Lipid Nanoparticle Encapsulation Empowers Poly(I:C) to Activate Cytoplasmic RLRs and Thereby Increases Its Adjuvanticity.

Poly(I:C) is a synthetic analogue of dsRNA capable of activating both TLR3 and RLRs, such as MDA-5 and RIG-I, as pathogen recognition receptors. While poly(I:C) is known to provoke a robust type I IFN, type III IFN, and Th1 cytokine response, its therapeutic use as a vaccine adjuvant is limited due to its vulnerability to nucleases and poor uptake by immune cells. is encapsulated poly(I:C) into lipid nanoparticles (LNPs) containing an ionizable cationic lipid that can electrostatically interact with poly(I:C). LNP-formulated poly(I:C) triggered both lysosomal TLR3 and cytoplasmic RLRs, in vitro and in vivo, whereas poly(I:C) in an unformulated soluble form only triggered endosomal-localized TLR3. Administration of LNP-formulated poly(I:C) in mouse models led to efficient translocation to lymphoid tissue and concurrent innate immune activation following intramuscular (IM) administration, resulting in a significant increase in innate immune activation compared to unformulated soluble poly(I:C). When used as an adjuvant for recombinant full-length SARS-CoV-2 spike protein, LNP-formulated poly(I:C) elicited potent anti-spike antibody titers, surpassing those of unformulated soluble poly(I:C) by orders of magnitude and offered complete protection against a SARS-CoV-2 viral challenge in vivo, and serum from these mice are capable of significantly reducing viral infection in vitro.

Host immune responses associated with SARS-CoV-2 Omicron infection result in protection or pathology during reinfection depending on mouse genetic background.

Rapid emergence of antigenic distinct SARS-CoV-2 variants implies a greater risk of reinfection as viruses can escape neutralizing antibodies induced by vaccination or previous viral exposure. Disease severity during COVID-19 depends on many variables such as age-related comorbidities, host immune status and genetic variation. The host immune response during infection with SARS-CoV-2 may contribute to disease severity, which can range from asymptomatic to severe with fatal outcome. Furthermore, the extent of host immune response activation may rely on underlying genetic predisposition for disease or protection. To address these questions, we performed immune profiling studies in mice with different genetic backgrounds - transgenic K18-hACE2 and wild-type 129S1 mice - subjected to reinfection with the severe disease-causing SARS-CoV-2 B.1.351 variant, 30 days after experimental milder BA.1 infection. BA.1 preinfection conferred protection against B.1.351-induced morbidity in K18-hACE2 mice but aggravated disease in 129S1 mice. We found that he cytokine/chemokine profile in B.1.351 re-infected 129S1mice is similar to that during severe SARS-CoV-2 infection in humans and is characterized by a much higher level of IL-10, IL-1ß, IL-18 and IFN-γ, whereas in B.1.351 re-infected K18-hACE2 mice, the cytokine profile echoes the signature of naïve mice undergoing viral infection for the first time. Interestingly, the enhanced pathology observed in 129S1 mice upon reinfection cannot be attributed to a less efficient induction of adaptive immune responses to the initial BA.1 infection, as both K18-hACE2 and 129S1 mice exhibited similar B and T cell responses at 30 DPI against BA.1, with similar anti-BA.1 or B.1.351 spike-specific ELISA binding titers, levels of germinal center B-cells, and SARS-CoV-2-Spike specific tissue-resident T-cells. Long-term effects of BA.1 infection are associated with differential transcriptional changes in bronchoalveolar lavage-derived CD11c + immune cells from K18-hACE2 and 129S1, with K18-hACE2 CD11c + cells showing a strong antiviral defense gene expression profile whereas 129S1 CD11c + cells showed a more pro-inflammatory response. In conclusion, initial infection with BA.1 induces cross-reactive adaptive immune responses in both K18-hACE2 and 129S1 mice, however the different disease outcome of reinfection seems to be driven by differential responses of CD11c + cells in the alveolar space.

Immune responses elicited by ssRNA(-) oncolytic viruses in the host and in the tumor microenvironment.

