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Altres ajuts: Funding information: O.L. was funded by the Program of FSR SAS no FMZF-2022-0012. M.B.-A. is currently funded by a MSCA-IF-2019 (GA No. 893735) and during part of this research was an Alexander von Humboldt post-doc fellow. R.P. was funded by ICREA Academia Program. The site Zamostje 2, located in Sergiev-Posad district of Moscow (Russia) on the west bank of the Dubna River, has provided two Mesolithic and one Early Neolithic occupations dated from 7000 to 5400 cal BC. Thanks to the waterlogged environment, the site has an exceptional preservation. The site has yielded fishing screens, fishing fences, wooden fishing traps, and several small cordage remains elaborated with plant fibres, pine bark floats, fragments of paddles, and other wooden objects. In this work, we present the study of the fragments of cordage and fishing nets with the objective of providing new insights into the production and use of implements made of plant fibres. We have characterized the production process by analysing the morphological and technical characteristics by carrying out experimentation with plant fibres in order to obtain reference material to recognize them at an archaeological level. The analysis of 82 knots and 23 fragments of strings has allowed to determine that they were elaborated with single threads from 0.5 to 1.5 mm thick, which is noticeably smaller than most examples from other sites. All of them were elaborated with woody bast fibres.

World's population is exponentially aging as people reaching 100 years old has increased. The number of areas with the highest centennial population rates (Blue Zones), are significantly higher. Are there any determinant factors that favor this situation in Spain? The goal of this study was to determine the possible influence of sex, rurality and socioeconomic factors (Gross Domestic Product (GDP)) on the prevalence of the centennial population of the Spanish society. The Spanish register of inhabitants was published in 2017 by the National Statistics Institute. The analysis was carried out both by Autonomous Communities and by provinces in phases: a first descriptive analysis, followed by an inferential analysis, based on statistical tests (independent T- Student test, Pearson correlation and ANOVA). There were significant interactions between: i) sex and longevity (in favor of the female population); ii) female and rural housing and iii) female, GDP and urban areas. Feminization was proven in the longevity revolution, but, in general, GDP per Capita was not a significant survival factor on its own. This study was the first step of further analysis related to extreme longevity in Spain, which will include other dependent variables such as state of health and well-being as well as social factors.

Background Sex differences are underappreciated in the current understanding of cardiovascular disease (CVD) in association with chronic kidney disease (CKD). A hallmark of CKD is vascular aging that is characterised, amongst others, by; systemic inflammation, microbiota disbalance, oxidative stress, and vascular calcification—features linked to atherosclerosis/arteriosclerosis development. Thus, it is the necessary to introduce novel biomarkers related to athero-/arteriosclerotic damage for better assessment of vascular ageing in patients CKD. However, little is known about the relationship between uraemia and novel CVD biomarkers, such as growth differentiation factor-15 (GDF-15), cartilage glycoprotein-39 (YKL-40) and matrix metalloproteinase-9 (MMP-9). Therefore, we hypothesise that there are sex-specific relationships between GDF-15, YKL-40, MMP-9 levels in end-stage kidney disease (ESKD) patients in relation to gut microbiota, vascular calcification, inflammation, comorbidities, and all-cause mortality. Methods ESKD patients, males (n = 151) and females (n = 79), not receiving renal replacement therapy were selected from two ongoing prospective ESKD cohorts. GDF-15, YKL-40 and MMP9 were analysed using enzyme-linked immunosorbent assay kits. Biomarker levels were analysed in the context of gut microbiota-derived trimethylamine N-oxide (TMAO), vascular calcification, inflammatory response, oxidative stress, comorbidities, and all-cause mortality. Results Increased GDF-15 correlated with higher TMAO in females only, and with higher coronary artery calcification and IL-6. In females, diabetes was associated with elevated GDF-15 and MMP-9, whilst males with diabetes only had elevated GDF-15. No associations were found between biomarkers and CVD comorbidity. Deceased males and females had higher GDF-15 concentrations (p = 0.01 and p p = 0.02). Conclusions In conclusion, in males GDF-15 and YKL-40 were related to vascular calcification, inflammation, and oxidative stress, whilst in females GDF-15 was related to TMAO. Increased levels of YKL-40 and GDF-15 in males, and only GDF-15 in females, were associated with all-cause mortality. Our findings suggest that sex-specific associations of novel CVD biomarkers have a potential to affect development of cardiovascular complications in patients with ESKD.

