MRI Accurately Visualizes RF Ablation Delivery Targeted to MRI-Defined Arrhythmia Substrates in the Left Ventricle.

OBJECTIVE: Investigate the capacity of MRI to evaluate efficacy of radiofrequency (RF) ablations delivered to MRI-defined arrhythmogenic substrates. METHODS: Baseline MRI was performed at 3T including 3D LGE in a swine model of chronic myocardial infarct (N=8). MRI-derived maps of scar and heterogeneous tissue channels (HTCs) were generated using ADAS 3D. Animals underwent electroanatomic mapping and ablation of the left ventricle in CARTO3, guided by MRI-derived scar maps. Post-ablation MRI (in vivo at 3T in 5/8 animals; ex vivo at 1.5T in 3/8) included 3D native T1-weighted IR-SPGR (TI=700-800ms) to visualize RF lesions. T1-derived RF lesions were compared against excised tissue. The locations of T1-derived RF lesions were compared against CARTO ablation tags, and segment-wise sensitivity and specificity of lesion detection were calculated within the AHA 17-segment model. RESULTS: RF lesions were clearly visualized in HTCs, scar, and myocardium. Ablation patterns delivered in CARTO matched T1-derived RF lesion patterns with high sensitivity (88.9%) and specificity (94.7%), and were closely matched in registered MR-EP data sets, with a displacement of 5.4 ±3.8mm (N=152 ablation tags). CONCLUSION: Integrating MRI into ablative procedures for RF lesion assessment is feasible. Patterns of RF lesions created using a standard 3D EAM system are accurately reflected by MRI visualization in healthy myocardium, scar, and HTCs comprising the MRI-defined arrhythmia substrate. SIGNIFICANCE: MRI visualization of RF lesions can provide near-immediate (<24h) assessment of ablation, potentially indicating whether critical MRI-defined ventricular tachycardia substrates have been adequately ablated.

Novel insecticidal proteins from ferns resemble insecticidal proteins from Bacillus thuringiensis.

Lepidopterans affect crop production worldwide. The use of transgenes encoding insecticidal proteins from Bacillus thuringiensis (Bt) in crop plants is a well-established technology that enhances protection against lepidopteran larvae. Concern about widespread field-evolved resistance to Bt proteins has highlighted an urgent need for new insecticidal proteins with different modes or sites of action. We discovered a new family of insecticidal proteins from ferns. The prototype protein from Pteris species (Order Polypodiales) and variants from two other orders of ferns, Schizaeales and Ophioglossales, were effective against important lepidopteran pests of maize and soybean in diet-based assays. Transgenic maize and soybean plants producing these proteins were more resistant to insect damage than controls. We report here the crystal structure of a variant of the prototype protein to 1.98 Å resolution. Remarkably, despite being derived from plants, the structure resembles the 3-domain Cry proteins from Bt but has only two out of three of their characteristic domains, lacking the C-terminal domain which is typically required for their activities. Two of the fern proteins were effective against strains of fall armyworm that were resistant to Bt 3-domain Cry proteins Cry1Fa or Cry2A.127. This therefore represents a novel family of insecticidal proteins that have the potential to provide future tools for pest control.

Structural journey of an insecticidal protein against western corn rootworm.

The broad adoption of transgenic crops has revolutionized agriculture. However, resistance to insecticidal proteins by agricultural pests poses a continuous challenge to maintaining crop productivity and new proteins are urgently needed to replace those utilized for existing transgenic traits. We identified an insecticidal membrane attack complex/perforin (MACPF) protein, Mpf2Ba1, with strong activity against the devastating coleopteran pest western corn rootworm (WCR) and a novel site of action. Using an integrative structural biology approach, we determined monomeric, pre-pore and pore structures, revealing changes between structural states at high resolution. We discovered an assembly inhibition mechanism, a molecular switch that activates pre-pore oligomerization upon gut fluid incubation and solved the highest resolution MACPF pore structure to-date. Our findings demonstrate not only the utility of Mpf2Ba1 in the development of biotechnology solutions for protecting maize from WCR to promote food security, but also uncover previously unknown mechanistic principles of bacterial MACPF assembly.

