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1.
PLoS One ; 18(3): e0281050, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36920944

RESUMEN

Effective masking policies to prevent the spread of airborne infections depend on public access to masks with high filtration efficacy. However, poor face-fit is almost universally present in pleated multilayer disposable face masks, severely limiting both individual and community respiratory protection. We developed a set of simple mask modifications to mass-manufactured disposable masks, the most common type of mask used by the public, that dramatically improves both their personalized fit and performance in a low-cost and scalable manner. These modifications comprise a user-moldable full mask periphery wire, integrated earloop tension adjusters, and an inner flange to trap respiratory droplets. We demonstrate that these simple design changes improve quantitative fit factor by 320%, triples the level of protection against aerosolized droplets, and approaches the model efficacy of N95 respirators in preventing the community spread of COVID-19, for an estimated additional cost of less than 5 cents per mask with automated production.


Asunto(s)
COVID-19 , Dispositivos de Protección Respiratoria , Humanos , COVID-19/prevención & control , Máscaras , Respiradores N95 , Filtración
2.
Acta Biomater ; 151: 174-182, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-35948175

RESUMEN

Cerebral aneurysms (CA), an abnormal bulge in the arteries that supply blood to the brain, are prone to rupture and can cause hemorrhagic stroke. Physicians can treat CA by blocking blood flow to the aneurysmal sac via clipping of the aneurysm neck via open procedure, or endovascular occlusion of the aneurysm with embolic materials to promote thrombus formation to prevent further inflow of blood into the aneurysm. Endovascular treatment options for CA still have significant limitations in terms of safety, usability in coagulopathic patients, and risks of device migration. Bioactive embolic therapies, consisting of non-toxic bioresorbable materials that encourage the growth of neointima across the aneurysm neck, are needed to improve the healing of CA. In this work, the bioinspired silk-elastinlike protein-based polymer (SELP 815K), was used to embolize aneurysms in a rabbit elastase model. SELP 815K effectively embolized the model aneurysms in vivo, achieving >90% occlusion, using commercial microcatheters. No device-associated adverse effects were observed in any of the animals, and SELP 815K showed no cytotoxicity. SELP embolization did not show any deleterious effects to local tissues, and features consistent with reendothelialization of the aneurysm neck were noted in histological examination one-month post-embolization. SELP 815K shows promise as an embolic treatment for unruptured CA. STATEMENT OF SIGNIFICANCE: Unruptured cerebral aneurysms are present in approximately 3% of the population, with a fatality rate of up to 65% upon rupture. In this work a silk-elastinlike protein polymer (SELP) is explored as a liquid embolic for occlusion of cerebral aneurysms. This embolic exists as a liquid at room temperature before rapidly forming a gel at physiological temperature. This shape filling property was used to successfully occlude cerebral aneurysms in rabbits, with stable occlusion persisting for over thirty days. SELP occlusions show evidence for reendothelialization of the aneurysm sac and provide an opportunity for delivery of bioactive agents to further improve treatments.


Asunto(s)
Embolización Terapéutica , Aneurisma Intracraneal , Animales , Embolización Terapéutica/métodos , Aneurisma Intracraneal/terapia , Elastasa Pancreática , Polímeros , Conejos , Seda , Resultado del Tratamiento
3.
Proc Natl Acad Sci U S A ; 119(15): e2122512119, 2022 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-35380904

RESUMEN

We identified the anti-Mullerian hormone (also known as Müllerian inhibiting substance or MIS) as an inhibitory hormone that induces long-term contraception in mammals. The type II receptor to this hormone, AMHR2 (also known as MISR2), represents a promising druggable target for the modulation of female reproduction with a mechanism of action distinct from steroidal contraceptives. We designed an in vitro platform to screen and validate small molecules that can activate MISR2 signaling and suppress ovarian folliculogenesis. Using a bone morphogenesis protein (BMP)­response element luciferase reporter cell­based assay, we screened 5,440 compounds from a repurposed drug library. Positive hits in this screen were tested for specificity and potency in luciferase dose­response assays, and biological activity was tested in ex vivo Mullerian duct regression bioassays. Selected candidates were further evaluated in ex vivo follicle/ovary culture assays and in vivo in mice and rats. Here, we report that SP600125, CYC-116, gandotinib, and ruxolitinib can specifically inhibit primordial follicle activation and repress folliculogenesis by stimulating the MISR2 pathway.


Asunto(s)
Anticonceptivos , Reposicionamiento de Medicamentos , Folículo Ovárico , Receptores de Péptidos , Receptores de Factores de Crecimiento Transformadores beta , Bibliotecas de Moléculas Pequeñas , Animales , Antracenos/química , Antracenos/farmacología , Anticonceptivos/química , Anticonceptivos/farmacología , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Ratones , Nitrilos/química , Nitrilos/farmacología , Folículo Ovárico/efectos de los fármacos , Folículo Ovárico/crecimiento & desarrollo , Pirazoles/química , Pirazoles/farmacología , Pirimidinas/química , Pirimidinas/farmacología , Ratas , Receptores de Péptidos/agonistas , Receptores de Factores de Crecimiento Transformadores beta/agonistas , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Tiazoles/química , Tiazoles/farmacología
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