Hybrid modeling of a biorefinery separation process to monitor short-term and long-term membrane fouling

Membrane filtration is commonly used in biorefineries to separate cells from fermentation broths containing the desired products. However, membrane fouling can cause short-term process disruption and long-term membrane degradation. The evolution of membrane resistance over time can be monitored to track fouling, but this calls for adequate sensors in the plant. This requirement might not be fulfilled even in modern biorefineries, especially when multiple, tightly interconnected membrane modules are used. Therefore, characterization of fouling in industrial facilities remains a challenge. In this study, we propose a hybrid modeling strategy to characterize both reversible and irreversible fouling in multi-module biorefinery membrane separation systems. We couple a linear data-driven model, to provide high-frequency estimates of trans-membrane pressures from the available measurements, with a simple nonlinear knowledge-driven model, to compute the resistances of the individual membrane modules. We test the proposed strategy using real data from the world's first industrial biorefinery manufacturing 1,4-bio-butanediol via fermentation of renewable raw materials. We show how monitoring of individual resistances, even when done by simple visual inspection, offers valuable insight on the reversible and irreversible fouling state of the membranes. We also discuss the advantage of the proposed approach, over monitoring trans-membrane pressures and permeate fluxes, from the standpoints of data variability, effect of process changes, interaction between module in multi-module systems, and fouling dynamics

Laryngeal mask airway in neonatal stabilization and transport: a retrospective study.

Laryngeal mask airway (LMA) may be considered by health caregivers of level I–II hospitals for neonatal resuscitation and stabilization before and during interhospital care, but literature provides little information on this aspect. This study reviewed the use of LMA during stabilization and transport in a large series of neonates. This is a retrospective study evaluating the use of LMA in infants who underwent emergency transport by the Eastern Veneto Neonatal Emergency Transport Service between January 2003 and December 2021. All data were obtained from transport registry, transport forms, and hospital charts. In total, 64/3252 transferred neonates (2%) received positive pressure ventilation with an LMA, with increasing trend over time (p = 0.001). Most of these neonates were transferred after birth (97%), due to a respiratory or neurologic disease (95%). LMA was used before the transport (n = 60), during the transport (n = 1), or both (n = 3). No device-related adverse effects were recorded. Sixty-one neonates (95%) survived and were discharged/transferred from the receiving center

PTX3 shapes profibrotic immune cells and epithelial/fibroblast repair and regeneration in a murine model of pulmonary fibrosis

The long pentraxin 3 (PTX3) is protective in different pathologies but was not analyzed in-depth in Idiopathic Pulmonary Fibrosis (IPF). Here, we have explored the influence of PTX3 in the bleomycin (BLM)-induced murine model of IPF by looking at immune cells (macrophages, mast cells, T cells) and stemness/regenerative markers of lung epithelium (SOX2) and fibro-blasts/myofibroblasts (CD44) at different time points that retrace the progression of the disease from onset at day 14, to full-blown disease at day 21, to incomplete regression at day 28. We took advantage of transgenic PTX3 overexpressing mice (Tie2-PTX3) and Ptx3 null ones (PTX3-KO) in which pulmonary fibrosis was induced. Our data have shown that PTX3 overexpression in Tie2-PTX3 compared to WT or PTX3-KO: reduced CD68+ and CD163+ macrophages and the Tryptase+ mast cells during the whole experimental time; on the contrary, CD4+ T cells are consistently present on day 14 and dramatically decreased on day 21; CD8+ T cells do not show significant differences on day 14, but are significantly reduced on day 21; SOX2 is reduced on days 14 and 21; CD44 is reduced on day 21. Therefore, PTX3 could act on the proimmune and fibrogenic microenvironment to prevent fibrosis in BLM-treated mice

