Examining the Longitudinal Relationship Between Olfactory Dysfunction and Frailty in Community-Dwelling, older US Adults.

OBJECTIVE: Olfactory dysfunction is a "canary in the coalmine" for aging conditions. We evaluated olfactory dysfunction as a biomarker of early frailty in older adults living in the United States. STUDY DESIGN: Prospective, longitudinal, nationally representative study. SETTING: National Social Life, Health and Aging Project (NSHAP). METHODS: We examined data from 1061 community-dwelling older US adults. Odor identification (5-item Sniffin' Stick) and frailty scores were measured at baseline and 5-year follow-up. Multivariate logistic regressions evaluated the association between olfactory dysfunction and frailty at baseline in cross-section and over time in the transition from robust to prefrail to frail, adjusting for confounding factors measured at baseline. RESULTS: Older US adults who were anosmic at baseline were more likely to be frail 5 years later compared to normosmic peers (odds ratio [OR]: 3.83, 95% confidence interval [CI]: 1.10-13.31, P = .035). Examining changes in frailty stage over time, we found that anosmics were more likely to transition from prefrail to frail over 5 years (OR: 3.25, 95% CI: 1.31-8.08, P = .011). Interestingly, hyposmics did not show a similar trajectory toward frailty (P > .05). In contrast, olfactory dysfunction was not associated with frailty in cross-section (OR: 0.90, 95% CI: 0.43-1.89, P = .787, hyposmia; OR: 0.72, 95% CI: 0.15-3.35, P = .673, anosmia). CONCLUSION: Older US adults with anosmia face higher odds of becoming frail over 5 years, especially those in the prefrail stage. Olfactory dysfunction may serve as a surrogate marker for early-stage neurodegenerative diseases, which are strong contributors to frailty.

Impact of social determinants of health on access to rhinology care and patient outcomes: A pilot study.

Objective: This novel pilot study constructs a social deprivation index (SDI) and utilizes an area deprivation index (ADI) to evaluate the link between social determinants of health and rhinology patient experiences. Methods: Adult patients undergoing outpatient care of chronic rhinitis and chronic rhinosinusitis at a tertiary academic medical center were recruited to participate in a telephone survey assessing symptoms, social/emotional consequences of disease, and barriers to care on a 5-point Likert scale. Sociodemographic characteristics were utilized to rate SDI on an 8-point scale. ADI was obtained by area code of residence. Ordered logistic regression was used to examine associations between the SDI/ADI and perceptions of rhinology care. Results: Fifty patients were included. Individuals with higher SDI scores (i.e., more socially deprived) experienced more severe nasal congestion (p = .007). Furthermore, higher national ADI correlated with increased severity of smell changes (p = .050) and facial pressure (p = .067). No association was seen between either deprivation index and global/psychiatric symptoms. While no correlations were found between higher SDI and difficulties with the costs of prescriptions, rhinologist's visits, or saline, higher SDI was correlated with decreased difficulty with surgery costs (p = .029), and individuals with higher national ADI percentile had increased difficulties obtaining nasal saline (p = .029). Conclusion: Worse social deprivation is associated with difficulties obtaining saline rinses and increased severity of nasal/sinus symptoms in an urban, underserved, majority-Black population. These findings suggest social factors affect access to and quality of rhinology care in a complex and nuanced way and highlight the need for a specific SDI to further study social determinants of health in rhinology. Level of Evidence: 2c.

Systematic Review of Nonsyndromic Craniosynostosis: Genomic Alterations and Impacted Signaling Pathways.

