COVID-19 Pandemic Associated With Increased Self-reported Depressive Symptoms in Patients With Congenital Craniofacial Diagnoses.

OBJECTIVE: The current study investigated the influence of the coronavirus (COVID-19) pandemic on patients with congenital craniofacial diagnoses. METHODS: Patients (n = 66) with craniofacial diagnoses aged between 8 and 17 were prospectively evaluated with longitudinal psychosocial assessments using the anger, anxiety, depressive symptoms, and peer relationships instruments within the pediatric Patient-Reported Outcomes Measurement Information System (PROMIS). The COVID-19 cohort (n = 33) included patients with assessments within 2 years prior to the pandemic (t0) and during the pandemic (t1; March 2020 to March 2021). An age-matched comparison cohort (n = 33) with similar demographics and diagnoses included patients assessed twice over 3 years prior to the pandemic. RESULTS: All PROMIS measures were in the average range clinically for both groups across time points. However, the COVID-19 group reported a significant increase in depressive symptoms during the pandemic (t1) compared to pre-pandemic (t0) scores (48.2 ± 10.1 vs 44.3 ± 9.4, P = .04, d = -0.37), while the comparison group did not demonstrate any differences in psychosocial functioning between t0 and t1. For the COVID-19 cohort, only the pandemic timeframe (r = 0.21, P = .03) was significantly associated with increased depressive symptom scores, and no other sociodemographic or medical variables were associated with depressive symptoms. CONCLUSIONS: Self-reported depressive symptoms increased during the COVID-19 pandemic in patients with congenital craniofacial diagnoses. Longitudinal studies are needed to elucidate whether such changes will be persistent or compound known variables associated with psychosocial functioning.

Bone-Anchored Maxillary Protraction for Adolescents with Cleft Palate and Class III Malocclusion: A Case Series.

To describe the long-term treatment course of bone-anchored maxillary protraction (BAMP) and evaluate orthognathic surgical indications after BAMP.Retrospective case series.Craniofacial/Cleft Palate Program at the Orthopaedic Institute for Children in Los Angeles, CA.Twelve male patients with cleft palate (CP), unilateral cleft lip and palate (UCLP), or bilateral cleft lip and palate (BCLP) and Class III malocclusion treated with BAMP (mean age: 11.4 ± 2.6 years) were included.BAMP treatment was performed by placement of bone-anchored maxillary and mandibular plates connected with intraoral Class III dental elastics or maxillary plates connected to a facemask.We retrospectively assessed BAMP treatment variables, including age at surgery, revision surgeries, and treatment duration. The primary goal was correction to class I occlusion.Twelve patients underwent BAMP treatment for an average of 4.4 ± 2.4 years. Two patients were corrected to class I occlusion at the time of this report. Le Fort I advancement was no longer required in two patients (16.7%), it was required for nine patients (75.0%) and was completed for one patient following BAMP treatment (8.3%).This preliminary report demonstrated that BAMP treatment may be associated with a minimal reduction in the requirement for Le Fort I advancement at skeletal maturity. Future studies with larger sample sizes are necessary to confirm this association.

Association of Patient-Reported Anxiety and Pain After Alveolar Bone Grafting.

