MASCC/ISOO Clinical Practice Statement: The risk of secondary oral cancer following hematopoietic cell transplantation.

PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the risk of secondary oral cancer following hematopoietic cell transplantation (HCT). METHODS: This CPS was developed based on critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets to generate a short manual about the best standard of care. RESULTS: Studies described a 7-16-fold higher risk of secondary oral cancer (mainly squamous cell carcinoma) in allogeneic HCT (alloHCT) recipients, particularly in those who developed chronic graft versus host disease (cGVHD). Risk increases over time and is influenced by several risk factors. In autologous HCT, oral cancer risk seemed only slightly elevated. CONCLUSION: Clinicians should be aware of the higher oral cancer risk in alloHCT survivors, and emphasize the importance of lifelong oral cancer surveillance (at least every 6-12 months) and avoiding cancer promoting lifestyle factors in an empathic way, particularly of those with (a history of) cGVHD. Post-HCT for Fanconi anemia or dyskeratosis congenita, education and rigorous follow-up is even more crucial. In case of suspected oral lesions in the presence of oral mucosal cGVHD, a GVHD intervention may facilitate diagnosis. Suspected lesions should be biopsied. More research is needed on the role of HPV in oral cancer post-HCT.

Perceptions of HPV-Linked Oropharyngeal Cancer Risk Messages Among a Sample of Young Adult Men in the US: A Pilot Study.

Awareness of risk for oropharyngeal cancer from oral human papillomavirus (HPV) infection is low among men in the United States. This pilot study tested messages communicating oral HPV and oropharyngeal cancer risk among a sample of U.S. young adult men (aged 18-26). Six oral HPV and cancer risk messages were tested in an online survey. Participants (N = 68) were randomly assigned to one of two message sets, each containing three unique text-based messages. Participants evaluated messages separately based on various measures (e.g., perceived message effectiveness [PME], novelty). One-way repeated measures ANOVAs were used to assess evaluation differences within message sets. Participants provided open-ended feedback about each message, which were synthesized into overarching themes. Participants were receptive to the risk messages, rating them high on PME (mean range = 3.72-4.25 out of 5) and other measures. Analyses identified three high-performing messages. For example, participants rated a message about HPV-linked oropharyngeal cancer risk rates in men versus women higher on attention and novelty than two other messages in the same set (both ps < .05). Participants were shown three messages (instead of all six) in each message set to minimize survey fatigue. Common themes from open-ended feedback were that participants liked the short-form structure of the messages and that the messages used gender-tailored language. In conclusion, oral HPV and oropharyngeal cancer risk messages may be useful for increasing risk awareness among men in the U.S. Further work should test such messages in rigorous experimental contexts to assess their efficacy in modifying other health outcomes, such as HPV vaccination behaviors.

Cytophagic histiocytic panniculitis leading to a diagnosis of acute myeloid leukemia with monocytic differentiation: A case report and literature review.

Cytophagic histiocytic panniculitis (CHP) is associated with a number of systemic conditions and is characterized by the presence of benign phagocytic histiocytes ("bean bag cells"), including phagocytosed erythrocytes, leukocytes, and platelets. We describe a case of a 72-year-old female who presented with a papular eruption that clinically mimicked pityriasis lichenoides et varioliformis acuta (PLEVA). Given that her skin biopsy had multiple features concerning PLEVA, this diagnosis was classified as a superficial pityriasis lichenoides-like variant of CHP. The histopathologic presence of cytophagic histiocytosis prompted workup for a systemic malignancy, leading to a diagnosis of underlying acute monocytic leukemia of myeloid lineage.

Patient-Provider Discussions About Alcohol Use by Cancer History.

INTRODUCTION: The U.S. Preventive Services Task Force recommends that all adults be screened for alcohol use and those with hazardous use be provided a brief discussion. However, it is unclear to what extent healthcare providers screen for and discuss alcohol use with cancer survivors. METHODS: Frequency and content of alcohol prescreening and provider discussion about alcohol use was examined comparing cancer survivors and non-cancer controls in the 2015-2019 National Survey on Drug Use and Health. Multivariable Poisson regression with robust variance and complex survey procedures were used to estimate prevalence ratios (PR) adjusted for demographic characteristics. Data were analyzed in 2022. RESULTS: The prevalence of alcohol prescreening in a healthcare setting (78.4% vs 74.3%; PR: 1.05 [95% CI: 1.03-1.08]) and self-report of an in-person discussion about alcohol use with a healthcare provider (58.7% vs 55.0%; PR: 1.07 [95% CI: 1.03-1.10]) was higher among cancer survivors compared with non-cancer controls. Among those who had a discussion, the prevalence of being asked about drinking quantity was higher among cancer survivors compared with non-cancer controls (PR: 1.05 [95% CI: 1.02-1.08]). Among cancer survivors who reported usually consuming 3+ drinks per day in the past 30 days, only 15% (95% CI: 10.8-20.5) reported that a healthcare provider advised them to cut down on their drinking. CONCLUSIONS: Cancer survivors are being screened for alcohol use, but heavier users are infrequently advised by healthcare providers to reduce their consumption.

