A cortico-collicular circuit for orienting to shelter during escape.

When faced with predatory threats, escape towards shelter is an adaptive action that offers long-term protection against the attacker. Animals rely on knowledge of safe locations in the environment to instinctively execute rapid shelter-directed escape actions1,2. Although previous work has identified neural mechanisms of escape initiation3,4, it is not known how the escape circuit incorporates spatial information to execute rapid flights along the most efficient route to shelter. Here we show that the mouse retrosplenial cortex (RSP) and superior colliculus (SC) form a circuit that encodes the shelter-direction vector and is specifically required for accurately orienting to shelter during escape. Shelter direction is encoded in RSP and SC neurons in egocentric coordinates and SC shelter-direction tuning depends on RSP activity. Inactivation of the RSP-SC pathway disrupts the orientation to shelter and causes escapes away from the optimal shelter-directed route, but does not lead to generic deficits in orientation or spatial navigation. We find that the RSP and SC are monosynaptically connected and form a feedforward lateral inhibition microcircuit that strongly drives the inhibitory collicular network because of higher RSP input convergence and synaptic integration efficiency in inhibitory SC neurons. This results in broad shelter-direction tuning in inhibitory SC neurons and sharply tuned excitatory SC neurons. These findings are recapitulated by a biologically constrained spiking network model in which RSP input to the local SC recurrent ring architecture generates a circular shelter-direction map. We propose that this RSP-SC circuit might be specialized for generating collicular representations of memorized spatial goals that are readily accessible to the motor system during escape, or more broadly, during navigation when the goal must be reached as fast as possible.

Meltable, Glass-Forming, Iron Zeolitic Imidazolate Frameworks.

We describe the first meltable iron-based zeolitic imidazolate framework (ZIF), denoted MUV-24. This material, elusive from direct synthesis, is obtained from the thermal treatment of [Fe3(im)6(Him)2], which yields Fe(im)2 upon loss of the neutral imidazole molecules. Different crystalline phase transformations are observed upon further heating, until the material melts at 482 °C. Vitrification upon cooling of the liquid phase gives rise to the first Fe-metal-organic framework glass. X-ray total scattering experiments show that the tetrahedral environment of the crystalline solids is maintained in the glass, whereas nanoindentation measurements reveal an increase in Young's modulus, in agreement with stiffening upon vitrification.

Levels of type XVII collagen (BP180) ectodomain are elevated in circulation from patients with multiple cancer types and is prognostic for patients with metastatic colorectal cancer.

BACKGROUND: Collagens are the major components of the extracellular matrix (ECM) and are known to contribute to tumor progression and metastasis. There are 28 different types of collagens each with unique functions in maintaining tissue structure and function. Type XVII collagen (BP180) is a type II transmembrane protein that provides stable adhesion between epithelial cells and the underlying basement membrane. Aberrant expression and ectodomain shedding of type XVII collagen have been associated with epithelial damage, tumor invasiveness, and metastasis in multiple tumor types and may consequently be used as a potential (non-invasive) biomarker in cancer and treatment target. METHOD: An ELISA targeting the type XVII collagen ectodomain (PRO-C17) was developed for use in serum. PRO-C17 was measured in a cohort of patients with 11 different cancer types (n = 214) and compared to healthy controls (n = 23) (cohort 1). Based on the findings from cohort 1, PRO-C17 and its association with survival was explored in patients with metastatic colorectal cancer (mCRC) treated with bevacizumab in combination with chemotherapy (n = 212) (cohort 2). RESULTS: PRO-C17 was robust and specific towards the ectodomain of type XVII collagen. In cohort 1, PRO-C17 levels were elevated (p < 0.05) in serum from patients with CRC, kidney, ovarian, bladder, breast, and head and neck cancer compared to healthy controls. PRO-C17 was especially good at discriminating between CRC patients and healthy controls with an AUROC of 0.904. In cohort 2, patients with mCRC and high levels (tertile 3) of PRO-C17 had shorter overall survival (OS) with a median OS of 390 days compared to 539 days for patients with low levels of PRO-C17. When evaluated by multivariate Cox regression analysis, high PRO-C17 was predictive for poor OS independent of risk factors and the tumor fibrosis biomarker PRO-C3. CONCLUSION: PRO-C17 measures the ectodomain of type XVII collagen in serum and is a promising non-invasive biomarker that can aid in understanding tumor heterogeneity as well as elaborate on the role of collagen XVII in tumor progression. Moreover, the findings in the study proposes PRO-C17 as novel biomarker of epithelial damage in specific cancer types including CRC.

