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Find video protocols related to scientific articles indexed in Pubmed.
Discovery and Characterization of MAPK-activated Protein Kinase-2 Prevention of Activation Inhibitors.
J. Med. Chem.
PUBLISHED: 09-26-2014
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Two structurally distinct series of novel, MAPK-activated kinase-2 prevention of activation inhibitors have been discovered by high throughput screening. Preliminary structure-activity relationship (SAR) studies revealed substructural features that influence the selective inhibition of the activation by p38? of the downstream kinase MK2 in preference to an alternative substrate, MSK1. Enzyme kinetics, surface plasmon resonance (SPR), 2D protein NMR, and X-ray crystallography were used to determine the binding mode and the molecular mechanism of action. The compounds bind competitively to the ATP binding site of p38? but unexpectedly with higher affinity in the p38?-MK2 complex compared with p38? alone. This observation is hypothesized to be the origin of the substrate selectivity. The two lead series identified are suitable for further investigation for their potential to treat chronic inflammatory diseases with improved tolerability over previously studied p38? inhibitors.
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Risk factors for self-reported arm lymphedema among female breast cancer survivors: a prospective cohort study.
Breast Cancer Res.
PUBLISHED: 08-22-2014
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Lymphedema is a potentially debilitating condition that occurs among breast cancer survivors. This study examines the incidence of self-reported lymphedema, timing of lymphedema onset, and associations between sociodemographic, clinical and lifestyle factors and lymphedema risk across racial-ethnic groups using data from a multicenter, multiethnic prospective cohort study of breast cancer survivors, the Health, Eating, Activity and Lifestyle Study.
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Balancing obligations: should written information about life-sustaining treatment be neutral?
J Med Ethics
PUBLISHED: 04-26-2014
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Parents who are facing decisions about life-sustaining treatment for their seriously ill or dying child are supported by their child's doctors and nurses. They also frequently seek other information sources to help them deal with the medical and ethical questions that arise. This might include written or web-based information. As part of a project involving the development of such a resource to support parents facing difficult decisions, some ethical questions emerged. Should this information be presented in a strictly neutral fashion? Is it problematic if narratives, arguments or perspectives appear to favour stopping over continuing life-sustaining treatment? Similar questions might arise with written materials about decisions for adults, or for other ethically contentious decisions. This paper explores the meaning of 'balance' in information provision, focusing particularly on written information about life-sustaining treatment for children. We contrast the norm of non-directiveness in genetic counselling with the shared decision-making model often endorsed in end-of-life care. We review evidence that parents do not find neutrality from medical professionals helpful in discussions. We argue that balance in written information must be understood in the light of the aim of the document, the most common situation in which it will be used, and any existing biases. We conclude with four important strategies for ensuring that non-neutral information is nevertheless ethically appropriate.
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Feasibility and outcomes of a community-based, pedometer-monitored walking program in chronic stroke: a pilot study.
Top Stroke Rehabil
PUBLISHED: 04-09-2014
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After stroke, many individuals have reduced physical activity. Pedometer use is reported to enhance physical activity in patients with other health conditions. The purpose of this study was to investigate the feasibility of a community-based, pedometer-monitored walking program and determine its effects on gait speed and distance, quality of life, and balance self-efficacy post stroke.
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Parents and end-of-life decision-making for their child: roles and responsibilities.
BMJ Support Palliat Care
PUBLISHED: 03-20-2014
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Whether parents want to be and should be the decision-maker for their child in end-of-life matters are contested clinical and ethical questions. Previous research outcomes are equivocal.
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Menopausal hormone therapy and lung cancer-specific mortality following diagnosis: the California Teachers Study.
PLoS ONE
PUBLISHED: 01-01-2014
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Previous results from research on menopausal hormone therapy (MHT) and lung cancer survival have been mixed and most have not studied women who used estrogen therapy (ET) exclusively. We examined the associations between MHT use reported at baseline and lung cancer-specific mortality in the prospective California Teachers Study cohort. Among 727 postmenopausal women diagnosed with lung cancer from 1995 through 2007, 441 women died before January 1, 2008. Hazard Ratios (HR) and 95% Confidence Intervals (CI) for lung-cancer-specific mortality were obtained by fitting multivariable Cox proportional hazards regression models using age in days as the timescale. Among women who used ET exclusively, decreases in lung cancer mortality were observed (HR, 0.69; 95% CI, 0.52-0.93). No association was observed for estrogen plus progestin therapy use. Among former users, shorter duration (<5 years) of exclusive ET use was associated with a decreased risk of lung cancer mortality (HR, 0.56; 95% CI, 0.35-0.89), whereas among recent users, longer duration (>15 years) was associated with a decreased risk (HR, 0.60; 95% CI, 0.38-0.95). Smoking status modified the associations with deceases in lung cancer mortality observed only among current smokers. Exclusive ET use was associated with decreased lung cancer mortality.
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"Fact" and "fiction": enlivening health care education.
J Health Organ Manag
PUBLISHED: 12-18-2013
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This paper aims to demonstrate how close analysis of cultural narratives can be employed as effective pedagogical tools in the explication and critique of specific workplace issues relevant to health management education.
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Outcome measures for individuals with stroke: process and recommendations from the American Physical Therapy Association neurology section task force.