Diagnostic Complexities of Oral Squamous Cell Carcinoma.

Prompt diagnosis of oral cancers is critical to increase survival rates. Treatment for oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) is mainly driven by cancer stage and may include surgery alone or surgery with adjuvant or neoadjuvant radiation, chemotherapy, and/or targeted therapy. This article describes a case of a patient who was referred by his general dentist to an oral medicine clinic for assessment of an exophytic lesion on the left lateral tongue. The case report discusses the differential diagnosis and treatment, examining critical elements in lesion assessment in the patient, who had a significant oral lesion history and who was ultimately diagnosed with OSCC. Highlighting various complexities that may arise in the diagnosis of OSCC, the article underscores the importance of surveillance, informed biopsy technique, and accurate interpretation of pathology reports to appropriately manage patients with potential oral malignancy.

The role of stiffness-matching in avoiding stress shielding-induced bone loss and stress concentration-induced skeletal reconstruction device failure.

It is well documented that overly stiff skeletal replacement and fixation devices may fail and require revision surgery. Recent attempts to better support healing and sustain healed bone have looked at stiffness-matching of these devices to the desired role of limiting the stress on fractured or engrafted bone to compressive loads and, after the reconstructed bone has healed, to ensure that reconstructive medical devices (implants) interrupt the normal loading pattern as little as possible. The mechanical performance of these devices can be optimized by adjusting their location, integration/fastening, material(s), geometry (external and internal), and surface properties. This review highlights recent research that focuses on the optimal design of skeletal reconstruction devices to perform during and after healing as the mechanical regime changes. Previous studies have considered auxetic materials, homogeneous or gradient (i.e., adaptive) porosity, surface modification to enhance device/bone integration, and choosing the device's attachment location to ensure good osseointegration and resilient load transduction. By combining some or all of these factors, device designers work hard to avoid problems brought about by unsustainable stress shielding or stress concentrations as a means of creating sustainable stress-strain relationships that best repair and sustain a surgically reconstructed skeletal site. STATEMENT OF SIGNIFICANCE: Although standard-of-care skeletal reconstruction devices will usually allow normal healing and improved comfort for the patient during normal activities, there may be significant disadvantages during long-term use. Stress shielding and stress concentration are amongst the most common causes of failure of a metallic device. This review highlights recent developments in devices for skeletal reconstruction that match the stiffness, while not interrupting the normal loading pattern of a healthy bone, and help to combat stress shielding and stress concentration. This review summarises various approaches to achieve stiffness-matching: application of materials with modulus close to that of the bone; adaptation of geometry with pre-defined mechanical properties; and/or surface modification that ensures good integration and proper load transfer to the bone.

Understanding Cannabis-Related Information Needs: An Analysis of Inquiries to the National Cancer Institute's Cancer Information Service.

Purpose: Given increased cannabis use for medical and nonmedical purposes alike, there is growing public interest related to the potential risks and benefits of cannabis use, particularly related to cancer. The purpose of this descriptive study was to analyze cannabis inquiries to the National Cancer Institute's Cancer Information Service (CIS). Materials and Methods: From September 2018 to June 2023, 190,070 noncannabis and 425 cannabis inquiries were documented by the CIS. Cannabis inquiries were delineated into two categories: nonmedical cannabis (NMC, n=240) or medical cannabis (MC, n=185). Chi-square tests were performed to determine differences between noncannabis and cannabis inquiries and descriptive analyses were used to identify patterns within cannabis-specific inquiries. Results: Statistically significant differences between noncannabis and cannabis inquiries were observed. In addition, there were variations in MC and NMC inquiries. For example, 73% of MC inquiries originated from cancer survivors and caregivers, whereas almost half of NMC inquiries (48%) were from individuals identifying as tobacco users. MC and NMC inquiries also differed by CIS access channel (e.g., instant chat, telephone), language used (English vs. Spanish), discussions of cancer continuum phases and cancer sites, and referrals provided to individuals for additional information and resources. Conclusion: Cannabis-related information needs of the public-as documented by the CIS-varied by several factors. Health information sources such as the CIS can help address cannabis-related questions and concerns, while noting differences in who is inquiring, how, and why.

