Engineering a Vascularized 3D Hybrid System to Model Tumor-Stroma Interactions in Breast Cancer

The stromal microenvironment of breast tumors, namely the vasculature, has a key role in tumor development and metastatic spread. Tumor angiogenesis is a coordinated process, requiring the cooperation of cancer cells, stromal cells, such as fibroblasts and endothelial cells, secreted factors and the extracellular matrix (ECM). In vitro models capable of capturing such complex environment are still scarce, but are pivotal to improve success rates in drug development and screening. To address this challenge, we developed a hybrid alginate-based 3D system, combining hydrogel-embedded mammary epithelial cells (parenchymal compartment) with a porous scaffold co-seeded with fibroblasts and endothelial cells (vascularized stromal compartment). For the stromal compartment, we used porous alginate scaffolds produced by freeze-drying with particle leaching, a simple, low-cost and non-toxic approach that provided storable ready-to-use scaffolds fitting the wells of standard 96-well plates. Co-seeded endothelial cells and fibroblasts were able to adhere to the surface, spread and organize into tubular-like structures. For the parenchymal compartment, a designed alginate gel precursor solution load with mammary epithelial cells was added to the pores of pre-vascularized scaffolds, forming a hydrogel in situ by ionic crosslinking. The 3D hybrid system supports epithelial morphogenesis in organoids/tumoroids and endothelial tubulogenesis, allowing heterotypic cell-cell and cell-ECM interactions, while presenting excellent experimental tractability for whole-mount confocal microscopy, histology and mild cell recovery for down-stream analysis. It thus provides a unique 3D in vitro platform to dissect epithelial-stromal interactions and tumor angiogenesis, which may assist in the development of selective and more effective anticancer therapies.We would like to acknowledge FEDER – Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 – Operational Programme Competitiveness and Internationalization (POCI), Portugal 2020, and Portuguese funds through FCT – Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of Project ANGIONICHE (POCI-01-0145-FEDER-028744 and PTDC/BTMMAT/28744/2017). The authors thank FCT for research contract DL 57/2016/CP1360/CT0006 (SB), junior research contract in the framework of the project Angioniche (AT), and IF research position IF/00296/2015 (CB)

Synthesis and characterization of VO2-based thermochromic thin films for energy-efficient windows

Thermochromic VO2 thin films have successfully been grown on SiO2-coated float glass by reactive DC and pulsed-DC magnetron sputtering. The influence of substitutional doping of V by higher valence cations, such as W, Mo, and Nb, and respective contents on the crystal structure of VO2 is evaluated. Moreover, the effectiveness of each dopant element on the reduction of the intrinsic transition temperature and infrared modulation efficiency of VO2 is discussed. In summary, all the dopant elements--regardless of the concentration, within the studied range-- formed a solid solution with VO2, which was the only compound observed by X-ray diffractometry. Nb showed a clear detrimental effect on the crystal structure of VO2. The undoped films presented a marked thermochromic behavior, specially the one prepared by pulsed-DC sputtering. The dopants effectively decreased the transition of VO2 to the proximity of room temperature. However, the IR modulation efficiency is markedly affected as a consequence of the increased metallic character of the semiconducting phase. Tungsten proved to be the most effective element on the reduction of the semiconducting-metal transition temperature, while Mo and Nb showed similar results with the latter being detrimental to the thermochromism

Evaluation of Intensivist-Nurses’ Knowledge Concerning Medication Administration Through Nasogastric and Enteral Tubes

This study evaluates the knowledge of nurses working in intensive care units concerning recommendations for the proper administration of medication through nasogastric and enteral tubes. This exploratory-descriptive study with a quantitative approach was carried out with 49 nurses in an intensive care unit of a tertiary hospital in Fortaleza, CE, Brazil. A total of 36.7% of nurses reported they disregard the dosage forms provided by the pharmacy at the time of administering the medication through tubes. Metal, wood, or a plastic mortar is the method most frequently reported (42.86%) for crushing prescribed solid forms; 32.65% leave the drugs in 20ml of water until dissolved; 65.3% place the responsibility for choosing the pharmaceutical formulation and its correlation with the tube site, either into the stomach or into the intestine, on the physician. The results indicate there is a gap between specific literature on medication administered through tubes and knowledge of nurses on the subject.El objetivo del estudio fue evaluar los conocimientos del enfermero de la unidad de cuidados intensivos sobre las recomendaciones para la correcta administración de medicamentos por sonda nasogástrica y nasoentérica. Se trata de un estudio exploratorio-descriptivo y cuantitativo con 49 enfermeros en una unidad de cuidados intensivos de un hospital terciario, en la ciudad de Fortaleza, estado de Ceará, Brasil. 36,7% no prestan atención a las formas disponibles en el sector de farmacia en el momento de su utilización por sonda. El pilón de metal, madera o plástico fue el método más citado (42,86%) para triturar las formas sólidas prescritas. 32,65% dejan los fármacos en 20mL de agua hasta que se disuelvan. 65,3% atribuyen al médico la responsabilidad de decidir sobre la formulación y la correlación con la ubicación de la sonda en el tracto gastrointestinal. Los resultados indican que hay una diferencia entre la literatura para los medicamentos administrados por sonda y el conocimiento de los enfermeros sobre el tema.O estudo objetivou avaliar o conhecimento do enfermeiro de unidade de terapia intensiva sobre as recomendações para a correta administração de medicamentos, por sondas nasogástrica e nasoenteral. Estudo exploratório-descritivo, com abordagem quantitativa, realizado com 49 enfermeiros em uma unidade de terapia intensiva de um hospital terciário, localizado na cidade de Fortaleza, no Estado do Ceará, Brasil. Dos enfermeiros, 36,7% relataram não dar atenção às formas farmacêuticas disponibilizadas pelo setor de farmácia na hora da utilização por sonda. O pilão de metal, madeira ou plástico foi o método mais referido (42,86%) para triturar as formas sólidas prescritas. Sendo que 32,65% costuma deixar os fármacos em 20mL de água até dissolver, 65,3% atribuem ao médico a responsabilidade sobre a decisão da formulação farmacêutica e a correlação com a localização da sonda no trato gastrointestinal. Os achados apontam para diferença entre a literatura específica para medicamentos administrados por sonda e o conhecimento de enfermeiros sobre o assunto

Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study

Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this study, we investigated the associations of genetic variants in alcohol-metabolising genes with prostate cancer incidence and survival. We analysed data from 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. Study-specific associations of 68 single nucleotide polymorphisms (SNPs) in 8 alcohol-metabolising genes (Alcohol Dehydrogenases (ADHs) and Aldehyde Dehydrogenases (ALDHs)) with prostate cancer diagnosis and prostate cancer-specific mortality, by grade, were assessed using logistic and Cox regression models, respectively. The data across the 25 studies were meta-analysed using fixed-effect and random-effects models. We found little evidence that variants in alcohol metabolising genes were associated with prostate cancer diagnosis. Four variants in two genes exceeded the multiple testing threshold for associations with prostate cancer mortality in fixed-effect meta-analyses. SNPs within ALDH1A2 associated with prostate cancer mortality were rs1441817 (fixed effects hazard ratio, HRfixed  = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HRfixed  = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HRfixed  = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HRfixed  = 1.43; 95%CI:1.14,1.79; p values = 0.002) was associated with prostate cancer mortality in men with low-grade prostate cancer. These results suggest that alcohol consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression

Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort

BACKGROUND: Epidemiological studies have observed a positive association between an earlier age at sexual development and prostate cancer, but markers of sexual maturation in boys are imprecise and observational estimates are likely to suffer from a degree of uncontrolled confounding. To obtain causal estimates, we examined the role of pubertal development in prostate cancer using genetic polymorphisms associated with Tanner stage in adolescent boys in a Mendelian randomization (MR) approach. METHODS: We derived a weighted genetic risk score for pubertal development, combining 13 SNPs associated with male Tanner stage. A higher score indicated a later puberty onset. We examined the association of this score with prostate cancer risk, stage and grade in the UK-based ProtecT case-control study (n = 2,927), and used the PRACTICAL consortium (n = 43,737) as a replication sample. RESULTS: In ProtecT, the puberty genetic score was inversely associated with prostate cancer grade (odds ratio (OR) of high- vs. low-grade cancer, per tertile of the score: 0.76; 95 % CI, 0.64-0.89). In an instrumental variable estimation of the causal OR, later physical development in adolescence (equivalent to a difference of one Tanner stage between pubertal boys of the same age) was associated with a 77 % (95 % CI, 43-91 %) reduced odds of high Gleason prostate cancer. In PRACTICAL, the puberty genetic score was associated with prostate cancer stage (OR of advanced vs. localized cancer, per tertile: 0.95; 95 % CI, 0.91-1.00) and prostate cancer-specific mortality (hazard ratio amongst cases, per tertile: 0.94; 95 % CI, 0.90-0.98), but not with disease grade. CONCLUSIONS: Older age at sexual maturation is causally linked to a reduced risk of later prostate cancer, especially aggressive disease

Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort

Background: Epidemiological studies have observed a positive association between an earlier age at sexual development and prostate cancer, but markers of sexual maturation in boys are imprecise and observational estimates are likely to suffer from a degree of uncontrolled confounding. To obtain causal estimates, we examined the role of pubertal development in prostate cancer using genetic polymorphisms associated with Tanner stage in adolescent boys in a Mendelian randomization (MR) approach.Methods: We derived a weighted genetic risk score for pubertal development, combining 13 SNPs associated with male Tanner stage. A higher score indicated a later puberty onset. We examined the association of this score with prostate cancer risk, stage and grade in the UK-based ProtecT case-control study (n = 2,927), and used the PRACTICAL consortium (n = 43,737) as a replication sample.Results: In ProtecT, the puberty genetic score was inversely associated with prostate cancer grade (odds ratio (OR) of high-vs. low-grade cancer, per tertile of the score: 0.76; 95 % CI, 0.64-0.89). In an instrumental variable estimation of the causal OR, later physical development in adolescence (equivalent to a difference of one Tanner stage between pubertal boys of the same age) was associated with a 77 % (95 % CI, 43-91 %) reduced odds of high Gleason prostate cancer. In PRACTICAL, the puberty genetic score was associated with prostate cancer stage (OR of advanced vs. localized cancer, per tertile: 0.95; 95 % CI, 0.91-1.00) and prostate cancer-specific mortality (hazard ratio amongst cases, per tertile: 0.94; 95 % CI, 0.90-0.98), but not with disease grade.Conclusions: Older age at sexual maturation is causally linked to a reduced risk of later prostate cancer, especially aggressive disease

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT