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Abstract Bdellovibrio bacteriovorus HD100 is an obligate predatory bacterium that preys upon Gram‐negative bacteria. It has been proposed to be applied as a “living antibiotic” in several fields such as agriculture or even medicine, since it is able to prey upon bacterial pathogens. Its interesting lifestyle makes this bacterium very attractive as a microbial chassis for co‐culture systems including two partners. A limitation to this goal is the scarcity of suitable synthetic biology tools for predator domestication. To fill this gap, we have firstly adapted the hierarchical assembly cloning technique Golden Standard (GS) to make it compatible with B. bacteriovorus HD100. The chromosomal integration of the Tn7 transposon's mobile element, in conjunction with the application of the GS technique, has allowed the systematic characterization of a repertoire of constitutive and inducible promoters, facilitating the control of the expression of heterologous genes in this bacterium. PJExD/EliR proved to be an exceptional promoter/regulator system in B. bacteriovorus HD100 when precise regulation is essential, while the synthetic promoter PBG37 showed a constitutive high expression. These genetic tools represent a step forward in the conversion of B. bacteriovorus into an amenable strain for microbial biotechnology approaches.

Objectives To evaluate the external validity of the FINDRISC, DESIR and ADA risk scores for the prediction of diabetes in a Spanish population aged >45 years and to test the possible improvement of FINDRISC by adding a new variable of high risk of depression when Patient Health Questionnaire-9 (PHQ-9) questionnaire score ≥10 (FINDRISC-MOOD).Design Prospective population-based cohort study.Setting 10 primary healthcare centres in the north of the city of Madrid (Spain).Participants A total of 1242 participants without a history of diabetes and with 2-hour oral glucose tolerance test (OGTT) plasma glucose

Abstract Cashew nut is a globally popular nut not only for its delicious and crunchy flavor but also for bioactive compounds, which present positive benefits to human health. Different parts of cashew have characteristic compounds. The kernel of cashew nut is rich in fatty acids, the testa is rich in polyphenols, cashew apple is rich in polyphenols and carotenoids, and phenols with aliphatic long chain are present in the cashew nutshell liquid. Therefore, the edible part of cashew possesses a wide range of bioactive compounds, with reported biological properties, including anti‐tumor, brain health, cardiovascular and cerebrovascular protection, anti‐diabetic, gastroprotection, pathophysiological disorders protection, and antioxidant. On the other hand, the inedible part of cashew, the cashew nutshell liquid, could play an important role in the industry as surface coatings, insulating formulations and so on. Hence, there are considerable demands to increase the added value of cashew, thereby exploring greater economic value. Thus, this review summarizes nutrients, bioactive compounds, biological functions, and applications of Anacardium occidentale to provide a theoretical basis and inspiration for further in‐depth studies and utilization.

Citrus fruits are widely grown, processed, and distributed in more than 140 countries, with annual global production exceeding 124.3 million metric tons. This substantial consumption generates significant organic waste, accounting for approximately 50–60% of the total fruit mass, primarily in the form of peel, pulp, and seeds. Often discarded or reused as animal feed, these wastes contribute to significant environmental pollution and economic losses. Therefore, the valorization of these by-products represents an important opportunity to mitigate these challenges and improve the sustainability of the Citrus-related industry. This review highlights Citrus seed waste concerning its invaluable bioactive compounds, including fatty acids, phenolic compounds, limonoids, dietary fibers, vitamins, and carotenoids. Chemical compositions of Citrus seed biowaste differ depending on a variety of factors, such as Citrus variety, fruit maturity, environmental conditions, waste storage conditions, and extraction methods. The extraction and purification of phytochemicals from Citrus seed biowaste are one of the major procedures for valorizing waste. The two types of effective extraction methods are traditional (conventional extraction) and innovative (green extraction). Furthermore, Citrus seeds have been demonstrated to exhibit several biological activities and health-promoting properties including antioxidative, anti-inflammatory, and anti-cancer activities. Therefore, these wastes are safe and beneficial compounds used in the production of functional foods, nutraceuticals, pharmaceuticals, and cosmetics. A conclusion can be reached by emphasizing the abundance of bioactive compounds in Citrus seed wastes, which makes them an excellent opportunity for increased environmental and economic utilization.

Summary: Bacterial polyhydroxyalkanoates (PHAs) have emerged as promising eco-friendly alternatives to petroleum-based plastics since they are synthesized from renewable resources and offer exceptional properties. However, their production is limited to the stationary growth phase under nutrient-limited conditions, requiring customized strategies and costly two-phase bioprocesses. In this study, we tackle these challenges by employing a model-driven approach to reroute carbon flux and remove regulatory constraints using synthetic biology. We construct a collection of Pseudomonas putida-overproducing strains at the expense of plastics and lignin-related compounds using growth-coupling approaches. PHA production was successfully achieved during growth phase, resulting in the production of up to 46% PHA/cell dry weight while maintaining a balanced carbon-to-nitrogen ratio. Our strains are additionally validated under an upcycling scenario using enzymatically hydrolyzed polyethylene terephthalate as a feedstock. These findings have the potential to revolutionize PHA production and address the global plastic crisis by overcoming the complexities of traditional PHA production bioprocesses.

