Focusing and imaging with increased numerical apertures through multimode fibers with micro-fabricated optics

The use of individual multimode optical fibers in endoscopy applications has the potential to provide highly miniaturized and noninvasive probes for microscopy and optical micromanipulation. A few different strategies have been proposed recently, but they all suffer from intrinsically low resolution related to the low numerical aperture of multimode fibers. Here, we show that two-photon polymerization allows for direct fabrication of micro-optics components on the fiber end, resulting in an increase of the numerical aperture to a value that is close to 1. Coupling light into the fiber through a spatial light modulator, we were able to optically scan a submicrometer spot (300 nm FWHM) over an extended region, facing the opposite fiber end. Fluorescence imaging with improved resolution is also demonstrated.Comment: 5 pages, 3 figure

Stacked optical antennas for plasmon propagation in a 5 nm-confined cavity

The sub-wavelength concentration and propagation of electromagnetic energy are two complementary aspects of plasmonics that are not necessarily co-present in a single nanosystem. Here we exploit the strong nanofocusing properties of stacked optical antennas in order to highly concentrate the electromagnetic energy into a 5 nm metal-insulator-metal (MIM) cavity and convert free radiation into guided modes. The proposed nano-architecture combines the concentration properties of optical nanoantennas with the propagation capability of MIM systems, paving the way to highly miniaturized on-chip plasmonic waveguiding

An Overview of Lipid Droplets in Cancer and Cancer Stem Cells

For decades, lipid droplets have been considered as the main cellular organelles involved in the fat storage, because of their lipid composition. However, in recent years, some new and totally unexpected roles have been discovered for them: (i) they are active sites for synthesis and storage of inflammatory mediators, and (ii) they are key players in cancer cells and tissues, especially in cancer stem cells. In this review, we summarize the main concepts related to the lipid droplet structure and function and their involvement in inflammatory and cancer processes

ROS and Lipid Droplet accumulation induced by high glucose exposure in healthy colon and Colorectal Cancer Stem Cells

Lipid Droplets (LDs) are emerging as crucial players in colon cancer development and maintenance. Their expression has been associated with high tumorigenicity in Cancer Stem Cells (CSCs), so that they have been proposed as a new functional marker in Colorectal Cancer Stem Cells (CR-CSCs). They are also indirectly involved in the modulation of the tumor microenvironment through the production of pro-inflammatory molecules. There is growing evidence that a possible connection between metabolic alterations and malignant transformation exists, although the effects of nutrients, primarily glucose, on the CSC behavior are still mostly unexplored. Glucose is an essential fuel for cancer cells, and the connections with LDs in the healthy and CSC populations merit to be more deeply investigated. Here, we showed that a high glucose concentration activated the PI3K/AKT pathway and increased the expression of CD133 and CD44v6 CSC markers. Additionally, glucose was responsible for the increased amount of Reactive Oxygen Species (ROS) and LDs in both healthy and CR-CSC samples. We also investigated the gene modulations following the HG treatment and found out that the healthy cell gene profile was the most affected. Lastly, Atorvastatin, a lipid-lowering drug, induced the highest mortality on CR-CSCs without affecting the healthy counterpart

Investigating the use of a hybrid plasmonic–photonic nanoresonator for optical trapping using finite-difference time-domain method

We investigate the use of a hybrid nanoresonator comprising a photonic crystal (PhC) cavity coupled to a plasmonic bowtie nanoantenna (BNA) for the optical trapping of nanoparticles in water. Using finite difference time-domain simulations, we show that this structure can confine light to an extremely small volume of ~30,000 nm3 (~30 zl) in the BNA gap whilst maintaining a high quality factor (5400–7700). The optical intensity inside the BNA gap is enhanced by a factor larger than 40 compared to when the BNA is not present above the PhC cavity. Such a device has potential applications in optical manipulation, creating high precision optical traps with an intensity gradient over a distance much smaller than the diffraction limit, potentially allowing objects to be confined to much smaller volumes and making it ideal for optical trapping of Rayleigh particles (particles much smaller than the wavelength of light)

A multicentre retrospective cohort study of ovarian germ cell tumours: evidence for chemotherapy de-escalation and alignment of paediatric and adult practice