MRI-Guided Cardiac RF Ablation for Comparing MRI Characteristics of Acute Lesions and Associated Electrophysiologic Voltage Reductions.

OBJECTIVE: Radiofrequency (RF) energy delivered to cardiac tissue produces a core ablation lesion with surrounding edema, the latter of which has been implicated in acute procedural failure of Ventricular Tachycardia (VT) ablation and late arrhythmia recurrence. This study sought to investigate the electrophysiological characteristics of acute RF lesions in the left ventricle (LV) visualized with native-contrast Magnetic Resonance Imaging (MRI). METHODS: An MR-guided electrophysiology system was used to deliver RF ablation in the LV of 8 swine (9 RF lesions in total), then perform MRI and electroanatomic mapping. The permanent RF lesions and transient edema were delineated via native-contrast MRI segmentation of T1-weighted images and T2 maps respectively. Bipolar voltage measurements were matched with image characteristics of pixels adjacent to the catheter tip. Native-contrast MR visualization was verified with 3D late gadolinium enhanced MRI and histology. RESULTS: The T2-derived edema was significantly larger than the T1-derived RF lesion (2.1 ±1.5 mL compared to 0.58 ±0.34 mL; p=0.01). Bipolar voltage was significantly reduced in the presence of RF lesion core (p 0.05) and edema (p 0.05), with similar trends suggesting that both the permanent lesion and transient edema contributed to the region of reduced voltage. While bipolar voltage was significantly decreased where RF lesions are present (p 0.05), voltage did not change significantly with lesion transmurality (p 0.05). CONCLUSION: Permanent RF lesions and transient edema are distinct in native-contrast MR images, but not differentiable using bipolar voltage. SIGNIFICANCE: Intraprocedural native-contrast MRI may provide valuable lesion assessment in MR-guided ablation, whose clinical application is now feasible.

Factors Influencing Attendees' Engagement with Group Psychoeducation: A Multi-stakeholder Perspective.

Few studies have explored the problem of engagement in relation to group psychoeducation from a multi-site and multi-stakeholder perspective. The aim of the study was to explore the factors influencing service user and family engagement with group psychoeducation programmes. The study design was qualitative descriptive. Data were collected through individual and focus group interviews with key stakeholders (n = 75) involved with the programme within 14 mental health sites in the Republic of Ireland. Enablers and barriers to engagement were identified at participant, provider, programme and organization level. Motivated participants and engaged clinicians, peer co-facilitation and support, and skilled and responsive facilitators were some of the factors which enhanced engagement. Barriers to engagement included readiness among participants, concerns related to stigma and confidentiality, desire to distance oneself from mental health services, a lack of support for programme participation within families, group discomfort, the time and length of the programme, issues with transport, visibility of the programme, and structural supports for clinicians. Findings from the study illustrate the multifaceted nature of engagement as well as provide a greater understanding of the multifactorial influences on engagement. Strategies to enhance engagement should therefore reflect a multipronged approach. At the outset of programme implementation, organizations should address their readiness to engage, conduct local needs assessments to anticipate individuals' needs and plan accordingly in order to maximize engagement, and bolster facilitators' engagement skills through the provision of training and mentoring opportunities.

Reactive oxygen species reprogram macrophages to suppress antitumor immune response through the exosomal miR-155-5p/PD-L1 pathway.

