Worldwide diversity in mammalian life histories: Environmental realms and evolutionary adaptations.

Mammalian life history strategies can be characterised by a few axes of variation, conforming a space where species are positioned based on the life history strategies favoured in the environment they exploit. Yet, we still lack global descriptions of the diversity of realised mammalian life history and how this diversity is shaped by the environment. We used six life history traits to build a life history space covering worldwide mammalian adaptation, and we explored how environmental realms (land, air, water) influence mammalian life history strategies. We demonstrate that realms are tightly linked to distinct life history strategies. Aquatic and aerial species predominantly adhere to slower life history strategies, while terrestrial species exhibit faster life histories. Highly encephalised terrestrial species are a notable exception to these patterns. Furthermore, we show that different mode of life may play a significant role in expanding the set of strategies exploitable in the terrestrial realm. Additionally, species transitioning between terrestrial and aquatic realms, such as seals, exhibit intermediate life history strategies. Our results provide compelling evidence of the link between environmental realms and the life history diversity of mammals, highlighting the importance of differences in mode of life to expand life history diversity.

An efficient inducible model for the control of gene expression in renin cells.

Fate mapping and genetic manipulation of renin cells have relied on either noninducible Cre lines that can introduce the developmental effects of gene deletion or bacterial artificial chromosome transgene-based inducible models that may be prone to spurious and/or ectopic gene expression. To circumvent these problems, we generated an inducible mouse model in which CreERT2 is under the control of the endogenous Akr1b7 gene, an independent marker of renin cells that is expressed in a few extrarenal tissues. We confirmed the proper expression of Cre using Akr1b7CreERT2/+;R26RmTmG/+ mice in which Akr1b7+/renin+ cells become green fluorescent protein (GFP)+ upon tamoxifen administration. In embryos and neonates, GFP was found in juxtaglomerular cells, along the arterioles, and in the mesangium, and in adults, GFP was present mainly in juxtaglomerular cells. In mice treated with captopril and a low-salt diet to induce recruitment of renin cells, GFP extended along the afferent arterioles and in the mesangium. We generated Akr1b7CreERT2/+;Ren1cFl/-;R26RmTmG/+ mice to conditionally delete renin in adult mice and found a marked reduction in kidney renin mRNA and protein and mean arterial pressure in mutant animals. When subjected to a homeostatic threat, mutant mice were unable to recruit renin+ cells. Most importantly, these mice developed concentric vascular hypertrophy ruling out potential developmental effects on the vasculature due to the lack of renin. We conclude that Akr1b7CreERT2 mice constitute an excellent model for the fate mapping of renin cells and for the spatial and temporal control of gene expression in renin cells.NEW & NOTEWORTHY Fate mapping and genetic manipulation are important tools to study the identity of renin cells. Here, we report on a novel Cre mouse model, Akr1b7CreERT2, for the spatial and temporal regulation of gene expression in renin cells. Cre is properly expressed in renin cells during development and in the adult under basal conditions and under physiological stress. Moreover, renin can be efficiently deleted in the adult, leading to the development of concentric vascular hypertrophy.

Proteomic diversification of spermatostyles among six species of whirligig beetles.

Seminal fluid protein composition is complex and commonly assumed to be rapidly divergent due to functional interactions with both sperm and the female reproductive tract (FRT), both of which evolve rapidly. In addition to sperm, seminal fluid may contain structures, such as mating plugs and spermatophores. Here, we investigate the evolutionary diversification of a lesser-known ejaculate structure: the spermatostyle, which has independently arisen in several families of beetles and true bugs. We characterized the spermatostyle proteome, in addition to spermatostyle and FRT morphology, in six species of whirligig beetles (family Gyrinidae). Spermatostyles were enriched for proteolytic enzymes, and assays confirmed they possess proteolytic activity. Sperm-leucylaminopeptidases (S-LAPs) were particularly abundant, and their localization to spermatostyles was confirmed by immunohistochemistry. Although there was evidence for functional conservation of spermatostyle proteomes across species, phylogenetic regressions suggest evolutionary covariation between protein composition and the morphology of both spermatostyles and FRTs. We postulate that S-LAPs (and other proteases) have evolved a novel structural role in spermatostyles and discuss spermatostyles as adaptations for delivering male-derived materials to females.

Autogenous and efficient acceleration of energetic ions upstream of Earth's bow shock.