Adherence to the Mediterranean diet and nasopharyngeal cancer risk in Italy

Purpose: Few studies investigated the role of diet on nasopharyngeal cancer (NPC) risk in non-endemic areas. The aim of this study was to assess the association between adherence to the traditional Mediterranean diet and NPC risk in a southern European low-risk population. Methods: We conducted a hospital-based case-control study in Italy, including 198 histologically confirmed NPC cases and 594 matched controls. Dietary habits were collected by means of a validated food-frequency questionnaire, including 83 foods, food groups, or beverages. Adherence to the traditional Mediterranean diet was assessed through a Mediterranean Diet Score (MDS), based on nine dietary components characterizing this dietary profile, i.e., high intake of vegetables, fruits and nuts, cereals, legumes, and fish; low intake of dairy products and meat; high monounsaturated to saturated fatty acid ratio; and moderate alcohol intake. We estimated odds ratios (ORs) of NPC, and the corresponding 95% confidence intervals (CIs), for increasing MDS (i.e., increasing adherence) using multiple logistic regression models, adjusted for major confounding factors. Results: As compared to MDS 64 4, the ORs of NPC were 0.83 (95% CI: 0.54\u20131.25) for MDS of 5 and 0.66 (95% CI: 0.44\u20130.99) for MDS 65 6, with a significant trend of decreasing risk (p 0.043). The corresponding population attributable fraction was 22%, indicating that 22% of NPC cases in this population would be avoided by shifting all subjects to a score 656. Conclusions: Our study supports a favorable role of the Mediterranean diet on NPC risk

Iron supplementation enhances RSL3-induced ferroptosis to treat naïve and prevent castration-resistant prostate cancer

Prostate cancer (PCa) is a leading cause of death in the male population commonly treated with androgen deprivation therapy that often relapses as androgen-independent and aggressive castration-resistant prostate cancer (CRPC). Ferroptosis is a recently described form of cell death that requires abundant cytosolic labile iron to promote membrane lipid peroxidation and which can be induced by agents that inhibit the glutathione peroxidase-4 activity such as RSL3. Exploiting in vitro and in vivo human and murine PCa models and the multistage transgenic TRAMP model of PCa we show that RSL3 induces ferroptosis in PCa cells and demonstrate for the first time that iron supplementation significantly increases the effect of RSL3 triggering lipid peroxidation, enhanced intracellular stress and leading to cancer cell death. Moreover, the combination with the second generation anti-androgen drug enzalutamide potentiates the effect of the RSL3 + iron combination leading to superior inhibition of PCa and preventing the onset of CRPC in the TRAMP mouse model. These data open new perspectives in the use of pro-ferroptotic approaches alone or in combination with enzalutamide for the treatment of PCa

Family history of cancer and the risk of cancer: a network of case-control studies

Background The risk of many cancers is higher in subjects with a family history (FH) of cancer at a concordant site. However, few studies investigated FH of cancer at discordant sites. Patients and methods This study is based on a network of Italian and Swiss case-control studies on 13 cancer sites conducted between 1991 and 2009, and including more than 12 000 cases and 11 000 controls. We collected information on history of any cancer in first degree relatives, and age at diagnosis. Odds ratios (ORs) for FH were calculated by multiple logistic regression models, adjusted for major confounding factors. Results All sites showed an excess risk in relation to FH of cancer at the same site. Increased risks were also found for oral and pharyngeal cancer and FH of laryngeal cancer (OR = 3.3), esophageal cancer and FH of oral and pharyngeal cancer (OR = 4.1), breast cancer and FH of colorectal cancer (OR = 1.5) and of hemolymphopoietic cancers (OR = 1.7), ovarian cancer and FH of breast cancer (OR = 2.3), and prostate cancer and FH of bladder cancer (OR = 3.4). For most cancer sites, the association with FH was stronger when the proband was affected at age <60 years. Conclusions Our results point to several potential cancer syndromes that appear among close relatives and may indicate the presence of genetic factors influencing multiple cancer site

Atividades lipolíticas em polpa e óleo de frutos de dendê.

