Chemically Modified Biomimetic Carbon-Coated Iron Nanoparticles for Stent Coatings: In Vitro Cytocompatibility and In Vivo Structural Changes in Human Atherosclerotic Plaques.

Atherosclerosis, a systematic degenerative disease related to the buildup of plaques in human vessels, remains the major cause of morbidity in the field of cardiovascular health problems, which are the number one cause of death globally. Novel atheroprotective HDL-mimicking chemically modified carbon-coated iron nanoparticles (Fe@C NPs) were produced by gas-phase synthesis and modified with organic functional groups of a lipophilic nature. Modified and non-modified Fe@C NPs, immobilized with polycaprolactone on stainless steel, showed high cytocompatibility in human endothelial cell culture. Furthermore, after ex vivo treatment of native atherosclerotic plaques obtained during open carotid endarterectomy surgery, Fe@C NPs penetrated the inner structures and caused structural changes of atherosclerotic plaques, depending on the period of implantation in Wistar rats, serving as a natural bioreactor. The high biocompatibility of the Fe@C NPs shows great potential in the treatment of atherosclerosis disease as an active substance of stent coatings to prevent restenosis and the formation of atherosclerotic plaques.

Distribution and Community Assembly of Trees Along an Andean Elevational Gradient.

Highlighting patterns of distribution and assembly of plants involves the use of community phylogenetic analyses and complementary traditional taxonomic metrics. However, these patterns are often unknown or in dispute, particularly along elevational gradients, with studies finding different patterns based on elevation. We investigated how patterns of tree diversity and structure change along an elevation gradient using taxonomic and phylogenetic diversity metrics. We sampled 595 individuals (36 families; 53 genera; 88 species) across 15 plots along an elevational gradient (2440-3330 m) in Ecuador. Seventy species were sequenced for the rbcL and matK gene regions to generate a phylogeny. Species richness, Shannon-Weaver diversity, Simpson's Dominance, Simpson's Evenness, phylogenetic diversity (PD), mean pairwise distance (MPD), and mean nearest taxon distance (MNTD) were evaluated for each plot. Values were correlated with elevation and standardized effect sizes (SES) of MPD and MNTD were generated, including and excluding tree fern species, for comparisons across elevation. Taxonomic and phylogenetic metrics found that species diversity decreases with elevation. We also found that overall the community has a non-random phylogenetic structure, dependent on the presence of tree ferns, with stronger phylogenetic clustering at high elevations. Combined, this evidence supports the ideas that tree ferns have converged with angiosperms to occupy the same habitat and that an increased filtering of clades has led to more closely related angiosperm species at higher elevations.

High-Dose Abiraterone Acetate in Men With Castration Resistant Prostate Cancer.

BACKGROUND: Abiraterone acetate (AA) inhibits androgen biosynthesis and prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC) when combined with prednisone (P). Resistance to therapy remains incompletely understood. In this open-label, single-arm, multicenter phase II study we investigated the clinical benefit of increasing the dose of AA at the time of resistance to standard-dose therapy. PATIENTS AND METHODS: Eligible patients had progressive mCRPC and started AA 1000 mg daily and P 5 mg twice daily. Patients who achieved any prostate-specific antigen (PSA) decline after 12 weeks of therapy continued AA with P until PSA or radiographic progression. At progression, AA was increased to 1000 mg twice daily with unchanged P dosing. Patients were monitored for response to therapy for a minimum of 12 weeks or until PSA or radiographic progression. The primary end point was PSA decline of at least 30% after 12 weeks of therapy at the increased dose of AA. RESULTS: Forty-one patients were enrolled from March 2013 through March 2014. Thirteen men experienced disease progression during standard-dose therapy and were subsequently treated with AA 1000 mg twice per day. Therapy was well tolerated. No PSA declines ≥ 30% nor radiographic responses were observed after 12 weeks of dose-escalated therapy. Higher baseline dehydroepiandrosterone levels, lower circulating tumor cell burden, and higher pharmacokinetic levels of abiraterone and abiraterone metabolites were associated with response to standard-dose therapy. CONCLUSION: Increasing the dose of abiraterone at the time of resistance has limited clinical utility and cannot be recommended. Lower baseline circulating androgen levels and interpatient pharmacokinetic variance appear to be associated with primary resistance to AA with P.

Nutrient enrichment effects on mycorrhizal fungi in an Andean tropical montane Forest.

Nitrogen (N) and phosphorus (P) deposition are increasing worldwide largely due to increased fertilizer use and fossil fuel combustion. Most work with N and P deposition in natural ecosystems has focused on temperate, highly industrialized, regions. Tropical regions are becoming more developed, releasing large amounts of these nutrients into the atmosphere. Nutrient enrichment in nutrient-poor systems such as tropical montane forest can represent a relatively large shift in nutrient availability, especially for sensitive microorganisms such as arbuscular mycorrhizal fungi (AMF). These symbiotic fungi are particularly critical, given their key role in ecosystem processes affecting plant community structure and function.To better understand the consequences of nutrient deposition in plant communities, a long-term nutrient addition experiment was set up in a tropical montane forest in the Andes of southern Ecuador. In this study, we investigated the impacts of 7 years of elevated N and P on AMF root colonization potential (AMF-RCP) through a greenhouse bait plant method in which we quantified root colonization. We also examined the relationship between AMF-RCP and rarefied tree diversity.After 7 years of nutrient addition, AMF-RCP was negatively correlated with soil P, positively correlated with soil N, and positively correlated with rarefied tree diversity. Our results show that AMF in this tropical montane forest are directly affected by soil N and P concentrations, but may also be indirectly impacted by shifts in rarefied tree diversity. Our research also highlights the need to fully understand the benefits and drawbacks of using different sampling methods (e.g., AMF-RCP versus direct root sampling) to robustly examine AMF-plant interactions in the future.

Programmed death-ligand 1 (PD-L1) characterization of circulating tumor cells (CTCs) in muscle invasive and metastatic bladder cancer patients.

BACKGROUND: While programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) checkpoint inhibitors have activity in a proportion of patients with advanced bladder cancer, strongly predictive and prognostic biomarkers are still lacking. In this study, we evaluated PD-L1 protein expression on circulating tumor cells (CTCs) isolated from patients with muscle invasive (MIBC) and metastatic (mBCa) bladder cancer and explore the prognostic value of CTC PD-L1 expression on clinical outcomes. METHODS: Blood samples from 25 patients with MIBC or mBCa were collected at UCSF and shipped to Epic Sciences. All nucleated cells were subjected to immunofluorescent (IF) staining and CTC identification by fluorescent scanners using algorithmic analysis. Cytokeratin expressing (CK)+ and (CK)-CTCs (CD45-, intact nuclei, morphologically distinct from WBCs) were enumerated. A subset of patient samples underwent genetic characterization by fluorescence in situ hybridization (FISH) and copy number variation (CNV) analysis. RESULTS: CTCs were detected in 20/25 (80 %) patients, inclusive of CK+ CTCs (13/25, 52 %), CK-CTCs (14/25, 56 %), CK+ CTC Clusters (6/25, 24 %), and apoptotic CTCs (13/25, 52 %). Seven of 25 (28 %) patients had PD-L1+ CTCs; 4 of these patients had exclusively CK-/CD45-/PD-L1+ CTCs. A subset of CTCs were secondarily confirmed as bladder cancer via FISH and CNV analysis, which revealed marked genomic instability. Although this study was not powered to evaluate survival, exploratory analyses demonstrated that patients with high PD-L1+/CD45-CTC burden and low burden of apoptotic CTCs had worse overall survival. CONCLUSIONS: CTCs are detectable in both MIBC and mBCa patients. PD-L1 expression is demonstrated in both CK+ and CK-CTCs in patients with mBCa, and genomic analysis of these cells supports their tumor origin. Here we demonstrate the ability to identify CTCs in patients with advanced bladder cancer through a minimally invasive process. This may have the potential to guide checkpoint inhibitor immune therapies that have been established to have activity, often with durable responses, in a proportion of these patients.

An improved CTC isolation scheme for pairing with downstream genomics: Demonstrating clinical utility in metastatic prostate, lung and pancreatic cancer.

