Meal replacement therapy for obesity and diabetes remission: efficacy assessment and considerations of barriers and facilitators to adherence among U.S. individuals with low economic resources.

Individuals in the United States with lower economic resources face a disproportionate burden of obesity and co-morbid conditions. This review summarizes the efficacy of MR programs for the treatment of obesity and diabetes and alerts clinicians to potential barriers and facilitators to the uptake of such programs so they may tailor their prescriptive approach. Implementation of effective behavioral and lifestyle interventions for obesity and diabetes in low-income settings is fraught with barriers and under-studied.

All chronic rhinosinusitis endotype clusters demonstrate improvement in patient-reported and clinical outcome measures after endoscopic sinus surgery.

Background: It is unclear whether chronic rhinosinusitis (CRS) endotypes show a differential response to endoscopic sinus surgery (ESS). We explored patient mucous inflammatory cytokine expression and associations with patient-reported and clinically measured post-operative outcome measures.

Methods: Patients with CRS were prospectively recruited between 2016 and 2021 into a national multicenter, observational study.

Sinonasal IgG4-related sclerosing disease: A rare entity and challenging diagnosis.

Objectives: To describe the rare presentation, imaging and histological findings, and treatments in patients with IgG4-related disease (IgG4-RD) and diagnostic pitfalls and difficulties.

Methods: Cases of sinonasal IgG4-RD were retrieved, and clinicopathological features were reviewed.

Results: Seven cases of sinonasal IgG4-RD were identified over an 11-year period, including four males and three females, with an age range of 19-66 years (median 58 years).

Utilization of Nasal Mucus to Investigate the Pathophysiology of Chronic Rhinosinusitis.

Background: Nasal mucus is proving to be a useful means by which to study the pathogenesis of chronic rhinosinusitis (CRS). Given the increase in publications examining nasal mucus and the lack of a review on this topic, we will focus on this noninvasive approach to studying CRS. Particular attention will be drawn towards inflammatory cytokines and biomarkers and their influence on disease severity.

Role of C3a as a Novel Regulator of 25(OH)D to 1α,25-Dihydroxyvitamin D Metabolism in Upper Airway Epithelial Cells.

In patients with chronic rhinosinusitis with nasal polyps, primary human sinonasal epithelial cell (HSNEC) 1α-hydroxylase levels are reduced, as is their ability to metabolize 25-hydroxycholecalciferol [25(OH)D] to its active metabolite, 1α,25-dihydroxyvitamin D [1,25(OH)D]. In this study, we sought to identify the factor responsible for the regulation of HSNEC metabolism of 25(OH)D, focusing on C3 and C3a. Multiple inhaled irritants trigger the release of complement components, C3 and C3a, leading to suppression of 1α-hydroxylase levels in HSNECs.

Sociodemographic factors affecting perceived stress during pregnancy and the association with immune-mediator concentrations.

Objectives: Determine which sociodemographic factors are most associated with increased maternal perceived stress during pregnancy. Evaluate the association between maternal stress and plasma immune-mediator concentrations (IMCs).

Methods: As part of a prospective, randomized clinical trial, 247 participants completed a Perceived Stress Scale survey (PSS-10) during each trimester of pregnancy.

Modulating donor mitochondrial fusion/fission delivers immunoprotective effects in cardiac transplantation.

Early insults associated with cardiac transplantation increase the immunogenicity of donor microvascular endothelial cells (ECs), which interact with recipient alloreactive memory T cells and promote responses leading to allograft rejection. Thus, modulating EC immunogenicity could potentially alter T cell responses. Recent studies have shown modulating mitochondrial fusion/fission alters immune cell phenotype.

Dexamethasone Alters Tracheal Aspirate T-Cell Cytokine Production in Ventilated Preterm Infants.

Postnatal corticosteroids improve respiratory status and facilitate respiratory support weaning in preterm infants with bronchopulmonary dysplasia (BPD). Older literature describes characteristic cytokine profiles in tracheal aspirates (TA) of BPD patients which are altered with corticosteroids. Corticosteroids also influence peripheral blood T-cell presence.

Endotyping chronic rhinosinusitis based on olfactory cleft mucus biomarkers.

Background: Although chronic rhinosinusitis (CRS) is considered the most treatable form of olfactory dysfunction, there has been relatively little clinical attention focused on assessing endotypes as they pertain to olfactory loss.

Objectives: The goal of this study was to explore inflammatory endotypes in CRS using an unsupervised cluster analysis of olfactory cleft (OC) biomarkers in a phenotype-free approach.

Methods: Patients with CRS were prospectively recruited and psychophysical olfactory testing, Questionnaire of Olfactory Dysfunction (QOD-NS), and bilateral OC endoscopy were obtained.

Olfactory cleft mucus proteome in chronic rhinosinusitis: a case-control pilot study.

Background: Mechanisms of smell loss in chronic rhinosinusitis (CRS) are still unclear and likely multifactorial. Little attention has been given to olfactory cleft (OC) mucus proteins involved in odorant binding and metabolizing enzymes and their potential role in smell loss.

Methods: Mucus from the OC was sampled from patients with CRS (n = 20) and controls (n = 10).

A Community-Based Study on the Prevalence of Olfactory Dysfunction.