[64Cu]Cu-DOTATATE PET metrics in the investigation of atherosclerotic inflammation in humans.

PURPOSE: The aim of this study was to assess and compare the arterial uptake of the inflammatory macrophage targeting PET tracer [64Cu]Cu-DOTATATE in patients with no or known cardiovascular disease (CVD) to investigate potential differences in uptake. METHODS: Seventy-nine patients who had undergone [64Cu]Cu-DOTATATE PET/CT imaging for neuroendocrine neoplasm disease were retrospectively allocated to three groups: controls with no known CVD risk factors (n = 22), patients with CVD risk factors (n = 24), or patients with known ischemic CVD (n = 33). Both maximum, mean of max and most-diseased segment (mds) standardized uptake value (SUV) and target-to-background ratio (TBR) uptake metrics were measured and reported for the carotid arteries and the aorta. To assess reproducibility between different reviewers, Bland-Altman plots were made. RESULTS: For the carotid arteries, SUVmax (P = .03), SUVmds (0.05), TBRmax (P < .01), TBRmds (P < .01), and mean-of-max TBR (P = .01) were overall shown to provide a group-wise difference in uptake. When measuring uptake values in the aorta, a group-wise difference was only observed with TBRmds (P = .04). Overall, reproducibility of the reported uptake metrics was excellent for SUVs and good to excellent for TBRs for both the carotid arteries and the aorta. CONCLUSION: Using [64Cu]Cu-DOTATATE PET imaging as a marker of atherosclerotic inflammation, we were able to demonstrate differences in some of the most frequently reported uptake metrics in patients with different degrees of CVD. Measurements of the carotid artery as either maximum uptake values or most-diseased segment analysis showed the best ability to discriminate between the groups.

Fibrotic activity quantified in serum by measurements of type III collagen pro-peptides can be used for prognosis across different solid tumor types.

Due to activation of fibroblast into cancer-associated fibroblasts, there is often an increased deposition of extracellular matrix and fibrillar collagens, e.g. type III collagen, in the tumor microenvironment (TME) that leads to tumor fibrosis (desmoplasia). Tumor fibrosis is closely associated with treatment response and poor prognosis for patients with solid tumors. To assure that the best possible treatment option is provided for patients, there is medical need for identifying patients with high (or low) fibrotic activity in the TME. Measuring unique collagen fragments such as the pro-peptides released into the bloodstream during fibrillar collagen deposition in the TME can provide a non-invasive measure of the fibrotic activity. Based on data from 8 previously published cohorts, this review provides insight into the prognostic value of quantifying tumor fibrosis by measuring the pro-peptide of type III collagen in serum of a total of 1692 patients with different solid tumor types and discusses the importance of tumor fibrosis for understanding prognosis and for potentially guiding future drug development efforts that aim at overcoming the poor outcome associated with a fibrotic TME.

New Collaborative Research on Suicide Prevention, Practice, and Policy With American Indian and Alaska Native Communities Holds Promise for All Peoples.

