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Find video protocols related to scientific articles indexed in Pubmed.
Molecular homology and difference between spontaneous canine mammary cancer and human breast cancer.
Cancer Res.
PUBLISHED: 07-31-2014
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Spontaneously occurring canine mammary cancer represents an excellent model of human breast cancer, but is greatly understudied. To better use this valuable resource, we performed whole-genome sequencing, whole-exome sequencing, RNA-seq, and/or high-density arrays on twelve canine mammary cancer cases, including seven simple carcinomas and four complex carcinomas. Canine simple carcinomas, which histologically match human breast carcinomas, harbor extensive genomic aberrations, many of which faithfully recapitulate key features of human breast cancer. Canine complex carcinomas, which are characterized by proliferation of both luminal and myoepithelial cells and are rare in human breast cancer, seem to lack genomic abnormalities. Instead, these tumors have about 35 chromatin-modification genes downregulated and are abnormally enriched with active histone modification H4-acetylation, whereas aberrantly depleted with repressive histone modification H3K9me3. Our findings indicate the likelihood that canine simple carcinomas arise from genomic aberrations, whereas complex carcinomas originate from epigenomic alterations, reinforcing their unique value. Canine complex carcinomas offer an ideal system to study myoepithelial cells, the second major cell lineage of the mammary gland. Canine simple carcinomas, which faithfully represent human breast carcinomas at the molecular level, provide indispensable models for basic and translational breast cancer research.
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Sleep Spindles Are Related to Schizotypal Personality Traits and Thalamic Glutamine/Glutamate in Healthy Subjects.
Schizophr Bull
PUBLISHED: 07-31-2014
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Background: Schizophrenia is a severe mental disorder affecting approximately 1% of the worldwide population. Yet, schizophrenia-like experiences (schizotypy) are very common in the healthy population, indicating a continuum between normal mental functioning and the psychosis found in schizophrenic patients. A continuum between schizotypy and schizophrenia would be supported if they share the same neurobiological origin. Two such neurobiological markers of schizophrenia are: (1) a reduction of sleep spindles (12-15 Hz oscillations during nonrapid eye movement sleep), likely reflecting deficits in thalamo-cortical circuits and (2) increased glutamine and glutamate (Glx) levels in the thalamus. Thus, this study aimed to investigate whether sleep spindles and Glx levels are related to schizotypal personality traits in healthy subjects. Methods: Twenty young male subjects underwent 2 all-night sleep electroencephalography recordings (128 electrodes). Sleep spindles were detected automatically. After those 2 nights, thalamic Glx levels were measured by magnetic resonance spectroscopy. Subjects completed a magical ideation scale to assess schizotypy. Results: Sleep spindle density was negatively correlated with magical ideation (r = -.64, P < .01) and thalamic Glx levels (r = -.70, P < .005). No correlation was found between Glx levels in the thalamus and magical ideation (r = .12, P > .1). Conclusions: The common relationship of sleep spindle density with schizotypy and thalamic Glx levels indicates a neurobiological overlap between nonclinical schizotypy and schizophrenia. Thus, sleep spindle density and magical ideation may reflect the anatomy and efficiency of the thalamo-cortical system that shows pronounced impairment in patients with schizophrenia.
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Posterior cingulate ?-aminobutyric acid and glutamate/glutamine are reduced in amnestic mild cognitive impairment and are unrelated to amyloid deposition and apolipoprotein E genotype.
Neurobiol. Aging
PUBLISHED: 07-29-2014
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The biomarker potential of the inhibitory neurotransmitter ?-aminobutyric acid (GABA) for the in vivo characterization of preclinical stages in Alzheimer's disease has not yet been explored. We measured GABA, glutamate + glutamine (Glx), and N-acetyl-aspartate (NAA) levels by single-voxel MEGA-PRESS magnetic resonance spectroscopy in the posterior cingulate cortex of 21 elderly subjects and 15 patients with amnestic mild cognitive impairment. Participants underwent Pittsburgh Compound B positron emission tomography, apolipoprotein E (APOE) genotyping, and neuropsychological examination. GABA, Glx, and NAA levels were significantly lower in patients. NAA was lower in Pittsburgh Compound B-positive subjects and APOE ?4 allele carriers. GABA, Glx, and NAA levels were positively correlated to CERAD word learning scores. Reductions in GABA, Glx, and NAA levels may serve as metabolic biomarkers for cognitive impairment in amnestic mild cognitive impairment. Because GABA and Glx do not seem to reflect amyloid ? deposition or APOE genotype, they are less likely biomarker candidates for preclinical Alzheimer's disease.
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The PI3K/AKT/mTOR pathway in breast cancer: targets, trials and biomarkers.
Ther Adv Med Oncol
PUBLISHED: 07-25-2014
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The phosphoinositide 3 kinase (PI3K)/Akt/mammalian (or mechanistic) target of rapamycin (mTOR) pathway is a complicated intracellular pathway, which leads to cell growth and tumor proliferation and plays a significant role in endocrine resistance in breast cancer. Multiple compounds targeting this pathway are being evaluated in clinical trials. These agents are generally well tolerated and can be used in combination with targeted therapies, endocrine therapy or cytotoxic agents. The identification of subtypes of tumors more likely to respond to these therapeutics cannot be overemphasized, since breast cancer is a very heterogeneous malignancy. Activation of pathways such as KRAS and MEK can act as escape mechanisms that lead to resistance, thus a combination of agents targeting multiple steps of the intracellular machinery is promising. There is evidence that tumors with PIK3CA mutations are more sensitive to inhibitors of the PI3K pathway but this has yet to be validated. Large clinical trials with correlative studies are necessary to identify reliable biomarkers of efficacy.
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Left Ventricular Geometry and All-cause Mortality in Advanced Age.
Heart Lung Circ
PUBLISHED: 07-08-2014
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Abnormalities of cardiac structure and function are common in a wide range of populations including those with and without established clinical cardiovascular disease (CVD). This study reports the prevalence of left ventricular hypertrophy (LVH), the four patterns of LV geometry and establishes clinical characteristics and five-year outcomes of each group in people of advanced age.
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Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance).
J. Clin. Oncol.
PUBLISHED: 06-16-2014
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Optimal adjuvant chemotherapy for early-stage breast cancer balances efficacy and toxicity. We sought to determine whether single-agent paclitaxel (T) was inferior to doxorubicin and cyclophosphamide (AC), when each was administered for four or six cycles of therapy, and whether it offered less toxicity.
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The prediction of study-emergent suicidal ideation in bipolar disorder: a pilot study using ecological momentary assessment data.
Bipolar Disord
PUBLISHED: 06-05-2014
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Bipolar disorder is associated with idiosyncratic precursors of clinically important states such as suicidal ideation. Ecological momentary assessment (EMA) - high frequency data collection in a subject's usual environment - provides the potential for development of temporal, individualized prediction of risk states. The present study tested the ability of EMA data to predict individual symptom change in clinician-rated suicidal ideation.
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Structural analysis of H1N1 and H7N9 influenza A virus PA in the absence of PB1.
