RESUMEN
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.
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Cara , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Adulto , Cara/anatomía & histología , Cara/diagnóstico por imagen , Cara/cirugía , Cirugía de Reasignación de Sexo/métodos , Etnicidad , Personas Transgénero , Antropometría/métodos , Estudios RetrospectivosRESUMEN
Controlling traumatic bleeding from damaged internal organs while effectively sealing the wound is critical for saving the lives of patients. Existing bioadhesives suffer from blood incompatibility, insufficient adhesion to wet surfaces, weak mechanical properties, and complex application procedures. Here, we engineered a ready-to-use hemostatic bioadhesive with ultra-strengthened mechanical properties and fatigue resistance, robust adhesion to wet tissues within a few seconds of gentle pressing, deformability to accommodate physiological function and action, and the ability to stop bleeding efficiently. The engineered hydrogel, which demonstrated high elasticity (>900%) and toughness (>4600 kJ/m3), was formed by fine-tuning a series of molecular interactions and crosslinking mechanisms involving N-hydroxysuccinimide (NHS) conjugated alginate (Alg-NHS), poly (ethylene glycol) diacrylate (PEGDA), tannic acid (TA), and Fe3+ ions. Dual adhesive moieties including mussel-inspired pyrogallol/catechol and NHS synergistically enhanced wet tissue adhesion (>400 kPa in a wound closure test). In conjunction with physical sealing, the high affinity of TA/Fe3+ for blood could further augment hemostasis. The engineered bioadhesive demonstrated excellent in vitro and in vivo biocompatibility as well as improved hemostatic efficacy as compared to commercial Surgicel®. Overall, the hydrogel design strategy described herein holds great promise for overcoming existing obstacles impeding clinical translation of engineered hemostatic bioadhesives.
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Hemostáticos , Humanos , Hemostáticos/farmacología , Adherencias Tisulares , Fenómenos Físicos , Hidrogeles , HemostasisRESUMEN
Type 2 diabetes (T2D) is associated with ß-cell dedifferentiation. Aldehyde dehydrogenase 1 isoform A3 (ALHD1A3) is a marker of ß-cell dedifferentiation and correlates with T2D progression. However, it is unknown whether ALDH1A3 activity contributes to ß-cell failure, and whether the decrease of ALDH1A3-positive ß-cells (A+) following pair-feeding of diabetic animals is due to ß-cell restoration. To tackle these questions, we (i) investigated the fate of A+ cells during pair-feeding by lineage-tracing, (ii) somatically ablated ALDH1A3 in diabetic ß-cells, and (iii) used a novel selective ALDH1A3 inhibitor to treat diabetes. Lineage tracing and functional characterization show that A+ cells can be reconverted to functional, mature ß-cells. Genetic or pharmacological inhibition of ALDH1A3 in diabetic mice lowers glycemia and increases insulin secretion. Characterization of ß-cells following ALDH1A3 inhibition shows reactivation of differentiation as well as regeneration pathways. We conclude that ALDH1A3 inhibition offers a therapeutic strategy against ß-cell dysfunction in diabetes.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Animales , Ratones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/genética , Línea Celular Tumoral , Células Secretoras de Insulina/metabolismo , Familia de Aldehído Deshidrogenasa 1 , Aldehído Oxidorreductasas/metabolismoRESUMEN
Encapsulation and transplantation of insulin-producing cells offer a promising curative treatment for type 1 diabetes (T1D) without immunosuppression. However, biomaterials used to encapsulate cells often elicit foreign body responses, leading to cellular overgrowth and deposition of fibrotic tissue, which in turn diminishes mass transfer to and from transplanted cells. Meanwhile, the encapsulation device must be safe, scalable, and ideally retrievable to meet clinical requirements. Here, a durable and safe nanofibrous device coated with a thin and uniform, fibrosis-mitigating, zwitterionically modified alginate hydrogel for encapsulation of islets and stem cell-derived beta (SC-ß) cells is reported. The device with a configuration that has cells encapsulated within the cylindrical wall, allowing scale-up in both radial and longitudinal directions without sacrificing mass transfer, is designed. Due to its facile mass transfer and low level of fibrotic reactions, the device supports long-term cell engraftment, correcting diabetes in C57BL6/J mice with rat islets for up to 399 days and SCID-beige mice with human SC-ß cells for up to 238 days. The scalability and retrievability in dogs are further demonstrated. These results suggest the potential of this new device for cell therapies to treat T1D and other diseases.
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Diabetes Mellitus Experimental , Insulinas , Trasplante de Islotes Pancreáticos , Animales , Diabetes Mellitus Experimental/terapia , Perros , Fibrosis , Trasplante de Islotes Pancreáticos/métodos , Ratones , Ratones SCID , RatasRESUMEN
Islet transplantation has shown promise as a curative therapy for type 1 diabetes (T1D). However, the side effects of systemic immunosuppression and limited long-term viability of engrafted islets, together with the scarcity of donor organs, highlight an urgent need for the development of new, improved, and safer cell-replacement strategies. Induction of local immunotolerance to prevent allo-rejection against islets and stem cell derived ß cells has the potential to improve graft function and broaden the applicability of cellular therapy while minimizing adverse effects of systemic immunosuppression. In this mini review, recent developments in non-encapsulation, local immunomodulatory approaches for T1D cell replacement therapies, including islet/ß cell modification, immunomodulatory biomaterial platforms, and co-transplantation of immunomodulatory cells are discussed. Key advantages and remaining challenges in translating such technologies to clinical settings are identified. Although many of the studies discussed are preliminary, the growing interest in the field has led to the exploration of new combinatorial strategies involving cellular engineering, immunotherapy, and novel biomaterials. Such interdisciplinary research will undoubtedly accelerate the development of therapies that can benefit the whole T1D population.
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Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/cirugía , Rechazo de Injerto/prevención & control , Inmunomodulación/inmunología , Células Secretoras de Insulina/trasplante , Trasplante de Islotes Pancreáticos/métodos , Rechazo de Injerto/inmunología , HumanosRESUMEN
Hydrogels with adhesive properties have potential for numerous biomedical applications. Here, the design of a novel, intrinsically adhesive hydrogel and its use in developing internal therapeutic bandages is reported. The design involves incorporation of "triple hydrogen bonding clusters" (THBCs) as side groups into the hydrogel matrix. The THBC through a unique "load sharing" effect and an increase in bond density results in strong adhesions of the hydrogel to a range of surfaces, including glass, plastic, wood, poly(tetrafluoroethylene) (PTFE), stainless steel, and biological tissues, even without any chemical reaction. Using the adhesive hydrogel, tissue-adhesive bandages are developed for either targeted and sustained release of chemotherapeutic nanodrug for liver cancer treatment, or anchored delivery of pancreatic islets for a potential type 1 diabetes (T1D) cell replacement therapy. Stable adhesion of the bandage inside the body enables almost complete tumor suppression in an orthotopic liver cancer mouse model and ≈1 month diabetes correction in chemically induced diabetic mice.