Diabetic ketoacidosis in pregnancy

Diabetic ketoacidosis in pregnancy is a rare but potential life-threatening condition for the mother and the fetus. It tends to occur latter in pregnancy and is more common in patients with pregestational diabetes. Obstetricians should be aware of the events that can trigger diabetic ketoacidosis in pregnancy. Prompt recognition and aggressive treatment of this condition are essential in order to reduce perinatal mortality and morbidity. The authors present a case of a pregnant woman with type 1 diabetes with a poor surveillance of pregnancy and noncompliance to treatment that develops severe diabetic ketoacidosis at 34 weeks of gestation

Sustainable exopolysaccharide production by rhizobium viscosum CECT908 using corn steep liquor and sugarcane molasses as sole substrates

Microbial exopolysaccharides (EPS) are promising alternatives to synthetic polymers in a variety of applications. Their high production costs, however, limit their use despite their outstanding properties. The use of low-cost substrates such as agro-industrial wastes in their production, can help to boost their market competitiveness. In this work, an alternative low-cost culture medium (CSLM) was developed for EPS production by Rhizobium viscosum CECT908, containing sugarcane molasses (60 g/L) and corn steep liquor (10 mL/L) as sole ingredients. This medium allowed the production of 6.1 ± 0.2 g EPS/L, twice the amount produced in the standard medium (Syn), whose main ingredients were glucose and yeast extract. This is the first report of EPS production by R.viscosum using agro-industrial residues as sole substrates. EPSCSLM and EPSSyn exhibited a similar carbohydrate composition, mainly 4-linked galactose, glucose and mannuronic acid. Although both EPS showed a good fit to the HerschelBulkley model, EPSCSLM displayed a higher yield stress and flow consistency index when compared with EPSSyn, due to its higher apparent viscosity. EPSCSLM demonstrated its potential use in Microbial Enhanced Oil Recovery by enabling the recovery of nearly 50% of the trapped oil in sand-pack column experiments using a heavy crude oil.info:eu-repo/semantics/publishedVersio

OC33 Chromatographic approaches to study pine nut skin: exploitation of its composition and bioactivities

Pine nut skin (PNS) is an unexploited and uncharacterized by-product recovered during pine nut processing. The exploitation of by-products as sources of valuable compounds agrees with the current demand for the reduction of waste, and a transition to more sustainable production and consumption1. Therefore, PNS characterization and bioactive potentialities were assessed. The utilization of several chromatographic techniques allowed the characterization of PNS phenolic compounds (HPLC-DAD-UV and HPLC-DAD-ESI-MSn), and the carbohydrates quantification and structural characterization, after specific derivatization (GC-FID and GC-MS). PNS subcritical water extraction using microwave was optimized and the obtained extracts, separated into low-molecularweight (rich in phenolic compounds) and high-molecular-weight (rich in carbohydrates), were evaluated regarding their digestibility and prebiotic activity. The prebiotic potential was assessed by quantifying the short-chain fatty acids (HPLC-UV) produced after the in vitro faecal fermentation. HPLC-DAD-ESI-MSn allowed to identify PNS phenolic compounds, namely protocatechuic, p-coumaric, and caffeic acids, while HPLC-DAD-UV enabled the monomers identification of proanthocyanidins ((epi)catechins) and hydrolysable tannins (protocatechuic acid), after acid methanolysis. GC techniques allowed to disclose the polysaccharides structures (xyloglucans and pectic polysaccharides) and their degradation by microbiota. The fermentation of both extracts rich in phenolic compounds and rich in polysaccharides resulted in an increased production of acetic, propionic, and butyric acids when compared to the commercial prebiotic inulin, proposing these PNS extracts as prebiotic agents.The work was supported through the projects UIDB/50006/2020 and UIDP/50006/2020, funded by FCT/MCTES through national funds. Soraia P. Silva, Alondra González and Dalila Roupar thank FCT/MCTES and ESF through NORTE 2020 for their PhD grants (ref. SFRH/BD/136471/2018, SFRH/BD/06268/2021 and SFRH/DB/139884/2018 respectively). Elisabete Coelho thanks the research contract (CDL-CTTRI-88-ARH/2018 – REF. 049-88-ARH/2018) funded by national funds (OE), through FCT, in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. Clarisse Nobre acknowledges FCT for the assistant research contract 2021.01234.CEECIND.info:eu-repo/semantics/publishedVersio

Compositional features and bioactive properties of aloe vera leaf (Fillet, mucilage, and rind) and flower

