Flexible solid immersion meniscus lens (SIMlens) approach for enhancing biological imaging of cleared samples.

Tissue-clearing techniques have revolutionized the field of biological imaging by rendering biological specimens transparent and enabling inside optical detection. Light-sheet fluorescence microscopy (LSFM) is a powerful tool for three-dimensional imaging of large biological samples. Combining tissue-clearing techniques with LSFM has advanced the efficient 3D visualization of these samples. A crucial challenge with LSFM is the requirement for the objective to operate within the clearing reagent, which can cause aberrations. To address this issue, we introduce a novel, to our knowledge, approach for the flexible design of the solid immersion refractive meniscus lens (SIMlens), facilitating the use of air objectives with cleared samples. Compared to the previous SIMlens, this method not only eliminates aberrations but also offers customized options for enhancing the numerical aperture and working distance of the objective lens, achieving at least a 10% improvement. We have demonstrated the feasibility of this new method using mouse brain samples.

Remote refocusing for multi-scale imaging.

Significance: The technique of remote focusing (RF) has attracted considerable attention among microscopists due to its ability to quickly adjust focus across different planes, thus facilitating quicker volumetric imaging. However, the difficulty in changing objectives to align with a matching objective in a remote setting while upholding key requirements remains a challenge. Aim: We aim to propose a customized yet straightforward technique to align multiple objectives with a remote objective, employing an identical set of optical elements to ensure meeting the criteria of remote focusing. Approach: We propose a simple optical approach for aligning multiple objectives with a singular remote objective to achieve a perfect imaging system. This method utilizes readily accessible, commercial optical components to meet the fundamental requirements of remote focusing. Results: Our experimental observations indicate that the proposed RF technique offers at least comparable, if not superior, performance over a significant axial depth compared with the conventional RF technique based on commercial lenses while offering the flexibility to switch the objective for multi-scale imaging. Conclusions: The proposed technique addresses various microscopy challenges, particularly in the realm of multi-resolution imaging. We have experimentally demonstrated the efficacy of this technique by capturing images of focal volumes generated by two distinct objectives in a water medium.

Effects of magnification on restorative dental preparation performance: a scoping review and level of evidence mapping.

OBJECTIVE: This scoping review aimed to identify and describe the available evidence on the effect of magnifying devices (loupe or microscope) on the performance of restorative dental preparations. MATERIALS AND METHODS: This study was conducted according to the PRISMA-ScR guidelines for scoping reviews and registered on the INPLASY database. An electronic search was performed in four databases and Grey literature for articles published until November 2023. Eligibility criteria were determined using the PICOS strategy and comprised studies that evaluated the performance of magnification devices for restorative dental preparations. A bibliographic mapping of the evidence was conducted. RESULTS: Sixteen studies met the inclusion criteria. Most of the studies (n = 12) compared the performance of dental preparations using magnification loupes vs. no magnification. The magnification for loupes and microscopes ranged from 2.5x to 4.0x and 6.4x to 10x, respectively. The use of magnifying loupes improved the performance of restorative preparations in 66.6% of the evaluated studies. However, when the magnifications were compared, the greater magnification provided by microscopes did not improve preparation performance compared to magnification loupes. Regarding the place of publication, the American continent concentrates the most significant number of evidence. CONCLUSIONS: Although evidence for magnification improving the performance of dental preparations has increased over the last decade, basically only in vitro studies (most of which have taken place in the Americas) have been reported in the literature. The evidence suggests that magnification significantly improves restorative preparation performance when compared to non-magnification. However, higher magnifications (e.g., microscopes) do not appear to improve tooth preparation performance compared with lower magnification devices (e.g., magnification loupes). CLINICAL RELEVANCE: Available evidence supports that using magnification can improve the performance of restored tooth preparations. However, high magnifications have no advantages over lower magnifications.

Extended depth-of-field wide-field fluorescence microscopy with a micro-mirror array lens system for versatile cellular examination.

We present a versatile extended depth-of-field (EDOF) wide-field fluorescence microscopy using a new, to the best of our knowledge, active device, micro-mirror array lens system (MALS) for calibration-free and orientation-insensitive EDOF imaging. The MALS changed the focal plane during image acquisition, and the system could be operated in any orientation. Two EDOF imaging modes of high-speed accumulation and low-speed surface sectioning were implemented. The performance was demonstrated in non-contact imaging of conjunctival goblet cells in live mice and depth-resolved cellular examination of ex-vivo human cancer specimens. MALS-based EDOF microscopy has potential for versatile cellular examination.

Upconversion nanoparticles doped optical lens: let's see the near-infrared light.