Consumers are increasingly interested in food products with high nutritional value and health benefits. For instance, fish consumption is linked with diverse positive health benefits and the prevention of certain widespread disorders, such as obesity, metabolic syndrome, or cardiovascular diseases. These benefits have been attributed to its excellent nutritional value (large amounts of high-quality fatty acids, proteins, vitamins, and minerals) and bioactive compounds, while being relatively low-caloric. Atlantic bluefin tuna (Thunnus tynnus) is one of the most consumed species worldwide, motivated by its good nutritional and organoleptic characteristics. Recently, some organizations have proposed limitations on its consumption due to the presence of contaminants, mainly heavy metals such as mercury. However, several studies have reported that most specimens hold lower levels of contaminants than the established limits and that their richness in selenium effectively limits the contaminants’ bioaccessibility in the human body. Considering this situation, this study aims to provide baseline data about the nutritional composition and the latest evidence regarding the beneficial effects of Atlantic bluefin tuna consumption. A review of the risk-benefit ratio was also conducted to evaluate the safety of its consumption, considering the current suggested limitations to this species’ consumption.

Abstract Bioplastics, comprised of bio‐based and/or biodegradable polymers, have the potential to play a crucial role in the transition towards a sustainable circular economy. The use of biodegradable polymers not only leads to reduced greenhouse gas emissions but also might address the problem of plastic waste persisting in the environment, especially when removal is challenging. Nevertheless, biodegradable plastics should not be considered as substitutes for proper waste management practices, given that their biodegradability strongly depends on environmental conditions. Among the challenges hindering the sustainable implementation of bioplastics in the market, the development of effective downstream recycling routes is imperative, given the increasing production volumes of these materials. Here, we discuss about the most advisable end‐of‐life scenarios for bioplastics. Various recycling strategies, including mechanical, chemical or biological (both enzymatic and microbial) approaches, should be considered. Employing enzymes as biocatalysts emerges as a more selective and environmentally friendly alternative to chemical recycling, allowing the production of new bioplastics and added value and high‐quality products. Other pending concerns for industrial implementation of bioplastics include misinformation among end users, the lack of a standardised bioplastic labelling, unclear life cycle assessment guidelines and the need for higher financial investments. Although further research and development efforts are essential to foster the sustainable and widespread application of bioplastics, significant strides have already been made in this direction.

Abstract Objectives Antiphospholipid syndrome (APS) is an autoimmune disease driven by antiphospholipid antibodies (aPL). Currently, APS diagnosis requires a combination of clinical manifestations (thrombosis and/or obstetric morbidity) and the persistent presence of at least one criteria aPL: anti‐cardiolipin antibodies (aCL), anti‐β2‐glycoprotein I antibodies (aβ2GPI) or lupus anticoagulant (LA). Patients with suggestive obstetric symptoms but lacking criteria aPL face diagnostic challenges. Non‐criteria aPL screening may enhance discrimination. This study proposes a classification incorporating both criteria and non‐criteria antibodies to improve obstetric APS diagnosis. Methods Blood samples from non‐pregnant women (n = 68) with a history of vascular, obstetric, or vascular and obstetric manifestations were analysed. Among them, 30 had previous diagnosis of APS. Healthy women with proven gestational success were included as controls (n = 16). Criteria and non‐criteria (anti‐phosphatidylglycerol, anti‐phosphatidylethanolamine, anti‐phosphatidylinositol, anti‐phosphatidylserine and anti‐phosphatidic acid) IgG aPL were evaluated by ELISA and coagulation tests. Based on the resulting aPL profile, patients were reclassified. Responsiveness to treatment was obtained from medical records. Results Criteria aPL levels marginally differentiated women previously managed as obstetric APS from unexplained/other causes of obstetric morbidity. Including non‐criteria aPL improved separation. The proposed classification identified an obstetric APS group that exhibits non‐criteria aPL and aβ2GPI titres below the cut‐off but higher than healthy women (7.88 vs. 2.47 SGU, P = 0.006). Compared to cases of other causes of obstetric morbidity, these patients retrospectively responded better to aspirin and/or heparin treatment (71.43% vs. 11.11%, P = 0.035). Conclusions Assessing non‐criteria antibodies may identify isolated obstetric APS cases benefiting from established therapies.