Resumo: Um dos principais desafios da coleta e extração de óleo de frutos de dendê (palma de óleo) é a manutenção da qualidade do óleo, de forma a evitar a liberação de ácidos graxos, que mudam as propriedades do óleo e, consequentemente, reduzem seu valor comercial. A liberação desses ácidos é atribuída à ação de lipases. Entretanto, não há um consenso quanto à fonte das enzimas que hidrolisam excessivamente o óleo, se ela é endógena (produzida pelo próprio fruto de dendê) ou exógena (produzida por um determinado microrganismo que colonizou o fruto de dendê). Neste trabalho, a verificação da presença de lipases no mesocarpo de frutos de dendê foi realizada por meio de reações de hidrólise. Dessa maneira, as proteínas contidas no mesocarpo de dendê foram adicionadas a reatores contendo óleo, e a liberação de ácidos graxos após a hidrólise desse óleo foi monitorada ao longo do tempo. As proteínas presentes no mesocarpo foram aplicadas ao reator de duas maneiras: 1) na forma de uma polpa macerada de mesocarpo e 2) na forma de um extrato proteico, ou seja, como proteínas parcialmente purificadas, isoladas dos demais componentes do mesocarpo. As amostras de frutos de dendê utilizadas neste estudo foram obtidas de uma variedade comercial de dendezeiro, Elaeis guineensis Jacq. BRS2501 (Lima et al., 2013). Os protocolos utilizados para detectar os produtos gerados (ácidos graxos) nos testes de atividade de lipases totais envolveram a titulação e a cromatografia líquida. Os testes para lipases realizados em titulador automático indicaram redução no valor de pH ao longo do tempo, quando a polpa macerada do mesocarpo foi adicionada ao reator contendo o substrato (óleo). Entretanto, a titulação não é um método seletivo e pode detectar qualquer fenômeno em que haja liberação de íons H+. Devido a isto, não se pode afirmar que a redução do pH observada nos testes de atividade enzimática estaria necessariamente sendo causada pela liberação dos ácidos graxos. Por isso as amostras foram também analisadas por cromatografia líquida. A análise cromatográfica de amostras coletadas dos ensaios de hidrólise da polpa macerada de dendê, realizados em titulador automático sob diferentes valores de pH, indicou a ação de lipase(s) na liberação de ácidos, tais como: oleico, linoleico, palmítico e esteárico. Pela análise dos produtos da hidrólise de óleo de dendê por meio de cromatografia líquida, conclui?se que o valor de pH em que a(s) lipase(s) apresentam melhor desempenho é o pH 5, enquanto os ensaios titulométricos indicam o pH 7. Isso ocorre, provavelmente, devido à limitação do método titulométrico para a detecção dos ácidos graxos a pH 5,0, no qual os ácidos graxos são fracamente dissociados. Neste trabalho, a ação de lipases sobre o óleo de dendê foi comprovada, mas os dados não são conclusivos quanto à origem dessa ação, se ela é endógena ou exógena. Assim, outras ações, como análise metagenômica (microrganismos cultiváveis e não cultiváveis) versus o secretoma (metabólitos e proteínas), devem ser aplicadas para que se possa identificar a procedência das lipases presentes na polpa dos frutos do dendê. Abstract: One of the main challenges during the harvest of palm fruits and the extraction of oil from them is the maintenance of oil quality, avoiding the release of fatty acids, which change the properties of the oil and, consequently, reduce its commercial value. Usually, the release of fatty acids in palm fruits is due to lipases. However, there is no consensus on which lipases (endogenous or exogenous) are responsible for acidification. Previous studies have confirmed the presence of endogenous and exogenous lipases in oil palm fruit mesocarp. However, data on the concentration of these enzymes and their biochemical characterization are scarce, and it is due to the difficulty in isolating the lipase from the oil palm fruit mesocarp in its active form. In this work, the lipolytic activity was studied in samples of palm fruits produced by cultivar BRS 2501. The hydrolysis assays were performed using both mesocarp paste and protein extracts obtained from it. The methods used to detect the products of enzyme reaction were: titration and liquid chromatography. Titration in the pH- ?stat indicated that mesocarp paste gave a rate of acid appearance. However, it is not a selective method, so the appearance of any substance that releases hydrogen ions could be mistaken for the release of fatty acids. The products of the enzyme reaction were also analyzed by liquid chromatography to determine if the reaction medium's pH reduction is due to the appearance of fatty acids. Samples from mesocarp paste hydrolysis tests performed at different pH values were analyzed by HPLC and confirmed the action of lipases, with pH 5 being the optimum value. The main products determined by HPLC were oleic, linoleic, palmitic, and stearic acids. On the other hand, titrimetric tests indicated pH 7 as the optimal pH value. This behavior is probably due to the limitation of the titrimetric method for the detection of fatty acids at pH 5.0, in which they are weakly dissociated. In this work, the action of lipases on palm oil was confirmed by chromatographic and titrimetric methods, however, the data are not conclusive as to their origin, whether endogenous or exogenous.Título em inglês: Determination of lipolytic activities in the palm oil fruit