BACKGROUND: Genetic research in nonsyndromic craniosynostosis remains limited compared with syndromic craniosynostosis. This systematic review aimed to comprehensively summarize the genetic literature of nonsyndromic craniosynostosis and highlight key signaling pathways. METHODS: The authors performed a systematic literature search of PubMed, Ovid, and Google Scholar databases from inception until December of 2021 using search terms related to nonsyndromic craniosynostosis and genetics. Two reviewers screened titles and abstract for relevance, and three reviewers independently extracted study characteristics and genetic data. Gene networks were constructed using Search Tool for Retrieval of Interacting Genes/Proteins (version 11) analysis. RESULTS: Thirty-three articles published between 2001 and 2020 met inclusion criteria. Studies were further classified into candidate gene screening and variant identification studies ( n = 16), genetic expression studies ( n = 13), and common and rare variant association studies ( n = 4). Most studies were good quality. Using our curated list of 116 genes extracted from the studies, two main networks were constructed. CONCLUSIONS: This systematic review concerns the genetics of nonsyndromic craniosynostosis, with network construction revealing TGF-ß/BMP, Wnt, and NF-κB/RANKL as important signaling pathways. Future studies should focus on rare rather than common variants to examine the missing heritability in this defect and, going forward, adopt a standard definition.

Olfactory decline develops in parallel with frailty in older US adults with obstructive lung diseases.

BACKGROUND: Frailty is prevalent among older adults with asthma or chronic obstructive pulmonary disease (obstructive lung diseases [OLDs]). Frailty and OLD's co-occurrence is associated with increased hospitalization/mortality. Chemosensory dysfunction is closely connected to both OLD and frailty. We evaluated the utility of olfactory decline as a biomarker of frailty in the setting of OLD. METHODS: We performed a prospective, longitudinal, nationally representative study of community-dwelling older US adults in the National Social Life, Health and Aging Project, an omnibus in-home survey. Respondents reported a physician's diagnosis of OLD. Decline in odor identification and sensitivity over 5 years and frailty (adapted fried frailty phenotype criteria) were measured using standard tools. Multivariate logistic regressions evaluated the association between OLD status, olfactory decline, and frailty. RESULTS: We compared individuals with OLD (n = 98; mean age 71.2 years, 59.2% women) and those without OLD (n = 1036; mean age 69.5 years, 58.9% women). Olfactory identification decline was associated with developing frailty over the 5-year follow-up period in individuals with OLD (odds ratio [OR] = 9.1, 95% confidence interval [CI] = 2.1-38.6, p = 0.003). Olfactory decline predicted incidence of frailty in individuals with OLD (identification: OR = 4.8, 95% CI = 1.3-17.5, P = 0.018; sensitivity: OR = 6.1, 95%CI = 1.2-31.0, p = 0.030) but not in those without OLD adjusting for demographics, heavy alcohol use, current smoking, and comorbidity. Results were robust to different thresholds for olfactory decline and frailty development. CONCLUSIONS: Older adults with OLD who experience olfactory decline face higher odds of developing frailty. Use of olfactory decline as a biomarker to identify frailty could allow earlier intervention and decrease adverse outcomes for high-risk older adults with OLD.

Regional distribution in female representation in US otolaryngology faculty.

Objectives: To quantify the current proportion of women in otolaryngology at different levels of professorship and determine whether these proportions differ by US region. Methods: Academic rank and gender at all ACGME-accredited otolaryngology programs in the United States were determined from departmental websites, Doximity, and LinkedIn from November 2021 to March 2022. Individuals were then further organized using US Census Bureau-designated regions. Results: Among the 2682 faculty positions at 124 ACGME-accredited programs, women held 706 (26.3%) of these positions. Female representation was highest at the assistant professorship level, with women holding 286 (37.2%) positions out of a total 769. At the associate professorship level, women held 141 (27.6%) of the 511 total positions. The largest gender disparity is seen at the full professorship level; only 69 (13.6%) positions out of 508 were held by women. Out of every region and rank, only assistant professorship in the West had no significant difference in percentages of men and women (p = .710). Female representation of professors in the Northeast was significantly lower than that of our reference group (the South; ß = -10.9, p = .020). Conclusions: Otolaryngology has exhibited great progress in increasing female representation, with assistant professorship in the West reaching gender parity. However, the gender gap at other faculty levels still leaves much to be desired, particularly in senior ranks. The lack of otolaryngologists at senior ranks is detrimental to mentorship of junior faculty, residents, and medical students. Renewed efforts should be made to decrease the gender disparity in the South, Northeast, and particularly at the professorship level.