OBJECTIVE: To evaluate the role of psychosocial well-being on perioperative pain and opioid use among patients with cleft lip and palate (CLP) undergoing alveolar bone grafting (ABG). DESIGN: Retrospective review. SETTING: Tertiary level craniofacial clinic. PARTICIPANTS: 34 patients with CLP (median age: 11.7 years), including 25 (73.5%) unilateral CLP and 9 (26.5%) bilateral CLP, who underwent ABG from 2015 to 2022. INTERVENTIONS: ABG using iliac crest bone graft. Patients were prospectively administered four patient-reported psychosocial instruments from the Patient-Reported Outcomes Measurement Information System. MAIN OUTCOME MEASURES: Perioperative opioid use in morphine equivalent dosage/kilogram, patient-reported pain scores, and length of hospital stay after ABG. RESULTS: Patient-reported anxiety (r = 0.41, p = 0.02) and depressive symptoms (r = 0.35, p = 0.04) correlated to higher perioperative opioid usage. Multivariable regression models including psychosocial scores, total acetaminophen usage, length of surgery, and other simultaneous surgeries were developed for total opioid usage, patient-reported pain, and length of hospital stay. Patient-reported anxiety was independently predictive of higher perioperative opioid use (ß=0.36, p = 0.01) and higher pain scores (ß=0.39, p = 0.02), but not length of hospital stay. CONCLUSIONS: We identified an association for patient-reported anxiety and perioperative opioid use and pain in a CLP cohort undergoing ABG. Future considerations in preoperative patient and family consultation may be indicated in patients self-reporting higher anxiety in an effort to minimize perioperative opioid usage.

Design, Synthesis, Computational and Biological Evaluation of Novel Structure Fragments Based on Lithocholic Acid (LCA).

The regulation of bile acid pathways has become a particularly promising therapeutic strategy for a variety of metabolic disorders, cancers, and diseases. However, the hydrophobicity of bile acids has been an obstacle to clinical efficacy due to off-target effects from rapid drug absorption. In this report, we explored a novel strategy to design new structure fragments based on lithocholic acid (LCA) with improved hydrophilicity by introducing a polar "oxygen atom" into the side chain of LCA, then (i) either retaining the carboxylic acid group or replacing the carboxylic acid group with (ii) a diol group or (iii) a vinyl group. These novel fragments were evaluated using luciferase-based reporter assays and the MTS assay. Compared to LCA, the result revealed that the two lead compounds 1a-1b were well tolerated in vitro, maintaining similar potency and efficacy to LCA. The MTS assay results indicated that cell viability was not affected by dose dependence (under 25 µM). Additionally, computational model analysis demonstrated that compounds 1a-1b formed more extensive hydrogen bond networks with Takeda G protein-coupled receptor 5 (TGR5) than LCA. This strategy displayed a potential approach to explore the development of novel endogenous bile acids fragments. Further evaluation on the biological activities of the two lead compounds is ongoing.

The Advice Given During Near-Peer Interactions Before and After Curriculum Change.

PhenomenonNear-peer interactions (NPIs) provide formal and informal mentorship that can allow medical students to share strategies for successful training. Such capacity to convey valuable advice, however, may depend on the similitude of experiences. Given that many factors can disrupt homogeneity, including curriculum renewal, we must better understand whether junior trainees feel disadvantaged when they do not have more senior peers with similar experiences. This study was, therefore, conducted to examine the focus of, and engagement with, advice available through NPIs during curriculum renewal. Approach: We used a generic exploratory qualitative research approach. Twenty MD undergraduate students, seven from the Class of 2019 (the first cohort post-curriculum change), and thirteen from the Class of 2020 (the first cohort with access to more senior students in the new curriculum), participated in semi-structured interviews. Anonymized transcriptions were analyzed with open, axial, and selective coding to generate themes until saturation was attained. Findings: Participants from the Class of 2019 reported having particularly few reasons to seek advice; because curriculum renewal disrupted their near peers' capacity to provide critical insights, students exerted little effort to learn from them. That said, this vacuum was not generally cause for concern. Deeper probing illustrated why: advice given during NPIs in both classes more commonly focused on nonacademic (e.g., work-life balance issues) than academic advice; academic advice, when sought or offered, tended not to be aimed at improving understanding of curriculum dependent content; and, while students in both classes welcomed advice, both were wary of accepting it at face value, precluding a sense of dependence on senior peers. Insights: Students' skepticism about the overall utility of academic advice raises a number of important issues for medical education and training. Positively, it shielded students from feeling loss when advice from similarly trained students was not available, reducing concerns about disadvantage that could arise during periods of curriculum revision. On the other hand, knowing that what students perceive and what educators claim to be important aspects of training can be at odds and knowing that self-assessment is flawed makes it surprising and unsettling, respectively, that participants so readily treated the lessons learned by those who came before them as irrelevant.