ABSTRACT Photosynthesis (PS) in purple non-Sulfur bacteria (PNSB) is strictly controlled to avoid energy consumption and to prevent oxidative stress when oxygen is present. PpsR, a transcriptional repressor encoded in the photosynthesis gene cluster (PGC), is one of the main players in the regulation of PS-related genes. In some cases, PpsR does not sense the environmental cue by itself but delegates this task to other proteins like PpaA/AerR anti-repressors, which can ultimately affect PpsR affinity to some promoter regions. In this work, the effects of locus Rru_A0625 product (HP1) on PS regulation of Rhodospirillum rubrum were studied by mutation/complementation and transcriptomic strategies. Rru_A0625 is located next to ppsR gene, just like other PpaA/AerR members, and its deletion annuls pigment synthesis in dark micro/anaerobic growth conditions. HP1 shows similarity to PpaA/AerR anti-repressors family, although it does not possess their typical cobalamin binding domain. A transcriptomic analysis of Rru_A0625 deletion mutant showed that HP1 not only has effects on bacteriochlorophyll and carotenoid biosynthesis, but also many other biological processes in the cell. The most notorious is the impact on the transcription of the nitrogenase complex components and accessory proteins. Our results suggest that this new member of the PpaA/AerR family has evolved losing the canonical cobalamin binding domain, but not the redox sensing capability, conserving a not fully understood mechanism of PS regulation.IMPORTANCERhodospirillum rubrum vast metabolic versatility places it as a remarkable model bacterium and an excellent biotechnological chassis. The key component of photosynthesis (PS) studied in this work (HP1) stands out among the other members of PpaA/AerR anti-repressor family since it lacks the motif they all share: the cobalamin B-12 binding motif. Despite being reduced and poorly conserved, HP1 stills controls PS as the other members of the family, allowing a fast response to changes in the redox state of the cell. This work also shows that HP1 absence affects genes from relevant biological processes other than PS, including nitrogen fixation and stress response. From a biotechnological perspective, HP1 could be manipulated in approaches where PS is not necessary, such as hydrogen or polyhydroxyalkanoates production, to save energy.

Abstract Finding a food system to feed the growing worldwide population remains a challenge, especially in the current era, where natural resources are being dramatically depleted. From a historical point of view, the Green Revolution, together with biofortification and sustainable intensification, was established as a possible solution to counter hunger and malnutrition during the second half of the 20th century. As a solution, to overcome the limitations attributed to the Green Revolution, food supply chains were developed. The current food system, based on the long food supply chain (LFSC), is characterized by globalization, promoting several advantages for both producers and consumers. However, LFSC has been demonstrated to be unable to feed the global population and, furthermore, it generates negative ecological, environmental, logistical, and nutritional pressures. Thus, novel efficient food systems are required to respond to current environmental and consumers’ demands, as is the case of short food supply chain (SFSC). As a recently emerging food system, the evaluation of SFSC sustainability in terms of environmental, economic, and social assessment is yet to be determined. This review is focused on the evolution of food supply systems, starting from the Green Revolution to food supply chains, providing a significant perspective on sustainability.

Abstract Background Microbially produced bioplastics are specially promising materials since they can be naturally synthesized and degraded, making its end-of-life management more amenable to the environment. A prominent example of these new materials are polyhydroxyalkanoates. These polyesters serve manly as carbon and energy storage and increase the resistance to stress. Their synthesis can also work as an electron sink for the regeneration of oxidized cofactors. In terms of biotechnological applications, the co-polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate), or PHBV, has interesting biotechnological properties due to its lower stiffness and fragility compared to the homopolymer poly(3-hydroxybutyrate) (P3HB). In this work, we explored the potentiality of Rhodospirillum rubrum as a producer of this co-polymer, exploiting its metabolic versatility when grown in different aeration conditions and photoheterotrophically. Results When shaken flasks experiments were carried out with limited aeration using fructose as carbon source, PHBV production was triggered reaching 29 ± 2% CDW of polymer accumulation with a 75 ± 1%mol of 3-hydroxyvalerate (3HV) (condition C2). Propionate and acetate were secreted in this condition. The synthesis of PHBV was exclusively carried out by the PHA synthase PhaC2. Interestingly, transcription of cbbM coding RuBisCO, the key enzyme of the Calvin-Benson-Bassham cycle, was similar in aerobic and microaerobic/anaerobic cultures. The maximal PHBV yield (81% CDW with 86%mol 3HV) was achieved when cells were transferred from aerobic to anaerobic conditions and controlling the CO2 concentration by adding bicarbonate to the culture. In these conditions, the cells behaved like resting cells, since polymer accumulation prevailed over residual biomass formation. In the absence of bicarbonate, cells could not adapt to an anaerobic environment in the studied lapse. Conclusions We found that two-phase growth (aerobic-anaerobic) significantly improved the previous report of PHBV production in purple nonsulfur bacteria, maximizing the polymer accumulation at the expense of other components of the biomass. The presence of CO2 is key in this process demonstrating the involvement of the Calvin-Benson-Bassham in the adaptation to changes in oxygen availability. These results stand R. rubrum as a promising producer of high-3HV-content PHBV co-polymer from fructose, a PHBV unrelated carbon source.

Abstract Background Primary care electronic medical records contain clinical-administrative information on a high percentage of the population. Before this information can be used for epidemiological purposes, its quality must be verified. This study aims to validate diagnoses of atrial fibrillation (AF) recorded in primary care electronic medical records and to estimate the prevalence of AF in the population attending primary care consultations. Methods We performed a cross-sectional validation study of all diagnoses of AF recorded in primary care electronic medical records in Madrid (Spain). We also performed simple random sampling of diagnoses of AF (ICPC-2 code K78) registered by 55 physicians and random age- and sex-matched sampling of the records that included a diagnosis of AF. Electrocardiograms, echocardiograms, and hospital discharge or cardiology clinic reports were matched. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and overall agreement were calculated using the kappa statistic (κ). The prevalence of AF in the community of Madrid was estimated considering the sensitivity and specificity obtained in the validation. All calculations were performed overall and by sex and age groups. Results The degree of agreement was very high (κ = 0.952), with a sensitivity of 97.84%, specificity of 97.39%, PPV of 97.37%, and NPV of 97.85%. The prevalence of AF in the population aged over 18 years was 2.41% (95%CI 2.39–2.42% [2.25% in women and 2.58% in men]). This increased progressively with age, reaching 16.95% in those over 80 years of age (15.5% in women and 19.44% in men). Conclusions The validation results obtained enable diagnosis of AF recorded in primary care to be used as a tool for epidemiological studies. A high prevalence of AF was found, especially in older patients.