Phys Ther
PUBLISHED: 05-23-2013
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The use of standardized outcome measures (OMs) can support clinicians development of appropriate care plans, guide educators in curricular decisions, and enhance the methodological quality and generalizability of clinical trials. The purposes of this case report are: (1) to describe a framework and process for assessing psychometrics and clinical utility of OMs used poststroke; (2) to describe a consensus process used to develop recommendations for stroke-related OMs in clinical practice, research, and professional (entry-level) physical therapist education; (3) to present examples demonstrating how the recommendations have been utilized to date; and (4) to make suggestions for future efforts.
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Mortality risk of black women and white women with invasive breast cancer by hormone receptors, HER2, and p53 status.
BMC Cancer
PUBLISHED: 05-01-2013
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Black women are more likely than white women to have an aggressive subtype of breast cancer that is associated with higher mortality and this may contribute to the observed black-white difference in mortality. However, few studies have investigated the black-white disparity in mortality risk stratified by breast cancer subtype, defined by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status. Furthermore, it is not known whether additional consideration of p53 protein status influences black-white differences in mortality risk observed when considering subtypes defined by ER, PR and HER2 status.
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ASCL1 reprograms mouse Muller glia into neurogenic retinal progenitors.
Development
PUBLISHED: 05-01-2013
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Non-mammalian vertebrates have a robust ability to regenerate injured retinal neurons from Müller glia (MG) that activate the gene encoding the proneural factor Achaete-scute homolog 1 (Ascl1; also known as Mash1 in mammals) and de-differentiate into progenitor cells. By contrast, mammalian MG have a limited regenerative response and fail to upregulate Ascl1 after injury. To test whether ASCL1 could restore neurogenic potential to mammalian MG, we overexpressed ASCL1 in dissociated mouse MG cultures and intact retinal explants. ASCL1-infected MG upregulated retinal progenitor-specific genes and downregulated glial genes. Furthermore, ASCL1 remodeled the chromatin at its targets from a repressive to an active configuration. MG-derived progenitors differentiated into cells that exhibited neuronal morphologies, expressed retinal subtype-specific neuronal markers and displayed neuron-like physiological responses. These results indicate that a single transcription factor, ASCL1, can induce a neurogenic state in mature MG.
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Amyloid-?1-42 slows clearance of synaptically released glutamate by mislocalizing astrocytic GLT-1.
J. Neurosci.
PUBLISHED: 03-22-2013
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GLT-1, the major glutamate transporter in the adult brain, is abundantly expressed in astrocytic processes enveloping synapses. By limiting glutamate escape into the surrounding neuropil, GLT-1 preserves the spatial specificity of synaptic signaling. Here we show that the amyloid-? peptide A?1-42 markedly prolongs the extracellular lifetime of synaptically released glutamate by reducing GLT-1 surface expression in mouse astrocytes and that this effect is prevented by the vitamin E derivative Trolox. These findings indicate that astrocytic glutamate transporter dysfunction may play an important role in the pathogenesis of Alzheimers disease and suggest possible mechanisms by which several current treatment strategies could protect against the disease.
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Quantitative measures of estrogen receptor expression in relation to breast cancer-specific mortality risk among white women and black women.
Breast Cancer Res.
PUBLISHED: 03-21-2013
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The association of breast cancer patients mortality with estrogen receptor (ER) status (ER+ versus ER-) has been well studied. However, little attention has been paid to the relationship between the quantitative measures of ER expression and mortality.
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The California Breast Cancer Survivorship Consortium (CBCSC): prognostic factors associated with racial/ethnic differences in breast cancer survival.
Cancer Causes Control
PUBLISHED: 02-08-2013
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Racial/ethnic disparities in mortality among US breast cancer patients are well documented. Our knowledge of the contribution of lifestyle factors to disease prognosis is based primarily on non-Latina Whites and is limited for Latina, African American, and Asian American women. To address this knowledge gap, the California Breast Cancer Survivorship Consortium (CBCSC) harmonized and pooled interview information (e.g., demographics, family history of breast cancer, parity, smoking, alcohol consumption) from six California-based breast cancer studies and assembled corresponding cancer registry data (clinical characteristics, mortality), resulting in 12,210 patients (6,501 non-Latina Whites, 2,060 African Americans, 2,032 Latinas, 1,505 Asian Americans, 112 other race/ethnicity) diagnosed with primary invasive breast cancer between 1993 and 2007. In total, 3,047 deaths (1,570 breast cancer specific) were observed with a mean (SD) follow-up of 8.3 (3.5) years. Cox proportional hazards regression models were fit to data to estimate hazards ratios (HRs) and 95 % confidence intervals (CIs) for overall and breast cancer-specific mortality. Compared with non-Latina Whites, the HR of breast cancer-specific mortality was 1.13 (95 % CI 0.97-1.33) for African Americans, 0.84 (95 % CI 0.70-1.00) for Latinas, and 0.60 (95 % CI 0.37-0.97) for Asian Americans after adjustment for age, tumor characteristics, and select lifestyle factors. The CBCSC represents a large and racially/ethnically diverse cohort of breast cancer patients from California. This cohort will enable analyses to jointly consider a variety of clinical, lifestyle, and contextual factors in attempting to explain the long-standing disparities in breast cancer outcomes.
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Retrospective claims analysis of best supportive care costs and survival in a US metastatic renal cell population.
