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The left atrial septal pouch (LASP) occurs due to incomplete fusion of septa primum and secundum at the inter-atrial septum, creating an open flap that may serve as a thromboembolic source. Prior studies have demonstrated increased prevalence of LASP in cryptogenic strokes. The aim of the current study was to validate the above findings in a separate, larger group of stroke and non-stroke patients. We examined transesophageal echocardiograms (TEEs) performed between July 2011 and December 2018. LASP prevalence was determined in TEEs referred for ischemic stroke or transient ischemic attack ("stroke") and compared with LASP prevalence in patients undergoing TEEs for other reasons ("non-stroke"). Stroke subtyping was performed using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. There were 306 TEEs from 144 non-stroke and 162 stroke patients. Mean age and sex distribution were 56 ± 1 (mean ± SE) and 65% male in the non-stroke group and 58 ± 1 and 54% male in the stroke group. The overall prevalence of LASP was 31%. The prevalence of LASP was 28% (41/144) in non-stroke patients, 25% (24/95) in non-cryptogenic stroke patients, and 43% (29/67) in cryptogenic stroke patients. LASP prevalence was significantly higher in the cryptogenic subgroup compared with the non-cryptogenic subgroup (p = 0.02). These findings demonstrate a significant association of LASP with risk of cryptogenic stroke, suggesting that LASP may serve as a thromboembolic nidus. Additional studies are needed to determine the generalizability of these findings, and their therapeutic implications, supporting LASP as a stroke risk factor.

Objective: The preventability of strokes treated by mechanical thrombectomy is unknown. The purpose of this study was to analyze stroke preventability for patients treated with mechanical thrombectomy for large vessel occlusion. Methods: We conducted retrospective analyses of 300 patients (mean ± SE age 69 ± 0.9 years, range 18-97 years; 53% male) treated with mechanical thrombectomy for large vessel occlusion from January 2008 to March 2019. We collected data including demographics, NIH Stroke Scale (NIHSS) at onset, and (beginning in 2015) classified 90-day outcome by modified Rankin Scale (mRS). Patients were evaluated using a Stroke Preventability Score (SPS, 0 to 10 points) based on how well patients had been treated given their hypertension, hyperlipidemia, atrial fibrillation, and prior stroke history. We examined the relationship of SPS with NIHSS at stroke onset and with mRS outcome at 90 days. Results: SPS was calculated for 272 of the 300 patients, with mean ± SE of 2.1 ± 0.1 (range 0-8); 89 (33%) had no preventability (score 0), 120 (44%) had low preventability (score 1-3), and 63 (23%) had high preventability (score 4 or higher). SPS was significantly correlated with age (r = 0.32, p < 0.0001), while NIHSS (n = 267) was significantly higher (p = 0.03) for patients with high stroke preventability vs. low/no preventability [18.8 ± 0.92 (n = 62) vs. 16.5 ± 0.51 (n = 205)]. Among 118 patients with mRS, outcome was significantly worse (p = 0.04) in patients with high stroke preventability vs. low/no preventability [4.7 ± 0.29 (n = 28) vs. 3.8 ± 0.21 (n = 90)]. The vast majority of patients with high stroke preventability had inadequately treated atrial fibrillation (85%, 53/62). Conclusions: Nearly one quarter of stroke patients undergoing mechanical thrombectomy had highly preventable strokes. While stroke preventability showed some relationship to stroke severity at onset and outcome after treatment, preventability had the strongest association with age. These findings emphasize the need for improved stroke prevention in the elderly.

Cerebral microbleeds (CMB) are a common MRI finding, representing underlying cerebral microhemorrhages (CMH). The etiology of CMB and microhemorrhages is obscure. We conducted a pathological investigation of CMH, combining standard and immunohistological analyses of postmortem human brains. We analyzed 5 brain regions (middle frontal gyrus, occipital pole, rostral cingulate cortex, caudal cingulate cortex, and basal ganglia) of 76 brain bank subjects (mean age ± SE 90 ± 1.4 years). Prussian blue positivity, used as an index of CMH, was subjected to quantitative analysis for all 5 brain regions. Brains from the top and bottom quartiles (n = 19 each) were compared for quantitative immunohistological findings of smooth muscle actin, claudin-5, and fibrinogen, and for Sclerosis Index (SI) (a measure of arteriolar remodeling). Brains in the top quartile (i.e. with most extensive CMH) had significantly higher SI in the 5 brain regions combined (0.379 ± 0.007 vs 0.355 ± 0.008; p

Brain microbleeds are increased in chronic kidney disease (CKD) and their presence increases risk of cognitive decline and stroke. We examined the interaction between CKD and brain microhemorrhages (the neuropathological substrate of microbleeds) in mouse and cell culture models and studied progression of microbleed burden on serial brain imaging from humans. Mouse studies: Two CKD models were investigated: adenine-induced tubulointerstitial nephritis and surgical 5/6 nephrectomy. Cell culture studies: bEnd.3 mouse brain endothelial cells were grown to confluence, and monolayer integrity was measured after exposure to 5-15% human uremic serum or increasing concentrations of urea. Human studies: Progression of brain microbleeds was evaluated on serial MRI from control, pre-dialysis CKD, and dialysis patients. Microhemorrhages were increased 2-2.5-fold in mice with CKD independent of higher blood pressure in the 5/6 nephrectomy model. IgG staining was increased in CKD animals, consistent with increased blood-brain barrier permeability. Incubation of bEnd.3 cells with uremic serum or elevated urea produced a dose-dependent drop in trans-endothelial electrical resistance. Elevated urea induced actin cytoskeleton derangements and decreased claudin-5 expression. In human subjects, prevalence of microbleeds was 50% in both CKD cohorts compared with 10% in age-matched controls. More patients in the dialysis cohort had increased microbleeds on follow-up MRI after 1.5 years. CKD disrupts the blood-brain barrier and increases brain microhemorrhages in mice and microbleeds in humans. Elevated urea alters the actin cytoskeleton and tight junction proteins in cultured endothelial cells, suggesting that these mechanisms explain (at least in part) the microhemorrhages and microbleeds observed in the animal and human studies.

