OBJECTIVES The goal of this study was to demonstrate that cardiac magnetic resonance could reveal anthracycline-induced early tissue remodeling and its relation to cardiac dysfunction and left ventricular (LV) atrophy. BACKGROUND Serum biomarkers of cardiac dysfunction, although elevated after chemotherapy, lack specificity for the mechanism of myocardial tissue alterations. METHODS A total of 27 women with breast cancer (mean age 51.8 ± 8.9 years, mean body mass index 26.9 ± 3.6 kg/m2), underwent cardiac magnetic resonance before and up to 3 times after anthracycline therapy. Cardiac magnetic resonance variables were LV ejection fraction, normalized T2-weighted signal intensity for myocardial edema, extracellular volume (ECV), LV cardiomyocyte mass, intracellular water lifetime (τic; a marker of cardiomyocyte size), and late gadolinium enhancement. RESULTS At baseline, patients had a relatively low (10-year) Framingham cardiovascular event risk (median 5%), normal LV ejection fractions (mean 69.4 ± 3.6%), and normal LV mass index (51.4 ± 8.0 g/m2), a mean ECV of 0.32 ± 0.038, mean τic of 169 ± 69 ms, and no late gadolinium enhancement. At 351 to 700 days after anthracycline therapy (240 mg/m2), mean LV ejection fraction had declined by 12% to 58 ± 6% (p < 0.001) and mean LV mass index by 19 g/m2 to 36 ± 6 g/m2 (p < 0.001), and mean ECV had increased by 0.037 to 0.36 ± 0.04 (p = 0.004), while mean τic had decreased by 62 ms to 119 ± 54 ms (p = 0.004). Myocardial edema peaked at about 146 to 231 days (p < 0.001). LV mass index was associated with τic (β = 4.1 ± 1.5 g/m2 per 100-ms increase in τic, p = 0.007) but not with ECV. Cardiac troponin T (mean 4.6 ± 1.4 pg/ml at baseline) increased significantly after anthracycline treatment (p < 0.001). Total LV cardiomyocyte mass, estimated as: (1 - ECV) × LV mass, declined more rapidly after anthracycline therapy, with peak cardiac troponin T >10 pg/ml. There was no evidence for any significant interaction between 10-year cardiovascular event risk and the effect of anthracycline therapy. CONCLUSIONS A decrease in LV mass after anthracycline therapy may result from cardiomyocyte atrophy, demonstrating that mechanisms other than interstitial fibrosis and edema can raise ECV. The loss of LV cardiomyocyte mass increased with the degree of cardiomyocyte injury, assessed by peak cardiac troponin T after anthracycline treatment. (Doxorubicin-Associated Cardiac Remodeling Followed by CMR in Breast Cancer Patients; NCT03000036) (J Am Coll Cardiol Img 2018;11:1045–55) © 2018 by the American College of Cardiology Foundation.
PurposeTo examine the impact of simulated medical consultations using standardized patients (SPs) on the empathy levels of fourth- and sixth-year students at the Unicamp medical school in Brazil.MethodThroughout 2011 and 2012, the authors conducted this study with two classes of fourth-year (n = 124) and two classes of sixth-year (n = 123) medical students. Students completed the medical student version of the Jefferson Scale of Physician Empathy before and after simulated medical consultations with SPs, followed by an in-depth debriefing dealing with the feelings of the patient about the disease, such as fear, guilt, anger, and abandonment; the feelings of the doctor towards the patient; and other topics as they arose.ResultsThe simulation activity increased the empathy scores of the fourth-year students (from 115.8 to 121.1, P < .001, effect size = 0.61) and of the sixth-year students (from 117.1 to 123.5, P < .001, effect size = 0.64).ConclusionsAlthough the study results were obtained via self-report—a limitation—they suggest that the effective simulation of medical consultations with SPs may improve medical students’ empathy levels. One unexpected result was that this activity, during the debriefing, became a forum for debating topics such as the doctor–patient relationship, the hidden curriculum, negative role models, and emotionally significant experiences of students in medical school. This kind of activity in itself may influence young doctors to become more empathetic and compassionate with their patients and foster a more meaningful way of practicing medicine.
Cancer and its morbidities, such as cancer cachexia, constitute a major public health problem. Although cancer cachexia has afflicted humanity for centuries, its underlying multifactorial and complex physiopathology has hindered the understanding of its mechanism. During the last few decades we have witnessed a dramatic increase in the understanding of cancer cachexia pathophysiology. Anorexia and muscle and adipose tissue wasting are the main features of cancer cachexia. These apparently independent symptoms have humoral factors secreted by the tumor as a common cause. Importantly, the hypothalamus has emerged as an organ that senses the peripheral signals emanating from the tumoral environment, and not only elicits anorexia but also contributes to the development of muscle and adipose tissue loss. Herein, we review the roles of factors secreted by the tumor and its effects on the hypothalamus, muscle and adipose tissue, as well as highlighting the key targets that are being exploited for cancer cachexia treatment.