Gliadin Nanoparticles Induce Immune Tolerance to Gliadin in Mouse Models of Celiac Disease.

BACKGROUND & AIMS: Celiac disease could be treated, and potentially cured, by restoring T-cell tolerance to gliadin. We investigated the safety and efficacy of negatively charged 500-nm poly(lactide-co-glycolide) nanoparticles encapsulating gliadin protein (TIMP-GLIA) in 3 mouse models of celiac disease. Uptake of these nanoparticles by antigen-presenting cells was shown to induce immune tolerance in other animal models of autoimmune disease. METHODS: We performed studies with C57BL/6; RAG1-/- (C57BL/6); and HLA-DQ8, huCD4 transgenic Ab0 NOD mice. Mice were given 1 or 2 tail-vein injections of TIMP-GLIA or control nanoparticles. Some mice were given intradermal injections of gliadin in complete Freund's adjuvant (immunization) or of soluble gliadin or ovalbumin (ear challenge). RAG-/- mice were given intraperitoneal injections of CD4+CD62L-CD44hi T cells from gliadin-immunized C57BL/6 mice and were fed with an AIN-76A-based diet containing wheat gluten (oral challenge) or without gluten. Spleen or lymph node cells were analyzed in proliferation and cytokine secretion assays or by flow cytometry, RNA sequencing, or real-time quantitative polymerase chain reaction. Serum samples were analyzed by gliadin antibody enzyme-linked immunosorbent assay, and intestinal tissues were analyzed by histology. Human peripheral blood mononuclear cells, or immature dendritic cells derived from human peripheral blood mononuclear cells, were cultured in medium containing TIMP-GLIA, anti-CD3 antibody, or lipopolysaccharide (controls) and analyzed in proliferation and cytokine secretion assays or by flow cytometry. Whole blood or plasma from healthy volunteers was incubated with TIMP-GLIA, and hemolysis, platelet activation and aggregation, and complement activation or coagulation were analyzed. RESULTS: TIMP-GLIA did not increase markers of maturation on cultured human dendritic cells or induce activation of T cells from patients with active or treated celiac disease. In the delayed-type hypersensitivity (model 1), the HLA-DQ8 transgenic (model 2), and the gliadin memory T-cell enteropathy (model 3) models of celiac disease, intravenous injections of TIMP-GLIA significantly decreased gliadin-specific T-cell proliferation (in models 1 and 2), inflammatory cytokine secretion (in models 1, 2, and 3), circulating gliadin-specific IgG/IgG2c (in models 1 and 2), ear swelling (in model 1), gluten-dependent enteropathy (in model 3), and body weight loss (in model 3). In model 1, the effects were shown to be dose dependent. Splenocytes from HLA-DQ8 transgenic mice given TIMP-GLIA nanoparticles, but not control nanoparticles, had increased levels of FOXP3 and gene expression signatures associated with tolerance induction. CONCLUSIONS: In mice with gliadin sensitivity, injection of TIMP-GLIA nanoparticles induced unresponsiveness to gliadin and reduced markers of inflammation and enteropathy. This strategy might be developed for the treatment of celiac disease.

Building an active medical product safety surveillance system in Taiwan: Adaptation of the U.S. Sentinel System common data model structure to the National Health Insurance Research Database in Taiwan.