Improvements in technologies to yield purer circulating tumor cells (CTCs) will enable a broader range of clinical applications. We have previously demonstrated the use of a commercially available cell-adhesion matrix (CAM) assay to capture invasive CTCs (iCTCs). To improve the purity of the isolated iCTCs, here we used fluorescence-activated cell sorting (FACS) in combination with the CAM assay (CAM + FACS). Our results showed an increase of median purity from the CAM assay to CAM + FACS for the spiked-in cell lines and patient samples analyzed from three different metastatic cancer types: castration resistant prostate cancer (mCRPC), non-small cell lung cancer (mNSCLC) and pancreatic ductal adenocarcinoma cancer (mPDAC). Copy number profiles for spiked-in mCRPC cell line and mCRPC patient iCTCs were similar to expected mCRPC profiles and a matched biopsy. A somatic epidermal growth factor receptor (EGFR) mutation specific to mNSCLC was observed in the iCTCs recovered from EGFR(+) mNSCLC cell lines and patient samples. Next-generation sequencing (NGS) of spiked-in pancreatic cancer cell line and mPDAC patient iCTCs showed mPDAC common mutations. CAM + FACS iCTC enrichment enables multiple downstream genomic characterizations across different tumor types.

Factores de riesgo modulados por los padres de familia o encargados, que influyen en la presencia de caries de la temprana infancia en niños y niñas de 3 a 5 años que asisten a las clínicas de odontopediatría de la Facultad de Odontología de la Universidad de El Salvador / Risk factors modulated by parents or guardians, which influence the presence of early childhood caries in boys and girls aged 3 to 5 years old who attend the pediatric dentistry clinics of the Faculty of Dentistry of the University of El Salvador

La presente investigación tenía como objetivo conocer la modulación que los padres de familia o encargados ejercen sobre los factores de riesgo que influyen en la presencia de Caries de la Temprana Infancia en niños y niñas de 3 a 5 años que asisten a la Clínica de Odontopediatría de la Facultad de Odontología de la Universidad de El Salvador, durante los meses de Abril y Mayo del 2010, en el turno clínico de 7 a 9 a.m. El universo de estudio fueron 37 niños, de los cuales se identificó tanto la edad y el género en que dicha patología es más predominante; así como también la cantidad de niños afectados por dicha enfermedad. De 37 niños examinados, 30 presentaron CTI, determinando que la prevalencia de dicha enfermedad en la población representó el 81.10%. De los cuales, la edad más afectada fue el grupo de 3 a 4 años con un porcentaje de 51.4%; con una prevalencia del género masculino, siempre en este mismo rango de edad, con un 27%; entre los factores de riesgo más influyentes modulados por los padres de familia o encargados se concluyó que la ingesta de leche materna representó el 89.2%; el consumo de leche por medio de la pacha fue de 73%; sumado al mal hábito de que los padres permitieran que el niño se durmiera tomando pacha o leche materna con un 89.2%; el consumo de golosinas en un100% de la población, y la contaminación cruzada por medio del beso en la boca o mano del niño con un 62.2%; siendo estos resultados los más representativos de la investigación.

The objective of the present investigation was to know the modulation that parents or guardians exert on the risk factors that influence the presence of Early Childhood Caries in boys and girls from 3 to 5 years old who attend the Pediatric Dentistry Clinic of the Faculty of Dentistry of the University of El Salvador, during the months of April and May 2010, in the clinical shift from 7 to 9 am The universe of study was 37 children, of which both age and gender were identified in that said pathology is more prevalent; as well as the number of children affected by this disease. Of 37 children examined, 30 presented ICC, determining that the prevalence of this disease in the population represented 81.10%. Of which, the most affected age was the group of 3 to 4 years with a percentage of 51.4%; with a prevalence of the male gender, always in this same age range, with 27%; Among the most influential risk factors modulated by parents or guardians, it was concluded that the intake of breast milk represented 89.2%; the consumption of milk through the pacha was 73%; added to the bad habit of parents allowing the child to fall asleep drinking pacha or breast milk with 89.2%; the consumption of sweets in 100% of the population, and cross contamination through kissing on the child's mouth or hand with 62.2%; these results being the most representative of the research.