© 2022 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.Background: Vesico-ureteral reflux (VUR) is considered to be a risk factor for recurrent febrile urinary tract infections and impaired renal transplant survival. Methods: An online survey supported by the European Society for Paediatric Nephrology was designed to evaluate current management strategies of VUR in native and transplanted kidneys of recipients aged

In everyday life, risky decision-making relies on multiple cognitive processes including sensitivity to reinforcers, exploration, learning, and forgetting. Neuroimaging evidence suggests that the dorsolateral prefrontal cortex (DLPFC) is involved in exploration and risky decision-making, but the nature of its computations and its causal role remain uncertain. We provide evidence for the role of the DLPFC in value-independent, directed exploration on the Iowa Gambling Task (IGT) and we describe a new computational model to account for the competition of directed exploration and exploitation in guiding decisions. Forty-two healthy human participants were included in a right DLPFC, left DLPFC or sham stimulation groups using continuous theta-burst stimulation (cTBS). Immediately after cTBS, the IGT was completed. Computational modelling was used to account for exploration and exploitation with different combinations with value-based and sensitivity to reinforcers for each group. Applying cTBS to the left and right DLPFC selectively decreased directed exploration on the IGT compared to sham stimulation. Model-based analyses further indicated that the right (but not the left) DLPFC stimulation increased sensitivity to reinforcers, leading to avoidance of risky choices and promoting advantageous choices during the task. Although these findings are based on small sample sizes per group, they nevertheless elucidate the causal role of the right DLPFC in governing the exploration-exploitation tradeoff during decision-making in uncertain and ambiguous contexts.

Plant-based artefacts are rarely preserved in archaeological contexts in the Iberian Peninsula. Very few sites with specific conditions such as waterlogging, aridity or carbonization have preserved organic material. The aim of this paper is to establish an identification criterion for identifying organic raw materials used for manufacturing plant-based artifacts by using optical microscopy. The coiled basketry remains found in La Draga (Banyoles, Girona) and Coves del Fem (Ulldemolins, Tarragona) have been studied using this method. The materials were exceptionally well-preserved by waterlogging in the case of La Draga, and carbonized or dehydrated in Coves del Fem. Samples of both coils and stitches from all the basket remains were analysed. The anatomy of their cross-sections was observed under a transmitted light bright-dark field (BF-DF) optical microscope and compared with modern reference collections. The results show the use of at least five species corresponding to four families: three monocotyledons (Poaceae, Cyperaceae and Typhaceae) and a dicotyledon (Malvaceae). Moreover, it has been possible to distinguish the part of the plant used. Variability in raw materials implied extensive environmental knowledge. Moreover, functional studies of wooden, faunal, lithic and malacological tools suggest a local production of baskets. This paper expands the current knowledge of raw materials used for basketry purposes during prehistory in the Mediterranean area as the examples from La Draga and the Coves del Fem are the oldest basketry remains that have been studied in depth in the Iberian Peninsula and Europe.

It has been more than 200 years since James Parkinson made the first descriptions of the disease that bears his name. Since then, knowledge about Parkinson’s disease has been improved, and its pathophysiology, diagnosis, and treatments are well described in the scientific and medical literature. However, there is no way to prevent the disease from its progressive nature yet and only its symptoms can be minimized. It is known that the process of neurodegeneration begins before the onset of motor signs and symptoms of the disease, when diagnosis is usually made. Therefore, recognizing manifested non-motor symptoms can make an early diagnosis possible and lead to a better understanding of the disease. Autonomic dysfunctions are important non-motor manifestations of Parkinson’s disease and affect the majority of patients. Importantly, heart failure is the third leading cause of death in people suffering from Parkinson’s disease. Several evidences have shown the correlation between Parkinson’s disease and the preexistence of cardiovascular diseases. Therefore, cardiovascular monitoring and identification of its dysfunctions can have a prodromal role for Parkinson’s disease. This review presents studies of the literature that can lead to a better understanding of Parkinson’s disease with special attention to its relation to heart and cardiovascular parameters.

Parkinson's disease (PD) is a neurodegenerative disorder marked primarily by motor symptoms such as rigidity, bradykinesia, postural instability and resting tremor associated with dopaminergic neuronal loss in the Substantia Nigra pars compacta (SNpc) and deficit of dopamine in the basal ganglia. These motor symptoms can be preceded by pre-motor symptoms whose recognition can be useful to apply different strategies to evaluate risk, early diagnosis and prevention of PD progression. Although clinical characteristics of PD are well defined, its pathogenesis is still not completely known, what makes discoveries of therapies capable of curing patients difficult to be reached. Several theories about the cause of idiopathic PD have been investigated and among them, the key role of inflammation, microglia and the inflammasome in the pathogenesis of PD has been considered. In this review, we describe the role and relation of both the inflammasome and microglial activation with the pathogenesis, symptoms, progression and the possibilities for new therapeutic strategies in PD.

Sugar monomers originating from well-controlled hydrolysis of hemicelluloses appearing in biomass are important platform molecules and they can be further valorized by catalytic hydrogenation, oxid...