Abstract Background Animal models are increasingly used in Nursing science to study care approaches. Despite the scientific relevance and the ethical debate surrounding the use of experimental animals, there is a scarcity of scholarly literature exploring this topic in Nursing Schools. Aim To evaluate perceptions and attitudes of nursing students enrolled in a Pharmacology course on the use of experimental animals and implementation of alternative methods, by comparing the experience for two academic years. An interdisciplinary collaboration has also been developed. Methods A descriptive cross-sectional, quantitative study was developed. Undergraduate nursing students were enrolled in the Pharmacology subject at the University of Leon (Spain). The study was carried out in the Pharmacology facilities. Students followed a two-session practical class regarding experimental animals and alternative methods in the Pharmacology course (Degree in Nursing) in two different academic years (2019–20/2020–21). At the end of the activity, they answered a questionnaire to assess their opinions on the use of experimental animals and alternative methods in Pharmacology and the 3Rs principle. Results A comparison of the students’ perception with and without direct participation in the evaluation of promazine effects in mice was made. A total of 190 students participated in the teaching experience, providing high scores in all items (4–5 out of 5 points) regarding the teaching experience. Students became also aware of the advantages and disadvantages on the use of experimental animals, as well as the ethical considerations to bear in mind for their use and the need for alternative methods. Conclusions In the students’ opinion, the total replacement of animals by alternative techniques was very difficult, and they preferred to do the practice face-to-face. The alternative method designed was useful for the students to accept the employment of experimental animals in biomedical research and education, and know the legislation applied in the protection of animals.

Designing cell factories for the production of novel polyhydroxyalkanoates (PHAs) via smart metabolic engineering is key to obtain à la carte materials with tailored physicochemical properties. To this end, we used the model medium-chain-length-PHA producing bacterium, P. putida KT2440 as a chassis, which is characterized by its metabolic versatility and stress tolerance. Different PHA biosynthetic modules were assembled in expression plasmids using the Golden gate/MoClo modular assembly technique to implement an orthogonal short-chain-lengh-PHA (scl-PHA) switch in a “deaf” PHA mutant. This was specifically constructed to override endogenous multilevel regulation of PHA synthesis in the native strain. We generated a panel of engineered approaches carrying the genes from Rhodospirillum rubrum, Cupriavidus necator and Pseudomonas pseudoalcaligenes, demonstrating that diverse scl-PHAs can be constitutively produced in the chassis strain to varying yields from 23% to 84% PHA/CDW. Co-feeding assays of the most promising engineered strain harboring the PHA machinery from C. necator resulted to a panel of PHBV from 0.6% to 19% C5 monomeric incorporation. Chromosomally integrated PHA machineries with high PhaCCn synthase dosage successfully resulted in 68% PHA/CDW production. Interestingly, an inverse relationship between PhaC synthase dosage and granule size distribution was demonstrated in the heterologous host. In this vein, it is proposed the key involvement of inclusion body protein IbpA to the heterologous production of tailored PHA in P. putida KT2440.

In Mediterranean vineyards, high temperatures and scarce water resources affect the quantity and quality of harvests. Crop forcing (F) is a novel approach that consists of inducing the bud burst of buds developed during the current season in order to modify the phenology of the vine and shift berry ripening to a period of moderate temperatures. The aim of this work is to evaluate the effect of F on cv. Tempranillo grapes in the semi-arid conditions of Extremadura (Spain) under different water regimes. A field experiment was carried out from 2017 to 2019 in a vineyard of cv. Tempranillo with three pruning treatments: winter pruning only (NF) and two F treatments, in which, in addition to winter pruning, forced pruning was carried out at two different phenological stages, after flowering (F1) and after fruit set (F2). These treatments were subjected to two watering regimes: irrigation covering the vines' water requirements (I) and deficit irrigation (DI) with moderate water stress during the pre-harvest period. The average delay in harvest of the F treatments compared to NF was 32 and 56 days in F1 and F2, respectively, with a decrease in the average temperature during ripening (veraison to harvest). Yield was lower in F1 and F2 than in NF regardless of water regime, although yield levels were more stable between seasons in these treatments. Titratable acidity, malic acid content, total polyphenol content and total anthocyanin content increased in the F treatments, and the combined application of F and DI improved grape composition but also resulted in a higher yield penalty.

