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Abstract This study explores a potential solution to the shortage of kidneys for transplantation in end-stage renal disease (ESRD). Currently, kidney transplantation stands as the optimal option, yet the scarcity of organs persists. Employing tissue engineering, researchers sought to assess the feasibility of generating kidneys for transplantation. Pig kidneys were utilized since they possess higher similarities to human kidneys. Cells were removed via decellularization, which maintains the organ’s microarchitecture. Subsequently, pig kidney cells and human red blood cells were perfused into the vacant kidney structure to reconstitute it. The methodologies employed showed promising results, suggesting a viable approach to increase the recellularization rate in whole pig kidneys. This proof-of-concept establishes a groundwork for potentially extending this technology to human kidneys, tackling the organ shortage, thus positively enhancing outcomes for ESRD patients by increasing the availability of transplantable organs.

Abstract The extended period of coexistence between Neanderthals and Homo sapiens in Europe coincided with the emergence of regionally distinctive lithic industries, signalling the onset of the Upper Palaeolithic. The Iberian Peninsula was on the periphery of pioneering Upper Palaeolithic developments, with archaeological remains primarily found in northern territories. We report the discovery of an initial Upper Palaeolithic lithic industry at Cueva Millán in the hinterlands of Iberia. This industry, termed here Arlanzian, not only represents the earliest and southernmost evidence of such industries in Iberia but also lacks a direct counterpart. However, it exhibits chronological and technological parallels with the lithic industries associated with the earliest expansion of Homo sapiens throughout Eurasia. We interpret this as potential evidence of its intrusive nature, but not necessarily associated with a migration event, as more complex scenarios derived from inter-population connectivity must be also considered. The biological identity of the Arlanzian makers remains unknown, but they coexisted with declining Neanderthal groups from neighbouring territories.

Abstract Spectral filters are fundamental building blocks in integrated photonics. Bragg grating filters have been demonstrated in silicon waveguides with a wide range of spectral responses and are suitable for wavelength division multiplexing applications. However, retrieving Bragg grating reflections typically requires external components such as fiber optic circulators. In this work, we develop fully integrated add-drop filters based on cladding-modulated Bragg gratings incorporated in a Mach–Zehnder interferometer configuration. We design complex spectral filtering devices with single and dual-band flat-top responses for the specified bandwidth. Additionally, we propose a novel design methodology which aims to minimize phase errors within the filters. We experimentally demonstrate add-drop filters with single-band and two-band rejection spectra at the datacom O-band, fabricated on a 220-nm thick silicon-on-insulator platform. Our results show an insertion loss below 1 dB and a crosstalk of around −20 dB at the channel center for a 4.5-nm wavelength grid and 3-nm wide channels.

Abstract Tritrichomonas foetus is a flagellated and anaerobic parasite able to infect cattle and felines. Despite its prevalence, there is no effective standardized or legal treatment for T. foetus-infected cattle; the vaccination still has limited success in mitigating infections and reducing abortion risk; and nowadays, the diagnosis of T. foetus presents important limitations in terms of sensitivity and specificity in bovines. Here, we characterize the plasma membrane proteome of T. foetus and identify proteins that are represented in different isolates of this protozoan. Additionally, we performed a bioinformatic analysis that revealed the antigenicity potential of some of those proteins. This analysis is the first study to identify common proteins at the plasma membrane of different T. foetus isolates that could be targets for alternative diagnostic or vaccine techniques in the future.