The early Neolithic site of La Draga (Banyoles, Spain) has provided a singular sample of plant-crafts, wooden tools, and other plant remains preserved in waterlogged conditions. This exceptional context of plant remains preservation provides an incomparable frame to study past botanical knowledge and the emergence and devel- opment of plant transformation technologies. The goal of this paper is to provide an integrated synthesis of the plant resources used by the inhabitants of La Draga, paying special attention to the main taxa used, the environ- ments exploited and the plant acquisition strategies. Through the results of the analysis of plant-crafts, timber and wooden tools, charcoal remains, exudates, fungi, and microremains as pollen, we discuss types of forest and plants exploited to obtain raw materials and the human impact on vegetation. The plant raw materials identified at La Draga indicate the exploitation of local resources available in deciduous and riparian forests where an anthropic disturbance is documented contemporary with the occupation., This work was supported by Ministerio de Ciencia, Innovacion y Universidades, Spain, projects: WOOD- PDLAKE -Archaeological Wooden Pile-Dwelling in Mediterranean European lakes: strategies for their exploitation, monitoring and conservation, JPICH -Conservation, Protection and Use Joint Call (PCI2020-111992)-, PID2019-109254GB-C21 -Paleoambiente, modelización del paisaje y análisis del uso de plantas en la transición a la agricultura en el Noreste de La Península Ibérica-. The archaeological excavation at La Draga was funded by the Departament de Cultura (Generalitat de Catalunya) CLT009/18/00050. The authors are member of the research group supported by AGAUR- Generalitat de Catalunya: TEDAS 2017 SGR 243 and ASD 2017 SGR 995. RP also acknowledges the sup- port of Catalan Institution for Research and Advanced Studies (ICREA, Generalitat de Catalunya, Spain), through the ICREA Academia Program. M. Berihuete-Azorín (2018 BP 00272) received funding from the postdoctoral fellowships pro- gramme Beatriu de Pinós, funded by the Secretary of Universities and Research (Government of Catalonia) and by the Horizon 2020 programme of research and innovation of the European Union under the Marie Skfodowska-Curie grant agreement 801370.M.

Electronic Health Records (EHR) data can provide novel insights into inpatient trajectories. Blood tests and vital signs from de-identified patients' hospital admission episodes (AE) were represented as multivariate time-series (MVTS) to train unsupervised Hidden Markov Models (HMM) and represent each AE day as one of 17 states. All HMM states were clinically interpreted based on their patterns of MVTS variables and relationships with clinical information. Visualization differentiated patients progressing toward stable 'discharge-like' states versus those remaining at risk of inpatient mortality (IM). Chi-square tests confirmed these relationships (two states associated with IM; 12 states with ≥1 diagnosis). Logistic Regression and Random Forest (RF) models trained with MVTS data rather than states had higher prediction performances of IM, but results were comparable (best RF model AUC-ROC: MVTS data = 0.85; HMM states = 0.79). ML models extracted clinically interpretable signals from hospital data. The potential of ML to develop decision-support tools for EHR systems warrants investigation., This research was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). VLK was funded by a MRC/NIHR Clinical Academic Research Partnership Grant (CARP; grant code: MR/T023902/1). VT is supported by Cancer Research UK. EB and TF were funded by the EMBL European Bioinformatics Institute (EMBL-EBI).

Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson's disease (PD) suggesting that a sustained neuroinflammation exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH+) and microglia markers (Iba-1+; CD68+) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68+/ Iba-1+ cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions. Graphical Abstract MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.

[Abstract]: Chimeric antigen receptor T-cells (CAR T-cells) for the treatment of relapsing/refractory B-cell precursor acute lymphoblastic leukemia have led to exciting clinical results. However, CAR T-cell approaches revealed a potential risk of CD19-/CAR+ leukemic relapse due to inadvertent transduction of leukemia cells. [Methods]: We evaluated the impact of a high percentage of leukemia blast contamination in patient-derived starting material (SM) on CAR T-cell drug product (DP) manufacturing. In vitro as well as in vivo models were employed to identify characteristics of the construct associated with better profile of safety in case of inadvertent B-cell leukemia transduction during CAR T-cell manufacturing. [Results]: The presence of large amounts of CD19+ cells in SM did not affect the transduction level of DPs, as well as the CAR T-cell rate of expansion at the end of standard production of 14 days. DPs were deeply characterized by flow cytometry and molecular biology for Ig-rearrangements, showing that the level of B-cell contamination in DPs did not correlate with the percentage of CD19+ cells in SM, in the studied patient cohort. Moreover, we investigated whether CAR design may affect the control of CAR+ leukemia cells. We provided evidences that CAR.CD19 short linker (SL) prevents complete epitope masking in CD19+CAR+ leukemia cells and we demonstrated in vitro and in vivo that CD19 +CAR(SL)+leukemic cells are killed by CAR.CD19 T-cells. [Conclusions]: Taken together, these data suggest that a VL-VH SL may result in a safe CAR-T product, even when manufacturing starts from biological materials characterized by heavy contamination of leukemia blasts., The experimental work was supported by grants awarded by Ricerca Finalizzata GR-2013 02359212 (CQ), GR-2016-02364546 (BDA), RF-2016- 02364388 (FL), Accelerator Award-Cancer Research UK/AIRC/AECC-INCAR project (FL and AO), Associazione Italiana Ricerca per la Ricerca sul Cancro (AIRC)-Special Project 5×1000 no. 9962 (FL), AIRC IG 2018 id. 21724 (FL), Ricerca Corrente (FL, CQ, BDA), Ministero dell’Università e della Ricerca (Grant PRIN 2017 to FL); Italian Healthy Ministry project on CAR T RCR-2019-23669115 (coordinator FL), Independent Research grant AIFA (FL PI: 2016 call).