BACKGROUND: Cancer cells have an imbalance in oxidation-reduction (redox) homeostasis. Understanding the precise mechanisms and the impact of the altered redox microenvironment on the immunologic reaction to tumors is limited. METHODS: We isolated exosomes from ovarian cancer cells through ultracentrifuge and characterized by Western-blots and Nanoparticle Tracking Analysis. 2D, 3D-coculture tumor model, and 3D live cell imaging were used to study the interactions between tumor cells, macrophages and CD3 T cells in vitro. The role of exosomal miR-155-5p in tumor growth was evaluated in xenograft nude mice models and immune-competent mice models. Flow cytometry and flow sorting were used to determine the expression levels of miR-155-5p and PD-L1 in ascites and splenic macrophages, and the percentages of CD3 T cells subpopulations. RESULTS: The elevation of reactive oxygen species (ROS) greatly downregulated exosomal miR-155-5p expression in tumor cells. Neutralization of ROS with N-acetyl-L-cysteine (NAC) increased the levels of miR-155-5p in tumor exosomes that were taken up by macrophages, leading to reduction of macrophage migration and tumor spheroid infiltration. We further found that programmed death ligand 1 (PD-L1) is a functional target of miR-155-5p. Co-culture of macrophages pre-treated with NAC-derived tumor exosomes or exosomal miR-155-5p with T-lymphocytes leading to an increased percentage of CD8+ T-lymphocyte and a decreased CD3+ T cell apoptosis through PD-L1 downregulation. Tumor growth in nude mice was delayed by treatment with NAC-derived tumor exosomes. Delivery of tumor exo-miR-155-5p in immune-intact mice suppressed ovarian cancer progression and macrophage infiltration, and activated CD8+ T cell function. It is of note that exo-miR-155-5p inhibited tumor growth more potently than the PD-L1 antibody, suggesting that in addition to PD-L1, other pathways may also be targeted by this approach. CONCLUSIONS: Our findings demonstrate a novel mechanism, ROS-induced down-regulation of miR-155-5p, by which tumors modulate the microenvironment that favors tumor growth. Understanding of the negative impact of ROS on the tumor immune response will improve current therapeutic strategies. Targeting miR-155-5p can be an alternative approach to prevent formation of an immunosuppressive TME through downregulation of PD-L1 and other immunosuppressive factors.

Scoping review of factors influencing the implementation of group psychoeducational initiatives for people experiencing mental health difficulties and their families.

BACKGROUND: Despite evidence to support the effectiveness of psychoeducation for people experiencing mental health difficulties and their families, understanding issues around the implementation of such programmes is limited. AIM: The aim of this scoping review was to synthesise the peer-reviewed literature on barriers and enablers influencing the implementation of group psychoeducation in adult mental health services. METHODS: Using a pre-defined search strategy and PRISMA guidelines, four databases were systematically searched. Two reviewers independently screened and applied exclusion/inclusion criteria. Qualitative, quantitative, and mixed-methods studies were included if they provided empirical evidence on the barriers and enablers. Three reviewers independently extracted data. Following this, data were analysed using a five-level implementation framework. RESULTS: Eight articles met the inclusion criteria. Barriers to implementation were identified at all five levels of the framework: participant; practitioner; intervention; organisational; and structural level. Enablers to implementation were evident at four levels: participant; provider; intervention; and organisational level. CONCLUSIONS: The findings of the review provide preliminary information on factors that impact implementation. However, large-scale studies informed by implementation theories are required. In addition, other studies are needed to address the potential impact of different models of intervention and explore strategies to minimize obstacles and support sustainability.

Myocardial blood flow is the dominant factor influencing cardiac magnetic resonance adenosine stress T2.

