Phase-locked µPIV analysis of flow dynamics in a simulated root canal with different laser-activated irrigations.

PURPOSE: To measure the dynamic characteristics of the flow field in a complex root canal model activated by two laser-activated irrigation (LAI) modalities at different activation energy outputs: photon-induced photoacoustic streaming (PIPS) and microshort pulse (MSP). METHODS: A phase-locked micro-scale Particle Image Velocimetry (µPIV) system was employed to characterise the temporal variations of LAI-induced velocity fields in the root canal following a single laser pulse. The wall shear stress (WSS) in the lateral root canal was subsequently estimated from the phase-averaged velocity fields. RESULTS: Both PIPS and MSP were able to generate the 'breath mode' of the irrigant current under all tested conditions. The transient irrigation flush in the root canal peaked at speeds close to 6 m/s. However, this intense flushing effect persisted for only about 2000 µs (or 3% of a single laser-pulse activation cycle). For MSP, the maximum WSS magnitude was approximately 3.08 Pa at an activation energy of E = 20 mJ/pulse, rising to 9.01 Pa at E = 50 mJ/pulse. In comparison, PIPS elevated the WSS to 10.63 Pa at E = 20 mJ/pulse. CONCLUSION: Elevating the activation energy can boost the peak flushing velocity and the maximum WSS, thereby enhancing irrigation efficiency. Given the same activation energy, PIPS outperforms MSP. Additionally, increasing the activation frequency may be an effective strategy to improve irrigation performance further.

Transient apical peak pressure measurement of Er:YAG laser-activated irrigation in different in vitro tooth models using a high-frequency sensor system.

The transient apical pressure side effect is an important safety consideration for Er:YAG laser-activated irrigation (LAI). Therefore, this study aimed to measure the transient apical peak pressure (TAPP) of LAI under different laser settings in various tooth models using a high-frequency sensor system. Tooth models with different pulp chamber structures, apical diameters, and curvatures were prepared using transparent resin and filled with deionised water. The Er:YAG laser fibre was placed 3 mm from the root canal orifice. Irrigation was performed at 10-40 mJ and 20-50 Hz using the super short pulse mode. The TAPP was measured using a 50,000-sample/second pressure sensor connected to the models' apices. The TAPP of LAI was significantly higher than that of other chemical preparation methods. Among all investigated factors, pulp chamber anatomy and apical diameters had the greatest effects and were highly related to the apical peak pressure. Root canal curvature showed no direct correlation with TAPP. The larger the final prepared working width, the greater the TAPP. Furthermore, both pulse energy and frequency had positive correlations with TAPP. In conclusion, tooth anatomy factors and laser parameter settings influenced TAPP during Er:YAG LAI. Therefore, proper settings of laser parameters are important to improve the safety of Er:YAG LAI.

Acute 1,2-Dichloropropane Poisoning due to Ingestion of Rubber Cement: An Autopsy Case Report and Review.

ABSTRACT: 1,2-Dichloropropane (1,2-DCP) is a common industrial solvent and chemical intermediate that can cause acute poisoning to humans through exposure during its production and industrial use. The target organs of 1,2-DCP include the eyes, respiratory system, liver, kidney, central nervous system, and skin. Forensic identification of 1,2-DCP poisoning is difficult because of the lack of characteristic pathological changes. This article reports an autopsy case of acute 1,2-DCP poisoning caused by self-ingestion of rubber cement. A woman developed seizures and coagulation dysfunction after ingesting approximately 10 mL of rubber cement and died 43 hours later. Autopsy revealed generalized subcutaneous hemorrhage, cardiopulmonary multifocal hemorrhage, bronchopneumonia, severe cerebral edema, focal hepatic necrosis, granular deposition in the glomerular capsule and renal tubules, and delipidation of the adrenal cortex. These findings indicate that 1,2-DCP poisoning can induce central nervous system dysfunction, respiratory system damage, liver and kidney function damage, hemolytic anemia, disseminated intravascular coagulation, and adrenal damage. This case may provide useful perspectives for forensic identification of 1,2-DCP poisoning in the future.

Characteristics of the Irrigant Flow in a Simulated Lateral Canal Under Two Typical Laser-Activated Irrigation Regimens.