The objective of this study is to assess the effectiveness of a stroke clinic in stroke prevention and progression of cerebral microbleeds (CMB). We conducted a retrospective observational study of patients who visited a stroke clinic between January 2011 and March 2017. Susceptibility-weighted imaging (SWI) MRI studies were obtained at baseline and follow-up visits to identify new infarctions and CMB progression. Patients with CMB who also underwent brain computed tomography (CT) imaging were identified and their cerebral arterial calcification was quantified to evaluate the relationship between the extent of intracranial calcification and CMB burden. A total of 64 stroke patients (mean age 73.1 ± 11.0, 47% males) had CMB on baseline and follow-up MRI studies. During a mean follow-up period of 22.6 months, four strokes occurred (4/64, 6%; 3 ischemic, 1 hemorrhagic), producing mild neurological deficit. Progression of CMB was observed in 54% of patients with two MRIs and was significantly associated with length of follow-up. Subjects with intracranial calcification score > 300 cm3 had higher CMB count than those with scores

The objective of this study is to assess the effectiveness of a stroke clinic in stroke prevention and progression of cerebral microbleeds (CMB). We conducted a retrospective observational study of patients who visited a stroke clinic between January 2011 and March 2017. Susceptibility-weighted imaging (SWI) MRI studies were obtained at baseline and follow-up visits to identify new infarctions and CMB progression. Patients with CMB who also underwent brain computed tomography (CT) imaging were identified and their cerebral arterial calcification was quantified to evaluate the relationship between the extent of intracranial calcification and CMB burden. A total of 64 stroke patients (mean age 73.1 ± 11.0, 47% males) had CMB on baseline and follow-up MRI studies. During a mean follow-up period of 22.6 months, four strokes occurred (4/64, 6%; 3 ischemic, 1 hemorrhagic), producing mild neurological deficit. Progression of CMB was observed in 54% of patients with two MRIs and was significantly associated with length of follow-up. Subjects with intracranial calcification score > 300 cm3 had higher CMB count than those with scores

Oral anticoagulants are a critical component of stroke prevention, but carry a risk of brain hemorrhage. These hemorrhagic complications tend to occur in elderly individuals, especially those with predisposing conditions such as cerebral amyloid angiopathy (CAA). Clinical evidence suggests that non-vitamin K antagonist oral anticoagulants are safer than traditional oral anticoagulants. We analyzed whether the anticoagulant dabigatran produces cerebral microhemorrhage (the pathological substrate of MRI-demonstrable cerebral microbleeds) or intracerebral hemorrhage in aged mice with and without hemorrhage-predisposing angiopathy. We studied aged (22 months old) Tg2576 (a model of CAA) and wild-type (WT) littermate mice. Mice received either dabigatran etexilate (DE) (Tg N = 7; WT N = 10) or vehicle (Tg N = 9; WT N = 7) by gavage for 4 weeks. Anticoagulation effects of DE were confirmed using thrombin time assay. No mice experienced intracerebral hemorrhage. Cerebral microhemorrhage analysis, performed using Prussian-blue and H&E staining, showed no significant change in either number or size of cerebral microhemorrhage in DE-treated animals. Analysis of biochemical parameters for endothelial activation (ICAM-1), blood-brain barrier disruption (IgG, claudin-5, fibrinogen), microglial activation (Iba-1), or astrocyte activation (GFAP) showed neither exacerbation nor protective effects of DE in either Tg2576 or WT mice. Our study provides histological and biochemical evidence that aged mice, with or without predisposing factors for brain hemorrhage, tolerate anticoagulation with dabigatran. The absence of dabigatran-induced intracerebral hemorrhage or increased frequency of acute microhemorrhage may provide some reassurance for its use in high-risk patient populations.

Purpose: To analyze the relationship between blood pressure (BP) variables, including circadian pattern, and cognition in 90+ year-olds. Methods: Twenty-four hour ambulatory BP monitoring was completed on 121 participants drawn from a longitudinal study of aging and dementia in the oldest-old. Various measures of BP and its variability, including nocturnal dipping, were calculated. Each person was given both a neuropsychological test battery covering different cognitive domains and a neurological examination to determine cognitive status. Seventy-one participants had a brain magnetic resonance imaging (MRI) scan. Results: Participants ranged in age from 90 to 102 years (mean = 93), about two-thirds were female, and nearly 80% had at least some college education. Mean nocturnal dips differed significantly between cognitively normal (n = 97) and impaired individuals (n = 24), with cognitively normal participants having on average greater nocturnal dips [6.6% vs. 1.3%, p = 0.006 for systolic BP (SBP); 11% vs. 4.4%, p = 0.002 for diastolic BP (DBP)]. Nocturnal dips were also related to performance on select cognitive test scores (especially those related to language, recent memory and visual-spatial ability), with individuals who performed below previously established median norms having significantly smaller nocturnal dips (both SBP and DBP) than those above the median. DBP reverse dippers had larger mean white matter hyperintensities (WMH as percent of total brain volume; 1.7% vs. 1.2%, 1.1% and 1.0% in extreme dippers, dippers, non-dippers) and a greater proportion had lobar cerebral microbleeds (CMBs; 44% vs. 0%, 7%, 16%, p < 0.05). Impaired participants had higher mean WMH than those with normal cognition (1.6% vs. 1.0% p = 0.03) and more tended to have CMB (31% vs. 20%, p = n.s.). Conclusion: These findings suggest that cognitive dysfunction is associated with dysregulation in the normal circadian BP pattern. Further study is warranted of the potential role of WHM and CMB as mediators of this association.