Youth suicide is increasing in the United States, with deaths among younger people of color driving this upward trend. For more than four decades, American Indian and Alaska Native (AIAN) communities have suffered disproportionate rates of youth suicide and years of productive life lost compared to other U.S. Races. The National Institute of Mental Health (NIMH) recently funded three regional Collaborative Hubs to carry out suicide prevention research, practice, and policy development with AIAN communities in Alaska and rural and urban areas of the Southwestern United States. The Hub partnerships are supporting a diverse array of tribally-driven studies, approaches, and policies with immediate value for increasing empirically driven public health strategies to address youth suicide. We discuss unique features of the cross-Hub work, including: (a) long-standing Community-Based Participatory Research processes that led to the Hubs' innovative designs and novel approaches to suicide prevention and evaluation, (b) comprehensive ecological theoretical approaches that contextualize individual risk and protective factors in multilevel social contexts; (c) unique task-shifting and systems of care approaches to increase reach and impact on youth suicide in low-resource settings; and (d) prioritization of strengths-based approaches. The work of the Collaborative Hubs for AIAN youth suicide prevention is generating specific and substantive implications for practice, policy, and research presented in this article at a time when youth suicide prevention is a dire national priority. Approaches also have relevance for historically marginalized communities worldwide.

Fabrication of Super-Sized Metal Inorganic-Organic Hybrid Glass with Supramolecular Network via Crystallization-Suppressing Approach.

Metal coordination compound (MCC) glasses [e.g., metal-organic framework (MOF) glass, coordination polymer glass, and metal inorganic-organic complex (MIOC) glass] are emerging members of the hybrid glass family. So far, a limited number of crystalline MCCs can be converted into glasses by melt-quenching. Here, we report a universal wet-chemistry method, by which the super-sized supramolecular MIOC glasses can be synthesized from non-meltable MOFs. Alcohol and acid were used as agents to inhibit crystallization. The MIOC glasses demonstrate unique features including high transparency, shaping capability, and anisotropic network. Directional photoluminescence with a large polarization ratio (≈47 %) was observed from samples doped with organic dyes. This crystallization-suppressing approach enables fabrication of super-sized MCC glasses, which cannot be achieved by conventional vitrification methods, and thus allows for exploring new MCC glasses possessing photonic functionalities.

Correction: A system for tracking whisker kinematics and whisker shape in three dimensions.

[This corrects the article DOI: 10.1371/journal.pcbi.1007402.].

Myocardial perfusion recovery induced by an α-calcitonin gene-related peptide analogue.

BACKGROUND: Endogenous calcitonin gene-related peptide (CGRP) induces cardioprotective effects through coronary vasodilation. However, the systemic administration of CGRP induces peripheral vasodilation and positive chronotropic and inotropic effects. This study aims to examine the net effect on coronary perfusion of the systemically administered α-calcitonin gene-related peptide analogue, SAX, in rats during myocardial infarction. METHODS: Forty Sprague-Dawley rats underwent myocardial infarction. Following left anterior descending artery occlusion, [99mTc]Tc-sestamibi was administered to determine the myocardial perfusion before treatment. Twenty minutes, 24 and 48 h after [99mTc]Tc-sestamibi injection, the rats were treated with either SAX or placebo. Final infarct size was determined three weeks later by [99mTc]Tc-sestamibi SPECT/CT scan. RESULTS: Thirty-one rats survived the surgery and 20 completed the follow-up SPECT/CT scan (SAX n = 12; Placebo n = 8). At baseline, there was no difference in size of perfusion defect between the groups (P = .88), but at follow-up the SAX group had improved myocardial recovery compared to the placebo group (P = .04), corresponding to a relative perfusion recovery of 55% in SAX-treated rats. CONCLUSION: The CGRP analogue, SAX, has a cardioprotective effect in this rat model of myocardial infarction, improving myocardial perfusion recovery after chronic occlusion of the coronary artery.

Amiodarone attenuates cardiac Rubidium-82 in consecutive PET/CT scans in a rodent model.

