Enhanced Immunomodulatory Effects of Thymosin-Alpha-1 in Combination with Polyanionic Carbosilane Dendrimers against HCMV Infection.

Resistance and toxicity associated with current treatments for human cytomegalovirus (HCMV) infection highlight the need for alternatives and immunotherapy has emerged as a promising strategy. This study examined the in vitro immunological effects of co-administration of Thymosin-alpha-1 (Tα1) and polyanionic carbosilane dendrimers (PCDs) on peripheral blood mononuclear cells (PBMCs) during HCMV infection. The biocompatibility of PCDs was assessed via MTT and LDH assays. PBMCs were pre-treated with the co-administered compounds and then exposed to HCMV for 48 h. Morphological alterations in PBMCs were observed using optical microscopy and total dendritic cells (tDCs), myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs), along with CD4+/CD8+ T cells and regulatory T cells (Treg), and were characterized using multiparametric flow cytometry. The findings revealed that Tα1 + PCDs treatments increased DC activation and maturation. Furthermore, increased co-receptor expression, intracellular IFNγ production in T cells and elevated Treg functionality and reduced senescence were evident with Tα1 + G2-S24P treatment. Conversely, reduced co-receptor expression, intracellular cytokine production in T cells, lower functionality and higher senescence in Treg were observed with Tα1 + G2S16 treatment. In summary, Tα1 + PCDs treatments demonstrate synergistic effects during early HCMV infection, suggesting their use as an alternative therapeutic for preventing virus infection.

Core self-evaluations and perceived classmate support: Independent predictors of psychological adjustment.

INTRODUCTION: The main aim of this research was to explore the contribution of both core self-evaluations (CSE) and classmate support as unique predictors of positive and negative psychological adjustment among adolescents. METHODS: In a cross-sectional study, 2,293 Spanish adolescents (Mage = 14.07) completed the Core Self-Evaluations Scale, the Classmate Support subscale, the Satisfaction with Life Scale, the Depression, Anxiety, and Stress Scales and the Frequency of Suicidal Ideation Inventory. Pearson correlations among assessed variables were examined, and three hierarchical regression analyses were conducted to examine the predictive role of CSE and classmate support on life satisfaction, depressive symptomatology, and suicidal ideation. RESULTS: Both CSE and classmate support were positively related to life satisfaction and negatively related to depressive symptoms and suicidal ideation. Hierarchical regression analyses identified CSE and classmate support as independent predictors of both positive and negative psychological outcomes in this sample. These results indicated support for a comprehensive model involving CSE and classmate support as additive predictors of both positive and negative outcomes among adolescents. CONCLUSION: These findings underscore the unique and additive role of both individual (i.e., CSE) and, to a lower degree, social factors (i.e., classmate support) to augment the prediction model of positive and negative psychological adjustment among adolescents. Practical implications are discussed, focusing on preventive programs that include strategies to increase positive self-appraisals and create a supportive classroom climate.

Variables that explain disordered eating behaviors among women: the mediating role of body dissatisfaction.

PURPOSE: To analyze the role of body dissatisfaction in the relationships of sociocultural influences, depression, and anxiety with disordered eating behaviors (DEB) in a sample of female Mexican university students. METHODS: A nonrandom sample of 526 female Mexican university students aged 18 to 25 years completed the Questionnaire of Influence on the Aesthetic Model of Body Shape (CIMEC-26), the Hospital Anxiety and Depression Scale (HADS), the Body Shape Questionnaire (BSQ-8D) and the Eating Attitudes Test (EAT-26). RESULTS: Through the mean model (χ2/df (5, n = 526) = 7.298, p = .199; NFI = .996; CFI = .999; RMSEA = .030; SRMR = .011), body dissatisfaction was found to mediate the relationships of influence of advertising, influence of social models and anxiety with DEB (restrictive dieting and bulimia). The variable with the most direct effect on restrictive dieting and bulimia was the influence of advertising. Body dissatisfaction partially mediated this relationship, as the influence of advertising had a significant direct effect on restrictive dieting and bulimia. The final model of direct and indirect effects explained 43% and 22% of the variance in restrictive dieting and bulimia, respectively. CONCLUSION: The present study showed that body dissatisfaction partially mediated the relationships between influence of advertising, influence of social models, and anxiety with DEB among women. Thus, these variables should be taken into account in prevention and intervention programs targeting BED. LEVEL V: Evidence obtained from a cross-sectional descriptive study. LEVEL V: Evidence obtained from a cross-sectional descriptive study.

