Non-invasive optical imaging techniques are essential diagnostic tools in many fields. Although various recent methods have been proposed to utilize and control light in multiple scattering media, ...non-invasive optical imaging through and inside scattering layers across a large field of view remains elusive due to the physical limits set by the optical memory effect, especially without wavefront shaping techniques. Here, we demonstrate an approach that enables non-invasive fluorescence imaging behind scattering layers with field-of-views extending well beyond the optical memory effect. The method consists in demixing the speckle patterns emitted by a fluorescent object under variable unknown random illumination, using matrix factorization and a novel fingerprint-based reconstruction. Experimental validation shows the efficiency and robustness of the method with various fluorescent samples, covering a field of view up to three times the optical memory effect range. Our non-invasive imaging technique is simple, neither requires a spatial light modulator nor a guide star, and can be generalized to a wide range of incoherent contrast mechanisms and illumination schemes.
Sensory information is encoded within the brain in distributed spatiotemporal patterns of neuronal activity. Understanding how these patterns influence behavior requires a method to measure and to ...bidirectionally perturb with high spatial resolution the activity of the multiple neuronal cell types engaged in sensory processing. Here, we combined two-photon holography to stimulate neurons expressing blue light-sensitive opsins (ChR2 and GtACR2) with two-photon imaging of the red-shifted indicator jRCaMP1a in the mouse neocortex in vivo. We demonstrate efficient control of neural excitability across cell types and layers with holographic stimulation and improved spatial resolution by opsin somatic targeting. Moreover, we performed simultaneous two-photon imaging of jRCaMP1a and bidirectional two-photon manipulation of cellular activity with negligible effect of the imaging beam on opsin excitation. This all-optical approach represents a powerful tool to causally dissect how activity patterns in specified ensembles of neurons determine brain function and animal behavior.
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•High-resolution bidirectional control of cell activity in the intact mouse brain•High-resolution manipulation is effective across cortical cell types and layers•Simultaneous all-optical imaging and bidirectional manipulation•Minimal crosstalk between imaging and opsin activation
Forli et al. developed an all-optical method to image and bidirectionally manipulate brain networks with high spatial resolution and minimal crosstalk in the intact mammalian brain. They validate the method across cell types and layers in the mouse neocortex.
Highlights • Whether frailty is a potential cardiovascular risk factor is currently poorly understood. • In this meta-analysis frailty was associated with a higher prevalence and incidence of CVD. • ...Interventional studies are needed to test if improving frail and prefrail status can reduce CV risk and outcomes.
The optimal antiaggregant therapy after coronary stenting in patients receiving oral anticoagulants (OACs) is currently debated. MEDLINE and Cochrane Library were searched for studies reporting ...outcomes of patients who underwent PCI and who were on triple therapy (TT) or dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel or dual therapy (DT) with OAC and clopidogrel. Major bleeding was the primary end point, whereas all-cause death, myocardial infarction (MI), stent thrombosis, and stroke were secondary ones. Results were reported for all studies and separately for those deriving from randomized controlled trials or multivariate analysis. In 9 studies, 1,317 patients were treated with DAPT and 1,547 with TT. DAPT offered a significant reduction of major bleeding at 1 year for overall studies and for the subset of observational works providing adjusted data (odds ratio OR 0.51, 95% confidence interval CI 0.39 to 0.68, I2 60% and OR 0.36, 95% CI 0.28 to 0.46) compared to TT. No increased risk of major adverse cardiac events (MACE: death, MI, stroke, and stent thrombosis) was reported (OR 0.71, 95% CI 0.46 to 1.08), although not deriving from randomized controlled trials or multivariate analysis. Six studies tested OAC and clopidogrel (1,263 patients) versus OAC, aspirin, and clopidogrel (3,055 patients) with a significant reduction of bleeding (OR 0.79, 95% CI 0.64 to 0.98), without affecting rates of death, MI, stroke, and stent thrombosis (OR 0.90, 95% CI 0.69 to 1.23) also when including clinical data from randomized controlled trials or multivariate analysis. In conclusion, compared to TT, both aspirin and clopidogrel and clopidogrel and OAC reduce bleeding. No difference in major adverse cardiac events is present for clopidogrel and OAC, whereas only low-grade evidence is present for aspirin and clopidogrel.
