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Objective As in other health sciences, a career in dentistry is associated with numerous stressors in practitioners. The main objective of this research was to examine the prevalence of emotional exhaustion, burnout, and perceived stress among dental students in Mexico. Methods A cross-sectional study was conducted among 73 dental students attending a private university in Northern Mexico. Three scales were administered to students to identify emotional exhaustion, burnout, and perceived stress, and parametric data analysis was performed. Results Among participants (mean age 19.7 years), the proportion with emotional exhaustion, perceived high stress, and burnout was 52.0%, 42.3%, and 17.8%, respectively. All students with perceived stress also had burnout. Conclusions We found that emotional exhaustion and perceived stress are experienced by a large proportion of dentistry students enrolled in the third semester at this private university in Northern Mexico. The proportions were independent of age and sex.

Introduction: Immune-based diagnostic tests for tuberculosis (TB) have suboptimal sensitivity in children and cannot differentiate between latent infection (LTBI) and active disease. This study evaluated the diagnostic potential of a broad range of biomarkers of tissue damage and inflammation in unstimulated plasma in children., Methods: We analyzed 17 biomarkers in 15 non-M. tuberculosis (MTB)-infected controls and 33 children with TB infection (LTBI, n = 8; probable TB, n = 19; confirmed TB, n = 6). Biomarker concentrations were measured using a Luminex magnetic bead-based platform and multiplex sandwich immunoassays. Concentrations, correlations and diagnostic accuracy assessments were conducted among patient groups., Results: Confirmed TB cases had significantly higher concentrations of IFN-γ and IL-2 and higher IFN-γ/MCP-1 and IL-2/MCP-1 ratios compared to LTBI and non-MTB-infected children. Among children with confirmed TB, there was a strong correlation between IFN-γ and IL-10 (r = 0.95; p < 0.001) and a significant correlation between IL-2 and IL-1ra (r = 0.92), IL-21 (r = 0.91), MCP-3 (r = 0.84), and MMP-1 (r = 0.85). The IFN-γ/MCP-1 ratio was the most accurate biomarker combination for differentiating between MTB-infected and non-MTB-infected children (AUC, 0.82; sensitivity, 87.9%; specificity, 66.6%; p < 0.001) and between active TB and non-MTB-infected children (AUC 0.82; sensitivity 88.0%; specificity 60.0%; p < 0.001). None of the biomarkers investigated were able to discriminate between LTBI and active TB., Conclusion: Our data suggest that combining the analyses of multiple biomarkers in plasma has the potential to enhance diagnosis of TB in children and, thus, warrants additional investigation. In particular, the diagnostic potential of IFN-γ/MCP-1 ratios should be further explored in larger pediatric cohorts., (Copyright © 2024. Published by Elsevier B.V.)

In this global phase 2 study in patients with relapsed/refractory follicular lymphoma (FL), zandelisib was administered on intermittent dosing to mitigate immune-related adverse events and infections that have been reported with oral PI3Kδ inhibitors administered daily continuously. Eligible patients with measurable disease and progression after at least two prior therapies were administered zandelisib until disease progression or intolerability. The primary efficacy endpoint was objective response rate (ORR) and the key secondary efficacy endpoint was duration of response (DOR). We report on 121 patients with FL administered zandelisib on intermittent dosing after 8 weeks of daily dosing for tumor debulking. The median number of prior therapies was 3 (range, 2-8) and 45% of patients had refractory disease. The ORR was 73% (95% confidence interval [CI], 63.9-80.4), the complete response (CR) rate was 38% (95% CI, 29.3-47.3), and the median DOR was 16.4 months (95% CI, 9.5-not reached). With a median follow-up of 14.3 months (range, 1-30.5), the median progression-free survival was 11.6 months (95% CI, 8.3-not reached). Twenty-one patients (17%) discontinued therapy due to an adverse event. Grade 3-4 class-related toxicities included 6% diarrhea, 5% lung infections, 3% colitis (confirmed by biopsy or imaging), 3% rash, 2% AST elevation, and 1% non-infectious pneumonitis. Zandelisib achieved a high rate of durable responses in heavily pretreated patients with relapsed/refractory FL. The intermittent dosing resulted in a relatively low incidence of severe class-related toxicities, which supports the evaluation of zandelisib as a single agent and in combination with indolent B-cell malignancies., (© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)

Niche selection and microbial dispersal are key factors that shape microbial communities. However, their relative significance varies across different environments and spatiotemporal scales. While most studies focus on the impact of these forces on community composition, few consider other structural levels such as the physiological stage of the microbial community and single-cell characteristics. To understand the relative influence of microbial dispersal and niche selection on various community structural levels, we concurrently examined the taxonomic composition, abundance and single-cell characteristics of bacterioplankton in an acidic reservoir (El Sancho, Spain) during stratification and mixing periods. A cluster analysis based on environmental variables identified five niches during stratification and one during mixing. Canonical correspondence analysis (CCA) revealed that communities within each niche differed in both, taxonomic and single-cell characteristics. The environmental variables that explained the variation in class-based ordination differed from those explaining the ordination based on single-cell characteristics. However, a Procrustes analysis indicated a high correlation between the CCA ordinations based on both structural levels, suggesting simultaneous changes in the microbial community at multiple structural levels. Our findings underscore the dominant role of environmental selection in occupying different microbial niches, given that microbial dispersal was not restricted., (© 2024 The Authors. Environmental Microbiology Reports published by John Wiley & Sons Ltd.)