Embolization in Juvenile Nasopharyngeal Angiofibroma Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare outcomes of juvenile nasopharyngeal angiofibroma (JNA) resection between embolized and non-embolized cohorts, and between transarterial embolization (TAE) and direct puncture embolization (DPE). DATA SOURCES: Per PRISMA guidelines, PubMed, Embase, Web of Science, Scopus, and Cochrane databases were searched for publications prior to or in 2021. MATERIALS AND METHODS: Original English manuscripts investigating the resection of JNA with and without preoperative embolization were included. Embolization type, recurrence rate, complication rates, blood loss, and transfusions were extracted. Risk of bias was assessed by the Risk of Bias in Non-randomized Studies-of Interventions method. RESULTS: There were 61 studies with 917 patients included. Preoperative embolization was performed in 79.3% of patients. Of those embolized, 75.8% (N = 551) underwent TAE and 15.8% (N = 115) underwent DPE. JNA recurrence in embolized patients was lower than in non-embolized patients (9.3% vs. 14.4%; odds ratio [OR]: 0.61, 95% confidence interval [CI]: 0.35, 1.06). DPE resulted in lower rates of disease recurrence (0% vs. 9.5%; OR: 0.066, 95% CI: 0.016, 0.272) and complications (1.8% vs. 21.9%; OR: 0.07, 95% CI: 0.02, 0.3) than TAE. A random effects Bayesian model was performed to analyze the difference in mean blood loss in 6 studies that included both embolized and non-embolized patients. This analysis showed a mean reduction in blood loss of 798 mL in the embolized group. CONCLUSIONS: We found embolization decreases blood loss in JNA resection. DPE led to improved recurrence and complication rates when compared to TAE, but future prospective studies are needed to further evaluate which embolization technique can optimize outcomes in JNA. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1529-1539, 2023.

IRF4 expression by lung dendritic cells drives acute but not Trm cell-dependent memory Th2 responses.

Expression of the transcription factor interferon regulatory factor 4 (IRF4) is required for the development of lung conventional DCs type 2 (cDC2s) that elicit Th2 responses, yet how IRF4 functions in lung cDC2s throughout the acute and memory allergic response is not clear. Here, we used a mouse model that loses IRF4 expression after lung cDC2 development to demonstrate that mice with IRF4-deficient DCs display impaired memory responses to allergen. This defect in the memory response was a direct result of ineffective Th2 induction and impaired recruitment of activated effector T cells to the lung after sensitization. IRF4-deficient DCs demonstrated defects in their migration to the draining lymph node and in T cell priming. Finally, T cells primed by IRF4-competent DCs mediated potent memory responses independently of IRF4-expressing DCs, demonstrating that IRF4-expressing DCs are not necessary during the memory response. Thus, IRF4 controlled a program in mature DCs governing Th2 priming and effector responses, but IRF4-expressing DCs were dispensable during tissue-resident memory T cell-dependent memory responses.

Measuring SARS-CoV-2 aerosolization in rooms of hospitalized patients.