The diurnal rodent Octodon degus (O. degus) is considered an attractive natural model for Alzheimer’s disease and other human age-related features. However, it has not been explored so far if the O. degus could be used as a model to study Parkinson’s disease. To test this idea, 10 adult male O. degus were divided into control group and MPTP-intoxicated animals. Motor condition and cognition were examined. Dopaminergic degeneration was studied in the ventral mesencephalon and in the striatum. Neuroinflammation was also evaluated in the ventral mesencephalon, in the striatum and in the dorsal hippocampus. MPTP animals showed significant alterations in motor activity and in visuospatial memory. Postmortem analysis revealed a significant decrease in the number of dopaminergic neurons in the ventral mesencephalon of MPTP animals, although no differences were found in their striatal terminals. We observed a significant increase in neuroinflammatory responses in the mesencephalon, in the striatum and in the hippocampus of MPTP-intoxicated animals. Additionally, changes in the subcellular expression of the calcium-binding protein S100β were found in the astrocytes in the nigrostriatal pathway. These findings prove for the first time that O. degus are sensitive to MPTP intoxication and, therefore, is a suitable model for experimental Parkinsonism in the context of aging.

An atypical clinical variant of hand-foot-and-mouth disease (HFMD) with more extensive lesions and affecting adults has emerged during the past years, usually associated to the Coxsackievirus serotype A6 (CV-A6). We present a 19-year-old woman with a 3-day evolution eruption of papulovesicular lesions, which first appeared around the mouth and frontal area and rapidly spread. In addition, we present a 61-year-old man with a 4-day evolution asymptomatic eruption of papulovesicular lesions in both the hands and feet after suffering a cold 1 week before. Skin biopsies of both patients showed intraepidermal vesicles with spongiosis and ballooning, leading to reticular degeneration, apoptotic keratinocytes, and epidermal necrosis of the upper layers with neutrophil sloughing. Immunohistochemical studies for Coxsackie, Enterovirus, herpes virus, adenovirus, and measles were all negative. Cultures of blister fluid, reverse transcription polymerase chain reaction of skin biopsies, blood tests and serologies for exanthematic virus, and serum viral arrays were also negative. Only reverse transcription polymerase chain reaction of blister fluid confirmed Cocksakie A6. In conclusion, immunohistochemical studies with the commercially available viral antibodies do not seem to be useful in atypical HFMD cases. In these cases, to determine the typical histopathological features in HE is the fastest diagnostic aid.

41 Pags.- 11 Figs. The definitive version is available at: https://link.springer.com/journal/497., Glycoproteins are significant players in the dialog that takes place between growing pollen tubes and the stigma and style in the angiosperms. Yet, information is scarce on their possible involvement in the ovule, a sporophytic organ that hosts the female gametophyte. Apple flowers have a prolonged lapse of time between pollination and fertilization, offering a great system to study the developmental basis of glycoprotein secretion and their putative role during the last stages of the progamic phase and early seed initiation. For this purpose, the sequential pollen tube elongation within the ovary was examined in relation to changes in arabinogalactan proteins (AGPs) in the tissues of the ovule before and after fertilization. To evaluate what of these changes are developmentally regulated, unpollinated and pollinated flowers were compared. AGPs paved the pollen tube pathway in the ovules along the micropylar canal, and the nucellus entrance toward the synergids, which also developmentally accumulated AGPs at the filiform apparatus. Glycoproteins vanished from all these tissues following pollen tube passage, strongly suggesting a role in pollen–ovule interaction. In addition, AGPs marked the primary cell walls of the haploid cells of the female gametophyte, and they further built up in the cell walls of the embryo sac and developing embryo, layering the interactive walls of the three generations hosted in the ovule, the maternal sporophytic tissues, the female gametophyte, and the developing embryo., This work was supported by Ministerio de Ciencia e Innovación (MICINN)-FEDER [AGL2006-13529-C02-01, AGL 12621-C02-01, AGL 2012–40239] and Gobierno de Aragón [group A43]. JIM antibodies distribution was partly supported by NSF grants [DBI-0421683, RCN 009281]. JML was supported by a FPI fellowship [BES-2007-16059] from MICINN.