Clinicoecon Outcomes Res
PUBLISHED: 01-01-2013
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Survival and best supportive care (BSC) costs for patients with metastatic renal cell carcinoma (mRCC), after stopping therapy, are poorly characterized yet an important aspect of patient care. This study examined survival and costs associated with BSC after one or two lines of therapy (LOTs) for mRCC.
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A surprisingly singular role for endophilin in synaptic vesicle recycling.
Neuron
PUBLISHED: 11-22-2011
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Synaptic vesicle endocytosis requires membrane curvature, fission, and uncoating. Endophilin has been proposed to play a role in all three steps, but in this issue of Neuron, De Camilli and colleagues show that at mammalian central synapses it is primarily involved in clathrin uncoating.
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Evaluating medical resource utilization and costs associated with thrombocytopenia in chronic liver disease patients.
J Med Econ
PUBLISHED: 11-04-2011
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Thrombocytopenia (TCP), defined as platelet counts <150,000/µL, is a common complication of severe chronic liver disease (CLD). This retrospective study estimated the prevalence of thrombocytopenia in a large population of CLD patients and compared medical resource utilization and medical care costs by TCP status.
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Ethics at the end of life: who should make decisions about treatment limitation for young children with life-threatening or life-limiting conditions?
J Paediatr Child Health
PUBLISHED: 09-29-2011
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It is now ethical orthodoxy that parents should be involved in the decision-making about their childrens health care. This extends to decisions about whether to continue or to limit life-sustaining medical treatment for a child with a life-limiting or life-threatening condition. What remains contested and uncertain is the extent and nature of parental involvement, especially in this emotionally charged situation. In particular, should it be the parents, who are the ultimate decision-makers, taking final responsibility, should it be a shared decision, or should it be a medical decision that parents are simply asked to consent to? One approach to this issue is to consider the in-principle ethical arguments and weigh their merits. The two key principles here are parental rights and authority, and the best interests of child, and the contested issue is what to do if these appear to clash. Another approach is to consider the principles in the practical clinical context. What would be the implications and consequences of adopting the model of parents as final decision-makers? Are parents able to carry out this role, and do they really want it? What is the effect on parents of taking this role? Answers to these questions could modify the in-principle ethical position. In this paper, we review the empirical evidence currently available on these questions, in relation to parents of infants and young children. Overall, the literature suggests that parents do want to be involved and do not suffer adverse psychological consequences from their involvement. However, the crucial ethical implication of the evidence is that the level and nature of parental involvement in decision-making should be negotiated with the parents in each case, because parents have a range of different views about taking final responsibility for decisions.
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Outcome measures in neurological physical therapy practice: part II. A patient-centered process.
J Neurol Phys Ther
PUBLISHED: 09-22-2011
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Physical therapists working in neurological practice must make choices about which standardized outcome measures are most appropriate for each patient. Significant time constraints in the clinic limit the number of measures that one can reasonably administer. Therapists must choose measures that will provide results that guide the selection of appropriate interventions and are likely to show clinically meaningful change. Therefore, therapists must be able to compare the merits of available measures to identify those that are most relevant for each patient and setting. This article describes a process for selecting outcome measures and illustrates the use of that process with a patient who has had a stroke. The link between selecting objective outcome measures and tracking patient progress is emphasized. Comparisons are made between 2 motor function measures (the Fugl-Meyer Assessment [FMA] of Physical Performance vs the Stroke Rehabilitation Assessment of Movement), and 2 balance measures (Berg Balance Scale vs the Activities-specific Balance Confidence Scale). The use of objective outcome measures allows therapists to quantify information that previously had been described in subjective terms. This allows the tracking of progress, and the comparison of effectiveness and costs across interventions, settings, providers, and patient characteristics.
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Outcome measures in neurological physical therapy practice: part I. Making sound decisions.
J Neurol Phys Ther
PUBLISHED: 09-22-2011
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Standardized outcome measures (OMs) are a vital part of evidence-based practice. Despite the recognition of the importance of OMs, recent evidence suggests that the use of OMs in clinical practice is limited. Selecting the most appropriate OM enhances clinical practice by (1) identifying and quantifying body function and structure limitations; (2) formulating the evaluation, diagnosis, and prognosis; (3) informing the plan of care; and (4) helping to evaluate the success of physical therapy interventions. This article (Part I) is the first of a 2-part series on the process of selecting OMs in neurological clinical practice. We introduce a decision-making framework to guide the selection of OMs and discuss 6 main factors-what to measure, the purpose of the measure, the type of measure, patient and clinic factors, psychometric factors, and feasibility-that should be considered when selecting OMs for clinical use. The framework will then be applied to a patient case in Part II of the series (see the article "Outcome Measures in Neurological Physical Therapy Practice: Part II. A Patient-Centered Process" in this issue).
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Obesity and survival among black women and white women 35 to 64 years of age at diagnosis with invasive breast cancer.
J. Clin. Oncol.
PUBLISHED: 07-25-2011
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To evaluate the effect of obesity on survival among black women and white women with invasive breast cancer and to determine whether obesity explains the poorer survival of black women relative to white women.
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Cigarette smoking, passive smoking, and non-Hodgkin lymphoma risk: evidence from the California Teachers Study.
Am. J. Epidemiol.