The human cannot detect light with a wavelength exceeding 700 nm, primarily due to limitations in the physiological structure of the human eye. However, in certain specific scenarios, the ability to detect near-infrared (NIR) light proves to be extremely valuable. To attain this desired capability, NIR up conversion nanoparticles (UCNPs) were prepared and doped in the optical lens materials, aiming to obtain a NIR light "visible" optical lens. It is demonstrated that the doping of UCNPs in the optical lens materials does not significantly impact on their mechanical properties, optical properties, surface properties and it exhibits excellent biocompatibility in cell and animal experiments. More importantly, the UCNPs doping can convert NIR light into visible light within the material effectively and stably. The eyes can "see" the NIR light after wearing such UCNPs doped optical lens. Such NIR light visible optical lens could have great potential in actual applications.

Microsphere lens array embedded microfluidic chip for SERS detection with simultaneous enhancement of sensitivity and stability.

Surface enhanced Raman spectroscopy (SERS) utilizes the fingerprint features of molecular vibrations to identify and detect substances. However, in traditional single focus excitation scenarios, its signal collection efficiency of the objective is restricted. Furthermore, the uneven distribution of samples on the SERS substrate would result in poor signal stability, while the excitation power is limited to avoid sample damage. SERS detection system always requires precise adjustment of focal length and spot size, making it difficult for point-of-care testing applications. Here, we proposed a SERS microfluidic chip with barium titanate microspheres array (BTMA) embedded using vacuum self-assembled hot-pressing method for SERS detection with simultaneous enhancement of sensitivity and stability. Due to photonic nano-jets and directional antenna effects, high index microspheres are perfect micro-lens for effective light focusing and signal collecting. The BTMA can not only disperse excitation beam into an array of focal points covering the target uniformly with very low signal fluctuation, but enlarge the power threshold for higher signal intensity. We conducted a proof-of-principle experiment on chip for the detection of bacteria with immuno-magnetic tags and immuno-SERS tags. Together with magnetic and ultrasonic operations, the target bacteria in the flow were evenly congregated on the focal plane of BTMA. It demonstrated a limit of detection of 5 cells/mL, excellent signal reproducibility (error∼4.84%), and excellent position tolerance of 500 µm in X-Y plane (error∼5.375%). It can be seen that BTMA-SERS microfluidic chip can effectively solve the contradiction between sensitivity and stability in SERS detection.

Acoustic Assembly and Scanning of Superlens Arrays for High-Resolution and Large Field-of-View Bioimaging.

High-resolution and dynamic bioimaging is essential in life sciences and biomedical applications. In recent years, microspheres combined with optical microscopes have offered a low cost but promising solution for super-resolution imaging, by breaking the diffraction barrier. However, challenges still exist in precisely and parallelly superlens controlling using a noncontact manner, to meet the demands of large-area scanning imaging for desired targets. This study proposes an acoustic wavefield-based strategy for assembling and manipulating micrometer-scale superlens arrays, in addition to achieving on-demand scanning imaging through phase modulation. In experiments, acoustic pressure nodes are designed to be comparable in size to microspheres, allowing spatially dispersed microspheres to be arranged into arrays with one unit per node. Droplet microlenses with various diameters can be adapted in the array, allowing for a wide range of spacing periods by applying different frequencies. In addition, through the continuous phase shifting in the x and y directions, this acoustic superlens array achieves on-demand moving for the parallel high-resolution virtual image capturing and scanning of nanostructures and biological cell samples. As a comparison, this noncontact and cost-effective acoustic manner can obtain more than ∼100 times the acquisition efficiency of a single lens, holding promise in advancing super-resolution microscopy and subcellular-level bioimaging.

Late Middle Ages-Europe.

At the end of the late Middle Ages, there had been changes in indications for surgery, with prophylactic trepanation falling out of favor. The management of wounds and the methods for opening the cranium had become fairly standardized. Narrow non-plunging trepans were the preferred drills, and cranial openings were widened by the use of multiple drill holes connected with chisels of which the lenticular was preferred. Concerns about damaging the dura led Theodoric to delay trepanation until the clinical changes reflected separation of the dura from the cranium, at least in his view. Draining pus remained the main indication for trepanation. In no case was the level of consciousness considered in determining the need to open the cranium.

High-Density Polyethylene Custom Focusing Lenses for High-Resolution Transient Terahertz Biomedical Imaging Sensors.