Stress imaging identifies ischemic myocardium by comparing hemodynamics during rest and hyperemic stress. Hyperemia affects multiple hemodynamic parameters in myocardium, including myocardial blood flow (MBF), myocardial blood volume (MBV), and venous blood oxygen levels (PvO2 ). Cardiac T2 is sensitive to these changes and therefore is a promising non-contrast option for stress imaging; however, the impact of individual hemodynamic factors on T2 is poorly understood, making the connection from altered T2 to changes within the tissue difficult. To better understand this interplay, we performed T2 mapping and measured various hemodynamic factors independently in healthy pigs at multiple levels of hyperemic stress, induced by different doses of adenosine (0.14-0.56 mg/kg/min). T1 mapping quantified changes in MBV. MBF was assessed with microspheres, and oxygen consumption was determined by the rate pressure product (RPP). Simulations were also run to better characterize individual contributions to T2. Myocardial T2, MBF, oxygen consumption, and MBV all changed to varying extents between each level of adenosine stress (T2 = 37.6-41.8 ms; MBF = 0.48-1.32 mL/min/g; RPP = 6507-4001 bmp*mmHg; maximum percent change in MBV = 1.31%). Multivariable analyses revealed MBF as the dominant influence on T2 during hyperemia (significant ß-values >7). Myocardial oxygen consumption had almost no effect on T2 (ß-values <0.002); since PvO2 is influenced by both oxygen consumption and MBF, PvO2 changes detected by T2 during adenosine stress can be attributed to MBF. Simulations varying PvO2 and MBV confirmed that PvO2 had the strongest influence on T2, but MBV became important at high PvO2 . Together, these data suggest a model where, during adenosine stress, myocardial T2 responds predominantly to changes in MBF, but at high hyperemia MBV is also influential. Thus, changes in adenosine stress T2 can now be interpreted in terms of the physiological changes that led to it, enabling T2 mapping to become a viable non-contrast option to detect ischemic myocardial tissue.

Coordinated binding of a two-component insecticidal protein from Alcaligenes faecalis to western corn rootworm midgut tissue.

AfIP-1A/1B is a two-component insecticidal protein identified from the soil bacterium Alcaligenes faecalis that has high activity against western corn rootworm (WCR; Diabrotica virgifera virgifera LeConte). Previous results revealed that AfIP-1A/1B is cross-resistant to the binary protein from Bacillus thuringiensis (Bt), Cry34Ab1/Cry35Ab1 (also known as Gpp34Ab1/Tpp35Ab1; Crickmore et al., 2020), which was attributed to shared binding sites in WCR gut tissue (Yalpani et al., 2017). To better understand the interaction of AfIP-1A/1B with its receptor, we have systematically evaluated the binding of these proteins with WCR brush border membrane vesicles (BBMVs). Our findings show that AfIP-1A binds directly to BBMVs, while AfIP-1B does not; AfIP-1B binding only occurred in the presence of AfIP-1A which was accompanied by the presence of stable, high molecular weight oligomers of AfIP-1B observed on denaturing protein gels. Additionally, we show that AfIP-1A/1B forms pores in artificial lipid membranes. Finally, binding of AfIP-1A/1B was found to be reduced in BBMVs from Cry34Ab1/Cry35Ab1-resistant WCR where Cry34Ab1/Cry35Ab1 binding was also reduced. The reduced binding of both proteins is consistent with recognition of a shared receptor that has been altered in the resistant strain. The coordination of AfIP-1B binding by AfIP-1A, the similar structures between AfIP-1A and Cry34Ab1, along with their shared binding sites and cross-resistance, suggest a similar role for AfIP1A and Cry34Ab1 in receptor recognition and docking site for their cognate partners, AfIP-1B and Cry35Ab1, respectively.

T2-based area-at-risk and edema are influenced by ischemic duration in acute myocardial infarction.

The purpose of our study was to assess whether T2 MRI identifies the infarcted myocardium or the true area-at-risk (AAR) and whether edema is present in the salvageable region following acute myocardial infarction (MI). The study involved a porcine model of MI with a coronary occlusion model of either 60 min or 90 min. Imaging was performed on a 3T MRI pre-occlusion and at day 3 post-MI. Prior-MI, myocardial perfusion territory (MPT) maps were obtained under MRI via direct intracoronary injection of contrast agent. Post-MI, edema extent was quantified by T2 mapping while infarction and microvascular obstruction (MVO) were assessed by late gadolinium enhancement (LGE). Anatomically registered short-axis slices were analyzed for MPT, T2-AAR and infarct areas and T2 relaxation values. Animals were divided into groups with (MVO+) and without MVO (MVO-). T2-AAR area was significantly greater than infarct area in both groups. In the MVO+ group, T2-AAR and MPT were comparable and highly correlated, whereas, in the MVO- group, T2-AAR significantly underestimated MPT without any trend. T2 values in the salvageable myocardium were found to be significantly higher than those in remote myocardium. Our methodology offers the advantage that all images are acquired within the same MRI reference as opposed to complex co-registration with gross pathology. Our study suggests that edema may expand beyond the infarct zone over the entire ischemic bed. T2-AAR may be more clinically relevant than true AAR by perfusion territory since it identifies the "salvageable" myocardium.