BACKGROUND: Risk stratification and diagnosis using Rubidium-82 (82Rb) positron emission tomography (PET) is a routine clinical approach in coronary artery disease (CAD). Various drugs are used to treat CAD; however, whether any of them change the uptake of 82Rb in the heart has not been investigated. The aim of this study is to determine whether drugs used in treatment of CAD affect the uptake of 82Rb in the heart in healthy rats. METHODS: Seventy-seven Sprague-Dawley rats were included in the cross-sectional study. All rats underwent baseline 82Rb PET/CT and divided into eleven groups treated with different drugs. One group was control group (no treatment), eight groups were treated with monotherapy (amiodarone, acetylsalicylic acid (ASA), clopidogrel, ticagrelor, atorvastatin, enalapril, amlodipine, metoprolol succinate), and two groups were treated with polypharmacy (ASA, ticagrelor, atorvastatin, amlodipine or ASA, clopidogrel, atorvastatin, amlodipine). Once a day, they were administered pharmacological therapy through oral gavage, and on day seven, follow-up scanned with 82Rb PET/CT. RESULTS: In the control group without pharmacological treatment, no difference in the standard uptake value (SUV) ratio between heart and muscle from baseline to follow-up (5.8 vs 7.0, P = .3) was found. The group treated with amiodarone had a significantly reduced SUV ratio from baseline to follow-up (5.8 vs 5.1, P = .008). All other drugs investigated had no difference in SUV ratio from baseline to follow-up. CONCLUSION: In this study, we showed that drugs normally used to treat CAD do not affect the uptake of 82Rb. However, amiodarone result in a significantly lowered 82Rb uptake, compared to control. This information about amiodarone would probably not change the size assessment of a myocardial perfusion defect in a clinical setting. However, it could change the kinetic parameters when assessing absolute myocardial blood flow in patients treated with amiodarone.

Non-invasive assessment of temporal changes in myocardial microvascular function in persons with type 2 diabetes and healthy controls.

BACKGROUND: Cardiac Rubidium-82 (82 Rb) positron emission tomography/computed tomography (PET/CT) provides a measure of the myocardial blood flow and the myocardial flow reserve, which reflects the function of both large epicardial arteries and the myocardial microcirculation. Knowledge on changes in the myocardial microvascular function over time is lacking. METHODS: In this cohort study, we recruited 60 persons with type 2 diabetes and 30 non-diabetic controls, in 2013; all free of overt cardiovascular disease. All underwent a cardiac 82 Rb PET/CT scan. In 2019, all survivors (n = 82) were invited for a repeated cardiac 82 Rb PET/CT scan using the same protocol, and 29 with type 2 diabetes and 19 controls participated. RESULTS: Median duration between visits was 6.2 years (IQR: 6.1-6.3). In the total cohort, the mean age was 66.4 years (SD: 9.3) and 33% were females. The myocardial flow reserve was lower in persons with type 2 diabetes compared to controls (p = 0.002) but there was no temporal change in the myocardial flow reserve in participants with type 2 diabetes: mean change: -0.22 (95% CI: -0.47 to 0.02) nor in controls: -0.12 (-0.49 to 0.25) or when comparing type 2 diabetes to controls: mean difference: -0.10 (95% CI: -0.52 to 0.31). The temporal reduction in stress-induced myocardial blood flow did not differ within the groups but was more pronounced in type 2 diabetes compared to controls: mean difference: -0.30 (95% CI: -0.55 to -0.04). CONCLUSION: The myocardial microvascular function was impaired in persons with type 2 diabetes compared to controls but did not change significantly in either of the groups when evaluated over 6 years.

A system for tracking whisker kinematics and whisker shape in three dimensions.

Quantification of behaviour is essential for biology. Since the whisker system is a popular model, it is important to have methods for measuring whisker movements from behaving animals. Here, we developed a high-speed imaging system that measures whisker movements simultaneously from two vantage points. We developed a whisker tracker algorithm that automatically reconstructs 3D whisker information directly from the 'stereo' video data. The tracker is controlled via a Graphical User Interface that also allows user-friendly curation. The algorithm tracks whiskers, by fitting a 3D Bezier curve to the basal section of each target whisker. By using prior knowledge of natural whisker motion and natural whisker shape to constrain the fits and by minimising the number of fitted parameters, the algorithm is able to track multiple whiskers in parallel with low error rate. We used the output of the tracker to produce a 3D description of each tracked whisker, including its 3D orientation and 3D shape, as well as bending-related mechanical force. In conclusion, we present a non-invasive, automatic system to track whiskers in 3D from high-speed video, creating the opportunity for comprehensive 3D analysis of sensorimotor behaviour and its neural basis.