Oncolytic viruses (OVs) are at the forefront of biologicals for cancer treatment. They represent a diverse landscape of naturally occurring viral strains and genetically modified viruses that, either as single agents or as part of combination therapies, are being evaluated in preclinical and clinical settings. As the field gains momentum, the research on OVs has been shifting efforts to expand our understanding of the complex interplay between the virus, the tumor and the immune system, with the aim of rationally designing more efficient therapeutic interventions. Nowadays, the potential of an OV platform is no longer defined exclusively by the targeted replication and cancer cell killing capacities of the virus, but by its contribution as an immunostimulator, triggering the transformation of the immunosuppressive tumor microenvironment (TME) into a place where innate and adaptive immunity players can efficiently engage and lead the development of tumor-specific long-term memory responses. Here we review the immune mechanisms and host responses induced by ssRNA(-) (negative-sense single-stranded RNA) viruses as OV platforms. We focus on two ssRNA(-) OV candidates: Newcastle disease virus (NDV), an avian paramyxovirus with one of the longest histories of utilization as an OV, and influenza A (IAV) virus, a well-characterized human pathogen with extraordinary immunostimulatory capacities that is steadily advancing as an OV candidate through the development of recombinant IAV attenuated platforms.

Engineering Non-Human RNA Viruses for Cancer Therapy.

Alongside the development and progress in cancer immunotherapy, research in oncolytic viruses (OVs) continues advancing novel treatment strategies to the clinic. With almost 50 clinical trials carried out over the last decade, the opportunities for intervention using OVs are expanding beyond the old-fashioned concept of "lytic killers", with promising breakthrough therapeutic strategies focused on leveraging the immunostimulatory potential of different viral platforms. This review presents an overview of non-human-adapted RNA viruses engineered for cancer therapy. Moreover, we describe the diverse strategies employed to manipulate the genomes of these viruses to optimize their therapeutic capabilities. By focusing on different aspects of this particular group of viruses, we describe the insights into the promising advancements in the field of virotherapy and its potential to revolutionize cancer treatment.

Expanding cross-presenting dendritic cells enhances oncolytic virotherapy and is critical for long-term anti-tumor immunity.

Immunotherapies directly enhancing anti-tumor CD8+ T cell responses have yielded measurable but limited success, highlighting the need for alternatives. Anti-tumor T cell responses critically depend on antigen presenting dendritic cells (DC), and enhancing mobilization, antigen loading and activation of these cells represent an attractive possibility to potentiate T cell based therapies. Here we show that expansion of DCs by Flt3L administration impacts in situ vaccination with oncolytic Newcastle Disease Virus (NDV). Mechanistically, NDV activates DCs and sensitizes them to dying tumor cells through upregulation of dead-cell receptors and synergizes with Flt3L to promote anti-tumor CD8+ T cell cross-priming. In vivo, Flt3L-NDV in situ vaccination induces parallel amplification of virus- and tumor-specific T cells, including CD8+ T cells reactive to newly-described neoepitopes, promoting long-term tumor control. Cross-presenting conventional Type 1 DCs are indispensable for the anti-tumor, but not anti-viral, T cell response, and type I IFN-dependent CD4+ Th1 effector cells contribute to optimal anti-tumor immunity. These data demonstrate that mobilizing DCs to increase tumor antigen cross-presentation improves oncolytic virotherapy and that neoepitope-specific T cells can be induced without individualized, ex vivo manufactured vaccines.

Variables associated with the success of group cognitive behavioral therapy for insomnia: preliminary results.

Insomnia Disorder (ID) is defined as the predominant dissatisfaction with the quantity or quality of sleep associated with difficulty in initiating or maintaining sleep or early-morning awakenings with the inability to go back to sleep.

Avian Paramyxovirus 4 Antitumor Activity Leads to Complete Remissions and Long-term Protective Memory in Preclinical Melanoma and Colon Carcinoma Models.