Hemorrhage promotes chronic adverse remodeling in acute myocardial infarction: a T1 , T2 and BOLD study.

Hemorrhage is recognized as a new independent predictor of adverse outcomes following acute myocardial infarction. However, the mechanisms of its effects are less understood. The aim of our study was to probe the downstream impact of hemorrhage towards chronic remodeling, including inflammation, vasodilator function and matrix alterations in an experimental model of hemorrhage. Myocardial hemorrhage was induced in the porcine heart by intracoronary injection of collagenase. Animals (N = 18) were subjected to coronary occlusion followed by reperfusion in three groups (six/group): 8 min ischemia with hemorrhage (+HEM), 45 min infarction with no hemorrhage (I - HEM) and 45 min infarction with hemorrhage (I + HEM). MRI was performed up to 4 weeks after intervention. Cardiac function, edema (T2 , T1 ), hemorrhage (T2 *), vasodilator function (T2 BOLD), infarction and microvascular obstruction (MVO) and partition coefficient (pre- and post-contrast T1 ) were computed. Hemorrhage was induced only in the +HEM and I + HEM groups on Day 1 (low T2 * values). Infarct size was the greatest in the I + HEM group, while the +HEM group showed no observable infarct. MVO was seen only in the I + HEM group, with a 40% occurrence rate. Function was compromised and ventricular volume was enlarged only in the hemorrhage groups and not in the ischemia-alone group. In the infarct zone, edema and matrix expansion were the greatest in the I + HEM group. In the remote myocardium, T2 elevation and matrix expansion associated with a transient vasodilator dysfunction were observed in the hemorrhage groups but not in the ischemia-alone group. Our study demonstrates that the introduction of myocardial hemorrhage at reperfusion results in greater myocardial damage, upregulated inflammation, chronic adverse remodeling and remote myocardial alterations beyond the effects of the initial ischemic insult. A systematic understanding of the consequences of hemorrhage will potentially aid in the identification of novel therapeutics for high-risk patients progressing towards heart failure.

"The Road We Travel": Developing a co-produced narrative for a photovoice project.

WHAT IS KNOWN ON THE SUBJECT?: PhotoVoice as a participatory methodology has been used within mental health to support marginalized communities in addressing the challenges they encounter. The PhotoVoice methodology aims to encourage and foster collaborative and equal partnerships. However, reports of previous projects highlight that not every stage of the process remains participant-centric. There is limited reporting on participant involvement in the latter stages of projects, such as exhibition design. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: It provides a detailed description of the phases involved in planning and executing a mental health PhotoVoice project. It provides an illustration of how collaborative partnerships can extend into the design and construction of a photography exhibition and its narrative. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: PhotoVoice is an ideal methodology for use within the field of mental health nursing as it promotes service user inclusion in research, places value on lived experiences and provides a creative medium through which service users and family members can advocate for themselves and others. PhotoVoice is an effective and creative methodology for disseminating and communicating both the individual and collective outcomes to the general public. When implementing this methodology, clinicians and researchers need to be cognisant of the necessity to include participants as equal partners at every stage, including in the design of photography exhibitions and disseminating the findings to academic and public audiences. ABSTRACT: Introduction PhotoVoice is a participatory methodology in which marginalized communities represent their lived experiences through photography. While the methodology aims to foster partnerships throughout all phases, the literature suggests that in the field of mental health, some phases are often completed without participant involvement. Aims This paper elaborates on how the PhotoVoice method was used to engage service users and family members around their experience of involvement in a co-produced and co-facilitated mental health education intervention, in order to enhance public and policymakers knowledge of the project. Methods Ten participants were recruited and trained in the PhotoVoice method. Participants documented, through photography, their experiences of involvement in the education intervention. Following this, participants came together to co-produce and disseminate the photography exhibition to the public. Results PhotoVoice proved to be a flexible and creative method by which to include marginalized groups. By adhering to the collaborative principles of the methodology, service users and family members can retain decision-making power from the project's inception to its conclusion. Implications for Practice PhotoVoice is ideal for use within mental health nursing as it coincides with the recovery principle of promoting collaborative partnership between service users, family members and clinicians. Mental health nurses work directly with service users and family members throughout their recovery journey. The PhotoVoice methodology is coherent with the recovery principles of empowerment, collaboration and prioritizing the lived experiences of the individual. As such, this methodology has the potential to enhance greatly what mental health nurses can know and understand about the lived experiences of service users and family members. In turn, engaging with the PhotoVoice methodology can provide a platform from which further collaborative engagement between service users, family members and clinicians can take place.