Earth and its magnetosphere are immersed in the supersonic flow of the solar-wind plasma that fills interplanetary space. As the solar wind slows and deflects to flow around Earth, or any other obstacle, a 'bow shock' forms within the flow. Under almost all solar-wind conditions, planetary bow shocks such as Earth's are collisionless, supercritical shocks, meaning that they reflect and accelerate a fraction of the incident solar-wind ions as an energy dissipation mechanism1,2, which results in the formation of a region called the ion foreshock3. In the foreshock, large-scale, transient phenomena can develop, such as 'hot flow anomalies'4-9, which are concentrations of shock-reflected, suprathermal ions that are channelled and accumulated along certain structures in the upstream magnetic field. Hot flow anomalies evolve explosively, often resulting in the formation of new shocks along their upstream edges5,10, and potentially contribute to particle acceleration11-13, but there have hitherto been no observations to constrain this acceleration or to confirm the underlying mechanism. Here we report observations of a hot flow anomaly accelerating solar-wind ions from roughly 1-10 kiloelectronvolts up to almost 1,000 kiloelectronvolts. The acceleration mechanism depends on the mass and charge state of the ions and is consistent with first-order Fermi acceleration14,15. The acceleration that we observe results from only the interaction of Earth's bow shock with the solar wind, but produces a much, much larger number of energetic particles compared to what would typically be produced in the foreshock from acceleration at the bow shock. Such autogenous and efficient acceleration at quasi-parallel bow shocks (the normal direction of which are within about 45 degrees of the interplanetary magnetic field direction) provides a potential solution to Fermi's 'injection problem', which requires an as-yet-unexplained seed population of energetic particles, and implies that foreshock transients may be important in the generation of cosmic rays at astrophysical shocks throughout the cosmos.

Organised and non-organised activities contribute to overall physical activity levels in adolescents and young adults with Down syndrome: a cross-sectional study.

BACKGROUND: Participation in organised and non-organised physical activities among adolescents and young adults with Down syndrome is underexplored. This study aimed to examine differences between organised and non-organised physical activities among adolescents and young adults with Down syndrome. METHODS: Forty participants with Down syndrome (27 woman; mean age 21.4 ± 4.9 years) were recruited. Data on physical activity participation were collected by self- or proxy-reported questionnaires about attendance, involvement and type of physical activity. RESULTS: Adolescents and young adults with Down syndrome participated in more organised than non-organised activities (P < 0.05), more often (P < 0.05), but there was no difference in the total time spent participating in these activities overall. Participants spent more time in vigorous physical activity during organised activities (P < 0.05) and spent more time in light physical activity during non-organised physical activities (P < 0.05). Dancing (organised activity) and walking (non-organised activity) were the most reported activities. CONCLUSIONS: Participation in both organised and non-organised physical activities is important to increase overall physical activity levels of adolescents and young adults with Down syndrome. Future research exploring physical activity preferences may help guide the planning and adaption of community programmes for this group.

[Social Security Profile of Cardiovascular Surgical Treated Patients of a Public Hospital in the Macro-Northern Zone, Analysis of a Decade]. / Perfil previsional de pacientes operados por patología cardiovascular de un hospital público en la macro zona norte, análisis de una década.

Cardiovascular pathology is the leading cause of death in Chile, with an inverse relationship between socioeconomic status and morbidity/ mortality. Currently, there is a lack of information regarding the Macro North Zone of Chile. Our aim is to describe the profile of patients undergoing interventions in a public hospital over a decade. METHODS: An observational ecological study was conducted on patients who underwent interventions from 2012 to 2022. Data were obtained through standardized searches using FONASA codes, including "major" cardiovascular interventions. "Minor" interventions and patients operated on in other centers were excluded. Data collection took place between 2021 and 2023. A database was created and analyzed using descriptive statistics, considering variables such as age range, health insurance, and the number of patients treated per year. RESULTS: A total of N= 9.075 records were obtained, with 8.908 corresponding to FONASA. The age ranges with the highest number of interventions were 18-60 years (49,8%) and over 60 years (49,6%). Since 2017, more than 50% of interventions have been in individuals over 60 years old. Annual interventions presented an increase in the percentage variation by 117%. Regarding interventions based on health insurance, tier B accounted for 46,7% (4.335) and tier A for 24,2% (2.194). We observed an increase in tier A by 24%. CONCLUSION: We found that patients are older and belong to lower-income tiers. Additionally, there is a migration towards tier A in recent years and an increase in interventions.