Heart failure is a prevalent syndrome with high mortality rates, representing a significant economic burden in terms of healthcare. The lack of systematic information about the treatment and adherence of patients with heart failure limits the understanding of these aspects and potentially the improvement of clinical outcomes., Objective: To describe the clinical characteristics, therapeutic management, adherence, persistence, and clinical results, as well as the association between these variables, in a cohort of patients with heart failure in Andalusia., Design: This study will be an observational, population-based, retrospective cohort study. Data of patients discharged from an Andalusian hospital with a diagnosis of heart failure between 2014 and 2023 will be extracted from the Andalusian population health database., Analysis: The statistical analysis will incorporate the following strategies: (1) Descriptive analysis of the characteristics of the population cohort, adherence measures, and clinical outcomes. (2) Bivariate analyses to study the association of covariates with adherence, persistence, and clinical results. (3) Multivariate logistic regression and Cox regression analysis including relevant covariates. (4) To evaluate changes over time, multivariate Poisson regression models will be used. By conducting this comprehensive study, we aim to gain valuable insights into the clinical characteristics, treatment management, and adherence of heart failure patients in Andalusia, as well as to identify factors that may influence clinical outcomes. These findings could be critical both for the development of optimised strategies that improve medical care and quality of life of patients and for mitigating the health burden of HF in the region., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Sociedad Española de Farmacia Hospitalaria (S.E.F.H). Publicado por Elsevier España, S.L.U. All rights reserved.)

Soil permeability tests require a time series of water level measurements to determine system losses, including both infiltration and evaporation. Laboratory measurements of flow are standardised by international regulations such as ASTM International, ISO or UNE, but field measurements are not as well described and in some cases may require definition and specification of test conditions. This is the case for geosynthetic clay liner (GCL) products, where permeability is assessed by a laboratory measurement using a flexible wall permeameter as defined in standard test method D 5887-04. This method is not able to evaluate the performance of such products in the field and therefore cannot guarantee their ability to be used for the repair of landfill liner overlays. For this reason, we have defined a field test in a confined steel ring and developed a real-time ultrasonic IoT device to evaluate water losses over a period of time. The test method was applied in Mallorca (Spain) and as a result the quality of a landfill cover repair solution was evaluated, the corresponding civil works were carried out and the basis for future field measurements of soil permeability tests on different materials and conditions was established., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

What can be considered an appropriate statistical method for the primary analysis of a randomized clinical trial (RCT) with a time-to-event endpoint when we anticipate non-proportional hazards owing to a delayed effect? This question has been the subject of much recent debate. The standard approach is a log-rank test and/or a Cox proportional hazards model. Alternative methods have been explored in the statistical literature, such as weighted log-rank tests and tests based on the Restricted Mean Survival Time (RMST). While weighted log-rank tests can achieve high power compared to the standard log-rank test, some choices of weights may lead to type-I error inflation under particular conditions. In addition, they are not linked to a mathematically unambiguous summary measure. Test statistics based on the RMST, on the other hand, allow one to investigate the average difference between two survival curves up to a pre-specified time point τ $$ \tau $$ -a mathematically unambiguous summary measure. However, by emphasizing differences prior to τ $$ \tau $$ , such test statistics may not fully capture the benefit of a new treatment in terms of long-term survival. In this article, we introduce a graphical approach for direct comparison of weighted log-rank tests and tests based on the RMST. This new perspective allows a more informed choice of the analysis method, going beyond power and type I error comparison., (© 2024 John Wiley & Sons Ltd.)

Cyclam, known for its potent chelation properties, is explored for diverse applications through selective N -functionalization, offering versatile ligands for catalysis, medical research, and materials science. The challenges arising from N -alkylation, which could decrease the coordination properties, are addressed by introducing a robust C -functionalization method. The facile two-step synthesis proposed here involves the click chemistry-based C -functionalization of a hydroxyethyl cyclam derivative using Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC). Boc-protecting groups prevent undesired copper coordination, resulting in compounds with a wide range of functionalities. The optimized synthesis conditions enable C -functional cyclams to be obtained easily and advantageously, with high application potential in the previously cited fields. The methodology has been extended to trehalose-based Siamese twin amphiphiles, enabling efficient gene delivery applications.

Heart failure is a prevalent syndrome with high mortality rates, representing a significant economic burden in terms of healthcare. The lack of systematic information about the treatment and adherence of patients with heart failure limits the understanding of these aspects and potentially the improvement of clinical outcomes., Objective: To describe the clinical characteristics, therapeutic management, adherence, persistence and clinical results, as well as the association between these variables, in a cohort of patients with heart failure in Andalusia., Design: This study will be an observational, population-based, retrospective cohort study. Data of patients discharged from an Andalusian hospital with a diagnosis of heart failure between 2014 and 2023 will be extracted from the Andalusian population health database., Analysis: The statistical analysis will incorporate the following strategies: 1) Descriptive analysis of the characteristics of the population cohort, adherence measures, and clinical outcomes. 2) Bivariate analyses to study the association of covariates with adherence, persistence and clinical results. 3) Multivariate logistic regression and Cox regression analysis including relevant covariates. 4) To evaluate changes over time, multivariate Poisson regression models will be used. By conducting this comprehensive study, we aim to gain valuable insights into the clinical characteristics, treatment management, and adherence of heart failure patients in Andalusia, as well as to identify factors that may influence clinical outcomes. These findings could be critical both for the development of optimized strategies that improve medical care and quality of life of patients and for mitigating the health burden of HF in the region., (Copyright © 2024. Publicado por Elsevier España, S.L.U.)

A novel family of precision-engineered gene vectors with well-defined structures built on trehalose and trehalose-based macrocycles (cyclotrehalans) comprising linear or cyclic polyamine heads have been synthesized through procedures that exploit click chemistry reactions. The strategy was conceived to enable systematic structural variations and, at the same time, ensuring that enantiomerically pure vectors are obtained. Notably, changes in the molecular architecture translated into topological differences at the nanoscale upon co-assembly with plasmid DNA, especially regarding the presence of regions with short- or long-range internal order as observed by TEM. In vitro and in vivo experiments further evidenced a significant impact on cell and organ transfection selectivity. Altogether, the results highlight the potential of trehalose-polyamine/pDNA nanocomplex monoformulations to achieve targeting transfection without the need for any additional cell- or organ-sorting component.