PURPOSE: Using real-world data to support regulatory decision has become a global movement. However, a robust platform for active surveillance of medical product safety has not been established in Taiwan. METHODS: Following the common data model structure of the U.S. Food and Drug Administration's Sentinel System, we built the Taiwan Sentinel Data Model (TSDM) using the National Health Insurance Research Database with longitudinal claims data from 23 million individuals, linked death and cause of death data from a national registry, and linked electronic health record data from a delivery system. We examined the conversion of the TSDM using the Sentinel Data Quality Review and Characterization Programs in a sample of sex- and age-stratified cohort of 3 million individuals. RESULTS: The TSDM fulfilled the requirements of data quality assurance. Only about 6% of sex and 0.0007% of birth year were missing, and <0.001% of date data had illogical values. CONCLUSIONS: The TSDM-converted database could be a valuable data resource for domestic pharmacovigilance analysis in Taiwan and cross-country evaluation.

Ramatroban-Based Analogues Containing Fluorine Group as Potential 18F-Labeled Positron Emission Tomography (PET) G-Protein Coupled Receptor 44 (GPR44) Tracers.

Diabetes remains one of the fastest growing chronic diseases and is a leading source of morbidity and accelerated mortality in the world. Loss of beta cell mass (BCM) and decreased sensitivity to insulin underlie diabetes pathogenesis. Yet, the ability to safely and directly assess BCM in individuals with diabetes does not exist. Measures such as blood glucose provide only a crude indirect picture of beta cell health. PET imaging could, in theory, allow for safe, direct, and precise characterization of BCM. However, identification of beta cell-specific radiolabeled tracers remains elusive. G-protein coupled receptor 44 (GPR44) is a transmembrane protein that was characterized in 2012 as highly beta cell-specific within the insulin-positive islets of Langerhans. Accordingly, radiolabeling of existing GPR44 antagonists could be a viable method to accelerate PET tracer development. The present study aims to evaluate and summarize published analogues of the GPR44 antagonist ramatroban to develop 18F-labeled PET tracers for BCM analysis. The 77 corresponding ramatroban analogues containing a fluorine nuclide were characterized for properties including binding affinity, selectivity, and pharmacokinetic and metabolic profile, and 32 compounds with favorable properties were identified. This review illustrates the potential of GPR44 analogues for the development of PET tracers.

Not all aspirin products have equivalent antiplatelet efficacy-Aspirin formulated with magnesium stearate is less effective in preventing ischemic stroke.

PURPOSE: Magnesium stearate (MgSt) is a widely used excipient in pharmaceutical formulations but should be avoided in aspirin preparations as it hydrolyzes aspirin. We hypothesized that preparations of aspirin-containing MgSt (MgSt-ASA) are less effective in preventing thrombosis in clinical settings. The risk of composite cardiovascular events in patients treated with MgSt-ASA preparations for preventing secondary stroke was evaluated. METHODS: This retrospective cohort study used Taiwan's claims data from 1997 to 2013. Patients who were discharged after ischemic stroke (IS) and administered with only MgSt-ASA or non-MgSt-ASA preparations were enrolled. Composite events including all-cause mortality, IS hospitalization, and myocardial infarction-related hospitalization in the follow-up period under therapy with MgSt-ASA or non-MgSt-ASA preparations were considered primary outcomes. Hazard ratios (HRs) were adjusted with the baseline comorbidities and medications using the Cox model. RESULTS: A total of 19 500 patients with IS (60% males, average age 67 years) were identified, which included 2064 patients receiving MgSt-ASA treatment initially and 17 436 patients receiving non-MgSt-ASA preparation initially. The crude incidence of composite events was 11.65 per 100 person-years, whereas it was 11.45 and 13.90 per 100 person-years for patients receiving non-MgSt-ASA and MgSt-ASA treatments, respectively. The risk of composite events was higher in patients receiving MgSt-ASA preparations than in those receiving non-MgSt-ASA formulations, with the adjusted HR being 1.23 at 95% confidence interval of 1.02 to 1.47. CONCLUSIONS: MgSt-ASA preparation use was associated with a higher risk of composite events than non-MgSt-ASA preparations. Review of aspirin formulations under regulatory intervention is warranted.

Blood Culture Results Before and After Antimicrobial Administration in Patients With Severe Manifestations of Sepsis: A Diagnostic Study.

