Reaching Out to Underserved High School Students: An Experiential Approach to Higher Education

Research indicates that underserved students are at a distinct disadvantage when it comes to entering and succeeding at college. However, with sufficient support, they can turn those disadvantages around. To address the persistent challenges of the underserved college-bound students, institutions of higher education created special pre-college outreach initiatives. This study provides finding regarding how an outreach program can apply experiential learning approach to motivate students through an experiential summer pre-business program that targets specifically targeted underserved high school juniors from various school districts in Southern California. This study also presents eleven years’ outcome assessment of this private university program. Using information from a survey and a lexical analysis of a sample of 574 students over 11-year period, this study finds that the experiential college outreach program increased underserved students’ drive for attending college and may be one promising practice to help close the gap in accessibility to higher education. The results illustrate the value of outreach programs provided by an institution of higher education to support underserved students through the fusion of business education and experiential learning

Changes in Lp-PLA 2 are associated with elevated alanine aminotransferase levels: A nested case-control study in a three-year prospective cohort

Background/Aim: Elevation in liver enzymes and hepatic fat may indicate a higher susceptibility to cardiovascular disease (CVD). This research sought to find anthropometric/biochemical variables significantly related to the alanine aminotransferase (ALT) increase in healthy populations. Methods: Nine hundred healthy subjects were included in a 3-year prospective cohort study. The initial screening revealed that 538 were found to be nondiabetic (fasting glucose < 126 mg/dL) and had normal ALT levels. Among them, 79 individuals with slightly elevated ALT levels after three years were assigned to the elevated ALT group. Of the remaining 459 participants, 241 subjects matched to the increased ALT group were the control group. Results: After three years of follow-up, individuals with elevated ALT showed notably higher aspartate aminotransferase (AST), ALT, gamma-glutamyl-transferase (g-GT), high sensitivity C-reactive protein (hs-CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2 ) activity, oxidised low-density lipoprotein (ox-LDL), urinary 8-epi-prostaglandin F2a (8-epi-PGF2a) levels and brachial-ankle pulse wave velocity (ba-PWV) in comparison to the control group. Changes (D) in ALT showed a positive correlation with D AST, D gammaGT, D hs-CRP, D Lp-PLA2 activity, D ox-LDL, D urinary 8-epi-PGF2a and D ba-PWV. Furthermore, a direct positive link was observed between the D Lp-PLA2 activity and D AST, D ox-LDL and D ba-PWV. Conclusion: Increased Lp-PLA2 activity and other CVD risk indicators were observed to have a pronounced association with elevated ALT levels. This mild ALT elevation could potentially contribute to chronic low-grade inflammation

Exercise training reverses cardiac aging phenotypes associated with heart failure with preserved ejection fraction in male mice.

Heart failure with preserved ejection fraction (HFpEF) is the most common type of HF in older adults. Although no pharmacological therapy has yet improved survival in HFpEF, exercise training (ExT) has emerged as the most effective intervention to improving functional outcomes in this age-related disease. The molecular mechanisms by which ExT induces its beneficial effects in HFpEF, however, remain largely unknown. Given the strong association between aging and HFpEF, we hypothesized that ExT might reverse cardiac aging phenotypes that contribute to HFpEF pathophysiology and additionally provide a platform for novel mechanistic and therapeutic discovery. Here, we show that aged (24-30 months) C57BL/6 male mice recapitulate many of the hallmark features of HFpEF, including preserved left ventricular ejection fraction, subclinical systolic dysfunction, diastolic dysfunction, impaired cardiac reserves, exercise intolerance, and pathologic cardiac hypertrophy. Similar to older humans, ExT in old mice improved exercise capacity, diastolic function, and contractile reserves, while reducing pulmonary congestion. Interestingly, RNAseq of explanted hearts showed that ExT did not significantly modulate biological pathways targeted by conventional HF medications. However, it reversed multiple age-related pathways, including the global downregulation of cell cycle pathways seen in aged hearts, which was associated with increased capillary density, but no effects on cardiac mass or fibrosis. Taken together, these data demonstrate that the aged C57BL/6 male mouse is a valuable model for studying the role of aging biology in HFpEF pathophysiology, and provide a molecular framework for how ExT potentially reverses cardiac aging phenotypes in HFpEF

Transcriptional regulatory networks of tumor-associated macrophages that drive malignancy in mesenchymal glioblastoma.

BACKGROUND: Glioblastoma (GBM) is a complex disease with extensive molecular and transcriptional heterogeneity. GBM can be subcategorized into four distinct subtypes; tumors that shift towards the mesenchymal phenotype upon recurrence are generally associated with treatment resistance, unfavorable prognosis, and the infiltration of pro-tumorigenic macrophages. RESULTS: We explore the transcriptional regulatory networks of mesenchymal-associated tumor-associated macrophages (MA-TAMs), which drive the malignant phenotypic state of GBM, and identify macrophage receptor with collagenous structure (MARCO) as the most highly differentially expressed gene. MARCO CONCLUSIONS: Collectively, our study characterizes the global transcriptional profile of TAMs driving mesenchymal GBM pathogenesis, providing potential therapeutic targets for improving the effectiveness of GBM immunotherapy

