these dyes is highly variable. It is important to rule out other causes of low pulse oximeter readings when this effect occurs; normal oxygenation can be verified with arterial blood gas analysis. Co-oximetry can be done to rule out methemoglobinemia as a cause of decreased SpO2.

Origins and distribution of cholinergically induced beta rhythms in hippocampal slices.

Regional variations and substrates of high-frequency rhythmic activity induced by cholinergic stimulation were studied in hippocampal slices with 64-electrode recording arrays. (1) Carbachol triggered beta waves (17.6 +/- 5.7 Hz) in pyramidal regions of 75% of the slices. (2) The waves had phase shifts across the cell body layers and were substantially larger in the apical dendrites than in cell body layers or basal dendrites. (3) Continuous, two-dimensional current source density analyses indicated apical sinks associated with basal sources, lasting approximately 10 msec, followed by apical sources and basal sinks, lasting approximately 20 msec, in a repeating pattern with a period in the range of 15-25 Hz. (4) Carbachol-induced beta waves in the hippocampus were accompanied by 40 Hz (gamma) oscillations in deep layers of the entorhinal cortex. (5) Cholinergically elicited beta and gamma rhythms were eliminated by antagonists of either AMPA or GABA receptors. Benzodiazepines markedly enhanced beta activity and sometimes introduced a distinct gamma frequency peak. (6) Twenty Hertz activity after orthodromic activation of field CA3 was distributed in the same manner as carbachol-induced beta waves and was generated by a current source in the apical dendrites of CA3. This source was eliminated by high concentrations of GABA(A) receptor blockers. It is concluded that cholinergically driven beta rhythms arise independently in hippocampal subfields from oscillatory circuits involving (1) bursts of pyramidal cell discharges, (2) activation of a subset of feedback interneurons that project apically, and (3) production of a GABA(A)-mediated hyperpolarization in the outer portions of the apical dendrites of pyramidal neurons.

Clonal restriction of T-cell receptor expression by infiltrating lymphocytes in inclusion body myositis persists over time. Studies in repeated muscle biopsies.

Inclusion body myositis (IBM) is an inflammatory myopathy characterized immunohistologically by prominent invasion of the non-necrotic, MHC-I class antigen-expressing muscle fibres by CD8+ cytotoxic T cells. If the autoinvasive CD8+ T cells are recruited specifically to the muscle and play a primary pathogenetic role in the disease, a clonal restriction persisting over time should be anticipated. In this study, we analysed the T-cell receptor (TCR) gene usage by endomysial T lymphocytes in three sequential muscle biopsies from three different IBM patients over a 19-22 month period using immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and sequence analysis of the complementarity determining region (CDR3) of the amplified TCRs. We found that CD8+ T lymphocytes persist in the endomysial infiltrates in all biopsies during a 19-22 month period. The most frequently detected TCRs were the V beta 3, V beta 5.1, V beta 6.7 and V beta 13 gene families, and several of the autoinvasive CD8+ T cells expressed the TCRs V beta 6.7 and V beta 5.1. A restricted usage of the examined V beta 6 gene family was found to persist in the complementarity CDR3 determining region of the autoinvasive T cells over the 22 month period. Identical V beta 6 CDR3 gene arrangements were also found in the multiple muscle biopsies from two of the three IBM patients. The results indicate that in IBM there is a restricted expression of the TCR gene families among the autoinvasive T lymphocytes with homologies in the CDR3 region that persist over the course of the disease. A continuous, antigen-driven T-cell response is prominent in the muscle of patients with IBM.

Gene, stimulus and cell-type specific regulation of activator protein-1 in mesangial cells by lipopolysaccharide and cytokines.