Abstract Phytic acid (PA) is an abundant natural plant component that exhibits a versatility of applications benefited from its chemical structure, standing out its use as food, packing and dental additive due to its antimicrobial properties. The capacity of PA to chelate ions is also well-established and the formation and thermodynamic properties of different metallic complexes has been described. However, research studies of these compounds in terms of chemistry and biological features are still demanded in order to extend the application scope of PA complexes. The main goal of this paper is to deepen in the knowledge of the bioactive metal complexes chemistry and their bactericide activity, to extend their application in biomaterial science, specifically in oral implantology. Thus, this work presents the synthesis and structural assessment of two metallic phytate complexes bearing the bioactive cations Zn2+ and Sr2+ (ZnPhy and SrPhy respectively), along with studies on the synergic biological properties between PA and cations. Metallic phytates were synthesized in the solid-state by hydrothermal reaction leading to pure solid compounds in high yields. Their molecular formulas were C6H12024P6Sr4·5H2O and C6H12024P6Zn6·6H2O, as determined by ICP and HRES-TGA. The metal coordination bond of the solid complexes was further analysed by EDS, Raman, ATR-FTIR and solid 13C and 31P-NMR spectroscopies. Likewise, we evaluated the in vitro ability of the phytate compounds for inhibiting biofilm production of Streptococcus mutans cultures. Results indicate that all compounds significantly reduced biofilm formation (PA

Polymeric nanoparticles (NPs) present some ideal properties as biomedical nanocarriers for targeted drug delivery such as enhanced translocation through body barriers. Biopolymers, such as polyhydroxyalkanoates (PHAs) are gaining attention as nanocarrier biomaterials due to their inherent biocompatibility, biodegradability, and ability to be vehiculized through hydrophobic media, such as the lung surfactant (LS). Upon colonization of the lung alveoli, below the LS layer, Streptococcus pneumoniae, causes community-acquired pneumonia, a severe respiratory condition. In this work, we convert PHA NPs into an antimicrobial material by the immobilization of an enzybiotic, an antimicrobial enzyme, via a minimal PHA affinity tag. We first produced the fusion protein M711, comprising the minimized PHA affinity tag, MinP, and the enzybiotic Cpl-711, which specifically targets S. pneumoniae. Then, a PHA nanoparticulate suspension with adequate physicochemical properties for pulmonary delivery was formulated, and NPs were decorated with M711. Finally, we assessed the antipneumococcal activity of the nanosystem against planktonic and biofilm forms of S. pneumoniae. The resulting system displayed sustained antimicrobial activity against both, free and sessile cells, confirming that tag-mediated immobilization of enzybiotics on PHAs is a promising platform for bioactive antimicrobial functionalization.

Abstract This work aimed to evaluate the predatory activity of Bdellovibrio bacteriovorus 109J on clinical isolates of Pseudomonas aeruginosa selected from well-characterized collections of cystic fibrosis (CF) lung colonization (n = 30) and bloodstream infections (BSI) (n = 48) including strains selected by genetic lineage (frequent and rare sequence types), antibiotic resistance phenotype (susceptible and multidrug-resistant isolates), and colony phenotype (mucoid and non-mucoid isolates). The intraspecies predation range (I-PR) was defined as the proportion of susceptible strains within the entire collection. In contrast, the predation efficiency (PE) is the ratio of viable prey cells remaining after predation compared to the initial inoculum. I-PR was significantly higher for CF (67%) than for BSI P. aeruginosa isolates (35%) probably related to an environmental origin of CF strains whereas invasive strains are more adapted to humans. I-PR correlation with bacterial features such as mucoid morphotype, genetic background, or antibiotic susceptibility profile was not detected. To test the possibility of increasing I-PR of BSI isolates, a polyhydroxyalkanoate depolymerase deficient B. bacteriovorus bd2637 mutant was used. Global median I-PR and PE values remained constant for both predators, but 31.2% of 109J-resistant isolates were susceptible to the mutant, and 22.9% of 109J-susceptible isolates showed resistance to predation by the mutant, pointing to a predator–prey specificity process. The potential use of predators in the clinical setting should be based on the determination of the I-PR for each species, and the PE of each particular target strain.