Background: Administering antimicrobial agents before obtaining blood cultures could potentially decrease time to treatment and improve outcomes, but it is unclear how this strategy affects diagnostic sensitivity. Objective: To determine the sensitivity of blood cultures obtained shortly after initiation of antimicrobial therapy in patients with severe manifestations of sepsis. Design: Patient-level, single-group, diagnostic study. (ClinicalTrials.gov: NCT01867905). Setting: 7 emergency departments in North America. Participants: Adults with severe manifestations of sepsis, including systolic blood pressure less than 90 mm Hg or a serum lactate level of 4 mmol/L or more. Intervention: Blood cultures were obtained before and within 120 minutes after initiation of antimicrobial treatment. Measurements: Sensitivity of blood cultures obtained after initiation of antimicrobial therapy. Results: Of 3164 participants screened, 325 were included in the study (mean age, 65.6 years; 62.8% men) and had repeated blood cultures drawn after initiation of antimicrobial therapy (median time, 70 minutes [interquartile range, 50 to 110 minutes]). Preantimicrobial blood cultures were positive for 1 or more microbial pathogens in 102 of 325 (31.4%) patients. Postantimicrobial blood cultures were positive for 1 or more microbial pathogens in 63 of 325 (19.4%) patients. The absolute difference in the proportion of positive blood cultures between pre- and postantimicrobial testing was 12.0% (95% CI, 5.4% to 18.6%; P < 0.001). Sensitivity of postantimicrobial culture was 52.9% (CI, 42.8% to 62.9%). When the results of other microbiological cultures were included, microbial pathogens were found in 69 of 102 (67.6% [CI, 57.7% to 76.6%]) patients. Limitation: Only a proportion of screened patients were recruited. Conclusion: Among patients with severe manifestations of sepsis, initiation of empirical antimicrobial therapy significantly reduces the sensitivity of blood cultures drawn shortly after treatment initiation. Primary Funding Source: Vancouver Coastal Health, St. Paul's Hospital Foundation Emergency Department Support Fund, the Fonds de recherche Santé-Québec, and the Maricopa Medical Foundation.

Selective Inhibition of Liver Cancer Cells Using Venom Peptide.

Increasingly cancer is being viewed as a channelopathy because the passage of ions via ion channels and transporters mediate the regulation of tumor cell survival, death, and motility. As a result, a potential targeted therapy for cancer is to use venom peptides that are selective for ion channels and transporters overexpressed in tumor cells. Here we describe the selectivity and mechanism of action of terebrid snail venom peptide, Tv1, for treating the most common type of liver cancer, hepatocellular carcinoma (HCC). Tv1 inhibited the proliferation of murine HCC cells and significantly reduced tumor size in Tv1-treated syngeneic tumor-bearing mice. Tv1's mechanism of action involves binding to overexpressed transient receptor potential (TRP) channels leading to calcium dependent apoptosis resulting from down-regulation of cyclooxygenase-2 (COX-2). Our findings demonstrate the importance of modulating ion channels and the unique potential of venom peptides as tumor specific ligands in the quest for targeted cancer therapies.

Virtual Modeling in Gender-Affirming Facial Masculinization Surgery.

SUMMARY: The increase in access to facial gender-affirming surgery has resulted in a rise in facial feminization surgeries for transfeminine and gender non-binary populations. However, refined execution of facial masculinization is challenged by the lack of defined measurements for facial augmentation, the lack of long-term predictability in autologous bone grafting in augmentation procedures, and the lack of precision in traditional facial augmentation procedures with generic alloplastic implants. In this work, we describe an innovation in facial masculinization surgery using modern reconstructive craniofacial surgical techniques with preoperative virtual modeling and the fabrication of three-dimensionally printed, patient-specific custom implants.

Long-term outcomes of sphincter pharyngoplasty in patients with cleft palate.