The role of Gata3 in renin cell identity.

Renin cells are precursors for other cell types in the kidney and show high plasticity in postnatal life in response to challenges to homeostasis. Our previous single-cell RNA-sequencing studies revealed that the dual zinc-finger transcription factor Gata3, which is important for cell lineage commitment and differentiation, is expressed in mouse renin cells under normal conditions and homeostatic threats. We identified a potential Gata3-binding site upstream of the renin gene leading us to hypothesize that Gata3 is essential for renin cell identity. We studied adult mice with conditional deletion of Gata3 in renin cells: Gata3fl/fl;Ren1dCre/+ (Gata3-cKO) and control Gata3fl/fl;Ren1d+/+ counterparts. Gata3 immunostaining revealed that Gata3-cKO mice had significantly reduced Gata3 expression in juxtaglomerular, mesangial, and smooth muscle cells, indicating a high degree of deletion of Gata3 in renin lineage cells. Gata3-cKO mice exhibited a significant increase in blood urea nitrogen, suggesting hypovolemia and/or compromised renal function. By immunostaining, renin-expressing cells appeared very thin compared with their normal plump shape in control mice. Renin cells were ectopically localized to Bowman's capsule in some glomeruli, and there was aberrant expression of actin-α2 signals in the mesangium, interstitium, and Bowman's capsule in Gata3-cKO mice. Distal tubules showed dilated morphology with visible intraluminal casts. Under physiological threat, Gata3-cKO mice exhibited a lower increase in mRNA levels than controls. Hematoxylin-eosin, periodic acid-Schiff, and Masson's trichrome staining showed increased glomerular fusion, absent cubical epithelial cells in Bowman's capsule, intraglomerular aneurysms, and tubular dilation. In conclusion, our results indicate that Gata3 is crucial to the identity of cells of the renin lineage.NEW & NOTEWORTHY Gata3, a dual zinc-finger transcription factor, is responsible for the identity and localization of renin cells in the kidney. Mice with a conditional deletion of Gata3 in renin lineage cells have abnormal kidneys with juxtaglomerular cells that lose their characteristic location and are misplaced outside and around arterioles and glomeruli. The fundamental role of Gata3 in renin cell development offers a new model to understand how transcription factors control cell location, function, and pathology.

Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper.

The exponential growth of precision diagnostic tools, including omic technologies, molecular diagnostics, sophisticated genetic and epigenetic editing, imaging and nano-technologies and patient access to extensive health care, has resulted in vast amounts of unbiased data enabling in-depth disease characterization. New disease endotypes have been identified for various allergic diseases and triggered the gradual transition from a disease description focused on symptoms to identifying biomarkers and intricate pathogenetic and metabolic pathways. Consequently, the current disease taxonomy has to be revised for better categorization. This European Academy of Allergy and Clinical Immunology Position Paper responds to this challenge and provides a modern nomenclature for allergic diseases, which respects the earlier classifications back to the early 20th century. Hypersensitivity reactions originally described by Gell and Coombs have been extended into nine different types comprising antibody- (I-III), cell-mediated (IVa-c), tissue-driven mechanisms (V-VI) and direct response to chemicals (VII). Types I-III are linked to classical and newly described clinical conditions. Type IVa-c are specified and detailed according to the current understanding of T1, T2 and T3 responses. Types V-VI involve epithelial barrier defects and metabolic-induced immune dysregulation, while direct cellular and inflammatory responses to chemicals are covered in type VII. It is notable that several combinations of mixed types may appear in the clinical setting. The clinical relevance of the current approach for allergy practice will be conferred in another article that will follow this year, aiming at showing the relevance in clinical practice where various endotypes can overlap and evolve over the lifetime.

Renin Cells, the Kidney, and Hypertension.

Renin cells are essential for survival perfected throughout evolution to ensure normal development and defend the organism against a variety of homeostatic threats. During embryonic and early postnatal life, they are progenitors that participate in the morphogenesis of the renal arterial tree. In adult life, they are capable of regenerating injured glomeruli, control blood pressure, fluid-electrolyte balance, tissue perfusion, and in turn, the delivery of oxygen and nutrients to cells. Throughout life, renin cell descendants retain the plasticity or memory to regain the renin phenotype when homeostasis is threatened. To perform all of these functions and maintain well-being, renin cells must regulate their identity and fate. Here, we review the major mechanisms that control the differentiation and fate of renin cells, the chromatin events that control the memory of the renin phenotype, and the major pathways that determine their plasticity. We also examine how chronic stimulation of renin cells alters their fate leading to the development of a severe and concentric hypertrophy of the intrarenal arteries and arterioles. Lastly, we provide examples of additional changes in renin cell fate that contribute to equally severe kidney disorders.