Abstract Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy for treating cancers. This method consists in modifying the patients’ T-cells to directly target antigen-presenting cancer cells. One of the barriers to the development of this type of therapies, is target antigen heterogeneity. It is thought that intratumour heterogeneity is one of the leading determinants of therapeutic resistance and treatment failure. While understanding antigen heterogeneity is important for effective therapeutics, a good therapy strategy could enhance the therapy efficiency. In this work we introduce an agent-based model (ABM), built upon a previous ABM, to rationalise the outcomes of different CAR T-cells therapies strategies over heterogeneous tumour-derived organoids. We found that one dose of CAR T-cell therapy should be expected to reduce the tumour size as well as its growth rate, however it may not be enough to completely eliminate it. Moreover, the amount of free CAR T-cells (i.e. CAR T-cells that did not kill any cancer cell) increases as we increase the dosage, and so does the risk of side effects. We tested different strategies to enhance smaller dosages, such as enhancing the CAR T-cells long-term persistence and multiple dosing. For both approaches an appropriate dosimetry strategy is necessary to produce “effective yet safe” therapeutic results. Moreover, an interesting emergent phenomenon results from the simulations, namely the formation of a shield-like structure of cells with low antigen expression. This shield turns out to protect cells with high antigen expression. Finally we tested a multi-antigen recognition therapy to overcome antigen escape and heterogeneity. Our studies suggest that larger dosages can completely eliminate the organoid, however the multi-antigen recognition increases the risk of side effects. Therefore, an appropriate small dosages dosimetry strategy is necessary to improve the outcomes. Based on our results, it is clear that a proper therapeutic strategy could enhance the therapies outcomes. In that direction, our computational approach provides a framework to model treatment combinations in different scenarios and to explore the characteristics of successful and unsuccessful treatments.

Abstract In this article, the Islamic gold coins collections of the University of Valencia is studied for the first time for its elemental composition and colorimetric properties. To that end, non-destructive elemental analysis using energy-dispersive X-ray fluorescence is applied to obtain the coins’ elemental profile. Additionally, the colour of the coins is assessed using smartphone-based colorimetry as an innovative non-invasive method. Results indicate that the Islamic coins could be attributed to Almoravids, and the gold origin could be the famous Sudanese gold, an ore which was valued all over the world. Also, the text found in the coins was translated and allowed to objectively identify the mint and year. Based on these results, it can be seen that the earliest coins struck in the Iberian Peninsula are characterised by slightly lower gold concentrations than the ones struck in the northern part of Africa, pointing towards a potential recycling of coins which already circulated in the area. In conclusion, this work provides new analytical insights into a peculiar and unique type of samples, allowing to draw some conclusions in terms of their origins and materials, and for the first time allows to characterise the chromatic coordinates of this type of samples.

Abstract Dopamine (DA) plays a critical role in striatal motor control. The drop in DA level within the dorsal striatum is directly associated with the appearance of motor symptoms in Parkinson’s disease (PD). The progression of the disease and inherent disruption of the DA neurotransmission has been closely related to accumulation of the synaptic protein α-synuclein. However, it is still unclear how α-synuclein affects dopaminergic terminals in different areas of dorsal striatum. Here we demonstrate that the overexpression of human α-synuclein (h-α-syn) interferes with the striatal DA neurotransmission in an age‐dependent manner, preferentially in the dorsolateral striatum (DLS) of PDGF-h-α-syn mice. While 3-month-old mice showed an increase at the onset of h-α-syn accumulation in the DLS, 12-month-old mice revealed a decrease in electrically-evoked DA release. The enhanced DA release in 3-month-old mice coincided with better performance in a behavioural task. Notably, DA amplitude alterations were also accompanied by a delay in the DA clearance independently from the animal age. Structurally, dopamine transporter (DAT) was found to be redistributed in larger DAT-positive clumps only in the DLS of 3- and 12-month-old mice. Together, our data provide new insight into the vulnerability of DLS and suggest DAT-related dysfunctionalities from the very early stages of h-α-syn accumulation.

Abstract Diversity of the naive T cell repertoire is maintained by competition for stimuli provided by self-peptides bound to major histocompatibility complexes (self-pMHCs). We extend an existing bi-variate competition model to a multi-variate model of the dynamics of multiple T cell clonotypes which share stimuli. In order to understand the late-time behaviour of the system, we analyse: (i) the dynamics until the extinction of the first clonotype, (ii) the time to the first extinction event, (iii) the probability of extinction of each clonotype, and (iv) the size of the surviving clonotypes when the first extinction event takes place. We also find the probability distribution of the number of cell divisions per clonotype before its extinction. The mean size of a new clonotype at quasi-steady state is an increasing function of the stimulus available to it, and a decreasing function of the fraction of stimuli it shares with other clonotypes. Thus, the probability of, and time to, extinction of a new clonotype entering the pool of T cell clonotypes is determined by the extent of competition for stimuli it experiences and by its initial number of cells.