PUBLISHED: 07-18-2011
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Epidemiologic studies conducted to date have shown evidence of a causal relation between smoking and non-Hodgkin lymphoma (NHL) risk. However, previous studies did not account for passive smoking exposure in the never-smoking reference group. The California Teachers Study collected information about lifetime smoking and household passive smoking exposure in 1995 and about lifetime exposure to passive smoking in 3 settings (household, workplace, and social settings) in 1997-1998. Multivariable-adjusted relative risks and 95% confidence intervals were estimated by fitting Cox proportional hazards models with follow-up through 2007. Compared with never smokers, ever smokers had a 1.11-fold (95% confidence interval (CI): 0.94, 1.30) higher NHL risk that increased to a 1.22-fold (95% CI: 0.95, 1.57) higher risk when women with household passive smoking were excluded from the reference category. Statistically significant dose responses were observed for lifetime cumulative smoking exposure (intensity and pack-years; both P s for trend = 0.02) when women with household passive smoking were excluded from the reference category. Among never smokers, NHL risk increased with increasing lifetime exposure to passive smoking (relative risk = 1.51 (95% CI: 1.03, 2.22) for >40 years vs. ?5 years of passive smoking; P for trend = 0.03), particularly for follicular lymphoma (relative risk = 2.89 (95% CI: 1.23, 6.80); P for trend = 0.01). The present study provides evidence that smoking and passive smoking may influence NHL etiology, particularly for follicular lymphoma.
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Age-specific effects of hormone therapy use on overall mortality and ischemic heart disease mortality among women in the California Teachers Study.
Menopause
PUBLISHED: 06-10-2011
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Although the Womens Health Initiative trial suggested that menopausal hormone therapy (HT) does not reduce coronary heart disease mortality overall, subsequent results have suggested that there may be a benefit in younger women. The California Teachers Study questionnaire and mortality data were used to examine whether age modified the association between HT and the relative risk of overall mortality and ischemic heart disease deaths.
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The roles of herbal remedies in survival and quality of life among long-term breast cancer survivors--results of a prospective study.
BMC Cancer
PUBLISHED: 06-06-2011
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Few data exist on survival or health-related quality of life (QOL) related to herbal remedy use among long-term breast cancer survivors. The objective of this report is to examine whether herbal remedy use is associated with survival or the health-related QOL of these long-term breast cancer survivors.
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Oral contraceptive use and survival in women with invasive breast cancer.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 05-06-2011
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Oral contraceptives (OC) are widely used in the United States. Although the relation between OC use and breast cancer incidence has been widely studied, the few studies examining associations between OC use prior to breast cancer diagnosis and survival are inconsistent.
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Lower risk in parous women suggests that hormonal factors are important in bladder cancer etiology.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 04-14-2011
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Urinary bladder cancer is two to four times more common among men than among women, a difference in risk not fully explained by established risk factors. Our objective was to determine whether hormonal and reproductive factors are involved in female bladder cancer.
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Health care utilization & costs for cystic fibrosis patients with pulmonary infections.
Manag Care
PUBLISHED: 03-25-2011
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To examine patterns of health care utilization and costs among cystic fibrosis (CF) patients with pulmonary infections.
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An initial exploration of the perceptual threshold test using electrical stimulation to measure arm sensation following stroke.
Clin Rehabil
PUBLISHED: 03-22-2011
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To explore the viability of the perceptual threshold test using electrical stimulation to measure light touch sensation in the hands of stroke survivors.
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Bereaved parents perceptions of the autopsy examination of their child.
Pediatrics
PUBLISHED: 03-14-2011
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In this study we explored parental views of their childs autopsy, their experiences with autopsy-related processes, and the impact of the examination on their grief.
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Medical resource utilisation and healthcare costs in patients with chronic hepatitis C viral infection and thrombocytopenia.
J Med Econ
PUBLISHED: 02-25-2011
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Thrombocytopenia is a significant risk for patients with chronic HCV infection and a common side-effect of treatment with pegylated (PEG) interferon (IFN). Thrombocytopenia predisposes patients to bleeding and requirements for platelet transfusions, and may thus place an increased burden on patients and on medical resource utilisation.
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Presenilin 1 regulates homeostatic synaptic scaling through Akt signaling.
Nat. Neurosci.
PUBLISHED: 02-23-2011
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Neurons adapt to long-lasting changes in network activity, both in vivo and in vitro, by adjusting their synaptic strengths to stabilize firing rates. We found that homeostatic scaling of excitatory synapses was impaired in hippocampal neurons derived from mice lacking presenilin 1 (Psen1(-/-) mice) or expressing a familial Alzheimers disease-linked Psen1 mutation (Psen1(M146V)). These findings suggest that deficits in synaptic homeostasis may contribute to brain dysfunction in Alzheimers disease.
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Bilateral oophorectomy is not associated with increased mortality: the California Teachers Study.
Fertil. Steril.
PUBLISHED: 02-17-2011
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To investigate the effect of surgical menopause due to bilateral oophorectomy on mortality, in light of evidence that bilateral oophorectomy among premenopausal women rapidly reduces endogenous hormone levels, thereby modifying risks of cardiovascular disease and breast cancer.
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Menopausal hormone therapy does not influence lung cancer risk: results from the California Teachers Study.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 01-25-2011
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Results from studies examining the association between hormone therapy (HT) and lung cancer risk disagree.