Background: Molecular diagnosis of cystic fibrosis (CF) is challenging in Mexico due to the population's high genetic heterogeneity. To date, 46 pathogenic variants (PVs) have been reported, yielding a detection rate of 77%. We updated the spectrum and frequency of PVs responsible for this disease in mexican patients., Methods: We extracted genomic DNA from peripheral blood lymphocytes obtained from 297 CF patients and their parents. First, we analyzed the five most frequent PVs in the Mexican population using PCR-mediated site-directed mutagenesis. In patients with at least one identified allele, CFTR sequencing was performed using next-generation sequencing tools and multiplex ligation-dependent probe amplification. For variants not previously classified as pathogenic, we used a combination of in silico prediction, CFTR modeling, and clinical characteristics to determine a genotype-phenotype correlation., Results: We identified 95 PVs, increasing the detection rate to 87.04%. The most frequent variants were p.(PheF508del) (42.7%), followed by p.(Gly542*) (5.6%), p.(Ser945Leu) (2.9%), p.(Trp1204*) and p.(Ser549Asn) (2.5%), and CFTRdel25-26 and p.(Asn386Ilefs*3) (2.3%). The remaining variants had frequencies of <2.0%, and some were exclusive to one family. We identified 10 novel PVs localized in different exons (frequency range: 0.1-0.8%), all of which produced structural changes, deletions, or duplications in different domains of the protein, resulting in dysfunctional ion flow. The use of different in silico software and American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) criteria allowed us to assume that all of these PVs were pathogenic, causing a severe phenotype., Conclusions: In a highly heterogeneous population, combinations of different tools are needed to identify the variants responsible for CF and enable the establishment of appropriate strategies for CF diagnosis, prevention, and treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Ecotechnology, quintessential for crafting sustainable socio-environmental strategies, remains tantalizingly uncharted. Our analysis, steered by the nuances of machine learning and augmented by bibliometric insights, delineates the expansive terrain of this domain, elucidates pivotal research themes and conundrums, and discerns the vanguard nations in this field. Furthermore, we deftly connect our discoveries to the United Nations' 2030 Sustainable Development Goals, thereby accentuating the profound societal ramifications of ecotechnology., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

In this paper, the precise design of a high-power amplifier (HPA) is shown, along with the problems associated with the stability of "on-wafer" measurements. Here, techniques to predict possible oscillations are discussed to ensure the stability of a monolithic microwave-integrated circuit (MMIC). In addition, a deep reflection is made on the instabilities that occur when measuring both on wafer and using a mounted chip. Stability techniques are used as tools to characterize measurement results. Both a precise design and instabilities are shown through the design of a three-stage X-band HPA in gallium nitride (GaN) from the WIN Semiconductors Corp. foundry. As a result, satisfactory performance was obtained, achieving a maximum output power equal to 42 dBm and power-added efficiency of 32% at a 20 V drain bias. In addition to identifying critical points in the design or measurement of the HPA, this research shows that the stability of the amplifier can be verified through a simple analysis and that instabilities are often linked to errors in the measurement process or in the characterization of the measurement process.

Research Background: Soursop nectar contains antioxidants and is preserved by pasteurization. However, this technology impairs its physicochemical properties and bioactive compounds. An alternative is therefore thermoultrasound, which could counteract these effects. The thermosonicated nectar was compared with a pasteurized one and the in vitro bioaccessibility of antioxidants was estimated., Experimental Approach: The soursop nectar (25 %) was processed and the response surface methodology was used to determine the optimal conditions for thermoultrasound treatment (TUS). The TUS (75-90 % amplitude, 3.15-15 min) was applied, and 2 % stevia and 6 % agave inulin were added as sweeteners. The microbiological, physicochemical, enzymatic and antioxidant properties were analyzed. The properties of thermosonicated nectar obtained under optimal conditions were compared with pasteurized nectar. In addition to the above determinations, microstructure, total dietary fiber (TDF) and in vitro bioaccessibility of antioxidants were determined., Results and Conclusions: The response variables that fit the mathematical model were L *, b *, chroma ( C *), total phenolic content (TPC) and antioxidant activity determined by ABTS •+ , DPPH˙ and Fe(III) reducing antioxidant power (FRAP). The L * and DPPH˙ were affected by quadratic time and TPC by time (p<0.0001). The optimum TUS condition was 82 % amplitude for 9.15 min and the responses variables were L*, b* and C* (45.48, 3.55 and 3.62, respectively), TPC expressed as gallic acid equivalents (38.40 mg/100 mL), ABTS •+ expressed as Trolox equivalents (TE) (31.28 μmol/100 mL), DPPH˙ expressed as TE (124.22 μmol/100 mL) and FRAP expressed as Fe(II) (3.06 μmol/100 mL). Compared to the pasteurized sample, thermosonicated sample had high values of L * (45.56), h ° (-56.49), TPC (26.63 mg/100 mL), ABTS •+ and DPPH˙ (22.03 and 129.22 μmol/100 mL, respectively), FRAP (3.10 μmol/100 mL) and low pectin methylesterase (PME) activity (0.28 U/mL). For in vitro bioaccessibility, thermosonicated nectar showed high absorption of TPC (15.26/100 mL) and high antioxidant activity determined by ABTS (34.92 μmol/100 mL) and FRAP (7.88 μmol/100 mL)., Novelty and Scientific Contribution: The thermoultrasound improves the physicochemical properties and in vitro bioaccessibility of antioxidants in soursop nectar. On the other hand, as an alternative, this beverage offers low-calorie alternative with prebiotic properties that benefits consumer health., Competing Interests: CONFLICT OF INTEREST The authors report no potential conflict of interest relevant to this paper., (Authors.)

Interleukin 7 receptor (IL7R) is vital in the adaptive immune response against human immunodeficiency viruses (HIV). We assessed IL7RA polymorphisms (SNPs) in antiretroviral therapy (ART)-naïve HIV patients for their association with spontaneous HIV infection control. We conducted a retrospective cohort study involving 667 ART-naïve patients categorized by HIV progression (ordinal variable): 150 rapid progressors, 334 moderate/typical progressors, 86 long-term nonprogressors elite controllers (LTNPs-EC), and 97 LTNPs-non-EC. We genotyped three IL7RA SNPs using Agena Bioscience's MassARRAY platform. The association between IL7RA SNPs and spontaneous HIV infection control was evaluated using ordinal logistic regression. Individuals carrying the rs10491434 G allele have a higher likelihood of spontaneous HIV infection control (adjusted odds ratio [aOR] = 1.33; p = 0.023). Moreover, the IL7RA GCT haplotype, consisting of three specific SNPs (rs6897932, rs987106, and rs10491434), demonstrated an association with the control of untreated HIV infection (aOR = 1.34; p = 0.050). Remarkably, the rs10491434 SNP and the IL7RA GCT haplotype exhibited similar aOR values, suggesting that rs10491434 may be primarily responsible for the observed effect of the haplotype. IL7RA rs10491434 G allele is associated with a higher likelihood of spontaneous HIV infection control, indicating its significant role in the pathogenesis of HIV, possibly influencing infection course and viral replication control., (© 2023 Wiley Periodicals LLC.)