Abstract Durum wheat cultivation in Mediterranean regions is threatened by abiotic factors, mainly related to the effects of climate change, and biotic factors such as the leaf rust disease. This situation requires an in-depth knowledge of how predicted elevated temperatures and [CO2] will affect durum wheat-leaf rust interactions. Therefore, we have characterised the response of one susceptible and two resistant durum wheat accessions against leaf rust under different environments in greenhouse assays, simulating the predicted conditions of elevated temperature and [CO2] in the far future period of 2070–2099 for the wheat growing region of Cordoba, Spain. Interestingly, high temperature alone or in combination with high [CO2] did not alter the external appearance of the rust lesions. However, through macro and microscopic evaluation, we found some host physiological and molecular responses to infection that would quantitatively reduce not only pustule formation and subsequent infection cycles of this pathogen, but also the host photosynthetic area under these predicted weather conditions, mainly expressed in the susceptible accession. Moreover, our results suggest that durum wheat responses to infection are mainly driven by temperature, being considered the most hampering abiotic stress. In contrast, leaf rust infection was greatly reduced when these weather conditions were also conducted during the inoculation process, resembling the effects of possible heat waves not only in disease development, but also in fungal germination and penetration success. Considering this lack of knowledge in plant-pathogen interactions combined with abiotic stresses, the present study is, to the best of our knowledge, the first to include the effects of the expected diurnal variation of maximum temperature and continuous elevated [CO2] in the durum wheat-leaf rust pathosystem.

Abstract The lumbopelvic muscle mechanical properties (MMPs) are clinically relevant, but their dependence on sex remains unknown. Therefore, this study aimed to identify if lumbopelvic MMPs depend on the sex in a young adult population. Thirty-five healthy nulliparous women and 35 healthy men were analyzed (age range: 18–50). Lumbopelvic MMPs, that is, tone, stiffness, elasticity, relaxation and creep, assessed with MyotonPRO®, and pelvic floor (PF) health questionnaires were compared between-sexes. Intra-group correlations between sociodemographic and clinical data, and MMPs were also determined. The MMPs of PF were different between healthy non-climacteric adults of both sexes, with women showing higher values of tone and stiffness and lower values of elasticity and viscoelastic properties than men (in all cases, p

Abstract Shoreline position is a key parameter of a beach state, often used as a descriptor of the response of the system to changes in external forcing, such as sea-level rise. Changes in shoreline position are the result of coupled hydrodynamic and morphodynamic processes happening in the nearshore and acting at different temporal scales. Due to this complexity, methodologies aimed at reproducing shoreline evolution at decadal time scale require many simplifications. Simpler methods usually consider an equilibrium beach profile whose shape depends only on beach morphology, and whose location varies depending on incoming forcing. Here, we derive a general equation for shoreline evolution using equilibrium beach profiles. We particularize it based on several common assumptions, and evaluate changes on shoreline position caused by sea-level rise, combined with simultaneous wave and high-frequency sea-level forcing. We compare our model against other analytical equilibrium beach profile-based models and with a dynamic model explicitly computing sediment transport. Results indicate that: (i) it is necessary to consider the area of the emerged beach subject to marine forcing rather than focusing only on the submerged part, (ii) the rates of shoreline recession may change for narrow beaches, defined as those for which marine forcings act onto all of their aerial surface, and (iii) Bruun’s Rule can describe beach shoreline evolution, but the uncertainty in selecting the landward boundary of the active profile entails a huge uncertainty in the magnitude of shoreline evolution. This problematic uncertainty can be drastically reduced if instantaneous forcing conditions are used instead of the arbitrary emerged/submerged active profile boundaries typically defined by only one statistic parameter of extreme conditions.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been and remains one of the major challenges modern society has faced thus far. Over the past few months, large amounts of information have been collected that are only now beginning to be assimilated. In the present work, the existence of residual information in the massive numbers of rRT-PCRs that tested positive out of the almost half a million tests that were performed during the pandemic is investigated. This residual information is believed to be highly related to a pattern in the number of cycles that are necessary to detect positive samples as such. Thus, a database of more than 20,000 positive samples was collected, and two supervised classification algorithms (a support vector machine and a neural network) were trained to temporally locate each sample based solely and exclusively on the number of cycles determined in the rRT-PCR of each individual. Overall, this study suggests that there is valuable residual information in the rRT-PCR positive samples that can be used to identify patterns in the development of the SARS-CoV-2 pandemic. The successful application of supervised classification algorithms to detect these patterns demonstrates the potential of machine learning techniques to aid in understanding the spread of the virus and its variants.