Renin Cell Baroreceptor, a Nuclear Mechanotransducer Central for Homeostasis.

[Figure: see text].

Environmental vs psychosocial barriers to active commuting to university: which matters more?

OBJECTIVES: The aims of this study were (1) to examine the differences in the mode of commuting and barriers to active commuting to university between the sexes (men and women) and in different countries (Chile and Spain); and (2) to analyse the association between the mode of commuting and the perceived barriers for male and female university students in Chile and Spain. STUDY DESIGN: This cross-sectional study took place between April 2017 and May 2018 in Chile and Spain. METHODS: The study population included 2269 university students (53.0% women). The mode of commuting and barriers to active commuting to university were assessed by a self-reported questionnaire. Multinomial logistic regression analysis was used to examine the associations. RESULTS: In both sexes, public and private transport were the main modes of commuting used in Chile and Spain, respectively, followed by active commuting in all participants, except for female students in Spain. Women perceived more environmental and psychosocial barriers compared to men (Chile: P < 0.001; Spain: P = 0.006). Perceived environmental barriers showed higher significant differences between students in Chile and Spain (P < 0.05). Private commuters reported a larger proportion of psychosocial barriers compared to active commuters (Chile: men P = 0.001, women P < 0.001; Spain: men P < 0.001, women P = 0.036). CONCLUSIONS: The study findings suggest that the mode of commuting and the barriers to active commuting to university may be influenced by sex and country.

Reduction of NrF2 as coadjuvant during the development of persistent periapical lesions.

BACKGROUND: Persistent periapical lesions (PPL) are the result of pulpar necrosis induced by bacterial infection resulting in bone degradation and culminating with the loss of dental piece. Pathological changes in the peripapice are associated with the presence of free radicals. The transcription factor Nrf2 is the main regulator of the endogenous antioxidant response against oxidative stress and has been implicated in the regulation of osteoclastogenesis.The aim is to determine the oxidative condition in samples from patients with Persistent Periapical Injuries as a detonating factor of tissue damage. MATERIAL AND METHODS: An observational, descriptive, cross-sectional study was carried out in samples with PPL (cases) and samples by removal of third molars (controls) obtained in the clinic of the specialty in endodontics, University of Guadalajara. Samples were submitted to histological staining with Hematoxylin-Eosin, lipoperoxide analysis, Superoxide Dismutase (SOD), Glutathione-Peroxidase (GPx) and Catalase (CAT) activities were determined by immunoenzymatic assays and NrF2 by Western Blot analysis. RESULTS: Samples from PPL patients histologically showed an increased presence of lymphocytes, plasma cells, and eosinophils, as well as a decrease in extracellular matrix proteins and fibroblast cells. There was a rise in lipid peroxidation, GPx and SOD activities, but an important decline (36%) in Catalase activity was observed (p<0.005); finally, NrF2-protein was diminished at 10.41%. All comparisons were between cases vs controls. CONCLUSIONS: The alterations in antioxidants endogenous NrF2-controlled are related to osseous destruction in patients with PPL.

Safety and efficacy of G2-S16 dendrimer as microbicide in healthy human vaginal tissue explants.

BACKGROUND: The absence of an effective treatment and vaccine in HIV-1 pandemic place preventive strategies such as safety and effective microbicide development as a central therapeutic approach to control HIV-1 pandemic nowadays. RESULTS: Studies of cytotoxicity, immune population status, inflammation or tissue damage and mainly prophylactic inhibition of HIV-1 infection in vaginal human explants demonstrate the biosafety and effectivity of G2-S16 dendrimer. Human explants treated with G2-S16 dendrimer or treated and HIV-1 infected do not presented signs of irritation, inflammation, immune activation or T cell populations deregulation. CONCLUSIONS: Herein we conclude that G2-S16 dendrimer has demonstrated sufficient efficacy, biosafety, effectivity and behavior in the closest to the real-life condition model represented by the human healthy donor vaginal tissue explants, to raise G2-S16 dendrimer as a promising candidate to clinical trials to develop an effective microbicide against HIV-1 infection.

Are there country-specific differences in the use of pegvisomant for acromegaly in clinical practice? An analysis from ACROSTUDY.