The production of an extracellular lipase using corn steep liquor (CSL) as the nitrogen source in the cultivation of Geotrichum candidum NRRLY‐552 was evaluated. The optimized conditions in shake flasks were CSL, 8.0 % w/v, soybean oil, 0.6 % w/v, pH 7.0, 30 °C, 250 rpm, and 48 h, resulting in a maximum lipase productivity of 0.438 U mL−1 h−1(U = the amount of enzyme required to liberate 1 μmol of fatty acid per minute). Scale‐up was evaluated with airlift and stirred tank reactors; the best conditions, respectively, were 1 vvm(volume of gas per volume of medium per minute) of aeration which resulted in 0.535 U mL−1 h−1 (32 h) and 1 vvm and 300 rpm resulting in 0.563 U mL−1 h−1 (16 h). To facilitate downstream processes, lipase production was also evaluated using CSL previously clarified with activated charcoal resulting in 0.275 U mL−1 h−1 (24 h) using 12 % (w/v) of clarified CSL in shake flasks. The obtained results showed that CSL leads to similar productivity compared to peptone using the same microorganism under similar conditions. In addition the cost of fermentation medium using CSL is much lower because it is a very inexpensive by‐product from corn processing.
Burnout syndrome is a common occurrence among oncologists. Doctors enrolled in residency programs in clinical oncology are exposed to similar risk factors; however, few data are available in this population. This study assessed the occurrence of burnout and associated factors among first-year residents at Brazilian institutions. The present prospective, multicenter, cohort study was conducted with doctors enrolled in residency programs in clinical oncology at Brazilian institutions affiliated with the public health system. The participants answered a sociodemographic questionnaire, the Maslach Burnout Inventory (MBI), Lipp's Stress Inventory, and the Beck Depression Inventory (BDI), upon admission to the program and 6 and 12 months later. Of 37 eligible residency programs in 2009, 11 (30.6 %) agreed to participate in the study. Fifty-four residents, representing 100 % of new admissions to the participating institutions, were included. Most of the participants met the criteria for severe burnout upon admission to the residency programs (emotional exhaustion in 49.0 % and depersonalization in 64.7 %). The scores on MBI domains emotional exhaustion and depersonalization increased significantly (p < 0.01) during the first year of residency, and the prevalence of burnout increased to 88 % at the end of that first year. The present study found a high prevalence of burnout among doctors enrolled in residency programs in clinical oncology at Brazilian institutions. A large fraction of the participants met the criteria for burnout syndrome upon admission to the program, which suggests that the problem began during the course of the previous residency program in internal medicine.
The mechanisms by which dietary sodium modulates cardiovascular risk are not fully understood. This study investigated whether sodium intake is related to carotid structure and hemodynamics and to plasma matrix metalloproteinase (MMP) activity in hypertensive adults. One hundred thirty-four participants were cross-sectionally evaluated by clinical history, anthropometry, carotid ultrasound, and analysis of hemodynamic, inflammatory, and metabolic variables. Daily sodium intake (DSI) was estimated by 24-h recall, discretionary sodium, and a FFQ. In 42 patients, plasma MMP-2 and MMP-9 activities were also analyzed. The mean DSI was 5.52 ± 0.29 g/d. Univariate analysis showed that DSI correlated with common carotid artery systolic and diastolic diameter (r = 0.36 and 0.34; both P < 0.001), peak and mean circumferential tension (r = 0.44 and 0.39; both P < 0.001), Young's Elastic Modulus (r = 0.40; P < 0.001), intima-media thickness (r = 0.19; P < 0.05), and internal carotid artery resistive index (r = 0.20; P < 0.05). Multivariate analyses revealed that only artery diameter, circumferential wall tension, and Young's Elastic Modulus were independently associated with DSI. Conversely, plasma MMP-9 activity was associated with DSI (r = 0.53; P < 0.001) as well as with common carotid systolic diameter (r = 0.33; P < 0.05) and Young's Elastic Modulus (r = 0.38; P < 0.01). In conclusion, sodium intake is associated with carotid alterations in hypertensive adults independently of systemic hemodynamic variables. The present findings also suggest that increased MMP-9 activity might play a role in sodium-induced vascular remodeling.
The influence of some variables in the in vitro synthesis of dextran by dextransucrase from Leusconostoc mesenteroides NRRL B512F, as well as in the acidic hydrolysis of the dextran produced, were studied in order to maximize the production of clinical dextran (dextran 70 and dextran 40). The experiments were conducted using a factorial design and surface response analysis
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