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A novel role for {gamma}-secretase: selective regulation of spontaneous neurotransmitter release from hippocampal neurons.
J. Neurosci.
PUBLISHED: 01-21-2011
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With a multitude of substrates, ?-secretase is poised to control neuronal function through a variety of signaling pathways. Presenilin 1 (PS1) is an integral component of ?-secretase and is also a protein closely linked to the etiology of Alzheimers disease (AD). To better understand the roles of ?-secretase and PS1 in normal and pathological synaptic transmission, we examined evoked and spontaneous neurotransmitter release in cultured hippocampal neurons derived from PS1 knock-out (KO) mice. We found no changes in the size of evoked synaptic currents, short-term plasticity, or apparent calcium dependence of evoked release. The rate of spontaneous release from PS1 KO neurons was, however, approximately double that observed in wild-type (WT) neurons. This increase in spontaneous neurotransmission depended on calcium influx but did not require activation of voltage-gated calcium channels or presynaptic NMDA receptors or release of calcium from internal stores. The rate of spontaneous release from PS1 KO neurons was significantly reduced by lentivirus-mediated expression of WT PS1 or familial AD-linked M146V PS1, but not the D257A PS1 mutant that does not support ?-secretase activity. Treatment of WT neuronal cultures with ?-secretase inhibitor mimicked the loss of PS1, leading to a selective increase in spontaneous release without any change in the size of evoked synaptic currents. Together, these results identify a novel role for ?-secretase in the control of spontaneous neurotransmission through modulation of low-level tonic calcium influx into presynaptic axon terminals.
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Does hormone therapy counter the beneficial effects of physical activity on breast cancer risk in postmenopausal women?
Cancer Causes Control
PUBLISHED: 01-07-2011
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Studies consistently demonstrate that physical activity is inversely associated with postmenopausal breast cancer. Whether this association is stronger among non-hormone users or former users of menopausal hormone therapy (HT) is of interest given the marked decline in HT use since 2002. The Womens Contraceptive and Reproductive Experiences Study, a population-based case-control study of invasive breast cancer, recruited white women and black women ages 35-64 years and collected histories of lifetime recreational physical activity and HT use including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT). Among postmenopausal women (1,908 cases, 2,013 control participants), breast cancer risk declined with increasing levels of lifetime physical activity among never HT users; among short-term HT users (fewer than 5 years); and among current ET users; P (trend) values ranged from 0.004 to 0.016. In contrast, physical activity had no significant association with risk among long-term and past HT users and among current EPT users. No statistical evidence of heterogeneity was demonstrated for duration or currency of HT use. Breast cancer risk decreases with increasing lifetime physical activity levels among postmenopausal women who have not used HT, have used HT for less than 5 years, or are current ET users, yet this study was unable to demonstrate statistically that HT use modifies the relationship between physical activity and breast cancer. With profound changes in HT use occurring since 2002, it will be important in future studies to learn whether or not any association between physical activity and breast cancer among former HT users is a function of time since last HT use.
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Breast cancer risk and ovariectomy, hysterectomy, and tubal sterilization in the womens contraceptive and reproductive experiences study.
Am. J. Epidemiol.
PUBLISHED: 11-25-2010
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Removal or impairment of ovaries before menopause may affect a womans breast cancer risk by altering her cumulative exposure to ovarian hormones. The Womens Contraceptive and Reproductive Experiences Study, a population-based, multicenter case-control study of incident invasive breast cancer, recruited women aged 35-64 years (4,490 cases and 4,611 controls) who provided data on ovariectomy, hysterectomy, and tubal sterilization during in-person interviews. Controls were frequency-matched to cases by age, race, and study site. Unconditional logistic regression analysis was used. Women who had not undergone premenopausal reproductive surgery were the referent group. Bilateral ovariectomy was associated with reduced breast cancer risk overall (odds ratio (OR) = 0.59, 95% confidence interval (CI): 0.50, 0.69) and among women <45 years of age (ORs ranged from 0.31 to 0.52), but not among those who were older at surgery. It was also associated with a reduced risk for estrogen and progesterone receptor-positive tumors (OR = 0.63, 95% CI: 0.52, 0.75) but not receptor-negative tumors. Hysterectomy with ovarian conservation (OR = 0.83, 95% CI: 0.72, 0.96) and hysterectomy with partial ovary removal (OR = 0.73, 95% CI: 0.59, 0.91) were also associated with lower risk. No association with breast cancer risk was observed with tubal sterilization only or partial ovariectomy without hysterectomy. Reproductive organ surgeries may alter ovarian hormone levels, thereby affecting breast cancer risk.
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MicroRNA132 modulates short-term synaptic plasticity but not basal release probability in hippocampal neurons.
PLoS ONE
PUBLISHED: 08-19-2010
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MicroRNAs play important regulatory roles in a broad range of cellular processes including neuronal morphology and long-term synaptic plasticity. MicroRNA-132 (miR132) is a CREB-regulated miRNA that is induced by neuronal activity and neurotrophins, and plays a role in regulating neuronal morphology and cellular excitability. Little is known about the effects of miR132 expression on synaptic function. Here we show that overexpression of miR132 increases the paired-pulse ratio and decreases synaptic depression in cultured mouse hippocampal neurons without affecting the initial probability of neurotransmitter release, the calcium sensitivity of release, the amplitude of excitatory postsynaptic currents or the size of the readily releasable pool of synaptic vesicles. These findings are the first to demonstrate that microRNAs can regulate short-term plasticity in neurons.
