Using the sectioning capability of third harmonic generation (THG) microscopy, we assessed the morphologic features of human adipocytes directly without fixation and labeling. At the plane of the largest cross-sectional area, both area-equivalent circular diameters (AECD) and perimeters of adipocytes were measured, and their statistical distributions were examined. We found, in patients with no cardiovascular risk factors, the average AECD of epicardial adipocytes were 70–90 μm with 11–17 μm standard deviations. In contrast, for patients with coronary artery disease, amounts of small-sized (AECD <40 µm) epicardial adipocytes were observed and the corresponding standard deviations of AECD were increased to 20–29 μm. Our results indicate that the THG tomography platform can be used to explore the histopathological features of adipocytes in clinical scenarios based on its superior resolution for virtual optical biopsy.
Harmonic generation microscopy (HGM) has become one unique tool of optical virtual biopsy for the diagnosis of cancer and the in vivo cytometry of leukocytes. Without labeling, HGM can reveal the submicron features of tissues and cells in vivo. For deep imaging depth and minimal invasiveness, people commonly adopt 1100- to 1300-nm femtosecond laser sources. However, those lasers are typically based on bulky oscillators whose performances are sensitive to environmental conditions. We demonstrate a fiber-based 1150-nm femtosecond laser source, with 6.5-nJ pulse energy, 86-fs pulse width, and 11.25-MHz pulse repetition rate. It was obtained by a bismuth borate or magnesium-doped periodically poled lithium niobate (MgO:PPLN) mediated frequency doubling of the 2300-nm solitons, generated from an excitation of 1550-nm femtosecond pulses on a large mode area photonic crystal fiber. Combined with a home-built laser scanned microscope and a tailor-made frame grabber, we achieve a pulse-per-pixel HGM imaging in vivo at a 30-Hz frame rate. This integrated solution has the potential to be developed as a stable HGM system for routine clinical use.
Rationale: Prediabetes can be reversed through lifestyle intervention, but its main pathologic hallmark, insulin resistance (IR), cannot be detected as conveniently as blood glucose testing. In consequence, the diagnosis of prediabetes is often delayed until patients have hyperglycemia. Therefore, developing a less invasive diagnostic method for rapid IR evaluation will contribute to the prognosis of prediabetes. Adipose tissue is an endocrine organ that plays a crucial role in the development and progression of prediabetes. Label-free visualizing the prediabetic microenvironment of adipose tissues provides a less invasive alternative for the characterization of IR and inflammatory pathology. Methods: Here, we successfully identified the differentiable features of prediabetic adipose tissues by employing the metabolic imaging of three endogenous fluorophores NAD(P)H, FAD, and lipofuscin-like pigments.Results: We discovered that 1040-nm excited lipofuscin-like autofluorescence could mark the location of macrophages. This unique feature helps separate the metabolic fluorescence signals of macrophages from those of adipocytes. In prediabetes fat tissues with IR, we found only adipocytes exhibited a low redox ratio of metabolic fluorescence and high free NAD(P)H fraction a1. This differential signature disappears for mice who quit the high-fat diet or high-fat-high-sucrose diet and recover from IR. When mice have diabetic hyperglycemia and inflamed fat tissues, both adipocytes and macrophages possess this kind of metabolic change. As confirmed with RNA-seq analysis and histopathology evidence, the change in adipocyte's metabolic fluorescence could be an indicator or risk factor of prediabetic IR. Conclusion:Our study provides an innovative approach to diagnosing prediabetes, which sheds light on the strategy for diabetes prevention.
Emerging advances in iron oxide nanoparticles exploit their high magnetization for various applications, such as bioseparation, hyperthermia, and magnetic resonance imaging. In contrast to their excellent magnetic performance, the harmonic generation and luminescence properties of iron oxide nanoparticles have not been thoroughly explored, thus limiting their development as a tool in photomedicine. In this work, a seed/growth‐inspired synthesis is developed combined with primary mineralization and a ligand‐assisted secondary growth strategy to prepare mesostructured α‐FeOOH nanorods (NRs). The sub‐wavelength heterogeneity of the refractive index leads to enhanced third‐harmonic generation (THG) signals under near‐infrared excited wavelengths at 1230 nm. The as‐prepared NRs exhibit an 11‐fold stronger THG intensity compared to bare α‐FeOOH NRs. Using these unique nonlinear optical properties, it is demonstrated that mesostructured α‐FeOOH NRs can serve as biocompatible and nonbleaching contrast agents in THG microscopy for long‐term labeling of cells as well as in angiography in vivo by modifying lectin to enhance the binding efficiency to the glycocalyx layers on the wall of blood vessels. These results provide a new insight into Fe‐based nanoplatforms capable of emitting coherent light as molecular probes in optical microscopy, thus establishing a complementary microscopic imaging method for macroscopic magnetic imaging systems.
Results There is strong evidence for an association between high exposure to ionising irradiation and stroke, from studies on patients undergoing therapeutic x-tray treatment and atomic bomb survivors. The evidence for an association with occupational exposure to ionising irradiation is limited. There is moderate evidence for an increased risk among smelter workers, and limited evidence for carbon disulfide. The evidence for dynamite, motor exhaust and other combustion products is insufficient. Conclusions This review identified limited evidence for an association between several chemical and physical occupational exposures and stroke. The few available studies on smelter workers all showed indications of an increased risk of stroke, and this association needs further investigation. 0252OCCUPATION AND SURGERY FOR SUBACROMIAL IMPINGEMENT SYNDROME -A NATIONWIDE DANISH COHORT STUDY Objectives Little is known about the time window for accumulation of occupational exposures and shoulder disorders. We aimed to evaluate cumulative occupational shoulder exposures as risk factors for surgery for subacromial impingement syndrome (SIS), and to examine how long the relevant exposure time period is. Method We conducted a nationwide register study of all persons born in Denmark (1933Denmark ( -1977, with at least 5 years of full-time employment (1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007). In the follow-up period (2003)(2004)(2005)(2006)(2007)(2008), first-time events of surgery for SIS were identified. Cumulative exposure estimates for a 10-year period were obtained by linking occupational codes with a job exposure matrix. Exposure estimates were expressed according to the pack-year concept of smoking (e.g. arm-elevation-years). We used logistic regression equivalent to discrete survival analysis with a one year time lag, adjusting for age, sex, region, and calendar year, and compared the ORs for exposure time windows of increasing length. Results The adjusted OR (ORadjusted) for surgery for SIS reached 2.0 for arm-elevation-years, repetitive-movement-years, and force-years, and the ORadjusted for hand-arm-vibrationyears reached 1.5. We found an increase in ORadjusted from 1.0 to 2.1 when expanding the exposure time window from 2 to 10 years back in time. Conclusions Our findings suggested that upper arm-elevation, repetitive movements, forceful exertions, and hand-arm-vibration were risk factors for surgery for SIS, and indicated a cumulative exposure effect within a 10 year time span. Objectives Commuting accidents are accidents occurring while travelling to and from work, and in the course of work. Effort to reducing commuting accidents is important in managing occupational accidents. In Malaysia, the number of claims for commuting accident has showed an increased of 28.3% (17 170 to 22 036) from 2001 to 2010, compared to a decreased in number workplace accident claims by 31.8% (61 163 to 35 603). This increase was despite the total number motor vehicle casualties decreased by...
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