Sci Rep
PUBLISHED: 06-02-2014
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Influenza A viruses cause the respiratory illness influenza, which can be mild to fatal depending on the strain and host immune response. The flu polymerase acidic (PA), polymerase basic 1 (PB1), and polymerase basic 2 (PB2) proteins comprise the RNA-dependent RNA polymerase complex responsible for viral genome replication. The first crystal structures of the C-terminal domain of PA (PA-CTD) in the absence of PB1-derived peptides show a number of structural changes relative to the previously reported PB1-peptide bound structures. The human A/WSN/1933 (H1N1) and avian A/Anhui1/2013 (H7N9) strain PA-CTD proteins exhibit the same global topology as other strains in the absence of PB1, but differ extensively in the PB1 binding pocket including a widening of the binding groove and the unfolding of a ?-turn. Both PA-CTD proteins exhibited a significant increase in thermal stability in the presence of either a PB1-derived peptide or a previously reported inhibitor in differential scanning fluorimetry assays. These structural changes demonstrate plasticity in the PA-PB1 binding interface which may be exploited in the development of novel therapeutics.
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Decreased Hypothalamic Functional Connectivity with Subgenual Cortex in Psychotic Major Depression.
Neuropsychopharmacology
PUBLISHED: 05-15-2014
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Hypothalamus communication with the rest of the brain and peripheral target tissues is critically important for many physiological and psychological functions. These functions include maintaining neuroendocrine circadian rhythms and managing affective processes. The hypothalamus maintains both direct neural connections within the brain and it also controls a variety of neuroendocrine processes that can influence target tissues throughout the body. Dysregulation of the hypothalamic pituitary adrenal axis and hyperactivity of the subgenual cortex are both frequently observed in depression. However, many details of how the hypothalamus, the hypothalamic pituitary adrenal (HPA) axis, and the subgenual cingulate interact with each other are unknown. We hypothesized that resting-state functional connectivity between the hypothalamus and the subgenual cortex would be associated with altered circadian rhythm in patients with depression and depressive symptoms. We also hypothesized that this would be most apparent in patients that have major depression with psychotic symptoms, who typically have the most robust HPA-axis dysregulation. Resting-state functional magnetic resonance imaging (fMRI) scans were collected to observe low-frequency resting-state functional connectivity patterns of the hypothalamus in 39 healthy participants, 39 patients with major depression, and 22 patients with major depression with psychotic symptoms. Hourly overnight measures of cortisol secretion and multiple measures of psychiatric symptom severity were also collected on all. Strong hypothalamic functional connectivity with the subgenual cortex was observed in healthy participants. This connectivity was significantly reduced in patients with psychotic major depression. Increased cortisol secretion during the circadian nadir and reduced connectivity were both associated with symptom severity. Reduced connectivity and high cortisol secretion during the circadian nadir are both useful for explaining a significant amount of variance in symptom severity that occurs between healthy participants and depressed patients. However, only cortisol secretion was useful for explaining the severity of symptoms within the depressed groups. This study suggests that the communication between the hypothalamus and the subgenual cortex is disrupted in patients with major depression with psychotic features. It also suggests that these disruptions are associated with increased symptom severity and may be a cause or a consequence of cortisol dysregulation.Neuropsychopharmacology advance online publication, 12 November 2014; doi:10.1038/npp.2014.259.
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Systemic therapy for early-stage HER2-positive breast cancers: Time for a less-is-more approach?
Cancer
PUBLISHED: 05-14-2014
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Trastuzumab-based chemotherapy has dramatically improved outcomes for patients with all stages of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Additional HER2-directed agents that have recently been approved are also expected to improve outcomes. Patients with small, lymph node-negative, HER2-positive breast cancers who are treated with trastuzumab-based chemotherapy demonstrate especially favorable responses, with 5-year recurrence rates of <5%. In this review, recent data regarding response rates among patients with early-stage HER2-positive breast cancer treated with trastuzumab-based chemotherapy are discussed. This review supports future studies of the possible omission of chemotherapy in a subset of patients with HER2-positive cancers, specifically those that coexpress hormone receptors. Cancer 2014. © 2014 American Cancer Society.
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Psychosocial predictors of salivary cortisol among older adults with depression.
Int Psychogeriatr
PUBLISHED: 04-17-2014
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ABSTRACT Background: Previous studies have identified a number of psychosocial risk factors of dysregulated cortisol (frequently referred to as the "stress hormone") among older adults with depression. However, these studies have typically only examined a handful of risk factors at a time and have sometimes yielded inconsistent results. Method: This study aims to address this gap in the literature by simultaneously examining a range of relevant psychosocial predictors of diurnal cortisol among 54 older adults with a depressive disorder. Salivary cortisol was assessed upon awakening, at 5 PM, and at 9 PM across two consecutive days. Participants also completed measures of global psychosocial stress, current psychiatric symptomatology, pervasive distress (e.g. history of past depression), and protective factors (e.g. social support, resiliency, extent to which one has "made sense" of a significant stressor). Results: High levels of current depressive symptoms, psychiatric comorbidities, past depressive episodes, trait anxiety, and poorer ability to make sense of one's stress were found to be associated with flatter (more abnormal) cortisol slopes. However, when all of these variables were entered simultaneously in a multiple regression analysis, only history of past depression and the degree of sense made of stress emerged as unique predictors of cortisol in the model. Conclusions: These findings have important implications for identifying depressed elderly individuals with dysregulated cortisol patterns who may be most at risk for health complications. Treatments that aim to limit the chronicity of depression and help to increase the sense made of stress could potentially have a positive impact on health.
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Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial.
Lancet Oncol.
PUBLISHED: 04-14-2014
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Disease progression in patients with HER2-positive breast cancer receiving trastuzumab might be associated with activation of the PI3K/Akt/mTOR intracellular signalling pathway. We aimed to assess whether the addition of the mTOR inhibitor everolimus to trastuzumab might restore sensitivity to trastuzumab.
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Does cognitive-behavioural therapy promote meaning making? A preliminary test in the context of geriatric depression.
Psychol Psychother
PUBLISHED: 03-19-2014
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This study examined the extent to which cognitive-behavioural therapy (CBT) for geriatric depression promoted meaning made of stress.
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Relationship between brain glutamate levels and clinical outcome in individuals at ultra high risk of psychosis.
Neuropsychopharmacology
PUBLISHED: 03-05-2014
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Alterations in brain glutamate levels may be associated with psychosis risk, but the relationship to clinical outcome in at-risk individuals is unknown. Glutamate concentration was measured in the left thalamus and anterior cingulate cortex (ACC) using 3-Tesla proton magnetic resonance spectroscopy in 75 participants at ultra high risk (UHR) of psychosis and 56 healthy controls. The severity of attenuated positive symptoms and overall functioning were assessed. Measures were repeated in 51 UHR and 33 Control subjects after a mean of 18 months. UHR subjects were allocated to either remission (no longer meeting UHR criteria) or non-remission (meeting UHR or psychosis criteria) status on follow-up assessment. Thalamic glutamate levels at presentation were lower in the UHR non-remission (N=29) compared with the remission group (N=22) (t(49)=3.03; P=0.004), and were associated with an increase in the severity of total positive symptoms over time (r=-0.33; df=47; P=0.02), most notably abnormal thought content (r=-0.442; df=47; P=0.003). In the UHR group, ACC glutamate levels were lower at follow-up compared with baseline (F(80)=4.28; P=0.04). These findings suggest that measures of brain glutamate function may be useful as predictors of clinical outcome in individuals at high risk of psychosis.