Avulaviruses represent a diverse subfamily of non-segmented negative strand RNA viruses infecting avian species worldwide. To date, 22 different serotypes have been identified in a variety of avian hosts, including wild and domestic birds. APMV-1, also known as Newcastle disease virus (NDV), is the only avulavirus that has been extensively characterized due to its relevance for the poultry industry and, more recently, its inherent oncolytic activity and potential as a cancer therapeutic. An array of both naturally-occurring and recombinant APMV-1 strains has been tested in different preclinical models and clinical trials, highlighting NDV as a promising viral agent for human cancer therapy. To date, the oncolytic potential of other closely related avulaviruses remains unknown. Here, we have examined the in vivo anti-tumor capability of prototype strains of APMV serotypes -2, -3, -4, -6, -7, -8 and -9 in syngeneic murine colon carcinoma and melanoma tumor models. Our studies have identified APMV-4 Duck/Hong Kong/D3/1975 virus as a novel oncolytic agent with greater therapeutic potential than one of the NDV clinical candidate strains, La Sota. Intratumoral administration of the naturally-occurring APMV-4 virus significantly extends survival, promotes complete remission, and confers protection against re-challenge in both murine colon carcinoma and melanoma tumor models. Furthermore, we have designed a plasmid rescue strategy that allows us to develop recombinant APMV-4-based viruses. The infectious clone rAPMV-4 preserves the extraordinary antitumor capacity of its natural counterpart, paving the way to a promising next generation of viral therapeutics.

Vigilancia ambiental de la circulación de poliovirus en tres municipios considerados como punto transitorio de migrantes en Colombia 2017-2019 / Environmental surveillance of the circulation of poliovirus in municipalities considered as transitory point of migrants in Colombia 2017-2019

Resumen Objetivo: Determinar la circulación de poliovirus en tres municipios considerados como punto transitorio de migrantes en Colombia. Material y método: Se colectaron muestras de aguas residuales (n=36) de municipios fronterizos, seleccionados por mayor tránsito de migrantes regulares como irregulares, en el periodo comprendido entre el 2017-2019. Las muestras fueron concentradas y cultivadas siguiendo el algoritmo de vigilancia ambiental para la circulación de poliovirus de la Organización Mundial de la Salud (OMS). La identificación molecular se realizo mediante reacción en cadena de la polimerasa empleando cebadores específicos de grupo, de serotipo y de cepa vacunal sabin. Resultados y Discusión: Se detectó la presencia de Enterovirus no polio (EVNP) en las muestras ambientales obtenidas y no se hallo circulación de poliovirus deriva dos de la vacuna ni de poliovirus salvaje en los tres municipos evaluados; sin embargo en dos estudios previos publicados por Gonzalez y col con una metodologia similar en el año 2005 y 2015 evaluando las aguas residuales de la ciudad de Armenia-Quindio; se logró identificar la presencia de virus derivado de vacuna, con resultados negativos para la identificación de poliovirus salvaje. Conclusiones: Los hallazgos indican que el sistema de monitoreo de aguas residuales con el fin de determinar la presencia de virus es una herramienta util para realizar vigilancia ambiental.

Abstract Objective: To determine the circulation of poliovirus in three municipalities considered as transitory points for migrants in Colombia. Material and Method: Wastewater samples (n = 36) were collected from border municipalities, selected for greater transit of regular and irregular migrants, in the period between 2017-2019. The samples were concentrated and cultured following the World Health Organization (WHO) environmental surveillance algorithm for poliovirus circulation. Molecular identification was performed by polymerase chain reaction using group-specific, serotype and sabin vaccine strain primers. Results: The presence of non-polio Enterovirus (NPV) was detected in the environmental samples obtained and no circulation of poliovirus derived from the vaccine or wild poliovirus was found in the three evaluated municipalities; However, in two previous studies published by Gonzales et al with a similar methodology in 2005 and 2015 evaluating the wastewater of the city of Armenia-Quindío; It was possible to identify the presence of virus derived from vaccine, with negative results for the identification of wild poliovirus. Conclusions: The findings indicate that the wastewater monitoring system in order to determine the presence of viruses is a useful tool to carry out environmental surveillance.

Description of the arterial supply and venous drainage of the abdominal viscera in the puma (Puma concolor) (Linnaeus, 1771).