Liraglutide reduces cardiac adipose tissue in type 2 diabetes: A secondary analysis of the LIRAFLAME randomized placebo-controlled trial.

AIM: To test the hypothesis that treatment with liraglutide can reduce cardiac adipose tissue. MATERIALS AND METHODS: LIRAFLAME is a randomized placebo-controlled, double-blind, parallel clinical study. Participants with type 2 diabetes were randomized to treatment with liraglutide 1.8 mg/d or placebo for 26 weeks. Computed tomography was performed at baseline and at end of treatment to evaluate the cardiac adipose tissue volume, quantified automatically. We report the results of a secondary endpoint evaluating changes in cardiac adipose tissue. RESULTS: A total of 102 participants were randomly assigned to liraglutide (n = 51) or placebo (n = 51). At baseline, the mean (SD) cardiac adipose tissue volume was comparable between the liraglutide and the placebo group (232.6 [112.8] vs. 227.0 [103.2] mL; P = 0.80). The mean change in body weight was -3.7 (-4.8, -2.6) kg in the liraglutide and -0.18 (-0.76, 0.40) kg in the placebo group. From baseline to end of treatment the mean cardiac adipose tissue change was -11.5 (95% confidence interval -17.6, -5.4) mL in the liraglutide (P < 0.001) and -0.01 (-5.3, 5.3) mL in the placebo (P = 1.00) groups. The reduction in cardiac adipose tissue was significantly greater in the liraglutide compared to the placebo group (mean difference -11.4 [-19.4, -3.3] mL; P = 0.006), but significance was lost after adjustment for changes in body mass index (P = 0.46). CONCLUSION: Treatment with liraglutide for 26 weeks was associated with a reduction in cardiac adipose tissue compared to placebo. The reduction was not independent of weight loss, suggesting that this is not a drug-specific effect.

Photoreceptive retinal ganglion cells control the information rate of the optic nerve.

Information transfer in the brain relies upon energetically expensive spiking activity of neurons. Rates of information flow should therefore be carefully optimized, but mechanisms to control this parameter are poorly understood. We address this deficit in the visual system, where ambient light (irradiance) is predictive of the amount of information reaching the eye and ask whether a neural measure of irradiance can therefore be used to proactively control information flow along the optic nerve. We first show that firing rates for the retina's output neurons [retinal ganglion cells (RGCs)] scale with irradiance and are positively correlated with rates of information and the gain of visual responses. Irradiance modulates firing in the absence of any other visual signal confirming that this is a genuine response to changing ambient light. Irradiance-driven changes in firing are observed across the population of RGCs (including in both ON and OFF units) but are disrupted in mice lacking melanopsin [the photopigment of irradiance-coding intrinsically photosensitive RGCs (ipRGCs)] and can be induced under steady light exposure by chemogenetic activation of ipRGCs. Artificially elevating firing by chemogenetic excitation of ipRGCs is sufficient to increase information flow by increasing the gain of visual responses, indicating that enhanced firing is a cause of increased information transfer at higher irradiance. Our results establish a retinal circuitry driving changes in RGC firing as an active response to alterations in ambient light to adjust the amount of visual information transmitted to the brain.

The Initial Cardiac Tissue Response to Cryopreserved Allogeneic Adipose Tissue-Derived Mesenchymal Stromal Cells in Rats with Chronic Ischemic Cardiomyopathy.