Activator protein-1 (AP-1) plays an important role in the regulation of gene expression in mesangial cells (MC) during the pathogenesis of glomerular inflammatory disease. The precise regulation of the AP-1 family by agents that are known to activate MC is, however, poorly understood. The action of platelet-derived growth factor (PDGF) and, for the first time, lipopolysaccharide (LPS), interleukin-6 (IL-6), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) on AP-1 gene expression in MC was therefore studied. Whilst the expression of JunD was not affected by any of the mediators, the mRNA levels of c-fos and JunB were induced by LPS, IL-6, IFN-gamma, PDGF and TNF-alpha, and that of c-jun by LPS, IFN-gamma, PDGF and TNF-alpha. Electrophoretic mobility shift assays showed a time-dependent increase in AP-1 DNA binding activity with JunB representing the major mediator-inducible member involved in DNA-protein interactions. However, stimulus-specific changes in the kinetics and magnitude of AP-1 mRNA expression and DNA binding activity were identified and, additionally, the results showed the potential existence of cell-type-specific mechanisms in the regulation of the AP-1 family. These studies provide novel insights into the mediator-specific modulation of AP-1-regulated gene expression and the activation of MC in renal diseases.

Stimulus- and cell-type-specific regulation of CCAAT-enhancer binding protein isoforms in glomerular mesangial cells by lipopolysaccharide and cytokines.

Binding sites for the CCAAT-enhancer binding protein (C/EBP) family are present in the promoter regions of several genes that are known to be expressed by mesangial cells (MC) during the pathogenesis of glomerular inflammatory diseases. The precise regulation of the C/EBP family by agents that are known to activate MC is, however, poorly understood. We report here the action of interleukin-1 (IL)-1 and, for the first time, lipopolysaccharide (LPS), platelet-derived growth factor (PDGF), IL-6, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) on the C/EBP expression profile and functional DNA binding activity in primary rat MC. Both cell-type- and stimulus-specific regulation of C/EBP mRNA expression and DNA binding activity were identified, with C/EBPalpha being induced by LPS, C/EBPbeta by LPS, IL-1, TNF-alpha and C/EBPdelta by LPS, IL-1, IFN-gamma, TNF-alpha and PDGF. Such differential regulation, particularly that of C/EBPbeta, may be responsible for the mediator-specific differences in the expression of C/EBP-regulated genes in MC. Additionally, the involvement of potential post-transcriptional mechanisms in the regulation of C/EBPdelta were identified. These studies provide novel insights into the stimulus-specific regulation of gene expression during renal diseases.

Downregulation of TGF-beta1 mRNA and protein in the muscles of patients with inflammatory myopathies after treatment with high-dose intravenous immunoglobulin.

We used reverse transcription-polymerase chain reaction to study the level of TGF-beta1 mRNA expression and immunocytochemistry to examine the immunoreactive TGF-beta1 in muscle biopsy specimens from five patients with dermatomyositis (DM) and five patients with inclusion body myositis (IBM) obtained before and after 3 months treatment with intravenous immunoglobulin (IVIg). At baseline, the mRNA expression of TGF-beta1 was increased up to fivefold in the muscles of DM patients compared to that of IBM patients. After IVIg, TGF-beta1 was downregulated and the TGF-beta1 mRNA decreased twofold in the muscles of patients with DM who had successfully responded to therapy, but remained unchanged in the muscles of patients with IBM who did not respond. The downregulation of TGF-beta1 in DM was associated with improvement of the muscle cytoarchitecture and reduction of the endomysial inflammation and connective tissue, suggesting that in DM the excess of TGF-beta1 may be involved in the pathogenesis of chronic inflammation, fibrosis, and accumulation of extracellular matrix proteins.

Teenage parent programs. A synthesis of the long-term effects of the New Chance Demonstration, Ohio's Learning, Earning, and Parenting Program, and the Teenage Parent Demonstration.

This article synthesizes the long-term findings from three major evaluations of programs that began in the late 1980s and were designed to improve the self-sufficiency of teenage mothers on welfare. Although each of the programs emphasized a different approach, an important story emerges. Economic outcomes for the mothers improved over time, and the interventions had some positive effects, particularly for the women who began these programs while they were enrolled is school. However, the interventions did not affect fertility, and the data on outcomes for the mothers' children raise concern.

A distinct member of the aspartic proteinase gene family from the human malaria parasite Plasmodium falciparum.