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Oral contraceptives, menopausal hormone therapy use and risk of B-cell non-Hodgkin lymphoma in the California Teachers Study.
Int. J. Cancer
PUBLISHED: 07-05-2010
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We examined oral contraceptive (OC) and menopausal hormonal therapy (MHT) use in relation to risk of B-cell non-Hodgkin lymphoma (NHL). Women under age 85 years participating in the California Teachers Study with no history of hematopoietic cancer were followed from 1995 through 2007. A total of 516 of 114,131 women eligible for OC use analysis and 402 of 54,758 postmenopausal women eligible for MHT use analysis developed B-cell NHL. Multivariable adjusted and age stratified Cox proportional hazards models were fit to estimate relative risks (RRs) and 95% confidence intervals (95% CI). Ever versus never OC use was marginally associated with lower B-cell NHL risk, particularly among women first using OCs before age 25 years (RR=0.72, 95% CI=0.51-0.99); yet, no duration-response effect was observed. No association was observed for ever versus never MHT use among postmenopausal women (RR=1.05, 95% CI=0.83-1.33) overall or by formulation (estrogen alone, ET, or estrogen plus progestin, EPT). Among women with no MHT use, having bilateral oophorectomy plus hysterectomy was associated with greater B-cell NHL risk than having natural menopause (RR=3.15, 95% CI=1.62-6.13). Bilateral oophorectomy plus hysterectomy was not associated with risk among women who used ET or EPT. These results indicate that exogenous hormone use does not strongly influence B-cell NHL risk.
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Parents ages at birth and risk of adult-onset hematologic malignancies among female teachers in California.
Am. J. Epidemiol.
PUBLISHED: 05-27-2010
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Although advanced parental age at ones birth has been associated with increased risk of breast and prostate cancers, few studies have examined its effect on adult-onset sporadic hematologic malignancies. The authors examined the association of parents ages at womens births with risk of hematologic malignancies among 110,999 eligible women aged 22-84 years recruited into the prospective California Teachers Study. Between 1995 and 2007, 819 women without a family history of hematologic malignancies were diagnosed with incident lymphoma, leukemia (primarily acute myeloid leukemia), or multiple myeloma. Multivariable-adjusted Cox proportional hazards models provided estimates of relative risks and 95% confidence intervals. Paternal age was positively associated with non-Hodgkin lymphoma after adjustment for race and birth order (relative risk for age > or =40 vs. <25 years = 1.51, 95% confidence interval: 1.08, 2.13; P-trend = 0.01). Further adjustment for maternal age did not materially alter the association. By contrast, the elevated non-Hodgkin lymphoma risk associated with advanced maternal age (> or =40 years) became null when paternal age was included in the statistical model. No association was observed for acute myeloid leukemia or multiple myeloma. Advanced paternal age may play a role in non-Hodgkin lymphoma etiology. Potential etiologic mechanisms include de novo gene mutations, aberrant paternal gene imprinting, or telomere/telomerase biology.
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Pregnancy-related factors and the risk of breast carcinoma in situ and invasive breast cancer among postmenopausal women in the California Teachers Study cohort.
Breast Cancer Res.
PUBLISHED: 04-01-2010
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Although pregnancy-related factors such as nulliparity and late age at first full-term pregnancy are well-established risk factors for invasive breast cancer, the roles of these factors in the natural history of breast cancer development remain unclear.
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Use of four biomarkers to evaluate the risk of breast cancer subtypes in the womens contraceptive and reproductive experiences study.
Cancer Res.
PUBLISHED: 01-12-2010
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Epidemiologic studies suggest that some hormone-related risk factors in breast cancer differentially influence risk for disease subtypes classified by the status of the estrogen and progesterone receptors (ER/PR). However, it remains unclear whether human epidermal growth factor receptor 2 (HER2) or p53 expression status further differentiates these exposure-risk group associations. We evaluated the associations of oral contraceptive (OC) use and reproductive factors with incident invasive breast cancer subtypes among 1,197 population-based cases and 2,015 controls from the Los Angeles County or Detroit components of the Womens Contraceptive and Reproductive Experiences Study. Case-control comparisons by ER/PR/HER2/p53 status were conducted by multivariable polychotomous unconditional logistic regression methods. We found that OC use was not associated with any breast cancer subtype as defined by ER/PR/HER2/p53 status, except for a 2.9-fold increased risk of so-called triple-negative tumors (ER(-)/PR(-)/HER2(-)) among women of 45 to 64 years of age who started OC use before age 18. Parity was associated with a decreased risk of luminal A (ER(+) or PR(+), HER2(-)), luminal B (ER(+) or PR(+)/HER2(+)), and ER(-)/PR(-)/HER2(+) tumors. Age at first full-term pregnancy was positively associated with luminal A tumors among older women. Neither of these reproductive factors was associated with triple-negative tumors. Long duration of breast-feeding lowered the risk of triple-negative and luminal A tumors. p53 status did not define further differential risk patterns. Our findings offer evidence of differences in the hormone-related risk factors between triple-negative cancers and other ER/PR/HER2-defined subtypes of breast cancer.