Abstract Iberian hare populations have suffered severe declines during recent decades in Spain. Between 1970 and 1990s, a rapid increase in irrigation crop surface in NW Spain (Castilla-y-León region) was followed by a common vole massive range expansion and complete colonization of lowland irrigated agricultural landscapes from mountainous habitats. The subsequent large cyclic fluctuations in abundance of colonizing common voles have contributed to a periodic amplification of Francisella tularensis, the etiological agent that causes human tularemia outbreaks in the region. Tularemia is a fatal disease to lagomorphs, so we hypothesize that vole outbreaks would lead to disease spill over to Iberian hares, increasing prevalence of tularemia and declines among hare populations. Here we report on the possible effects that vole abundance fluctuations and concomitant tularemia outbreaks had on Iberian hare populations in NW Spain. We analysed hare hunting bag data for the region, which has been recurrently affected by vole outbreaks between 1996 and 2019. We also compiled data on F. tularensis prevalence in Iberian hares reported by the regional government between 2007 and 2016. Our results suggest that common vole outbreaks may limit the recovery of hare populations by amplifying and spreading tularemia in the environment. The recurrent rodent-driven outbreaks of tularemia in the region may result in a "disease pit" to Iberian hares: at low host densities, the rate of population growth in hares is lower than the rate at which disease-induced mortality increases with increased rodent host density, therefore, keeping hare populations on a low-density equilibrium. We highlight future research needs to clarify tularemia transmission pathways between voles and hares and confirm a disease pit process.

Abstract This study investigated the intra-rater reliability of a novice ultrasound (US) examiner and the inter-rater reliability of two examiners (novice, expert) in the measures of coracohumeral distance at rest (CHD) and at 60° of elevation without (CHD60) or with weights (CHD60w), tendon thickness of the long head of the biceps (LHB) and subscapularis (SCP). Twenty-one patients with subacromial pain syndrome (SAPS) and 20 asymptomatic participants were included. Intra and inter-rater reliability were tested with intraclass-correlation-coefficient (ICC), differences between raters were analyzed with Bland–Altman plots. Intra-rater reliability for CHD, CHD60 and CHD60w was excellent (ICC = 0.97–0.98) in asymptomatic participants, and good-to-excellent (0.88–0.93) in SAPS, while intra-rater reliability for LHB and SCP was good-to-excellent in asymptomatic participants (0.88–0.97) and in SAPS (0.90–0.92). Inter-rater reliability for CHD, CHD60 and CHD60w was moderate-to-good (0.70–0.90) in asymptomatic participants and good (0.85–0.87) in SAPS, in contrast inter-rater reliability for LHB and SCP was poor in asymptomatic participants (0.10–0.46) and poor-to-moderate (0.49–0.61) in SAPS. Bland–Altman plots revealed systematic and/or proportional bias for tendons’ thickness. A novice showed good-to-excellent intra-rater reliability in all US measures, whereas in comparison to an expert a novice can measure reliably CHD, CHD60 and CHD60w, but not LHB and SCP, where more training is recommended.