Transient terahertz time-domain spectroscopy (THz-TDS) imaging has emerged as a novel non-ionizing and noninvasive biomedical imaging modality, designed for the detection and characterization of a variety of tissue malignancies due to their high signal-to-noise ratio and submillimeter resolution. We report our design of a pair of aspheric focusing lenses using a commercially available lens-design software that resulted in about 200 × 200-µm2 focal spot size corresponding to the 1-THz frequency. The lenses are made of high-density polyethylene (HDPE) obtained using a lathe fabrication and are integrated into a THz-TDS system that includes low-temperature GaAs photoconductive antennae as both a THz emitter and detector. The system is used to generate high-resolution, two-dimensional (2D) images of formalin-fixed, paraffin-embedded murine pancreas tissue blocks. The performance of these focusing lenses is compared to the older system based on a pair of short-focal-length, hemispherical polytetrafluoroethylene (TeflonTM) lenses and is characterized using THz-domain measurements, resulting in 2D maps of the tissue refractive index and absorption coefficient as imaging markers. For a quantitative evaluation of the lens effect on the image resolution, we formulated a lateral resolution parameter, R2080, defined as the distance required for a 20-80% transition of the imaging marker from the bare paraffin region to the tissue region in the same image frame. The R2080 parameter clearly demonstrates the advantage of the HDPE lenses over TeflonTM lenses. The lens-design approach presented here can be successfully implemented in other THz-TDS setups with known THz emitter and detector specifications.

Storylines of family medicine IV: perspectives on practice-lenses of appreciation.

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine, as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'IV: perspectives on practice-lenses of appreciation', authors address the following themes: 'Relational connections in the doctor-patient partnership', 'Feminism and family medicine', 'Positive family medicine', 'Mindful practice', 'The new, old ethics of family medicine', 'Public health, prevention and populations', 'Information mastery in family medicine' and 'Clinical courage.' May readers nurture their curiosity through these essays.

[Structural and functional features of the eye in Marfan syndrome. Report 2. Changes in the anatomical complex of the lens]. / Strukturno-funktsional'nye osobennosti glaza pri sindrome Marfana. Soobshchenie 2. Izmeneniya anatomicheskogo kompleksa khrustalika.

Analysis of lens changes in Marfan syndrome (MS), in addition to assessing the position of the lens itself, should include the possibility of examining its supporting and accommodative components (ciliary zonule and ciliary body), or what can be called the entire anatomical complex of the lens. Optical methods of studying the structures of the anterior segment of the eye, due to iris opacity, allow only to analyze the state of the lens within the natural or medically enlarged pupil width. Visualization of the structures located behind the iris is possible with the use of radiation diagnostic methods, in particular ultrasound biomicroscopy (UBM). PURPOSE: This study assesses the state of the anatomical complex of the lens in MS using UBM. MATERIAL AND METHODS: The study was carried out on clinical material previously used by us to analyze changes in the fibrous membrane of the eye in MS. At the first stage, the main (19 patients with MS, 38 eyes) and the control (24 patients with myopia, 48 eyes) groups were formed for comparative evaluation. The formed groups were standardized according to the age of the patients and the axial length of the eye. At the second stage, patients with MS were divided into subgroups depending on the absence or presence of biomicroscopic signs of ectopia lentis (22 and 16 eyes, respectively). For UBM, an ultrasound linear sensor with a scanning frequency of 50 MHz was used (Aviso device, Quantel Medical, France). Various biometric UBM indicators were determined: lens thickness, diameter of the lens, lens-axial length factor, iris-lens angle, iris-lens contact distance, posterior chamber depth, length of the fibers of ciliary zonule, thickness of the ciliary body, sclera-ciliary process angle. RESULTS: There are changes in the anatomical complex of the lens as a whole in MS (in the lens itself, the ciliary zonule, and the ciliary body), which are characterized by an increase in lens thickness and a decrease in the diameter of the lens, an increase in the length of the fibers of the ciliary zonule and a decrease in the thickness of the ciliary body. At the same time, the displacement of the lens detected by optical biomicroscopy (ectopia lentis) can be considered as an advanced stage of changes in the anatomical complex of the lens. CONCLUSION: UBM provides the possibility of full-fledged visualization of all components of the anatomical complex of the lens in terms of both diagnostics, and monitoring of changes in MS. The question of the advisability of including this method in the algorithm for diagnosing ocular manifestations in order to verify the MS remains open. Possible obstacles may be, on the one hand, related to the need for special and expensive equipment, and on the other hand, the absence of a generally accepted «normal¼ values of UBM indicators of the anatomical complex of the lens.

Comparison of visual performance between diffractive bifocal and diffractive trifocal intraocular lenses.