Dental evaluation and clearance prior to allogeneic hematopoietic cell transplantation.

INTRODUCTION: Dental examination and stabilization are performed prior to allogeneic hematopoietic cell transplantation to decrease infection risk during neutropenia. Burden of dental disease and treatment need is not well characterized in this population. OBJECTIVES: This report describes the dental status of a cohort of patients within the Chronic Graft-versus-Host Disease Consortium and treatment rendered prior to transplant. METHODS: The cohort included 486 subjects (Fred Hutchinson: n = 245; Dana-Farber: n = 241). Both centers have institutional-based dental clearance programs. Data were retrospectively abstracted from medical records by calibrated oral health specialists. RESULTS: The median age at transplant was 55.9 years, 62.1% were male, and 88% were white. Thirteen patients were edentulous (2.7%). The mean teeth among dentate patients before clearance was 26.0 (SD, 4.6). Dental findings included untreated caries (31.2%), restorations (91.6%), endodontically treated teeth (48.1%), and dental implants (5.7%). Pretransplant procedures during clearance included endodontic therapy (3.6%; mean = 0.1 teeth), restorations (25.1%; mean = 0.7), dental prophylaxis (59.2%), scaling/root planing (5.1%), and extraction (13.2%; mean = 0.3). The mean teeth after clearance was 25.6 (SD, 5.0). CONCLUSIONS: Retrospective analysis of pre-AlloHCT dental data in subjects at two large transplant centers identified low levels of dental need. Findings suggest high access to care.

Autologous mesenchymal stem cells offer a new paradigm for salivary gland regeneration.

Salivary gland (SG) dysfunction, due to radiotherapy, disease, or aging, is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life. Currently, the standard-of-care for this condition remains palliative. A variety of approaches have been employed to restore saliva production, but they have largely failed due to damage to both secretory cells and the extracellular matrix (niche). Transplantation of allogeneic cells from healthy donors has been suggested as a potential solution, but no definitive population of SG stem cells, capable of regenerating the gland, has been identified. Alternatively, mesenchymal stem cells (MSCs) are abundant, well characterized, and during SG development/homeostasis engage in signaling crosstalk with the SG epithelium. Further, the trans-differentiation potential of these cells and their ability to regenerate SG tissues have been demonstrated. However, recent findings suggest that the "immuno-privileged" status of allogeneic adult MSCs may not reflect their status post-transplantation. In contrast, autologous MSCs can be recovered from healthy tissues and do not present a challenge to the recipient's immune system. With recent advances in our ability to expand MSCs in vitro on tissue-specific matrices, autologous MSCs may offer a new therapeutic paradigm for restoration of SG function.

Upregulation of alveolar fluid clearance is not sufficient for Na+,K+-ATPase ß subunit-mediated gene therapy of LPS-induced acute lung injury in mice.

Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) is characterized by diffuse alveolar damage and significant edema accumulation, which is associated with impaired alveolar fluid clearance (AFC) and alveolar-capillary barrier disruption, leading to acute respiratory failure. Our previous data showed that electroporation-mediated gene delivery of the Na+, K+-ATPase ß1 subunit not only increased AFC, but also restored alveolar barrier function through upregulation of tight junction proteins, leading to treatment of LPS-induced ALI in mice. More importantly, our recent publication showed that gene delivery of MRCKα, the downstream effector of ß1 subunit-mediated signaling towards upregulation of adhesive junctions and epithelial and endothelial barrier integrity, also provided therapeutic potential for ARDS treatment in vivo but without necessarily accelerating AFC, indicating that for ARDS treatment, improving alveolar capillary barrier function may be of more benefit than improving fluid clearance. In the present study, we investigated the therapeutical potential of ß2 and ß3 subunits, the other two ß isoforms of Na+, K+-ATPase, for LPS-induced ALI. We found that gene transfer of either the ß1, ß2, or ß3 subunits significantly increased AFC compared to the basal level in naïve animals and each gave similar increased AFC to each other. However, unlike that of the ß1 subunit, gene transfer of the ß2 or ß3 subunit into pre-injured animal lungs failed to show the beneficial effects of attenuated histological damage, neutrophil infiltration, overall lung edema, or increased lung permeability, indicating that ß2 or ß3 gene delivery could not treat LPS induced lung injury. Further, while ß1 gene transfer increased levels of key tight junction proteins in the lungs of injured mice, that of either the ß2 or ß3 subunit had no effect on levels of tight junction proteins. Taken together, this strongly suggests that restoration of alveolar-capillary barrier function alone may be of equal or even more benefit than improving AFC for ALI/ARDS treatment.

