Racial Disparities in Obesity Treatment Byrd, Angel S.; Toth, Alexander T.; Stanford, Fatima Cody
Current obesity reports,
06/2018, Letnik:
7, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Purpose of Review
Obesity rates in the USA have reached pandemic levels with one third of the population with obesity in 2015–2016 (39.8% of adults and 18.5% of youth). It is a major public health ...concern, and it is prudent to understand the factors which contribute. Racial and ethnic disparities are pronounced in both the prevalence and treatment of obesity and must be addressed in the efforts to combat obesity.
Recent Findings
Disparities in prevalence of obesity in racial/ethnic minorities are apparent as early as the preschool years and factors including genetics, diet, physical activity, psychological factors, stress, income, and discrimination, among others, must be taken into consideration. A multidisciplinary team optimizes lifestyle and behavioral interventions, pharmacologic therapy, and access to bariatric surgery to develop the most beneficial and equitable treatment plans.
Summary
The reviewed studies outline disparities that exist and the impact that race/ethnicity have on disease prevalence and treatment response. Higher prevalence and reduced treatment response to lifestyle, behavior, pharmacotherapy, and surgery, are observed in racial and ethnic minorities. Increased research, diagnosis, and access to treatment in the pediatric and adult populations of racial and ethnic minorities are proposed to combat the burgeoning obesity epidemic and to prevent increasing disparity.
The armament of neutrophil-mediated host defense against pathogens includes the extrusion of a lattice of DNA and microbicidal enzymes known as neutrophil extracellular traps (NETs). The ...receptor/ligand interactions and intracellular signaling mechanisms responsible for elaborating NETs were determined for the response to Candida albicans. Because the host response of extravasated neutrophils to mycotic infections within tissues necessitates contact with extracellular matrix, this study also identified a novel and significant regulatory role for the ubiquitous matrix component fibronectin (Fn) in NET release. We report that recognition of purified fungal pathogen-associated molecular pattern β-glucan by human neutrophils causes rapid (≤ 30 min) homotypic aggregation and NET release by a mechanism that requires Fn. Alone, immobilized β-glucan induces reactive oxygen species (ROS) production but not NET release, whereas in the context of Fn, ROS production is suppressed and NETs are extruded. NET release to Fn with β-glucan is robust, accounting for 17.2 ± 3.4% of total DNA in the cell population. Release is dependent on β-glucan recognition by complement receptor 3 (CD11b/CD18), but not Dectin-1, or ROS. The process of NET release included filling of intracellular vesicles with nuclear material that was eventually extruded. We identify a role for ERK in homotypic aggregation and NET release. NET formation to C. albicans hyphae was also found to depend on β-glucan recognition by complement receptor 3, require Fn and ERK but not ROS, and result in hyphal destruction. We report a new regulatory mechanism of NETosis in which the extracellular matrix is a key component of the rapid antifungal response.
Hidradenitis suppurativa in skin of colour Zouboulis, Christos C.; Goyal, Mankul; Byrd, Angel S.
Experimental dermatology,
June 2021, 2021-06-00, 20210601, Letnik:
30, Številka:
S1
Journal Article
Recenzirano
Hidradenitis suppurativa/acne inversa (HS) more prevalent and disproportionally affects African American females. Although there are limited studies in HS skin of colour populations in the USA, there ...is more scarcity of HS skin of colour studies in other countries, which limits the overall understanding of the disease among these patients. Herein, our overview of the 10th European Hidradenitis Suppurativa Foundation (EHSF) e.V. Conference provided a crude example of the limited number of skin of colour physicians, physician scientists and inclusion of skin of colour patients highlighting the need to increase awareness of this important issue. We summarized the epidemiology, pathogenesis, clinical picture and focused on treatment options from southeast Asia and Africa. Our outlined general recommendations for diagnosis will render better clinical care and outcomes for diverse patient populations.
Hidradenitis suppurativa (HS) is a debilitating inflammatory skin disorder characterized by abscess-like nodules and boils resulting in fistulas and tissue scarring. We previously reported evidence ...of an autoimmune signature in HS, characterized by enhanced neutrophil extracellular trap (NET) infiltration in HS skin lesions and dysregulation of the adaptive immune system characterized by the presence of autoantibodies. Timely removal of NETs is critical for tissue homeostasis to prevent a dysregulated generation of modified autoantigens and tissue damage. DNases 1 and 1L3 play important roles in proper NET removal. We tested the hypothesis that NETs in patients with HS are not effectively cleared owing to the presence of antibodies against DNase 1 and DNase 1L3. We report that HS serum poorly degraded NETs. Addition of exogenous DNase 1 restored NET degradation capabilities in a subset of HS samples. DNase 1 activity was significantly decreased in HS sera. Anti‒DNase 1 and ‒DNase 1L3 antibodies were detected in serum samples and skin lesions from patients with HS. Purified IgGs from HS decreased DNase 1 activity and NET degradation. Taken together, this identification of neutralizing antibodies against nucleases in HS expands the understanding of the pathogenesis of this disease to support an autoimmune mechanism in its underlying pathogenesis.
