Versatile and efficient protein association through chemically modified Sphingomyelin Nanosystems (SNs) for enhanced delivery.

Proteins are biological macromolecules well known to regulate many cellular signaling mechanisms. For instance, they are very appealing for their application as therapeutic agents, presenting high specificity and activity. Nonetheless, they suffer from unfolding, instability and low bioavailability making their administration through systemic and other routes very tough. To overcome these drawbacks, drug delivery systems and nanotechnology have arisen to deliver biomolecules in a sustained manner while, at the same time, increasing dose availability, protecting the cargo without compromising proteins' bioactivity, and enhancing intracellular delivery. In this work, we proposed the optimization of sphingomyelin nanosystems (SNs) for the delivery of a wide collection of proteins (ranging from 10-500 kDa and pI) using diverse chemical association strategies. We have further characterized SNs by varied analytical methodologies. We have also carried out in vitro experiments to validate the potential of the developed formulations. As the final goal, we aim to obtain evidence of the potential use of SNs for the development of protein therapeutics.

Repeated intravenous doses of human umbilical cord-derived mesenchymal stromal cells for bronchopulmonary dysplasia: results of a phase 1 clinical trial with 2-year follow-up.

BACKGROUND: Currently, there is a lack of effective treatments or preventive strategies for bronchopulmonary dysplasia (BPD). Pre-clinical studies with mesenchymal stromal cells (MSCs) have yielded encouraging results. The safety of administering repeated intravenous doses of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs) has not yet been tested in extremely-low-gestational-age newborns (ELGANs). AIMS: to test the safety and feasibility of administering three sequential intravenous doses of UC-MSCs every 7 days to ELGANs at risk of developing BPD. METHODS: In this phase 1 clinical trial, we recruited ELGANs (birth weight ≤1250 g and ≤28 weeks in gestational age [GA]) who were on invasive mechanical ventilation (IMV) with FiO2 ≥ 0.3 at postnatal days 7-14. Three doses of 5 × 106/kg of UC-MSCs were intravenously administered at weekly intervals. Adverse effects and prematurity-related morbidities were recorded. RESULTS: From April 2019 to July 2020, 10 patients were recruited with a mean GA of 25.2 ± 0.8 weeks and a mean birth weight of 659.8 ± 153.8 g. All patients received three intravenous UC-MSC doses. The first dose was administered at a mean of 16.6 ± 2.9 postnatal days. All patients were diagnosed with BPD. All patients were discharged from the hospital. No deaths or any serious adverse events related to the infusion of UC-MSCs were observed during administration, hospital stays or at 2-year follow-up. CONCLUSIONS: The administration of repeated intravenous infusion of UC-MSCs in ELGANs at a high risk of developing BPD was feasible and safe in the short- and mid-term follow-up.

Transcatheter pulmonary valve replacement after arterial switch operation.

BACKGROUND: Patients with d-transposition of the great arteries (d-TGA) who have undergone an arterial switch operation (ASO) can develop right ventricular outflow tract (RVOT) dysfunction with pulmonary regurgitation (PR) or stenosis. In these patients, treatment may include transcatheter pulmonary valve replacement (TPVR). Coronary compression is a contraindication occurring in 5% of typical TPVR cases. After ASO, there are various anatomical considerations that can confound TPVR, including potential coronary artery compression. Our goal is to understand feasibility of TPVR in patients following ASO. METHODS: This was a retrospective multicenter cohort study of patients with RVOT dysfunction after ASO who underwent cardiac catheterization with intention to perform TPVR from 2008 to 2020. RESULTS: Across nine centers, 33 patients met inclusion criteria. TPVR was successful in 22 patients (66%), 19 receiving a Melody valve and 3 a SAPIEN valve. RVOT stenosis in isolation or with PR dictated need for TPVR in nearly all patients. One serious adverse event occurred with valve embolization. After TPVR, the RVOT peak gradient decreased from 43 to 9 mm Hg (p < 0.001); PR was trivial/none in all but one patient, in whom it was mild. Coronary compression prohibiting TPVR occurred in eight patients (24%) and two patients (6%) had severe aortic regurgitation from aortic root deformation precluding TPVR. Seven patients underwent RVOT reintervention with a median of 5.3 years post-TPVR. CONCLUSIONS: TPVR in patients with d-TGA after ASO is feasible, but in this cohort, coronary compression or aortic root distortion precluded TPVR in one-third of patients. The rate of RVOT reintervention after TPVR was higher in this cohort of ASO patients that in prior studies.