Detailed descriptions of the abdominal vasculature have not been reported on Puma concolor; thus, herein we provided a thorough description. Our findings include the following: a celiac artery branching into the hepatic and gastrolienal arteries, and this latter further branched into the left gastric, the left gastroepiploic, the lienal and three more arteries that supplied the greater omentum. We also found a cystic artery that derived from the right gastroduodenal artery; a right gastric artery that derived from the right hepatic artery; and an antimesenteric ileal artery that derived from the lateral cecal artery. The right gastric vein did not form the gastroduodenal vein as in other species, but it drained directly into the portal vein. Also, a middle pancreaticoduodenal vein was identified as the last branch of the cranial mesenteric vein. Finally, the left caudal phrenic vein drained into the left renal vein. The abdominal blood supply described herein corresponds to a single individual; further reviews are desirable to corroborate our observations and to detect potential intraspecific anatomical variations.

Antithrombotic therapy and clinical outcomes at 1 year in the Spanish cohort of the EORP-AF Long-term General Registry.

BACKGROUND: Atrial fibrillation (AF) increases the risk of thromboembolism. We investigate the efficacy and safety of oral anticoagulation (OAC) therapy and explored the number needed to treat for net effect (NNTnet) of OAC in the Spanish cohort of the EURObservational Research Programme-AF (EORP-AF) Long-term General Registry. METHODS: The EORP-AF General Registry is a prospective, multicentre registry conducted in ESC countries, including consecutive AF patients. For the present analysis, we used the Spanish cohort, and the primary outcome was any thromboembolism (TE)/acute coronary syndrome (ACS)/cardiovascular death during the first year of follow-up. RESULTS: 729 AF patients were included (57.1% male, median age 75 [IQR 67-81] years, median CHA2 DS2 -VASc and HAS-BLED of 3 [IQR 2-5] and 2 [IQR 1-2], respectively). 548 (75.2%) patients received OAC alone (318 [43.6%] on VKAs and 230 [31.6%] on DOACs). After 1 year, the use of OAC alone showed lower rates of any TE/ACS/cardiovascular death (3.0%/year; p < 0.001) compared to other regimens, and non-use of OAC alone (HR 4.18, 95% CI 2.12-8.27) was independently associated with any TE/ACS/cardiovascular death. Balancing the effects of treatment, the NNTnet to provide an overall benefit of OAC therapy was 24. The proportion of patients on OAC increased at 1 year (87% to 88.1%), particularly on DOACs (33.6% to 39.9%) (p = 0.015), with low discontinuation rates. CONCLUSIONS: In this contemporary cohort of AF patients, OAC therapy was associated with better clinical outcomes at 1 year and positive NNTnet. OAC use slightly increased during the follow-up, with low discontinuation rates and higher prescription of DOACs.

Effect of Computer-Aided Navigation Techniques on the Accuracy of Endodontic Access Cavities: A Systematic Review and Meta-Analysis.

The present systematic review and meta-analysis aims to determine the effect of computer-aided navigation techniques on the accuracy of endodontic access cavities. MATERIALS AND METHODS: A systematic literature review and meta-analysis of clinical studies, based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, was performed that evaluated the root canal location rate of computer-aided navigation techniques applied to endodontic access cavities. Four different databases were used to consult the literature: PubMed-Medline, Scopus, Cochrane, and Web of Science. After discarding duplicate articles and applying inclusion criteria, 14 articles were selected for qualitative analysis and 13 for quantitative analysis. RESULTS: the root canal location success rate started at 98.1% (CI: 95.7-100%) of the cases performed through a computer-aided navigation technique. The prediction interval ranged from 93.3% to 100%. The meta-analysis did not detect heterogeneity between the combined studies (Q-test = 17.3; p = 0.185; I2 = 25%). No statistically significant differences were found between computer-aided static navigation techniques (success rate: 98.5%) and computer-aided dynamic navigation techniques (success rate: 94.5%) (Q test = 0.57; p = 0.451), nor between in vitro studies (success rate: 96.2%) and in vivo studies (success rate: 100%) (Q test = 2.53; p-value = 0.112). An odds success ratio of 13.1 (CI: 95%; 3.48, 49.1) encourages the use of computer-aided navigation techniques over conventional endodontic access cavity procedures. CONCLUSIONS: the endodontic access cavities created using static and dynamic computer-aided navigation techniques are highly accurate in locating the root canal system.