Highly stable, antiviral, antibacterial cotton textiles via molecular engineering.

Cotton textiles are ubiquitous in daily life and are also one of the primary mediums for transmitting viruses and bacteria. Conventional approaches to fabricating antiviral and antibacterial textiles generally load functional additives onto the surface of the fabric and/or their microfibres. However, such modifications are susceptible to deterioration after long-term use due to leaching of the additives. Here we show a different method to impregnate copper ions into the cellulose matrix to form a copper ion-textile (Cu-IT), in which the copper ions strongly coordinate with the oxygen-containing polar functional groups (for example, hydroxyl) of the cellulose chains. The Cu-IT displays high antiviral and antibacterial performance against tobacco mosaic virus and influenza A virus, and Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa and Bacillus subtilis bacteria due to the antimicrobial properties of copper. Furthermore, the strong coordination bonding of copper ions with the hydroxyl functionalities endows the Cu-IT with excellent air/water retainability and superior mechanical stability, which can meet daily use and resist repeated washing. This method to fabricate Cu-IT is cost-effective, ecofriendly and highly scalable, and this textile appears very promising for use in household products, public facilities and medical settings.

Organ-specific extracellular matrix directs trans-differentiation of mesenchymal stem cells and formation of salivary gland-like organoids in vivo.

BACKGROUND: Current treatments for salivary gland (SG) hypofunction are palliative and do not address the underlying cause or progression of the disease. SG-derived stem cells have the potential to treat SG hypofunction, but their isolation is challenging, especially when the tissue has been damaged by disease or irradiation for head and neck cancer. In the current study, we test the hypothesis that multipotent bone marrow-derived mesenchymal stem cells (BM-MSCs) in a rat model are capable of trans-differentiating to the SG epithelial cell lineage when induced by a native SG-specific extracellular matrix (SG-ECM) and thus may be a viable substitute for repairing damaged SGs. METHODS: Rat BM-MSCs were treated with homogenates of decellularized rat SG-ECM for one hour in cell suspension and then cultured in tissue culture plates for 7 days in growth media. By day 7, the cultures contained cell aggregates and a cell monolayer. The cell aggregates were hand-selected under a dissecting microscope, transferred to a new tissue culture dish, and cultured for an additional 7 days in epithelial cell differentiation media. Cell aggregates and cells isolated from the monolayer were evaluated for expression of SG progenitor and epithelial cell specific markers, cell morphology and ultrastructure, and ability to form SG-like organoids in vivo. RESULTS: The results showed that this approach was very effective and guided the trans-differentiation of a subpopulation of CD133-positive BM-MSCs to the SG epithelial cell lineage. These cells expressed amylase, tight junction proteins (Cldn 3 and 10), and markers for SG acinar (Aqp5 and Mist 1) and ductal (Krt 14) cells at both the transcript and protein levels, produced intracellular secretory granules which were morphologically identical to those found in submandibular gland, and formed SG-like organoids when implanted in the renal capsule in vivo. CONCLUSIONS: The results of this study suggest the feasibility of using autologous BM-MSCs as an abundant source of stem cells for treating SG hypofunction and restoring the production of saliva in these patients.

Matrix-bound Cyr61/CCN1 is required to retain the properties of the bone marrow mesenchymal stem cell niche but is depleted with aging.

