Early- and late anthracycline-induced cardiac dysfunction: echocardiographic characterization and response to heart failure therapy

Background: Anthracycline-induced cardiac dysfunction (ACD) is a notorious side effect of anticancer treatment. It has been described as a phenomenon of a continuous progressive decline of cardiac function, eventually leading to dilated cardiomyopathy (DCM). This progressive nature suggests that patients with a delayed ACD diagnosis have greater compromise of cardiac function and more adverse remodeling, with a poor response to heart failure (HF) treatment. This study aimed to delineate the impact of a delayed ACD diagnosis on echocardiographic characteristics and response to HF treatment. Methods and results: From the population of our cardio-oncology outpatient clinic, 92 ACD patients were included in this study (age 51.6 ± 16.2 years, median cumulative anthracycline dose 329 [200–329] mg/m2), and a median follow-up of 25.0 [9.6–37.2] months after ACD diagnosis. Median time to ACD diagnosis for patients diagnosed early ( 1 year) was 4.0 vs. 47.7 months respectively. There were no echocardiographic differences between patients diagnosed early vs. late (LVEF 43.6 ± 4.9% vs. 43.0 ± 6.2% and iEDV 63.6 vs. 62.9 mL/m2). Eighty-three percent of patients presented with mild LV dysfunction and in 79% the LV was not dilated. Patients diagnosed early were more likely to have (partial) recovery of cardiac function upon HF treatment initiation (p = 0.015). Conclusions: In the setting of a cardio-oncology outpatient clinic, patients with ACD presented with a hypokinetic non-dilated cardiomyopathy, rather than typical DCM. Timing of ACD diagnosis did not impact HF disease severity. However, in patients receiving an early diagnosis, cardiac function was more likely to recover upon HF treatment

LVEF by Multigated Acquisition Scan Compared to Other Imaging Modalities in Cardio-Oncology: a Systematic Review

Purpose of Review: The prevalence of cancer therapy-related cardiac dysfunction (CTRCD) is increasing due to improved cancer survival. Serial monitoring of cardiac function is essential to detect CTRCD, guiding timely intervention strategies. Multigated radionuclide angiography (MUGA) has been the main screening tool using left ventricular ejection fraction (LVEF) to monitor cardiac dysfunction. However, transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) may be more suitable for serial assessment. We aimed to assess the concordance between different non-radiating imaging modalities with MUGA to determine whether they can be used interchangeably. / Recent Findings: In order to identify relevant studies, a PubMed search was performed. We included cross-sectional studies comparing MUGA LVEF to that of 2D TTE, 3D TTE, and CMR. From 470 articles, 22 were selected, comprising 1017 patients in total. Among others, this included three 3D TTE, seven 2D harmonic TTE + contrast (2DHC), and seven CMR comparisons. The correlations and Bland-Altman limits of agreement varied for CMR but were stronger for 3D TTE and 2DHC. / Summary: Our findings suggest that MUGA and CMR should not be used interchangeably whereas 3D TTE and 2DHC are appropriate alternatives following an initial MUGA scan. We propose a multimodality diagnostic imaging strategy for LVEF monitoring in patients undergoing cancer treatment

Pensamiento crítico en estudiantes del Grado de Educación Social

El presente artículo se centra en una investigación cualitativa sobre las creencias acerca del pensamiento crítico que poseen 72 estudiantes de tercer curso del Grado de Educación Social de la Universidad de Huelva (España). Los resultados, en consonancia con otras investigaciones, muestran que el alumnado tiene un conocimiento poco detallado aunque certero de lo que significa dicha competencia, ofreciendo explicaciones generales que van en acuerdo con las ideas que tienen acerca de la Universidad, la Sociedad y la finalidad de la Educación Social. La buena disposición que muestra la mayoría del alumnado investigado choca con escasos hábitos para el pensamiento crítico, achacándolo a una formación reproductiva, a la influencia perniciosa de determinados poderes sociales y a un no-saber-hacer-y-actuar de los futuros educadores sociales.This article focuses on qualitative research on the beliefs about critical thinking held by 72 third year students of the Social Education Degree of the University of Huelva (Spain). The results show that the students have a little detailed but accurate knowledge of what this competence means, offering general explanations that are in line with the ideas they have about the University, Society and the purpose of Social Education. The willingness shown by the majority of the students researched clashes with scarce habits for critical thinking, blaming it on reproductive training, the pernicious influence of certain social powers and the non-know-how-to-act of future social educators

Dopaminergic modulation of affective and social deficits induced by prenatal glucocorticoid exposure

Prenatal stress or exposure to elevated levels of glucocorticoids (GCs) can impair specific neurobehavioral circuits leading to alterations in emotional processes later in life. In turn, emotional deficits may interfere with the quality and degree of social interaction. Here, by using a comprehensive behavioral approach in combination with the measurement of ultrasonic vocalizations, we show that in utero GC (iuGC)-exposed animals present increased immobility in the forced swimming test, pronounced anhedonic behavior (both anticipatory and consummatory), and an impairment in social interaction at different life stages. Importantly, we also found that social behavioral expression is highly dependent on the affective status of the partner. A profound reduction in mesolimbic dopaminergic transmission was found in iuGC animals, suggesting a key role for dopamine (DA) in the etiology of the observed behavioral deficits. Confirming this idea, we present evidence that a simple pharmacological approach—acute L-3,4-dihydroxyphenylacetic acid (L-DOPA) oral administration, is able to normalize DA levels in iuGC animals, with a concomitant amelioration of several dimensions of the emotional and social behaviors. Interestingly, L-DOPA effects in control individuals were not so straightforward; suggesting that both hypo- and hyperdopaminergia are detrimental in the context of such complex behaviors.This work was supported by a grant of Institute for the Study of Affective Neuroscience (ISAN) and Janssen Neurosciences Prize. SB and AJR have Fundacao para a Ciencia e Tecnologia (FCT) fellowships (SFRH/BD/89936/2012; SFRH/BPD/33611/2009)