Interleukin 18 (IL-18) and IL-3 in Extracellular Vesicles: Biomarkers for Durable Elite Control of HIV-1.

Plasma extracellular vesicle (EV)-associated cytokines were quantified in people with HIV (PWH) with different virological control status, including elite controllers (EC) who maintain persistent control (PC) or not (TC). Cytokine signatures and pathways were determined for each group. Median EV-associated cytokine levels were higher among PWH than HIV-uninfected. EC showed the highest levels of EV-associated cytokines among PWH with PC levels higher than TC levels. IL-18 levels best distinguished PWH from uninfected controls, and EC from ART-treated, and IL-3 distinguished PC from TC. The role of EV-cytokines in intercellular communication and endogenous control of HIV expression should be investigated further.

Poly I:C and STING agonist-primed DC increase lymphoid tissue polyfunctional HIV-1-specific CD8+ T cells and limit CD4+ T-cell loss in BLT mice.

Effective function of CD8+ T cells and enhanced innate activation of DCs in response to HIV-1 is linked to protective antiviral immunity in controllers. Manipulation of DC targeting the master regulator TANK-binding Kinase 1 (TBK1) might be useful to acquire controller-like properties. Here, we evaluated the impact of the combination of 2´3´-c´diAM(PS)2 and Poly I:C as potential adjuvants capable of potentiating DC´s abilities to induce polyfunctional HIV-1 specific CD8+ T-cell responses in vitro and in vivo using a humanized BLT mouse model. Adjuvant combination enhanced TBK-1 phosphorylation and IL-12 and IFN-ß expression on DC and increased their ability to activate polyfunctional HIV-1-specific CD8+ T cells in vitro. Moreover, higher proportions of hBLT mice vaccinated with ADJ-DC exhibited less severe CD4+ T-cell depletion following HIV-1 infection compared to control groups. This was associated with infiltration of CD8+ T cells in the white pulp from the spleen, reduced spread of infected p24+ cells to LN, and with preserved abilities of CD8+ T cells from the spleen and blood of vaccinated animals to induce specific polyfunctional responses upon antigen stimulation. Therefore, priming of DC with PolyI:C and STING agonists might be useful for future HIV-1 vaccine studies.

Long-Term Omalizumab in Elderly Patients with Chronic Urticaria: Is It a Safe Therapy?

BACKGROUND: Biologics have revolutionized the treatment of many diseases. In this regard, omalizumab (OMA), an anti-IgE monoclonal antibody, is the recommended therapeutic option for patients with chronic spontaneous urticaria (CSU) refractory to second-generation H1-antihistamines. Several studies confirm the efficacy and safety of the drug. However, the literature focusing on the elderly population is scarce, as this age group is often excluded from clinical trials. Therefore, the pharmacological treatment of CSU in elderly patients is a challenge that is increased by their comorbidities and consequent polypharmacy. OBJECTIVES: We describe the real-life safety profile of OMA in elderly patients (≥70 years) with CSU and chronic inducible urticaria (CIndU). We aimed to provide data for daily clinical practice in this vulnerable patient group. METHOD: A retrospective review was performed of the records of patients with CSU/CIndU from May 2003 to December 2019 in the Hospital Universitario La Paz. We describe qualitative and quantitative data according to measures of central tendency. Comparisons between qualitative and quantitative data were performed with the Mann-Whitney U test and the Fisher's test for qualitative variables. A p value <0.05 was considered statistically significant. RESULTS AND CONCLUSIONS: Eighty-nine patients were included, divided into two groups (<70 vs. ≥70 years). The overall rate of adverse events (AEs) was 48%, mainly mild. No association between age and AE was found (p = 0.789). No serious AE such as anaphylaxis was detected. CSU predominated in both groups. CIndU was less prevalent in the elderly (p = 0.017). There was no association between age and the other variables. Although the frequency of neoplasms was slightly higher in the elderly with OMA, we found no difference compared to the incidence of neoplasms in the general population. Therefore, our data suggest that OMA may be a safe treatment in elderly people with CSU/CIndU for prolonged periods of treatment, although further studies with larger samples are needed to corroborate our observations.

IgG antibody levels against the SARS-CoV-2 spike protein in mother-child dyads after COVID-19 vaccination.

