Genome-wide CRISPR screening identifies a role for ARRDC3 in TRP53-mediated responses.

Whole-genome screens using CRISPR technologies are powerful tools to identify novel tumour suppressors as well as factors that impact responses of malignant cells to anti-cancer agents. Applying this methodology to lymphoma cells, we conducted a genome-wide screen to identify novel inhibitors of tumour expansion that are induced by the tumour suppressor TRP53. We discovered that the absence of Arrestin domain containing 3 (ARRDC3) increases the survival and long-term competitiveness of MYC-driven lymphoma cells when treated with anti-cancer agents that activate TRP53. Deleting Arrdc3 in mice caused perinatal lethality due to various developmental abnormalities, including cardiac defects. Notably, the absence of ARRDC3 markedly accelerated MYC-driven lymphoma development. Thus, ARRDC3 is a new mediator of TRP53-mediated suppression of tumour expansion, and this discovery may open new avenues to harness this process for cancer therapy.

NCCN Guidelines® Insights: Head and Neck Cancers, Version 1.2022.

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses. Occult primary cancer, salivary gland cancer, and mucosal melanoma (MM) are also addressed. The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding management of HPV-positive oropharynx cancer and ongoing research in this area.

The Role of Laser Speckle Imaging in Port-Wine Stain Research: Recent Advances and Opportunities.

Here, we review our current knowledge on the etiology and treatment of port-wine stain (PWS) birthmarks. Current treatment options have significant limitations in terms of efficacy. With the combination of 1) a suitable preclinical microvascular model, 2) laser speckle imaging (LSI) to evaluate blood-flow dynamics, and 3) a longitudinal experimental design, rapid preclinical assessment of new phototherapies can be translated from the lab to the clinic. The combination of photodynamic therapy (PDT) and pulsed-dye laser (PDL) irradiation achieves a synergistic effect that reduces the required radiant exposures of the individual phototherapies to achieve persistent vascular shutdown. PDL combined with anti-angiogenic agents is a promising strategy to achieve persistent vascular shutdown by preventing reformation and reperfusion of photocoagulated blood vessels. Integration of LSI into the clinical workflow may lead to surgical image guidance that maximizes acute photocoagulation, is expected to improve PWS therapeutic outcome. Continued integration of noninvasive optical imaging technologies and biochemical analysis collectively are expected to lead to more robust treatment strategies.

Fiber-based laser speckle imaging for the detection of pulsatile flow.

BACKGROUND AND OBJECTIVE: In endodontics, a major diagnostic challenge is the accurate assessment of pulp status. In this study, we designed and characterized a fiber-based laser speckle imaging system to study pulsatile blood flow in the tooth. STUDY DESIGN/MATERIALS AND METHODS: To take transilluminated laser speckle images of the teeth, we built a custom fiber-based probe. To assess our ability to detect changes in pulsatile flow, we performed in vitro and preliminary in vivo tests on tissue-simulating phantoms and human teeth. We imaged flow of intralipid in a glass microchannel at simulated heart rates ranging from 40 beats/minute (bpm) to 120 bpm (0.67-2.00 Hz). We also collected in vivo data from the upper front incisors of healthy subjects. From the measured raw speckle data, we calculated temporal speckle contrast versus time. With frequency-domain analysis, we identified the frequency components of the contrast waveforms. RESULTS: With our approach, we observed in vitro the presence of pulsatile flow at different simulated heart rates. We characterized simulated heart rate with an accuracy of and >98%. In the in vivo proof-of-principle experiment, we measured heart rates of 69, 90, and 57 bpm, which agreed with measurements of subject heart rate taken with a wearable, commercial pulse oximeter. CONCLUSIONS: We designed, built, and tested the performance of a dental imaging probe. Data from in vitro and in -vivo tests strongly suggest that this probe can detect the presence of pulsatile flow. LSI may enable endodontists to noninvasively assess pulpal vitality via direct measurement of blood flow.

Intraoperative, real-time monitoring of blood flow dynamics associated with laser surgery of port wine stain birthmarks.

BACKGROUND AND OBJECTIVE: Port-wine stain (PWS) birthmarks affect ∼22 million people worldwide. After several treatment sessions, complete disappearance of the PWS occurs in only ∼10% of treated patients. There is a need to develop a new strategy to improve the efficacy of each treatment session and the overall treatment outcome. The study objective was to determine how intraoperative measurements of blood flow correlate with treatment response assessed several weeks post treatment. STUDY DESIGN/MATERIALS AND METHODS: We employed Laser Speckle Imaging (LSI) to measure intraoperative blood-flow dynamics. We collected data from 24 subjects undergoing laser therapy for facial PWS birthmarks. Photographs were taken before treatment and at a follow-up visit, and analyzed by two expert observers. RESULTS: Intraoperative LSI enables real-time monitoring of blood-flow dynamics in response to laser treatment and can inform clinicians on the need for focused re-treatment. The degree of PWS blanching achieved is positively correlated with the log-transformed acute blood-flow reduction (P = 0.022). CONCLUSION: LSI is a simple, intraoperative monitoring tool during laser therapy of PWS birthmarks. LSI provides a single value for blood flow that correlates well with the degree of blanching achieved with laser therapy.