Are Rattus rattus fleas invasive? Evaluation of flea communities in invasive and native rodents in Chile.

Co-invasion, characterized by the simultaneous introduction of hosts and parasites with the latter establishing themselves in native hosts, is a phenomenon of ecological concern. Rattus rattus, a notorious invasive species, has driven the extinction and displacement of numerous avian and mammalian species and serves as a key vector for diseases affecting both humans and wildlife. Among the parasites hosted by R. rattus are fleas, which exhibit obligate parasitic behaviour, a generalist nature and high prevalence, increasing the likelihood of flea invasion. Simultaneously, invasive species can serve as hosts for native parasites, leading to potential amplification or dilution of parasite populations in the environment. In Chile, R. rattus has been present since the 17th century because of the arrival of the Spanish colonizers through the ports and has spread throughout urban, rural and wild Chilean territories. This study aims to evaluate whether co-invasion of native fleas of invasive rats occurs on native rodents in Chile and to determine whether black rats have acquired flea native to Chile during their invasion. For this, we captured 1132 rodents from 26 localities (20° S-53° S). Rattus rattus was found coexisting with 11 native rodent species and two species of introduced rodents. Among the native rodents, Abrothrix olivacea and Oligoryzomys longicaudatus exhibited more extensive sympatry with R. rattus. We identified 14 flea species associated with R. rattus, of which only three were native to rats: Xenopsylla cheopis, Leptopsylla segnis and Nosopsyllus fasciatus. These three species presented a higher parasite load in black rats compared to native fleas. Leptopsylla segnis and N. fasciatus were also found associated with native rodent species that cohabit with R. rattus. The remaining species associated with R. rattus were fleas of native rodents, although they were less abundant compared to those associated with native rodents, except for Neotyphloceras pardinasi and Sphinctopsylla ares. Although there has been evidence of flea transmission from rats to native species, the prevalence and abundance were relatively low. Therefore, it cannot be definitively concluded that these fleas have established themselves in native rodent populations, and hence, they cannot be classified as invasive fleas. This study underscores R. rattus' adaptability to diverse environmental and geographical conditions in Chile, including its capacity to acquire fleas from native rodents. This aspect has critical implications for public health, potentially facilitating the spread of pathogens across various habitats where these rats are found.

Morphological and molecular data on the bat flies, Basilia silvae (Brèthes, 1913) and Trichobius parasiticus Gervais, 1844 parasitizing Chilean bats.

Among mammals, bats harbour the greatest taxonomic diversity of ectoparasitic arthropods. This is mainly due to their high mobility, wide distribution range and gregarious social behaviour. In Chile, 17 species of bats have been reported; however, their ectoparasitic arthropofauna has been little studied. There are currently 12 taxa recorded, belonging to two classes and associated with only four species of bats. This study aimed to investigate the diversity of parasitic flies associated with bats in three ecoregions: Atacama Desert, Chilean Matorral and Valdivian temperate forest. During 2021, using mist nets, bats were captured in Anzota caves (Atacama Desert ecoregion), Huelquén and Alto Jahuel (Chilean Matorral ecoregion), Cherquenco and San Patricio (Valdivian temperate forest). Each bat was carefully checked during a 15-min interval for the collection of ectoparasites. The arthropods were deposited in vials with 96% ethanol. A total of 26 bats corresponding to three species (Vespertilionidae: Histiotus magellanicus Philippi, 1866, Myotis arescens (Osgood, 1943); Phyllostomidae: Desmodus rotundus (Geoffroy, 1810)) were captured from which a total of 142 ectoparasitic arthropods were collected. Bat flies were separated/identified under a stereomicroscope. Additionally, from the fieldwork, we report the presence of other ectoparasites associated with Chilean bats. In our study, we report new host-parasite associations between Trichobius parasiticus Gervais, 1844 (Diptera: Streblidae) on D. rotundus, and Basilia silvae (Brèthes, 1913) (Diptera: Nycteribiidae) in M. arescens in Chile. Our study extended the latitudinal range of distribution for B. silvae to Araucanía region, and we report for first time T. parasiticus in the country. Additionally, partial sequences of the cytochrome c oxidase I gene were obtained from these specimens. Although there is slight morphological variation in the specimens of T. parasiticus, phylogenetic analyses suggest that they correspond to the same species. The sequences generated for B. silvae represent the first for the species. Authors recommend the use of an integrative approach in the identification of ectoparasites in poorly studied ecoregions and hosts. The integration of different markers is necessary to determine more precisely the phylogenetic relationships between South American populations and species of the genera Basilia and Trichobius.