Objective: Airborne spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a significant risk for healthcare workers. Understanding transmission of SARS-CoV-2 in the hospital could help minimize nosocomial infection. The objective of this pilot study was to measure aerosolization of SARS-CoV-2 in the hospital rooms of COVID-19 patients. Methods: Two air samplers (Inspirotec) were placed 1 and 4 m away from adults with SARS-CoV-2 infection hospitalized at an urban, academic tertiary care center from June to October 2020. Airborne SARS-CoV-2 concentration was measured by quantitative reverse transcription polymerase chain reaction and analyzed by clinical parameters and patient demographics. Results: Thirteen patients with COVID-19 (eight females [61.5%], median age: 57 years old, range 25-82) presented with shortness of breath (100%), cough (38.5%) and fever (15.4%). Respiratory therapy during air sampling varied: mechanical ventilation via endotracheal tube (n = 3), high flow nasal cannula (n = 4), nasal cannula (n = 4), respiratory helmet (n = 1), and room air (n = 1). SARS-CoV-2 RNA was identified in rooms of three out of three intubated patients compared with one out of 10 of the non-intubated patients (p = .014). Airborne SARS-CoV-2 tended to decrease with distance (1 vs. 4 m) in rooms of intubated patients. Conclusions: Hospital rooms of intubated patients had higher levels of aerosolized SARS-CoV-2, consistent with increased aerosolization of virus in patients with severe disease or treatment with positive pressure ventilation through an endotracheal tube. While preliminary, these data have safety implications for health care workers and design of protective measures in the hospital. Level of Evidence: 2.

Beyond the Lung: Geriatric Conditions Afflict Community-Dwelling Older Adults With Self-Reported Chronic Obstructive Pulmonary Disease.

RATIONALE: Chronic obstructive pulmonary disease (COPD) predominantly affects older adults. However, the co-morbid occurrence of geriatric conditions has been understudied. OBJECTIVE: Characterize the prevalence of geriatric conditions among community-dwelling U.S. older adults with self-reported COPD. METHODS: We conducted a nationally representative, cross-sectional study of 3,005 U.S. community-dwelling older adults (ages 57-85 years) from the National Social Life, Health, and Aging Project (NSHAP). We evaluated the prevalence of select geriatric conditions (multimorbidity, functional disability, impaired physical function, low physical activity, modified frailty assessment, falls, polypharmacy, and urinary incontinence) and psychosocial measures (frequency of socializing, sexual activity in the last year, loneliness, cognitive impairment, and depressive symptoms) among individuals with self-reported COPD as compared to those without. Using multivariate logistic and linear regressions, we investigated the relationships between COPD and these geriatric physical and psychosocial conditions. MAIN RESULTS: Self-reported COPD prevalence was 10.7%, similar to previous epidemiological studies. Individuals with COPD had more multimorbidity [modified Charlson score 2.6 (SD 1.9) vs. 1.6 (SD 1.6)], more functional disability (58.1 vs. 29.6%; adjusted OR 3.1, 95% CI 2.3, 4.3), falls in the last year (28.4 vs. 20.8%; adjusted OR 1.4, 95% CI 1.01, 2.0), impaired physical function (75.8 vs. 56.6%; adjusted OR 2.1, 95% CI 1.1, 3.7), more frequently reported extreme low physical activity (18.7 vs. 8.1%; adjusted OR 2.3, 95% CI 1.5, 3.5) and higher frailty prevalence (16.0 vs. 2.7%; adjusted OR 6.3, 95% CI 3.0,13.0) than those without COPD. They experienced more severe polypharmacy (≥10 medications, 37.5 vs. 16.1%; adjusted OR 2.9, 95% CI 2.0, 4.2). They more frequently reported extreme social disengagement and were lonelier, but the association with social measures was eliminated when relationship status was accounted for, as those with COPD were less frequently partnered. They more frequently endorsed depressive symptoms (32.0 vs. 18.9%, adjusted OR 1.9, 95% CI 1.4, 2.7). There was no noted difference in cognitive impairment between the two populations. CONCLUSIONS: Geriatric conditions are common among community-dwelling older adults with self-reported COPD. A "beyond the lung" approach to COPD care should center on active management of geriatric conditions, potentially leading to improved COPD management, and quality of life.

One-Pot Self-Assembly of Dinuclear, Tetranuclear, and H-Bonding-Directed Polynuclear Cobalt(II), Cobalt(III), and Mixed-Valence Co(II)/Co(III) Complexes of Schiff Base Ligands with Incomplete Double Cubane Core.