Combination of several anticancer treatments has typically been presumed to have enhanced drug activity. Motivated by a real clinical trial, this paper considers phase I-II dose finding designs for dual-agent combinations, where one main objective is to characterize both the toxicity and efficacy profiles. We propose a two-stage Bayesian adaptive design that accommodates a change of patient population in-between. In stage I, we estimate a maximum tolerated dose combination using the escalation with overdose control (EWOC) principle. This is followed by a stage II, conducted in a new yet relevant patient population, to find the most efficacious dose combination. We implement a robust Bayesian hierarchical random-effects model to allow sharing of information on the efficacy across stages, assuming that the related parameters are either exchangeable or nonexchangeable. Under the assumption of exchangeability, a random-effects distribution is specified for the main effects parameters to capture uncertainty about the between-stage differences. The inclusion of nonexchangeability assumption further enables that the stage-specific efficacy parameters have their own priors. The proposed methodology is assessed with an extensive simulation study. Our results suggest a general improvement of the operating characteristics for the efficacy assessment, under a conservative assumption about the exchangeability of the parameters a priori., (© 2023 The Authors. Biometrical Journal published by Wiley-VCH GmbH.)

Gender dysphoria is the diagnosis included in the Diagnostic and Statistical Manual of Mental Disorders, published by the American Psychiatric Association, which refers to the marked incongruence that exists between the gender that is felt or expressed and the one assigned at birth. The discomfort generated by the incongruity can cause gender affirmation to be requested through hormonal treatment or surgical sex reassignment, which is expected to disappear such discomfort. However, not all people with gender incongruence manifest discomfort and when the discomfort exists it is not always of psychopathological characteristics (dysphoria), which for some authors represents gender affirmation for aesthetic purposes (correct the incongruity). There are reports of increased medical care for transgender people who request somatic transition, but in Mexico there are no standardized protocols for their care; it is only recommended to promote access to hormonal treatment and mental health services to transgender people who request it. The eventual inclusion of surgical management in the Mexican guidelines will require clarity of concepts and unification of criteria to select the cases that should enter the health system for treatment, which is why health personnel must be prepared to identify those who can benefit from the somatic transition. The presence of dysphoria and psychiatric comorbidity may be key elements when the evaluation is carried out., (Licencia CC 4.0 (BY-NC-ND) © 2023 Revista Médica del Instituto Mexicano del Seguro Social.)

The casts of Pompeii bear witness to the people who died during the Vesuvius 79 AD eruption. However, studies on the cause of death of these victims have not been conclusive. A previous important step is the understanding of the post-depositional processes and the impact of the plaster in bones, two issues that have not been previously evaluated. Here we report on the anthropological and the first chemical data obtained from the study of six casts from Porta Nola area and one from Terme Suburbane. A non-invasive chemical analysis by portable X-ray fluorescence was employed for the first time on these casts of Pompeii to determine the elemental composition of the bones and the plaster. Elemental profiles were determined providing important data that cross-referenced with anthropological and stratigraphic results, are clearly helpful in the reconstruction of the perimortem and post-mortem events concerning the history of these individuals. The comparative analyses carried out on the bone casts and other collections from burned bones of the necropolis of Porta Nola in Pompeii and Rome Sepolcreto Ostiense, and buried bones from Valencia (Spain), reveal the extent of high temperature alteration and post-depositional plaster contamination. These factors make bioarchaeological analyses difficult but still allow us to support asphyxia as the likely cause of death., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Alapont et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

High mountain lakes (HMLs) are considered unique and comparable ecosystems for monitoring global climate change. The food web structure can indicate the response of these ecosystems to ecological threats, such as fish introduction, by analyzing the trophic dynamics. Nonetheless, the food webs of tropical HMLs are less well-studied than temperate HMLs. The present study assessed the food webs of two neighboring (600 m apart) tropical HMLs, El Sol and La Luna, inside the crater of the Nevado de Toluca volcano, Mexico. It used stable isotopes (δ13C and δ15N) and Bayesian mixing models with different trophic discrimination factors and priors to assess the impacts of introduced rainbow trout, persisting only in the larger lake, El Sol. The food web in Lake El Sol was more complex than in Lake La Luna, mainly due to its larger size, extensive vegetated littoral zone, and being fueled by autochthonous primary production. In contrast, the smaller and fishless Lake La Luna has a reduced and bare littoral zone that harbored a simple food web substantially sustained by allochthonous carbon inputs. The persistence of introduced rainbow trout in Lake El Sol but not in Lake La Luna accentuated the differences between the lakes. The models suggested that rainbow trout fed on key consumers of littoral macroinvertebrates (70-80%) and pelagic zooplankton (20-30%), increasing the linkage between sub-networks. In both tropical HMLs, the species richness and herbivorous fraction were elevated compared with temperate HMLs, while the linkage density and omnivorous fraction were lower. Basal nodes dominated these tropical HMLs, and the vegetated littoral zone of Lake El Sol had more intermediate (omnivore) nodes. Our results showed the convenience of food web analysis to compare the effects of introduced fish in originally fishless lakes in different latitudes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jiménez-Seinos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

