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Monodisperse aqueous upconverting nanoparticles (UCNPs) were covalently immobilized on aldehyde modified cellulose paper via reductive amination to evaluate the multiplexing capacity of luminescence resonance energy transfer (LRET) between UCNPs and quantum dots (QDs). This is the first account of a multiplexed bioassay strategy that demonstrates the principle of use of a single form of UCNP as donor and three different color emitting QDs as acceptors to concurrently determine three analytes. Broad absorbance profiles of green, orange and red QDs that spanned from the first exciton absorption peak to the UV region were in overlap with a blue emission band from UCNPs composed of NaYF 4 that was doped with 30% Yb 3+ , 0.5% Tm 3+ , allowing for LRET that was stimulated using 980 nm near-infrared radiation. The characteristic narrow and well-defined emission peaks of UCNPs and QDs allowed for the collection of luminescence from each nanoparticle using a band-pass optical filter and an epi-fluorescence microscope. The LRET system was used for the concurrent detection of uidA, Stx1A and tetA gene fragments with selectivity even in serum samples, and reached limits of detection of 26 fmol, 56 fmol and 76 fmol, respectively. [ABSTRACT FROM AUTHOR]

Monodisperse aqueous upconverting nanoparticles (UCNPs) were covalently immobilized on aldehyde modified cellulose paper via reduction amination to develop a luminescence resonance energy transfer (LRET)-based nucleic acid hybridization assay. This first account of covalent immobilization of UCNPs on paper for a bioassay reports an optically responsive method that is sensitive, reproducible and robust. The immobilized UCNPs were decorated with oligonucleotide probes to capture HPRT1 housekeeping gene fragments, which in turn brought reporter conjugated quantum dots (QDs) in close proximity to the UCNPs for LRET. This sandwich assay could detect unlabeled oligonucleotide target, and had a limit of detection of 13 fmol and a dynamic range spanning nearly 3 orders of magnitude. The use of QDs, which are excellent LRET acceptors, demonstrated improved sensitivity, limit of detection, dynamic range and selectivity compared to similar assays that have used molecular fluorophores as acceptors. The selectivity of the assay was attributed to the decoration of the QDs with polyethylene glycol to eliminate non-specific adsorption. The kinetics of hybridization were determined to be diffusion limited and full signal development occurred within 3 min. [ABSTRACT FROM AUTHOR]

Organic fluorophores and quantum dots are ubiquitous as contrast agents for bio-imaging and as labels in bioassays to enable the detection of biological targets and processes. Upconversion nanoparticles (UCNPs) offer a different set of opportunities as labels in bioassays and for bioimaging. UCNPs are excited at near-infrared (NIR) wavelengths where biological molecules are optically transparent, and their luminesce in the visible and ultraviolet (UV) wavelength range is suitable for detection using complementary metal-oxide-semiconductor (CMOS) technology. These nanoparticles provide multiple sharp emission bands, long lifetimes, tunable emission, high photostability, and low cytotoxicity, which render them particularly useful for bio-imaging applications and multiplexed bioassays. This paper surveys several key concepts surrounding upconversion nanoparticles and the systems that detect and process the corresponding luminescence signals. The principle of photon upconversion, tuning of emission wavelengths, UCNP bioassays, and UCNP time-resolved techniques are described. Electronic readout systems for signal detection and processing suitable for UCNP luminescence using CMOS technology are discussed. This includes recent progress in miniaturized detectors, integrated spectral sensing, and high-precision time-domain circuits. Emphasis is placed on the physical attributes of UCNPs that map strongly to the technical features that CMOS devices excel in delivering, exploring the interoperability between the two technologies. [ABSTRACT FROM AUTHOR]

Highlights: [•] UCNP synthesis and surface modifications, and UC mechanisms and theory are discussed. [•] Examples of UCNPs as passive labels and as donors in LRET based assays are described. [•] Optical multiplexing capacity of UCNPs for diagnostics and imaging is considered. [•] UCNPs are described for use as in vivo biomarkers for multi-modal imaging and theranostics. [Copyright &y& Elsevier]