PhotoVoice: An Ideal Methodology for Use within Recovery-Oriented Mental Health Research.

At the heart of recovery-orientated mental health care and the Patient and Public Involvement (PPI) movement, is the inclusion of experts by experience as collaborators on mental health research projects. However, embedding Public and Patient Involvement (PPI) can be challenging in academic institutions that have long-standing researcher-as-expert structures in place. PhotoVoice is a collaborative, participant-centric community-based methodology that has potential to overcome some of the challenges encountered within Public and Patient Involvement (PPI). This discursive paper describes what PhotoVoice is, why it was developed, it's application in research and its alignment to recovery principles. Thereby arguing that PhotoVoice is an ideal methodology for use within recovery-orientated research.

Factors impacting the implementation of a psychoeducation intervention within the mental health system: a multisite study using the consolidation framework for implementation research.

BACKGROUND: Despite a strong evidence base and policy recommendation supporting the implementation of psychoeducation interventions within the mental health system, equitable access for many service users and family members has not been achieved. To enhance translation, developing an evidence-base around the factors that influence implementation of interventions is critical. METHODS: The aim of the study was to explore the factors influencing implementation of a group cofacilitated recovery focused psychoeducation intervention. The study design was explorative qualitative descriptive, involving the collection of data through individual and focus group interviews with key stakeholders (n = 75) involved with the implementation within 14 mental health sites in the Republic of Ireland. The Consolidation Framework for Implementation Research (CFIR) was used as a conceptual framework to guide data collection and analysis. RESULTS: Key enablers and barriers were identified across all CFIR domains of the framework with some factors (depending on context) being both an enabler and a barrier. Important factors in the outer setting domain included structural stability within national systems and the peer payment system, while the extent of a recovery-oriented culture, leadership, implementation readiness, and buy-in were influential factors in the inner setting. The characteristics of the intervention in terms of design, evidence-base and adaptability also shaped the intervention's implementation as did the knowledge, beliefs and self-efficacy of facilitators. In terms of processes, implementation was influenced by the degree of engagement of key individuals who championed and supported the programme. The results highlight that while some of the barriers were specific to the programme, many reflected systemic and structural challenges within health services more generally. CONCLUSION: Findings from this study provide an enhanced understanding of the different layers of determinants to implementation of an intervention. Overcoming challenges will involve positive and ongoing engagement and collaboration across the full range of stakeholders that are active within each domain, including policy and operational levels. The quality of leadership at each domain level is of crucial importance to successful implementation.

Beyond the moment: Influence of a co-facilitated education intervention on practitioners' recovery beliefs and practices.