The reaction of 2,6-diformyl-4-methylphenol (DFMF) with 1-amino-2-propanol (AP) and tris(hydroxymethyl)aminomethane (THMAM) was investigated in the presence of Cobalt(II) salts, (X = ClO4-, CH3CO2-, Cl-, NO3-), sodium azide (NaN3), and triethylamine (TEA). In one pot, the variation in Cobalt(II) salt results in the self-assembly of dinuclear, tetranuclear, and H-bonding-directed polynuclear coordination complexes of Cobalt(III), Cobalt(II), and mixed-valence CoIICoIII: [Co2III(H2L-1)2(AP-1)(N3)](ClO4)2 (1), [Co4(H2L-1)2(µ3-1,1,1-N3)2(µ-1,1-N3)2Cl2(CH3OH)2]·4CH3OH (2), [Co2IICo2III(HL-2)2(µ-CH3CO2)2(µ3-OH)2](NO3)2·2CH3CH2OH (3), and [Co2IICo2III (H2L12-)2(THMAM-1)2](NO3)4 (4). In 1, two cobalt(III) ions are connected via three single atom bridges; two from deprotonated ethanolic oxygen atoms in the side arms of the ligands and one from the1-amino-2-propanol moiety forming a dinuclear unit with a very short (2.5430(11) Å) Co-Co intermetallic separation with a coordination number of 7, a rare feature for cobalt(III). In 2, two cobalt(II) ions in a dinuclear unit are bridged through phenoxide O and µ3-1,1,1-N3 azido bridges, and the two dinuclear units are interconnected by two µ-1,1-N3 and two µ3-1,1,1-N3 azido bridges generating tetranuclear cationic [Co4(H2L-1)2(µ3-1,1,1-N3)2(µ-1,1-N3)2Cl2(CH3OH)2]2+ units with an incomplete double cubane core, which grow into polynuclear 1D-single chains along the a-axis through H-bonding. In 3, HL2- holds mixed-valent Co(II)/Co(III) ions in a dinuclear unit bridged via phenoxide O, µ-1,3-CH3CO2-, and µ3-OH- bridges, and the dinuclear units are interconnected through two deprotonated ethanolic O in the side arms of the ligands and two µ3-OH- bridges generating cationic tetranuclear [Co2IICo2III(HL-2)2(µ-CH3CO2)2(µ3-OH)2]2+ units with an incomplete double cubane core. In 4, H2L1-2 holds mixed-valent Co(II)/Co(III) ions in dinuclear units which dimerize through two ethanolic O (µ-RO-) in the side arms of the ligands and two ethanolic O (µ3-RO-) of THMAM bridges producing centrosymmetric cationic tetranuclear [Co2IICo2III (H2L1-2)2(THMAM-1)2]4+ units which grow into 2D-sheets along the bc-axis through a network of H-bonding. Bulk magnetization measurements on 2 demonstrate that the magnetic interactions are completely dominated by an overall ferromagnetic coupling occurring between Co(II) ions.

Self-Assembly of Antiferromagnetically-Coupled Copper(II) Supramolecular Architectures with Diverse Structural Complexities.