Simple Summary: Radiotherapy is a standard of care therapy that kills cancer cells but has limited efficacy in targeting the resistant cancer stem cells (CSCs). The use of radiosensitizers in experimental studies and clinical practice is a successful strategy for eradicating CSCs. Here, we investigated the radiosensitizing potential of thymoquinone (TQ), a natural compound with known anti-cancer activity, in 2D and 3D cultures of colorectal cancer, and in patient-derived organoids. We show that TQ sensitized cancer cells and stem/progenitor cells to radiation mainly through the inhibition of cell survival, DNA repair, and stemness in addition to regulating major pathways implicated in this process. Thus, TQ could be used as a sensitizer to effectively target and kill colorectal cancer cells. Resistance of cancer cells and normal tissue toxicity of ionizing radiation (IR) are known to limit the success of radiotherapy. There is growing interest in using IR with natural compounds to sensitize cancer cells and spare healthy tissues. Thymoquinone (TQ) was shown to radiosensitize several cancers, yet no studies have investigated its radiosensitizing effects on colorectal cancer (CRC). Here, we combined TQ with IR and determined its effects in two-dimensional (2D) and three-dimensional (3D) culture models derived from HCT116 and HT29 CRC cells, and in patient-derived organoids (PDOs). TQ sensitized CRC cells to IR and reduced cell viability and clonogenic survival and was non-toxic to non-tumorigenic intestinal cells. TQ sensitizing effects were associated with G2/M arrest and DNA damage as well as changes in key signaling molecules involved in this process. Combining a low dose of TQ (3 µM) with IR (2 Gy) inhibited sphere formation by 100% at generation 5 and this was associated with inhibition of stemness and DNA repair. These doses also led to ~1.4- to ~3.4-fold decrease in organoid forming ability of PDOs. Our findings show that combining TQ and IR could be a promising therapeutic strategy for eradicating CRC cells. [ABSTRACT FROM AUTHOR]

Introduction. With the increasing prevalence of colorectal cancer (CRC) worldwide, especially in the elderly, and the variability between physiological and chronological age and its impact on functional status, acute symptoms leading to emergent surgery due to colorectal malignancy may lead to increased morbidity and mortality. The aim of this study is to identify the outcome differences of elective vs. emergent open colectomy in patients above 80 years. Methods. The National Surgical Quality Improvement Program (NSQIP) database was reviewed from 2010 to 2014 for open colectomy based on CPT codes. Comparison between groups was done based on the clinical context at presentation as elective or emergent surgery. Data were analyzed using SAS. Results. Elective colectomies were performed in 8289 (70.8%) vs. emergent colectomies in 3409 (29.1%). Emergent colectomy patients had higher American Society of Anesthesiologists (ASA) preoperative classification III-IV, 1429 (42.0%) and 224 (6.6%), vs. 1238 (14.9%) and 21 (0.2%) in elective colectomy patients p < 0.0001 . Emergent colectomy patients had more comorbidities such as chronic obstructive pulmonary disorder (493 (14.5%) vs. 796 (9.6%)), congestive heart failure (206 (6.0%) vs. 310 (3.8%)), dialysis (106 (3.1%) vs. 56 (0.7%)), and acute renal failure (166 (4.9%) vs. 46 (0.6%)) p < 0.0001 , respectively. Postoperative morbidity and mortality were significantly higher in emergent colectomy (1651 (48.4%) and 872 (25.6%)) vs. elective colectomy (1859 (22.4%) and 567 (6.8%)) p < 0.0001 , respectively. Conclusion. Emergent open colectomy in elderly patients carries a higher risk of morbidity and mortality when compared to elective open colectomy with risk factors being higher ASA classification and more comorbidities. [ABSTRACT FROM AUTHOR]

Key Clinical Message This case highlights the possible complications of biliary stents, which may include migration and impaction in the gastrointestinal tract. It also emphasizes the need for a robust follow-up system after stent placement, to minimize the risks and possible sequelae of a forgotten stent. [ABSTRACT FROM AUTHOR]

Bioassays for the rapid detection and quantification of specific nucleic acids, proteins, and peptides are fundamental tools in many clinical settings. Traditional optical emission methods have focused on the use of molecular dyes as labels to track selective binding interactions and as probes that are sensitive to environmental changes. Such dyes can offer good detection limits based on brightness but typically have broad emission bands and suffer from time-dependent photobleaching. Inorganic nanoparticles such as quantum dots and upconversion nanoparticles are photostable over prolonged exposure to excitation radiation and tend to offer narrow emission bands, providing a greater opportunity for multiwavelength multiplexing. Importantly, in contrast to molecular dyes, nanoparticles offer substantial surface area and can serve as platforms to carry a large number of conjugated molecules. The surface chemistry of inorganic nanoparticles offers both challenges and opportunities for the control of solubility and functionality for selective molecular interactions by the assembly of coatings through coordination chemistry. This report reviews advances in the compositional design and methods of conjugation of inorganic quantum dots and upconversion nanoparticles and the assembly of combinations of nanoparticles to achieve energy exchange. Our interest is the exploration of configurations where the modified nanoparticles can be immobilized to solid substrates for the development of bioassays and biosensors that operate by resonance energy transfer (RET). [ABSTRACT FROM AUTHOR]

We present the first documented case of laparoscopically assisted resection of a jejunal diverticulum. A 53 year old gentleman presented with right sided abdominal pain along with raised inflammatory markers. Computed tomography revealed multiple diverticula in the proximal jejunum, one of which was inflamed. The patient was managed conservatively, and subsequently underwent an elective laparoscopically assisted resection of a jejunal diverticulum with no complications. [ABSTRACT FROM AUTHOR]