Sentinel lymph node biopsy versus observation in high-risk cutaneous squamous cell carcinoma in immunosuppressed and immunocompetent patients: An inverse probability of treatment weighting study.

BACKGROUND: The survival benefit of sentinel lymph node biopsy (SLNB) in immunocompetent and immunosuppressed patients with high-risk cutaneous squamous cell carcinoma (cSCC) has not been established. OBJECTIVE: To determine whether SLNB improves disease-specific survival (DSS) in high-risk cSCC. Secondary objectives were to analyse disease-free survival, nodal recurrence-free survival and overall survival (OS). METHODS: Multicentre, retrospective, observational cohort study comparing survival outcomes in immunosuppressed and immunocompetent patients treated with SLNB or watchful waiting. Inverse probability of treatment weighting was used to adjust for possible confounding effects. RESULTS: We studied 638 tumours in immunocompetent patients (SLNB n = 42, observation n = 596) and 173 tumours in immunosuppressed patients (SLNB n = 28, observation n = 145). Overall, SLNB was positive in 15.7% of tumours. SLNB was associated with a reduced risk of nodal recurrence (NR) (hazard ratio [HR], 0.05 [95% CI, 0.01-0.43]; p = 0.006), disease specific mortality (HR, 0.17 [95% CI, 0.04-0.72]; p = 0.016) and all-cause mortality (HR, 0.33 [95% CI, 0.15-0.71]; p = 0.004) only in immunocompetent patients. CONCLUSIONS: SLNB was associated with improvements in NR, DSS and OS in immunocompetent but not in immunosuppressed patients with high-risk cSCC.

Anakinra-Loaded Sphingomyelin Nanosystems Modulate In Vitro IL-1-Dependent Pro-Tumor Inflammation in Pancreatic Cancer.

Pancreatic cancer is a very aggressive disease with a dismal prognosis. The tumor microenvironment exerts immunosuppressive activities through the secretion of several cytokines, including interleukin (IL)-1. The IL-1/IL-1 receptor (IL-1R) axis is a key regulator in tumor-promoting T helper (Th)2- and Th17-type inflammation. Th2 cells are differentiated by dendritic cells endowed with Th2-polarizing capability by the thymic stromal lymphopoietin (TSLP) that is secreted by IL-1-activated cancer-associated fibroblasts (CAFs). Th17 cells are differentiated in the presence of IL-1 and other IL-1-regulated cytokines. In pancreatic cancer, the use of a recombinant IL-1R antagonist (IL1RA, anakinra, ANK) in in vitro and in vivo models has shown efficacy in targeting the IL-1/IL-1R pathway. In this study, we have developed sphingomyelin nanosystems (SNs) loaded with ANK (ANK-SNs) to compare their ability to inhibit Th2- and Th17-type inflammation with that of the free drug in vitro. We found that ANK-SNs inhibited TSLP and other pro-tumor cytokines released by CAFs at levels similar to ANK. Importantly, inhibition of IL-17 secretion by Th17 cells, but not of interferon-γ, was significantly higher, and at lower concentrations, with ANK-SNs compared to ANK. Collectively, the use of ANK-SNs might be beneficial in reducing the effective dose of the drug and its toxic effects.

Occupational Therapy Practice in Schools: National Survey in Spain.

AIMS: Interdisciplinary collaboration between health and education professionals is one of the principles of inclusive education. This study aimed to describe the practices and service delivery by pediatric occupational therapists (OTs) in schools in Spain. METHODS: Data came from a convenience sample of pediatric OTs recruited through Spanish professional colleges and associations for a web-based survey, mixed-method research study. Thirty-five respondents were excluded because they didn't meet the eligibility criteria. Ninety-two responses were obtained for data analysis. Twenty-nine OTs (31.5%) work in schools (school-OTs), and sixty-three participants (68.5%) don't work there but collaborate with schools (non-school OTs). RESULTS: Participants support students with and without a medical diagnosis. Services provided by OTs external to the educational system are mainly funded by families or only partially covered. Findings show that most participants use standardized assessments and apply several intervention approaches. They believe there are barriers to the collaboration and implementation of occupational therapy services in schools. CONCLUSIONS: This preliminary study shows a need for changes in Spain's State and Regional Education legislation and provides recommendations to improve school service delivery. Pediatric OTs are encouraged to reflect on and identify opportunities for changes to enhance school-based occupational therapy practice in Spain.