Previously, we showed that extracellular matrices (ECMs), produced ex vivo by various types of stromal cells, direct bone marrow mesenchymal stem cells (BM-MSCs) in a tissue-specific manner and recapitulate physiologic changes characteristic of the aging microenvironment. In particular, BM-MSCs obtained from elderly donors and cultured on ECM produced by young BM stromal cells showed improved quantity, quality and osteogenic differentiation. In the present study, we searched for matrix components that are required for a functional BM-MSC niche by comparing ECMs produced by BM stromal cells from "young" (≤25 y/o) versus "elderly" (≥60 y/o) donors. With increasing donor age, ECM fibrillar organization and mechanical integrity deteriorated, along with the ability to promote BM-MSC proliferation and responsiveness to growth factors. Proteomic analyses revealed that the matricellular protein, Cyr61/CCN1, was present in young, but undetectable in elderly, BM-ECM. To assess the role of Cyr61 in the BM-MSC niche, we used genetic methods to down-regulate the incorporation of Cyr61 during production of young ECM and up-regulate its incorporation in elderly ECM. The results showed that Cyr61-depleted young ECM lost the ability to promote BM-MSC proliferation and growth factor responsiveness. However, up-regulating the incorporation of Cyr61 during synthesis of elderly ECM restored its ability to support BM-MSC responsiveness to osteogenic factors such as BMP-2 and IGF-1. We next examined aging bone and compared bone mineral density and Cyr61 content of L4-L5 vertebral bodies in "young" (9-11 m/o) and "elderly" (21-33 m/o) mice. Our analyses showed that low bone mineral density was associated with decreased amounts of Cyr61 in osseous tissue of elderly versus young mice. Our results strongly demonstrate a novel role for ECM-bound Cyr61 in the BM-MSC niche, where it is responsible for retention of BM-MSC proliferation and growth factor responsiveness, while depletion of Cyr61 from the BM niche contributes to an aging-related dysregulation of BM-MSCs. Our results also suggest new potential therapeutic targets for treating age-related bone loss by restoring specific ECM components to the stem cell niche.

Oral Chronic Graft-Versus-Host Disease.

Chronic oral graft-versus-host disease (cGVHD) is a complex, frequent, and highly impactful complication of allogeneic hematopoietic cell transplantation (alloHCT). It represents the leading cause of morbidity and mortality in long-term alloHCT survivors. cGVHD can affect almost any visceral organ system and commonly affects the skin, eyes and mouth, manifesting with signs and symptoms similar to other known immune-mediated and autoimmune diseases. Oral manifestations of GVHD include inflammation, thinning, and ulceration of oral mucosal tissues (similar to lichen planus), lymphocyte-mediated salivary gland dysfunction (similar to Sjögren/Sicca Syndrome), and decreased oral opening (trismus) secondary to sclerosis of oral and perioral tissues (analogous to limitation in scleroderma). Potential sequelae include severe mucosal pain, compromised nutrition, weight loss, limitation in opening, and sometimes irreversible fibrosis of the salivary glands. While some cases can be managed with topical therapies, management may also require long-term targeted immunosuppressive and/or corticosteroid therapy with associated risk of local and systemic infection, hyperglycemia, kidney dysfunction, osteopenia/osteoporosis, and possibly secondary malignancies. The aim of this mini-review is to provide an up-to-date review of literature related to the diagnosis and management of oral cGVHD to aid dental and medical clinicians in optimizing oral cGVHD therapy while minimizing potential adverse effects.

MASCC/ISOO expert opinion on the management of oral problems in patients with advanced cancer.

PURPOSE: The Palliative Care Study Group in conjunction with the Oral Care Study Group of the Multinational Association for Supportive Care in Cancer (MASCC) formed a sub-group to develop evidence-based guidance on the management of common oral problems in patients with advanced cancer. METHODS: This guidance was developed in accordance with the MASCC Guidelines Policy. A search strategy for Medline was developed, and the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials were explored for relevant reviews and trials, respectively. Guidance was categorised by the level of evidence, and "category of guideline" (i.e., "recommendation", "suggestion" or "no guideline possible"). RESULTS: Twelve generic suggestions (level of evidence - 5), three problem-specific recommendations and 14 problem-specific suggestions were generated. The generic suggestions relate to oral hygiene measures, assessment of problems, principles of management, re-assessment of problems and the role of dental/oral medicine professionals. CONCLUSIONS: This guidance provides a framework for the management of common oral problems in patients with advanced cancer, although every patient requires individualised management.

A Review of Oral Chronic Graft-Versus-Host Disease: Considerations for dental hygiene practice.