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High Pathologic Complete Response in Her2-Positive, Early-Stage Breast Cancer to a Novel Nonanthracycline Neoadjuvant Chemotherapy.
Clin. Breast Cancer
PUBLISHED: 02-20-2014
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Neoadjuvant chemotherapy is widely used to downstage breast cancers before surgery and is an accepted standard of care among patients with early-stage breast cancer in whom adjuvant chemotherapy would be recommended. Pathologic complete response (pCR) rate is a robust predictor of outcome for certain breast cancer subtypes, including Her2-overexpressing breast cancer. The incorporation of Her2-targeted therapies has significantly increased the pCR rate in the neoadjuvant setting. Although regimens composed of trastuzumab, nab-paclitaxel, and vinorelbine have demonstrated clinical efficacy in patients with metastatic breast cancer, few studies have examined this combination in early-stage Her2+ breast cancer. We hypothesized that the combination of neoadjuvant nab-paclitaxel followed by vinorelbine could represent a nonanthracycline-based treatment option for early-stage Her2-overexpressing breast cancer.
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Prenatal and perinatal risk factors in a twin study of autism spectrum disorders.
J Psychiatr Res
PUBLISHED: 02-18-2014
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Multiple studies associate prenatal and perinatal complications with increased risks for autism spectrum disorders (ASDs). The objectives of this study were to utilize a twin study design to 1) Investigate whether shared gestational and perinatal factors increase concordance for ASDs in twins, 2) Determine whether individual neonatal factors are associated with the presence of ASDs in twins, and 3) Explore whether associated factors may influence males and females differently.
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Serial N-terminal pro-brain natriuretic peptide measurement as a predictor of significant patent ductus arteriosus in preterm infants beyond the first week of life.
Eur. J. Pediatr.
PUBLISHED: 02-13-2014
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The aim of the study was to assess the role of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration as a predictor of patent ductus arteriosus (PDA) in very low birth weight infants beyond the first week of life. This was a prospective observational study; newborns with a birth weight?
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Investigation of glutamine and GABA levels in patients with idiopathic generalized epilepsy using MEGAPRESS.
J Magn Reson Imaging
PUBLISHED: 02-11-2014
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Idiopathic generalized epilepsies (IGE) comprise a group of clinical syndromes associated with spike wave discharges, putatively linked to alterations in neurotransmission. The purpose of this study was to investigate whether patients with IGE have altered glutamine and ?-aminobutyric acid (GABA) levels indicative of altered excitatory and inhibitory neurotransmission in frontal regions.
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fMRI Activation During Executive Function Predicts Response to Cognitive Behavioral Therapy in Older, Depressed Adults.
Am J Geriatr Psychiatry
PUBLISHED: 02-03-2014
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To test our hypothesis that pre-treatment executive function and brain regional activation during executive function would discriminate between responders and non-responders to cognitive behavioral therapy (CBT) in elderly depressed outpatients.
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Modifiable risk factors for adherence to adjuvant endocrine therapy among breast cancer patients.
Patient Educ Couns
PUBLISHED: 01-10-2014
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Breast cancer incidence and mortality are declining due to improvements in early detection and treatment. One advance in treatment is the development of adjuvant endocrine therapy (AET) for women with hormone receptor positive breast cancer. Despite strong evidence linking AET to better health outcomes, AET adherence continues to be suboptimal. This study tests the hypothesis that patient beliefs about medication mediate the relationship between frequency of physician communication and AET adherence.
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Health-related quality of life in children and adolescents with celiac disease: patient-driven data from focus group interviews.
Qual Life Res
PUBLISHED: 01-07-2014
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Celiac disease (CD) is a chronic inflammatory disease requiring constant management with a gluten-free diet (GFD). Little is known about how CD impacts on health-related quality of life (HRQOL) in children and adolescents, and how they feel about and cope with CD and GFD. This qualitative study explores the impact of CD and GFD on HRQOL in everyday living of children and adolescents.
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Cortisol, cytokines, and hippocampal volume interactions in the elderly.
Front Aging Neurosci
PUBLISHED: 01-01-2014
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Separate bodies of literature report that elevated pro-inflammatory cytokines and cortisol negatively affect hippocampal structure and cognitive functioning, particularly in older adults. Although interactions between cytokines and cortisol occur through a variety of known mechanisms, few studies consider how their interactions affect brain structure. In this preliminary study, we assess the impact of interactions between circulating levels of IL-1Beta, IL-6, IL-8, IL-10, IL-12, TNF-alpha, and waking cortisol on hippocampal volume. Twenty-eight community-dwelling older adults underwent blood draws for quantification of circulating cytokines and saliva collections to quantify the cortisol awakening response. Hippocampal volume measurements were made using structural magnetic resonance imaging. Elevated levels of waking cortisol in conjunction with higher concentrations of IL-6 and TNF-alpha were associated with smaller hippocampal volumes. In addition, independent of cortisol, higher levels of IL-1beta and TNF-alpha were also associated with smaller hippocampal volumes. These data provide preliminary evidence that higher cortisol, in conjunction with higher IL-6 and TNF-alpha, are associated with smaller hippocampal volume in older adults. We suggest that the dynamic balance between the hypothalamic-pituitary adrenal axis and inflammation processes may explain hippocampal volume reductions in older adults better than either set of measures do in isolation.
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Effects of body mass index-related disorders on cognition: preliminary results.
Diabetes Metab Syndr Obes
PUBLISHED: 01-01-2014
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Well-known risk factors for cognitive impairment are also associated with obesity. Research has highlighted genetic risk factors for obesity, yet the relationship of those risk factors with cognitive impairment is unknown. The objective of this study was to determine the associations between cognition, hypertension, diabetes, sleep-disordered breathing, and obesity. Genetic risk factors of obesity were also examined.
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Oocyte size, egg index, and body lipid content in relation to body size in the solitary bee Megachile rotundata.
PeerJ
PUBLISHED: 01-01-2014
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Females of solitary, nest-provisioning bees have relatively low fecundity, but produce large eggs as part of their overall strategy of investing substantially in each offspring. In intraspecific comparisons of several species of solitary, nest-provisioning bees and wasps, the size of the mature eggs produced increases with female body size. We further examined oocyte size-body size correlations in the solitary bee Megachile rotundata (F.), an important crop pollinator. We hypothesized that larger females carry larger basal oocytes (i.e., those next in line to be oviposited) but that body size-oocyte size correlations would be absent soon after emergence, before their first eggs fully matured. Because egg production is likely affected by the quantity of stored lipids carried over from the bees' immature stages, we also tested the hypothesis that female body size is correlated with the body lipid content at adult emergence, the time during which oocyte growth accelerates. We found significant correlations of body size with oocyte size variables chosen to reflect: (1) the magnitude of the investment in the next egg to be laid (i.e., the length and volume of the basal oocyte) and (2) the longer term potential to produce mature oocytes (i.e., the summed lengths and volumes of the three largest oocytes in each female). Positive correlations existed throughout the nesting season, even during the first week following adult emergence. The ability to produce and carry larger oocytes may be linked to larger females starting the nesting season with greater lipid stores (which we document here) or to greater space within the abdomen of larger females. Compared to other species of solitary bees, M. rotundata appears to have (1) smaller oocytes than solitary nest-provisioning bees in general, (2) comparable oocyte sizes relative to congeners, and (3) larger oocytes than related brood parasitic megachilids.
