Activity

Obesity and type 2 diabetes mellitus (T2DM) associate with increased incidence and mortality from many cancers, including breast cancer. The mechanisms involved in this relation remain poorly understood. Our study aimed to investigate the in vitro effect of high levels of glucose, insulin, leptin, TNF-α, INF-γ and oxidative stress (induced with tert-butylhydroperoxide (TBH)), which are associated with T2DM, upon glucose uptake by breast cancer (MCF-7 and MDA-MB-231) and non-cancer (MCF-12A) cells and to correlate this effect with their effects upon cellular characteristics associated with cancer progression (cell proliferation, viability, migration, angiogenesis and apoptosis). 3H-DG uptake was markedly inhibited by a selective GLUT1 inhibitor (BAY-876) in all cell lines, proving that 3H-DG uptake is mainly GLUT1-mediated. TBH (2.5 μM), insulin (50 nM), leptin (500 ng/ml) and INF-y (100 ng/ml) stimulate GLUT1-mediated 3H-DG (1 mM) uptake by both ER-positive and triple-negative breast cancer cell lines. TBH and leptin, but not insulin and INF-γ, increase GLUT1 mRNA levels. Insulin and leptin (in both ER-positive and triple-negative breast cancer cell lines) and TBH (in the triple-negative cell line) have a proproliferative effect and leptin possesses a cytoprotective effect in both breast cancer cell lines that can contribute to cancer progression. The effects of TBH, insulin, leptin and INF-γ upon breast cancer cell proliferation and viability are GLUT1-dependent. In conclusion, T2DM-associated characteristics induce changes in GLUT1-mediated glucose uptake that can contribute to cancer progression. Moreover, we conclude that BAY-876 can be a strong candidate for development of a new effective anticancer agent against breast cancer.

To perform a multicenter study to assess growth failure in hospitalized infants with gastroschisis.

This study included neonates with gastroschisis within sites in the University of California Fetal Consortium. The study’s primary outcome was growth failure at hospital discharge, defined as a weight or length z score decrease >0.8 from birth. Regression analysis was performed to assess changes in z scores over time.

Among 125 infants with gastroschisis, the median gestational age was 37weeks (IQR 35-37). Length of stay was 32days (23-60); 55% developed weight or length growth failure at discharge (28% had weight growth failure, 42% had length growth failure, and 15% had both weight and length growth failure). Weight and length z scores at 14days, 30days, and discharge were less than birth (P<.01 for all). Weight and length z scores declined from birth to 30days (-0.10 and -0.11 z score units/week, respectively, P<.001). Length growth failure at discharge was associated with weight and length z score changes over time (P<.05 for both). Lower gestational age was associated with weight growth failure (OR 0.70 for each gestational age week, 95% CI 0.55-0.89, P=.004).

Growth failure, in particular linear growth failure, is common in infants with gastroschisis. These data suggest the need to improve nutritional management in these infants.

Growth failure, in particular linear growth failure, is common in infants with gastroschisis. These data suggest the need to improve nutritional management in these infants.

Transfemoral access is the most common approach for transcatheter aortic valve replacement (TAVR). However, a subset of patients require alternative access. This study describes the evolution and outcomes of alternative access TAVR at Cleveland Clinic.

From January 2006 to January 2019, 2,446 patients underwent TAVR, 414 (17%) via alternative access (247 transapical, 95 transaortic, 56 transaxillary, 2 transcarotid, 10 transiliac, 4 transcaval). Patients undergoing alternative access TAVR had high preoperative risk. Propensity-matched comparisons were targeted at comparing the transfemoral vs. transaxillary approaches since 2012.

Over time, the favored alternative access approach shifted from transapical and transaortic to transaxillary. Pacemaker requirement was similar for alternative access and transfemoral approaches. Compared with transfemoral access, major vascular injuries were higher in the alternative access group (n=12/2.9% vs. n=27/1.3%, P=.02), but minor vascular injuries were lower (n=13/3.pproaches, and results are comparable to those of the transfemoral approach.

Mast cells (MCs) play a pivotal role in innate and adaptive immune responses. However, MCs are also involved in different pathologic conditions. Studies on the mechanisms that govern human MC functions are impeded by their limited and difficult recovery. Therefore, several research groups have developed protocols to culture human MCs from progenitor cells. These protocols vary with respect to culture duration and used maturation cytokines. How MCs obtained by different protocols differ in phenotype and functionality is currently unknown.

To compare different protocols for the generation of human MCs from peripheral blood progenitors.

Thirteen paired human MC cultures were investigated. MCs were cultured form CD34

progenitors cells for 4 or 8weeks and with or without the addition of IL-6. Phenotyping comprised staining for CD117, CD203c, FcεRI, MRGPRX2, CD300a and CD32. Functional studies included measurements of the up-regulation of CD63 and CD203c after allergen-specific cross-linking of sIgE/FcεRI clls from blood progenitors, thereby enabling simultaneous exploration of allergen-specific sIgE/FcεRI cross-linking and non-specific activation via MRGPRX2.

Exogenous lipoid pneumonia (ELP) develops when lipid-containing substances enter the airways through aspiration or inhalation and incite an inflammatory response. The diagnosis of ELP often is difficult because findings may be nonspecific. The clinical course of ELP has not been well characterized.

What are the presenting clinicoradiologic features of ELP, its causative agents, and clinical course?

We searched the Mayo Clinic electronic medical records for patients diagnosed with ELP between 1998 and 2020. Inclusion diagnostic criteria were (1) lipoid pneumonia (LP) on histopathologic examination, (2) lipid-laden macrophages in BAL fluid, or (3) fatty attenuation of parenchymal opacities on chest CT imaging. Additionally, all patients were required to have a clinician diagnosis of LP in the absence of conditions known to cause endogenous LP.

Thirty-four patients were identified. selleck compound Mean age was 71 years, with no sex predominance; one-half were asymptomatic. The diagnosis was confirmed by lung biopsy (including three lobectomies for suspected malignancy) in 71%of patients, CT scan in 24%of patients, and BAL in 5%of patients.