Mesenchymal stromal cells have proven capable of improving cardiac pump function in patients with chronic heart failure, yet little is known about their mode of action. The aim of the study was to investigate the short-term effect of cryopreserved allogeneic rat adipose tissue-derived stromal cells (ASC) on cardiac composition, cellular subpopulations, and gene transcription in a rat model of chronic ischemic cardiomyopathy (ICM). Myocardial infarction (MI) was induced by permanent ligation of the left anterior descending coronary artery. After 6 weeks, the rats were treated with ASCs, saline, or no injection, using echo-guided trans-thoracic intramyocardial injections. The cardiac tissue was subsequently collected for analysis of cellular subpopulations and gene transcription 3 and 7 days after treatment. At day 3, an upregulation of genes associated with angiogenesis were present in the ASC group. On day 7, increases in CCR2+ and CD38+ macrophages (p = 0.047 and p = 0.021), as well as in the CD4/CD8 lymphocyte ratio (p = 0.021), were found in the ASC group compared to the saline group. This was supported by an upregulation of genes associated with monocytes/macrophages. In conclusion, ASC treatment initiated an immune response involving monocytes/macrophages and T-cells and induced a gene expression pattern associated with angiogenesis and monocyte/macrophage differentiation.

Prediction of Choice from Competing Mechanosensory and Choice-Memory Cues during Active Tactile Decision Making.

Perceptual decision making is an active process where animals move their sense organs to extract task-relevant information. To investigate how the brain translates sensory input into decisions during active sensation, we developed a mouse active touch task where the mechanosensory input can be precisely measured and that challenges animals to use multiple mechanosensory cues. Male mice were trained to localize a pole using a single whisker and to report their decision by selecting one of three choices. Using high-speed imaging and machine vision, we estimated whisker-object mechanical forces at millisecond resolution. Mice solved the task by a sensory-motor strategy where both the strength and direction of whisker bending were informative cues to pole location. We found competing influences of immediate sensory input and choice memory on mouse choice. On correct trials, choice could be predicted from the direction and strength of whisker bending, but not from previous choice. In contrast, on error trials, choice could be predicted from previous choice but not from whisker bending. This study shows that animal choices during active tactile decision making can be predicted from mechanosensory and choice-memory signals, and provides a new task well suited for the future study of the neural basis of active perceptual decisions.SIGNIFICANCE STATEMENT Due to the difficulty of measuring the sensory input to moving sense organs, active perceptual decision making remains poorly understood. The whisker system provides a way forward since it is now possible to measure the mechanical forces due to whisker-object contact during behavior. Here we train mice in a novel behavioral task that challenges them to use rich mechanosensory cues but can be performed using one whisker and enables task-relevant mechanical forces to be precisely estimated. This approach enables rigorous study of how sensory cues translate into action during active, perceptual decision making. Our findings provide new insight into active touch and how sensory/internal signals interact to determine behavioral choices.

Visualization of sodium dynamics in the kidney by magnetic resonance imaging in a multi-site study.

Sodium magnetic resonance imaging (MRI) is a powerful, non-invasive technique to assess sodium distribution within the kidney. Here we undertook pre-clinical and clinical studies to quantify the corticomedullary sodium gradient in healthy individuals and in a porcine model of diuresis. The results demonstrated that sodium MRI could detect spatial differences in sodium biodistribution across the kidney. The sodium gradient of the kidney changed significantly after diuresis in the pig model and was independent of blood electrolyte measurements. Thus, rapid sodium MRI can be used to dynamically quantify sodium biodistribution in the porcine and human kidney.

The impact of the glucagon-like peptide-1 receptor agonist liraglutide on natriuretic peptides in heart failure patients with reduced ejection fraction with and without type 2 diabetes.