OBJECTIVE: A comprehensive picture of pegvisomant use for treating acromegaly in routine clinical practice in different countries is lacking. We aimed, therefore, to document country-specific behaviors in real-life pegvisomant use, and the main safety and effectiveness outcomes in the ACROSTUDY. DESIGN: ACROSTUDY is an open-label, non-interventional, post-marketing safety surveillance study. METHODS: A descriptive analysis was performed using data from the six top-recruiter ACROSTUDY countries, i.e., Germany (n = 548 patients), Italy (n = 466), France (n = 312), USA (n = 207), Spain (n = 200) and the Netherlands (n = 175). These nations accounted for > 85% of the ACROSTUDY cases. RESULTS: The mean pegvisomant dose at treatment start was lowest in the Netherlands (9.4 mg/day), whereas it ranged between 10.9 and 12.6 mg/day in the other countries. At year 5, the mean pegvisomant dose was around 15 mg/day in all countries, except France (18.1 mg/day). At starting pegvisomant, patients treated with monotherapy ranged between 15% in the Netherlands and 72% in Spain. Monotherapy remained lowest over time in the Netherlands. In all countries, the percentage of patients with normal IGF-1 increased steeply from < 20% at baseline to 43-58% at month 6 and 51-67% at year 1. After that, we observed minor changes in the rate of acromegaly control in all countries. The Netherlands peaked in disease control at year 2 (72%). The proportion of patients reporting changes in pituitary tumor size was generally low. Serious treatment-related adverse events were < 5% in all countries. CONCLUSIONS: Our study provided a detailed summary of real-life use of pegvisomant in the six top-recruiter ACROSTUDY nations.

A randomised controlled trial in patients undergoing arthroscopic shoulder surgery comparing interscalene block with either 10 ml or 20 ml levobupivacaine 0.25.

The interscalene brachial plexus block is recommended for analgesia after shoulder surgery but it may cause hemidiaphragmatic dysfunction. We tested whether ipsilateral hemidiaphragmatic contraction was better after a smaller dose of local anaesthetic without impairing analgesic effect. We randomly allocated 48 adults to 10 ml or 20 ml levobupivacaine 0.25% before arthroscopic shoulder surgery. The primary outcome was hemidiaphragmatic paralysis, defined as inspiratory thickness < 1.2 times expiratory thickness, measured by ultrasound 4 h after block. Hemidiaphragmatic paralysis was recorded for 6/24 vs. 23/24 supine participants after 10 ml vs. 20 ml levobupivacaine 0.25%, respectively, and for 4/24 vs. 23/24 sitting participants, respectively, p < 0.001 for both. Pain scores after 10 ml injectate were not worse than after 20 ml injectate. Median (IQR [range]) morphine doses in the first 24 postoperative hours after 10 ml and 20 ml levobupivacaine 0.25% were 2 (0-6 [0-23]) mg vs. 1 (0-2 [0-11]) mg, respectively, p = 0.12. No participant had a complication after 10 ml interscalene levobupivacaine, whereas seven had complications after 20 ml levobupivacaine, p = 0.009. Hemidiaphragmatic function was better after 10 ml vs. 20 ml interscalene levobupivacaine 0.25% without impairing analgesia for 24 postoperative hours.

A systematic review of the literature on the impact of the Seguro Popular.

BACKGROUND: The Seguro Popular (SP) was launched in 2004 to increase access to healthcare and reduce catastrophic expenditures among the Mexican population. To document the evidence on its effectiveness, we conducted a systematic review of impact evaluations of the SP. METHODS: We included papers using rigorous quasi-experimental designs to assess the effectiveness of the SP. We evaluated the quality of each study and presented the statistical significance of the effects by outcome category. RESULTS: We identified 26 papers that met the inclusion criteria. Sixteen studies that evaluated the impact of SP on financial protection found consistent and statistically significant positive effects in 55% of the 65 outcomes analyzed. Nine studies evaluating utilization of health services for the general and infant populations found effectiveness on 40% of 30 outcomes analyzed. Concerning screening services for hypertension, diabetes, and cervical and prostate cancer, we found three studies evaluating 14 outcomes and finding significant effects on 50% of them. Studies looking at the impact of SP on diabetes, hypertension, and general health care and treatment evaluated 19 outcomes and found effects on 21% of them. One study assessed five diabetes monitoring services and found positive effects on four of them. The only study on morbidity and mortality found positive results on three of the four outcomes of interest. CONCLUSION: We found mixed evidence on the impact of SP on financial protection, healthcare utilization, morbidity and mortality. In the 26 studies included in this review, researchers found positive effects in roughly half of the outcomes and null results on the rest.

