OP01.31: Incorporation of nasal bone assessment into first‐trimester Down syndrome screening with free beta hCG, PAPP‐A and nuchal translucency

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Searching for antimicrobial photosensitizers among a panel of BODIPYs

In recent years, antimicrobial Photodynamic Therapy (aPDT) gained increasing attention for its potential to inhibit the growth and spread of microorganisms, both as free-living cells and/or embedded in biofilm communities. In this scenario, compounds belonging to the family of boron-dipyrromethenes (BODIPYs) represent a very promising class of photosensitizers for applications in antimicrobial field. In this study, twelve non-ionic and three cationic BODIPYs were assayed for the inactivation of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. As expected, S. aureus showed to be very sensitive to BODIPYs and mild conditions were sufficient to reach good rates of photoinactivation with both neutral and monocationic ones. Surprisingly, one neutral compound (named B9 in this study) resulted the best BODIPY to photoinactivate P. aeruginosa PAO1. The photoinactivation of C. albicans was reached with both neutral and mono-cationic BODIPYs. Furthermore, biofilms of the three model microorganisms were challenged with BODIPYs in light-based antimicrobial technique. S. aureus biofilms were successfully inhibited with milder conditions than those applied to P. aeruginosa and C. albicans. Notably, it was possible to eradicate 24-h-old biofilms of both S. aureus and P. aeruginosa. In conclusion, this study supports the potential of neutral BODIPYs as pan-antimicrobial PSs. Graphical abstract: [Figure not available: see fulltext.]

Screening Antibacterial Photodynamic Effect of Monascus Red Yeast Rice (Hong-Qu) and Mycelium Extracts

The fungus Monascus is a well-known source of secondary metabolites with interesting pharmaceutical and nutraceutical applications. In particular, Monascus pigments possess a wide range of biological activities (e.g. antimicrobial, antioxidant, anti-inflammatory or antitumoral). To broaden the scope of their possible application, this study focused on testing Monascus pigment extracts as potential photosensitizing agents efficient in antimicrobial photodynamic therapy (aPDT) against bacteria. For this purpose, eight different extracts of secondary metabolites from the liquid- and solid-state fermentation of Monascus purpureus DBM 4360 and Monascus sp. DBM 4361 were tested against Gram-positive and Gram-negative model bacteria, Bacillus subtilis and Escherichia coli and further screened for ESKAPE pathogens, Staphylococcus aureus and Pseudomonas aeruginosa. To the bacterial culture, increasing concentration of extracts was added and it was found that all extracts showed varying antimicrobial activity against Gram-positive bacteria in dark, which was further increased after irradiation. Gram-negative bacteria were tolerant to the extracts’ exposure in the dark but sensitivity to almost all extracts that occurred after irradiation. The Monascus sp. DBM 4361 extracts seemed to be the best potential candidate for aPDT against Gram-positive bacteria, being efficient at low doses, i.e. the lowest total concentration of Monascus pigments exhibiting aPDT effect was 3.92 ± 1.36 mg/L for E. coli. Our results indicate that Monascus spp., forming monascuspiloin as the major yellow pigment and not-forming mycotoxin citrinin, is a promising source of antimicrobials and photoantimicrobials

Photo-Inactivation of Staphylococcus aureus by Diaryl-Porphyrins

Photodynamic Antimicrobial Chemotherapy (PACT) has received great attention in recent years since it is an effective and promising modality for the treatment of human oral and skin infections with the advantage of bypassing pathogens' resistance to antimicrobials. Moreover, PACT applications demonstrated a certain activity in the inhibition and eradication of biofilms, overcoming the well-known tolerance of sessile communities to antimicrobial agents. In this study, 13 diaryl-porphyrins (mono-, di-cationic, and non-ionic) P1-P13 were investigated for their potential as photosensitizer anti-Staphylococcus aureus. The efficacy of the diaryl-porphyrins was evaluated through photo-inactivation tests. Crystal-violet staining combined with viable count techniques were aimed at assaying their anti-biofilm activity. Among the tested compounds, the neutral photosensitizer P4 was better than the cationic ones, irrespective of their corresponding binding rates. In particular, P4 was active in inhibiting the biofilm formation and in impairing the viability of the adherent and planktonic populations of a 24 h old biofilm. The inhibitory activity was also efficient against a methicillin resistant S. aureus strain. In conclusion, the diaryl-porphyrin family represents a reservoir of promising compounds for photodynamic applications against the pathogen S. aureus and in preventing the formation of biofilms that cause many infections to become chronic

Antimicrobial Blue Light (aBL) as a potential tool to reduce bacterial spoilage in the fishery chain

