RESUMEN
In the coal mining regions of Eastern Kentucky, access to potable water has been diminished due to industrial pollution and aging infrastructure. Current communications regarding contaminated water are often too inaccessible and too infrequent to appropriately address the issues in target communities. To explore possible improvements to the community's communication infrastructure, the researchers explored what types of stories should be used to communicate about water quality risks, who should communicate about these stories, and how these stories should be communicated. Researchers enlisted a key community member to conduct 24 individual interviews with community members, using snowball sampling. Open and axial coding was used to conduct a constant comparative analysis of the data for emergent themes. Analyzing the verbatim interviews, the researchers concluded communication infrastructure should be enhanced to engage the public about water quality risks. Risk messaging should share water quality information through stories that are designed to be easily digested and frequently distributed using laypeople's terms, visuals, graphs, and maps. These stories should be shared using an integrated communication infrastructure where key community storytellers, such as local news, social media, and interstitial agents, work together to share risk information across platforms and channels.
RESUMEN
Obesity plays a major role in type II diabetes (T2DM) progression because it applies metabolic and oxidative stress resulting in dysfunctional beta-cells and activation of intra-islet pancreatic stellate cells (PaSCs) which cause islet fibrosis. Administration of antioxidant N-acetyl-L-cysteine (NAC) in vivo improves metabolic outcomes in diet-induced obese diabetic mice, and in vitro inhibits PaSCs activation. However, the effects of NAC on diabetic islets in vivo are unknown. This study examined if dosage and length of NAC treatment in HFD-induced diabetic mice effect metabolic outcomes associated with maintaining healthy beta-cells and quiescent PaSCs, in vivo. Male C57BL/6N mice were fed normal chow (ND) or high-fat (HFD) diet up to 30 weeks. NAC was administered in drinking water to HFD mice in preventative treatment (HFDpNAC) for 23 weeks or intervention treatment for 10 (HFDiNAC) or 18 (HFDiNAC+) weeks, respectively. HFDpNAC and HFDiNAC+, but not HFDiNAC, mice showed significantly improved glucose tolerance and insulin sensitivity. Hyperinsulinemia led by beta-cell overcompensation in HFD mice was significantly rescued in NAC treated mice. A reduction of beta-cell nuclear Pdx-1 localization in HFD mice was significantly improved in NAC treated islets along with significantly reduced beta-cell oxidative stress. HFD-induced intra-islet PaSCs activation, labeled by αSMA, was significantly diminished in NAC treated mice along with lesser intra-islet collagen deposition. This study determined that efficiency of NAC treatment is beneficial at maintaining healthy beta-cells and quiescent intra-islet PaSCs in HFD-induced obese T2DM mouse model. These findings highlight an adjuvant therapeutic potential in NAC for controlling T2DM progression in humans.
Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Acetilcisteína/metabolismo , Acetilcisteína/farmacología , Acetilcisteína/uso terapéutico , Animales , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/complicaciones , Obesidad/etiología , Estrés Oxidativo , Células Estrelladas Pancreáticas/metabolismoRESUMEN
Zika virus (ZIKV) is the cause of a pandemic associated with microcephaly in newborns and Guillain-Barre syndrome in adults. Currently, there are no available treatments or vaccines for ZIKV, and the development of a safe and effective vaccine is a high priority for many global health organizations. We describe the development of ZIKV vaccine candidates using the self-amplifying messenger RNA (SAM) platform technology delivered by cationic nanoemulsion (CNE) that allows bedside mixing and is particularly useful for rapid responses to pandemic outbreaks. Two immunizations of either of the two lead SAM (CNE) vaccine candidates elicited potent neutralizing antibody responses to ZIKV in mice and nonhuman primates. Both SAM (CNE) vaccines protected these animals from ZIKV challenge, with one candidate providing complete protection against ZIKV infection in nonhuman primates. The data provide a preclinical proof of concept that a SAM (CNE) vaccine candidate can rapidly elicit protective immunity against ZIKV.