To evaluate the visual performance of a diffractive bifocal intraocular lens (IOL) with + 4.0 D near addition (ZMB00) and a diffractive trifocal IOL with + 2.17 D and + 3.25 D near addition (AcrySof IQ PanOptix TFNT00), we investigated the 10-week postoperative parameters after cataract surgery in which ZMB00 or TFNT00 lenses were implanted bilaterally from 2011 to 2020 (with a 3-month interval between implantation of the right and left lenses). The study included 1448 eyes of 724 patients. The diffractive bifocal group comprised 1326 eyes of 663 patients (aged 67.0 ± 7.8 years; females/males, 518/145), and the diffractive trifocal group comprised 122 eyes of 61 patients (aged 66.6 ± 7.3 years; females/males, 35/26). A linear mixed-effects model using data for both eyes, with strict adjustments for sex, age, subjective refraction spherical equivalent, subjective refraction cylinder, corneal astigmatism, axial length, corneal higher-order aberrations, and pupil diameter, ensured statistical validity. Uncorrected near visual acuity and higher-order aberrations (ocular/internal, scaled to a pupil size of 4 mm) (Wavefront_4mm_postoperative_Ocular/Internal_Spherical) were significantly better in the bifocal group (p < 0.00068, Wald test). Uncorrected intermediate visual acuity, contrast sensitivity (6.3/4.0/2.5/1.6/1.0/0.7 degrees), and contrast sensitivity with glare (4.0/1.6/1.0/0.7 degrees) were significantly better in the trifocal group (p < 0.00068, Wald test).

Full-aperture extended-depth oblique plane microscopy through dynamic remote focusing.

Significance: The reprojection setup typical of oblique plane microscopy (OPM) limits the effective aperture of the imaging system, and therefore its efficiency and resolution. Large aperture system is only possible through the use of custom specialized optics. A full-aperture OPM made with off the shelf components would both improve the performance of the method and encourage its widespread adoption. Aim: To prove the feasibility of an OPM without a conventional reprojection setup, retaining the full aperture of the primary objective employed. Approach: A deformable lens based remote focusing setup synchronized with the rolling shutter of a complementary metal-oxide semiconductor detector is used instead of a traditional reprojection system. Results: The system was tested on microbeads, prepared slides, and zebrafish embryos. Resolution and pixel throughput were superior to conventional OPM with cropped apertures, and comparable with OPM implementations with custom made optical components. Conclusions: An easily reproducible approach to OPM imaging is presented, eliminating the conventional reprojection setup and exploiting the full aperture of the employed objective.

Comparison of proximal and minus lens autorefraction techniques to measure monocular accommodative amplitude.

SIGNIFICANCE: This study provides a faster method for objectively measuring accommodative amplitude with an open-field autorefractor in a research setting. PURPOSE: Objective measures of accommodative amplitude with an autorefractor take time because of the numerous stimulus demands tested. This study compares protocols using different amounts and types of demands to shorten the process. METHODS: One hundred participants were recruited for four age bins (5 to 9, 10 to 14, 15 to 19, and 20 to 24 years) and monocular amplitude measured with an autorefractor using three protocols: proximal, proximal-lens (letter), and proximal-lens (picture). For proximal, measurements were taken as participants viewed a 0.9 mm "E" placed at 13 demands (40 to 3.3 cm = 2.5 to 30 D). The other protocols used a target (either the "E" or a detailed picture) placed at 33 and 12.5 cm followed by 12.5 cm with a series of lenses (-2, -4, and -5.5 D). Adjustments were made for lens effectivity for the three lens conditions, which were thus 9.6, 11.1, and 12.0 D for individuals without additional spectacle lenses. Accommodative amplitude was defined as the greatest response measured with each technique. One-way analysis of variance was used to compare group mean amplitudes across protocols and differences between letter protocols by age bin. RESULTS: Amplitudes were significantly different between protocols (p < 0.001), with proximal having higher amplitudes (mean ± standard deviation, 8.04 ± 1.70 D) compared with both proximal-lens protocols (letter, 7.48 ± 1.42 D; picture, 7.43 ± 1.42 D) by post hoc Tukey analysis. Differences in amplitude between the proximal and proximal-lens (letter) protocol were different by age group (p = 0 .003), with the youngest group having larger differences (1.14 ± 1.58 D) than the oldest groups (0.17 ± 0.58 and 0.29 ± 0.48 D, respectively) by post hoc Tukey analysis. CONCLUSIONS: The proximal-lens protocols took less time and identified the maximum accommodative amplitude in participants aged 15 to 24 years; however, they may underestimate true amplitude in younger children.