Despite health policy and research increasingly advocating for recovery-enabling principles to be better integrated into mental health services, finding solutions to enhance the translation of recovery policy into practice remains a challenge. This study sought to understand whether a co-facilitated group education intervention for service users and family members reached beyond the intervention and impacted the everyday recovery promoting beliefs and practices of the practitioners involved and the wider organization. The study employed a qualitative design involving semi-structured interviews with a purposively selected sample of 28 participants (mental health nurses and other members of the multidisciplinary team) who were involved in delivering the intervention. Data were analysed using thematic analysis, with the assistance of NVivo. Participants reported that not only did involvement with the programmes help them reconnect with the contextual realities of service user and family members lived experience, but it enabled them to move beyond traditional power relationships and pathologizing discourses. Having engaged with and experienced the feasibility and positive impact of the co-facilitation process practitioners' self-efficacy around partnership working and co-production was enhanced. In addition, those involved demonstrated a willingness to challenge paternalistic practices and advocate for the perspectives of service users and families to be further embedded within the organizational infrastructure and operational spaces. Providing mental health practitioners with real-life examples of partnership working and peer support in action within a co-facilitated psychoeducation context has potential to be a forum for promoting second-order change around recovery-oriented practice within mental health services.

Action of iron chelator on intramyocardial hemorrhage and cardiac remodeling following acute myocardial infarction.

Intramyocardial hemorrhage is an independent predictor of adverse outcomes in ST-segment elevation myocardial infarction (STEMI). Iron deposition resulting from ischemia-reperfusion injury (I/R) is pro-inflammatory and has been associated with adverse remodeling. The role of iron chelation in hemorrhagic acute myocardial infarction (AMI) has never been explored. The purpose of this study was to investigate the cardioprotection offered by the iron-chelating agent deferiprone (DFP) in a porcine AMI model by evaluating hemorrhage neutralization and subsequent cardiac remodeling. Two groups of animals underwent a reperfused AMI procedure: control and DFP treated (N = 7 each). A comprehensive MRI examination was performed in healthy state and up to week 4 post-AMI, followed by histological assessment. Infarct size was not significantly different between the two groups; however, the DFP group demonstrated earlier resolution of hemorrhage (by T2* imaging) and edema (by T2 imaging). Additionally, ventricular enlargement and myocardial hypertrophy (wall thickness and mass) were significantly smaller with DFP, suggesting reduced adverse remodeling, compared to control. The histologic results were consistent with the MRI findings. To date, there is no effective targeted therapy for reperfusion hemorrhage. Our proof-of-concept study is the first to identify hemorrhage-derived iron as a therapeutic target in I/R and exploit the cardioprotective properties of an iron-chelating drug candidate in the setting of AMI. Iron chelation could potentially serve as an adjunctive therapy in hemorrhagic AMI.

Identification and Evaluations of Novel Insecticidal Proteins from Plants of the Class Polypodiopsida for Crop Protection against Key Lepidopteran Pests.

Various lepidopteran insects are responsible for major crop losses worldwide. Although crop plant varieties developed to express Bacillus thuringiensis (Bt) proteins are effective at controlling damage from key lepidopteran pests, some insect populations have evolved to be insensitive to certain Bt proteins. Here, we report the discovery of a family of homologous proteins, two of which we have designated IPD083Aa and IPD083Cb, which are from Adiantum spp. Both proteins share no known peptide domains, sequence motifs, or signatures with other proteins. Transgenic soybean or corn plants expressing either IPD083Aa or IPD083Cb, respectively, show protection from feeding damage by several key pests under field conditions. The results from comparative studies with major Bt proteins currently deployed in transgenic crops indicate that the IPD083 proteins function by binding to different target sites. These results indicate that IPD083Aa and IPD083Cb can serve as alternatives to traditional Bt-based insect control traits with potential to counter insect resistance to Bt proteins.

Collaborative Goals for Communicative Life Participation in Aphasia: The FOURC Model.

