Pharmacological strategies to reduce anthracycline-associated cardiotoxicity in cancer patients.

INTRODUCTION: Anthracycline chemotherapeutic agents are widely used in the treatment of hematological and solid tumors, working principally through DNA intercalation and topoisomerase II inhibition. However, they are also well known to have cardiotoxic sequelae, commonly denoted as a reduction in ejection fraction. Drug-associated cardiotoxicity remains a significant limiting factor in the use of anthracyclines. AREAS COVERED: In this review, we explore the potential mechanisms of anthracycline-associated cardiotoxicity, identifying high-risk cohorts and approaches to cardiovascular monitoring. The mechanisms through which cardiotoxicity occurs are complex and diverse, ultimately leading to increased oxidative stress, mitochondrial dysfunction, and subsequent cellular apoptosis. Many of the cardiotoxic effects of anthracyclines exhibit a dose-dependent cumulative relationship and are more apparent in patients with previously existing cardiovascular risk factors. Long-term cardiovascular monitoring and optimization of risk factors, prior to commencing treatment as well as beyond the time of treatment, is therefore essential. EXPERT OPINION: We discuss some of the pharmacological strategies proposed to mitigate anthracycline-associated cardiotoxicity as well as prevention strategies to reduce the burden of coexisting cardiovascular risk factors. We highlight methods of early detection of patient cohorts who are at increased risk of developing anthracycline-associated cardiotoxicity and identify potential avenues for further research

Integrating personality research and animal contest theory: aggressiveness in the green swordtail <i>Xiphophorus helleri</i>

&lt;p&gt;Aggression occurs when individuals compete over limiting resources. While theoretical studies have long placed a strong emphasis on context-specificity of aggression, there is increasing recognition that consistent behavioural differences exist among individuals, and that aggressiveness may be an important component of individual personality. Though empirical studies tend to focus on one aspect or the other, we suggest there is merit in modelling both within-and among-individual variation in agonistic behaviour simultaneously. Here, we demonstrate how this can be achieved using multivariate linear mixed effect models. Using data from repeated mirror trials and dyadic interactions of male green swordtails, &lt;i&gt;Xiphophorus helleri&lt;/i&gt;, we show repeatable components of (co)variation in a suite of agonistic behaviour that is broadly consistent with a major axis of variation in aggressiveness. We also show that observed focal behaviour is dependent on opponent effects, which can themselves be repeatable but were more generally found to be context specific. In particular, our models show that within-individual variation in agonistic behaviour is explained, at least in part, by the relative size of a live opponent as predicted by contest theory. Finally, we suggest several additional applications of the multivariate models demonstrated here. These include testing the recently queried functional equivalence of alternative experimental approaches, (e. g., mirror trials, dyadic interaction tests) for assaying individual aggressiveness.&lt;/p&gt

Daily Activity Patterns of Two Co-Occurring Tropical Satyrine Butterflies

Adult males and females of many insect species are expected to adjust their daily activity pattern in order to avoid stressful climatic conditions and increase the chances to encounter sexual partners. Using scan sampling methods associated with focal individual observations it was found that two satyrine butterflies of similar size and morphology, Hermeuptychia hermes (Fabricius) (Leptidoptera: Nymphalidae) and Paryphthimoides phronius (Godart), show completely different daily activity patterns on forest edges in southeastern Brazil. Hermeuptychia hermes presents one abundance peak in the morning and another in the late afternoon, while P. phronius abundance peaks in the mid-day, remaining stable until 1700 h. This difference is probably due to the occurrence of territorial behavior in the later species. The beginning of territorial defense by P. phronius males coincided with the time of new-born female activity. However, newly hatched females were not sexually receptive. The afternoon territoriality in male P. phronius may be in part related to mate acquisition. However, why the abundance of H. hermes decreases when the abundance of P. phronius increases is less clear

The spectrum of EWSR1-rearranged neoplasms at a tertiary sarcoma centre; assessing 772 tumour specimens and the value of current ancillary molecular diagnostic modalities.

Background EWSR1 rearrangements were first identified in Ewing sarcoma, but the spectrum of EWSR1-rearranged neoplasms now includes many soft tissue tumour subtypes including desmoplastic small round cell tumour (DSRCT), myxoid liposarcoma (MLPS), extraskeletal myxoid chondrosarcoma (EMC), angiomatoid fibrous histiocytoma (AFH), clear cell sarcoma (CCS) and myoepithelial neoplasms. We analysed the spectrum of EWSR1-rearranged soft tissue neoplasms at our tertiary sarcoma centre, by assessing ancillary molecular diagnostic modalities identifying EWSR1-rearranged tumours and reviewing the results in light of our current knowledge of these and other Ewing sarcoma-like neoplasms.Methods We retrospectively analysed all specimens tested for EWSR1 rearrangements by fluorescence in situ hybridisation (FISH) and/or reverse transcription-PCR (RT-PCR) over a 7-year period.Results There was a total of 772 specimens. FISH was performed more often than RT-PCR (n=753, 97.5% vs n=445, 57.6%). In total, 210 (27.9%) specimens were FISH-positive for EWSR1 rearrangement compared to 111 (14.4%) that showed EWSR1 fusion transcripts with RT-PCR. Failure rates for FISH and RT-PCR were 2.5% and 18.0%. Of 109 round cell tumours with pathology consistent with Ewing sarcoma, 15 (13.8 %) cases were FISH-positive without an identifiable EWSR1 fusion transcript, 4 (3.7%) were FISH-negative but RT-PCR positive and 4 (3.7%) were negative for both. FISH positivity for DSRCT, MLPS, EMC, AFH and CCS was 86.3%, 4.3%, 58.5%, 60.0% and 87.9%, respectively. A positive FISH result led to diagnostic change in 40 (19.0%) EWSR1-rearranged cases. 13 FISH-positive cases remained unclassifiable.Conclusions FISH is more sensitive for identifying EWSR1 rearrangements than RT-PCR. However, there can be significant morphologic and immunohistochemical overlap between groups of EWSR1-rearranged neoplasms, with important prognostic and therapeutic implications. FISH and RT-PCR should be used as complementary modalities in diagnosing EWSR1-rearranged neoplasms, but as tumour groups harbouring EWSR1 rearrangements are increasingly characterised and because given translocations involving EWSR1 and its partner genes are not always specific for tumour types, it is critical that these are evaluated by specialist soft tissue surgical pathologists noting the morphologic and immunohistochemical context. As RT-PCR using commercial primers is limited to only the most prevalent EWSR1 fusion transcripts, the incorporation of high-throughput sequencing technologies into the standard diagnostic repertoire to assess for multiple molecular abnormalities of soft tissue tumours in parallel (including detection of newly characterised Ewing sarcoma-like tumours) might be the most effective and efficient means of ancillary diagnosis in future