OBJECTIVE: The purpose of this study was to evaluate long-term outcomes of sphincter pharyngoplasties, including speech outcomes, revision surgeries, and postoperative incidence of obstructive sleep apnea (OSA). DESIGN: Retrospective matched-cohort study SETTING: Two craniofacial centers in Los Angeles, CA PATIENTS: Patients (n = 166) with cleft lip and palate (CLP) or isolated cleft palate (iCP) who underwent sphincter pharyngoplasty from 1992 to 2022 were identified. An age- and diagnosis-matched control group of 67 patients with CLP/iCP without velopharyngeal insufficiency (VPI) was also identified. INTERVENTIONS: The pharyngoplasty group underwent sphincter pharyngoplasty, whereas the non-VPI group had no history of VPI surgery or sphincter pharyngoplasty. MAIN OUTCOME MEASURES: Postoperative speech outcomes, revision surgeries, and incidence of OSA were evaluated. Multivariable regression was used to evaluate independent predictors of OSA. RESULTS: Among the patients in the pharyngoplasty cohort, 63.9% demonstrated improved and sustained speech outcomes after a single pharyngoplasty, with a median postoperative follow-up of 8.8 years (interquartile range [IQR], 3.6-12.0 years). One-third of the patients who underwent pharyngoplasty required a revision surgery, with a median time to primary revision of 3.9 years (IQR, 1.9-7.0 years). OSA rates increased significantly among the pharyngoplasty cohort, from 3% before surgery to 14.5% after surgery (p < 0.001). The average time from sphincter pharyngoplasty to OSA diagnosis was 4.4 ± 2.4 years. Multivariable analysis results indicated that sphincter pharyngoplasty surgery was independently associated with a fourfold increase in OSA (p = 0.03). CONCLUSIONS: Although sphincter pharyngoplasty remains successful in improving long-term speech outcomes, persistent OSA is a sequela that should be monitored beyond the immediate postoperative period.

Ethnic variation in lower face anthropometry on facial computed tomography scans for patients seeking facial feminization surgery.

BACKGROUND: Facial feminization surgery (FFS) is the most common form of facial gender-affirming surgery. One of the current knowledge gaps is the understanding of differences among racial groups in baseline craniofacial norms for transgender and nonbinary patients. METHODS: All patients who sought consultation for FFS and underwent craniofacial computed tomography (CT) scans at a single institution between 2018 and 2023 were included. Patients who underwent previous facial surgeries were excluded. Chart reviews were conducted for patient characteristics, including race, age, hormone therapy duration, and prior gender-affirming surgeries. Racial categorizations included White, Latinx, African American, or Asian. Patients with other or multiracial identities were excluded. Lower face measurements were derived from preoperative facial CT scans. Comparative analyses were performed on all measurements among the racial groups. RESULTS: In this study, 204 patients were included with an average age of 32.0 ± 10.2 years and a median hormone therapy duration of 2.0 years. The notable differences among the racial groups were: 1. Zygomatic width was the largest in Asian patients (13.5 ± 0.6 cm) compared to all other racial groups (p = 0.03), 2. Nasolabial angle was the smallest in African American patients (82.5 ± 13.1 degrees, p < 0.001), 3. Lower face height was the largest in African American patients (6.9 ± 0.7 cm, p < 0.001), and 4. Lateral mandibular flare was the largest in African American patients (0.4 ± 0.1 cm) and the smallest in Latinx patients (0.2 ± 0.1 cm, p < 0.001). CONCLUSIONS: Specific target areas of FFS should be carefully considered to account for possible baseline ethnic differences. Relative facial proportions may also be a more salient surgical planning tool in transgender and gender nonbinary patients rather than absolute measurements alone.

United States Health Policies on Gender-Affirming Care in 2022.