IRF5-TNPO3 polymorphisms have previously been related to immune response, and TNPO3 plays a role in human immunodeficiency virus (HIV)-1 infection after nuclear import. Therefore, we analyzed the genetic association between IRF5-TNPO3 polymorphisms and the HIV elite control in long-term nonprogressors (LTNPs). We performed a retrospective cohort study on 183 LTNPs, who were antiretroviral therapy-naïve with CD4 +  ≥ 500 cells/mm 3 , viral load ≤10 000 copies/mL, and asymptomatic over 10 years after HIV seroconversion. The primary outcome variable was HIV elite control (undetectable viral load in at least 90% of the measurements for at least 1 year). Seven IRF5-TNPO3 polymorphisms were genotyped using Agena Bioscience's MassARRAY platform. We found a significant association between specific IRF5-TNPO3 genotypes and HIV elite control: rs2004640 TT (aOR = 2.05; p = 0.041), rs10954213 AA (aOR = 1.95; p = 0.035), rs2280714 TT (aOR = 2.02; p = 0.031), and rs10279821 CC (aOR = 2.12; p = 0.017). We also found a significant association between IRF5-TNPO3 haplotype TATC composed of the favorable significant polymorphisms (rs2004640, rs10954213, rs2280714, and rs10279821) and the HIV elite control (aOR = 1.59; p = 0.048). IRF5-TNPO3 rs2004640, rs10954213, rs2280714, and rs10279821 polymorphisms were related to HIV elite control in LTNPs. Our data provide new knowledge about the impact of IRF5-TNPO3 polymorphisms on HIV pathogenesis to understand the phenomenon of natural HIV control., (© 2023 Wiley Periodicals LLC.)

Delayed separation of survival curves is a common occurrence in confirmatory studies in immuno-oncology. Many novel statistical methods that aim to efficiently capture potential long-term survival improvements have been proposed in recent years. However, the vast majority do not consider stratification, which is a major limitation considering that most large confirmatory studies currently employ a stratified primary analysis. In this article, we combine recently proposed weighted log-rank tests that have been designed to work well under a delayed separation of survival curves, with stratification by a baseline variable. The aim is to increase the efficiency of the test when the stratifying variable is highly prognostic for survival. As there are many potential ways to combine the two techniques, we compare several possibilities in an extensive simulation study. We also apply the techniques retrospectively to two recent randomized clinical trials., (© 2023 Wiley-VCH GmbH.)

Background: In recent years, different tools have been developed to facilitate analysis of social determinants of health (SDH) and apply this to health policy. The possibility of generating predictive models of health outcomes which combine a wide range of socioeconomic indicators with health problems is an approach that is receiving increasing attention. Our objectives are twofold: (1) to predict population health outcomes measured as hospital morbidity, taking primary care (PC) morbidity adjusted for SDH as predictors; and (2) to analyze the geographic variability of the impact of SDH-adjusted PC morbidity on hospital morbidity, by combining data sourced from electronic health records and selected operations of the National Statistics Institute ( Instituto Nacional de Estadística/INE )., Methods: The following will be conducted: a qualitative study to select socio-health indicators using RAND methodology in accordance with SDH frameworks, based on indicators published by the INE in selected operations; and a quantitative study combining two large databases drawn from different Spain's Autonomous Regions (ARs) to enable hospital morbidity to be ascertained, i.e., PC electronic health records and the minimum basic data set (MBDS) for hospital discharges. These will be linked to socioeconomic indicators, previously selected by geographic unit. The outcome variable will be hospital morbidity, and the independent variables will be age, sex, PC morbidity, geographic unit, and socioeconomic indicators., Analysis: To achieve the first objective, predictive models will be used, with a test-and-training technique, fitting multiple logistic regression models. In the analysis of geographic variability, penalized mixed models will be used, with geographic units considered as random effects and independent predictors as fixed effects., Discussion: This study seeks to show the relationship between SDH and population health, and the geographic differences determined by such determinants. The main limitations are posed by the collection of data for healthcare as opposed to research purposes, and the time lag between collection and publication of data, sampling errors and missing data in registries and surveys. The main strength lies in the project's multidisciplinary nature (family medicine, pediatrics, public health, nursing, psychology, engineering, geography)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Couso-Viana, Bentué-Martínez, Delgado-Martín, Cabeza-Irigoyen, León-Latre, Concheiro-Guisán, Rodríguez-Álvarez, Román-Rodríguez, Roca-Pardiñas, Zúñiga-Antón, García-Flaquer, Pericàs-Pulido, Sánchez-Recio, González-Álvarez, Rodríguez-Pastoriza, Gómez-Gómez, Motrico, Jiménez-Murillo, Rabanaque and Clavería.)

In parametric Bayesian designs of early phase cancer clinical trials with drug combinations exploring a discrete set of partially ordered doses, several authors claimed that there is no added value in including an interaction term to model synergism between the two drugs. In this paper, we investigate these claims in the setting of continuous dose levels of the two agents. Parametric models will be used to describe the relationship between the doses of the two agents and the probability of dose limiting toxicity and efficacy. Trial design proceeds by treating cohorts of two patients simultaneously receiving different dose combinations and response adaptive randomization. We compare trial safety and efficiency of the estimated maximum tolerated dose (MTD) curve between models that include an interaction term with models without the synergism parameter with extensive simulations. Under a selected class of dose-toxicity models and dose escalation algorithm, we found that not including an interaction term in the model can compromise the safety of the trial and reduce the pointwise reliability of the estimated MTD curve., Competing Interests: Conflicts of Interest José L. Jiménez is employed by Novartis Pharma A.G. who provided support in the form of salary for the author, but did not have any additional role in the preparation of the manuscript. Also, the views expressed in this publication are those of the authors and should not be attributed to any of the funding institutions or organisations to which the authors are affiliated.

In this paper, a comparative analysis between the PM2.5 concentration in downtown Quito, Ecuador, during the COVID-19 pandemic in 2020 and the previous five years (from 2015 to 2019) was carried out. Here, in order to fill in the missing data and achieve homogeneity, eight datasets were constructed, and 35 different estimates were used together with six interpolation methods to put in the estimated value of the missing data. Additionally, the quality of the estimations was verified by using the sum of squared residuals and the following correlation coefficients: Pearson's r , Kendall's τ, and Spearman's ρ. Next, feature vectors were constructed from the data under study using the wavelet transform, and the differences between feature vectors were studied by using principal component analysis and multidimensional scaling. Finally, a robust method to impute missing data in time series and characterize objects is presented. This method was used to support the hypothesis that there were significant differences between the PM2.5 concentration in downtown Quito in 2020 and 2015-2019.