BACKGROUND:Cerebral microhemorrhages (CMH) are commonly found in the aging brain. CMH are also the neuropathological substrate of cerebral microbleeds (CMB), demonstrated on brain MRI. Recent studies demonstrate the importance of systemic inflammation in CMH development, but the relationships among inflammation, aging, and CMH development are not well-defined. In the current study, we hypothesized that the pathogenesis of inflammation-induced CMH in mice differs by age. METHODS:We studied young (3 months, n = 20) and old (18 months, n = 25) C57BL/6 mice injected with low-dose lipopolysaccharide (LPS; 1 mg/kg, i.p.) or saline at 0, 6, and 24 h. Seven days after the first LPS/saline injection, brains were harvested, sectioned, and stained with hematoxylin and eosin (H&E) and Prussian blue (PB) to estimate acute/fresh and sub-acute CMH development, respectively. The relationships between microglial/macrophage activation (ionized calcium-binding adapter molecule-1), astrocyte activation (glial fibrillary acidic protein), blood-brain barrier (BBB) disruption (brain immunoglobulin G), aging, and CMH development were examined using immunohistochemistry. RESULTS:Aging alone did not increase spontaneous H&E-positive CMH development but significantly increased the number, size, and total area of LPS-induced H&E-positive CMH in mice. LPS- and saline-treated aged mice had significantly larger PB-positive CMH compared with young mice, but the total area of PB-positive CMH was increased only in LPS-treated aged mice. Aged mice had significantly increased microglial/macrophage activation, which correlated with H&E- and PB-positive CMH development. Aged mice treated with LPS had significantly increased astrocyte activation and BBB disruption compared with young LPS-treated mice. CONCLUSIONS:Aging makes the brain more susceptible to inflammation-induced CMH in mice, and this increase in CMH with aging is associated with microglial/macrophage activation.

BackgroundCerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic cause of stroke. In addition to ischemic stroke, CADASIL predisposes to development of cerebral microbleeds (CMB). CMB and hypertension are known to be associated with intracerebral hemorrhage (ICH). The purpose of this study was to analyze the relationships among CMB, hypertension, and ICH in CADASIL.Materials and methodsWe enrolled 94 genetically confirmed CADASIL patients from 76 unrelated families at Jeju National University Hospital (Korea) between March 2012 and February 2015. We analyzed CMB presence, number, and distribution on susceptibility-weighted imaging MRI using the microbleed anatomical rating scale. Multiple logistic regression was used to determine factors associated with the presence of CMB and ICH.ResultsCMB were observed in 62 patients (66%), median number of CMB per patient was 4 (range 0-121). Twenty-two ICHs were found in 16 patients (17%). There was incongruence between the most common site of CMB (thalamus) and that of ICH (basal ganglia). Hypertension was independently associated with the presence of CMB (multiple regression OR, 2.71; 95% CI 1.02-7.18, p

BackgroundAnterior and posterior circulation atherosclerosis differ in vascular risk factors and stroke mechanisms. However, few studies have compared the pathological features between these lesions. Using a series of intracranial artery specimens, we characterized the intracranial atherosclerotic lesions and compared pathological features among different arteries of the intracranial vasculature.MethodsIntracranial large arteries of 32 consecutively recruited autopsy cases of Chinese adults aged 45 years or older were examined pathologically using routine histology and immunostaining, to characterize the pathological features of the atherosclerotic lesions. We analyzed middle cerebral arteries (MCAs) (both left and right), vertebral arteries (VAs) (side more affected), and basilar arteries (BAs).ResultsProgressive atherosclerotic lesions were present in 91(71%) of the 128 arteries examined. Features of complicated plaques were infrequently detected: plaque hemorrhage was encountered in 12%, neovasculature in 12%, lumen thrombi in 13%, macrophage infiltration in 20%, and calcification in 25% of arteries. Luminal narrowing of MCA was the most severe, followed by VA; the BA least stenotic (37 ± 25 vs. 30 ± 24 vs. 20 ± 20%, all p

BackgroundCerebral microhemorrhages (CMH) are tiny deposits of blood degradation products in the brain and are pathological substrates of cerebral microbleeds. The existing CMH animal models are β-amyloid-, hypoxic brain injury-, or hypertension-induced. Recent evidence shows that CMH develop independently of hypoxic brain injury, hypertension, or amyloid deposition and CMH are associated with normal aging, sepsis, and neurodegenerative conditions. One common factor among the above pathologies is inflammation, and recent clinical studies show a link between systemic inflammation and CMH. Hence, we hypothesize that inflammation induces CMH development and thus, lipopolysaccharide (LPS)-induced CMH may be an appropriate model to study cerebral microbleeds.MethodsAdult C57BL/6 mice were injected with LPS (3 or 1 mg/kg, i.p.) or saline at 0, 6, and 24 h. At 2 or 7 days after the first injection, brains were harvested. Hematoxylin and eosin (H&E) and Prussian blue (PB) were used to stain fresh (acute) hemorrhages and hemosiderin (sub-acute) hemorrhages, respectively. Brain tissue ICAM-1, IgG, Iba1, and GFAP immunohistochemistry were used to examine endothelium activation, blood-brain barrier (BBB) disruption, and neuroinflammation. MRI and fluorescence microscopy were used to further confirm CMH development in this model.ResultsLPS-treated mice developed H&E-positive (at 2 days) and PB-positive (at 7 days) CMH. No surface and negligible H&E-positive CMH were observed in saline-treated mice (n = 12). LPS (3 mg/kg; n = 10) produced significantly higher number, size, and area of H&E-positive CMH at 2 days. LPS (1 mg/kg; n = 9) produced robust development of PB-positive CMH at 7 days, with significantly higher number and area compared with saline (n = 9)-treated mice. CMH showed the highest distribution in the cerebellum followed by the sub-cortex and cortex. LPS-induced CMH were predominantly adjacent to cerebral capillaries, and CMH load was associated with indices of brain endothelium activation, BBB disruption, and neuroinflammation. Fluorescence microscopy confirmed the extravasation of red blood cells into the brain parenchyma, and MRI demonstrated the presence of cerebral microbleeds.ConclusionsLPS produced rapid and robust development of H&E-positive (at 2 days) and PB-positive (at 7 days) CMH. The ease of development of both H&E- and PB-positive CMH makes the LPS-induced mouse model suitable to study inflammation-induced CMH.

Psychiatric staff are faced with multiple forms of hostility, aggression, and assault at work, collectively referred to as workplace violence, which typically is activated by patients but can also come from coworkers and supervisors. Whether workplace violence adversely affects staff well-being may be related not only to its presence, but also to an individual's stress reactivity. At a large public psychiatric hospital, an online survey was completed by 323 clinical care staff, of whom 69.5 % had experienced physical assault in the previous 12 months. Staff well-being (depression, anger, and physical health) and staff safety concerns were adversely affected by conflicts with other staff members and by individual reactivity to social conflict and to assault. To improve staff well-being, in addition to safety protocols, interventions should target staff relationships, personal health maintenance practices, and individual coping skills for dealing with adverse workplace experiences.