BACKGROUND: Within the United States, access to gender-affirming operations covered by health insurance has increased dramatically over the past decade. However, the perpetually changing landscape and inconsistencies of individual state health policies governing private and public insurance coverage present a lack of clarity for reconstructive surgeons and other physicians attempting to provide gender-affirming care. This work systematically reviewed the current U.S. health policies for both private insurance and Medicaid on a state-by-state basis. METHODS: Individual state health policies in effect as of August of 2022 on gender-affirming care were reviewed using the LexisNexis legal database, state legislature publications, and Medicaid manuals. Primary outcomes were categorization of policies as protective, restrictive, or unclear for each state. Secondary outcomes included analyses of demographics covered by current health policies and geographic differences. RESULTS: Protective state-level health policies related to gender-affirming care were present in approximately half of the nation for both private insurance (49.0%) and Medicaid (52.9%). Explicitly restrictive policies were found in 5.9% and 17.6% of states for private insurance and Medicaid, respectively. Regionally, the Northeast and West had the highest rates of protective policies, whereas the Midwest and South had the highest rates of restrictive policies on gender-affirming care. CONCLUSIONS: State-level health policies on gender-affirming care vary significantly across the United States with regional associations. Clarity in the current and evolving state-specific health policies governing gender-affirming care is essential for surgeons and physicians caring for transgender and gender-diverse individuals.

Correlating Material Properties to Osteoprotegerin Expression on Nanoparticulate Mineralized Collagen Glycosaminoglycan Scaffolds.

Precision material design directed by cell biological processes represents a frontier in developing clinically translatable regenerative technologies. While understanding cell-material interactions on multipotent progenitor cells yields insights on target tissue differentiation, equally if not more important is the quantification of indirect multicellular interactions. In this work, the relationship of two material properties, phosphate content and stiffness, of a nanoparticulate mineralized collagen glycosaminoglycan scaffold (MC-GAG) in the expression of an endogenous anti-osteoclastogenic secreted protein, osteoprotegerin (OPG) by primary human mesenchymal stem cells (hMSCs) is evaluated. The phosphate content of MC-GAG requires the type III sodium phosphate symporter PiT-1/SLC20A1 for OPG expression, correlating with ß-catenin downregulation, but is independent of the effects of phosphate ion on osteogenic differentiation. Using three stiffness MC-GAG variants that do not differ significantly by osteogenic differentiation, it is observed that the softest material elicited ≈1.6-2 times higher OPG expression than the stiffer materials. Knockdown of the mechanosensitive signaling axis of YAP, TAZ, ß-catenin and combinations thereof in hMSCs on MC-GAG demonstrates that ß-catenin downregulation increases OPG expression by 1.5-fold. Taken together, these data constitute a roadmap for material properties that can used to suppress osteoclast activation via osteoprotegerin expression separately from the anabolic processes of osteogenesis.

Medicaid coverage for gender-affirming surgery: A state-by-state review.

OBJECTIVE: To systematically review Medicaid policies state-by-state for gender-affirming surgery coverage. DATA SOURCES AND STUDY SETTING: Primary data were collected for each US state utilizing the LexisNexis legal database, state legislature publications, and Medicaid manuals. STUDY DESIGN: A cross-sectional study evaluating Medicaid coverage for numerous gender-affirming surgeries. DATA COLLECTION/EXTRACTION METHODS: We previously reported on state health policies that protect gender-affirming care under Medicaid coverage. Building upon our prior work, we systematically assessed the 27 states with protective policies to determine coverage for each type of gender-affirming surgery. We analyzed Medicaid coverage for gender-affirming surgeries in four domains: chest, genital, craniofacial and neck reconstruction, and miscellaneous procedures. Medicaid coverage for each type of surgery was categorized as explicitly covered, explicitly noncovered, or not described. PRINCIPAL FINDINGS: Among the 27 states with protective Medicaid policies, 17 states (63.0%) provided explicit coverage for at least one gender-affirming chest procedure and at least one gender-affirming genital procedure, while only eight states (29.6%) provided explicit coverage for at least one craniofacial and neck procedure (p = 0.04). Coverage for specific surgical procedures within these three anatomical domains varied. The most common explicitly covered procedures were breast reduction/mastectomy and hysterectomy (n = 17, 63.0%). The most common explicitly noncovered surgery was reversal surgery (n = 12, 44.4%). Several states did not describe the specific surgical procedures covered; thus, final coverage rates are indeterminate. CONCLUSIONS: In 2022, 52.9% of states had health policies that protected gender-affirming care under Medicaid; however, coverage for various gender-affirming surgical procedures remains both variable and occasionally unspecified. When specified, craniofacial and neck reconstruction is the least covered anatomical area compared with chest and genital reconstruction.