Prognostic factors for satellitosis or in-transit metastasis in cutaneous squamous cell carcinoma: A multicentric cohort study.

BACKGROUND: Satellitosis or in-transit metastasis (S-ITM) has clinical outcomes comparable to node-positivity in cutaneous squamous cell carcinoma (cSCC). There is a need to stratify the risk groups. OBJECTIVE: To determine which prognostic factors of S-ITM confer an increased risk of relapse and cSCC-specific-death. METHODS: A retrospective, multicenter cohort study. Patients with cSCC developing S-ITM were included. Multivariate competing risk analysis evaluated which factors were associated with relapse and specific death. RESULTS: Of a total of 111 patients with cSCC and S-ITM, 86 patients were included for analysis. An S-ITM size of ≥20 mm, >5 S-ITM lesions, and a primary tumor deep invasion was associated with an increased cumulative incidence of relapse (subhazard ratio [SHR]: 2.89 [95% CI, 1.44-5.83; P = .003], 2.32 [95% CI, 1.13-4.77; P = .021], and 2.863 [95% CI, 1.25-6.55; P = .013]), respectively. Several >5 S-ITM lesions were also associated with an increased probability of specific death (SHR: 3.48 [95% CI, 1.18-10.2; P = .023]). LIMITATIONS: Retrospective study and heterogeneity of treatments. CONCLUSION: The size and the number of S-ITM lesions confer an increased risk of relapse and the number of S-ITM an increased risk of specific-death in patients with cSCC presenting with S-ITM. These results provide new prognostic information and can be considered in the staging guidelines.

DNMR measurements of an asymmetric odd liquid crystal dimer: determination of the intramolecular angle and the degree of order of the two rigid cores.

In this work, we present a Deuteron Nuclear Magnetic Resonance (DNMR) study of the non-symmetric odd liquid crystal dimer α-(4-cyanobiphenyl-4'-yloxy)-ω-(1-pyrenimine-benzylidene-4'-oxy) heptane (CBO7O.Py), formed by a pro-mesogenic cyanobiphenyl unit and a bulky pyrene-containing unit, linked via alkoxy flexible chain. We have synthesized two partially deuterated samples: one with the deuterium atoms in the cyanobiphenyl moiety (dCBO7O.Py) and the other one with the deuterium atoms in the pyrenimine-benzylidene unit (CBO7O.dPy). We have performed angular distribution analysis in the SmA glassy state, obtaining the degree of order of both rigid cores and an estimation of the internal molecular angle between both structures. With the results from the angular study, we have been able to determine the degree of order of both rigid units in either the N phase and the SmA phase, far enough from the glass transition. Both rigid cores have the same degree of order close to the nematic-isotropic phase transition, but as the compound is cooled down, the degree of order of the cyanobiphenyl moiety is clearly higher than that of the pyrene-containing unit. The critical behaviour of the order parameter of the pyrene-containing moiety is consistent with the fact that, for CBO7O.Py, the N-I phase transition is tricritical, which seems to indicate that the uniaxial order parameter of the dimer is dominated by the degree of order of the pyrene-containing core.

PRGF Membrane with Tailored Optical Properties Preserves the Cytoprotective Effect of Plasma Rich in Growth Factors: In Vitro Model of Retinal Pigment Epithelial Cells.

The present study evaluates the ability of a novel plasma rich in growth factors (PRGF) membrane with improved optical properties to reduce oxidative stress in retinal pigment epithelial cells (ARPE-19 cells) exposed to blue light. PRGF was obtained from three healthy donors and divided into four main groups: (i) PRGF membrane (M-PRGF), (ii) PRGF supernatant (S-PRGF), (iii) platelet-poor plasma (PPP) membrane diluted 50% with S-PRGF (M-PPP 50%), and (iv) M-PPP 50% supernatant (S-PPP 50%). ARPE-19 cells were exposed to blue light and then incubated with the different PRGF-derived formulations or control for 24 and 48 h under blue light exposure. Mitochondrial and cell viability, reactive oxygen species (ROS) production, and heme oxygenase-1 (HO-1) and ZO-1 expression were evaluated. Mitochondrial viability and cell survival were significantly increased after treatment with the different PRGF-derived formulations. ROS synthesis and HO-1 expression were significantly reduced after cell treatment with any of the PRGF-derived formulations. Furthermore, the different PRGF-derived formulations significantly increased ZO-1 expression in ARPE-19 exposed to blue light. The new PRGF membrane with improved optical properties and its supernatant (M-PPP 50% and S-PPP 50%) protected and reversed blue light-induced oxidative stress in ARPE-19 cells at levels like those of a natural PRGF membrane and its supernatant.