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Improving the nurse-family partnership in community practice.
Pediatrics
PUBLISHED: 11-05-2013
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Evidence-based preventive interventions are rarely final products. They have reached a stage of development that warrant public investment but require additional research and development to strengthen their effects. The Nurse-Family Partnership (NFP), a program of nurse home visiting, is grounded in findings from replicated randomized controlled trials.
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Helping the helpers: mindfulness training for burnout in pediatric oncology--a pilot program.
J Pediatr Oncol Nurs
PUBLISHED: 10-09-2013
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Burnout, a syndrome of emotional exhaustion, depersonalization, and diminished feelings of accomplishment, is common among pediatric oncology staff. This study explores a mindfulness-based course (MBC) to decrease burnout in a multidisciplinary group of pediatric oncology staff members in the United States and Israel.
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DSM-5 sleep-wake disorders classification: overview for use in clinical practice.
Am J Psychiatry
PUBLISHED: 10-03-2013
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Mental health clinicians should appreciate that sleep is a fundamental human behavior and that inadequate sleep has adverse medical, psychiatric, and psychosocial consequences. Sleep disturbances interact with common mental disorders; the two are mutually exacerbating, and both must be appropriately addressed to ensure optimal outcomes for our patients. Sleep is by the brain, of the brain, and for the brain.
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A phase 2 study of everolimus combined with trastuzumab and paclitaxel in patients with HER2-overexpressing advanced breast cancer that progressed during prior trastuzumab and taxane therapy.
Breast Cancer Res. Treat.
PUBLISHED: 06-28-2013
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Increased activation of the PI3K/Akt/mTOR pathway is a common factor in putative mechanisms of trastuzumab resistance, resulting in dysregulation of cell migration, growth, proliferation, and survival. Data from preclinical and phase 1/2 clinical studies suggest that adding everolimus (an oral mTOR inhibitor) to trastuzumab plus chemotherapy may enhance the efficacy of, and restore sensitivity to, trastuzumab-based therapy. In this phase 2 multicenter study, adult patients with HER2-positive advanced breast cancer resistant to trastuzumab and pretreated with a taxane received everolimus 10 mg/day in combination with paclitaxel (80 mg/m(2) days 1, 8, and 15 every 4 weeks) and trastuzumab (4 mg/kg loading dose followed by 2 mg/kg weekly), administered in 28-day cycles. Endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Fifty-five patients were enrolled; one remained on study treatment at the time of data cutoff. The median number of prior chemotherapy lines for advanced disease was 3.5 (range 1-11). The ORR was 21.8 %, the clinical benefit rate was 36.4 %, the median PFS estimate was 5.5 months (95 % confidence interval [CI]: 4.99-7.69 months), and the median OS estimate was 18.1 months (95 % CI: 12.85-24.11 months). Hematologic grade 3/4 adverse events (AEs) included neutropenia (25.5 % grade 3, 3.6 % grade 4), anemia (7.3 % grade 3), and thrombocytopenia (5.5 % grade 3, 1.8 % grade 4). Nonhematologic grade 3/4 AEs included stomatitis (20.0 %), diarrhea (5.5 %), vomiting (5.5 %), fatigue (5.5 %), and pneumonia (5.5 %), all grade 3. These findings suggest that the combination of everolimus plus trastuzumab and paclitaxel is feasible, with promising activity in patients with highly resistant HER2-positive advanced breast cancer. This combination is currently under investigation in the BOLERO-1 phase 3 trial.
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The unique impact of late-life bereavement and prolonged grief on diurnal cortisol.
J Gerontol B Psychol Sci Soc Sci
PUBLISHED: 06-05-2013
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Objectives. This study expands on previous research by examining the effects of prolonged grief disorder (PGD) symptoms and bereavement on diurnal cortisol patterns above and beyond depressive symptomatology.
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Everolimus: side effect profile and management of toxicities in breast cancer.
Breast Cancer Res. Treat.
PUBLISHED: 06-04-2013
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Everolimus is an orally available inhibitor of the mammalian target of rapamycin (mTOR), which has been approved in combination with exemestane for hormone receptor-positive (HR) breast cancer after failure of treatment with non-steroidal aromatase inhibitors. Everolimus is generally very well tolerated with most common side effects including stomatitis, rash, fatigue, hyperglycemia, hyperlipidemia, and myelosuppression. Most of these side effects are mild and resolve with dose interruptions or dose reductions. Symptomatic non-infectious pneumonitis is a relatively uncommon class effect of mTOR inhibitors, which can be life threatening. Given the efficacy of everolimus in HR-positive metastatic breast cancer, it is crucial for physicians to recognize toxicities related to everolimus and start timely interventions. This review will focus on the adverse events reported with everolimus in breast cancer trials and will provide practical guidelines for the management of these adverse events.
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Genomic subtypes in choosing adjuvant therapy for breast cancer.
Oncology (Williston Park, N.Y.)
PUBLISHED: 05-22-2013
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The use of gene expression profiling has impacted our understanding of breast cancer biology and increasingly has played a role in guiding clinical decisions. We have used hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status for years to guide selection of therapy. More recently, gene expression analysis has facilitated the identification of at least five intrinsic subtypes of breast cancer. Potential therapeutic targets have also been identified using genomic profiling. Several tests, such as the 21-gene recurrence score assay (Oncotype DX) and the 70-gene prognosis signature (MammaPrint), have been well validated as prognostic tools for early-stage breast cancer, and have aided in adjuvant therapy decisions for early-stage, HR-positive breast cancer patients. Genomic profiling has the potential to provide additional insight into drug discovery and clinical trial design by identifying appropriate targeted therapies for subtypes of breast cancer.
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A comparative study of the speeds attained by captive cheetahs during the enrichment practice of the "cheetah run".
Zoo Biol.
PUBLISHED: 05-21-2013
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The enrichment practice of the "cheetah run" is becoming increasingly popular within zoological institutions as a method to enrich captive cheetahs. A lure moving at speed represents an artificial prey item that the cursorial cheetah can pursue, therefore allowing it to perform an important hunting behavior within a captive setting. This study was conducted in order to highlight how employing different forms of this type of enrichment may influence its efficacy. This is important in relation to the future development of an optimum type of "cheetah run" enrichment which maximizes the potential beneficial effects and therefore positively impacts upon cheetah welfare in captivity. Video recordings were carried out at three separate institutions (Fota Wildlife Park, Ireland; Ann van Dyk Cheetah Centre, South Africa; Cheetah Conservation Fund, Namibia). Randomization tests were carried out to compare the highest speeds attained between males and females, trained and untrained cheetahs and also between the three institutions. Females and trained individuals reached significantly higher speeds compared with males and untrained individuals, respectively. The only significant difference between the three institutions was between the Ann van Dyk Cheetah Centre and the Cheetah Conservation Fund, where cheetahs at the Ann van Dyk center reached significantly higher speeds. The current study represents the first detailed study of any aspect of the "cheetah run" across multiple institutions. It also includes the first quantification of the speed of cheetahs in captivity in relation to differing enrichment practices.
