Orofacial Pain and Snoring/Obstructive Sleep Apnea in Individuals with Head and Neck Cancer: A Critical Review.

AIMS: (1) To summarize current knowledge on the prevalence, intensity, and descriptors of orofacial pain and snoring/obstructive sleep apnea (OSA) before and after head and neck cancer (HNC) treatment; and (2) to propose future directions for research. METHODS: The median prevalence for each condition was estimated from the most recent systematic reviews (SRs) and updated with new findings retrieved from the PubMed, Web of Science, Embase, and Cochrane databases up to December 2021. RESULTS: The prevalence of HNC pain seems relatively stable over time, with a median of 31% before treatment in three studies to a median of 39% at 1 month to 16 years after treatment in six studies. HNC pain intensity remains mild to moderate. There was a threefold increase in temporomandibular pain prevalence after surgery (median 7.25% before to 21.3% after). The data for snoring prevalence are unreliable. The OSA/HNC prevalence seems relatively stable over time, with a median of 72% before treatment in three studies to 77% after treatment in 14 studies. CONCLUSION: With the exception of temporomandibular pain, the prevalence of HNC pain and OSA seems to be stable over time. Future studies should: (1) compare the trajectory of change over time according to each treatment; (2) compare individuals with HNC to healthy subjects; (3) use a standardized and comparable method of data collection; and (4) assess tolerance to oral or breathing devices, since HNC individuals may have mucosal sensitivity or pain.

Relaxation and Aging of Nanosphere Assemblies at a Water-Oil Interface.

The relaxation and aging of an assembly of spherical nanoparticles (NPs) at a water-oil interface are characterized in situ by grazing incidence X-ray photon correlation spectroscopy. The dynamics of the interfacial assembly is measured while the interface saturates with NPs. Weak attractions between NPs lead to gel-like structures in the assembly, where the in-plane ordering is inhibited by the broad size distribution of the NPs. Structural rearrangements on the length scale of the NP-NP center-to-center distances proceed by intermittent fluctuations instead of continuous cooperative motions. The coexistence of rapid and slow NP populations is confirmed, as commonly observed in soft glass-forming materials. Dynamics are increasingly slowed as the NPs initially segregate to the locally clustered interface. The structural relaxation of the NPs in these localized clusters is 5 orders of magnitude slower than that of free particles in the bulk. When the interface is nearly saturated, the time for relaxation increases suddenly due to the onset of local jamming, and the dynamics slow exponentially afterward until the system reaches collective jamming by cooperative rearrangements. This investigation provides insights into structural relaxations near the glass transition and the evolution of the structure and dynamics of the assemblies as they transition from an isotropic liquid to a dense disordered film.

Incidence of osteoradionecrosis of the jaws: a retrospective study of 620 patients with head and neck cancer.

This study aimed to assess systemic and local risk factors for the development of osteoradionecrosis (ORN) of the jaws and its incidence in patients with head and neck cancer undergoing radiotherapy (RT). This was a retrospective cohort study of 620 adults following irradiation for head and neck cancer in 2011 or 2012. Among 181 patients who did not require any tooth extractions, the incidence of ORN was 0.5%. Among 266 patients with a total of 1491 tooth extractions (mean, 5.5 teeth per patient) performed before RT, the incidence of ORN was 3.7%. In all cases, ORN was observed in extraction sites located in the field of radiation. No extractions were performed during RT. Fifteen patients underwent extractions both before and after RT. Of the 53 tooth extractions performed after RT (20 patients; mean, 2.7 teeth per patient), 15 were in the field of radiation. No case of ORN was reported in that group. Among 168 edentulous patients, the incidence of ORN was 1.8%. Within the limitations of this study, the results suggest that the incidence of ORN can be minimized with a meticulous pre-RT dental examination, a comprehensive treatment plan, and diligent post-RT follow-up examinations conducted by an experienced multidisciplinary team.

Use of continuous sample translation to reduce radiation damage for XPCS studies of protein diffusion.

An experimental setup to measure X-ray photon correlation spectroscopy during continuous sample translation is presented and its effectiveness as a means to avoid sample damage in dynamics studies of protein diffusion is evaluated. X-ray damage from focused coherent synchrotron radiation remains below tolerable levels as long as the sample is translated through the beam sufficiently quickly. Here it is shown that it is possible to separate sample dynamics from the effects associated with the transit of the sample through the beam. By varying the sample translation rate, the damage threshold level, Dthresh = 1.8 kGy, for when beam damage begins to modify the dynamics under the conditions used, is also determined. Signal-to-noise ratios, Rsn ≥ 20, are obtained down to the shortest delay times of 20 µs. The applicability of this method of data collection to the next generation of multi-bend achromat synchrotron sources is discussed and it is shown that sub-microsecond dynamics should be obtainable on protein samples.

E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning.

Generation of a barrier in multi-layered epithelia like the epidermis requires restricted positioning of functional tight junctions (TJ) to the most suprabasal viable layer. This positioning necessitates tissue-level polarization of junctions and the cytoskeleton through unknown mechanisms. Using quantitative whole-mount imaging, genetic ablation, and traction force microscopy and atomic force microscopy, we find that ubiquitously localized E-cadherin coordinates tissue polarization of tension-bearing adherens junction (AJ) and F-actin organization to allow formation of an apical TJ network only in the uppermost viable layer. Molecularly, E-cadherin localizes and tunes EGFR activity and junctional tension to inhibit premature TJ complex formation in lower layers while promoting increased tension and TJ stability in the granular layer 2. In conclusion, our data identify an E-cadherin-dependent mechanical circuit that integrates adhesion, contractile forces and biochemical signaling to drive the polarized organization of junctional tension necessary to build an in vivo epithelial barrier.

A modular approach to the design of protein-based smart gels.

The modular nature of repeat proteins makes them a versatile platform for the design of smart materials with predetermined properties. Here, we present a general strategy for combining protein modules with specified stability and function into arrays for the assembly of stimuli-responsive gels. We have designed tetratricopeptide repeat (TPR) arrays which contain peptide-binding modules that specify the strength and reversibility of network crosslinking in combination with spacer modules that specify crosslinking geometry and overall stability of the array. By combining such arrays with multivalent peptide ligands, self-supporting stimuli-responsive gels are formed. Using microrheology, we characterized the kinetics of gelation as a function of concentration and stoichiometry of the components. We also show that such gels are effective in encapsulating and releasing small molecules. Moreover, TPR gels alone are fully compatible with cell growth, whereas gels loaded with an anticancer compound release the compound, resulting in cell death. Thus, we have demonstrated that this new class of tunable biomaterials is ripe for further development as tissue engineering and drug delivery platform.

Membrane tension maintains cell polarity by confining signals to the leading edge during neutrophil migration.

Little is known about how neutrophils and other cells establish a single zone of actin assembly during migration. A widespread assumption is that the leading edge prevents formation of additional fronts by generating long-range diffusible inhibitors or by sequestering essential polarity components. We use morphological perturbations, cell-severing experiments, and computational simulations to show that diffusion-based mechanisms are not sufficient for long-range inhibition by the pseudopod. Instead, plasma membrane tension could serve as a long-range inhibitor in neutrophils. We find that membrane tension doubles during leading-edge protrusion, and increasing tension is sufficient for long-range inhibition of actin assembly and Rac activation. Furthermore, reducing membrane tension causes uniform actin assembly. We suggest that tension, rather than diffusible molecules generated or sequestered at the leading edge, is the dominant source of long-range inhibition that constrains the spread of the existing front and prevents the formation of secondary fronts.