Background Adult guidelines recommend BEP (bleomycin, etoposide, cisplatin) for all ovarian germ cell tumours, causing debilitating toxicities in young patients who will survive long term. Paediatricians successfully reduce toxicities by using lower bleomycin doses and substituting carboplatin for cisplatin, while testicular and paediatric immature teratomas (ITs) are safely managed with surgery alone. Aim The aim was to determine whether reduced-toxicity treatment could rationally be extended to patients older than 18 years. Methods Multicentre cohort study was carried out in four large UK cancer centres over 12 years. Results One hundred thirty-eight patients were enrolled. Overall survival was 93%, and event-free survival (EFS) was 72%. Neoadjuvant/adjuvant chemotherapy (82% BEP) caused 27 potentially chronic toxicities, and one patient subsequently died from acute lymphoblastic leukaemia. There was no difference in histology, stage or grade in patients ≤/>18 years, and EFS was not different in these age groups (≤18:28% and >18:28%; log-rank P = 0.96). Histological subtype powerfully predicted EFS (log-rank P = 4.9 × 10−7). Neoadjuvant/adjuvant chemotherapy reduced future relapse/progression in dysgerminoma (n = 37, chemo:0% vs. no chemo:20%), yolk sac tumour (n = 23, 26.3% vs.75%) and mixed germ cell tumour (n = 32, 40%vs.70%) but not in IT (n = 42, 33% vs.15%). Additionally, we observed no radiological responses to chemotherapy in ITs, pathological IT grade did not predict EFS (univariate hazard ratio 0.82, 95% confidence interval: 0.57–1.19, P = 0.94) and there were no deaths in this subtype. Conclusion Survival was excellent but chemotherapy toxicities were severe, implying significant overtreatment. Our data support the extension of reduced-toxicity, paediatric regimens to adults. Our practice-changing findings that IT was chemotherapy resistant and pathological grade uninformative strongly endorse exclusive surgical management of ovarian ITs at all ages

Use of fluorescence imaging and indocyanine green during colorectal surgery: Results of an intercontinental Delphi survey

BACKGROUND: Fluorescence imaging with indocyanine green is increasingly being used in colorectal surgery to assess anastomotic perfusion, and to detect sentinel lymph nodes. METHODS: In this 2-round, online, Delphi survey, 35 international experts were asked to vote on 69 statements pertaining to patient preparation and contraindications to fluorescence imaging during colorectal surgery, indications, technical aspects, potential advantages/disadvantages, and effectiveness versus limitations, and training and research. Methodological steps were adopted during survey design to minimize risk of bias. RESULTS: More than 70% consensus was reached on 60 of 69 statements, including moderate-strong consensus regarding fluorescence imaging's value assessing anastomotic perfusion and leak risk, but not on its value mapping sentinel nodes. Similarly, although consensus was reached regarding most technical aspects of its use assessing anastomoses, little consensus was achieved for lymph-node assessments. Evaluating anastomoses, experts agreed that the optimum total indocyanine green dose and timing are 5 to 10 mg and 30 to 60 seconds pre-evaluation, indocyanine green should be dosed milligram/kilogram, lines should be flushed with saline, and indocyanine green can be readministered if bright perfusion is not achieved, although how long surgeons should wait remains unknown. The only consensus achieved for lymph-node assessments was that 2 to 4 injection points are needed. Ninety-six percent and 100% consensus were reached that fluorescence imaging will increase in practice and research over the next decade, respectively. CONCLUSION: Although further research remains necessary, fluorescence imaging appears to have value assessing anastomotic perfusion, but its value for lymph-node mapping remains questionable

Three-dimensional holographic optical manipulation through a high-numerical-aperture soft-glass multimode fibre

Holographic optical tweezers (HOT) hold great promise for many applications in biophotonics, allowing the creation and measurement of minuscule forces on biomolecules, molecular motors and cells. Geometries used in HOT currently rely on bulk optics, and their exploitation in vivo is compromised by the optically turbid nature of tissues. We present an alternative HOT approach in which multiple three-dimensional (3D) traps are introduced through a high-numerical-aperture multimode optical fibre, thus enabling an equally versatile means of manipulation through channels having cross-section comparable to the size of a single cell. Our work demonstrates real-time manipulation of 3D arrangements of micro-objects, as well as manipulation inside otherwise inaccessible cavities. We show that the traps can be formed over fibre lengths exceeding 100 mm and positioned with nanometric resolution. The results provide the basis for holographic manipulation and other high-numerical-aperture techniques, including advanced microscopy, through single-core-fibre endoscopes deep inside living tissues and other complex environments

Breaking the diffusion limit with super-hydrophobic delivery of molecules to plasmonic nanofocusing SERS structures

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Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care