Calcination-free production of calcium hydroxide at sub-boiling temperatures.

Calcium hydroxide (Ca(OH)2), a commodity chemical, finds use in diverse industries ranging from food, to environmental remediation and construction. However, the current thermal process of Ca(OH)2 production via limestone calcination is energy- and CO2-intensive. Herein, we demonstrate a novel aqueous-phase calcination-free process to precipitate Ca(OH)2 from saturated solutions at sub-boiling temperatures in three steps. First, calcium was extracted from an archetypal alkaline industrial waste, a steel slag, to produce an alkaline leachate. Second, the leachate was concentrated using reverse osmosis (RO) processing. This elevated the Ca-abundance in the leachate to a level approaching Ca(OH)2 saturation at ambient temperature. Thereafter, Ca(OH)2 was precipitated from the concentrated leachate by forcing a temperature excursion in excess of 65 °C while exploiting the retrograde solubility of Ca(OH)2. This nature of temperature swing can be forced using low-grade waste heat (≤100 °C) as is often available at power generation, and industrial facilities, or using solar thermal heat. Based on a detailed accounting of the mass and energy balances, this new process offers at least ≈65% lower CO2 emissions than incumbent methods of Ca(OH)2, and potentially, cement production.

Newcastle Disease Virus (NDV) Oncolytic Activity in Human Glioma Tumors Is Dependent on CDKN2A-Type I IFN Gene Cluster Codeletion.

Glioblastoma (GBM) is the most aggressive and frequent primary brain tumor in adults with a median overall survival of 15 months. Tumor recurrence and poor prognosis are related to cancer stem cells (CSCs), which drive resistance to therapies. A common characteristic in GBM is CDKN2A gene loss, located close to the cluster of type I IFN genes at Ch9p21. Newcastle disease virus (NDV) is an avian paramyxovirus with oncolytic and immunostimulatory properties that has been proposed for the treatment of GBM. We have analyzed the CDKN2A-IFN I gene cluster in 1018 glioma tumors and evaluated the NDV oncolytic effect in six GBM CSCs ex vivo and in a mouse model. Our results indicate that more than 50% of GBM patients have some IFN deletion. Moreover, GBM susceptibility to NDV is dependent on the loss of the type I IFN. Infection of GBM with an NDV-expressing influenza virus NS1 protein can overcome the resistance to oncolysis by NDV of type I-competent cells. These results highlight the potential of using NDV vectors in antitumor therapies.

An HER2-Displaying Virus-Like Particle Vaccine Protects from Challenge with Mammary Carcinoma Cells in a Mouse Model.

Human epidermal growth factor receptor-2 (HER2) is upregulated in 20% to 30% of breast cancers and is a marker of a poor outcome. Due to the development of resistance to passive immunotherapy with Trastuzumab, active anti-HER2 vaccination strategies that could potentially trigger durable tumor-specific immune responses have become an attractive research area. Recently, we have shown that budded virus-like particles (VLPs) produced in Sf9 insect cells are an ideal platform for the expression of complex membrane proteins. To assess the efficacy of antigen-displaying VLPs as active cancer vaccines, BALB/c mice were immunized with insect cell glycosylated and mammalian-like glycosylated HER2-displaying VLPs in combination with two different adjuvants and were challenged with HER2-positive tumors. Higher HER2-specific antibody titers and effector functions were induced in mice vaccinated with insect cell glycosylated HER2 VLPs compared to mammalian-like glycosylated counterparts. Moreover, insect cell glycosylated HER2 VLPs elicited a protective effect in mice grafted with HER2-positive mammary carcinoma cells. Interestingly, no protection was observed in mice that were adjuvanted with Poly (I:C). Here, we show that antigen-displaying VLPs produced in Sf9 insect cells were able to induce robust and durable immune responses in vivo and have the potential to be utilized as active cancer vaccines.