A gene (hap) transcribed during the intra-erythrocytic life cycle stages of the human malaria parasite Plasmodium falciparum was cloned and sequenced. It was found to encode a protein belonging to the aspartic proteinase family but which carried replacements of catalytically crucial residues in the hallmark sequences contributing to the active site of this type of proteinase. Consideration is given as to whether this protein is the first known parasite equivalent of the pregnancy-associated glycoproteins that have been documented in ungulate mammals. Alternatively, it may be operative as a new type of proteinase with a distinct catalytic mechanism. In this event, since no counterpart is known to exist in humans, it affords an attractive potential target against which to develop new anti-malarial drugs.

The effects of retroperitoneal carbon dioxide insufflation on hemodynamics and arterial carbon dioxide.

BACKGROUND: Laparoscopic techniques are being increasingly used for retroperitoneal surgery. However, hemodynamic and ventilatory efforts of retroperitoneal carbon dioxide (CO2) insufflation have not been studied. We hypothesized that differences in absorptive surface, anatomy, and compartment compliance could result in different hemodynamic and ventilatory effects between retroperitoneal and intraperitoneal insufflation. METHODS: Pigs (n = 7) were anesthetized and stabilized. The peritoneal cavity was incrementally insufflated with CO2 to a maximum pressure of 25 cm H2O and the gas released. Hemodynamics and arterial blood gas values were recorded initially, at each level of insufflation, and following the pneumoperitoneum release until baseline values were reached. This insufflation protocol was repeated in the retroperitoneum. RESULTS: Mean arterial pressure (111 mm Hg, 95% confidence interval 99 to 156) and cardiac output (3.7 L/min, 2.8 to 5.2) did not change with increasing insufflation pressure of either intraperitoneum or retroperitoneum. PaCO2 was directly related to insufflation pressure in both spaces, increasing from 41.2 mm Hg (37.3 to 43.4) at baseline to 57.7 mm Hg (47.6 to 82.1) at insufflation pressure of 25 cm H2O. After release of the insufflation gas, time to return to baseline PaCO2 was slightly less from the retroperitoneal space (73 minutes, 45 to 105) than the intraperitoneal (107 minutes, 35 to 175). CONCLUSIONS: The effects of CO2 insufflation on hemodynamics and PaCO2 are the same in the retroperitoneal and intraperitoneal spaces.

Regulation of arousal and attention in preschool children exposed to cocaine prenatally.

Four lines of evidence suggest a plausible link between prenatal cocaine exposure (CE) and specific effects on the mechanisms subserving arousal and attention regulation in infants and preschool-aged children. These are (1) the association of prenatal CE with alterations in monoaminergic system ontogeny; (2) neurobehavioral effects of prenatal CE in animals consistent with an enduring increased level of activity in response to novelty and inhibited exploration and altered responses to stress, suggesting overarousal in the face of novel/stressful situations and disrupted attention and exploration; (3) altered norepinephrine system function in cocaine-exposed human infants; and (4) neurobehavioral findings in infants and preschool-aged children suggestive of disrupted arousal regulation in the face of novelty, increased distractibility, and consequent impaired attention to novel, structured tasks. This paper summarizes findings on response to novel challenges from a cohort of prenatally cocaine-exposed infants and preschool-aged children followed longitudinally since birth. Arousal regulation in the face of novel challenges is operationalized behaviorally as state and emotional reactivity and neurophysiologically as the startle response and heart rate variability. Across different ages and tasks, behavioral and neurophysiological findings suggest that prenatally cocaine-exposed children are more likely to exhibit disrupted arousal regulation. Because the regulation of arousal serves as a gating mechanism to optimize orientation and attention, arousal regulation has important implications for ongoing information processing, learning, and memory. Furthermore, impaired arousal regulation predisposes children to a lower threshold for activation of "stress circuits" and may increase their vulnerability to the developmentally detrimental effects of stressful conditions particularly when such children are also exposed to the chaotic environmental conditions often characterizing substance-abusing families.