Phase I-II cancer clinical trial designs are intended to accelerate drug development. In cases where efficacy cannot be ascertained in a short period of time, it is common to divide the study in two stages: i) a first stage in which dose is escalated based only on toxicity data and we look for the maximum tolerated dose (MTD) set and ii) a second stage in which we search for the most efficacious dose within the MTD set. Current available approaches in the area of continuous dose levels involve fixing the MTD after stage I and discarding all collected stage I efficacy data. However, this methodology is clearly inefficient when there is a unique patient population present across stages. In this article, we propose a two-stage design for the combination of two cytotoxic agents assuming a single patient population across the entire study. In stage I, conditional escalation with overdose control (EWOC) is used to allocate successive cohorts of patients. In stage II, we employ an adaptive randomization approach to allocate patients to drug combinations along the estimated MTD curve, which is constantly updated. The proposed methodology is assessed with extensive simulations in the context of a real case study.

The aim of this study is to automatically analyze, characterize and classify physical performance and body composition data of a cohort of Mexican community-dwelling older adults. Self-organizing maps (SOM) were used to identify similar profiles in 562 older adults living in Mexico City that participated in this study. Data regarding demographics, geriatric syndromes, comorbidities, physical performance, and body composition were obtained. The sample was divided by sex, and the multidimensional analysis included age, gait speed over height, grip strength over body mass index, one-legged stance, lean appendicular mass percentage, and fat percentage. Using the SOM neural network, seven profile types for older men and women were identified. This analysis provided maps depicting a set of clusters qualitatively characterizing groups of older adults that share similar profiles of body composition and physical performance. The SOM neural network proved to be a useful tool for analyzing multidimensional health care data and facilitating its interpretability. It provided a visual representation of the non-linear relationship between physical performance and body composition variables, as well as the identification of seven characteristic profiles in this cohort.

Background: Mental health is an integral part of health. Having some psychiatric condition without treatment predisposes to a poor quality of life. These alterations have been found with an incidence of up to 50% in the general population. There are very few studies in Mexico on these conditions in health workers during the COVID-19 pandemic., Objective: To determine the prevalence of stress, anxiety, and depression during the COVID-19 pandemic in health workers., Material and Methods: A descriptive, cross-sectional observational study was conducted on health workers in a tertiary hospital, through the application of randomized and self-completed surveys, in search of levels of stress, anxiety, and depression during the COVID-19 pandemic., Results: 44.7% of those surveyed showed depression, 83.1% anxiety, and 66.3% stress. The main groups affected were female staff, singles, and medical residents. Those with type 2 diabetes mellitus had higher anxiety and depression., Conclusion: The prevalence of stress, anxiety, and depression in health workers is similar to that of the general population in our study. Depression was the alteration most found. The scrutiny of alterations in mental health in health workers is of the utmost importance, with greater emphasis in the context of the aforementioned pandemic., (© 2022 Revista Médica del Instituto Mexicano del Seguro Social.)

A robust strategy is reported to build perfectly monodisperse star polycations combining a trehalose-based cyclooligosaccharide (cyclotrehalan, CT) central core onto which oligoethyleneimine radial arms are installed. The architectural perfection of the compounds is demonstrated by a variety of physicochemical techniques, including NMR, MS, DLS, TEM, and GPC. Key to the strategy is the possibility of customizing the cavity size of the macrocyclic platform to enable/prevent the inclusion of adamantane motifs. These properties can be taken into advantage to implement sequential levels of stimuli responsiveness by combining computational design, precision chemistry and programmed host-guest interactions. Specifically, it is shown that supramolecular dimers implying a trimeric CT-tetraethyleneimine star polycation and purposely designed bis-adamantane guests are preorganized to efficiently complex plasmid DNA (pDNA) into transfection-competent nanocomplexes. The stability of the dimer species is responsive to the protonation state of the cationic clusters, resulting in dissociation at acidic pH. This process facilitates endosomal escape, but reassembling can take place in the cytosol then handicapping pDNA nuclear import. By equipping the ditopic guest with a redox-sensitive disulfide group, recapturing phenomena are prevented, resulting in drastically improved transfection efficiencies both in vivo and in vitro., (© 2022 The Authors. Macromolecular Rapid Communications published by Wiley-VCH GmbH.)

Aim: The initial cases of COVID-19 appeared in December 2019 and Spain was one of the most affected countries during the first wave (March to June). Since then, HIV HGM BioBank has been restructured as an established Paediatrics and Adults HIV&#95;COVID-19 BioBank that aims at the long-term storage of samples obtained from not only HIV-1, but also from COVID-19 patients and HIV-1&#95;COVID-19 coinfected patients., Methods: HIV HGM BioBank holds high quality biological samples from newborns, children, adolescents and adults with their associated clinical data. Research groups trying to establish large networks focused on research on specific clinical problems in epidemiology, biology, routes of transmission and therapies, are potential users of the clinical samples and of associated data of HIV-1&#95;COVID-19 HGM BioBank., Results: The HIV HGM BioBank is an academic and ethical enterprise complying with all the legal regulatory rules to provide service to the society. HIV&#95;COVID-19 HGM BioBank has been repurposed to offer an important resource for global research of COVID-19 in newborns, children, adolescents, adults and elders to study the biological effect of the pandemic., Conclusion: Herein, we present a description of how HIV HGM BioBank has rapidly become an indispensable structure in modern biomedical research, including COVID-19 research., (© 2022. The Author(s).)

The carbide precipitation kinetics in a Fe-22Mn-0.45C TWIP steel subjected to three different cold-deformation levels, annealed at various temperatures, were studied. The studied carbides included chemical compositions, morphology, precipitation sites, volume fraction, and size. Manganese carbides were precipitated in a temperature range between 525 and 650 °C. Volume fraction increased with cold-deformation and decreased with annealing temperature. Carbide size increased with cold-deformation and annealing temperatures up to 625 °C, suffering a notable reduction at 650 °C. Precipitation kinetics were described by means of precipitation curves for 0.1% (vol.) of Fe-Mn-carbides. A kinetic model was used, and two stages were found. Complementarily, austenite grain size and microhardness were also measured. With increases in annealing time, microhardness decreased until it reached a nearly constant value, indicating that recrystallization was complete, while, with increases in annealing temperature, grain size increased.