A Cyclic Undecamer Peptide Mimics a Turn in Folded Alzheimer Amyloid β and Elicits Antibodies against Oligomeric and Fibrillar Amyloid and Plaques

The 39- to 42-residue amyloid β (Aβ) peptide is deposited in extracellular fibrillar plaques in the brain of patients suffering from Alzheimer's Disease (AD). Vaccination with these peptides seems to be a promising approach to reduce the plaque load but results in a dominant antibody response directed against the N-terminus. Antibodies against the N-terminus will capture Aβ immediately after normal physiological processing of the amyloid precursor protein and therefore will also reduce the levels of non-misfolded Aβ, which might have a physiologically relevant function. Therefore, we have targeted an immune response on a conformational neo-epitope in misfolded amyloid that is formed in advance of Aβ-aggregation. A tetanus toxoid-conjugate of the 11-meric cyclic peptide Aβ(22–28)-YNGK′ elicited specific antibodies in Balb/c mice. These antibodies bound strongly to the homologous cyclic peptide-bovine serum albumin conjugate, but not to the homologous linear peptide-conjugate, as detected in vitro by enzyme-linked immunosorbent assay. The antibodies also bound—although more weakly—to Aβ(1–42) oligomers as well as fibrils in this assay. Finally, the antibodies recognized Aβ deposits in AD mouse and human brain tissue as established by immunohistological staining. We propose that the cyclic peptide conjugate might provide a lead towards a vaccine that could be administered before the onset of AD symptoms. Further investigation of this hypothesis requires immunization of transgenic AD model mice

Factor structure and measurement invariance across various demographic groups and over time for the phq-9 in primary care patients in spain

The Patient Health Questionnaire (PHQ-9) is a widely-used screening tool for depression in primary care settings. The purpose of the present study is to identify the factor structure of the PHQ-9 and to examine the measurement invariance of this instrument across different sociodemographic groups and over time in a sample of primary care patients in Spain. Data came from 836 primary care patients enrolled in a randomized controlled trial (PsicAP study) and a subsample of 218 patients who participated in a follow-up assessment at 3 months. Confirmatory factor analysis (CFA) was used to test one- and two-factor structures identified in previous studies. Analyses of multiple-group invariance were conducted to determine the extent to which the factor structure is comparable across various demo- graphic groups (i.e., gender, age, marital status, level of education, and employment situa- tion) and over time. Both one-factor and two-factor re-specified models met all the pre- established fit criteria. However, because the factors identified in the two-factor model were highly correlated (r = .86), the one-factor model was preferred for its parsimony. Multi-group CFA indicated measurement invariance across different demographic groups and across time. The present findings suggest that physicians in Spain can use the PHQ-9 to obtain a global score for depression severity in different demographic groups and to reliably monitor changes over time in the primary care setting

Severe Pandemic H1N1 2009 Infection Is Associated with Transient NK and T Deficiency and Aberrant CD8 Responses

BACKGROUND: It is unclear why the severity of influenza varies in healthy adults or why the burden of severe influenza shifts to young adults when pandemic strains emerge. One possibility is that cross-protective T cell responses wane in this age group in the absence of recent infection. We therefore compared the acute cellular immune response in previously healthy adults with severe versus mild pandemic H1N1 infection. METHODS AND PRINCIPAL FINDINGS: 49 previously healthy adults admitted to the National Hospital of Tropical Diseases, Viet Nam with RT-PCR-confirmed 2009 H1N1 infection were prospectively enrolled. 39 recovered quickly whereas 10 developed severe symptoms requiring supplemental oxygen and prolonged hospitalization. Peripheral blood lymphocyte subset counts and activation (HLADR, CD38) and differentiation (CD27, CD28) marker expression were determined on days 0, 2, 5, 10, 14 and 28 by flow cytometry. NK, CD4 and CD8 lymphopenia developed in 100%, 90% and 60% of severe cases versus 13% (p<0.001), 28%, (p = 0.001) and 18% (p = 0.014) of mild cases. CD4 and NK counts normalized following recovery. B cell counts were not significantly associated with severity. CD8 activation peaked 6-8 days after mild influenza onset, when 13% (6-22%) were HLADR+CD38+, and was accompanied by a significant loss of resting/CD27+CD28+ cells without accumulation of CD27+CD28- or CD27-CD28- cells. In severe influenza CD8 activation peaked more than 9 days post-onset, and/or was excessive (30-90% HLADR+CD38+) in association with accumulation of CD27+CD28- cells and maintenance of CD8 counts. CONCLUSION: Severe influenza is associated with transient T and NK cell deficiency. CD8 phenotype changes during mild influenza are consistent with a rapidly resolving memory response whereas in severe influenza activation is either delayed or excessive, and partially differentiated cells accumulate within blood indicating that recruitment of effector cells to the lung could be impaired

Selecting interventions to promote fruit and vegetable consumption: from policy to action, a planning framework case study in Western Australia

The Department of Health in Western Australia identified access to, and daily consumption of recommended amounts of fruit and vegetables, as priority health determinants. The numerous factors that influence supply and consumption of fruit and vegetables indicated that a comprehensive approach would be required. A government and non-government sector steering group was set up to select priority interventions using the National Public Health Partnership\u27s Framework for Implementing Public Health Strategies. This structured framework was used for developing strategies to improve fruit and vegetable consumption and supply, and to identify implementation priorities. After one year a desktop audit of progress on framework interventions was undertaken