The left atrial septal pouch (LASP) occurs due to incomplete fusion of septa primum and secundum at the inter-atrial septum, creating an open flap that may serve as a thromboembolic source. Prior studies have demonstrated increased prevalence of LASP in cryptogenic strokes. The aim of the current study was to validate the above findings in a separate, larger group of stroke and non-stroke patients. We examined transesophageal echocardiograms (TEEs) performed between July 2011 and December 2018. LASP prevalence was determined in TEEs referred for ischemic stroke or transient ischemic attack ("stroke") and compared with LASP prevalence in patients undergoing TEEs for other reasons ("non-stroke"). Stroke subtyping was performed using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. There were 306 TEEs from 144 non-stroke and 162 stroke patients. Mean age and sex distribution were 56 ± 1 (mean ± SE) and 65% male in the non-stroke group and 58 ± 1 and 54% male in the stroke group. The overall prevalence of LASP was 31%. The prevalence of LASP was 28% (41/144) in non-stroke patients, 25% (24/95) in non-cryptogenic stroke patients, and 43% (29/67) in cryptogenic stroke patients. LASP prevalence was significantly higher in the cryptogenic subgroup compared with the non-cryptogenic subgroup (p = 0.02). These findings demonstrate a significant association of LASP with risk of cryptogenic stroke, suggesting that LASP may serve as a thromboembolic nidus. Additional studies are needed to determine the generalizability of these findings, and their therapeutic implications, supporting LASP as a stroke risk factor.

In the real world, decision making processes must be able to integrate non-stationary information that changes systematically while the decision is in progress. Although theories of decision making have traditionally been applied to paradigms with stationary information, non-stationary stimuli are now of increasing theoretical interest. We use a random-dot motion paradigm along with cognitive modeling to investigate how the decision process is updated when a stimulus changes. Participants viewed a cloud of moving dots, where the motion switched directions midway through some trials, and were asked to determine the direction of motion. Behavioral results revealed a strong delay effect: after presentation of the initial motion direction there is a substantial time delay before the changed motion information is integrated into the decision process. To further investigate the underlying changes in the decision process, we developed a Piecewise Linear Ballistic Accumulator model (PLBA). The PLBA is efficient to simulate, enabling it to be fit to participant choice and response-time distribution data in a hierarchal modeling framework using a non-parametric approximate Bayesian algorithm. Consistent with behavioral results, PLBA fits confirmed the presence of a long delay between presentation and integration of new stimulus information, but did not support increased response caution in reaction to the change. We also found the decision process was not veridical, as symmetric stimulus change had an asymmetric effect on the rate of evidence accumulation. Thus, the perceptual decision process was slow to react to, and underestimated, new contrary motion information.

ImportanceAlthough patients with acute stroke are routinely evaluated for potential treatment (ie, treatability of the stroke), preventability of the presenting stroke is generally not seriously considered.ObjectiveTo systematically analyze stroke preventability.Design, setting, and participantsWe evaluated medical records of 274 consecutive patients discharged with a diagnosis of ischemic stroke between December 2, 2010, and June 11, 2012, at the University of California Irvine Medical Center. Mean (SE) patient age was 67.2 (0.8) years. Data analysis was conducted from July 3, 2014, to August 4, 2015.ExposuresMedical records were systematically examined for demographic information, stroke risk factors, stroke severity, and acute stroke treatment.Main outcomes and measuresWe defined stroke preventability as the degree to which the patient's presenting stroke was preventable. Using variables easily determined at onset of stroke, we developed a 10-point scale (0, not preventable; 10, most preventable) to classify the degree of stroke preventability. Our focus was effectiveness of treatment of hypertension (0-2 points), hyperlipidemia (0-2 points), and atrial fibrillation (0-4 points), as well as use of antithrombotic treatment for known prior cerebrovascular and cardiovascular disease (0-2 points).ResultsTotal risk scores ranged from 0 to 8 (mean [SE], 2.2 [0.1]), with 207 patients (75.5%) exhibiting some degree of preventability (score of 1 or higher). Seventy-one patients (25.9%) had scores of 4 or higher, indicating that the stroke was highly preventable. Severity of stroke as determined by the National Institutes of Health Stroke Scale score was not related to preventability of stroke. However, 21 of 71 patients (29.6%) whose stroke was highly preventable were treated with intravenous or intra-arterial acute stroke therapy while these treatments were provided for only 13 of 67 patients (19.4%) with scores of 0 (no preventability) and 19 of 136 patients (14.0%) with scores of 1 to 3 (low preventability) (P = .03).Conclusions and relevanceMost patients with acute stroke exhibited some degree of preventability. Preventability and treatment of stroke were significantly associated, indicating that the most preventable strokes paradoxically were more likely to receive acute treatment.

Perceived racial discrimination (PRD) has been associated with altered diurnal cortisol rhythms in past cross-sectional research. We investigate whether developmental histories of PRD, assessed prospectively, are associated with adult diurnal cortisol profiles. One-hundred and twelve (N=50 Black, N=62 White) adults from the Maryland Adolescent Development in Context Study provided saliva samples in adulthood (at approximately age 32 years) at waking, 30min after waking, and at bedtime for 7 days. Diurnal cortisol measures were calculated, including waking cortisol levels, diurnal cortisol slopes, the cortisol awakening response (CAR), and average daily cortisol (AUC). These cortisol outcomes were predicted from measures of PRD obtained over a 20-year period beginning when individuals were in 7th grade (approximately age 12). Greater average PRD measured across the 20-year period predicted flatter adult diurnal cortisol slopes for both Black and White adults, and a lower CAR. Greater average PRD also predicted lower waking cortisol for Black, but not White adults. PRD experiences in adolescence accounted for many of these effects. When adolescent and young adult PRD are entered together predicting cortisol outcomes, PRD experiences in adolescence (but not young adulthood) significantly predicted flatter diurnal cortisol slopes for both Black and White adults. Adolescent, but not young adult PRD, also significantly predicted lower waking and lower average cortisol for Black adults. Young adult PRD was, however, a stronger predictor of the CAR, predicting a marginally lower CAR for Whites, and a significantly larger CAR for Blacks. Effects were robust to controlling for covariates including health behaviors, depression, income and parent education levels. PRD experiences interacted with parent education and income to predict aspects of the diurnal cortisol rhythm. Although these results suggest PRD influences on cortisol for both Blacks and Whites, the key findings suggest that the effects are more pervasive for Blacks, affecting multiple aspects of the cortisol diurnal rhythm. In addition, adolescence is a more sensitive developmental period than adulthood for the impacts of PRD on adult stress biology.