Abstract Soil contamination by Pb can result from different anthropogenic sources such as lead-based paints, gasoline, pesticides, coal burning, mining, among others. This work aimed to evaluate the potential of P-loaded biochar (Biochar-based slow-release P fertilizer) to remediate a Pb-contaminated soil. In addition, we aim to propose a biomonitoring alternative after soil remediation. First, rice husk-derived biochar was obtained at different temperatures (450, 500, 550, and 600 °C) (raw biochars). Then, part of the resulting material was activated. Later, the raw biochars and activated biochars were immersed in a saturated KH2PO4 solution to produce P-loaded biochars. The ability of materials to immobilize Pb and increase the bioavailability of P in the soil was evaluated by an incubation test. The materials were incorporated into doses of 0.5, 1.0, and 2.0%. After 45 days, soil samples were taken to biomonitor the remediation process using two bioindicators: a phytotoxicity test and enzyme soil activity. Activated P-loaded biochar produced at 500 °C has been found to present the best conditions for soil Pb remediation. This material significantly reduced the bioavailability of Pb and increased the bioavailability of P. The phytotoxicity test and the soil enzymatic activity were significantly correlated with the decrease in bioavailable Pb but not with the increase in bioavailable P. Biomonitoring using the phytotoxicity test is a promising alternative for the evaluation of soils after remediation processes.

Abstract Several studies propose that Retinopathy of Prematurity (ROP) is a multifactorial disorder implicating many prenatal and postnatal factors. The objective of our study was to determine the incidence and the risk factors that influenced ROP development and progression. We retrospectively compiled data of preterms with birth weight (BW) ≤ 1.500 g and/or gestational age (GA) 72 h or unstable clinical course screened for ROP in Regional University Hospital of Málaga from 2015 to 2018. 202 infants (44.7%) developed ROP and 66 exhibited progression (32.7% of ROP infants). In the univariate analysis, many risk factors were associated with ROP. In the subsequent multivariate analysis, GA, oxygen therapy and weight at 28 days of life, mechanical ventilation duration, non-invasive ventilation, surfactant administration and late-onset sepsis were independently associated with the development. However, oxygen therapy duration, late-onset sepsis and weight at 28 days were associated with the progression. The ROP development and progression risk factors were different. Our results are important to facilitate screening, early diagnosis and ROP treatment while reducing unneeded examinations.

Abstract This systematic review and meta-analysis aim to provide the best evidence on the association between metabolic syndrome (MetS) and uric acid (UA) by determining the size of the effect of this biomarker on MetS. The review protocol is registered with PROSPERO (CRD42021231124). The search covered the PubMed and Scopus databases. Methodological quality was assessed with the STROBE tool, overall risk of bias with RevMan (Cochrane Collaboration) and quality of evidence with Grade Pro. Initially, 1582 articles were identified. Then, after excluding duplicates and reviewing titles and abstracts, 1529 articles were excluded from applying the eligibility criteria. We included 43 papers (56 groups) comparing UA concentrations between subjects 91,845 with MetS and 259,931 controls. Subjects with MetS had a higher mean UA of 0.57 mg/dl (95% CI 0.54–0.61) (p

Abstract Hypertension is a public health issue that can have its origin in the early phases of development. Maternal smoking during pregnancy (MSDP) could play a role in offspring’s cardio-metabolic programming. To assess the relationship between MSDP and later blood pressure (BP) in children we conducted a secondary analysis of a randomized dietary intervention trial (EU-Childhood Obesity Project). Healthy term infants with normal birth weight were recruited during the first 8 weeks of life in 5 European countries and followed until 11 years of age. Data on MSDP was collected at recruitment. BP and anthropometry were assessed at 11 years of age. Children were classified according to AAP guidelines as normal BP: BP 95th percentile categorized as hypertensive. Out of 572 children, 20% were exposed to MSDP. At 11 years, 26.8% had BP over the 90th centile. MSDP beyond 12 weeks of gestation was associated with higher systolic BP percentile (adjusted B 6.935; 95% CI 0.454, 13.429; p = 0.036) and over twofold increase likelihood of hypertension (OR 2.195; 95% CI 1.089, 4.423; p = 0.028) in children at 11 years. MSDP was significantly associated with later BP in children.