5 Pags. The definitive version is available at: https://www.ishs.org/ishs-book/1231, Mango (Mangifera indica) is a tropical fruit tree originated in southeastern Asia, which is cultivated in regions with tropical and subtropical climates worldwide. Mango cultivation has significantly increased in the last decades, often spreading to areas where environmental conditions are not the most favorable for optimal fruit set. In this work, we describe the reproductive biology of mango in the coastal areas of southern Spain, the furthest region from the equator where mango is produced commercially at a significant scale. As in other regions, mango trees produced several inflorescences per tree with hundreds to thousands of male and hermaphrodite flowers, depending on the cultivar, but only a very small percentage of the flowers are able to set fruits due to a massive drop of flowers and fruitlets. Although about half of the flowers in the inflorescence are male flowers and, consequently, contribute to this massive drop, a high proportion of the hermaphrodite flowers were not receptive to pollen germination. In receptive flowers, the characterization of the pollen tube pathway within the pistil showed chalazogamy. A detailed study of the ovules indicates that a high proportion of them showed degenerated embryo sacs, both before and after fertilization. Paternity analysis with molecular markers showed a high proportion of embryos resulting from self-pollination in orchards planted with a single cultivar. However, without pollination restrictions, the offspring shows a higher proportion of genotypes resulting from cross-pollination, suggesting preferential cross-fertilization. The variable response of this parameter, together to the variable proportion of hermaphrodite/male flower ratio, also obtained in response to environmental conditions, suggests a reproductive plasticity in this species., This research was supported by the Ministerio de Economía y Competitividad – European Regional Development Fund, European Union (AGL2012-40239 and AGL2013-43732-R) and Gob. Aragón A-43. V. Pérez was supported by a Cabildo de La Palma-CSIC PhD scholarship.

The impact of age-associated disorders is increasing as the life expectancy of the population increments. Cardiovascular diseases and neurodegenerative disorders, such as Parkinson’s disease, have the highest social and economic burden and increasing evidence show interrelations between them. Particularly, dysfunction of the cardiovascular nervous system is part of the dysautonomic symptoms of Parkinson’s disease, although more studies are needed to elucidate the role of cardiac function on it. We analyzed the dopaminergic system in the nigrostriatal pathway of Parkinsonian and dyskinetic monkeys and the expression of some key proteins in the metabolism and synthesis of catecholamines in the heart: total and phosphorylated (phospho) tyrosine hydroxylase (TH), and membrane (MB) and soluble (S) isoforms of catechol-O-methyl transferase (COMT). The dopaminergic system was significantly depleted in all MPTP-intoxicated monkeys. MPTP- and MPTP+L-DOPA-treated animals also showed a decrease in total TH expression in both right (RV) and left ventricle (LV). We found a significant increase of phospho-TH in both groups (MPTP and MPTP+L-DOPA) in the LV, while this increase was only observed in MPTP-treated monkeys in the RV. MB-COMT analysis showed a very significant increase of this isoform in the LV of MPTP- and MPTP+L-DOPA-treated animals, with no significant differences in S-COMT levels. These data suggest that MB-COMT is the main isoform implicated in the cardiac noradrenergic changes observed after MPTP treatment, suggesting an increase in NA metabolism. Moreover, the increase of TH activity indicates that cardiac noradrenergic neurons still respond despite MPTP treatment.

Altres ajuts: Institució Catalana de Recerca i Estudis Avançats FJC2018 The role of the adoption of farming economies in the transformation of mid-Holocene landscapes in Northeast Iberia is under discussion given that the Neolithization coincides with the cold climatic phase dated ca. 7500-7000 cal BP. The main aim of this paper is to assess whether human activities or climate were the main driver of vegetation changes during the Middle Holocene through the study of the archaeobotanical data from three case studies: Cova del Sardo, La Draga, and Coves del Fem. The application of diverse archaeobotanical techniques to the different plant remains provides a complete picture of the vegetation composition and plant uses. During the early Neolithic, settlement surroundings were intensively exploited for firewood, wood raw material, timber, and plant fibers. The resources were obtained mainly from deciduous and pine forests, de-pending on the site localization, but also from riparian zones. The diversity of plants exploited was high, not only trees but shrubs and herbs. Evidence of deforestation has been identified in the settlement surroundings in La Draga and Cova del Sardo. The combination of plant exploitation with other agropastoral activities favored the expansion of colonizing species and enhanced biodiversity at a local scale.

Numerous studies have demonstrated that sex (a biological variable) and gender (a psychosocial construct) impact health and have discussed the mechanisms that may explain these relationships. Funding agencies have called for all health researchers to incorporate sex and gender into their studies; however, the way forward has been unclear to many, particularly due to the varied definition of gender. We argue that just as there is no standardized definition of gender, there can be no standardized measurement thereof. However, numerous measurable gender-related variables may influence individual or population-level health through various pathways. The initial question should guide the selection of specific gender-related variables based on their relevance to the study, to prospectively incorporate gender into research. We outline various methods to provide clarification on how to incorporate gender into the design of prospective clinical and epidemiological studies as well as methods for statistical analysis.