BACKGROUND AND OBJECTIVES: Photon-induced photoacoustic streaming (PIPS) and shockwave-enhanced emission photoacoustic streaming (SWEEPS) are two promising laser-activated irrigation (LAI) methods for root canal irrigation. Their performance in driving irrigant flush in a complex root canal system will be evaluated by microscale particle image velocimetry (µPIV) measurement and will be compared with that of ultrasonic-activated irrigation (UAI). STUDY DESIGN/MATERIALS AND METHODS: A µPIV system with 7 µm fluorescent tracer particles was adopted to measure two-dimensional (2D) velocity fields around the junction region, with a size of 1.8 mm × 1.5 mm, between one main canal and one lateral canal in an endodontic training block, which was driven by SWEEPS (Er:YAG laser) operating at 15 Hz and 20 mJ. The flow field driven by PIPS (Er:YAG laser) at the same frequency and energy, as well as by UAI (with non-cutting insert) operating at 40% unit power, was also measured for a direct comparison. RESULTS: It was found that both SWEEPS and PIPS can activate a so-called "breath mode" during the irrigation. Namely, the induced irrigant flush presented a back-and-forth oscillation along both the main canal and the lateral one. The maximum flow speed in the lateral canal was observed to be up to 10 m/s in the SWEEPS modality, while reduced to around 7 m/s in the PIPS modality. The penetration length in the lateral canal in both modalities was estimated to be larger than 1 mm. In comparison, the flow field induced by UAI was characterized as irregular vortical structures, the maximum flow speed in the lateral canal was 0.15 m/s and significantly lower than LAI (P < 0.01), and the penetration length was less than 300 µm and lower than LAI (P < 0.05). CONCLUSION: Compared to UAI, PIPS, and SWEEPS are more capable of delivering the irrigant deeper into the lateral canal. Furthermore, the back-and-forth flush in the breath mode is ideal for removing debris during irrigation. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Disulfide-crosslinked nanomicelles confer cancer-specific drug delivery and improve efficacy of paclitaxel in bladder cancer.

Chemotherapy commonly used in the treatment of advanced bladder cancer is only moderately effective and associated with significant toxicity. There has been no appreciable improvement in overall survival over the last three decades. The goal of this project is to develop and characterize bladder cancer-specific nanometer-scale micelles loaded with the chemotherapeutic drug paclitaxel (PTX) and determine the anti-tumor activity and toxicity. Micelle-building-material telodendrimers were synthesized through the stepwise conjugation of eight cholic acid units at one terminus of polyethylene glycol (PEG) and a bladder cancer-specific targeting peptide named PLZ4 at the other terminus. To synthesize disulfide-crosslinked PLZ4 nanomicelles (DC-PNM), cysteine was introduced between the cholic acid and PEG. DC-PNM-PTX was synthesized through the evaporation method by loading PTX in the core. The loading capacity of PTX in DC-PNM was 25% (W/W). The loading efficiency was over 99%. DC-PNM-PTX was spherical with the median size of 25 nm. The stability of DC-PNM-PTX was determined in a solution containing sodium docecyl sulfate (SDS). It was stable in a SDS solution, but dissolved within 5 min after the addition of glutathione at the physiological intracellular concentration of 10 mM. In vivo targeting and anti-tumor activity were determined in immunodeficient mice carrying patient-derived bladder cancer xenografts (PDXs). After intravenous administration, DC-PNM specifically targeted the bladder cancer PDXs, but very little to the lung cancer xenografts in the same mice (p < 0.001). DC-PNM loaded with PTX overcame cisplatin resistance, and improved the median survival from 55 d with free PTX to 69.5 d (p = 0.03) of mice carrying PDXs. In conclusion, DC-PNM remained stable in the SDS solution, specifically targeted the bladder cancer xenografts in vivo, and improved the anti-cancer efficacy of PTX.

Miniature optoelectronic compound eye camera.