AIM: To assess the effect of liraglutide, a glucagon-like peptide-1 receptor agonist, on urinary sodium excretion as well as on circulating adrenomedullin and copeptin levels in patients with type 2 diabetes (T2D). MATERIALS AND METHODS: In the LIVE study, patients (n = 241) with left ventricular ejection fraction ≤45% were randomized to liraglutide 1.8 mg daily or placebo for 24 weeks, and 30% had a concomitant diagnosis of T2D. Plasma levels of N-terminal brain-natriuretic-peptide (NT-proBNP) (a predefined secondary endpoint), midregional pro-atrial-natriuretic-peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM) and copeptin were measured at baseline and after 24 weeks in this substudy. The potential effect modification of T2D was assessed. RESULTS: In the eligible subgroup of 231 patients with available biomarkers (115 randomized to liraglutide and 116 to placebo), MR-proANP decreased by 12% (P = .002) and NT-proBNP by 9% (P = .009) during liraglutide treatment compared with placebo at week 24. Interaction with T2D for the treatment effect of change in MR-proANP and NT-proBNP levels was P = .003 and P = .03, respectively. Consequently, in patients with T2D, liraglutide decreased MR-proANP by 27% (P < .001) and NT-proBNP by 25% (P = .02) compared with placebo, whereas no change was observed in patients without T2D. There was no effect of liraglutide on MR-proADM (P = .10) or copeptin (P = .52). CONCLUSION: Liraglutide decreased the A- and B-type natriuretic peptides significantly in patients with heart failure with reduced ejection fraction (HFrEF) and concomitant T2D, suggesting a beneficial mechanism of liraglutide in T2D patients with HFrEF.

Radiofrequency ablation lesions in low-, intermediate-, and normal-voltage myocardium: an in vivo study in a porcine heart model.

AIMS: Contact force (CF) between radiofrequency (RF) ablation catheter and myocardium and ablation index (AI) correlates with RF lesion depth and width in normal-voltage (>1.5 mV) myocardium (NVM). We investigate the impact of CF on RF lesion depth and width in low (<0.5 mV) (LVM) and intermediate-voltage (0.5-1.5 mV) myocardium (IVM) following myocardial infarction. Correlation between RF lesion depth and width evaluated by native contrast magnetic resonance imaging (ncMRI) and gross anatomical evaluation was investigated. METHODS AND RESULTS: Twelve weeks after myocardial infarction, 10 pigs underwent electroanatomical mapping and endocardial RF ablations were deployed in NVM, IVM, and LVM myocardium. In vivo ncMRI was performed before the heart was excised and subjected to gross anatomical evaluation. Ninety (82%) RF lesions were evaluated. Radiofrequency lesion depth and width were smaller in IVM and LVM compared with NVM (P < 0.001). Radiofrequency lesion depth and width correlated with CF, AI, and impedance drop in NVM (CF and AI P < 0.001) and IVM (CF and AI depths P < 0.001; CF and AI widths P < 0.05). Native contrast magnetic resonance imaging evaluated RF lesion depth and width correlated with gross anatomical depth and width (NVM and IVM P < 0.001; LVM P < 0.05). CONCLUSIONS: Radiofrequency lesions deployed by similar duration, power and CF are smaller in IVM and LVM than in NVM. Radiofrequency lesion depth and width correlated with CF, AI, and impedance drop in NVM and IVM but not in LVM. Native contrast magnetic resonance imaging may be useful to assess RF lesion depth and width in NVM, IVM, and LVM.

Seclusion versus mechanical restraint in psychiatry - a systematic review.

OBJECTIVE: Seclusion and mechanical restraint are coercive interventions used at psychiatric hospitals when patients are at imminent risk of harming themselves and/or others. Although these interventions have been used for decades, it remains unclear whether seclusion or mechanical restraint is superior in terms of efficacy and safety. Therefore, we aimed to systematically review studies comparing the intended and unintended effects of seclusion and mechanical restraint. METHODS: A systematic search of PubMed and Embase was conducted in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Quantitative studies comparing the intended and unintended effects of seclusion and mechanical restraint were included. RESULTS: The search identified 868 unique records. Fourteen of these (3 reporting on randomized controlled trials and 11 reporting on observational studies) met the predefined inclusion criteria. The study methodology including outcome measures varied significantly across studies. The results of the 11 studies using a subjective outcome measure (patient preference/emotions) were in favour of seclusion, while the 3 studies using an objective outcome measure (duration of coercion/need for transition to other coercive measure) favoured mechanical restraint. There was a high risk of residual confounding by indication and/or bias affecting the reported results. CONCLUSION: Based on the available literature, it cannot be determined whether seclusion is superior to mechanical restraint or vice versa. Further studies using stringent methodology are required to answer this question. A cautious conclusion based on this review is that the availability of both methods seems necessary - as both have their pros and cons.