The therapeutic effect of death: Newcastle disease virus and its antitumor potential.

Programmed cell death is essential to survival of multicellular organisms. Previously restricted to apoptosis, the concept of programmed cell death is now extended to other mechanisms, as programmed necrosis or necroptosis, autophagic cell death, pyroptosis and parthanatos, among others. Viruses have evolved to manipulate and take control over the programmed cell death response, and the infected cell attempts to neutralize viral infections displaying different stress signals and defensive pathways before taking the critical decision of self-destruction. Learning from viruses and their interplay with the host may help us to better understand the complexity of the self-defense death response that when altered might cause disorders as important as cancer. In addition, as the fields of immunotherapy and oncolytic viruses advance as promising novel cancer therapies, the programmed cell death response reemerges as a key point for the success of both therapeutic approaches. In this review we summarize the research of the multimodal cell death response induced by Newcastle disease viruses (NDV), considered nowadays a promising viral oncolytic therapeutic, and how the manipulation of the host programmed cell death response can enhance the NDV antitumor capacity.

Enhancement of the proapoptotic properties of newcastle disease virus promotes tumor remission in syngeneic murine cancer models.

Newcastle disease virus (NDV) is considered a promising agent for cancer therapy due to its oncolytic properties. These include preferential replication in transformed cells, induction of innate and adaptive immune responses within tumors, and cytopathic effects in infected tumor cells due to the activation of apoptosis. To enhance the latter and thus possibly enhance the overall oncolytic activity of NDV, we generated a recombinant NDV encoding the human TNF receptor Fas (rNDV-B1/Fas). rNDV-B1/Fas replicates to similar titers as its wild-type (rNDV-B1) counterpart; however, overexpression of Fas in infected cells leads to higher levels of cytotoxicity correlated with faster and increased apoptosis responses, in which both the intrinsic and extrinsic pathways are activated earlier. Furthermore, in vivo studies in syngeneic murine melanoma models show an enhancement of the oncolytic properties of rNDV-B1/Fas, with major improvements in survival and tumor remission. Altogether, our data suggest that upregulation of the proapoptotic function of NDV is a viable approach to enhance its antitumor properties and adds to the currently known, rationally based strategies to design optimized therapeutic viral vectors for the treatment of cancer.

Thermal stability of matrix protein from Newcastle disease virus.

The thermal stability of the matrix protein (M protein) of Newcastle disease virus (NDV) has been investigated using high-sensitivity differential scanning calorimetry (DSC) at pH 7.4. The thermal folding/unfolding of M protein at this pH value is a reversible process involving a highly cooperative transition between folded and unfolded monomers with a transition temperature (Tm) of 63 °C, an unfolding enthalpy, ΔH(Tm), of 340 kcal mol(-1), and the difference in heat capacity between the native and denatured states of the protein, ΔCp, of 5.1 kcal K(-1) mol(-1). The heat capacity of the native state of the protein is in good agreement with the values calculated using a structure-based parameterization, whereas the calculated values for the hypothetical fully-unfolded state of the protein is higher than those determined experimentally. This difference between the heat capacity of denatured M protein and the heat capacity expected for an unstructured polypeptide of the same sequence, together with the data derived from the heat-induced changes in the steady-state fluorescence of the protein, indicates that the polypeptide chain maintains a significant amount of residual structure after thermal denaturation.

New strategies for echocardiographic evaluation of left ventricular function in a mouse model of long-term myocardial infarction.