Unlike spiking neurons which compress continuous inputs into digital signals for transmitting information via action potentials, non-spiking neurons modulate analog signals through graded potential responses. Such neurons have been found in a large variety of nervous tissues in both vertebrate and invertebrate species, and have been proven to play a central role in neuronal information processing. If general and vast efforts have been made for many years to model spiking neurons using conductance-based models (CBMs), very few methods have been developed for non-spiking neurons. When a CBM is built to characterize the neuron behavior, it should be endowed with generalization capabilities (i.e. the ability to predict acceptable neuronal responses to different novel stimuli not used during the model's building). Yet, since CBMs contain a large number of parameters, they may typically suffer from a lack of such a capability. In this paper, we propose a new systematic approach based on multi-objective optimization which builds general non-spiking models with generalization capabilities. The proposed approach only requires macroscopic experimental data from which all the model parameters are simultaneously determined without compromise. Such an approach is applied on three non-spiking neurons of the nematode Caenorhabditis elegans (C. elegans), a well-known model organism in neuroscience that predominantly transmits information through non-spiking signals. These three neurons, arbitrarily labeled by convention as RIM, AIY and AFD, represent, to date, the three possible forms of non-spiking neuronal responses of C. elegans., Competing Interests: The authors have declared that no competing interests exist.

Background: A common feature of many recent trials evaluating the effects of immunotherapy on survival is that non-proportional hazards can be anticipated at the design stage. This raises the possibility to use a statistical method tailored towards testing the purported long-term benefit, rather than applying the more standard log-rank test and/or Cox model. Many such proposals have been made in recent years, but there remains a lack of practical guidance on implementation, particularly in the context of group-sequential designs. In this article, we aim to fill this gap., Methods: We illustrate how the POPLAR trial, which compared immunotherapy versus chemotherapy in non-small-cell lung cancer, might have been re-designed to be more robust to the presence of a delayed effect using the modestly-weighted log-rank test in a group-sequential setting., Conclusion: We provide step-by-step instructions on how to analyse a hypothetical realization of the trial, based on this new design. Basic theory on weighted log-rank tests and group-sequential methods is covered, and an accompanying R package (including vignette) is provided.

Human immunodeficiency virus-1 (HIV-1) elite controllers are heterogeneous due to different immunovirological features. We aimed to identify plasma biomarkers associated with loss of spontaneous HIV-1 control in long-term elite controllers (HIV-LTECs). We performed a retrospective study in 60 HIV-LTECs [36 true-LTECs and 24 LTECs losing control (LTECs-LC)]. We selected a plasma sample from true-LTECs (towards the middle of the follow-up period) and two samples from LTECs-LC (one far from the loss of control and another close to loss of control). Plasma biomarkers were evaluated using multiplex immunoassays. The partial least squares-discriminant analysis provided the variable importance in projection (VIP), and the adjusted Generalized Linear Model provided the adjusted arithmetic mean ratio (aAMR). At the moment of the first LTECs-LC samples, the only plasma biomarker with a VIP≥1.5 was sTNF-R1, which showed higher values in LTECs-LC than true-LTECs [aAMR=1.62 (95%CI=1.20-2.19); p=0.001]. After a median of 3.9 (IQR=4.5) years of follow-up from the first sample, we also had access to a second plasma sample from 10 LTECs-LC patients. At the moment of this second LTECs-LC sample, the only plasma biomarker with VIP≥1.5 was also sTNF-R1, which showed higher values in LTECs-LC than true-LTECs [aAMR=1.93 (95%CI=1.41-2.65); p<0.001]. The difference between the first and second samples of LTECs-LC was significant (Δx= 6.58 (95%=0.3; 12.88); p=0.040). In conclusion, high plasma values of sTNF-R1 appear to discriminate HIV-LTECs that lose the natural control of HIV-1, helping to define a specific phenotype that may be useful for the clinical management of these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sepúlveda-Crespo, Rallón, Muñoz-Gómez, Brochado-Kith, Jiménez, Muñoz-Fernández, Benito and Resino.)

Infections caused by viruses from the Herpesviridae family produce some of the most prevalent transmitted diseases in the world, constituting a serious global public health issue. Some of the virus properties such as latency and the appearance of resistance to antiviral treatments complicate the development of effective therapies capable of facing the infection. In this context, dendrimers present themselves as promising alternatives to current treatments. In this study, we propose the use of PEGylated cationic carbosilane dendrimers as inhibitors of herpes simplex virus 2 (HSV-2) and human cytomegalovirus (HCMV)infections. Studies of mitochondrial toxicity, membrane integrity, internalization and viral infection inhibition indicated that G2-SN15-PEG, G3-SN31-PEG, G2-SN15-PEG fluorescein isothiocyanate (FITC) labeled and G3-SN31-PEG-FITC dendrimers are valid candidates to target HSV-2 and HCMV infections since they are biocompatible, can be effectively internalized and are able to significantly inhibit both infections. Later studies (including viral inactivation, binding inhibition, heparan sulphate proteoglycans (HSPG)binding and surface plasmon resonance assays) confirmed that inhibition takes place at first infection stages. More precisely, these studies established that their attachment to cell membrane heparan sulphate proteoglycans impede the interaction between viral glycoproteins and these cell receptors, thus preventing infection. Altogether, our research confirmed the high capacity of these PEGylated carbosilane dendrimers to prevent HSV-2 and HCMV infections, making them valid candidates as antiviral agents against Herpesviridae infections.