Abstract Life tables summarise a population’s mortality experience during a time period. Sex- and age-specific life tables are needed to compute various cancer survival measures. However, mortality rates vary according to socioeconomic status. We present sex- and age-specific life tables based on socioeconomic status at the census tract level in Spain during 2011–2013 that will allow estimating cancer relative survival estimates and life expectancy measures by socioeconomic status. Population and mortality data were obtained from the Spanish Statistical Office. Socioeconomic level was measured using the Spanish Deprivation Index by census tract. We produced sex- and age-specific life expectancies at birth by quintiles of deprivation, and life tables by census tract and province. Life expectancy at birth was higher among women than among men. Women and men in the most deprived census tracts in Spain lived 3.2 and 3.8 years less than their counterparts in the least deprived areas. A higher life expectancy in the northern regions of Spain was discovered. Life expectancy was higher in provincial capitals than in rural areas. We found a significant life expectancy gap and geographical variation by sex and socioeconomic status in Spain. The gap was more pronounced among men than among women. Understanding the association between life expectancy and socioeconomic status could help in developing appropriate public health programs. Furthermore, the life tables we produced are needed to estimate cancer specific survival measures by socioeconomic status. Therefore, they are important for cancer control in Spain.

Helicobacter pylori infection induces a number of pro-inflammatory signaling pathways contributing to gastric inflammation and carcinogenesis. Among those, NF-κB signaling plays a pivotal role during infection and malignant transformation of the gastric epithelium. However, deficiency of the adaptor molecule myeloid differentiation primary response 88 (MyD88), which signals through NF-κB, led to an accelerated development of gastric pathology upon H. felis infection, but the mechanisms leading to this phenotype remained elusive. Non-canonical NF-κB signaling was shown to aggravate H. pylori-induced gastric inflammation via activation of the lymphotoxin β receptor (LTβR). In the present study, we explored whether the exacerbated pathology observed in MyD88-deficient (Myd88-/-) mice was associated with aberrant activation of non-canonical NF-κB. Our results indicate that, in the absence of MyD88, H. felis infection enhances the activation of non-canonical NF-κB that is associated with increase in Cxcl9 and Icam1 gene expression and CD3+ lymphocyte recruitment. In addition, activation of signal transducer and activator of transcription 3 (STAT3) signaling was higher in Myd88-/- compared to wild type (WT) mice, indicating a link between MyD88 deficiency and STAT3 activation in response to H. felis infection. Thereby, MyD88 deficiency results in accelerated and aggravated gastric pathology induced by Helicobacter through activation of non-canonical NF-κB.

Abstract Identifying high-yield genotypes under low water availability is essential for soybean climate-smart breeding. However, a major bottleneck lies in phenotyping, particularly in selecting cost-efficient markers associated with stress tolerance and yield stabilization. Here, we conducted in-depth phenotyping experiments in two soybean genotypes with contrasting drought tolerance, MUNASQA (tolerant) and TJ2049 (susceptible), to better understand soybean stress physiology and identify/statistically validate drought-tolerance and yield-stabilization traits as potential breeding markers. Firstly, at the critical reproductive stage (R5), the molecular differences between the genotype’s responses to mild water deficit were explored through massive analysis of cDNA ends (MACE)-transcriptomic and gene ontology. MUNASQA transcriptional profile, compared to TJ2049, revealed significant differences when responding to drought. Next, both genotypes were phenotyped under mild water deficit, imposed in vegetative (V3) and R5 stages, by evaluating 22 stress-response, growth, and water-use markers, which were subsequently correlated between phenological stages and with yield. Several markers showed high consistency, independent of the phenological stage, demonstrating the effectiveness of the phenotyping methodology and its possible use for early selection. Finally, these markers were classified and selected according to their cost-feasibility, statistical weight, and correlation with yield. Here, pubescence, stomatal density, and canopy temperature depression emerged as promising breeding markers for the early selection of drought-tolerant soybeans.