Genetically encoded calcium indicators and optogenetic actuators can report and manipulate the activity of specific neuronal populations. However, applying imaging and optogenetics simultaneously has ...been difficult to establish in the mammalian brain, even though combining the techniques would provide a powerful approach to reveal the functional organization of neural circuits. Here, we developed a technique based on patterned two-photon illumination to allow fast scanless imaging of GCaMP6 signals in the intact mouse brain at the same time as single-photon optogenetic inhibition with Archaerhodopsin. Using combined imaging and electrophysiological recording, we demonstrate that single and short bursts of action potentials in pyramidal neurons can be detected in the scanless modality at acquisition frequencies up to 1 kHz. Moreover, we demonstrate that our system strongly reduces the artifacts in the fluorescence detection that are induced by single-photon optogenetic illumination. Finally, we validated our technique investigating the role of parvalbumin-positive (PV) interneurons in the control of spontaneous cortical dynamics. Monitoring the activity of cellular populations on a precise spatiotemporal scale while manipulating neuronal activity with optogenetics provides a powerful tool to causally elucidate the cellular mechanisms underlying circuit function in the intact mammalian brain.
The precision of echocardiography in estimating pulmonary pressures has been debated. A value of right atrial pressure (RAP) is needed for pulmonary pressure estimation, and it could be partly ...responsible for the estimation error. Several schemes based on the inferior vena cava (IVC) are commonly used in clinical practice and in experimental studies for RAP estimation. However, the majority lack proper validation, and thus far, no study has compared them all. In this prospective, blinded study, a comprehensive transthoracic echocardiography was performed on 200 patients referred for right heart catheterization. The IVC was measured in different views and RAP was estimated according to 6 different schemes. One hundred ninety patients were suitable for analysis. IVC measurements were significantly but poorly associated with invasive RAP. All RAP schemes showed poor accuracy compared with invasive RAP (average accuracy 34%). None of the schemes showed a clear superiority over the others. No echocardiographic or clinical variables showed a relevant impact on the estimation error. In conclusion, RAP estimation based on the IVC is highly inaccurate irrespective of the method used and should be avoided whenever possible. Whether adding estimated RAP values affects the estimation of pulmonary pressures is yet to be determined.
Introduction Accuracy of intracoronary imaging to discriminate functionally significant coronary stenosis according to vessel diameter remains to be defined. Methods PubMed, Scopus, and Google ...Scholar were systematically searched for studies assessing diagnostic accuracy (area under the receiver operating characteristic curve AUC, the primary end point) and sensitivity and specificity (the secondary end points) of minimal luminal area (MLA) or of minimal luminal diameter (MLD) derived from intravascular ultrasound (IVUS) or optical coherence tomography (OCT) to detect functionally significant stenosis as determined with fractional flow reserve (FFR). Results Fifteen studies were included, 2 with 110 patients analyzing only left main (LM), 5 with 224 patients and 306 lesions using OCT, and 9 with 1532 patients and 1681 lesions with IVUS. Median MLA for the OCT studies was 1.96 mm2 (1.85-1.98 mm2 ), 2.9 mm2 (2.7-3.1 mm2 ) for MLA of all lesions assessed with IVUS, 2.8 mm2 (2.7-2.9 mm2 ) for lesions with an angiographic diameter >3 mm, 2.4 mm2 (2.4-2.5 mm2 ) for lesions <3 mm, and 5.4 mm2 (5.1-5.6 mm2 ) for LM lesions. For OCT-MLA, AUC was 0.80 (0.74-0.86), with a sensitivity of 0.81 (0.74-0.87) and specificity of 0.77 (0.71-0.83), whereas OCT-MLD had an AUC of 0.85 (0.79-0.91), sensitivity of 0.74 (0.69-0.78), and specificity of 0.70 (0.68-0.73). For IVUS-MLA, AUC was 0.78 (0.75-0.81) for all lesions, 0.78 (0.73-0.84) for vessels with a diameter >3 mm, and 0.79 (0.70-0.89) for those with a diameter <3 mm. Left main AUC was 0.97 (0.93-1). Conclusion Intravascular ultrasound and OCT had modest diagnostic accuracy for identification hemodynamically significant lesions, also with specific cutoff for different diameters. Invasive imaging for assessment of LM severity demonstrated excellent correlation with FFR. What is already known about this subject? Fractional flow reserve represents the criterion standard to evaluate the prognostic value of coronary stenosis, whereas its relationship with IVUS and OCT remains to be assessed. What does this study add? Despite improvement, IVUS and OCT do not predict functional stenosis, even with dedicated cutoff, apart from LM disease. How might this impact on clinical practice? The recent guidelines of myocardial revascularization have stressed the crucial role of FFR before performing percutaneous coronary intervention on LM, whereas intravascular imaging is often exploited to drive revascularization. The present analysis stresses the point that LM percutaneous coronary intervention may be driven only by intravascular imaging, given the high accuracy for significant ischemic lesions, whereas for other vessels, these 2 techniques mirror 2 different aspects.