BACKGROUND: The aim of this article is to present an optimized acquisition and analysis protocol for the echocardiographic evaluation of left ventricle (LV) remodeling in a mouse model of myocardial infarction (MI). METHODOLOGY: 13 female DBA/2J mice underwent permanent occlusion of the left anterior descending (LAD) coronary artery leading to MI. Mice echocardiography was performed using a Vevo 770 (Visualsonics, Canada) before infarction, and 7, 14, 30, 60, 90 and 120 days after LAD ligation. LV systolic function was evaluated using different parameters, including the fractional area change (FAC%) computed in four high-temporal resolution B-mode short axis images taken at different ventricular levels, and in one parasternal long axis. Pulsed wave and tissue Doppler modes were used to evaluate the diastolic function and Tei Index for global cardiac function. The echocardiographic measurements of infarct size were validated histologically using collagen deposition labeled by Sirius red staining. All data was analyzed using Shapiro-Wilk and Student's t-tests. PRINCIPAL FINDINGS: Our results reveal LV dilation resulting in marked remodeling an severe systolic dysfunction, starting seven days after MI (LV internal apical diameter, basal = 2.82±0.24, 7d = 3.49±0.42; p<0.001. End-diastolic area, basal = 18.98±1.81, 7d = 22.04±2.11; p<0.001). A strong statistically significant negative correlation exists between the infarct size and long-axis FAC% (r = -0.946; R(2) = 0.90; p<0.05). Moreover, the measured Tei Index values confirmed significant post-infarction impairment of the global cardiac function (basal = 0.46±0.07, 7d = 0.55±0.08, 14 d = 0.57±0.06, 30 d = 0.54±0.06, 60 d = 0.54±0.07, 90 d = 0.57±0.08; p<0.01). CONCLUSIONS/SIGNIFICANCE: In summary, we have performed a complete characterization of LV post-infarction remodeling in a DBA/2J mouse model of MI, using parameters adapted to the particular characteristics of the model In the future, this well characterized model will be used in both investigative and pharmacological studies that require accurate quantitative monitoring of cardiac recovery after myocardial infarction.

Bicaval versus standard technique in orthotopic heart transplant: assessment of atrial performance at magnetic resonance and transthoracic echocardiography.

Despite a more physiological morphology of atrial anastomosis in the bicaval technique with respect to standard biatrial anastomosis in orthotopic heart transplantation (OHT), the impact on the long-term outcome is still not clear. In this retrospective study, we sought to investigate the morphology and function of the atria through magnetic resonance imaging (MRI) and transthoracic echocardiography (TTE). Moreover, we aimed to analyse the accuracy of TTE with respect to MRI. Cox regression analysis of 216 consecutive patients receiving OHT between August 1987 and January 2010 identified only recipient age at the time of transplant to be an independent predictor of mortality (P = 0.048, odds ratio = 1.04). After a mean follow-up of 96.6 ± 77.7 months, 108 patients were alive, of which 35 were found to be eligible for MRI assessment. In this analysis, left and right atrial volumes were found to be significantly larger in the standard group in comparison with the bicaval group (P = 0.001), and no significant difference between the two techniques was observed in left and right atrio-ventricular output. Moreover, a significantly reduced accuracy was observed (CCC < 0.3) when TTE results were compared with MRI assessment in evaluating atrial dimensions. Although left and right atrial volumes are significantly larger in the standard group in comparison with the bicaval group, we concluded that no significant difference in the atrial output and survival between the two techniques could be demonstrated.

Dual-source CT coronary angiogram in heart transplant recipients in comparison with dobutamine stress echocardiography for detection of cardiac allograft vasculopathy.

Conventional coronary angiography (CCA) is the gold standard in the diagnosis of cardiac allograft vasculopathy (CAV) in heart transplant recipients. Dobutamine stress echocardiography (DSE) is a useful technique for screening. Dual-source computed tomography (DSCT) is the last generation of computed tomography scanners, which could be useful to noninvasively assess CAV. Thirty cardiac transplant recipients underwent DSE and DSCT coronary angiogram. Exclusion criteria were as follows: renal insufficiency, iodinated contrast media allergy, less than 12 months since transplant, and unstable clinical conditions. DSE showed ischemia in two patients. At DSCT scan 13 patients had a normal angiogram, 13 ones wall thickening and four significant diseases. DSCT showed a sensitivity of 100% with a specificity of 92%. DSCT allowed detection of more patients with CAV than DSE. Four patients showed significant CAV at DSCT compared with two at DSE. Thirteen patients showed initial signs of disease at DSCT despite a normal DSE.