Novel Vector of Scrub Typhus in Sub-Antarctic Chile: Evidence From Human Exposure.

The exposure of a research team to chigger mites in southern Chile allowed the first identification of a trombiculid species as vector and reservoir of scrub typhus outside the tsutsugamushi triangle, providing unique insights into the ecology and transmission of this recently discovered rickettsial infection in South America.

Association of the dysfunctional placentation endotype of prematurity with bronchopulmonary dysplasia: a systematic review, meta-analysis and meta-regression.

BACKGROUND: Antenatal pathological conditions are key in the pathogenesis of bronchopulmonary dysplasia (BPD). Pathophysiological pathways or endotypes leading to prematurity and perinatal lung injury can be clustered into two groups: infection and dysfunctional placentation, which include hypertensive disorders of pregnancy (HDP) and intrauterine growth restriction (IUGR). We conducted a systematic review of observational studies exploring the association between the dysfunctional placentation endotype and BPD. METHODS: MEDLINE, Embase and Web of Science databases were searched up to February 2020 for studies reporting data on the diagnosis of HDP, IUGR or small for gestational age (SGA) and BPD risk. BPD was classified as BPD28 (supplemental oxygen on day 28), BPD36 (oxygen at 36 weeks postmenstrual age), severe BPD (≥ 30% oxygen or mechanical ventilation), BPD36/death and BPD-associated pulmonary hypertension. RESULTS: Of 6319 studies screened, 211 (347 963 infants) were included. Meta-analysis showed an association between SGA/IUGR and BPD36 (OR 1.56, 95% CI 1.37 to 1.79), severe BPD (OR 1.82, 95% CI 1.36 to 2.29) and BPD/death (OR 1.91, 95% CI 1.55 to 2.37). Exposure to HDP was not associated with BPD but was associated with decreased odds of BPD/death (OR 0.77, 95% CI 0.64 to 0.94). Both HDP (OR 1.41, 95% CI 1.10 to 1.80) and SGA/IUGR (OR 2.37, 95% CI 1.86 to 3.02) were associated with BPD-associated pulmonary hypertension. CONCLUSION: When placental vascular dysfunction is accompanied by fetal growth restriction or being born SGA, it is associated with an increased risk of developing BPD and pulmonary hypertension. The placental dysfunction endotype of prematurity is strongly associated with the vascular phenotype of BPD. PROSPERO REGISTRATION NUMBER: Review protocol was registered in PROSPERO database (ID=CRD42018086877).

PAR4 activation involves extracellular loop 3 and transmembrane residue Thr153.

Protease-activated receptor 4 (PAR4) mediates sustained thrombin signaling in platelets and is required for a stable thrombus. PAR4 is activated by proteolysis of the N terminus to expose a tethered ligand. The structural basis for PAR4 activation and the location of its ligand binding site (LBS) are unknown. Using hydrogen/deuterium exchange (H/D exchange), computational modeling, and signaling studies, we determined the molecular mechanism for tethered ligand-mediated PAR4 activation. H/D exchange identified that the LBS is composed of transmembrane 3 (TM3) domain and TM7. Unbiased computational modeling further predicted an interaction between Gly48 from the tethered ligand and Thr153 from the LBS. Mutating Thr153 significantly decreased PAR4 signaling. H/D exchange and modeling also showed that extracellular loop 3 (ECL3) serves as a gatekeeper for the interaction between the tethered ligand and LBS. A naturally occurring sequence variant (P310L, rs2227376) and 2 experimental mutations (S311A and P312L) determined that the rigidity conferred by prolines in ECL3 are essential for PAR4 activation. Finally, we examined the role of the polymorphism at position 310 in venous thromboembolism (VTE) using the International Network Against Venous Thrombosis (INVENT) consortium multi-ancestry genome-wide association study (GWAS) meta-analysis. Individuals with the PAR4 Leu310 allele had a 15% reduction in relative risk for VTE (odds ratio, 0.85; 95% confidence interval, 0.77-0.94) compared with the Pro310 allele. These data are consistent with our H/D exchange, molecular modeling, and signaling studies. In conclusion, we have uncovered the structural basis for PAR4 activation and identified a previously unrecognized role for PAR4 in VTE.