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Menopausal hormone therapy use and risk of invasive colon cancer: the California Teachers Study.
Am. J. Epidemiol.
PUBLISHED: 01-11-2010
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Results from epidemiologic studies of hormone therapy use and colon cancer risk are inconsistent. This question was investigated in the California Teachers Study (1995-2006) among 56,864 perimenopausal or postmenopausal participants under 80 years of age with no prior colorectal cancer by using Cox proportional hazards regression. Incident invasive colon cancer was diagnosed among 442 participants. Baseline-recent hormone therapy users were at 36% lower risk for colon cancer versus baseline-never users (baseline-recent users: relative risk (RR) = 0.64, 95% confidence interval (CI): 0.51, 0.80). Results did not differ by formulation. Estimated risk was lower among baseline-recent hormone therapy users with increasing duration between 5 and 15 years of use (RR = 0.49, 95% CI: 0.35, 0.68), but the trend did not persist in the longest duration group, more than 15 years of use (RR = 0.69, 95% CI: 0.52, 0.92; P(trend) = 0.60). Long-term recreational physical activity, obesity, regular use of nonsteroidal antiinflammatory medications, and daily alcohol intake did not modify these effects; baseline-recent use was more strongly associated with colon cancer risk among women with a family history of colorectal cancer (P(heterogeneity) = 0.04). Baseline-recent hormone therapy use was inversely associated with invasive colon cancer risk among perimenopausal and postmenopausal women in the California Teachers Study.
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Long-term and recent recreational physical activity and survival after breast cancer: the California Teachers Study.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 10-20-2009
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Long-term physical activity is associated with lower breast cancer risk. Little information exists on its association with subsequent survival.
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Body size, recreational physical activity, and B-cell non-Hodgkin lymphoma risk among women in the California teachers study.
Am. J. Epidemiol.
PUBLISHED: 10-12-2009
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Nutritional status and physical activity are known to alter immune function, which may be relevant to lymphomagenesis. The authors examined body size measurements and recreational physical activity in relation to risk of B-cell non-Hodgkin lymphoma (NHL) in the prospective California Teachers Study. Between 1995 and 2007, 574 women were diagnosed with incident B-cell NHL among 121,216 eligible women aged 22-84 years at cohort entry. Multivariable-adjusted relative risks and 95% confidence intervals were estimated by fitting Cox proportional hazards models for all B-cell NHL combined and for the 3 most common subtypes: diffuse large B-cell lymphoma, follicular lymphoma, and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma. Height was positively associated with risk of all B-cell NHLs (for >1.70 vs. 1.61-1.65 m, relative risk = 1.50, 95% confidence interval: 1.16, 1.96) and chronic lymphocytic leukemia/small lymphocytic lymphoma (relative risk = 1.93, 95% confidence interval: 1.09, 3.41). Weight and body mass index at age 18 years were positive predictors of B-cell NHL risk overall. These findings indicate that greater height, which may reflect genetics, early life immune function, infectious exposures, nutrition, or growth hormone levels, may play a role in NHL etiology. Adiposity at age 18 years may be more relevant to NHL etiology than that in later life.
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Reproductive factors and non-Hodgkin lymphoma risk in the California Teachers Study.
PLoS ONE
PUBLISHED: 09-20-2009
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Non-Hodgkin lymphoma (NHL) is a malignancy etiologically linked to immunomodulatory exposures and disorders. Endogenous female sex hormones may modify immune function and influence NHL risk. Few studies have examined associations between reproductive factors, which can serve as surrogates for such hormonal exposures, and NHL risk by subtype.
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Breast cancer receptor status: do results from a centralized pathology laboratory agree with SEER registry reports?
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 08-08-2009
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We investigated the extent to which estrogen receptor (ER) and progesterone receptor (PR) status results from a centralized pathology laboratory agree with ER and PR results from community pathology laboratories reported to two Surveillance, Epidemiology and End Results (SEER) registries (Los Angeles County and Detroit) and whether statistical estimates for the association between reproductive factors and breast cancer receptor subtypes differ by the source of data. The agreement between the centralized laboratory and SEER registry classifications was substantial for ER (kappa = 0.70) and nearly so for PR status (kappa = 0.60). Among the four subtypes defined by joint ER and PR status, the agreement between the two sources was substantial for the two major breast cancer subtypes (ER-/PR-, kappa = 0.69; ER+/PR+, kappa = 0.62) and poor for the two rarer subtypes (ER+/PR-, kappa = 0.30; ER-/PR+, kappa = 0.05). Estimates for the association between reproductive factors (number of full-term pregnancies, age at first full-term pregnancy, and duration of breastfeeding) and the two major subtypes (ER+/PR+ and ER-/PR-) differed minimally between the two sources of data. For example, parous women with at least four full-term pregnancies had 40% lower risk for ER+/PR+ breast cancer than women who had never been pregnant [centralized laboratory, odds ratio, 0.60 (95% confidence interval, 0.39-0.92); SEER, odds ratio, 0.57 (95% confidence interval, 0.38-0.85)]; no association was observed for ER-/PR- breast cancer (both P(trend) > 0.30). Our results suggest that conclusions based on SEER registry data are reasonably reliable for ER+/PR+ and ER-/PR- subtypes.