Resumen: Objetivo: Conocer las repercusiones del confinamiento por la pandemia de COVID-19 en los autocuidados de personas con enfermedades crónicas y en su salud percibida, e identificar factores para el manejo y la gestión de su enfermedad en situaciones de emergencia. Método: Estudio cualitativo realizado en marzo-abril de 2020, durante el confinamiento por la pandemia de COVID-19, en Andalucía (España), mediante grupos focales virtuales usando la herramienta telemática Zoom. Se realizaron tres grupos con 34 pacientes (17 hombres y 17 mujeres) con enfermedades crónicas: artritis, diabetes, enfermedad cardiovascular, enfermedad inflamatoria intestinal, cáncer de mama y fibromialgia. Resultados: Las personas con enfermedades crónicas refirieron repercusiones del confinamiento en relación con su vivencia emocional, sus recursos de afrontamiento, la información recibida, las dificultades para el autocuidado y el contacto/acceso a los servicios sanitarios, además de sugerir aprendizajes para el futuro. Más y mejor información, formación de pacientes, colaboración directa con asociaciones de pacientes por parte de los gestores y una mejora de la accesibilidad telemática a los servicios sanitarios destacan como las principales líneas de mejora para minimizar el impacto de futuros confinamientos en el autocuidado y en la salud de las personas con enfermedades crónicas. Conclusiones: Durante el confinamiento, las personas con enfermedades crónicas experimentaron dificultades más allá del riesgo de contagio: interferencias en el cuidado y en la atención sanitaria recibida. Es necesaria mayor información y más formación a los/las pacientes y mejoras en la accesibilidad a los servicios sanitarios en situaciones de crisis sanitaria. Abstract: Objective: To understand the consequences of the COVID-19 pandemic lockdown on the self-care of people living with chronic diseases and on their self-perceived health, and to identify factors that may influence the management of their disease in emergency situations. Method: A qualitative study conducted in 2020 (March and April) in Andalusia (Spain) during the COVID-19 pandemic lockdown, through virtual focus groups, using the Zoom telematics tool. Three virtual focus groups were conducted, including 34 patients from Andalusia with different chronic conditions such as arthritis, diabetes, cardiovascular disease, inflammatory bowel disease, breast cancer and fibromyalgia. Results: People with chronic diseases reported effects of the lockdown in relation to their emotional experience, their coping resources, the information they received, the difficulties to manage self-care, and the contact or access to health services. They also suggested some lessons learned for the future. The need for more and better information, patient training, involving patient associations, and improving telematics access to health services are the main areas for improvement to minimize the impact of future quarantines on the self-care and the health of people with chronic diseases. Conclusions: Besides the risk of contracting COVID-19, the difficulties encountered by people with chronic diseases during the lockdown include interferences in the self-care and the health care received. Health crisis situations demand more information, training for patients and improvements in the health services accessibility for patients with chronic conditions.

Curcumin (CUR) is a bioactive compound that has been proposed for the treatment of various neurodegenerative diseases. However, its use is limited due to its low solubility in aqueous media and chemical instability under physiological conditions. Herein, we propose a strategy to overcome these limitations by using PAMAM dendrimers of generation 4.5 (DG4.5). Using a combination of biophysical techniques together with in vitro models, we demonstrate that CUR-DG4.5 complexes: (i) increased the solubility and stability of CUR via internalization into dendrimer's pockets and interaction with terminal carboxylic groups; (ii) showed in vitro biocompatibility and increased CUR uptake; (iii) presented DPPH radical scavenging activity and in vitro inhibition of H2O2-induced stress; and (iv) interfere with α-synuclein aggregation. In conclusion, this work lays the foundation to use curcumin-loaded PAMAM dendrimers of generation 4.5 as nanodrugs capable of reducing oxidative stress and inhibiting α-synuclein aggregation to treat synucleinopathies.

Placenta accreta spectrum (PAS) is one of the major causes of maternal morbidity and mortality worldwide with increasing incidence. PAS refers to a group of pathological conditions ranging from the abnormal attachment of the placenta to the uterus wall to its perforation and, in extreme cases, invasion into surrounding organs. Among them, placenta accreta is characterized by a direct adhesion of the villi to the myometrium without invasion and remains the most common diagnosis of PAS. Here, we identify the potential regulatory miRNA and target networks contributing to placenta accreta development. Using small RNA-Seq followed by RT-PCR confirmation, altered miRNA expression, including that of members of placenta-specific miRNA clusters (e.g., C19MC and C14MC), was identified in placenta accreta samples compared to normal placental tissues. In situ hybridization (ISH) revealed expression of altered miRNAs mostly in trophoblast but also in endothelial cells and this profile was similar among all evaluated degrees of PAS. Kyoto encyclopedia of genes and genomes (KEGG) analyses showed enriched pathways dysregulated in PAS associated with cell cycle regulation, inflammation, and invasion. mRNAs of genes associated with cell cycle and inflammation were downregulated in PAS. At the protein level, NF-κB was upregulated while PTEN was downregulated in placenta accreta tissue. The identified miRNAs and their targets are associated with signaling pathways relevant to controlling trophoblast function. Therefore, this study provides miRNA:mRNA associations that could be useful for understanding PAS onset and progression.

Summary Bacterial biopolymers such as bacterial cellulose (BC), alginate or polyhydroxyalkanotes (PHAs) have aroused the interest of researchers in many fields, for instance biomedicine and packaging, due to their being biodegradable, biocompatible and renewable. Their properties can easily be tuned by means of microbial biotechnology strategies combined with materials science. This provides them with highly diverse properties, conferring them non‐native features. Herein we highlight the enormous structural diversity of these macromolecules, how are they produced, as well as their wide range of potential applications in our daily lives. The emergence of new technologies, such as synthetic biology, enables the creation of next‐generation‐advanced materials presenting smart functional properties, for example the ability to sense and respond to stimuli as well as the capacity for self‐repair. All this has given rise to the recent emergence of biohybrid materials, in which a synthetic component is brought to life with living organisms. Two different subfields have recently garnered particular attention: hybrid living materials (HLMs), such as encapsulation or bioprinting, and engineered living materials (ELMs), in which the material is created bottom‐up with the use of microbial biotechnology tools. Early studies showed the strong potential of alginate and PHAs as HLMs, whilst BC constituted the most currently promising material for the creation of ELMs.