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Sleep disturbance in pediatric PTSD: current findings and future directions.
J Clin Sleep Med
PUBLISHED: 05-16-2013
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Many studies have provided strong evidence of a fundamental and complex role for sleep disturbances in adult posttraumatic stress disorder (PTSD). Investigations of adult PTSD using subjective and objective measures document sleep architecture abnormalities and high prevalence of sleep disordered breathing, periodic limb movement disorder, nightmares, and insomnia. PTSD treatment methods do appear to significantly improve sleep disturbance, and also studies suggest that treatments for sleep disorders often result in improvements in PTSD symptoms. Further, the most recent evidence suggests sleep abnormalities may precede the development of PTSD. Given the importance of sleep disorders to the onset, course, and treatment of adult PTSD, examination of sleep disturbances far earlier in the life course is imperative. Here we review the literature on what we know about sleep disturbances and disorders in pediatric PTSD. Our review indicates that the extant, empirical data examining sleep disturbance and disorders in pediatric PTSD is limited. Yet, this literature suggests there are significantly higher reports of sleep disturbances and nightmares in children and adolescents exposed to trauma and/or diagnosed with PTSD than in non-trauma-exposed samples. Sleep questionnaires are predominantly employed to assess sleep disorders in pediatric PTSD, with few studies utilizing objective measures. Given the important, complex relationship being uncovered between adult PTSD and sleep, this review calls for further research of sleep in children with PTSD using more specific subjective measures and also objective measures, such as polysomnography and eventually treatment trial studies.
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Nocturnal rapid eye movement sleep latency for identifying patients with narcolepsy/hypocretin deficiency.
JAMA Neurol
PUBLISHED: 05-08-2013
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Narcolepsy, a disorder associated with HLA-DQB1*06:02 and caused by hypocretin (orexin) deficiency, is diagnosed using the Multiple Sleep Latency Test (MSLT) following nocturnal polysomnography (NPSG). In many patients, a short rapid eye movement sleep latency (REML) during the NPSG is also observed but not used diagnostically.
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Psychosocial predictors of treatment response to cognitive-behavior therapy for late-life depression: an exploratory study.
Aging Ment Health
PUBLISHED: 04-30-2013
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The primary objective of this study was to examine a variety of potential predictors of response to Cognitive Behavioral Therapy (CBT) in depressed older adults.
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BDNF and CREB1 genetic variants interact to affect antidepressant treatment outcomes in geriatric depression.
Pharmacogenet. Genomics
PUBLISHED: 04-27-2013
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Brain-derived neurotrophic factor (BDNF) is associated with antidepressant response on the cellular level, in animal models, and in clinical studies. A common variant in the BDNF gene results in a substitution of a methionine (Met) for a valine at the amino acid position 66. Previous studies reported that the Met variant results in enhanced response to antidepressant medications. These findings may be at odds with studies indicating that on a cellular level the Met variant impairs the secretion of BDNF.
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Connectivity Underlying Emotion Conflict Regulation in Older Adults with 5-HTTLPR Short Allele: A Preliminary Investigation.
Am J Geriatr Psychiatry
PUBLISHED: 04-11-2013
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The serotonin transporter polymorphism short (s) allele is associated with heightened emotional reactivity and reduced emotion regulation, which increases vulnerability to depression and anxiety disorders. We investigated behavioral and neural markers of emotion regulation in community-dwelling older adults, contrasting s allele carriers and long allele homozygotes.
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Silencing CDK4 radiosensitizes breast cancer cells by promoting apoptosis.
Cell Div
PUBLISHED: 04-03-2013
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The discovery of molecular markers associated with various breast cancer subtypes has greatly improved the treatment and outcome of breast cancer patients. Unfortunately, breast cancer cells acquire resistance to various therapies. Mounting evidence suggests that resistance is rooted in the deregulation of the G1 phase regulatory machinery.
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Serotonin transporter polymorphism is associated with increased apnea-hypopnea index in older adults.
Int J Geriatr Psychiatry
PUBLISHED: 04-01-2013
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RATIONALE: A functional polymorphism of the serotonin transporter gene (5-HTTLPR) has previously been related to upper airway pathology, but its contribution to obstructive sleep apnea (OSA), a highly prevalent sleep disorder in older adults, remains unclear. OBJECTIVES: We aimed to investigate the relationship between apnea-hypopnea index (AHI) and genetic variations in the promoter region of the 5-HTTLPR in older adults. METHODS: DNA samples from 94 community-dwelling older adults (57% female, mean age 72?±?8) were genotyped for the 5-HTTLPR polymorphism. All participants were assessed in their homes with full ambulatory polysomnography in order to determine AHI and related parameters such as hypoxia, sleep fragmentation, and self-reported daytime sleepiness. RESULTS: The 5-HTT l allele was significantly associated with AHI (p?=?0.019), with l allele carriers displaying a higher AHI than s allele homozygotes. A single allele change in 5-HTTLPR genotype from s to l resulted in an increase of AHI by 4.46 per hour of sleep (95% CI, 0.75-8.17). The l allele was also associated with increased time during sleep spent at oxygen saturation levels below 90% (p?=?0.014). CONCLUSIONS: The observed significant association between the 5-HTTLPR l allele and severity of OSA in older adults suggests that the l allele may be important to consider when assessing for OSA in this age group. This association may also explain some of the observed variability among serotonergic pharmacological treatment studies for OSA, and 5-HTT genotype status may have to be taken into account in future therapeutic trials involving serotonergic agents. Copyright © 2013 John Wiley & Sons, Ltd.
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Elevated prefrontal myo-inositol and choline following breast cancer chemotherapy.
Brain Imaging Behav
PUBLISHED: 03-29-2013
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Breast cancer survivors are at increased risk for cognitive dysfunction, which reduces quality of life. Neuroimaging studies provide critical insights regarding the mechanisms underlying these cognitive deficits as well as potential biologic targets for interventions. We measured several metabolite concentrations using (1)H magnetic resonance spectroscopy as well as cognitive performance in 19 female breast cancer survivors and 17 age-matched female controls. Women with breast cancer were all treated with chemotherapy. Results indicated significantly increased choline (Cho) and myo-inositol (mI) with correspondingly decreased N-acetylaspartate (NAA)/Cho and NAA/mI ratios in the breast cancer group compared to controls. The breast cancer group reported reduced executive function and memory, and subjective memory ability was correlated with mI and Cho levels in both groups. These findings provide preliminary evidence of an altered metabolic profile that increases our understanding of neurobiologic status post-breast cancer and chemotherapy.
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The long-term impact of early adversity on late-life psychiatric disorders.
Curr Psychiatry Rep
PUBLISHED: 02-28-2013
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Early adversity is a strong and enduring predictor of psychiatric disorders including mood disorders, anxiety disorders, substance abuse or dependence, and posttraumatic stress disorder. However, the mechanisms of this effect are not well understood. The purpose of this review is to summarize and integrate the current research knowledge pertaining to the long-term effects of early adversity on psychiatric disorders, particularly in late life. We explore definitional considerations including key dimensions of the experience such as type, severity, and timing of adversity relative to development. We then review the potential biological and environmental mediators and moderators of the relationships between early adversity and psychiatric disorders. We conclude with clinical implications, methodological challenges and suggestions for future research.