Foraging networks and social tolerance in a cooperatively breeding primate (Callithrix jacchus).

Within-group competition over food resources can be a major cost of social living. In the wild, foragers are confronted with social (e.g. hierarchical rank) and ecological (e.g. food availability and distribution) challenges that affect their foraging decisions and feeding success. Exhibiting prosocial behaviours, such as tolerance at feeding sites, can benefit group members by developing affiliative social relationships, enhancing access to resources and maximizing fitness. We examined social tolerance at feeding sites in Callithrix jacchus, a cooperatively breeding primate species. We investigated the set of social (rank, age and sex) and ecological (food availability) factors that influence the structure and dynamics of within-group foraging association networks. We designed and conducted an experimental field study of four wild groups of common marmosets in which we controlled food distribution (concentrated or scattered) and productivity (high, medium or low food rewards). Then, we used social network analyses to assess the number and strength of foraging associations among group members, their effects on individual food consumption, and whether recent experiences with conspecifics during foraging affected subsequent associations. Overall, common marmoset foraging association networks were cohesive, as group members jointly occupied feeding sites. The number and strength of associations varied depending on the ecological context. Associations were stronger during conditions in which food was concentrated at a single site. Individuals obtained greater access to food resources when sharing a feeding site with conspecifics, but once a food item was obtained, the forager moved to a nearby tree and consumed it away from others. Additionally, the strength of previous foraging associations and subsequent levels of social tolerance at feeding sites were positively related, a relationship compatible with the ability of memorizing associations over time and recalling the information in future decision-making. In sum, marmosets adjusted their partner choices and the strength of foraging associations in response to food availability. They exhibited increased social tolerance at feeding sites during conditions in which opportunities for contest competition were expected to be greatest. These cooperative breeding primates appear to mutually benefit by maintaining cohesive and strong affiliative relationships, and by increasing opportunities for coordinated behaviour and offspring survival.

A competição por recursos alimentares dentro do grupo pode ser um grande custo da vida social. Na natureza, os forrageadores são confrontados com desafios sociais (e.g. posição hierárquica) e ecológicos (e.g. disponibilidade e distribuição de alimentos) que afetam suas decisões de forrageio e seu sucesso alimentar. Exibir comportamentos pró-sociais, como tolerância em sítios de alimentação, pode beneficiar os membros do grupo, desenvolvendo relações sociais afiliativas, melhorando o acesso aos recursos e maximizando sua aptidão evolutiva. Examinamos a tolerância social de um primata com reprodução cooperativa (Callithrix jacchus) em sítios de alimentação. Investigamos a influência de um conjunto de fatores sociais (hierarquia, idade, sexo) e ecológicos (disponibilidade de alimento) na estrutura e dinâmica das redes de associação de forrageio dentro do grupo social. Planejamos e conduzimos um experimento de campo com quatro grupos de saguis-comuns de vida livre, no qual controlamos a distribuição (concentrada e dispersa) e a produtividade de alimento (altas, médias ou baixas recompensas). Usamos análise de redes sociais para avaliar o número e a força das associações de forrageio entre os membros do grupo, seu efeito no consumo individual de alimento, e se experiências recentes de forrageio entre coespecíficos afetam associações subsequentes. Em geral, as redes de associação de forrageio dos saguis foram coesas e os membros de cada grupo ocuparam sítios de alimentação em conjunto. O número e a força das associações variaram dependendo do contexto ecológico. As associações foram mais fortes durante as condições em que o alimento se encontrava concentrado em um sítio. Os indivíduos obtiveram maior acesso aos recursos quando compartilharam o sítio de alimentação com coespecíficos, e uma vez que o item alimentar era obtido, o forrageador o consumia em uma árvore próxima, longe dos outros. Além disso, a força das associações recentes e os níveis subsequentes de tolerância social em sítios de alimentação foram positivamente relacionados, compatível com a capacidade de memorizar associações ao longo do tempo e relembrá-las em tomadas de decisão futuras. Em conclusão, os saguis ajustaram suas escolhas de parceiros e a força das associações de forrageio em resposta à disponibilidade de alimento. Eles exibiram uma maior tolerância social em sítios de alimentação durante as condições em que se esperava que as oportunidades de competição direta fossem maiores. Estes primatas com reprodução cooperativa parecem se beneficiar mutuamente ao manterem relações afiliativas coesas e fortes, as quais aumentam as oportunidades para comportamentos coordenados e a sobrevivência da prole.