Purpose: Allogeneic hematopoietic cell transplantation (alloHCT), also known as stem cell or bone marrow transplantation, is a cellular therapy performed to treat a variety of malignant and non-malignant hematologic diseases. Chronic graft-versus-host disease (cGVHD) is a common immune-mediated complication of alloHCT that can affect various organs of the body, with approximately 70% of affected patients presenting with oral features. Oral manifestations of cGVHD include lichenoid lesions (diagnostic feature), erythema, pseudomembranous ulcerations, superficial mucoceles, salivary gland hypofunction, xerostomia, orofacial sclerosis, trismus, and increased sensitivity to spicy, acidic, hard, and crunchy foods. Patients with oral cGVHD are also at increased risk for developing secondary conditions, such as oral candidiasis, dental caries, and oral squamous cell carcinoma. Given these complex oral health challenges, the dental hygienist can play a key role in optimizing patients' oral health care from pre-stem cell transplantation through survivorship. Optimal care includes a comprehensive health history assessment, thorough extraoral and intraoral examinations, detailed hard and soft tissue evaluations, oral hygiene, and dietary assessment, along with the delivery of patient-centered, oral health instruction and preventive therapies. Appropriate monitoring and management of oral cGVHD require a collaborative care approach between dental, oncology, and oral medicine providers. As part of a multidisciplinary care team, dental hygienists play an important role in the management of patients with oral cGVHD. The purpose of this review is to provide an overview of alloHCT and its oral health considerations, with a focus on oral cGVHD etiology, signs and symptoms, and management considerations for the dental team.

Chemical Polishing of Additively Manufactured, Porous, Nickel-Titanium Skeletal Fixation Plates.

Nickel-titanium (NiTi) alloys have shown promise for a variety of biomedical applications because of their unique properties of shape memory, superelasticity, and low modulus of elasticity (Young's modulus). Nevertheless, NiTi bulk components cannot be easily machined (e.g., CNC, rolling, grinding, casting, or press molding) due to their thermomechanical sensitivity as well as inherent superelasticity and shape memory. Thus, powder bed fusion (PBF) additive manufacturing has been used to successfully fabricate NiTi medical devices that match the geometric and mechanical needs of a particular patient's condition. However, NiTi PBF fabrication leaves unmelted particles from the source powder adhered to external surfaces, which cause minor dimensional inaccuracy, increase the risk of mechanical failure, and once loose, may irritate or inflame surrounding tissues. Therefore, there is a need to develop a chemical polishing (cleaning) technique to remove unmelted powder from the surfaces of PBF-fabricated implants, especially from inner surfaces that are difficult to access with mechanical polishing tools. This technique is especially useful for highly porous devices printed at high resolution. In this study, a chemical polishing method utilizing HF/HNO3 solution was used to remove loosely attached (i.e., unmelted) powder particles from surfaces of porous, skeletal fixation plates manufactured by PBF AM. It was observed that 7 min of polishing in an HF/HNO3 solution comprising 7.5 HF: 50 HNO3: 42.5 H2O enabled successful removal of all relatively loose and unmelted powder particles. A microcomputed tomography study examination found that the volumetric accuracy of the polished skeletal fixation plates was ±10% compared with the computer-aided design (CAD) model from which it was rendered. This postprocessing chemical polishing protocol is also likely to be useful for removing loose powder, while maintaining CAD model accuracy and mechanical stability for other complexly shaped, porous, three-dimensional (3D), printed NiTi devices.

The Na+, K+-ATPase ß1 subunit regulates epithelial tight junctions via MRCKα.

An intact lung epithelial barrier is essential for lung homeostasis. The Na+, K+-ATPase (NKA), primarily serving as an ion transporter, also regulates epithelial barrier function via modulation of tight junctions. However, the underlying mechanism is not well understood. Here, we show that overexpression of the NKA ß1 subunit upregulates the expression of tight junction proteins, leading to increased alveolar epithelial barrier function by an ion transport-independent mechanism. Using IP and mass spectrometry, we identified a number of unknown protein interactions of the ß1 subunit, including a top candidate, myotonic dystrophy kinase-related cdc42-binding kinase α (MRCKα), which is a protein kinase known to regulate peripheral actin formation. Using a doxycycline-inducible gene expression system, we demonstrated that MRCKα and its downstream activation of myosin light chain is required for the regulation of alveolar barrier function by the NKA ß1 subunit. Importantly, MRCKα is expressed in both human airways and alveoli and has reduced expression in patients with acute respiratory distress syndrome (ARDS), a lung illness that can be caused by multiple direct and indirect insults, including the infection of influenza virus and SARS-CoV-2. Our results have elucidated a potentially novel mechanism by which NKA regulates epithelial tight junctions and have identified potential drug targets for treating ARDS and other pulmonary diseases that are caused by barrier dysfunction.