The UNAIDS objective for 2020 was 500,000 new HIV-1 infections per year; however, the latest annual reported data confirmed 1.7 million new HIV-1 infections in that year. Those data evidences the need for new prevention strategies and prophylactic treatments. This prevention crisis occurred in spite of the knowledge and availability of efficient prevention strategies. The G2-S16 is a microbicidal polyanionic carbosilane dendrimer currently being tested for topical vaginal application, which has been shown to be efficient in the prevention of HIV-1 infection. However, safety tests were lacked. For this purpose, we injected intravenously G2-S16 dendrimer to CD1 mice, thereby analyzing the hemogram, blood biochemical markers of systemic damage, accumulation in the organs and organ-tissue damage in heart, spleen, kidney, liver and brain. This work shows that even if the G2-S16 dendrimer penetrates the epithelial tissue, it does not cause vaginal irritation or tissue damage. Moreover, the i.v. injection of the G2-S16 dendrimer did not cause a damaging effect on the studied organs and it did not modify the hemogram or the biochemical plasma markers. In conclusion, the G2-S16 dendrimer has a very good safety profile, indicating that this molecule can be a very safe and efficient vaginal microbicide.

miRNAs have been extensively studied in pathological conditions, including viral infections, such as those provoked by HIV-1. Several cellular and circulating miRNAs are altered during HIV-1 infection, with either beneficial effects on host defenses or enhanced virus infectivity. Blood samples were collected in sterile EDTA tubes and plasma was separated and stored, as were PBMCs. RNA was isolated and reverse-transcribed. Finally, the miRNA gene expression profile was assessed using TaqMan Array Human microRNA Card A v2.0. A comprehensive statistical analysis was performed on the results obtained. This is the first study on miRNAs in HIV-1 paediatric patients, and a miRNA profile differentiating patients starting combination antiretroviral therapy (cART) at different times after HIV-1 diagnosis was established. Thirty-four miRNAs were observed to have different expression levels between the control group and the cART group. The data indicates the need to start cART as soon as possible after the establishment of HIV-1 infection to assure the best outcome possible. Finally, the selected 34 miRNAs may be used as biomarkers for prognosis and assessing therapy effectiveness. However, more research must be conducted to establish adequate quantitative correlations., (© 2021. The Author(s).)

In confirmatory cancer clinical trials, overall survival (OS) is normally a primary endpoint in the intention-to-treat (ITT) analysis under regulatory standards. After the tumor progresses, it is common that patients allocated to the control group switch to the experimental treatment, or another drug in the same class. Such treatment switching may dilute the relative efficacy of the new drug compared to the control group, leading to lower statistical power. It would be possible to decrease the estimation bias by shortening the follow-up period but this may lead to a loss of information and power. Instead we propose a modified weighted log-rank test (mWLR) that aims at balancing these factors by down-weighting events occurring when many patients have switched treatment. As the weighting should be pre-specified and the impact of treatment switching is unknown, we predict the hazard ratio function and use it to compute the weights of the mWLR. The method may incorporate information from previous trials regarding the potential hazard ratio function over time. We are motivated by the RECORD-1 trial of everolimus against placebo in patients with metastatic renal-cell carcinoma where almost 80% of the patients in the placebo group received everolimus after disease progression. Extensive simulations show that the new test gives considerably higher efficiency than the standard log-rank test in realistic scenarios., Competing Interests: JJ is employed by Novartis Pharma A.G. and JN, AB, CF are employed by AstraZeneca. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The genetic makeup of Indigenous populations inhabiting Mexico has been strongly influenced by geography and demographic history. Here, we perform a genome-wide analysis of 716 newly genotyped individuals from 60 of the 68 recognized ethnic groups in Mexico. We show that the genetic structure of these populations is strongly influenced by geography, and our demographic reconstructions suggest a decline in the population size of all tested populations in the last 15-30 generations. We find evidence that Aridoamerican and Mesoamerican populations diverged roughly 4-9.9 ka, around the time when sedentary farming started in Mesoamerica. Comparisons with ancient genomes indicate that the Upward Sun River 1 (USR1) individual is an outgroup to Mexican/South American Indigenous populations, whereas Anzick-1 was more closely related to Mesoamerican/South American populations than to those from Aridoamerica, showing an even more complex history of divergence than recognized so far., (© 2021. The Author(s).)

People vulnerable to mental health problems during the COVID-19 outbreak include hospitalized patients and frontline health professionals; mostly reported discomforts include: insomnia, anxiety and depression. Under strict infection measures, non-essential personnel such as clinical psychiatrists and psychologists are strongly discouraged from entering isolation wards; therefore, frontline health-care workers become the main personnel providing psychological interventions to patients in hospitals without knowing how to mitigate patient distress. Health personnel do not receive adequate care for due to lack of time, stigma associated with using mental health services and fear of unwanted intervention. Remote care tools such as tele-psychiatry and online psychological intervention have disadvantages for conditions requiring physical examination. The National Health Commission of China released guiding principles to reduce the psychosocial effects of the COVID-19 outbreak recommending the creation of mental health teams. In this article we present the data obtained by a mental health team in a COVID-19 hospital of the Mexican Institute of Social Security, showing differences in emotional discomfort and diagnoses of mental disorders in patients in isolation and in frontline health personnel, suggesting the need for teams made up of psychiatry and psychology staff with face-to-face on-site assessments., (© 2021 Instituto Mexicano del Seguro Social.)

Instilling segregated cationic and lipophilic domains with an angular disposition in a trehalose-based trifaceted macrocyclic scaffold allows engineering patchy molecular nanoparticles leveraging directional interactions that emulate those controlling self-assembling processes in viral capsids. The resulting trilobular amphiphilic derivatives, featuring a Mickey Mouse architecture, can electrostatically interact with plasmid DNA (pDNA) and further engage in hydrophobic contacts to promote condensation into transfectious nanocomplexes. Notably, the topology and internal structure of the cyclooligosaccharide/pDNA co-assemblies can be molded by fine-tuning the valency and characteristics of the cationic and lipophilic patches, which strongly impacts the transfection efficacy in vitro and in vivo. Outstanding organ selectivities can then be programmed with no need of incorporating a biorecognizable motif in the formulation. The results provide a versatile strategy for the construction of fully synthetic and perfectly monodisperse nonviral gene delivery systems uniquely suited for optimization schemes by making cyclooligosaccharide patchiness the focus., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

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.