Self-medication in nonhuman primates: A systematic evaluation of the possible function of the use of medicinal plants.

Animal self-medication is thought to provide an adaptive advantage, as species would actively respond to a disease state or homeostatic imbalances. In wild nonhuman primates, it is challenging to differentiate plant use as part of the diet or as medication, especially because self-medication can be preventive or therapeutic. Here, we aimed to compile the available potential evidence on primate self-medication modes, investigating which proposed requirements are fulfilled for each plant species reported to date. We systematically reviewed the scientific literature on plant use for potential self-medication in wild nonhuman primates. To construct the extensive database, we extracted data on the primate species, study area, plant/plant's part used, the requirement(s) met for demonstrating self-medication modes, and self-medicative behavioral patterns. We also updated available information on plant's biological compounds and/or physical characteristics, pharmacological properties, and ethnomedical uses. We identified 575 plant species (135 families), used by 25 primate species (9 families). Plants were used by Old World monkeys (46.5%, n = 268 plant species), followed by apes (41%, n = 235), New World monkeys (13.4%, n = 77), and prosimians (1%, n = 6). We found three general types of self-medicative behaviors: ingestion (including, but not limited to, leaf-swallowing, seed-swallowing, and bitter pith chewing), topical (fur-rubbing), and nest fumigation. Plant uses were associated with antiparasitic, antibacterial, antimalarial, anti-inflammatory, insect repellent, among other properties. Self-medication is widespread in nonhuman primate species across Central and South America, Africa, Madagascar, and Asia. Long-term field research efforts and studies integrating different research sites and topics are urgent to advance our knowledge into the evolution of plant selection, medical traditions, and to bring insights into potentially novel medicinal plants and bioactive compounds to treat emergent or established primate and human diseases.

Temperature and exudativory as drivers of the marmoset (Callithrix spp.) daily activity period.

Primates are affected by fluctuations in ambient temperatures, mostly through thermoregulatory costs and changes in the availability of food. In the present study, we investigate whether the ambient temperature and proxies of food availability affect the activity period of marmosets (Callithrix spp.). We predicted that: (i) at colder sites, marmosets would spend more time at sleeping sites; (ii) midday resting bouts would be longer at hotter sites; (iii) the onset/cessation of activity and resting behavior at midday would be more closely related to temperature than food availability, and (iv) highly exudativorous groups would have higher total levels of resting. We compiled data on the onset and cessation of activity and the time spent resting at midday from seven marmoset studies from sites with a wide range of temperatures. We used generalized linear mixed models to verify the relationship between the dependent variables (lag between dawn and the onset of activities, lag between cessation of activities and dusk, and proportion of resting during midday) and the minimum and maximum temperatures at the respective study sites, together with proxies of food availability (exudativory rates, the amount of habitat available per individual, and net primary productivity) using each sample month as a sampling unit and the identity of the study as a categorical random factor. At colder sites and during colder months, the marmosets left sleeping trees later in the morning and ceased their activities earlier, while at hotter sites and during hotter months, they spent more time resting during midday. More exudativorous groups become active later in the morning, but also ceased their activities later. The abundance of food did not affect the timing of activities. We provide evidence that both low and high temperatures affect marmosets' activities, and that their activity period appears to be more influenced by the thermal environment than food availability.

Apicomplexans in small mammals from Chile, with the first report of the Babesia microti group in South American rodents.