Background Patient attitudes about health and healthcare have emerged as important outcomes to assess in clinical studies. Gender is increasingly recognized as an intersectional social construct that may influence health. Our objective was to determine potential sex differences in self-reported overall health and access to healthcare and whether those differences are influenced by individual social factors in two relatively similar countries. Methods Two public health surveys from countries with high gender equality (measured by UN GII) and universal healthcare systems, Canada (CCHS2014, n = 57,041) and Austria (AT-HIS2014, n = 15,212), were analysed. Perceived health was assessed on a scale of 1 (very bad) to 4 (very good) and perceived unmet healthcare needs was reported as a dichotomous variable (yes/no). Interactions between sex and social determinants (i.e. employment, education level, immigration and marital status) on outcomes were analysed. Results Individuals in both countries reported high perceived health (Scoring > 2, 85.0% in Canada, 79.9% in Austria) and a low percentage reported unmet healthcare needs (4.6% in Canada, 10.7% in Austria). In both countries, sex and several social factors were associated with high perceived health, and a sex-by-marital status interaction was observed, with a greater negative impact of divorce for men. Female sex was positively associated with unmet care needs in both countries, and sex-by-social factors interactions were only detected in Canada. Conclusions The intersection of sex and social factors in influencing patient-relevant outcomes varies even among countries with similar healthcare and high gender equality.

4 Pags.- 1 Fig. Esta obra está licenciada com uma Licença Creative Commons Atribuição-NãoComercial-CompartilhaIgual 4.0 Internacional., [EN] Pitangueira (E. uniflora) is considered a diploid species with n = 11 and 2n = 22 chromosomes, in genotypes with the presence of seeds in the fruits. With the pitangueira production of apyrenic fruits existence, such behavior may be related to the ploidy level. The objective of this study was to determine the ploidy level of the pitangueira accessions producing fruit with and without seed, as well as to observe the meiotic behavior and possible chromosomal abnormalities. To check the ploidy level of the pitangueira, freshly expanded mature leaves were collected from the pyrenic pitangueira and from two pyrenic accessions, with suspensions of intact nuclei being prepared. Samples were analyzed in a flow cytometer equipped with multiple parameters data acquisition and UV laser. All analyses were performed using peak-height detection (>6000 fluorescent events, for example, nuclei, were analyzed per sample) and logarithmic amplification. The data were presented as histograms of the number of nuclei along the y-axis and the relative fluorescence intensity on the x-axis. The pyrenean pitangueira and other two pyrenic accessions were characterized as diploid., [PO] A pitangueira (E. uniflora) é considerada espécie diplóide com n=11 e 2n=22 cromossomos, em genótipos com presença de sementes nos frutos. Com a existência de pitangueira produtora de frutos apirênicos, tal comportamento pode estar relacionado ao nível de ploidia. O objetivo deste estudo foi determinar o nível de ploidia dos acessos de pitangueira produtora de frutos sem e com semente, bem como, observar o comportamento meiótico e possíveis anormalidades cromossômicas. Para verificar o nível de ploidia da pitangueira, folhas maduras recém-expandidas foram coletadas da pitangueira apirênica e de dois acessos pirênicos, sendo preparados suspensões de núcleos intactos. As amostras foram analisadas em citômetro de fluxo equipado com aquisição de dados de múltiplos parâmetros e de laser UV. Todas as análises foram realizadas utilizando detecção de pico-altura (>6000 eventos fluorescentes, por exemplo, núcleos, foram analisados por amostra) e amplificação logarítmica. Os dados foram apresentados como histogramas do número de núcleos ao longo do eixo-y e a intensidade da fluorescência relativa no eixo-x. A pitangueira apirênica e outros dois acessos pirênicos, foram caracterizadas como diplóides.

Background Evidence differentiating the effect of biological sex from psychosociocultural factors (gender) in different societies and its relation to cardiovascular diseases is scarce. We explored the association between sex, gender, and cardiovascular health (CVH) among Canadian (CAN) and Austrian (AT) populations. Methods The Canadian Community Health Survey (CCHS) (n = 63,522; 55% female) and Austrian Health Interview Survey (AT-HIS) (n = 15,771; 56% female) were analyzed in a cross-sectional survey design. The CANHEART/ATHEART index, a measure of ideal CVH composed of 6 cardiometabolic risk factors (smoking, physical activity, fruit and vegetable consumption, overweight/obesity, diabetes, and hypertension; range 0-6; higher scores reflecting better CVH) was calculated for both databases. A composite measure of psychosociocultural gender was computed for each country (range 0-1, higher score identifying characteristics traditionally ascribed to women). Results Median CANHEART 4 (interquartile range 3-5) and CAN gender scores 0.55 (0.49-0.60) were similar to median ATHEART 4 (3-5) and AT gender scores 0.55 (0.46-0.64). Although higher gender scores (CCHS: β = −1.33, 95% confidence interval [CI] −1.44 to −1.22; AT-HIS: β = −1.08, 95% CI −1.26 to −0.89)) were associated with worse CVH, female sex (CCHS: β = 0.35, 95% CI (0.33-0.37); AT-HIS: β = 0.60, 95% CI (0.55-0.64)) was associated with better CVH in both populations. In addition, higher gender scores were associated with increased prevalence of heart disease compared with female sex. The magnitude of this risk was higher in Austrians. Conclusions These results demonstrate that individuals with characteristics typically ascribed to women reported poorer cardiovascular health and higher risk of heart disease, independently from biological sex and baseline CV risk factors, in both countries. Female sex exhibited better CV health and a lower prevalence of heart disease than male in both populations. However, gender factors and magnitude of gender impact varied by country.