Pharmacogenomic analysis of patient-derived tumor cells in gynecologic cancers

Background Gynecologic malignancy is one of the leading causes of mortality in female adults worldwide. Comprehensive genomic analysis has revealed a list of molecular aberrations that are essential to tumorigenesis, progression, and metastasis of gynecologic tumors. However, targeting such alterations has frequently led to treatment failures due to underlying genomic complexity and simultaneous activation of various tumor cell survival pathway molecules. A compilation of molecular characterization of tumors with pharmacological drug response is the next step toward clinical application of patient-tailored treatment regimens. Results Toward this goal, we establish a library of 139 gynecologic tumors including epithelial ovarian cancers (EOCs), cervical, endometrial tumors, and uterine sarcomas that are genomically and/or pharmacologically annotated and explore dynamic pharmacogenomic associations against 37 molecularly targeted drugs. We discover lineage-specific drug sensitivities based on subcategorization of gynecologic tumors and identify TP53 mutation as a molecular determinant that elicits therapeutic response to poly (ADP-Ribose) polymerase (PARP) inhibitor. We further identify transcriptome expression of inhibitor of DNA biding 2 (ID2) as a potential predictive biomarker for treatment response to olaparib. Conclusions Together, our results demonstrate the potential utility of rapid drug screening combined with genomic profiling for precision treatment of gynecologic cancers

Children’s and adolescents’ rising animal-source food intakes in 1990–2018 were impacted by age, region, parental education and urbanicity

Animal-source foods (ASF) provide nutrition for children and adolescents’ physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the world’s child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 15–19 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes.publishedVersio

RNA delivery by extracellular vesicles in mammalian cells and its applications.

The term 'extracellular vesicles' refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell-cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications

Incident type 2 diabetes attributable to suboptimal diet in 184 countries

The global burden of diet-attributable type 2 diabetes (T2D) is not well established. This risk assessment model estimated T2D incidence among adults attributable to direct and body weight-mediated effects of 11 dietary factors in 184 countries in 1990 and 2018. In 2018, suboptimal intake of these dietary factors was estimated to be attributable to 14.1 million (95% uncertainty interval (UI), 13.8–14.4 million) incident T2D cases, representing 70.3% (68.8–71.8%) of new cases globally. Largest T2D burdens were attributable to insufficient whole-grain intake (26.1% (25.0–27.1%)), excess refined rice and wheat intake (24.6% (22.3–27.2%)) and excess processed meat intake (20.3% (18.3–23.5%)). Across regions, highest proportional burdens were in central and eastern Europe and central Asia (85.6% (83.4–87.7%)) and Latin America and the Caribbean (81.8% (80.1–83.4%)); and lowest proportional burdens were in South Asia (55.4% (52.1–60.7%)). Proportions of diet-attributable T2D were generally larger in men than in women and were inversely correlated with age. Diet-attributable T2D was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, central and eastern Europe and central Asia, where burdens were larger in rural residents and in lower educated individuals. Compared with 1990, global diet-attributable T2D increased by 2.6 absolute percentage points (8.6 million more cases) in 2018, with variation in these trends by world region and dietary factor. These findings inform nutritional priorities and clinical and public health planning to improve dietary quality and reduce T2D globally.publishedVersio

Polymeric Nanoparticles for Use as Gadolinium-Based Magnetic Resonance Imaging Contrast Agents

Medical imaging is an important tool in modern medicine for the purpose of diagnosis, therapy, and research. Magnetic resonance imaging (MRI) is a powerful clinical imaging tool as it is noninvasive and provides a higher level of detail compared to other imaging methods, making it an important tool for early diagnosis. Early detection of small lesions is especially important when cancers metastasize as the number, size, and location of lesions affect the treatment regime and patient outcome. While MRI provides high-quality images, smaller lesions are more difficult to detect and can benefit from contrast agents. Recently, nanoparticles have become an active field of study for imaging. Nanoparticles have shown great potential for use in imaging for several reasons. Their small size (usually 1-200 nanometers) means they are taken up more easily by cells than larger particles. In addition, imaging applications for nanoparticles depend heavily on the ability to target specific tissues, organs, or even cells. Nanoparticles can be designed and surface modified to enhance targeting and increase loading.$^{1}$ Targeting with nanoparticles can be achieved either through active or passive targeting, which can be achieved through size control. For application to imaging, it is important to use a nanoparticle synthesis method that is scalable, provides size control, and creates nanoparticles with low polydispersity and high loading. The Flash NanoPrecipitation (FNP) method meets these requirements and has been used to encapsulate hydrophobic therapeutics. Recently, the FNP process has been adapted to encapsulate hydrophilic therapeutics such as proteins and peptides using poly(butyl acrylate-b-acrylic acid) (PBA-b-PAA). The first aim was to determine the formulation conditions that affect the size of hydrophilic-encapsulating nanoparticles. The effects of the total mass concentration of materials, percent core, molecular weight, and water in the core were tested on nanoparticles encapsulating polyacrylic acid (PAA) homopolymer. Nanoparticles from ~80-120 nm in diameter with hydrophilic cores and hydrophobic shells were made using the FNP process. As most clinically used MRI contrast agents are gadolinium-based, the second aim of this study was to encapsulate a gadolinium-based contrast agent, gadopentetic acid (Gd-DTPA). Gadolinium-based T1 contrast agents must interact with water in order to be used as contrast agents in MRI so the core of the nanoparticles needed to be hydrophilic. Gd-DTPA was encapsulated at 50% loading and at a size of ~50 nm. These nanoparticles were coated with polystyrene-b-polyethylene glycol (PS-b-PEG), resulting in a final size of ~85 nm. Enhanced passive targeting and higher loading of contrast agents through the use of nanoparticles could improve the use of MRI in clinical and scientific settings

Second-Harmonic Generation and Photoluminescence Imaging of Few-Layer Hexagonal Boron Nitride

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