Small mammals play an essential role as disseminators of pathogens because they reach high population densities and have ubiquitous distributions. In the Northern Hemisphere rodents are well recognized as reservoirs for tick-borne bacteria of the Anaplasmataceae family and also apicomplexan protozoans. In contrast, South American rodents hosting these microorganisms have been rarely identified. In this study, we collected blood from rodents and marsupials in northern Chile and screened for Anaplasmataceae bacteria and apicomplexan protozoa. Overall, 14.7% of the samples were positive for Babesia, Hepatozoon, and Sarcocystidae using conventional PCR assays targeting the structural 18S rRNA locus (18S). Phylogenetic analyses performed with amplicons derived from 18S and cytochrome c oxidase (COI) gene provided evidence of a Babesia sp. belonging to the Babesia microti group in Phyllotis darwini, and a novel Babesia genotype in P. darwini and Abrothrix jelskii. Furthermore, four novel genotypes of Hepatozoon retrieved from Abrothrix olivacea, P. darwini, and Oligoryzomys longicaudatus, formed independent lineages within a clade that includes additional Hepatozoon spp. detected in South American rodents. Moreover, an incidental finding of a previously detected apicomplexan, herein designated as Sarcocystidae sp., was recorded in Thylamys opossums with a high prevalence, indicating a possible specific association with these mammals. Phylogenetic analysis of Sarcoystidae sp. clearly demonstrated its relatedness to apicomplexans detected in Australian marsupials. Our results expand the range of mammals hosting tick-borne apicomplexans in South America, highlight a novel clade consisting of South American babesias, and report for the first time the B. microti group infecting rodents in the region.

Clinical Implications of the Genetic Background in Pediatric Pulmonary Arterial Hypertension: Data from the Spanish REHIPED Registry.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a severe and rare disease with an important genetic background. The influence of genetic testing in the clinical classification of pediatric PAH is not well known and genetics could influence management and prognosis. OBJECTIVES: The aim of this work was to identify the molecular fingerprint of PH children in the REgistro de pacientes con HIpertensión Pulmonar PEDiátrica (REHIPED), and to investigate if genetics could have an impact in clinical reclassification and prognosis. METHODS: We included pediatric patients with a genetic analysis from REHIPED. From 2011 onward, successive genetic techniques have been carried out. Before genetic diagnosis, patients were classified according to their clinical and hemodynamic data in five groups. After genetic analysis, the patients were reclassified. The impact of genetics in survival free of lung transplantation was estimated by Kaplan-Meier curves. RESULTS: Ninety-eight patients were included for the analysis. Before the genetic diagnoses, there were idiopathic PAH forms in 53.1%, PAH associated with congenital heart disease in 30.6%, pulmonary veno-occlusive disease-PVOD-in 6.1%, familial PAH in 5.1%, and associated forms with multisystemic disorders-MSD-in 5.1% of the patients. Pathogenic or likely pathogenic variants were found in 44 patients (44.9%). After a genetic analysis, 28.6% of the cohort was "reclassified", with the groups of heritable PAH, heritable PVOD, TBX4, and MSD increasing up to 18.4%, 8.2%, 4.1%, and 12.2%, respectively. The MSD forms had the worst survival rates, followed by PVOD. CONCLUSIONS: Genetic testing changed the clinical classification of a significant proportion of patients. This reclassification showed relevant prognostic implications.

Enhanced nitrogen and carbon removal in natural seawater by electrochemical enrichment in a bioelectrochemical reactor.

Municipal and industrial wastewater discharges in coastal and marine environments are of major concern due to their high carbon and nitrogen loads and the resulted phenomenon of eutrophication. Bioelectrochemical reactors (BERs) for simultaneous nitrogen and carbon removal have gained attention owing to their cost efficiency and versatility, as well as the possibility of electrochemical enrich specific groups. This study presented a scalable two-chamber BERs using graphite granules as electrode material. BERs were inoculated and operated for 37 days using natural seawater with high concentrations of ammonium and acetate. The BERs demonstrated a maximum current density of 0.9 A m-3 and removal rates of 7.5 mg NH4+-N L-1 d-1 and 99.5 mg L-1 d-1 for total organic carbon (TOC). Removals observed for NH4+-N and TOC were 96.2% and 68.7%, respectively. The results of nutrient removal (i.e., ammonium, nitrate, nitrite and TOC) and microbial characterization (i.e., next-generation sequencing of the 16S rRNA gene and fluorescence in situ hybridization) showed that BERs operated with a poised cathode at -260 mV (vs. Ag/AgCl) significantly enriched nitrifying microorganisms in the anode and denitrifying microorganisms and planctomycetes in the cathode. Interestingly, the electrochemical enrichment did not increase the total number of microorganisms in the formed biofilms but controlled their composition. Thus, this work shows the first successful attempt to electrochemically enrich marine nitrifying and denitrifying microorganisms and presents a technique to accelerate the start-up process of BERs to remove dissolved inorganic nitrogen and total organic carbon from seawater.