Most flowering plants show porogamy in which the pollen tubes reach the egg apparatus through the micropyle. However, several species show chalazogamy, an unusual pollen tube growth, in which the pollen tubes reach the embryo sac through the chalaza. While ovary signals for pollen tube growth and guidance have been extensively studied in porogamous species, few studies have addressed the process in chalazogamous species such as mango (Mangifera indica L.), one of the five most important fruit crops worldwide in terms of production. In this study, we characterize pollen–pistil interaction in mango, paying special attention to three key players known to be involved in the directional pollen tube growth of porogamous species such as starch, arabinogalactan proteins (AGPs), and γ-aminobutyric acid (GABA). Starch grains were observed in the style and in the ponticulus at anthesis, but their number decreased 1 day after anthesis. AGPs, revealed by JIM8 and JIM13 antibodies, were homogenously observed in the style and ovary, but were more conspicuous in the nucellus around the egg apparatus. GABA, revealed by anti-GABA antibodies, was specifically observed in the transmitting tissue, including the ponticulus. Moreover, GABA was shown to stimulate in vitro mango pollen tube elongation. The results support the heterotrophic growth of mango pollen tubes in the style at the expense of starch, similarly to the observations in porogamous species. However, unlike porogamous species, the micropyle of mango does not show high levels of GABA and starch, although they were observed in the ponticulus and could play a role in supporting the unusual pollen tube growth in chalazogamous species.

Different cellular mechanisms have been described as being potentially involved in the progression of neurodegeneration in Parkinson’s disease, although their role is still unclear. The present study aimed to identify in detail, through differentially expressed genes analysis by bioinformatics approaches, the molecular mechanisms triggered after a systemic insult in parkinsonian mice. To address this objective, we combined a dextran sodium sulfate (DSS)-induced ulcerative colitis experimental mice model with an acute 1-methyl-4-phenyl-1,2,3,6-tetradropyridine (MPTP) intoxication. The animals were divided into four experimental groups based on the different treatments: (i) control, (ii) DSS, (iii) MPTP and (iv) MPTP + DSS. The data obtained by microarray and functional enrichment analysis point out the implication of different molecular mechanisms depending on the experimental condition. We see, in the striatum of animals intoxicated only with DSS, dysfunction processes related to the blood. On the other hand, oxidative stress processes are more prominent at the MPTP intoxicated mice. Finally, differentially expressed genes within the MPTP + DSS show functional enrichment in inflammation and programmed cell death. Interestingly, we identify a significant synergistic negative effect of both toxins since the expression of differentially expressed genes (DEGs) related to balanced cellular homeostasis was not enough to prevent processes associated with cell death. This work provides detailed insights into the involvement of systemic inflammation, triggered after an insult in the colon, in the progression of the degeneration in Parkinsonism. In this way, we will be able to identify promising therapeutic targets that prevent the contribution of inflammatory processes in the progression of Parkinson’s disease.

Integrating the multifactorial processes co-occurring in both physiological and pathological human conditions still remains one of the main challenges in translational investigation. Moreover, the impact of age-associated disorders has increased, which underlines the urgent need to find a feasible model that could help in the development of successful therapies. In this sense, the Octodon degus has been indicated as a 'natural' model in many biomedical areas, especially in ageing. This rodent shows complex social interactions and high sensitiveness to early-stressful events, which have been used to investigate neurodevelopmental processes. Interestingly, a high genetic similarity with some key proteins implicated in human diseases, such as apolipoprotein-E, β-amyloid or insulin, has been demonstrated. On the other hand, the fact that this animal is diurnal has provided important contribution in the field of circadian biology. Concerning age-related diseases, this rodent could be a good model of multimorbidity since it naturally develops cognitive decline, neurodegenerative histopathological hallmarks, visual degeneration, type II diabetes, endocrinological and metabolic dysfunctions, neoplasias and kidneys alterations. In this review we have collected and summarized the studies performed on the Octodon degus through the years that support its use as a model for biomedical research, with a special focus on ageing.