The self-assembly of 2,6-diformyl-4-methylphenol (DFMP) and 1-amino-2-propanol (AP)/2-amino-1,3-propanediol (APD) in the presence of copper(II) ions results in the formation of six new supramolecular architectures containing two versatile double Schiff base ligands (H3L and H5L1) with one-, two-, or three-dimensional structures involving diverse nuclearities: tetranuclear [Cu4(HL2-)2(N3)4]·4CH3OH·56H2O (1) and [Cu4(L3-)2(OH)2(H2O)2] (2), dinuclear [Cu2(H3L12-)(N3)(H2O)(NO3)] (3), polynuclear {[Cu2(H3L12-)(H2O)(BF4)(N3)]·H2O}n (4), heptanuclear [Cu7(H3L12-)2(O)2(C6H5CO2)6]·6CH3OH·44H2O (5), and decanuclear [Cu10(H3L12-)4(O)2(OH)2(C6H5CO2)4] (C6H5CO2)2·20H2O (6). X-ray studies have revealed that the basic building block in 1, 3, and 4 is comprised of two copper centers bridged through one µ-phenolate oxygen atom from HL2- or H3L12-, and one µ-1,1-azido (N3-) ion and in 2, 5, and 6 by µ-phenoxide oxygen of L3- or H3L12- and µ-O2- or µ3-O2- ions. H-bonding involving coordinated/uncoordinated hydroxy groups of the ligands generates fascinating supramolecular architectures with 1D-single chains (1 and 6), 2D-sheets (3), and 3D-structures (4). In 5, benzoate ions display four different coordination modes, which, in our opinion, is unprecedented and constitutes a new discovery. In 1, 3, and 5, Cu(II) ions in [Cu2] units are antiferromagnetically coupled, with J ranging from -177 to -278 cm-1.

A Screened GPR1 Peptide Exerts Antitumor Effects on Triple-Negative Breast Cancer.

The adipokine chemerin has been considered an important regulator of tumor immune surveillance. Chemerin recruits leukocytes through the receptor CMKLR1 to improve clinical outcomes of tumors and overall patient survival, but the role of GPR1 in tumors has not been widely investigated. Here, we found that GPR1 expression is elevated in breast cancer-especially triple-negative breast cancer (TNBC) tissues and cell lines. Herein, we screened a phage display peptide library to identify LRH7-G5, a peptide antagonist that blocks chemerin/GPR1 signaling. This peptide performed as an anticancer agent to suppress the proliferation of the TNBC cell lines MDA-MB-231 and HCC1937 but has little effect on T47D cells. LRH7-G5 treatment significantly blocked tumor growth in a TNBC cell-bearing orthotopic mouse model. Last, our results showed that this peptide's antitumor role is mediated through the PI3K/AKT signaling pathway. In conclusion, these data collectively suggest that the chemerin receptor GPR1 is a novel target for controlling TNBC progression and establish peptide LRH7-G5 as a new therapeutic agent for suppressing TNBC tumor growth.

Placenta-Derived Osteoprotegerin Is Required for Glucose Homeostasis in Gestational Diabetes Mellitus.

Osteoprotegerin (OPG) is involved in various biological processes, including bone remodeling, vascular calcification and pancreatic ß-cell function. Although some clinical studies have shown an increase in serum OPG level during pregnancy, the role of OPG in gestational diabetes mellitus (GDM) is largely unknown. Therefore, we explored the effect of OPG in metabolic homeostasis during pregnancy. We initially evaluated serum OPG levels using ELISA and western blotting techniques on samples from GDM patients. We also assessed OPG expression levels in maternal mice. We then used blastocysts transduced with lentiviruses capable of trophoblast-specific transgene expression to establish placenta-specific OPG knockdown or overexpression mouse models for functional and mechanistic investigation after embryo transplantation. We found that OPG expression was positively associated with GDM in clinical samples, and OPG levels were significantly increased in GDM patient sera and term placenta. Serum OPG was significantly increased in maternal compared to non-pregnant mice, and expression levels of OPG were the highest in placenta compared with other organs, including bone, liver and pancreas. OPG was also significantly increased in pregnant mice fed a high-fat diet (HFD). Placenta-specific OPG knockdown induced glucose intolerance, decreased ß-cell proliferation and decreased serum insulin levels, whereas placenta-specific OPG overexpression promoted glucose tolerance and enhanced ß-cell proliferation, which increased serum insulin production and decreased fetal weight in HFD-feeding pregnant mice. Placenta-derived OPG (pl-OPG) regulated glucose homeostasis during pregnancy via enhancement of ß-cell proliferation, which suggests a potential therapeutic application of OPG for GDM.