RAGE inhibits human respiratory syncytial virus syncytium formation by interfering with F-protein function.

Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infection. Infection is critically dependent on the RSV fusion (F) protein, which mediates fusion between the viral envelope and airway epithelial cells. The F protein is also expressed on infected cells and is responsible for fusion of infected cells with adjacent cells, resulting in the formation of multinucleate syncytia. The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor that is constitutively highly expressed by type I alveolar epithelial cells. Here, we report that RAGE protected HEK cells from RSV-induced cell death and reduced viral titres in vitro. RAGE appeared to interact directly with the F protein, but, rather than inhibiting RSV entry into host cells, virus replication and budding, membrane-expressed RAGE or soluble RAGE blocked F-protein-mediated syncytium formation and sloughing. These data indicate that RAGE may contribute to protecting the lower airways from RSV by inhibiting the formation of syncytia, viral spread, epithelial damage and airway obstruction.

Talimogene Laherparepvec (T-VEC): A Review of the Recent Advances in Cancer Therapy.

The landscape of melanoma treatment has undergone a dramatic revolution in the past decade. The use of oncolytic viruses (OVs) represents a novel therapeutic approach that can selectively infect and lyse tumor cells and induce local and systemic antitumor immune responses. As the first OV approved by the Food and Drug Administration (FDA) for melanoma treatment, talimogene laherparepvec (T-VEC), a genetically modified herpes simplex virus (HSV), has shown promising therapeutic effects in the treatment of advanced melanoma, both as a monotherapy or in combination with other immunotherapies, such as the immune checkpoint inhibitors (ICIs). With proven efficacy, T-VEC has been evaluated against a variety of other cancer types in a clinical trial setting. In this article, we will provide a review on OVs and the application of T-VEC in melanoma monotherapy and combination therapy. In addition, we will review the recent progress of T-VEC application in other cutaneous cancer types. Moreover, we will briefly describe our experience of T-VEC therapy at City of Hope, aiming to provide more insight for expanding its future application.

Convergence of Calcium Channel Regulation and Mechanotransduction in Skeletal Regenerative Biomaterial Design.

Cells are known to perceive their microenvironment through extracellular and intracellular mechanical signals. Upon sensing mechanical stimuli, cells can initiate various downstream signaling pathways that are vital to regulating proliferation, growth, and homeostasis. One such physiologic activity modulated by mechanical stimuli is osteogenic differentiation. The process of osteogenic mechanotransduction is regulated by numerous calcium ion channels-including channels coupled to cilia, mechanosensitive and voltage-sensitive channels, and channels associated with the endoplasmic reticulum. Evidence suggests these channels are implicated in osteogenic pathways such as the YAP/TAZ and canonical Wnt pathways. This review aims to describe the involvement of calcium channels in regulating osteogenic differentiation in response to mechanical loading and characterize the fashion in which those channels directly or indirectly mediate this process. The mechanotransduction pathway is a promising target for the development of regenerative materials for clinical applications due to its independence from exogenous growth factor supplementation. As such, also described are examples of osteogenic biomaterial strategies that involve the discussed calcium ion channels, calcium-dependent cellular structures, or calcium ion-regulating cellular features. Understanding the distinct ways calcium channels and signaling regulate these processes may uncover potential targets for advancing biomaterials with regenerative osteogenic capabilities.