The aim of this study was to identify predictors of 30-day and midterm mortality after transcatheter aortic valve implantation (TAVI) by means of a systemic review. TAVI was demonstrated to be safe ...and efficacious in patients with severe aortic stenosis. An accurate estimation of procedural risk of these patients represents an actual challenge. The PubMed and Cochrane Collaboration databases were systematically searched for studies reporting on the incidence and independent predictors of 30-day and midterm mortality. Adverse events were pooled with random effect, whereas independent predictors are reported as odds ratios (ORs) with 95% confidence intervals (CIs). A total of 25 studies with 8,874 patients were included (median age 82.5 ± 1.5 years, 54.6% women). At 30 days, 7.5% of patients (n = 663) died. At midterm follow-up (median 365 days, interquartile range 267 to 365 days), the cumulative mortality rate was 21.6% (n = 1,917). Acute kidney injury (AKI) stage ≥2 (OR 18.0, 95% CI 6.3 to 52), preprocedural hospitalization for heart failure (OR 9.4, 95% CI 2.6 to 35), periprocedural acute myocardial infarction (OR 8.5, 95% CI 2.6 to 33.5), and increased pro–brain natriuretic peptide (pro-BNP) levels (OR 5.4, 95% CI 1.7 to 16.5) were the most important independent predictors of 30-day mortality. Increased pro-BNP levels (OR 11, 95% CI 1.5 to 81), AKI stage 3 (OR 6.8, 95% CI 2.6 to 15.7), left ventricular ejection fraction <30% (OR 6.7, 95% CI 3.5 to 12.7), and periprocedural acute myocardial infarction (OR 6.5, 95% CI 2.3 to 18.1) represented the predictors of midterm mortality. In conclusion, in this large meta-analysis of patients undergoing TAVI, we found that high pro-BNP levels and postprocedural AKI were the strongest independent predictors of both 30-day and 1-year mortality. These findings may contribute to a better understanding of the risk assessment process of patients undergoing TAVI.
The timing of stimulus-evoked spikes encodes information about sensory stimuli. Here we studied the neural circuits controlling this process in the mouse primary somatosensory cortex. We found that ...brief optogenetic activation of layer V pyramidal cells just after whisker deflection modulated the membrane potential of neurons and interrupted their long-latency whisker responses, increasing their accuracy in encoding whisker deflection time. In contrast, optogenetic inhibition of layer V during either passive whisker deflection or active whisking decreased accuracy in encoding stimulus or touch time, respectively. Suppression of layer V pyramidal cells increased reaction times in a texture discrimination task. Moreover, two-color optogenetic experiments revealed that cortical inhibition was efficiently recruited by layer V stimulation and that it mainly involved activation of parvalbumin-positive rather than somatostatin-positive interneurons. Layer V thus performs behaviorally relevant temporal sharpening of sensory responses through circuit-specific recruitment of cortical inhibition.
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•Layer V pyramidal neurons sharpen the temporal profile of sensory responses in S1•Layer V pyramidal cells control the precision of encoding of whisker stimulus time•Inhibition of layer V increases behavioral reaction time in a discrimination task•The effect of layer V activation is largely mediated by PV-positive interneurons
Using cell-type-specific optogenetic manipulations, Vecchia et al. show that layer V pyramidal cells control the precision of encoding of whisker stimulus time in the primary somatosensory cortex through the activation of a specific inhibitory circuit. Layer V activity impacts behavioral reaction time in a whisker-based texture discrimination task.
Background The effect of gender on patients with aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) remains to be defined. Methods MEDLINE, Cochrane Library, and Scopus ...databases were searched for articles describing sex differences in baseline characteristics, procedures, and outcomes. All-cause death at follow-up of at least 1 year was the primary end point, and the independent effect of female gender was evaluated with pooled analysis using a random-effect model and with meta-regression. Results Six studies with 6,645 patients were included, half of them being women presenting with lower European System for Cardiac Operative Risk Evaluation (EuroSCORE) compared with men. At 30 days, more frequent major vascular complications and major and life-threatening bleeding occurred in women, with lower rates of moderate to severe aortic regurgitation, whereas 30-day mortality was similar. After a median follow-up of 365 days (range, 365 to 730 days) all-cause mortality was 24.0% in women and 34.0% in men. A pooled analysis of the multivariable approach found female gender was significantly related to a lower risk of death (odds ratio, 0.82; 95% CI, confidence interval, 0.73 to 0.93; I2 = 0%). A meta-regression analysis showed age, ejection fraction, previous cardiovascular accident, renal insufficiency, and access site did not influence these data. Conclusions Female patients undergoing TAVI present with a lower burden of comorbidities. The counterbalance between higher rates of vascular complications but lower of valve regurgitation may explain the reduced risk for women after TAVI, independently from baseline features and access site.
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