Along the fishery chain, a high amount of fish is lost for the activity of spoilage microorganisms originating from the environment, human handling and fish themselves. Different techniques are conventionally used to reduce the growth of bacteria: from cold temperature and icing to high concentration of salts, from drying to natural antimicrobial compounds. In this study, the antimicrobial Blue Light (aBL) was considered as an innovative tool. In particular, the irradiation with light at 410 nm inhibited the growth of most bacteria isolated from skin samples of anchovies and sardines chosen for their worldwide commercial importance. Bacterial strains showed a different sensitivity to light treatment: the ones isolated from anchovy were more sensitive than those from sardine. Investigations were performed on Aeromonas bestiarum, an emerging foodborne pathogen. Upon irradiation with light at 410 nm (200 J/cm2), a statistically significant decrease of 3 log units was observed. The same fluence rate successfully inhibited the biofilm formation of A. bestiarum, and disrupted 50 % of the adherent biomass of a 24-h old biofilm. The irradiation of Staphyococcus vitulinus compromised its viability and the associated proteolytic activity known to contribute to meat spoilage. In vivo experiments showed that aBL caused a remarkable decrease (at least 50 %) of viable counts of bacteria from anchovy and sardine skin samples conserved at 4 °C for one day. In conclusion, these results support the potential use of blue light in reducing the growth of skin microorganisms potentially responsible for loss of food safety, quality and decrease of storage life

Exploring the role of RNASET2 in the immune response of black soldier fly larvae

T2 RNases are transferase-type enzymes distributed across phyla, crucial for breaking down single-stranded RNA molecules. In addition to their canonical function, several T2 enzymes exhibit pleiotropic roles, contributing to various biological processes, such as the immune response in invertebrates and vertebrates. This study aims at characterizing RNASET2 in the larvae of black soldier fly (BSF), Hermetia illucens, which are used for organic waste reduction and the production of valuable insect biomolecules for feed formulation and other applications. Given the exposure of BSF larvae to pathogens present in the feeding substrate, it is likely that the mechanisms of their immune response have undergone significant evolution and increased complexity. After in silico characterization of HiRNASET2, demonstrating the high conservation of this T2 homolog, we investigated the expression pattern of the enzyme in the fat body and hemocytes, two districts mainly involved in the insect immune response, in larvae challenged with bacterial infection. While no variation in HiRNASET2 expression was observed in the fat body following infection, a significant upregulation of HiRNASET2 synthesis occurred in hemocytes shortly after the injection of bacteria in the larva. The intracellular localization of HiRNASET2 in lysosomes of plasmatocytes, its extracellular association with bacteria, and the presence of a putative antimicrobial domain in the molecule, suggest its potential role in RNA clean-up and as an alarm molecule promoting phagocytosis activation by hemocytes. These insights contribute to the characterization of the immune response of Hermetia illucens larvae and may facilitate the development of animal feedstuff enriched with highly valuable BSF bioactive compounds

Uso do jardim aquícola no tratamento e reuso da água de piscicultura

As áreas alagadas construídas (AACs) compõem uma série de tecnologias de tratamento de efluentes e que vêm sendo cada vez mais exploradas. As principais vantagens, além da eficiência do tratamento, são o baixo custo de manutenção, implantação e operação. O presente trabalho teve como objetivo analisar o desempenho de uma AAC, denominada de ?Jardim Aquícola?, de fluxo eminentemente horizontal e subsuperficial, no tratamento de um efluente oriundo de tanque escavado para produção de tilápia-do-nilo (Oreochromis niloticus), para fins de tratamento e reuso no mesmo tanque. O sistema foi instalado no Sítio São João, em São Carlos, SP (22°09'16,1?S e 47°50'49,0?W). A água do tanque escavado é bombeada inicialmente para um tanque de equalização e, na sequência, o fluxo ocorre por gravidade. A tecnologia é composta por 3 caixas construídas acima do nível do solo, niveladas, com um desnível de 10 cm entre elas e com tubos e conexões para conectá-las em série e fluxo contínuo. Essas caixas são impermeabilizadas, preenchidas com argila expandida e saturadas com água, com um volume útil total de 2,28 m³. Em cada caixa foram plantadas aproximadamente 80 mudas de Copo de Leite (Zantedeschia aethiopica). Após a saída da terceira caixa, o líquido passa por um sistema de aeração com degraus em série, até retornar ao tanque escavado, operando com um tempo de detenção hidráulica (TDH) médio de 20,2 h. Foram coletadas amostras no tanque escavado (TE) e logo após à saída da terceira caixa (água tratada, AT). Foram analisados parâmetros físicoquímicos da água, para averiguar se a qualidade está em acordo o mínimo adequado para produção do pescado. A eficiência de remoção de DBO, por exemplo, encontrava-se com -1 -1 um valor médio absoluto em TE de 21,40 mg L e em AT o valor cai para 7,60 mg L (64,5 % de eficiência), a DQO segue o mesmo padrão de queda, em TE o valor médio era de -1 -1 74,60 mg L e em AT o valor cai para 19,20 mg L (74,2 % de eficiência). Outros parâmetros que obtiveram uma boa redução de seus valores médios absolutos foram a E. 3 coli, saindo de 5,4 x 10 NMP/100mL para 24,5 NMP/100mL (99,5 %), o fósforo, com -1 -1 valor médio encontrado em TE de 0,71 mg L para 0,27 mg L (62,0%). O nitrogênio total -1 não obteve queda significativa, com valores médios entre TE e AT da ordem de 24 mg L , -1 entretanto, os valores de NH em AT (0,0043 mg L ), obtidos a partir da relação pH, 3 + temperatura e nitrogênio amoniacal NH , mostraram-se dentro dos padrões estabelecidos 4 -1 na literatura (0,01 mg L ). Os resultados mostraram que a água tratada está dentro dos padrões estabelecidos para produção de tilápia-do-nilo. O Jardim Aquícola pode ser utilizado no tratamento e reuso de efluente oriundo de produção em tanque escavado. O reuso em outras espécies, além da tilápia-do-nilo, dependerá da exigência do pescado com relação à qualidade da água

Melanocortin Receptor-4 Gene Polymorphisms in Glioblastoma Patients Treated with Concomitant Radio-Chemotherapy.