High school students with high long-term educational expectations attain higher levels of education than those with lower expectations. Less studied is the role of students' short-term college enrollment expectations for the year after high school graduation. The purpose of the current study was to examine the costs and benefits of ambitious short-term expectations and the impact of falling short of these expectations on mental health, motivation, and educational outcomes. Over 1000 youth with expectations to attend college were surveyed during their senior year of high school, one year later, and four years later. Participants who did not achieve their short-term expectations had lower educational attainment four years later but were not less satisfied with their educational progress. The negative consequences of falling short of one's expectations were restricted to individuals with less ambitious short-term expectations. Thus, the benefits of ambitious short-term expectations for youth may outweigh the costs.

Demonstrations of a link between genetic variants and criminal behavior have stimulated increasing use of genetic evidence to reduce perceptions of defendants' responsibility for criminal behavior and to mitigate punishment. However, because only limited data exist regarding the impact of such evidence on decision makers and the public at large, we recruited a representative sample of the U.S. adult population (n=960) for a web-based survey. Participants were presented with descriptions of three legal cases and were asked to: determine the length of incarceration for a convicted murderer; adjudicate an insanity defense; and decide whether a defendant should receive the death penalty. A fully crossed, between-participants, factorial design was used, varying the type of evidence (none, genetic, neuroimaging, both), heinousness of the crime, and past criminal record, with sentence or verdict as the primary outcome. Also assessed were participants' apprehension of the defendant, belief in free will, political ideology, and genetic knowledge. Across all three cases, genetic evidence had no significant effects on outcomes. Neuroimaging data showed an inconsistent effect in one of the two cases in which it was introduced. In contrast, heinousness of the offense and past criminal record were strongly related to participants' decisions. Moreover, participants' beliefs about the controllability of criminal behavior and political orientations were significantly associated with their choices. Our findings suggest that neither hopes that genetic evidence will modify judgments of culpability and punishment nor fears about the impact of genetic evidence on decision makers are likely to come to fruition.

The association between posttraumatic stress disorder (PTSD) symptoms and suicide ideation was examined in a sample of 2,298 child survivors of the Wenchuan earthquake. Results indicated that intrusion, avoidance, hyperarousal symptom clusters, and PTSD total score were significantly associated with suicide ideation. Except for intrusion, other measures of PTSD remained as statistically significant correlates of suicide ideation even after controlling for age, gender, direct exposure, indirect exposure, and depression. Furthermore, results showed that PTSD symptoms had an indirect influence on suicide ideation that was mediated by depression. The findings suggest that avoidance and hyperarousal symptom clusters of PTSD may be two important indicators of suicide ideation among child survivors of the Wenchuan earthquake. Implications of the results for intervention and prevention of suicide behavior are discussed.

Problematic sleep can be detrimental to the development of important cognitive functions, such as working memory, and may have the potential for negative behavioral consequences, such as risk-taking. In this way, sleep problems may be particularly harmful for youth-whose cognitive abilities are still developing and who are more susceptible to risky behavior. Using data from a large, national, longitudinal study, continuity and change in sleep problems were examined from 2 to 15 years of age and associated with deficits in working memory at age 15 and risk taking behaviors at age 18. Participants (N = 1,364 children; 48.3% female) were assessed for sleep problems (parent-report), working memory (behavioral task), and risk taking behavior (youth self-report). The sample was predominantly White (80.4%); additional races represented in the sample included Black/African American (12.9%), Asian/Pacific Islander (1.6%), American Indian/Eskimo/Aleut (.4%), and Other (4.7%). The findings suggest that sleep problems are likely to cascade across development, with sleep problems demonstrating continuity from infancy to early childhood, early childhood to middle childhood, and middle childhood to adolescence. Although sleep problems in infancy, early childhood, and middle childhood were not directly related to adolescent working memory, sleep problems during adolescence were associated with poorer adolescent working memory. In turn, these deficits in working memory were related to greater risk taking in late adolescence. In summary, the present results suggest that sleep problems in earlier periods are indicative of risk for sleep problems later in development, but that sleep problems in adolescence contribute uniquely to deficits in working memory that, in turn, lead to risky behavior during late adolescence.

Past research has shown that locus of control plays an important role in a wide range of behaviors, such as academic achievement and positive social behaviors. However, little is known about whether locus of control plays the same role in minority adolescents' peer relationships. The current study examined ethnic differences in the associations between locus of control and peer relationships in early adolescence using samples from the Early Childhood Longitudinal Study (ECLS-K: 5,612 Caucasian, 1,562 Hispanic, 507 Asian, and 908 African-American adolescents) and the National Education Longitudinal Study (NELS: 8,484 Caucasian, 1,604 Hispanic, and 860 Asian, and 1,228 African American adolescents). Gender was approximately evenly split in both samples. The results from the two datasets were highly consistent. Significant interactions between ethnicity and locus of control indicated that having a more internal locus of control was particularly important for Caucasian students' peer relationships (ECLS-K) and social status (NELS), but less so for Asian, Hispanic, and African American students. Our findings suggest that the role of locus of control in peer relationship is contingent upon culture.

BackgroundThe left atrial septal pouch (LASP), an anatomic variant of the interatrial septum, has uncertain clinical significance. We examined the association between LASP and ischemic stroke subtypes in patients undergoing transesophageal echocardiography (TEE).MethodsWe determined the prevalence of LASP among consecutive patients who underwent TEE at our institution. Patients identified with ischemic strokes were further evaluated for stroke subtype using standard and modified criteria from the Trial of Org 10172 in Acute Stroke Treatment (TOAST). We compared the prevalence of LASP in ischemic stroke, cryptogenic stroke, and non-stroke patients using prevalence ratios (PR).ResultsThe mean age of all 212 patients (including stroke and non-stroke patients) was 57 years. The overall prevalence of LASP was 17% (n = 35). Of the 75 patients who were worked-up for stroke at our institution during study period, we classified 31 as cryptogenic using standard TOAST criteria. The prevalence of LASP among cryptogenic stroke patients (using standard and modified TOAST criteria) was increased compared to the prevalence among other ischemic stroke patients (26 vs. 9%, p = 0.06; PR = 1.8, 95% CI = 1.1-3.1, and 30 vs. 10%, p = 0.04; PR = 2.2, 95% CI = 1.2-4.1, respectively).ConclusionIn this population of relatively young patients, prevalence of LASP was increased in cryptogenic stroke compared to stroke patients of other subtypes. These findings suggest LASP is associated with cryptogenic stroke, which should be verified by future large-scale studies.