Abstract Prebiotics and probiotics have shown a number of beneficial impacts preventing diseases in cultured shrimps. Complex soluble carbohydrates are considered ideal for fostering microbiota biodiversity by fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPS). Here we evaluated the growth performance and microbiota composition of the white shrimp Litopenaeus vannamei after dietary intervention using agavin as a FODMAP prebiotic under farming conditions. Adult L. vannamei were raised at a shrimp farm and the effect of agavin supplemented at 2% (AG2) or 10% (AG10) levels were compared to an agavin-free basal diet (BD). After 28 days-trial, the feed conversion ratio, total feed ingested, and protein efficiency ratio was significantly improved on animals fed with AG2. At the same time, no effect on growth performance was observed in AG10. Surprisingly, after sequencing the V3–V4 regions of the 16S rRNA gene a higher microbial richness and diversity in the hepatopancreas and intestine was found only in those animals receiving the AG10 diet, while those receiving the AG2 diet had a decreased richness and diversity, both diets compared to the BD. The beta diversity analysis showed a clear significant microbiota clustering by agavin diets only in the hepatopancreas, suggesting that agavin supplementation had a more substantial deterministic effect on the microbiota of hepatopancreas than on the intestine. We analyzed the literature to search beneficial microbes for shrimp’s health and found sequences for 42 species in our 16S data, being significantly increased Lactobacillus pentosus, Pseudomonas putida and Pseudomonas synxantha in the hepatopancreas of the AG10 and Rodopseudomonas palustris and Streptococcus thermophiles th1435 in the hepatopancreas of the AG2, both compared to BD. Interestingly, when we analyzed the abundance of 42 beneficial microbes as a single microbial community "meta-community," found an increase in their abundance as agavin concentration increases in the hepatopancreas. In addition, we also sequenced the DNA of agavin and found 9 of the 42 beneficial microbes. From those, Lactobacillus lactis and Lactobacillus delbrueckii were found in shrimps fed with agavin (both AG2 and AG10), and Lysinibacillus fusiformis in AG10 and they were absent the BD diet, suggesting these three species could be introduced with the agavin to the diet. Our work provides evidence that agavin supplementation is associated with an increase of beneficial microbes for the shrimp microbiota at farming conditions. Our study provides the first evidence that a shrimp prebiotic may selectively modify the microbiota in an organ-dependent effect.

Abstract Endothelial dysfunction is a key player in both the onset and development of atherosclerosis. No study has examined whether healthy dietary patterns can improve microvascular endothelial function in patients with coronary heart disease (CHD) in the long-term and whether this relationship can affect patient’s risk of CHD recurrence. In the CORDIOPREV study, a randomized, double-blind, controlled trial, dietary intervention with either the Mediterranean diet or a low-fat diet was implemented in 1,002 CHD patients. A laser-doppler flowmetry was performed at baseline and after 6 years of follow up in 664 patients, evaluating the effects of this dietary intervention on microvascular basal flow and reactive hyperaemia area, as well as on the risk of CHD recurrence, based on the TRS2P risk score. Basal flow (97.78 ± 2.79 vs. 179.31 ± 5.06 arbitrary perfusion units, 83.38% increase, p 0.05 for the diet-effect). When patients were stratified to low, moderate or high-risk of recurrence, basal flow was similarly increased in all three groups. However, reactive hyperaemia area was improved to a greater extent in patients at the low-risk group compared with those at moderate or high-risk. No differences were observed between diets. Healthy dietary patterns can improve microvascular endothelial function and this improvement persists in the long-term. Patients with a low-risk of CHD recurrence show a greater improvement in reactive vasodilation to ischemia than patients in the moderate or high-risk groups.