To the memory of Jordi Marsal

Abstract Background Rhodospirillum rubrum is a purple non-sulphur bacterium that produces H2 by photofermentation of several organic compounds or by water gas-shift reaction during CO fermentation. Successful strategies for both processes have been developed in light-dependent systems. This work explores a dark fermentation bioprocess for H2 production from water using CO as the electron donor. Results The study of the influence of the stirring and the initial CO partial pressure (p CO) demonstrated that the process was inhibited at p CO of 1.00 atm. Optimal p CO value was established in 0.60 atm. CO dose adaptation to bacterial growth in fed-batch fermentations increased the global rate of H2 production, yielding 27.2 mmol H2 l−1 h−1 and reduced by 50% the operation time. A kinetic model was proposed to describe the evolution of the molecular species involved in gas and liquid phases in a wide range of p CO conditions from 0.10 to 1.00 atm. Conclusions Dark fermentation in R. rubrum expands the ways to produce biohydrogen from CO. This work optimizes this bioprocess at lab-bioreactor scale studying the influence of the stirring speed, the initial CO partial pressure and the operation in batch and fed-batch regimes. Dynamic CO supply adapted to the biomass growth enhances the productivity reached in darkness by other strategies described in the literature, being similar to that obtained under light continuous syngas fermentations. The kinetic model proposed describes all the conditions tested.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease of unknown cause, which mainly affects women of childbearing age, especially between 15 and 55 years of age. During pregnancy, SLE is associated with a high risk of perinatal morbidity and mortality. Among the most frequent complications are spontaneous abortion, fetal death, prematurity, intrauterine Fetal growth restriction (FGR), and preeclampsia (PE). The pathophysiology underlying obstetric mortality and morbidity in SLE is still under investigation, but several studies in recent years have suggested that placental dysfunction may play a crucial role. Understanding this association will contribute to developing therapeutic options and improving patient management thus reducing the occurrence of adverse pregnancy outcomes in this group of women. In this review, we will focus on the relationship between SLE and placental insufficiency leading to adverse pregnancy outcomes.

The concept of biological identity has been traditionally a central issue in immunology. The assumption that entities foreign to a specific organism should be rejected by its immune system, while self-entities do not trigger an immune response is challenged by the expanded immunotolerance observed in pregnancy. To explain this “immunological paradox”, as it was first called by Sir Peter Medawar, several mechanisms have been described in the last decades. Among them, the intentional transfer and retention of small amounts of cells between a mother and her child have gained back attention. These microchimeric cells contribute to expanding allotolerance in both organisms and enhancing genetic fitness, but they could also provoke aberrant alloimmune activation. Understanding the mechanisms used by microchimeric cells to exert their function in pregnancy has proven to be challenging as per definition they are extremely rare. Profiting from studies in the field of transplantation and cancer research, a synergistic effect of microchimerism and cellular communication based on the secretion of extracellular vesicles (EVs) has begun to be unveiled. EVs are already known to play a pivotal role in feto-maternal tolerance by transferring cargo from fetal to maternal immune cells to reshape their function. A further aspect of EVs is their function in antigen presentation either directly or on the surface of recipient cells. Here, we review the current understanding of microchimerism in the feto-maternal tolerance during human pregnancy and the potential role of EVs in mediating the allorecognition and tropism of microchimeric cells.

Los trabajos de limpieza y un sondeo valorativo superficial realizado sobre el túmulo de Perravella 1 (Acevedo, Cerceda, A Coruña) para evaluar su estado de conservación han sacado a la luz fragmentos de un vaso campaniforme y algunas muestras que pudieron datarse. El estudio combinado de la estratigrafía, los resultados radiocarbónicos y el estudio de la cerámica (formal y arqueométrico) ha permitido constatar un uso prolongado y complejo de un túmulo que apenas se percibe en el terreno. Nuestro objetivo es realizar una síntesis de los datos que tenemos del yacimiento, siendo estos referentes a las reutilizaciones del monumento a lo largo del tiempo, y no a la construcción del mismo. De esta forma, hemos podido identificar tres momentos de uso: por un lado, el III milenio BC, gracias a los restos de una vasija campaniforme, y, por otro lado, la Época Altomedieval y el Periodo Moderno, reflejados en las dataciones radiocarbónicas y la estratigrafía del túmulo. [gl] Os traballos de limpeza e unha sondaxe valorativa superficial realizada sobre o túmulo de Perravella 1 (Acevedo, Cerceda, A Coruña) para avaliar o seu estado de conservación sacaron á luz fragmentos dun vaso campaniforme e algunhas mostras que puideron datarse. O estudo combinado da estratigrafía, os resultados radiocarbónicos e o estudo da cerámica (formal e arqueométrico) permitiron constatar un uso prolongado e complexo dun túmulo que apenas é perceptible no terreo. O noso obxectivo é realizar unha síntese dos datos obtidos do xacemento, sendo estes referentes ás reutilizacións do monumento ao longo do tempo, e non á construción do mesmo. Deste modo, puidemos identificar tres momentos de uso: por unha banda, o III milenio BC, grazas aos restos dun vaso campaniforme, e, doutra, a Época Altomedieval e o Período Moderno, reflectidos nas datacións radiocarbónicas e na estratigrafía do túmulo.