Purpose Collaborative goal setting is at the heart of person-centered rehabilitation but can be challenging, particularly in the area of aphasia. The purpose of this clinical focus article is to present a step-by-step model for forming a collaborative partnership with clients to develop an intervention plan that follows the client's lead, addresses communicative participation, and integrates multiple treatment strategies. Method We introduce the rationale and core features of a 4-step and 4-pronged process (the FOURC model) and illustrate its application through 3 cases of people with aphasia who were treated in outpatient rehabilitation. Conclusions The model invites client initiative in a clinically feasible manner while supporting the clinician's role in guiding the intervention based on professional expertise and growing familiarity with the case. Outcomes observed in case studies include strengthened motivation and improved real-life communication.

Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate the Infarcted Pig Heart but Induce Ventricular Tachyarrhythmias.

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) show considerable promise for regenerating injured hearts, and we therefore tested their capacity to stably engraft in a translationally relevant preclinical model, the infarcted pig heart. Transplantation of immature hESC-CMs resulted in substantial myocardial implants within the infarct scar that matured over time, formed vascular networks with the host, and evoked minimal cellular rejection. While arrhythmias were rare in infarcted pigs receiving vehicle alone, hESC-CM recipients experienced frequent monomorphic ventricular tachycardia before reverting back to normal sinus rhythm by 4 weeks post transplantation. Electroanatomical mapping and pacing studies implicated focal mechanisms, rather than macro-reentry, for these graft-related tachyarrhythmias as evidenced by an abnormal centrifugal pattern with earliest electrical activation in histologically confirmed graft tissue. These findings demonstrate the suitability of the pig model for the preclinical development of a hESC-based cardiac therapy and provide new insights into the mechanistic basis of electrical instability following hESC-CM transplantation.

Non-contrast assessment of microvascular integrity using arterial spin labeled cardiovascular magnetic resonance in a porcine model of acute myocardial infarction.

BACKGROUND: Following acute myocardial infarction (AMI), microvascular integrity and function may be compromised as a result of microvascular obstruction (MVO) and vasodilator dysfunction. It has been observed that both infarcted and remote myocardial territories may exhibit impaired myocardial blood flow (MBF) patterns associated with an abnormal vasodilator response. Arterial spin labeled (ASL) CMR is a novel non-contrast technique that can quantitatively measure MBF. This study investigates the feasibility of ASL-CMR to assess MVO and vasodilator response in swine. METHODS: Thirty-one swine were included in this study. Resting ASL-CMR was performed on 24 healthy swine (baseline group). A subset of 13 swine from the baseline group underwent stress ASL-CMR to assess vasodilator response. Fifteen swine were subjected to a 90-min left anterior descending (LAD) coronary artery occlusion followed by reperfusion. Resting ASL-CMR was performed post-AMI at 1-2 days (N = 9, of which 6 were from the baseline group), 1-2 weeks (N = 8, of which 4 were from the day 1-2 group), and 4 weeks (N = 4, of which 2 were from the week 1-2 group). Resting first-pass CMR and late gadolinium enhancement (LGE) were performed post-AMI for reference. RESULTS: At rest, regional MBF and physiological noise measured from ASL-CMR were 1.08 ± 0.62 and 0.15 ± 0.10 ml/g/min, respectively. Regional MBF increased to 1.47 ± 0.62 ml/g/min with dipyridamole vasodilation (P < 0.001). Significant reduction in MBF was found in the infarcted region 1-2 days, 1-2 weeks, and 4 weeks post-AMI compared to baseline (P < 0.03). This was consistent with perfusion deficit seen on first-pass CMR and with MVO seen on LGE. There were no significant differences between measured MBF in the remote regions pre and post-AMI (P > 0.60). CONCLUSIONS: ASL-CMR can assess vasodilator response in healthy swine and detect significant reduction in regional MBF at rest following AMI. ASL-CMR is an alternative to gadolinium-based techniques for assessment of MVO and microvascular integrity within infarcted, as well as salvageable and remote myocardium. This has the potential to provide early indications of adverse remodeling processes post-ischemia.