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Pretreatment cortisol levels predict posttreatment outcomes among older adults with depression in cognitive behavioral therapy.
Psychiatry Res
PUBLISHED: 02-24-2013
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Previous studies suggest that individuals with elevated levels of cortisol (the "stress hormone") could be particularly resistant to treatment for depression. However, most of these studies have been conducted in the context of antidepressant medications, and no study has examined pretreatment cortisol levels as a predictor of treatment outcomes among older adults with depression in cognitive-behavioral therapy (CBT), despite the relevance of this population for such a research question. The current study includes 54 older adults with depression who provided salivary cortisol samples at baseline and completed measures of depression at pretreatment and posttreatment, following a 12-week course of CBT. Structural equation modeling results suggest that those with higher daily outputs of cortisol and flatter diurnal slopes were less likely to benefit from CBT-a finding which if replicated could have important implications for clinical practice and future research.
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Climate change impacts on potential recruitment in an ecosystem engineer.
Ecol Evol
PUBLISHED: 02-04-2013
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Climate variability and the rapid warming of seas undoubtedly have huge ramifications for biological processes such as reproduction. As such, gametogenesis and spawning were investigated at two sites over 200 km apart on the south coast of Ireland in an ecosystem engineer, the common cockle, Cerastoderma edule. Both sites are classed as Special Areas of Conservation (SACs), but are of different water quality. Cerastoderma edule plays a significant biological role by recycling nutrients and affecting sediment structure, with impacts upon assemblage biomass and functional diversity. It plays a key role in food webs, being a common foodstuff for a number of marine birds including the oystercatcher. Both before and during the study (early 2010-mid 2011), Ireland experienced its two coldest winters for 50 years. As the research demonstrated only slight variation in the spawning period between sites, despite site differences in water and environmental quality, temperature and variable climatic conditions were the dominant factor controlling gametogenesis. The most significant finding was that the spawning period in the cockle extended over a greater number of months compared with previous studies and that gametogenesis commenced over winter rather than in spring. Extremely cold winters may impact on the cockle by accelerating and extending the onset and development of gametogenesis. Whether this impact is positive or negative would depend on the associated events occurring on which the cockle depends, that is, presence of primary producers and spring blooms, which would facilitate conversion of this extended gametogenesis into successful recruitment.
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Arterial spin labelling MRI for assessment of cerebral perfusion in children with moyamoya disease: comparison with dynamic susceptibility contrast MRI.
Neuroradiology
PUBLISHED: 02-01-2013
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This study seeks to evaluate the diagnostic accuracy of cerebral perfusion imaging with arterial spin labelling (ASL) MR imaging in children with moyamoya disease compared to dynamic susceptibility contrast (DSC) imaging.
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Cortical and cerebellar modulation of autonomic responses to loud sounds.
Psychophysiology
PUBLISHED: 01-22-2013
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Detecting unexpected environmental change causes modulation of autonomic activity essential for survival. Understanding the neural mechanisms associated with responses to loud sounds may provide insights into the pathophysiology of posttraumatic stress disorder (PTSD), since individuals with PTSD exhibit heightened autonomic responses to unexpected loud sounds. We combined fMRI with autonomic psychophysiological assessment to investigate central and peripheral reactivity to loud tones in 20 healthy participants. Activity in anterior insula, pregenual anterior cingulate cortex, anterior midcingulate cortex, supplementary motor area, supramarginal gyrus, and cerebellar lobules VIII-IX was associated with both tones and concomitant skin conductance responses. Since regions signaling unexpected external events modulate autonomic activity, heightened loud tone autonomic responses in PTSD may reflect sensitization of this "salience" network.
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Final results from phase II trial of neoadjuvant docetaxel and capecitabine given sequentially or concurrently for HER2-negative breast cancers.
Clin. Breast Cancer
PUBLISHED: 01-16-2013
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The combination of docetaxel and capecitabine has been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in patients with metastatic breast cancer compared with docetaxel alone. We hypothesized that the combination of docetaxel and capecitabine, given concomitantly or sequentially, would present a nonanthracycline-based treatment option for patients with early stage and locally advanced breast cancer.
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New and emerging treatments for estrogen receptor-positive breast cancer: focus on everolimus.
Ther Clin Risk Manag
PUBLISHED: 01-14-2013
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Management of patients with metastatic hormone receptor-positive breast cancer poses a challenge due to the inevitable development of endocrine resistance. Hormone resistance is associated with a complex interaction of the estrogen receptor with growth factors, transmembrane receptors, and intracellular growth cascades. The PI3K/Akt/mTOR pathway plays a major role in hormone resistance and proliferation of breast cancer. Preclinical and clinical data indicate that inhibitors of human epidermal growth factor receptor-2, epidermal growth factor receptor, insulin-like growth factor-1 receptor, and the mammalian target of rapamycin pathway may act synergistically with hormone therapy to circumvent endocrine resistance. Everolimus is currently approved for combination with exemestane in postmenopausal women with advanced hormone receptor-positive breast cancer. However, we still need to unfold the full potential of targeted agents in the hormone-refractory setting and to identify the subsets of patients who will benefit from combination hormonal therapy using targeted agents.
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Atypical visual processing in posttraumatic stress disorder.
Neuroimage Clin
PUBLISHED: 01-01-2013
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Many patients with Posttraumatic Stress Disorder (PTSD) feel overwhelmed in situations with high levels of sensory input, as in crowded situations with complex sensory characteristics. These difficulties might be related to subtle sensory processing deficits similar to those that have been found for sounds in electrophysiological studies.
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Early exposure to traumatic stressors impairs emotional brain circuitry.
PLoS ONE
PUBLISHED: 01-01-2013
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Exposure to early life trauma (ELT) is known to have a profound impact on mental development, leading to a higher risk for depression and anxiety. Our aim was to use multiple structural imaging methods to systematically investigate how traumatic stressors early in life impact the emotional brain circuits, typically found impaired with clinical diagnosis of depression and anxiety, across the lifespan in an otherwise healthy cohort. MRI data and self-reported histories of ELT from 352 healthy individuals screened for no psychiatric disorders were analyzed in this study. The volume and cortical thickness of the limbic and cingulate regions were assessed for all participants. A large subset of the cohort also had diffusion tensor imaging data, which was used to quantify white matter structural integrity of these regions. We found a significantly smaller amygdala volume and cortical thickness in the rostral anterior cingulate cortex associated with higher ELT exposure only for the adolescence group. White matter integrity of these regions was not affected. These findings demonstrate that exposure to early life trauma is associated with alterations in the gray matter of cingulate-limbic regions during adolescence in an otherwise healthy sample. These findings are interesting in the context that the affected regions are central neuroanatomical components in the psychopathology of depression, and adolescence is a peak period for risk and onset of the disorder.
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Development, clinical utility, and place of ivacaftor in the treatment of cystic fibrosis.