A Flexible Strategy for Modular Synthesis of Curcuminoid-BF2 /Curcuminoid Pairs and Their Comparative Antiproliferative Activity in Human Cancer Cell Lines.

A facile protocol that enables synthetic interconversion of CUR-BF2 and CUR compounds is described that significantly widens the preparative scope of curcuminoids, providing access to larger libraries of compounds, thus enabling comparative antiproliferative and apoptotic study of a larger library of synthetic analogs in cancer cell lines.

Role of G protein-coupled receptor 1 in choriocarcinoma progression.

Choriocarcinoma is characterized by malignant proliferation and transformation of trophoblasts and is currently treated with systemic chemotherapeutic agents. The lack of specific targets for chemotherapeutic agents results in indiscriminate drug distribution. In our study, we aimed to delineate the mechanism by which G protein-coupled receptor 1 (GPR1) regulates the development of choriocarcinoma and thus investigated GPR1 as a prospective chemotherapeutic target. In this study, GPR1 expression levels were examined in several trophoblast cell lines. We found significantly higher GPR1 expression in choriocarcinoma cells (JEG3 and BeWo) than in normal trophoblast cells (HTR-8/SVneo). Additionally, we studied the role of GPR1 in choriocarcinoma in vitro and in vivo. GPR1 knockdown suppressed proliferation, invasion, and Akt and ERK phosphorylation in vitro and slowed tumor growth in vivo. Interestingly, GPR1 overexpression promoted increased proliferation, invasion, and Akt and ERK phosphorylation in vitro. Furthermore, we identified a specific GPR1-binding seven-amino acid peptide, LRH7-G3, that might also suppress choriocarcinoma in vitro and in vivo through phage display. Our study is the first to report that GPR1 may play a role in regulating choriocarcinoma progression through the Akt and ERK pathways. GPR1 could be a promising potential pharmaceutical target for choriocarcinoma.

Hyaluronan in immune dysregulation and autoimmune diseases.

The tissue microenvironment contributes to local immunity and to the pathogenesis of autoimmune diseases - a diverse set of conditions characterized by sterile inflammation, immunity against self-antigens, and destruction of tissues. However, the specific factors within the tissue microenvironment that contribute to local immune dysregulation in autoimmunity are poorly understood. One particular tissue component implicated in multiple autoimmune diseases is hyaluronan (HA), an extracellular matrix (ECM) polymer. HA is abundant in settings of chronic inflammation and contributes to lymphocyte activation, polarization, and migration. Here, we first describe what is known about the size, amount, and distribution of HA at sites of autoimmunity and in associated lymphoid structures in type 1 diabetes, multiple sclerosis, and rheumatoid arthritis. Next, we examine the recent literature on HA and its impact on adaptive immunity, particularly in regards to the biology of lymphocytes and Foxp3+ regulatory T-cells (Treg), a T-cell subset that maintains immune tolerance in healthy individuals. We propose that HA accumulation at sites of chronic inflammation creates a permissive environment for autoimmunity, characterized by CD44-mediated inhibition of Treg expansion. Finally, we address potential tools and strategies for targeting HA and its receptor CD44 in chronic inflammation and autoimmunity.

The effects of autoimmune blistering diseases on work productivity: A review.

This review examines the work productivity in patients with autoimmune blistering diseases (AIBDs). Work productivity and employment are important aspects of a patient's life, which can be affected by diseases. The Work Productivity and Activity Impairment Questionnaire (WPAIQ) is a validated instrument that can measure work productivity and assess the impact of disease on patients' work lives. There is currently a paucity of research that investigates the reason why AIBDs cause such a large impact on work productivity and whether AIBDs affect employment status. Using quality of life (QoL) instruments in conjunction with the creation of an adapted WPAIQ to examine the reasons behind work impairment may further characterize these effects and unveil a deeper understanding of stigmatization in the workplace as a factor of loss of work productivity.