Only 20-40% of U.S. women conduct breast self-examination (BSE). This Southwest Oncology Group experimental study compared the impact of three interventions on BSE compliance.Subjects were randomly assigned to one of three arms: (1) physician message; (2) physician message and BSE class; or (3) physician message, BSE class, and reinforcement (phone and postcard). Compliance (frequency and accuracy) was measured by interview at intake and at 6 months and by phone contact at 1 year. Logistic and multiple regression were employed.This analysis included 2,233 subjects from six institutions. At 1 year the percentages of women doing BSE were 59, 62, and 78% for Arms 1-3, respectively; gains over intake frequency (27% average) were significant within each arm (P < or = 0.0001). At both 6 months and 1 year the differences between Arm 1 and Arm 2 average accuracy scores and the differences between Arm 2 and Arm 3 in the percentage of women doing BSE were significant (P < or = 0.0001). Findings within institutions were consistent with the overall findings.The addition of a BSE class increased accuracy over physician message alone; physician message, BSE class, and reinforcement gave the highest percentage of women doing BSE.

It is essential to identify intermediate marker endpoints of carcinogenesis for the evaluation of the effectiveness of cancer-chemopreventive agents. We have observed that levels of proteolytic activities (as detected by 4 different substrates) are increased 2-3-fold (P < 0.003) in oral buccal mucosa cells of smokers and patients with oral leukoplakia or erythroplakia as compared to a nonsmoking comparison group. In addition, proteolytic activity levels in the buccal cells were increased nearly 3-fold in patients with oral trauma (P < 0.01) or diabetes (P < 0.02), as well as pregnant women (P < 0.04). Excluding these subgroups of patients in epidemiological studies increase the differences in levels of proteolytic activities between both the nonsmoking comparison group and smokers and between the comparison group and patients with oral leukoplakia or erythroplakia. Evaluation of prerandomization levels of proteolytic activities of patients in cancer chemoprevention trials will increase the statistical power by allowing stratified randomization based on levels of proteolytic activities. The observed increases in levels of proteolytic activities in tissues at higher than normal risk of cancer development suggest that levels of proteolytic activities should be used as immediate marker endpoints in human cancer prevention trials using protease inhibitors as potential anticarcinogenic agents.

In order to quantify the invasiveness of melanoma tumor cells in vitro, a modification of the amniotic basement membrane (BM) model, described by Liotta et al. (Cancer Letters, 11, 141, 1980), was used in combination with radiolabeled tumor cells. B16-F10 metastatic murine melanoma cells and a derived clone (B16-F10L) were prelabeled with 0.1 muCi/ml of [14C]thymidine for 20-24 h in serum-free medium at 37 degrees C. Following incubation, fetal bovine serum was added to a concentration of 5 per cent, and the cells were allowed to grow to confluency for the next 24-28 h. The labeled cells were seeded onto amniotic membranes situated in Membrane Invasion Culture System (MICS) chambers at a density of 2.5 X 10(4) per well. At various times points, radioactivity of tumor cells that completely traversed the membrane was determined using an under-the-membrane sampling method. The average percent invasion demonstrated by the B16-F10 line was 2.75 per cent, and 3.65 per cent exhibited by the B16-F10L cell line after 48-53 h in vitro. Since it was apparent that some variability in thickness existed among membrane samples, a morphological analysis was performed on five sectors of a three-inch-diameter sample from four different placentae. Differences and similarities in BM thickness within the same sector were noted by this technique and could possibly contribute to some variability observed in tumor cell invasion in this model. Another parameter examined was the proliferation of tumor cells in the upper and lower wells of the MICS chambers. By 48 h, approximately 32.1 per cent of the B16-F10 cell line as well as the clone had replicated in the upper wells associated with the BMs compared with a 32.9 per cent replication in the lower wells, which reaffirmed the viability of the tumor cells under experimental conditions and insured similarly replicating populations of cells. In order to quantify the invasiveness of radiolabeled tumor cells accurately through a biological membranous barrier, the proper concentration of cells must be used, tumor cell heterogeneity should be taken into consideration, the technique of sampling radiolabeled invasive cells should be critically analysed, and thickness of the membranous barrier should all be considered as possible important factors in the quantitative analyses.

Peers are a powerful socializing force, especially during adolescence. Whether peer status holds the same meaning, correlates, and consequences for female offenders remains unknown. Using a peer nomination technique in a sample of incarcerated females (N = 86, age 15-24 years), our study is the first to examine the association between peer status and psychopathology in a correctional facility. Results indicated that a key indicator of likeability was prosocial behavior; popularity was related to leadership; and social impact was associated with aggression. Popularity might serve as a buffer against, and social impact as a risk factor for, psychosocial problems. Findings shed light on peer status as a mechanism underpinning female offenders' problem behaviors and an entry point for targeted interventions.

Endometriosis is characterized by the presence of endometrial glands and stroma in extrauterine sites. Our objective was to determine whether endometriotic lesions (ELs) from women with endometriosis have altered retinoid levels compared with their eutopic endometrium, and to test the hypothesis that defects in all-trans retinoic acid (ATRA) biosynthesis in EL is related to reduced expression of cellular retinol-binding protein type 1 (RBP1). Retinoids were evaluated by liquid chromatography-tandem mass spectrometry and high-performance liquid chromatography in eutopic endometrial biopsies (EBs) and ELs from 42 patients with pathologically confirmed endometriosis. The ATRA levels were reduced, whereas the retinol and retinyl ester concentrations were elevated in EL compared with EB tissue. Similar results were found in a mouse model of endometriosis that used green fluorescent protein-positive endometrial tissue injected into the peritoneum of syngeneic hosts to mimic retrograde menses. The ATRA biosynthesis in vitro in retinol-treated primary human endometrial stromal cell (ESC) cultures derived from ELs was reduced compared with that of ESCs derived from patient-matched EBs. Correspondingly, RBP1 expression was reduced in tissue and ESCs derived from EL versus EB. Rbp1(-/-) mice showed reduced endometrial ATRA concentrations compared with wild type, associated with loss of tissue organization and hypercellularity. These findings provide the first quantitative measurements of ATRA in human endometrium and endometriosis, demonstrating reduced ATRA in ectopic tissue and corresponding ESC cultures. Quantitation of retinoids in murine endometriosis and in Rbp1(-/-) mice supports the contention that impaired ATRA synthesis caused by reduced RBP1 promotes an "endometriosis phenotype" that enables cells to implant and grow at ectopic sites.