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Niacin and fibrate use among patients with high triglycerides and low high-density lipoprotein cholesterol.
Curr Med Res Opin
PUBLISHED: 05-12-2009
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National guidelines recommend treating low HDL and/or high triglycerides (TG) with adjunctive therapy that supplements statin monotherapy in patients with multiple cardiovascular disease (CVD) risk factors. Niacin and fibrates have been shown in clinical trials to be effective as adjunctive therapy for these lipid abnormalities.
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Dyslipidemia treatment of patients with diabetes mellitus in a US managed care plan: a retrospective database analysis.
Cardiovasc Diabetol
PUBLISHED: 03-11-2009
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To evaluate real-world pharmacologic treatment of mixed dyslipidemia in patients with diabetes mellitus (DM).
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Risk factors for arm lymphedema following breast cancer diagnosis in Black women and White women.
Breast Cancer Res. Treat.
PUBLISHED: 02-07-2009
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Purpose Lymphedema of the arm is a potential complication of breast cancer therapy. This study examines pre-disposing factors that may operate in conjunction with treatment-related factors in the development of arm lymphedema in a large cohort of White and Black breast cancer survivors. Methods 494 women (271 White and 223 Black) with in situ to Stage III-A primary breast cancer completed a baseline interview within 18 months of diagnosis. Information on lymphedema was collected during a follow-up interview, conducted on average 50 months after diagnosis. Self-reported data were used to classify women with or without lymphedema. Multivariable logistic regression models were developed to identify risk factors for arm lymphedema. Results Arm lymphedema was associated with younger age at diagnosis (odds ratio, OR per year of age = 0.96; 95% confidence interval, CI = 0.93-0.99), positive history of hypertension (OR = 2.31; 95% CI = 1.38-3.88), obesity (OR for body mass index, BMI> or =30 = 2.48; 95% CI = 1.05-5.84) and having had surgery where 10 or more lymph nodes were excised (OR = 2.16; 95% CI = 1.12-4.17). While Black women had higher prevalence of arm lymphedema than White women (28% vs. 21%), race was not associated with lymphedema risk in models adjusted for multiple factors (adjusted OR = 1.01; 95% CI = 0.63-1.63). Conclusion Risk of arm lymphedema did not differ significantly for Black and White women. Risk factors identified in this study offer opportunities for interventions (weight loss, control of blood pressure, use of sentinel node biopsy where possible) for reducing incidence of lymphedema or controlling the symptoms associated with this condition.
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Antacid drug use and risk of esophageal and gastric adenocarcinomas in Los Angeles County.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 02-03-2009
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Concern has been expressed that antacid drugs increase the risk of esophageal and gastric adenocarcinomas.
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Recreational physical activity and risk of papillary thyroid cancer among women in the California Teachers Study.
Cancer Epidemiol
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Little is known about the relationship between physical activity and thyroid cancer risk, and few cohort data on this association exist. Thus, the present study aimed to prospectively examine long-term activity and risk of papillary thyroid cancer among women.
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Afferent stimulation provided by glove electrode during task-specific arm exercise following stroke.
Clin Rehabil
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Sensory amplitude electrical stimulation (SES) and repetitive task practice reduce impairments and arm dysfunction when delivered separately following stroke.
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Asynchronous Ca2+ current conducted by voltage-gated Ca2+ (CaV)-2.1 and CaV2.2 channels and its implications for asynchronous neurotransmitter release.
Proc. Natl. Acad. Sci. U.S.A.
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We have identified an asynchronously activated Ca(2+) current through voltage-gated Ca(2+) (Ca(V))-2.1 and Ca(V)2.2 channels, which conduct P/Q- and N-type Ca(2+) currents that initiate neurotransmitter release. In nonneuronal cells expressing Ca(V)2.1 or Ca(V)2.2 channels and in hippocampal neurons, prolonged Ca(2+) entry activates a Ca(2+) current, I(Async), which is observed on repolarization and decays slowly with a half-time of 150-300 ms. I(Async) is not observed after L-type Ca(2+) currents of similar size conducted by Ca(V)1.2 channels. I(Async) is Ca(2+)-selective, and it is unaffected by changes in Na(+), K(+), Cl(-), or H(+) or by inhibitors of a broad range of ion channels. During trains of repetitive depolarizations, I(Async) increases in a pulse-wise manner, providing Ca(2+) entry that persists between depolarizations. In single-cultured hippocampal neurons, trains of depolarizations evoke excitatory postsynaptic currents that show facilitation followed by depression accompanied by asynchronous postsynaptic currents that increase steadily during the train in parallel with I(Async). I(Async) is much larger for slowly inactivating Ca(V)2.1 channels containing ?(2a)-subunits than for rapidly inactivating channels containing ?(1b)-subunits. I(Async) requires global rises in intracellular Ca(2+), because it is blocked when Ca(2+) is chelated by 10 mM EGTA in the patch pipette. Neither mutations that prevent Ca(2+) binding to calmodulin nor mutations that prevent calmodulin regulation of Ca(V)2.1 block I(Async). The rise of I(Async) during trains of stimuli, its decay after repolarization, its dependence on global increases of Ca(2+), and its enhancement by ?(2a)-subunits all resemble asynchronous release, suggesting that I(Async) is a Ca(2+) source for asynchronous neurotransmission.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.