Melanocortins are peptides with well-recognized antiinflammatory and neuroprotective activity. No data are currently available on melanocortin receptor-4 (MC4R) gene polymorphisms and tumors, including glioblastomas (GBMs), or their relationship with radiotherapy or chemotherapy. The aim of this study was to evaluate the possible predictive/prognostic role of the MC4R SNPs on GBM patients. Fifty-five patients with a proven diagnosis of GBM, treated with radiotherapy and temozolomide, were consecutively enrolled. MC4R gene SNPs (rs17782313, rs489693, rs8087522, rs17700633) were analyzed by a validated TaqMan® SNP genotyping assays. Univariate and multivariate analyses were performed. A P < 0.0125 (Bonferroni's correction) was considered significant ( Clinicaltrial.gov identifier NCT02458508). The median progression-free survival (PFS) and median overall survival (OS) of these patients were 9.54 (95% CI 5.4-14.3) months and 24.9 (95% CI 17.8-34.6) months, respectively. The MC4R rs489693 AA genotype was significantly associated with a shorter PFS and OS. Indeed, with regard to PFS, patients harboring the rs489693 AA genotype had a median PFS of 2.99 months whereas patients with AC/CC genotypes had a median PFS of 10.82 months (P = 0.009). Interestingly, the rs489693 AA patients also had a lower median OS as compared with the median OS of the AC/CC genotypes (10.75 vs. 29.5 months, respectively, P = 0.0001). This study suggests that the MC4R rs489693 AA genotype is significantly associated with a shorter PFS and OS in patients treated with radiotherapy and temozolomide. These findings represent a relevant effort to identify novel clinical markers for RT-CT therapy in GBM to be validated in future pharmacogenetic clinical trials

The CUORE Cryostat: A 1-Ton Scale Setup for Bolometric Detectors

The cryogenic underground observatory for rare events (CUORE) is a 1-ton scale bolometric experiment whose detector consists of an array of 988 TeO2 crystals arranged in a cylindrical compact structure of 19 towers. This will be the largest bolometric mass ever operated. The experiment will work at a temperature around or below 10 mK. CUORE cryostat consists of a cryogen-free system based on pulse tubes and a custom high power dilution refrigerator, designed to match these specifications. The cryostat has been commissioned in 2014 at the Gran Sasso National Laboratories and reached a record temperature of 6 mK on a cubic meter scale. In this paper, we present results of CUORE commissioning runs. Details on the thermal characteristics and cryogenic performances of the system will be also given.Comment: 7 pages, 2 figures, LTD16 conference proceedin

Silver sulfadiazine eradicates antibiotic-tolerant Staphylococcus aureus and Pseudomonas aeruginosa biofilms in patients with infected diabetic foot ulcers

Infections are among the most frequent and challenging events in diabetic foot ulcers (DFUs). Pathogenic bacteria growing in biofilms within host tissue are highly tolerant to environmental and chemical agents, including antibiotics. The present study was aimed at assessing the use of silver sulfadiazine (SSD) for wound healing and infection control in 16 patients with DFUs harboring biofilm-growing Staphylococcus aureus and Pseudomonas aeruginosa. All patients received a treatment based on a dressing protocol including disinfection, cleansing, application of SSD, and application of nonadherent gauze, followed by sterile gauze and tibio-breech bandage, in preparation for toilet surgery after 30 days of treatment. Clinical parameters were analyzed by the T.I.M.E. classification system. In addition, the activity of SSD against biofilm-growing S. aureus and P. aeruginosa isolates was assessed in vitro. A total of 16 patients with S. aureus and P. aeruginosa infected DFUs were included in the study. Clinical data showed a statistically significant (p &lt; 0.002) improvement of patients’ DFUs after 30 days of treatment with SSD with significant amelioration of all the parameters analyzed. Notably, after 30 days of treatment, resolution of infection was observed in all DFUs. In vitro analysis showed that both S. aureus and P. aeruginosa isolates developed complex and highly structured biofilms. Antibiotic susceptibility profiles indicated that biofilm cultures were significantly (p ≤ 0.002) more tolerant to all tested antimicrobials than their planktonic counterparts. However, SSD was found to be effective against fully developed biofilms of both S. aureus and P. aeruginosa at concentrations below those normally used in clinical preparations (10 mg/mL). These results strongly suggest that the topical administration of SSD may represent an effective alternative to conventional antibiotics for the successful treatment of DFUs infected by biofilm-growing S. aureus and P. aeruginosa