Racial/ethnic (R/E) socialization is widely practiced in R/E minority families. However, only recently have models been developed to understand how parents' R/E socialization messages influence adolescent development. The primary goal of the present study was to clarify and extend existing work on R/E socialization in African American (Black) families by distinguishing between parent and youth reports of parents' R/E socialization messages and examining the extent to which adolescents and their parents agree about these socialization messages. In addition, we tested a theoretical model in which parent-reported R/E socialization messages have an indirect effect on the development of youth R/E identity through youth reports of their parents' R/E socialization messages. Using a combination of open- and close-ended data from a longitudinal study of self-identified Black adolescents and their parents, we found statistically significant parent-youth agreement about whether parents send both general R/E socialization messages and, for daughters, specific R/E socialization messages. R/E socialization messages focused on promoting cultural pride and history were associated positively with R/E identity development, whereas messages focused on preparing youth for discrimination tended to be unrelated to R/E identity development. The results largely supported the hypothesis that parent reports of parents' R/E socialization messages are related indirectly to the development of adolescent R/E identity via youth reports of parents' R/E socialization messages.

On the basis of large cardiovascular clinical trials of lipid-lowering agents that showed a considerable decrease in the incidence of primary melanomas in the active agent arm, we have carried out a randomized, double-blind clinical trial examining the impact of lovastatin on various biomarkers of melanoma pathogenesis. Subjects with at least two clinically atypical nevi were randomized to receive oral lovastatin or placebo for a 6-month period. Clinical, histopathologic, and molecular biomarkers were evaluated for change in the two groups. Eighty subjects were randomized, evaluable, and included in the analyses. Lovastatin showed no benefit in comparison with placebo in the primary endpoint of decreasing the level of histopathologic atypia, nor in any of the secondary endpoints of decreasing clinical atypia, impact on nevus number, nor in showing significant changes in any of the molecular biomarkers. There were no significant differences in adverse event profiles for lovastatin compared with placebo. The lovastatin arm did show a significant and considerable decrease in total serum cholesterol and serum low-density lipoprotein (LDL) levels compared with placebo, an expected result. This finding bolsters confidence in subject compliance. Given the results of this trial, it is concluded that if lovastatin were to lower the incidence of melanoma, it would appear not to be doing so by reversing atypia of precursor atypical nevi over the 6-month time frame studied. Further research into the pathogenesis of melanoma and in other potential chemopreventive agents is needed. ©2014 AACR.

The presence of callous-unemotional (CU) traits designates a subgroup of antisocial youth at risk for severe, aggressive, and stable conduct problems. As a result, these traits should be considered as part of the criteria for conduct disorder. The present study tests 2 possible symptom sets (4- and 9-item criteria sets) of CU traits that could be used in diagnostic classification, assessed using self-report with a sample of 643 incarcerated adolescent (M age = 16.50, SD = 1.63 years) boys (n = 493) and girls (n = 150). Item response theory analysis was employed to examine the unique characteristics of each criterion comprising the 2 sets to determine their clinical utility. Results indicated that most items comprising the measure of CU traits demonstrated adequate psychometric properties. Whereas the 9-item criteria set provided more information and was internally consistent, the briefer 4-item set was equally effective at identifying youth at-risk for poor outcomes associated with the broader CU construct. Supporting the clinical utility of the criteria sets, incarcerated boys and girls who endorsed high levels of CU symptoms across criteria sets were particularly at-risk for proactive aggression and violent delinquency.

The current study investigates how romantic relationships are related to antisocial behavior longitudinally among delinquent males and females (n=354; ages 14-25). While being in a relationship or not is unrelated to antisocial behavior, romantic partner characteristics (antisocial behavior and antisocial influence) are associated with greater antisocial behavior. As males age, they become increasingly resistant to romantic partner characteristics. In contrast, females become increasingly vulnerable to the effects of romantic partner characteristics on antisocial behavior as they age, particularly when these relationships are relatively shorter. Females in shorter romantic relationships with partners who are antisocial or exert antisocial influence are at risk of persisting in antisocial behavior.

This paper examined whether previously identified community-level factors (high proportion of crowded households and/or persons below the poverty level) remained associated with childhood pneumococcal carriage in the heptavalent pneumococcal conjugate vaccine (PCV7) era. Using logistic regression, individual factors were used to develop base models to which community-level factors were added to evaluate impact on pneumococcal carriage within two paediatric study cohorts from Massachusetts (urban Boston, outside Boston). Six years after introduction of universal childhood PCV7 vaccination, we found no consistent evidence that census tract characteristics (e.g. population size and density, age and race distribution, percent participating in group childcare, parental education, percent lacking in-unit plumbing, poverty, and community stability) affected odds of pneumococcal carriage when added to individual predictors (e.g. younger age, current respiratory tract infections, and attendance in group childcare). How community-level factors influence pneumococcal carriage continues to change in the era of increasing immunization coverage.

We surveyed administrators at 13 nursing homes in Orange County, CA, on their likelihood to admit methicillin-resistant Staphylococcus aureus (MRSA) carriers and assessed applicant characteristics associated with rejection. In multivariate models, denial of admission was associated with MRSA carriage (odds ratio, 2.7; P = .02) and receiving lower ratings for overall suitability for admission (odds ratio, 5.9; P < .001). Larger studies are needed to determine whether decolonization may remove barriers to accessing postdischarge care for MRSA carriers.