Inspired by insect compound eyes (CEs) that feature unique optical schemes for imaging, there has recently been growing interest in developing optoelectronic CE cameras with comparable size and functions. However, considering the mismatch between the complex 3D configuration of CEs and the planar nature of available imaging sensors, it is currently challenging to reach this end. Here, we report a paradigm in miniature optoelectronic integrated CE camera by manufacturing polymer CEs with 19~160 logarithmic profile ommatidia via femtosecond laser two-photon polymerization. In contrast to µ-CEs with spherical ommatidia that suffer from defocusing problems, the as-obtained µ-CEs with logarithmic ommatidia permit direct integration with a commercial CMOS detector, because the depth-of-field and focus range of all the logarithmic ommatidia are significantly increased. The optoelectronic integrated µ-CE camera enables large field-of-view imaging (90°), spatial position identification and sensitive trajectory monitoring of moving targets. Moreover, the miniature µ-CE camera can be integrated with a microfluidic chip and serves as an on-chip camera for real-time microorganisms monitoring. The insect-scale optoelectronic µ-CE camera provides a practical route for integrating well-developed planar imaging sensors with complex micro-optics elements, holding great promise for cutting-edge applications in endoscopy and robot vision.

A phase II trial of gefitinib and pegylated IFNα in previously treated renal cell carcinoma.

BACKGROUND: This study was conducted to evaluate the efficacy of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib with pegylated-IFNα (PEG-IFNα) in patients with advanced renal cell carcinoma. METHODS: Progression-free survival (PFS) rate at 6 months >50% was considered promising for further evaluation. Patients with unresectable or metastatic disease, unlimited prior therapies, and adequate performance status and end-organ function were eligible. PEG-IFNα was dosed subcutaneously once weekly (initially 6 µg/kg/week, later reduced to 4 µg/kg/week) for 12 weeks. Gefitinib was given 250 mg orally once daily until progression or intolerance. RESULTS: Twenty-one patients were accrued. Fourteen patients had a prior nephrectomy, and twelve had prior systemic therapy. The 6-month PFS was 29% (95%CI 15-56%). Best responses by RECIST criteria: complete, partial (1, plus 3 unconfirmed) stable (Uhlman et al. Clin Cancer Res 1:913-920, 1995), and progression (Sirotnak et al. Clin Cancer Res 6:4885-4892, 2000). Response duration: complete response (35+ months) and partial response (2, 3, 3, 37 months). Median PFS and overall survival were 5.3 (95%CI 3-10.1) and 13.6 (95%CI 10.3-NA) months, respectively. Most common toxicities included myelosuppression, rash, and nausea. CONCLUSIONS: Although generally well tolerated, gefitinib plus PEG-IFNα did not meet the pre-specified 6-month PFS rate >50%. Further evaluation of similar regimens would require appropriate molecular selection of subjects most likely to benefit. Thus, preclinical studies to determine candidate predictive markers for this combination are warranted.

Phase I Trial of Arginine Deprivation Therapy with ADI-PEG 20 Plus Docetaxel in Patients with Advanced Malignant Solid Tumors.

PURPOSE: This phase I study examined the toxicity and tolerability of pegylated arginine deiminase (ADI-PEG 20) in combination with docetaxel in patients with advanced solid malignancies. EXPERIMENTAL DESIGN: Eligible patients had histologically proven advanced solid malignancies, with any number of prior therapies, Zubrod performance status 0-2, and adequate organ function. Patients received ADI-PEG 20 weekly intramuscular injection ranging from 4.5 to 36 mg/m(2) and up to 10 doses of docetaxel (75 mg/m(2)) every 3 weeks. Primary endpoints were safety, toxicity, and a recommended phase II dose. Circulating arginine levels were measured before each cycle. Tumor response was measured as a secondary endpoint every 6 weeks on study. RESULTS: Eighteen patients received a total of 116 cycles of therapy through four dose levels of ADI-PEG 20. A single dose-limiting toxicity (grade 3 urticarial rash) was observed at the 1st dose level, with no additional dose-limiting toxicities observed. Hematologic toxicities were common with 14 patients experiencing at least one grade 3 to 4 leukopenia. Fatigue was the most prevalent toxicity reported by 16 patients. Arginine was variably suppressed with 10 patients achieving at least a 50% reduction in baseline values. In 14 patients with evaluable disease, four partial responses (including 2 patients with PSA response) were documented, and 7 patients had stable disease. CONCLUSIONS: ADI-PEG 20 demonstrated reasonable toxicity in combination with docetaxel. Promising clinical activity was noted, and expansion cohorts are now accruing for both castrate-resistant prostate cancer and non-small cell lung cancer at a recommended phase II dose of 36 mg/m(2).