Bruusclapp0144

BACKGROUND Longer time from diagnosis to definitive surgery (TTDS) is associated with increased melanoma-specific mortality. Although Black patients present with later stage melanoma and have worse survival than non-Hispanic white (NHW) patients, the association between race and TTDS is unknown. OBJECTIVE To investigate racial differences in time to melanoma treatment. METHODS Retrospective review of the National Cancer Database (2004-2015). Multivariable logistic regression was used to evaluate the association of race with TTDS controlling for sociodemographic/disease characteristics. RESULTS Of the 233,982 melanoma patients identified, 1,221 (0.52%) were Black. Black patients had longer TTDS for stage I-III melanoma (p0.05 for both). Controlling for sociodemographic characteristics, Black patients had over twice the odds of having TTDS between 41-60 days, over three times the odds of having TTDS between 61-90 days, and over five times the odds of having TTDS over 90 days. Racial differences in TTDS persisted within each insurance type. Patients with Medicaid had the longest TTDS (mean 60.4 days), and those with private insurance had the shortest TTDS (mean 44.6 days; p less then 0.001 for both). CONCLUSIONS Targeted approaches to improve TTDS for Black patients are integral in reducing racial disparities in melanoma outcomes. BACKGROUND To explore the significance of SAA in evaluating the severity and prognosis of COVID-19. METHODS A total of 132 patients with confirmed COVID-19 who were admitted to a designated COVID-19 hospital in Wuhan, China from January 18, 2020 to February 26, 2020 were collected. The dynamic changes of blood SAA, CRP, PCT, WBC, Lymphocyte (L), PLT, CT imaging, and disease progression were studied. All patients completed at least twice laboratory data collection and clinical condition assessment at three time points indicated for this study; The length of hospital stay was longer than 14 days prior to February 26, 2020. RESULTS COVID-19 patients had significantly increased SAA and CRP levels, while L count decreased, and PCT, WBC, and PLT were in the normal range. As disease progressed from mild to critically severe, SAA and CRP gradually increased, while L decreased, and PLT, WBC, and PCT had no significant changes; ROC curve analysis suggests that SAA/L, CRP, SAA, and L count are valuable in evaluating the severity of COVID-19 and distinguishing critically ill patients from mild ones; Patients with SAA consistently trending down during the course of disease have better prognosis, compared with the patients with SAA continuously rising; The initial SAA level is positively correlated with the dynamic changes of the serial CT scans. Patient with higher initial SAA level are more likely to have poor CT imaging. CONCLUSIONS SAA and L are sensitive indicators in evaluating the severity and prognosis of COVID-19. Monitoring dynamic changes of SAA, combined with CT imaging could be valuable in diagnosis and treatment of COVID-19. Owing to the binding capacity to ɑvβ3 integrin overexpressed on glioma, vasculogenic mimicry and neovasculature, the peptide c(RGDyK) has been exploited pervasively to functionalize nanocarriers for targeted delivery of bioactives. The former study in our group substantiated the immunotoxicity of c(RGDyK)-modified liposome, and this unfavorable immunogenicity is known to compromise blood circulation, targeting efficacy and therapeutic outcome. Therefore, we need to find a superior alternative ligand in order to evade the exquisite immuno-sensitization. We developed mn by structure-guided peptide design and retro-inverso isomerization technique, which was experimentally substantiated to have exceptional binding affinity to ɑvβ3 integrin. Besides mn does not have affinity toward normal liver cells and kidney cells, which c(RGDyK) possesses in a certain degree. learn more Warranting that mn and c(RGDyK) anchored ɑvβ3, we formulated peptide-tethered liposomes and investigated in vivo bio-fate. Compared with c(RGDyK)-modified liposome, mn-modified liposome presented longer blood circulation and reduced ingestion by Kupffer cells with decreased retention in liver accordingly, benefitting from attenuated anti-liposome IgG and IgM response elicited by multiple sequential doses. Those merits strengthened the anti-glioma efficacy of ɑvβ3-targeted doxorubicin-loaded liposomes, proving the importance of immunocompatibility in process of targeted drug delivery. The epithelium is a formidable barrier to the absorption of orally delivered nano-vehicles. Here, by exploring a nutrient-absorption pathway, a self-amplified nanoplatform was developed to promote apical-to-basolateral transcytosis across the epithelium. The nanoplatform consisted of fructose-modified polyethylene glycol coated nanoparticles (Fru-PEG NPs) and a sweetener, acesulfame potassium (AceK) in combination. Compared with regular PEGylated nanoparticles, the combination exhibited a 3.9-fold increase of absorption following oral gavage in mice and an 8.8-fold increase of transepithelial transport in vitro. When encapsulated with insulin, the combination regimen elicited a stronger hypoglycemic effect, with a pharmacological bioavailability of 18.56%, which was 3.2-fold higher than that of PEG NPs. We demonstrated that a large proportion of Fru-PEG NPs underwent internalization and basolateral exocytosis via a glucose transporter type 2 (GLUT2)-dependent process, which is an important fructose assimilation pathway. Notably, co-administered AceK could prime the epithelial cells with increased apical distribution of GLUT2, thus amplifying this unidirectional transcytosis of nanoparticles. This work is the first proof-of-concept study of manipulating and amplifying a nutrient-absorption pathway to facilitate the unidirectional trans-epithelial transport of orally administered nano-delivery vehicles. V.Death-associated protein kinase 1 (DAPK1) is a key protein that mediates neuronal death in ischemic stroke. Although the substrates of DAPK1 and molecular signal in stroke have been gradually discovered, the modulation of DAPK1 itself is still unclear. Here we first reveal that Caytaxin, a brain-specific member of BCL2/adenovirus E1B -interacting protein (BNIP-2), increases and interacts with DAPK1 as early as 2 h after middle cerebral artery occlusion (MCAO) in the penumbra area of mouse brain. Furthermore, Caytaxin binds to DAPK1 at the presynaptic site and inhibits DAPK1 catalytic activity. Silencing Caytaxin by Caytaxin shRNA (Sh-Caytaxin) enhances DAPK1 activity, deteriorates neuronal apoptosis and brain injuries both in vivo and in vitro. Thus, elevating presynaptic Caytaxin could prevent neuronal apoptosis by inhibiting DAPK1 activation in the acute stage of ischemic stroke. Caytaxin may physiologically protect neuronal cells and represent a potential prevention and therapeutic target in the early phase of cerebral ischemic stroke.