Drug Des Devel Ther
PUBLISHED: 01-01-2013
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Cystic fibrosis (CF) is a life-limiting, multisystem disease characterized by thick viscous secretions leading to recurrent lung infections, bronchiectasis, and progressive deterioration in lung function. CF is caused by loss or dysfunction of the CF transmembrane conductance regulator (CFTR) protein which is responsible for transepithelial chloride and water transport. Improved understanding of CFTR protein dysfunction has allowed the development of mutation-specific small-molecule compounds which directly target the underlying CFTR defect. Ivacaftor is the first licensed small-molecule compound for CF patients which targets the CFTR gating mutation Gly551Asp (previously termed G551D) and has the potential to be truly disease-modifying. Ivacaftor is an oral medication given twice daily and has shown benefit in terms of an increase in lung function, decreased sweat chloride, weight gain, improvement in patient-reported quality of life, and reduction in number of respiratory exacerbations in clinical trials. Although ivacaftor is currently only licensed for use in approximately 5% of the CF population (those who have at least one Gly551Asp mutation), the developmental pathway established by ivacaftor paves the way for other CFTR modulators that may benefit many more patients. In particular, a CFTR modulator for those with the Phe508del deletion (previously ?F508) would allow 90% of the CF population to benefit from disease-modifying treatment.
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Prefrontal cortex and executive function impairments in primary breast cancer.
Arch. Neurol.
PUBLISHED: 11-16-2011
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To examine differences in prefrontal-executive function between breast cancer (BC) survivors with and without a history of chemotherapy treatment compared with healthy control women and to determine the associations between prefrontal cortex deficits and behavioral impairments, as well as certain demographic and disease variables.
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Effect of temperature on post-wintering development and total lipid content of alfalfa leafcutting bees.
Environ. Entomol.
PUBLISHED: 10-14-2011
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Temperature plays an important role in effective management of the alfalfa leafcutting bee [Megachile rotundata (F.); Megachilidae], the major commercial pollinator of seed alfalfa [Medicago sativa (L.); Fabaceae] in North America. To improve our understanding of threshold and optimum rearing temperatures of M. rotundata, we examined the effect of temperature on postwintering development by using a greater number of temperature treatments than applied in previous studies (19 versus eight or fewer) and analytical tools formulated to model nonlinear relationships between temperature and insect development rates. We also tested the hypothesis that rearing temperature influences adult body lipid content at emergence, which could affect adult survival, establishment and performance as a pollinator, and reproductive success. We found that the Lactin-2 and Briere-2 models provided the best fits to data and gave reasonable estimates of lower (16-18°C) and upper (36-39°C) developmental thresholds and optimum (33-34°C) rearing temperatures for maximizing development rate. Bees successfully emerged over a broad range of temperatures (22-35°C), but variation in development rate among individuals reared at the same temperature was lowest at 31-33°C. The optimum rearing temperature to maximize the proportion of body lipids in adults was 27-29°C. Our results are discussed in relation to previous findings and speak to the difficulties in designing practical rearing guidelines that simultaneously maximize development rate, survival, and adult condition, while synchronizing adult emergence with alfalfa bloom.
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Gender differences in sexual behaviors of AD patients and their relationship to spousal caregiver well-being.
Aging Ment Health
PUBLISHED: 10-14-2011
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Little is known about gender differences in sexuality among community-dwelling heterosexual couples in which one partner has Alzheimers disease (AD). Few studies have examined gender differences in specific sexual behaviors or their associations with caregiver well-being. This study evaluated the impact of gender differences on intimacy and sexual satisfaction in marital relationships in which one partner has AD.
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Specialised antenatal clinics for women with a pregnancy at high risk of preterm birth (excluding multiple pregnancy) to improve maternal and infant outcomes.
Cochrane Database Syst Rev
PUBLISHED: 09-09-2011
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Amongst the risk factors for preterm birth, previous preterm delivery is a strong predictor. Specialised clinics for women with a history of spontaneous preterm delivery have been advocated as a way of improving outcomes for women and their infants.
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Modeling the effects of obstructive sleep apnea and hypertension in Vietnam veterans with PTSD.
Sleep Breath
PUBLISHED: 09-08-2011
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The present work aimed to extend models suggesting that obstructive sleep apnea (OSA) is associated with worse cognitive performance in community-dwelling older adults. We hypothesized that in addition to indices of OSA severity, hypertension is associated with worse cognitive performance in such adults.
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Structural characterization of a ribose-5-phosphate isomerase B from the pathogenic fungus Coccidioides immitis.
BMC Struct. Biol.
PUBLISHED: 07-01-2011
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Ribose-5-phosphate isomerase is an enzyme that catalyzes the interconversion of ribose-5-phosphate and ribulose-5-phosphate. This family of enzymes naturally occurs in two distinct classes, RpiA and RpiB, which play an important role in the pentose phosphate pathway and nucleotide and co-factor biogenesis.
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Design considerations for characterizing psychiatric trajectories across the lifespan: application to effects of APOE-?4 on cerebral cortical thickness in Alzheimers disease.
Am J Psychiatry
PUBLISHED: 07-01-2011
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Characterization of developmental trajectories across the lifespan is integral to understanding the prodromal course of many neuropsychiatric illnesses and the significant risk factors for disease onset or unfavorable outcomes. However, the standard experimental designs used in psychiatric research are not ideal for this purpose. The authors review the limitations of the most commonly employed designs in studies that make developmental or lifespan inferences in psychiatry: cross-sectional, single-cohort longitudinal, and unstructured multicohort longitudinal designs. Cross-sectional studies completely confound within- and between-subject sources of variation and hence rely on the presence of parallel trajectories and negligible sampling and age cohort differences for making valid developmental inferences. Delineating trajectories of within-individual change over substantial periods of time requires data covering long age spans that often cannot be covered using single-cohort longitudinal designs. Unstructured multicohort longitudinal designs are a commonly used alternative that can cover a longer age span in a shorter interval than necessary for a single-cohort design. However, the impact of cohort and sampling effects is often minimized or ignored in unstructured multicohort longitudinal designs. The authors propose that structured multicohort longitudinal designs are a particularly viable and underutilized class of designs in psychiatry that represents a significant improvement over cross-sectional designs and unstructured multicohort longitudinal designs for making developmental inferences while being more practical to implement than single-cohort longitudinal designs. As an example of this approach, the authors analyze changes in entorhinal cortex thickness in Alzheimers disease in relation to APOE-?4 genotype.
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Circadian clock gene polymorphisms and sleep-wake disturbance in Alzheimer disease.
Am J Geriatr Psychiatry
PUBLISHED: 06-29-2011
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One of the hypothesized causes of the breakdown in sleep-wake consolidation often occurring in individuals with Alzheimer disease (AD) is the dysfunction of the circadian clock. The goal of this study is to report indices of sleep-wake function collected from individuals with AD in relation to relevant polymorphisms in circadian clock-related genes.
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Cortical network for gaze control in humans revealed using multimodal MRI.