This study examined the relationships of trauma exposure and control beliefs with posttraumatic growth (PTG) in a sample of adolescent survivors of the Wenchuan earthquake (Time 1 n = 788, Time 2 n = 243). Results suggested that two aspects of exposure severity (indirect exposure and worry about others) had significantly positive associations with concurrently measured PTG, but only indirect exposure was significantly correlated with changes in PTG from Time 1 to Time 2. Primary and secondary control beliefs were also found to be significantly correlated with concurrently measured PTG, but only secondary control beliefs were significantly associated with changes in PTG. In addition, primary control beliefs moderated the association between worry about others and concurrently measured PTG as well as changes in PTG. These results are discussed in terms of their implications for psychological service providers to adolescents who have had traumatic experiences. © 2013 American Psychological Association.

Resveratrol, a natural polyphenol found in grapes, berries and other plants, has been proposed as an ideal chemopreventative agent due to its plethora of health promoting activities. However, despite its lofty promise as a cancer prevention agent its success in human clinical trials has been limited due to its poor bioavailability. Thus, interest in other natural polyphenols is intensifying including the naturally occurring dimethylated analog of resveratrol, pterostilbene. The UDP-glucuronosyltransferase (UGT) family of enzymes plays a vital role in the metabolism of both resveratrol and pterostilbene. The current study sought to elucidate the UGT family members responsible for the metabolism of pterostilbene and to examine gender differences in the glucuronidation of resveratrol and pterostilbene. We demonstrate that UGT1A1 and UGT1A3 are mainly responsible for pterostilbene glucuronidation although UGT1A8, UGT1A9 and UGT1A10 also had detectable activity. Intriguingly, UGT1A1 exhibits the highest activity against both resveratrol and pterostilbene despite altered hydroxyl group specificity. Using pooled human liver microsomes, enzyme kinetics were determined for pterostilbene and resveratrol glucuronides. In all cases females were more efficient than males, indicating potential gender differences in stilbene metabolism. Importantly, the glucuronidation of pterostilbene is much less efficient than that of resveratrol, indicating that pterostilbene will have dramatically decreased metabolism in humans. Copyright © 2014 by the Japanese Society for the Study of Xenobiotics (JSSX).

Some claim that recent advances in neuroscience will revolutionize the way we think about human nature and legal culpability. Empirical support for this proposition is mixed. Two highly-cited empirical studies found that irrelevant neuroscientific explanations and neuroimages were highly persuasive to laypersons. However, attempts to replicate these effects have largely been unsuccessful. Two separate experiments tested the hypothesis that neuroscience is susceptible to motivated reasoning, which refers to the tendency to selectively credit or discredit information in a manner that reinforces preexisting beliefs. Participants read a newspaper article about a cutting-edge neuroscience study. Consistent with the hypothesis, participants deemed the hypothetical study sound and the neuroscience persuasive when the outcome of the study was congruent with their prior beliefs, but gave the identical study and neuroscience negative evaluations when it frustrated their beliefs. Neuroscience, it appears, is subject to the same sort of cognitive dynamics as other types of scientific evidence. These findings qualify claims that neuroscience will play a qualitatively different role in the way in which it shapes people's beliefs and informs issues of social policy.

In a retrospective cohort study of 1,140 patients harboring methicillin-resistant Staphylococcus aureus, the nasal burden was low in 31%, category 1+ to 2+ in 54%, and category 3+ to 4+ in 15%. There was a significant trend in infection risk with increasing nasal burden (P = 0.007). In multivariate models, high nasal burden remained significantly associated with invasive infection.

BackgroundPublic reporting of surgical site infections (SSIs) by hospitals is largely limited to infections detected during surgical hospitalizations or readmissions to the same facility. SSI rates may be underestimated if patients with SSIs are readmitted to other hospitals. We assessed the impact of readmissions to other facilities on hospitals' SSI rates following primary total hip arthroplasty (THA) or total knee arthroplasty (TKA).MethodsThis was a retrospective cohort study of all patients who underwent primary THA or TKA at California hospitals between 1 January 2006 and 31 December 2009. SSIs were identified using ICD-9-CM diagnosis codes predictive of SSI assigned at any California hospital within 365 days of surgery using a statewide repository of hospital data that allowed tracking of patients between facilities. We used statewide data to estimate the fraction of each hospital's THA and TKA SSIs identified at the operative hospital versus other hospitals.ResultsA total of 91 121 THA and 121 640 TKA procedures were identified. Based on diagnosis codes, SSIs developed following 2214 (2.3%) THAs and 2465 (2.0%) TKAs. Seventeen percent of SSIs would have been missed by operative hospital surveillance alone. The proportion of hospitals' SSIs detected at nonoperative hospitals ranged from 0% to 100%. Including SSIs detected at nonoperative hospitals resulted in better relative ranking for 61% of THA hospitals and 61% of TKA hospitals.ConclusionsLimiting SSI surveillance to the operative hospital caused varying degrees of SSI underestimation and substantially impacted hospitals' relative rankings, suggesting that alternative methods for comprehensive postdischarge surveillance are needed for accurate benchmarking.

Nursing homes represent a unique and important methicillin-resistant Staphylococcus aureus (MRSA) reservoir. Not only are strains imported from hospitals and the community, strains can be transported back into these settings from nursing homes. Since MRSA bacteria are prevalent in nursing homes and yet relatively poorly studied in this setting, a multicenter, regional assessment of the frequency and diversity of MRSA in the nursing home reservoir was carried out and compared to that of the MRSA from hospitals in the same region. The prospective study collected MRSA from nasal swabbing of residents of 26 nursing homes in Orange County, California, and characterized each isolate by spa typing. A total of 837 MRSA isolates were collected from the nursing homes. Estimates of admission prevalence and point prevalence of MRSA were 16% and 26%, respectively. The spa type genetic diversity was heterogeneous between nursing homes and significantly higher overall (77%) than the diversity in Orange County hospitals (72%). MRSA burden in nursing homes appears largely due to importation from hospitals. As seen in Orange County hospitals, USA300 (sequence type 8 [ST8]/t008), USA100 (ST5/t002), and a USA100 variant (ST5/t242) were the dominant MRSA clones in Orange County nursing homes, representing 83% of all isolates, although the USA100 variant was predominant in nursing homes, whereas USA300 was predominant in hospitals. Control strategies tailored to the complex problem of MRSA transmission and infection in nursing homes are needed in order to minimize the impact of this unique reservoir on the overall regional MRSA burden.