[Clinical characteristics and comorbidities associated with mortality in patients with COVID-19 in Coahuila (Mexico)]. / Características clínicas y comorbilidades asociadas a mortalidad en pacientes con COVID-19 en Coahuila (México).

Background and objective: This study aims to describe the characteristics of patients with COVID-19 in a state in northern Mexico and establish the comorbidities associated with mortality. Methods: Patients with COVID-19, divided into survivors and non-survivors, were analyzed. The data were analyzed using the chi-square test, Student's t-test, and Cox's regression model. Results: A total of 17,479 patients were included and mortality rate of 6.3% was reported. Age over 60 years (HR = 8.04; 95% CI 7.03-9.19), diabetes (HR = 1.63; 95% CI 1.40-1.89), high blood pressure (HR = 1.48; 95% CI 1.28-1.72), obesity (HR = 1.37; 95% CI 1.18-1.60) and chronic kidney disease (HR = 2.06; 95% CI 1.64-2.59) were significantly associated with mortality. Conclusions: Diabetes, high blood pressure, obesity, and chronic kidney disease increased mortality among patients with COVID-19 in the population of Coahuila, Mexico. The factor that most contributed to risk of death was age over 60 years.

Patterns of differentiation of renin lineage cells during nephrogenesis.

Developmentally heterogeneous renin-expressing cells serve as progenitors for mural, glomerular, and tubular cells during nephrogenesis and are collectively termed renin lineage cells (RLCs). In this study, we quantified different renal vascular and tubular cell types based on specific markers and assessed proliferation and de novo differentiation in the RLC population. We used kidney sections of mRenCre-mT/mG mice throughout nephrogenesis. Marker positivity was evaluated in whole digitalized sections. At embryonic day 16, RLCs appeared in the developing kidney, and the expression of all stained markers in RLCs was observed. The proliferation rate of RLCs did not differ from the proliferation rate of non-RLCs. RLCs expanded mainly by de novo differentiation (neogenesis). Fractions of RLCs originating from the stromal progenitors of the metanephric mesenchyme (renin-producing cells, vascular smooth muscle cells, and mesangial cells) decreased during nephrogenesis. In contrast, aquaporin-2-positive RLCs in the collecting duct system, which embryonically emerges almost exclusively from the ureteric bud, expanded postpartum. The cubilin-positive RLC fraction in the proximal tubule, deriving from the cap mesenchyme, remained constant. In summary, RLCs were continuously detectable in the vascular and tubular compartments of the kidney during nephrogenesis. Therein, various patterns of RLC differentiation that depend on the embryonic origin of the cells were identified.NEW & NOTEWORTHY The unifying feature of the renal renin lineage cells (RLCs) is their origin from renin-expressing progenitors. RLCs evolve to an embryologically heterogeneous large population in structures with different ancestry. RLCs are also targets for the widely used renin-angiotensin-system blockers, which modulate their phenotype. Unveiling the different differentiation patterns of RLCs in the developing kidney contributes to understanding changes in their cell fate in response to homeostatic challenges and the use of antihypertensive drugs.

Promising PEGylated cationic dendrimers for delivery of miRNAs as a possible therapy against HIV-1 infection.

BACKGROUND: The appearance of resistance against new treatments and the fact that HIV-1 can infect various cell types and develop reservoirs and sanctuaries makes it necessary to develop new therapeutic approaches to overcome those failures. RESULTS: Studies of cytotoxicity, genotoxicity, complexes formation, stability, resistance, release and particle size distribution confirmed that G2-SN15-PEG, G3-SN31-PEG, G2-SN15-PEG-FITC and G3-SN31-PEG-FITC dendrimers can form complexes with miRNAs being biocompatible, stable and conferring protection to these nucleic acids. Confocal microscopy and flow cytometry showed effective delivery of these four dendrimers into the target cells, confirming their applicability as delivery systems. Dendriplexes formed with the dendrimers and miRNAs significantly inhibited HIV-1 infection in PBMCs. CONCLUSIONS: These dendrimers are efficient delivery systems for miRNAs and they specifically and significantly improved the anti-R5-HIV-1 activity of these RNA molecules.