This work aimed to characterize compositional and bioactive features of Aloe vera leaf (fillet, mucilage, and rind) and flower. The edible fillet was analysed for its nutritional value, and all samples were studied for phenolic composition and antioxidant, anti-inflammatory, antimicrobial, tyrosinase inhibition, and cytotoxic activities. Dietary fibre (mainly mannan) and available carbohydrates (mainly free glucose and fructose) were abundant macronutrients in fillet, which also contained high amounts of malic acid (5.75 g/100 g dw) and -tocopherol (4.8 mg/100 g dw). The leaf samples presented similar phenolic profiles, with predominance of chromones and anthrones, and the highest contents were found in mucilage (131 mg/g) and rind (105 mg/g) extracts, which also revealed interesting antioxidant properties. On the other hand, the flower extract was rich in apigenin glycoside derivatives (4.48 mg/g), effective against Pseudomonas aeruginosa (MIC = 0.025 mg/mL and MBC = 0.05 mg/mL) and capable of inhibiting the tyrosinase activity (IC50 = 4.85 mg/mL). The fillet, rind, and flower extracts also showed a powerful antifungal activity against Aspergillus flavus, A. niger, Penicillium funiculosum, and Candida albicans, higher than that of ketoconazole. Thus, the studied Aloe vera samples displayed high potential to be exploited by the food or cosmetic industries, among others.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) and FEDER(European Regional Development Fund) under Programme PT2020 for financial support to CIMO (UID/AGR/00690/2019) and the research contracts of J. Pinela, R.C. Calhelha, and L. Barros (national funding by FCT, through the institutional scientific employment program-contract); to the Project AllNat—POCI-01-0145-FEDER-030463 (PTDC/EQU-EPQ/30463/2017), funded by FEDER funds through COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI)—and by national funds through FCT/MCTES; and to FEDER-Interreg España-Portugal programme for financial support through the project 0377_Iberphenol_6_E.info:eu-repo/semantics/publishedVersio

Hydrolysates containing xylooligosaccharides produced by different strategies: structural characterization, antioxidant and prebiotic activities

" Available online 22 May 2022"This study explores the structural characterization, antioxidant and prebiotic activities of hydrolysates containing xylooligosaccharides (XOS) produced by different strategies: direct fermentation of beechwood xylan (FermBX) and enzymatic treatment of beechwood (EnzBX) and rice husk (EnzRH) xylans. EnzBX and EnzRH showed XOS with a backbone of (1 4)-linked-xylopyranosyl residues and branches of arabinose, galactose, and uronic acids. FermBX presented the highest content of total phenolic compounds (14 mg GAE/g) and flavonoids (0.6 mg QE/g), which may contribute to its antioxidant capacity 39.1 mol TE/g (DPPH), 45.7 mol TE/g (ABTS), and 79.9 mol Fe II/g (FRAP). The fermentation of hydrolysates decreased the abundance of microorganisms associated with intestinal diseases from Eubacteriales, Desulfovibrionales and Methanobacteriales orders, while stimulating the growth of organisms belonging to Bacteroides, Megamonas and Limosilactobacillus genera. The production of short-chain fatty acids, ammonia, and CO2 suggested the prebiotic potential. In conclusion, hydrolysates without previous purification and obtained from non-chemical approaches demonstrated promising biological activities for further food applications.This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) – Finance Code 001; by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) – Grant numbers 423285/2018-1 and 304857/2018-1; by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UIDB/04469/2020 unit; by the BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 – Programa Operacional Regional do Norte; by the COMPETE 2020 (POCI-01-0145- FEDER-006684); by the FoSynBio (POCI-01-0145-FEDER-029549); and LAQV/REQUIMTE (UIDB/50006/2020, UIDP/50006/2020) through national founds and, where applicable, co-financed by the FEDER, within the PT2020 Partnership Agreement. GG acknowledges the Universidade Federal do Rio Grande for the financial support from Postgraduate Student Mobility Program (PROPESP/FURG). BC, CA, and SPS acknowledge their grants (SFRH/BD/132324/2017, 2020.00293 CEECIND, and SFRH/BD/136471/2018) from FCT. LB also acknowledge FCT for the junior research contract (CEECIND/03280/2020). EC thanks the research contract (CDL-CTTRI-88-ARH/2018 – REF. 049-88-ARH/2018) funded by national funds (OE), through FCT, in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19.info:eu-repo/semantics/publishedVersio

Rabbit derived VL single-domains as promising scaffolds to generate antibody–drug conjugates