Cereb. Cortex
PUBLISHED: 06-21-2011
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Functional magnetic resonance imaging (fMRI) techniques allow definition of cortical nodes that are presumed to be components of large-scale distributed brain networks involved in cognitive processes. However, very few investigations examine whether such functionally defined areas are in fact structurally connected. Here, we used combined fMRI and diffusion MRI-based tractography to define the cortical network involved in saccadic eye movement control in humans. The results of this multimodal imaging approach demonstrate white matter pathways connecting the frontal eye fields and supplementary eye fields, consistent with the known connectivity of these regions in macaque monkeys. Importantly, however, these connections appeared to be more prominent in the right hemisphere of humans. In addition, there was evidence of a dorsal frontoparietal pathway connecting the frontal eye field and the inferior parietal lobe, also right hemisphere dominant, consistent with specialization of the right hemisphere for directed attention in humans. These findings demonstrate the utility and potential of using multimodal imaging techniques to define large-scale distributed brain networks, including those that demonstrate known hemispheric asymmetries in humans.
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Combinatorial effects of lapatinib and rapamycin in triple-negative breast cancer cells.
Mol. Cancer Ther.
PUBLISHED: 06-20-2011
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Triple-negative breast cancers, which lack estrogen receptor, progesterone receptor, and HER2/neu overexpression, account for approximately 15% of breast cancers, but occur more commonly in African Americans. The poor survival outcomes seen with triple-negative breast cancers patients are, in part, due to a lack of therapeutic targets. Epidermal growth factor receptor (EGFR) is overexpressed in 50% of triple-negative breast cancers, but EGFR inhibitors have not been effective in patients with metastatic breast cancers. However, mTOR inhibition has been shown to reverse resistance to EGFR inhibitors. We examined the combination effects of mTOR inhibition with EGFR inhibition in triple-negative breast cancer in vitro and in vivo. The combination of EGFR inhibition by using lapatinib and mTOR inhibition with rapamycin resulted in significantly greater cytotoxicity than the single agents alone and these effects were synergistic in vitro. The combination of rapamycin and lapatinib significantly decreased growth of triple-negative breast cancers in vivo compared with either agent alone. EGFR inhibition abrogated the expression of rapamycin-induced activated Akt in triple-negative breast cancer cells in vitro. The combination of EGFR and mTOR inhibition resulted in increased apoptosis in some, but not all, triple-negative cell lines, and these apoptotic effects correlated with a decrease in activated eukaryotic translation initiation factor (eIF4E). These results suggest that mTOR inhibitors could sensitize a subset of triple-negative breast cancers to EGFR inhibitors. Given the paucity of effective targeted agents in triple-negative breast cancers, these results warrant further evaluation.
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The impact of skin-sparing mastectomy with immediate reconstruction in patients with Stage III breast cancer treated with neoadjuvant chemotherapy and postmastectomy radiation.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 05-26-2011
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The safety and efficacy of skin-sparing mastectomy (SSM) with immediate reconstruction (IR) in patients with locally advanced breast cancer are unclear. The purpose of this study is to compare the outcomes of women with noninflammatory Stage III SSM with IR vs. non-SSM-treated women who underwent neoadjuvant chemotherapy and adjuvant radiation therapy (XRT).
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In vivo detection of GABA and glutamate with MEGA-PRESS: reproducibility and gender effects.
J Magn Reson Imaging
PUBLISHED: 04-22-2011
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To evaluate the reproducibility of ?-amino-butyric acid (GABA) and glutamate concentrations derived using three different spectral fitting methods, and to investigate gender-related differences in neurotransmitter levels.
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mTOR inhibition in breast cancer: unraveling the complex mechanisms of mTOR signal transduction and its clinical implications in therapy.
Expert Opin. Ther. Targets
PUBLISHED: 04-08-2011
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The mammalian target of rapamycin (mTOR)/PI3K/Akt pathway is altered in breast cancer cells, as demonstrated by mutations in both the upstream and downstream regulators of mTOR, including phosphatase and tensin homolog deleted in chromosome 10 (PTEN) loss or Akt/PI3K activation, and potentially in the mTOR protein itself. This contributes to increased cell proliferation, as well as growth-factor independence and endocrine resistance. Thus, mTOR inhibition holds considerable promise as a rational therapeutic strategy in breast cancer.
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Structural and functional properties of an upper airway dilator muscle in aged obese male rats.
Respiration
PUBLISHED: 03-28-2011
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Age, obesity and male sex are risk factors for the development of obstructive sleep apnoea syndrome.
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The negative effect of triple-negative breast cancer on outcome after breast-conserving therapy.
Ann. Surg. Oncol.
PUBLISHED: 03-26-2011
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To evaluate disease failure patterns and overall survival (OS) of women with triple-negative (TN) breast cancer who underwent breast-conserving therapy (BCT) and to understand the relationship of TN tumors with other prognostic factors.
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The role of thromboxane A(2) in the pathogenesis of intrauterine growth restriction associated with maternal smoking in pregnancy.
Prostaglandins Other Lipid Mediat.
PUBLISHED: 02-27-2011
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To examine the effect of maternal smoking in pregnancy on the production of two eicosanoids, thromboxane A(2) and prostacyclin I2, and their role in the pathogenesis of intrauterine growth restriction.
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Treatment adherence and outcome in women with inflammatory breast cancer: does race matter?
Cancer
PUBLISHED: 02-08-2011
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The authors compared treatment adherence rates and outcome in Caucasian and African American patients with inflammatory breast cancer (IBC).
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Hippocampal proton MR spectroscopy in early Alzheimers disease and mild cognitive impairment.
Brain Topogr
PUBLISHED: 01-19-2011
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Proton magnetic resonance spectroscopy ((1)H-MRS) studies have previously reported reduced brain N-acetyl aspartate (NAA) and increased myo-inositol (mI) in people with established Alzheimers disease (AD). The earliest structure affected by AD is the hippocampus but relatively few studies have examined its neuronal integrity by MRS in AD and fewer still in people with amnestic mild cognitive impairment (MCI). We measured the hippocampal concentration of NAA, mI, choline (Cho) and creatine + phosphocreatine (Cr + PCr) in 39 patients with AD, 21 subjects with MCI and 38 age matched healthy elderly controls. Patients with AD had a significantly lower hippocampal [NAA] than controls, with subjects with MCI intermediate between the other two groups. [NAA] was positively correlated with memory in the impaired groups. Using mean hippocampal [NAA] and [Cr + PCr] we correctly classified 72% of people with AD, and 75% of controls. Reductions in [NAA] can be detected in the hippocampi of subjects with MCI and hippocampal [NAA] and [Cr + PCr] can distinguish between mild AD and normal elderly controls.
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21-Gene recurrence scores: racial differences in testing, scores, treatment, and outcome.
Cancer
PUBLISHED: 01-15-2011
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African American (AA) women experience higher breast cancer mortality than white (W) women. These differences persist even among estrogen receptor (ER)-positive breast cancers. The 21-gene recurrence score (RS) predicts recurrence in patients with ER-positive/lymph node-negative breast cancer according to RS score-low risk (RS, 0-18), intermediate risk (RS, 19-31), and high risk (RS, >31). The high-risk group is most likely to benefit from chemotherapy, to achieve minimal benefit from hormonal therapy, and to exhibit lower ER levels (intrinsically luminal B cancers). In the current study, the authors investigated racial differences in RS testing, scores, treatment, and outcome.
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What is Visualize?

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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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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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.