Functional subtypes of synaptic dynamics in mouse and human.

Synapses preferentially respond to particular temporal patterns of activity with a large degree of heterogeneity that is informally or tacitly separated into classes. Yet, the precise number and properties of such classes are unclear. Do they exist on a continuum and, if so, when is it appropriate to divide that continuum into functional regions? In a large dataset of glutamatergic cortical connections, we perform model-based characterization to infer the number and characteristics of functionally distinct subtypes of synaptic dynamics. In rodent data, we find five clusters that partially converge with transgenic-associated subtypes. Strikingly, the application of the same clustering method in human data infers a highly similar number of clusters, supportive of stable clustering. This nuanced dictionary of functional subtypes shapes the heterogeneity of cortical synaptic dynamics and provides a lens into the basic motifs of information transmission in the brain.

Intracapsular accommodation mechanism in terms of lens curvature gradient.

The intracapsular accommodation mechanism (IAM) may be understood as an increase in the lens equivalent refractive index as the eye accommodates. Our goal was to evaluate the existence of an IAM by analysing observed changes in the inner curvature gradient of the lens. To this end, we fitted a gradient index and curvature lens model to published experimental data on external and nucleus geometry changes during accommodation. For each case analysed, we computed the refractive power and equivalent index for each accommodative state using a ray transfer matrix. All data sets showed an increase in the effective refractive index, indicating a positive IAM, which was stronger for older lenses. These results suggest a strong dependence of the lens equivalent refractive index on the inner curvature gradient.

Geometric transformation adaptive optics (GTAO) for volumetric deep brain imaging through gradient-index lenses.

The advance of genetic function indicators has enabled the observation of neuronal activities at single-cell resolutions. A major challenge for the applications on mammalian brains is the limited optical access depth. Currently, the method of choice to access deep brain structures is to insert miniature optical components. Among these validated miniature optics, the gradient-index (GRIN) lens has been widely employed for its compactness and simplicity. However, due to strong fourth-order astigmatism, GRIN lenses suffer from a small imaging field of view, which severely limits the measurement throughput and success rate. To overcome these challenges, we developed geometric transformation adaptive optics (GTAO), which enables adaptable achromatic large-volume correction through GRIN lenses. We demonstrate its major advances through in vivo structural and functional imaging of mouse brains. The results suggest that GTAO can serve as a versatile solution to enable large-volume recording of deep brain structures and activities through GRIN lenses.

The effect of Galilean magnification loupes on the visual acuity and working distance of dental students.

OBJECTIVE: This study aimed to evaluate the visual acuity and working distance of dental students using Galilean loupes at different magnification levels. METHODS: The participants included 50 undergraduate dentistry students selected from each class in the second to fifth years (N = 200) of São Paulo State University, School of Dentistry, Araraquara. The response variables were (i) the working distance between the operator's eyes and the mouth of the dental phantom head, and (ii) visual acuity. The independent variables were the five levels of the Galilean magnification system (naked eye, Galilean loupe simulator without magnification, and Galilean loupes with 2.5×, 3.0×, or 3.5× magnification) and academic year. Visual acuity was measured using a miniature Snellen eye chart inserted into the Class I cavities of the maxillary molars. After verifying the assumptions of normality and sphericity, a mixed repeated measures analysis was performed (α = 0.05). RESULTS: Statistical significance was found between the "magnification system" and "academic year" for visual acuity (p < 0.001). For the second-, fourth-, and fifth-year participants, there were no significant differences in visual acuity between the naked eye and different magnifications of the Galilean loupes, which were superior to and significantly different from that of the loupe simulator. For the working distance, statistical significance was observed in the interaction between "magnification system" and "academic year" (p = 0.008). For the third-, fourth-, and fifth-year participants, there was no significant difference in the working distance between the naked eye and different magnifications of the Galilean loupes, which were superior to and significantly different from that of the simulator. CONCLUSION: It was concluded that the different magnification levels of the Galilean loupes did not influence the visual acuity or distance between the eyes of the operator and the mouth of the dental phantom head in the evaluated students.

Development and Usability Evaluation of an Opioid Management App.

We describe the development and usability evaluation of a novel patient engagement tool (OPY) in its early stage from perspectives of both experts and end-users. The tool is aimed at engaging patients in positive behaviors surrounding the use, weaning, and disposal of opioid medications in the post-surgical setting. The messaging and design of the application were created through a behavioral economics lens. Expert-based heuristic analysis and user testing were conducted and demonstrated that while patients found the tool to be easy to use and subjectively somewhat useful, additional work to enhance the user interface and features is needed in close partnership with developers and stakeholders.