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Antibody-drug conjugates (ADCs) are among the fastest-growing classes of therapeutics in oncology. Although ADCs are in the spotlight, they still present significant engineering challenges. Therefore, there is an urgent need to develop more stable and effective ADCs. Most rabbit light chains have an extra disulfide bridge, that links the variable and constant domains, between Cys80 and Cys171, which is not found in the human or mouse. Thus, to develop a new generation of ADCs, we explored the potential of rabbit-derived VL-single-domain antibody scaffolds (sdAbs) to selectively conjugate a payload to Cys80. Hence, a rabbit sdAb library directed towards canine non-Hodgkin lymphoma (cNHL) was subjected to in vitro and in vivo phage display. This allowed the identification of several highly specific VL-sdAbs, including C5, which specifically target cNHL cells in vitro and present promising in vivo tumor uptake. C5 was selected for SN-38 site-selective payload conjugation through its exposed free Cys80 to generate a stable and homogenous C5-DAB-SN-38. C5-DAB-SN-38 exhibited potent cytotoxicity activity against cNHL cells while inhibiting DNA-TopoI activity. Overall, our strategy validates a platform to develop a novel class of ADCs that combines the benefits of rabbit VL-sdAb scaffolds and the canine lymphoma model as a powerful framework for clinically translation of novel therapeutics for cancer.This work was supported by the Portuguese Funding Agency, Fundação para a Ciência e Tecnologia, FCT IP (SAICT/2017/32085, PTDC/QUI-OUT/3989/2021 and Ph.D. fellowship SFRH/BD/131468/2017 to ASA and SFRH/BD/90514/2012 to JD). CIISA has provided support through Project UIDB/00276/2020, funded by FCT and LA/P/0059/2020-AL4AnimalS. Research Institute for Medicines (iMed.ULisboa) acknowledges the financial support of Fundação para a Ciência e Tecnologia (Projects: PTDC/QUI-OUT/3989/2021; UIDB/04138/2020 and UIDP/04138/2020). The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project Nº 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC).info:eu-repo/semantics/publishedVersio

Phylogenetic Group of Escherichia coli

The aim of the study was to determine the phylogenetic groups of E. coli strains isolated from seemingly healthy broiler and broiler condemned suspected of colibacillosis in a Brazilian slaughterhouse. Samples from respiratory tract and edible giblets (liver and heart) of broilers with and without macroscopic lesions of colibacillosis were collected at slaughter. There were 84 strains isolated from broilers condemned of which 11 were obtained from swabs of the heart, 7 from the liver, and 66 from the respiratory tract. Of the 53 E. coli strains isolated from broilers not condemned, 5 were isolated from the heart, 4 from the liver, and 44 from the respiratory tract. E coli strains were tested via PCR for phylogenetic groups A, B1, B2, C, D, E, and F. Phylogroups A and B1 were the most common phylogroups of E. coli obtained from healthy and sick-appearing broiler carcasses. The results of the study showed that phylogroups B2 and E were associated with the heart samples and phylogroup A was associated with respiratory tract samples, phylogroup B1 with not condemned carcass, and phylogroup D with liver samples

Toxoplasmosis-associated IRIS involving the CNS: a case report with longitudinal analysis of T cell subsets

Background: HIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality. Hence, a deeper knowledge of CNS-IRIS pathogenesis is needed. Case presentation: A 37-year-old man was diagnosed with AIDS and cerebral toxoplasmosis. Anti-toxoplasma treatment was initiated immediately, followed by active antiretroviral therapy (HAART) 1 month later. At 2 months of HAART, he presented with progressive hyposensitivity of the right lower limb associated with brain and dorsal spinal cord lesions, compatible with paradoxical toxoplasmosis-associated CNS-IRIS, a condition with very few reported cases. A stereotactic biopsy was planned but was postponed based on its inherent risks. Patient showed clinical improvement with no requirement of corticosteroid therapy. Routine laboratorial analysis was complemented with longitudinal evaluation of blood T cell subsets at 0, 1, 2, 3 and 6 months upon HAART initiation. A control group composed by 9 HIV-infected patients from the same hospital but with no IRIS was analysed for comparison. The CNS-IRIS patient showed lower percentage of memory CD4(+) T cells and higher percentage of activated CD4(+) T cells at HAART initiation. The percentage of memory CD4(+) T cells drastically increased at 1 month after HAART initiation and became higher in comparison to the control group until clinical recovery onset; the percentage of memory CD8(+) T cells was consistently lower throughout follow-up. Interestingly, the percentage of regulatory T cells (Treg) on the CNS-IRIS patient reached a minimum around 1 month before symptoms onset. Conclusion: Although both stereotactic biopsies and steroid therapy might be of use in CNS-IRIS cases and should be considered for these patients, they might be unnecessary to achieve clinical improvement as shown in this case. Immunological characterization of more CNS-IRIS cases is essential to shed some light on the pathogenesis of this condition.Portuguese Foundation for Science and Technology (FCT; PIC/IC/83313/2007) and co-financed by the Portuguese North Regional Operational Program (ON.2 - O Novo Norte) under the National Strategic Reference Framework (QREN) through the European Regional Development Fund (FEDER). A FCT fellowship was attributed to RRS (PD/BD/106047/2015; Inter-University Doctoral Program in Ageing and Chronic Disease) and to CN [SFRH/BPD/65380/2009; Programa Operacional Potencial Humano (POPH) through the Fundo Social Europeu (FSE)]info:eu-repo/semantics/publishedVersio