Background: Olfactory dysfunction (OD) is common, affecting an estimated 13 million adults in the United States. Prior studies may underestimate OD prevalence due to use of brief smell identification tests or age-adjusted cutoff values, which concede that it is acceptable for older people to have a decreased sense of smell.

Objective: To determine OD prevalence in the healthy community when the goal and expectation is ideal olfactory function, rather than age-based population norms.

Effects of vitamin D supplementation on circulating concentrations of growth factors and immune-mediators in healthy women during pregnancy.

Background: For the second aim of the Kellogg Foundation grant, this double-blind RCT investigated the impact of plasma vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) on plasma immune-mediators during pregnancy. We hypothesized that higher 25(OH)D concentrations would associate with reduced pro-inflammatory and increased tolerogenic immune-mediator concentrations.

Methods: Pregnant women enrolled at 10-14 weeks gestation were randomized to 400 or 4400 IU vitamin D/day.

Correlation of mucus inflammatory proteins and olfaction in chronic rhinosinusitis.

Background: Chronic rhinosinusitis (CRS) is one of the most common causes of olfactory loss, but the pathophysiology underlying olfactory dysfunction in CRS has not been fully elucidated. Previous studies found correlations between olfactory cleft (OC) inflammatory cytokines/chemokines and olfaction in CRS. The purpose of this study was to evaluate the relationship between OC mucus inflammatory proteins and olfaction in a multi-institutional cohort.

Olfactory cleft mucus proteins associated with olfactory dysfunction in a cohort without chronic rhinosinusitis.

Background: Olfactory dysfunction (OD) is a common problem, affecting up to 20% of the general population. Previous studies identified olfactory cleft mucus proteins associated with OD in chronic rhinosinusitis (CRS) but not in a healthy population. In this study we aimed to identify olfactory cleft mucus proteins associated with olfaction in individuals without sinus disease.

Contribution of Epithelial Cell Dysfunction to the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps.

Background: In the past, the airway epithelium was thought to be primarily an inert physical barrier. We now know that the upper airway epithelium plays a critical role in both innate and adaptive immunity, and that epithelial dysfunction is strongly associated with inflammatory airway disease. The pathogenesis of chronic rhinosinusitis is poorly understood, but growing evidence supports a key role for the airway epithelium in the pathophysiology of the disease.

C3a receptor antagonism as a novel therapeutic target for chronic rhinosinusitis.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease with an unknown etiology. Recent studies have implicated the complement system as a potential modulator of disease immunopathology. We performed proteomic pathway enrichment analysis of differentially increased proteins, and found an enrichment of complement cascade pathways in the nasal mucus of individuals with CRSwNP as compared to control subjects.

Glucocorticoid receptor isoform expression in peripheral blood mononuclear leukocytes of patients with chronic rhinosinusitis.

Background: In several inflammatory disorders, altered peripheral blood mononuclear leukocyte (PBML) glucocorticoid (GC) receptor isoform expression has been associated with GC resistance and disease severity. However, it is unclear if PBML GC receptor isoforms are expressed differentially and are associated with worsened disease severity in chronic rhinosinusitis (CRS).

Methods: PBMLs were isolated from control (n = 8), CRS without nasal polyps (CRSsNP) (n = 8), atopic CRS with nasal polyps (CRSwNP) (n = 8), non-atopic CRSwNP (n = 8), and allergic fungal rhinosinusitis (AFRS) (n = 8) patients.

Novel Radiographic Assessment of the Cribriform Plate.

Background The cribriform plate (CP) is a common site of spontaneous cerebrospinal fluid (SCSF) leaks. Radiographic assessment of the anterior and lateral skull base has shown thinner bone in patients with SCSFs; however, prior assessment of the CP has required postmortem cadaver dissection. Objective To develop novel radiographic techniques to assess the anatomy of the CP.

Impact of Mitochondrial Permeability on Endothelial Cell Immunogenicity in Transplantation.

Background: Microvascular endothelial cells (ECs) are central to an allograft's immunogenicity. Cold ischemia and reperfusion injury associated with static cold storage and warm reperfusion activates ECs and increases the immunogenicity of the allograft. After reperfusion, mitochondrial permeability transition pore (mPTP) opening contributes to mitochondrial dysfunction in the allograft, which correlates to alloimmune rejection.

Sinonasal T-cell expression of cytotoxic mediators granzyme B and perforin is reduced in patients with chronic rhinosinusitis.

Background: CD8+ T cells and natural killer (NK) cells are cytotoxic cells that use granzyme B (GrB) and perforin. Defective cytotoxic function is known to play a role in dysregulated immune response as seen in chronic sinusitis, also referred to as chronic rhinosinusitis (CRS). However, to our knowledge, in the United States, neither GrB or perforin expression has been reported in patients with CRS.

The role of regulatory T cells in the regulation of upper airway inflammation.

Allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP) are inflammatory diseases of the upper airway, with a similar immunologic profile, characterized by aberrant and persistent type 2 inflammation. One cell population that has been identified as altered in both disease types is regulatory T cell (Treg). Tregs have the capacity to modulate T-effector function and suppress inflammatory cytokine production in a broad range of cell types.

Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local 25(OH)D3 metabolism.

Rationale: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be vitamin D3 (VD3) deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic rhinosinusitis (Af-CRS).

Methods: Balb/c mice were fed control or VD3 deficient diet for 4 weeks.