Methylphenidate Treatment in Children with Borderline IQ and Mental Retardation: Analysis of Three Aggregated Studies

Objective: To determine response of low-IQ children with attention deficit hyperactivity disorder (ADHD) symptoms to methylphenidate (MPH). Methods: An aggregated analysis was conducted in 90 children with low IQ who received the same dose regimen of MPH in three independent, placebo-controlled studies. Active drug and placebo were given from 2 to 4 weeks each. Outcome measures included teacher and parent ratings on standardized behavior scales (mean n = 84), performance on computer-controlled cognitive-motor tests (n = 62), and measures of cardiovascular response (n = 85). Results: Both teachers and parents rated the children consistently as being improved on subscales assessing attention, overactivity, and conduct problems. Some 44% of the subjects showed at least a 30% reduction compared with placebo on teacher ratings. MPH improved accuracy on several cognitive tests, response speed was increased on some, and seat activity declined for one of three tests; heart rate was mildly increased (3.9 beats/minute) with MPH. Analyses of IQ and mental age as moderator variables suggested that lower functional level (especially lower IQ) may be associated with a less favorable response to MPH. Conclusions: Children with low IQ and ADHD clearly respond to MPH, but their rate of beneficial response appears to be well under that of normal-IQ children and more varied. Different attentional mechanisms may moderate response to psychostimulants

Health-Related Quality of Life and Experiences of Sarcoma Patients during the COVID-19 Pandemic

Sarcomas are rare cancers with a spectrum of clinical needs and outcomes. We investigated care experiences and health-related quality of life (HRQoL) in sarcoma patients during the COVID-19 pandemic. Patients with appointments during the first two months of the UK lockdown were invited to complete a survey. Questions included views on care modifications, COVID-19 worry and psychosocial impact, and EORTC-QLQ-C30 items. 350 patients completed the survey; median age 58 (16–92) years. Care modifications included telemedicine (74%) and postponement of appointments (34%), scans (34%) or treatment (10%). Most felt the quality of care was not affected (72%), however, social life (87%) and emotional wellbeing (41%) were affected. Worry about COVID-19 infection was moderately high (mean 5.8/10) and significantly related to higher cancer-related worry; associated with lower emotional functioning irrespective of treatment intent. Curative patients (44%) with low resilient coping scores had significantly higher COVID-19 worry. Patients who did not know their treatment intent (22%) had significantly higher COVID-19 worry and insomnia. In summary, care experiences were generally positive; however, cancer-related worry, low resilient coping and uncertainty about treatment intent were associated with COVID-19 worry. These patients may benefit from additional psychological support during the pandemic and beyond

Source Evaluation and Trace Metal Contamination in Benthic Sediments from Equatorial Ecosystems Using Multivariate Statistical Techniques

race metals (Cd, Cr, Cu, Ni and Pb) concentrations in benthic sediments were analyzed through multi-step fractionation scheme to assess the levels and sources of contamination in estuarine, riverine and freshwater ecosystems in Niger Delta (Nigeria). The degree of contamination was assessed using the individual contamination factors (ICF) and global contamination factor (GCF). Multivariate statistical approaches including principal component analysis (PCA), cluster analysis and correlation test were employed to evaluate the interrelationships and associated sources of contamination. The spatial distribution of metal concentrations followed the pattern Pb>Cu>Cr>Cd>Ni. Ecological risk index by ICF showed significant potential mobility and bioavailability for Cu, Cu and Ni. The ICF contamination trend in the benthic sediments at all studied sites was Cu>Cr>Ni>Cd>Pb. The principal component and agglomerative clustering analyses indicate that trace metals contamination in the ecosystems was influenced by multiple pollution sources

Right coronary artery originating from left anterior descending artery: a case report

Right Coronary Artery (RCA) originating from left anterior descending artery is a very rare congenital coronary artery anomaly. A 66-year-old man presented with hypertension and complaints of exertional chest pain. The angiography was performed. Aortic root angiography showed no coronary ostium orginating from the right sinus of valsalva. Right coronary artery was vizualized as anomalously originating from the midportion of left anterior descending artery. Severe stenosis were seen in ostium of anomalous right coronary artery, in midportion of left anterior descending and in midportion of circumflex artery. The patient was referred for coronary artery bypass grafting. The patient underwent coronary artery bypass surgery for three vessels. He was discharged home on postoperative day 7 without any complication. His echocardiogram on follow-up visit revealed good biventricular function