Introduction Conversion disorder (a term that describes what was previously called hysteria) refers to motor or sensory symptoms, or both, that resemble a neurological disease, but that do not originate from or cannot be explained by a known physical disease. Objectives To find reliable tools that can guide the difficult diagnosis of conversion disorder. Methods Bibliographic review Results The exact prevalence of the disorder is unknown. It is estimated that approximately 5% of referrals to neurology are for this disorder. Approximately one third of patients referred to the neurologist have symptoms that cannot be explained by an organic disease. Involuntary movements are the most common motor manifestations of the conversive syndrome, being tremor one of the most frequent manifestations. The first differential diagnosis of conversion disorder is neurological disease. It is currently not necessary for the diagnosis to assess whether or not the symptoms are produced intentionally, as the assessment of conscious intentionality is unreliable. The neurological examination is the fundamental tool for the diagnostic approach, being even more enlightening than the complementary tests. Hoover’s sign, Babinski’s combined leg flexion, plantar flexion of the ankle, tremor and its distraction and synchronisation manoeuvres, as well as the clinical differences between epileptic seizures and non-epileptic seizures of psychogenic origin, are some of the reliable tools for a correct diagnosis. Conclusions The diagnosis of the disease should be one of exclusion. There must be clinical data showing clear evidence of incompatibility with a neurological disease and conversion symptoms do not correspond to known physiological mechanisms and anatomical pathways. Disclosure No significant relationships.

Introduction The lack of a standardised definition for the concept of TRD and an adequate criteria for therapeutic response make difficult the management of patients with MDD who do not achieve remission with one or more courses of treatment. All classifications suggested to define TRD are arbitrary, partially evidence-based, subordinated to the pharmacological findings of the time in which they are written and with serious inconsistencies, making it difficult to construct a universal and enduring diagnostic system. Objectives Considering that the most important goal in treating a patient with Major Depressive Disorder (MDD) should be remission and return to previous functionality, the search for a standardised, evidence-based classification system will allow timely and effective interventions leading to the reduction of this devastating condition. Methods Bibliographic review Results The proposed therapeutic algorithm arises from the combination of several fundamental principles for the management of treatment-resistant depression: the different classification systems of the concept, as well as the concepts of response, relapse, recurrence and remission; the scientific evidence found in the current literature, routine clinical practice, knowledge of switching and augmentation strategies, the new pharmacological targets and neurobiological hypothesis discovered, without forgetting finally the different clinical profiles of depressive symptomatology and the specific indications of each antidepressant. Conclusions Resistant depression is difficult to treat successfully and is not a uniform entity. Recently there has been a move to characterise treatment-resistant depression as ‘difficult-to-treat’ depression on the basis that the former description implies that depression treatments are normally effective and that non-response is therefore somehow abnormal. Disclosure No significant relationships.

Abstract De novo mutations (DNMs), including germinal and postzygotic mutations (PZMs), are a strong source of causality for Autism Spectrum Disorder (ASD). However, the biological processes involved behind them remain unexplored. Our aim was to detect DNMs (germinal and PZMs) in a Spanish ASD cohort (360 trios) and to explore their role across different biological hierarchies (gene, biological pathway, cell and brain areas) using bioinformatic approaches. For the majority of the analysis, a combined ASD cohort (N = 2171 trios) was created using previously published data by the Autism Sequencing Consortium (ASC). New plausible candidate genes for ASD such as FMR1 and NFIA were found. In addition, genes harboring PZMs were significantly enriched for miR-137 targets in comparison with germinal DNMs that were enriched in GO terms related to synaptic transmission. The expression pattern of genes with PZMs was restricted to early mid-fetal cortex. In contrast, the analysis of genes with germinal DNMs revealed a spatio-temporal window from early to mid-fetal development stages, with expression in the amygdala, cerebellum, cortex and striatum. These results provide evidence of the pathogenic role of PZMs and suggest the existence of distinct mechanisms between PZMs and germinal DNMs that are influencing ASD risk.

In the Mediterranean scenery of the south-western Iberian Peninsula, vineyards and wine-making have consistently been key pieces of the man-made cultural landscape, influencing urban design and even housing. This paper compares wine production influence in the cities of Borba, in Portuguese Alentejo, Jerez de la Frontera and Bollullos Par del Condado, in Spanish Andalusia, throughout the spheres of territorial organization, urban layout, presence of production buildings inside urban areas, and winemaker and wineworker housing. The study is based on architectonic surveys of building types: wineries, dwellings and houses with integrated wine production on both sides of the Guadiana River. The information gathered in surveys is complemented with data from historical documents, such as transaction records from the 16th to the 19th centuries. The research analyses cycles of prosperity for the three case studies – which are often coincident and related, within the frame of pre-industrial global trade – and the effects of those in winery and housing typologies. Across the studied area, vernacular winery types adhere to the same two categories, or typological lines, of building: the domestic winery and the autonomous building. Wine related architecture is still a key asset in these cities' material and cultural heritage, as it provides scale and uniqueness to the urban and rural ensembles, despite the fact that wine production has been removed from cities’ centres to outer industrial wineries. The memory of wine-induced prosperity is imprinted on the cities’ physical realities, giving meaning to their collective memories and proving to be an asset to future development.