What causes hidradenitis suppurativa ?—15 years after Zouboulis, Christos C.; Benhadou, Farida; Byrd, Angel S. ...
Experimental dermatology,
December 2020, 2020-12-00, 20201201, Letnik:
29, Številka:
12
Journal Article
Recenzirano
Odprti dostop
The 14 authors of the first review article on hidradenitis suppurativa (HS) pathogenesis published 2008 in EXPERIMENTAL DERMATOLOGY cumulating from the 1st International Hidradenitis Suppurativa ...Research Symposium held March 30–April 2, 2006 in Dessau, Germany with 33 participants were prophetic when they wrote “Hopefully, this heralds a welcome new tradition: to get to the molecular heart of HS pathogenesis, which can only be achieved by a renaissance of solid basic HS research, as the key to developing more effective HS therapy.” (Kurzen et al. What causes hidradenitis suppurativa? Exp Dermatol 2008;17:455). Fifteen years later, there is no doubt that the desired renaissance of solid basic HS research is progressing with rapid steps and that HS has developed deep roots among inflammatory diseases in Dermatology and beyond, recognized as “the only inflammatory skin disease than can be healed”. This anniversary article of 43 research‐performing authors from all around the globe in the official journal of the European Hidradenitis Suppurativa Foundation e.V. (EHSF e.V.) and the Hidradenitis Suppurativa Foundation, Inc (HSF USA) summarizes the evidence of the intense HS clinical and experimental research during the last 15 years in all aspects of the disease and provides information of the developments to come in the near future.
Hidradenitis suppurativa (HS), also known as acne inversa, is a debilitating inflammatory skin disorder that is characterized by nodules that lead to the development of connected tunnels and scars as ...it progresses from Hurley stages I to III. HS has been associated with several autoimmune diseases, including inflammatory bowel disease and spondyloarthritis. We previously reported dysregulation of humoral immune responses in HS, characterized by elevated serum total IgG, B-cell activation, and antibodies recognizing citrullinated proteins. In this study, we characterized IgG autoreactivity in HS sera and lesional skin compared with those in normal healthy controls using an array-based high-throughput autoantibody screening. The Cy3-labeled anti–human assay showed the presence of autoantibodies against nuclear antigens, cytokines, cytoplasmic proteins, extracellular matrix proteins, neutrophil proteins, and citrullinated antigens. Most of these autoantibodies were significantly elevated in stages II‒III in HS sera and stage III in HS skin lesions compared with those of healthy controls. Furthermore, immune complexes containing both native and citrullinated versions of antigens can activate M1 and M2 macrophages to release proinflammatory cytokines such as TNF-α, IL-8, IL-6, and IL-12. Taken together, the identification of specific IgG autoantibodies that recognize circulating and tissue antigens in HS suggests an autoimmune mechanism and uncovers putative therapeutic targets.
T cell cytokines contribute to immunity against Staphylococcus aureus, but the predominant T cell subsets involved are unclear. In an S. aureus skin infection mouse model, we found that the IL- 17 ...response was mediated by γδ T cells, which trafficked from lymph nodes to the infected skin to induce neutrophil recruitment, proinflammatory cytokines IL-1α, IL-1β, and TNF, and host defense peptides. RNA-seq for TRG and TRD sequences in lymph nodes and skin revealed a single clonotypic expansion of the encoded complementarity-determining region 3 amino acid sequence, which could be generated by canonical nucleotide sequences of TRGV5 or TRGV6 and TRDV4. However, only TRGV6 and TRDV4 but not TRGV5 sequences expanded. Finally, Vγ6⁺ T cells were a predominant γδ T cell subset that produced IL-17A as well as IL-22, TNF, and IFNγ, indicating a broad and substantial role for clonal Vγ6⁺Vδ4⁺ T cells in immunity against S. aureus skin infections.
Dyschromia is the result of irregular facial pigmentation. These cutaneous manifestations can have a significant impact on the quality of life of those affected, especially among females and skin of ...color. In this randomized, double-blinded, two-cell, single-center, 16-week clinical study, all subjects had moderate to severe (scores 4-9 on the modified Griffiths Scale) hyperpigmentation and skin unevenness of the face such that approximately 20% of subjects had post-inflammatory hyperpigmentation (PIH), 40% had overall mottled hyperpigmentation, and 40% had superficial melasma (Superficial Melasma was determined by Wood's Lamp Assessment). Study participants received either Product A (proprietary new formulation - Cysteamine HSA) or Product B (current marketed product - Cyspera®) and used the test product either in the morning or at night, beginning with every other day application, and then advanced to every day, or as tolerated. The results revealed that both Product A (Cysteamine HSA) and Product B (Cyspera®) had statistically significant improvement in facial hyperpigmentation and skin unevenness, however, Product A (Cysteamine HSA) had better tolerability results for scaling, peeling, burning, stinging, erythema, and dryness, indicating that Product A (Cysteamine HSA) outperformed Product B (Cyspera®). J Drugs Dermatol. 2024;23(1):1260-1265. doi:10.36849/JDD.7584.
PDF