Influência da iluminação e da aeração sobre o crescimento de Chlorella sorokiniana em meio BG11.

Representando uns dos principais objetos de estudos atualmente, microalgas são, em geral, microrganismos fotossintetizantes altamente capazes de retirar CO2 atmosférico e gerar biomassa rica em biomoléculas de interesse industrial e comercial. No entanto, para obtenção de altos valores de rendimento e produtividade, condições ideais de crescimento são muito importantes. Diante disso, o objetivo deste trabalho foi comparar a influência de biorreatores, ou modelos utilizados para o cultivo, sobre o crescimento e o rendimento de biomassa de Chlorella sorokiniana em meio BG11 e, também, verificar os resultados que o uso de diferentes luzes pode gerar. Para tanto, foram realizados dois experimentos não simultâneos em que, primeiramente, a cepa foi cultivada em dois módulos de cultivos diferentes: módulo novo (MN), com biorreatores e sistema de aeração novos da sala de microalgas; e módulo antigo (MA), utilizando Erlenmeyers, pipeta estéril para passagem de ar e outros componentes. Em um segundo momento, com o intuito de analisar quais luzes e combinações geram maiores crescimentos e, por conseguinte, maiores biomassas secas finais, as microalgas foram cultivadas sob três condições de iluminação diferentes: luz branca (B), luz branca + luz colorida (B+C) e luz colorida (C). Para os dois módulos, temperatura, aeração e pH também foram por espectrofotometria, contagem de células, leitura de turbidez por OD manual e centrifugação e liofilização das biomassas, para saber o peso de massa seca final, foram feitas. Com isso, as análises e os testes mostraram rendimento de biomassa bem maior em MN em comparação com MA e maior crescimento dos cultivos crescidos sob luz B+C, havendo diferenças significativas em ambos os experimentos. Esses resultados permitiram demonstrar a maior eficiência dos novos módulos de cultivo de microalgas da Embrapa Agroenergia e quais luzes utilizadas geram maiores crescimentos, destacando&#8209;se também a importância de se ter condições de cultivo adequadas

Mediterranean diet and bladder cancer risk in Italy

Previous studies have reported that Mediterranean diet is inversely related to the risk of several neoplasms; however, limited epidemiological data are available for bladder cancer. Thus, we examined the association between Mediterranean diet and this neoplasm in an Italian multicentric case-control study consisting of 690 bladder cancer cases and 665 controls. We assessed the adherence to the Mediterranean diet via a Mediterranean Diet Score (MDS), which represents the major characteristics of the Mediterranean diet and ranges from 0 to 9 (from minimal to maximal adherence, respectively). We derived odds ratios (ORs) of bladder cancer according to the MDS score from multiple logistic regression models, allowing for major confounding factors. The ORs of bladder cancer were 0.72 (95% confidence interval, CI, 0.54\u20130.98) for MDS of 4\u20135 and 0.66 (95% CI, 0.47\u20130.93) for MDS of 6\u20139 (p for trend = 0.02) compared to MDS = 0\u20133. Results were similar in strata of sex, age, and education, while the risk appeared somewhat lower in never-smokers and patients with pT1\u2013pT4 bladder carcinomas. Among individual components of the MDS, we observed inverse associations for greater consumption of legumes, vegetables, and fish. In our study, which was carried out on an Italian population, the higher adherence to the Mediterranean diet was related to a lower risk of bladder cancer