Long-Term Follow-Up of a Nonprogressive Left Main Coronary Artery Fistula to Right Atrium

Coronary artery fistula is a rare cardiac abnormality, occurring more frequently in young patients and treated with cardiac surgery or percutaneous interventions in most cases. We present the case of a 63-year-old man with an incidental diagnosis of coronary artery fistula, treated with conservative strategy. (Level of Difficulty: Intermediate.

Diagnostic accuracy of multislice computed tomography coronary angiography is improved at low heart rates

Purpose: Assess the effect of heart rate on diagnostic accuracy for the detection of significant coronary artery stenosis using 16-row multislice computed tomography (MSCT). Material and methods: About 120 patients (105 males; 59 ± 11 years) with suspected coronary artery disease who underwent conventional coronary angiography (CA) and MSCT-CA were retrospectively enrolled for the study. Patients underwent a MSCT-CA (Sensation 16, Siemens, Germany), with the following protocol: Collimation 16 × 0.75 mm, gantry rotation time 420 ms, feed/rotation 3.0 mm, kV 120, mAs 400-500. The protocol for contrast material administration was 100 ml of Iodixanol (Visipaque 320 mg l/ml, Amersham, UK) at 4 ml/s and the delay was defined with a bolus tracking technique. In all patients the mean heart rate (HR) during the scan was used as a criteria to divide the population in two groups of 60 patients each. In one group (Low HR) the 60 patients with lower heart rates, and in the other group (High HR) the patients with higher heart rates. In the two groups diagnostic accuracy (per coronary segment) for the detection of significant stenosis (≥50% lumen reduction) was evaluated in vessels ≥2 mm of diameter using quantitative CA as reference standard. The difference in diagnostic accuracy were compared with a Chi2 test and a p < 0.05 was considered significant. Results: There was no significant difference between the two groups regarding age, gender, weight, mean intravascular attenuation, and calcium score. Overall 1310 (652 for Low HR and 658 for High HR) segments with 219 (105 for Low HR and 114 for High HR) significant lesions were available for the analysis. The average heart rate was 52 ± 4HU and 63 ± 5HU for Low HR and High HR, respectively (p < 0.001). The sensitivity and specificity were 92 and 96% for Low HR and 90 and 92% for High HR (p < 0.05). There were 22 vs. 44 false positives, and 8 vs. 12 false negatives in the Low HR and High HR, respectively. Conclusion: Increasing HR significantly deteriorates diagnostic accuracy in MSCT-CA

Different features of tumor-associated NK cells in patients with low-grade or high-grade peritoneal carcinomatosis

Peritoneal carcinomatosis (PC) is a rare disease defined as diffused implantation of neoplastic cells in the peritoneal cavity. This clinical picture occurs during the evolution of peritoneal tumors, and it is the main cause of morbidity and mortality of patients affected by these pathologies, though cytoreductive surgery with heated intra-peritoneal chemotherapy (CRS/HIPEC) is yielding promising results. In the present study, we evaluated whether the tumor microenvironment of low-grade and high-grade PC could affect the phenotypic and functional features and thus the anti-tumor potential of NK cells. We show that while in the peritoneal fluid (PF) of low-grade PC most CD56dim NK cells show a relatively immature phenotype (NKG2A+KIR\u2013CD57\u2013CD16dim), in the PF of high-grade PC NK cells are, in large majority, mature (CD56dimKIR+CD57+CD16bright). Furthermore, in low-grade PC, PF-NK cells are characterized by a sharp down-regulation of some activating receptors, primarily NKp30 and DNAM-1, while, in high-grade PC, PF-NK cells display a higher expression of the PD-1 inhibitory checkpoint. The compromised phenotype observed in low-grade PC patients corresponds to a functional impairment. On the other hand, in the high-grade PC patients PF-NK cells show much more important defects that only partially reflect the compromised phenotype detected. These data suggest that the PC microenvironment may contribute to tumor escape from immune surveillance by inducing different NK cell impaired features leading to altered anti-tumor activity. Notably, after CRS/HIPEC treatment, the altered NK cell phenotype of a patient with a low-grade disease and favorable prognosis was reverted to a normal one. Our present data offer a clue for the development of new immunotherapeutic strategies capable of restoring the NK-mediated anti-tumor responses in association with the CRS/HIPEC treatment to increase the effectiveness of the current therapy

Using Food Webs and Metabolic Theory to Monitor, Model, and Manage Atlantic Salmon-A Keystone Species Under Threat

Populations of Atlantic salmon are crashing across most of its natural range: understanding the underlying causes and predicting these collapses in time to intervene effectively are urgent ecological and socioeconomic priorities. Current management techniques rely on phenomenological analyses of demographic population time-series and thus lack a mechanistic understanding of how and why populations may be declining. New multidisciplinary approaches are thus needed to capitalize on the long-term, large-scale population data that are currently scattered across various repositories in multiple countries, as well as marshaling additional data to understand the constraints on the life cycle and how salmon operate within the wider food web. Here, we explore how we might combine data and theory to develop the mechanistic models that we need to predict and manage responses to future change. Although we focus on Atlantic salmon-given the huge data resources that already exist for this species-the general principles developed here could be applied and extended to many other species and ecosystems

Achieving temperature-size changes in a unicellular organism.

