We present cleared tissue Axially Swept Light-Sheet Microscopy (ctASLM), which enables isotropic, subcellular resolution, high optical sectioning capability, and large field of view imaging over a broad range of immersion media. ctASLM can image live, expanded, and both aqueous and organic chemically cleared tissue preparations. Depending on the optical configuration, ctASLM provides up to 260 nm axial resolution, an improvement over confocal and other reported cleared tissue light-sheet microscopes by a factor 3-10. We image millimeter-scale tissues with subcellular 3D resolution, which enabled us to automatically detect with computer vision multicellular tissue architectures, individual cells, synaptic spines, and rare cell-cell interactions.Human tissues are composed of multiple polarized cell types organized in well-defined three-dimensional architectures. Interestingly, it has been shown that rare subsets of cells play a crucial role in disease progression, 1 and interdisciplinary efforts now aim to generate comprehensive atlases of human cells in diverse tissue types. To date, this has largely relied on massively parallel sequencing and machine learning-based analyses to identify unique sub-populations of cells. Combined with advanced imaging, such efforts could not only shed light on the diversity of cell types, but the biological context in which each population operates. However, imaging large tissues with subcellular resolution remains challenging due to the heterogeneous refractive index and composition of tissues, which results in complex aberrations and an increased scattering coefficient, both of which decrease spatial resolution and limit imaging depth. 2

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We present an oblique plane microscope (OPM) that uses a bespoke glass-tipped tertiary objective to improve the resolution, field of view, and usability over previous variants. Owing to its high numerical aperture optics, this microscope achieves lateral and axial resolutions that are comparable to the square illumination mode of lattice light-sheet microscopy, but in a user friendly and versatile format. Given this performance, we demonstrate high-resolution imaging of clathrin-mediated endocytosis, vimentin, the endoplasmic reticulum, membrane dynamics, and Natural Killer-mediated cytotoxicity. Furthermore, we image biological phenomena that would be otherwise challenging or impossible to perform in a traditional light-sheet microscope geometry, including cell migration through confined spaces within a microfluidic device, subcellular photoactivation of Rac1, diffusion of cytoplasmic rheological tracers at a volumetric rate of 14 Hz, and large field of view imaging of neurons, developing embryos, and centimeter-scale tissue sections.

Objective: To qualitatively and quantitatively assess the association of prehypertension with incident stroke through a meta-analysis of prospective cohort studies. Methods:We searched Medline, Embase, the Cochrane Library, and bibliographies of retrieved articles. Prospective cohort studies were included if they reported multivariate-adjusted relative risks (RRs) and corresponding 95% confidence intervals (CI) of stroke with respect to baseline prehypertension. Results Conclusions:Prehypertension is associated with a higher risk of incident stroke. This risk is largely driven by higher values within the prehypertensive range and is especially relevant in nonelderly persons. Randomized trials to evaluate the efficacy of blood pressure reduction in persons with this designation are warranted. In recognition of the profound impact of elevated blood pressure on cardiovascular risk, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) proposed a new category of individuals within the range of normal blood pressure at risk for developing hypertension and its untoward sequela. 1This new designation, called prehypertension, comprises persons with systolic blood pressure between 120 and 139 mm Hg or diastolic blood pressure between 80 and 89 mm Hg.1 Since the JNC 7 proposal, epidemiologic studies have shown that the prevalence of prehypertension among adults in the general population is roughly 31% in the United States.2 However, the rationale and relevance of diagnosing prehypertension in otherwise healthy patients have recently been called into question.3 Indeed, even though stroke is the condition most highly correlated with blood pressure among various vascular disease entities, 4 the association of prehypertension with stroke risk in published studies has been inconsistent.Given its high prevalence and potential to identify persons at great stroke risk who may benefit from risk reduction strategies, we undertook a meta-analysis of prospective cohort studies to qualitatively and quantitatively assess the association of baseline prehypertension and risk of incident stroke.

The axial resolving power of a light-sheet microscope is determined by the thickness of the illumination beam and the numerical aperture of its detection optics. Bessel-beam based optical lattices have generated significant interest owing to their reportedly narrow beam waist and propagation-invariant characteristics. Yet, despite their significant use in lattice light-sheet microscopy and recent incorporation into commercialized systems, there are very few quantitative reports on their physical properties and how they compare to standard Gaussian illumination beams. Here, we measure the beam properties in the transmission of dithered square lattices, which is the most commonly used variant of lattice light-sheet microscopy, and Gaussian-based light-sheets. After a systematic analysis, we find that square lattices are very similar to Gaussian-based light-sheets in terms of thickness, confocal parameter, propagation length and overall imaging performance.