Anterior shoulder dislocation increases the propensity for recurrence: a cadaveric study of the number of dislocations and type of capsulolabral lesion.

BACKGROUND: The number of anterior shoulder dislocations that predispose to recurrence is unknown; some clinicians recommend surgical repair after the initial episode and others after multiple recurrences. The purpose of this study was to quantify the forces during successive anterior dislocations of cadaveric shoulders and to inspect the capsule and labrum afterwards, in order to assess the propensity for recurrence. MATERIALS AND METHODS: Twenty-two human cadaveric shoulders were tested using a custom cadaveric shoulder dislocation device with simulated muscle loading. Each was positioned in the apprehension position and the humerus was moved in horizontal abduction until the shoulder dislocated. The joint reaction force was measured, as was the force that developed passively in the pectoralis major muscle. Following 3 successive dislocations, each was inspected for anterior capsulolabral lesions. RESULTS: There was a significant decrease in force after the second dislocation. In 11, there was no labral avulsion and a significant decrease in force after the first dislocation. In the other 11, there was a labral avulsion and a significant decrease in force after the second dislocation. CONCLUSION: Two successive anterior shoulder dislocations may increase propensity for recurrence; but this is influenced by the type of capsulolabral lesion that occurs. No labral avulsion, likely a result of capsular stretching, may be a worse prognostic finding than labral avulsion after the initial episode.

An overview of three promising mechanical, optical, and biochemical engineering approaches to improve selective photothermolysis of refractory port wine stains.

During the last three decades, several laser systems, ancillary technologies, and treatment modalities have been developed for the treatment of port wine stains (PWSs). However, approximately half of the PWS patient population responds suboptimally to laser treatment. Consequently, novel treatment modalities and therapeutic techniques/strategies are required to improve PWS treatment efficacy. This overview therefore focuses on three distinct experimental approaches for the optimization of PWS laser treatment. The approaches are addressed from the perspective of mechanical engineering (the use of local hypobaric pressure to induce vasodilation in the laser-irradiated dermal microcirculation), optical engineering (laser-speckle imaging of post-treatment flow in laser-treated PWS skin), and biochemical engineering (light- and heat-activatable liposomal drug delivery systems to enhance the extent of post-irradiation vascular occlusion).

Glenohumeral joint translation after arthroscopic thermal capsuloplasty of the posterior capsule.

Treatment of recurrent posterior or multidirectional glenohumeral instability in athletes with traditional operative management has produced variable results at long-term follow-up. The purpose of this study was to determine whether an arthroscopic thermal capsuloplasty of the posterior capsule with a radiofrequency probe significantly decreases anterior-posterior glenohumeral translation. Successive posterior and anterior loads of 10, 15, and 20 N were applied sequentially to 7 cadaveric shoulder joints that were mounted in a translation testing apparatus with an electromagnetic tracking device measuring posterior and anterior glenohumeral translation. Arthroscopic thermal capsuloplasty was then performed on the posterior capsular tissue with a radiofrequency probe. The identical posterior-anterior loading protocol was then repeated, and translations were recorded. The results demonstrated no statistically significant differences in the mean posterior translation measurements before and after arthroscopic thermal capsuloplasty of the posterior capsule for the 10-N (+8.9%), 15-N (-3.1%), or 20-N (-1.8%) load (P >.50 to.62). Slightly greater changes occurred in anterior translation after posterior capsuloplasty at 10 N (-1.0%), 15 N (-6.0%), and 20 N (-10.3%). However, these changes were not found to be significant either (P =.06 to.62). The results of this study demonstrated that neither posterior nor anterior glenohumeral translation was significantly decreased by thermal capsuloplasty of the posterior capsule. Perhaps the lack of substantial collagenous material in the thin posterior capsule accounts for the inability of thermal capsuloplasty to be effective in this region.

Glenohumeral joint translation after arthroscopic thermal capsuloplasty of the rotator interval.

The treatment of recurrent anterior, posterior, or multidirectional glenohumeral instability by operative closure of the rotator interval has been proposed. The purpose of this study was to determine whether arthroscopic thermal capsuloplasty of the rotator interval with the radiofrequency probe significantly decreases anterior-posterior glenohumeral translation. Anterior and posterior loads of 10, 15, and 20 N were sequentially applied to 8 cadaveric shoulder joints while mounted in a translation testing apparatus with an electromagnetic tracking device measuring anterior and posterior glenohumeral translation. Arthroscopic thermal capsuloplasty was then performed on the rotator interval with a radiofrequency probe. The identical anterior-posterior loading protocol was then repeated, and translations were recorded. The results showed a significant reduction in anterior and posterior translation after thermal capsuloplasty. After rotator interval thermal capsuloplasty, anterior translation decreased by 31.5%, 28.8%, and 27.2% for the 10-, 15-, and 20-N loads, respectively. Posterior translation decreased by 43.1%, 43.8%, and 40.7%, respectively. The results of this study indicate that arthroscopic thermal capsuloplasty of the rotator interval is an effective way by which to decrease both anterior and posterior glenohumeral translation in vitro. To date, no in vivo studies that sufficiently document long-term clinically successful outcomes of such a procedure exist. Future studies are warranted to evaluate the effects of the biologic response to thermal shrinkage and whether these reduced glenohumeral translations will be maintained.