The temperature-size rule (TSR) is an intraspecific phenomenon describing the phenotypic plastic response of an organism size to the temperature: individuals reared at cooler temperatures mature to be larger adults than those reared at warmer temperatures. The TSR is ubiquitous, affecting >80% species including uni- and multicellular groups. How the TSR is established has received attention in multicellular organisms, but not in unicells. Further, conceptual models suggest the mechanism of size change to be different in these two groups. Here, we test these theories using the protist Cyclidium glaucoma. We measure cell sizes, along with population growth during temperature acclimation, to determine how and when the temperature-size changes are achieved. We show that mother and daughter sizes become temporarily decoupled from the ratio 2:1 during acclimation, but these return to their coupled state (where daughter cells are half the size of the mother cell) once acclimated. Thermal acclimation is rapid, being completed within approximately a single generation. Further, we examine the impact of increased temperatures on carrying capacity and total biomass, to investigate potential adaptive strategies of size change. We demonstrate no temperature effect on carrying capacity, but maximum supported biomass to decrease with increasing temperature

Using Food Webs and Metabolic Theory to Monitor, Model, and Manage Atlantic Salmon—A Keystone Species Under Threat

Populations of Atlantic salmon are crashing across most of its natural range: understanding the underlying causes and predicting these collapses in time to intervene effectively are urgent ecological and socioeconomic priorities. Current management techniques rely on phenomenological analyses of demographic population time-series and thus lack a mechanistic understanding of how and why populations may be declining. New multidisciplinary approaches are thus needed to capitalize on the long-term, large-scale population data that are currently scattered across various repositories in multiple countries, as well as marshaling additional data to understand the constraints on the life cycle and how salmon operate within the wider food web. Here, we explore how we might combine data and theory to develop the mechanistic models that we need to predict and manage responses to future change. Although we focus on Atlantic salmon—given the huge data resources that already exist for this species—the general principles developed here could be applied and extended to many other species and ecosystems

Disruption of a GATA4/Ankrd1 Signaling Axis in Cardiomyocytes Leads to Sarcomere Disarray: Implications for Anthracycline Cardiomyopathy

Doxorubicin (Adriamycin) is an effective anti-cancer drug, but its clinical usage is limited by a dose-dependent cardiotoxicity characterized by widespread sarcomere disarray and loss of myofilaments. Cardiac ankyrin repeat protein (CARP, ANKRD1) is a transcriptional regulatory protein that is extremely susceptible to doxorubicin; however, the mechanism(s) of doxorubicin-induced CARP depletion and its specific role in cardiomyocytes have not been completely defined. We report that doxorubicin treatment in cardiomyocytes resulted in inhibition of CARP transcription, depletion of CARP protein levels, inhibition of myofilament gene transcription, and marked sarcomere disarray. Knockdown of CARP with small interfering RNA (siRNA) similarly inhibited myofilament gene transcription and disrupted cardiomyocyte sarcomere structure. Adenoviral overexpression of CARP, however, was unable to rescue the doxorubicin-induced sarcomere disarray phenotype. Doxorubicin also induced depletion of the cardiac transcription factor GATA4 in cardiomyocytes. CARP expression is regulated in part by GATA4, prompting us to examine the relationship between GATA4 and CARP in cardiomyocytes. We show in co-transfection experiments that GATA4 operates upstream of CARP by activating the proximal CARP promoter. GATA4-siRNA knockdown in cardiomyocytes inhibited CARP expression and myofilament gene transcription, and induced extensive sarcomere disarray. Adenoviral overexpression of GATA4 (AdV-GATA4) in cardiomyocytes prior to doxorubicin exposure maintained GATA4 levels, modestly restored CARP levels, and attenuated sarcomere disarray. Interestingly, siRNA-mediated depletion of CARP completely abolished the Adv-GATA4 rescue of the doxorubicin-induced sarcomere phenotype. These data demonstrate co-dependent roles for GATA4 and CARP in regulating sarcomere gene expression and maintaining sarcomeric organization in cardiomyocytes in culture. The data further suggests that concurrent depletion of GATA4 and CARP in cardiomyocytes by doxorubicin contributes in large part to myofibrillar disarray and the overall pathophysiology of anthracycline cardiomyopathy