In Parkinson’s disease, synucleinopathy is hypothesized to spread from the enteric nervous system, via the vagus nerve, to the CNS. Here, we compare, in baboon monkeys, the pathological consequences of either intrastriatal or enteric injection of α-synuclein-containing Lewy body extracts from patients with Parkinson’s disease. This study shows that patient-derived α-synuclein aggregates are able to induce nigrostriatal lesions and enteric nervous system pathology after either enteric or striatal injection in a non-human primate model. This finding suggests that the progression of α-synuclein pathology might be either caudo-rostral or rostro-caudal, varying between patients and disease subtypes. In addition, we report that α-synuclein pathological lesions were not found in the vagal nerve in our experimental setting. This study does not support the hypothesis of a transmission of α-synuclein pathology through the vagus nerve and the dorsal motor nucleus of the vagus. Instead, our results suggest a possible systemic mechanism in which the general circulation would act as a route for long-distance bidirectional transmission of endogenous α-synuclein between the enteric and the central nervous systems. Taken together, our study provides invaluable primate data exploring the role of the gut-brain axis in the initiation and propagation of Parkinson’s disease pathology and should open the door to the development and testing of new therapeutic approaches aimed at interfering with the development of sporadic Parkinson’s disease.

Background: Neurocysticercosis (NCC) is the most common parasitic neurological disease worldwide and a major cause of epilepsy. Spain is the country reporting the highest number of NCC imported cases in Europe. Methodology: Retrospective case series of NCC patients registered in the +REDIVI Network from October 1, 2009 to July 2018. A specific questionnaire, including clinical and diagnostic characteristics, was created and sent to the collaborator centers. Results: 46 cases were included in the analysis. 55% were male, mean age of 40 years. 95.6% were migrants. The median duration since migration from an endemic area was 10 years. Predominant nationalities were Ecuadorians (50%) and Bolivians (30.4%). Frequent locations were parenchymal (87%), subarachnoid (26.1%) and intraventricular cysts (10.9%). Serological analysis was performed in 91.3%, being 54.8% positive. Most prevalent clinical manifestations were persistent headache (60.9%), epilepsy (43.5%) and visual changes (13%). Patients were mainly treated with albendazole (76.1%), corticosteroids (67.4%), and anticonvulsionants (52.2%). 82.5% had a favorable clinical outcome. Conclusions: Most NCC cases were long-standing migrants. Few clinical differences were observed depending on the cysticerci location. The treatment was often not according to current recommendations, and no uniform criteria were followed when it came to the therapeutic regimen. NCC case management in Spain (including clinician awareness and laboratory capacity improvements) needs to be strengthened., We would thanks Maria Jesus Perteguer from the National Center of Microbiology for the information and update on NCC lab techniques currently performed in Spain. The corresponding author's affiliation centre belongs to the ISCIII-Sub. Gral. Redes-Network Biomedical Research on Tropical Diseases (RICET in Spanish) grant RD16CIII/0003/0001, RD16/0027/0020, RD16CIII/0003/0001 and the European Regional Development Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Machine learning–based approach unravels distinct pathological signatures induced by patient-derived α-synuclein seeds in monkeys., Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)–rich protein aggregates [termed “Lewy bodies” (LBs)], is a well-established characteristic of Parkinson’s disease (PD). Much evidence, accumulated from multiple experimental models, has suggested that α-syn plays a role in PD pathogenesis, not only as a trigger of pathology but also as a mediator of disease progression through pathological spreading. Here, we have used a machine learning–based approach to identify unique signatures of neurodegeneration in monkeys induced by distinct α-syn pathogenic structures derived from patients with PD. Unexpectedly, our results show that, in nonhuman primates, a small amount of singular α-syn aggregates is as toxic as larger amyloid fibrils present in the LBs, thus reinforcing the need for preclinical research in this species. Furthermore, our results provide evidence supporting the true multifactorial nature of PD, as multiple causes can induce a similar outcome regarding dopaminergic neurodegeneration.

The inferior colliculus (IC) is an important midbrain relay station for the integration of descending and ascending auditory information. Additionally, the IC has been implicated in processing sensorimotor responses. Glutamatergic and GABAergic manipulations in the IC can improve motor deficits as demonstrated by the animal model of haloperidol-induced catalepsy. However, how the IC influences motor function remains unclear. We investigated the effects of either intracollicular deep brain stimulation (DBS) or microinjection of the glutamatergic antagonist MK-801 or the agonist NMDA in C57BL/6J mice chronically treated with saline or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). After DBS or microinjections, the mice were submitted to rotarod and open field tests, respectively. DBS in the IC was effective to increase the time spent on the rotarod in MPTP-treated mice. After unilateral microinjection of MK-801, but not NMDA, MPTP-treated mice increased the distance travelled in the open field (p 0.05). In conclusion, intracollicular DBS or MK-801 microinjection can improve motor performance in parkinsonian mice suggesting the IC as a new and non-conventional therapeutic target in motor impairment.