PURPOSE: We aimed to assess IgG antibodies against the SARS-CoV-2 spike protein (anti-SARS-CoV-2 S IgG) in vaccinated mothers and their infants at delivery and 2-3 months of age. METHODS: We conducted a prospective study on mothers who received at least one dose of the COVID-19 vaccine (Pfizer-BNT162b2, Moderna mRNA-1273, or Oxford-AstraZeneca ChAdOx1-S) during pregnancy and on their infants. The baseline was at the time of delivery (n = 93), and the end of follow-up was 2 to 3 months post-partum (n = 53). Serum anti-SARS-CoV-2 S IgG titers and ACE2 binding inhibition levels were quantified by immunoassays. RESULTS: Mothers and infants had high anti-SARS-CoV-2 S IgG titers against the B.1 lineage at birth. However, while antibody titers were maintained at 2-3 months post-partum in mothers, they decreased significantly in infants (p < 0.001). Positive and significant correlations were found between anti-SARS-CoV-2 S IgG titers and ACE2-binding inhibition levels in mothers and infants at birth and 2-3 months post-partum (r > 0.8, p < 0.001). Anti-S antibodies were also quantified for the Omicron variant at 2-3 months post-partum. The antibody titers against Omicron were significantly lower in mothers and infants than those against B.1 (p < 0.001). Again, a positive correlation was observed for Omicron between IgG titers and ACE2-binding inhibition both in mothers (r = 0.818, p < 0.001) and infants (r = 0.386, p < 0.005). Previous SARS-CoV-2 infection and COVID-19 vaccination near delivery positively impacted anti-SARS-CoV-2 S IgG levels. CONCLUSIONS: COVID-19 mRNA vaccines induce high anti-SARS-CoV-2 S titers in pregnant women, which can inhibit the binding of ACE2 to protein S and are efficiently transferred to the fetus. However, there was a rapid decrease in antibody levels at 2 to 3 months post-partum, particularly in infants.

The moderating role of emotional intelligence in the link between self-esteem and symptoms of eating disorders.

OBJECTIVE: This research aimed to explore the moderating role of emotional intelligence (EI) in the relationship between self-esteem and eating disorders (ED) symptomatology. METHOD: A battery of online questionnaires was administered to a sample of 516 adults including university students and a community population. The sample, age range of 18-77 years (X = 38.90; SD = 14.76), was made up of 63% women and 32% men. RESULTS: EI moderated the association between self-esteem and ED symptomatology for the total sample. However, a gender-specific analysis showed that the moderation effect was only significant for women. Specifically, when women reported a low level of self-esteem, those with high scores in EI reported lower scores in ED symptoms than those with low EI. DISCUSSION: Our findings are discussed in terms of the need for future research to understand the different gender associations and to consider these differences in further intervention programs for reducing the risk of ED, in which training in emotional skills may be more beneficial for women than men.

Emotional intelligence subdimensions as moderators in the association between body dissatisfaction and symptoms of eating disorders among female Mexican adolescents.

OBJECTIVE: Strong empirical research has shown a relationship between body dissatisfaction and symptoms of eating disorders (ED) and the direct and combined influence of emotional factors and dimensions of emotional intelligence (EI) on ED symptoms. However, whether these emotional variables and competencies moderate the well-established relationship between body dissatisfaction and ED symptomatology has not yet been tested. Neither have studies of this nature been performed among high at-risk populations such as Mexican female adolescents. Thus, this research aimed to explore the moderator role of EI subdimensions in the relationship between body dissatisfaction and ED symptoms among female adolescents from Sinaloa, Mexico. METHODS: A total of 485 female adolescents aged 14-19 years old (M = 16.81, SD = 1.33) who were students in middle school, high school, and college completed questionnaires about body dissatisfaction, ED symptomatology, and EI. We conducted moderating analyses. RESULTS: Subdimensions of EI significantly moderated the relationship between body dissatisfaction and symptoms of ED. For participants high in body dissatisfaction, lower levels in stress management ability and higher levels in the interpersonal EI and Adaptability EI dimensions were associated with higher levels of ED symptomatology. DISCUSSION: Subdimensions of EI have an important role in moderating the association between body dissatisfaction and symptoms of ED. The findings of this study contribute to improving the knowledge about the role of emotional competencies in ED. Proposals for future research and to improve preventative approaches are discussed. PUBLIC SIGNIFICANCE STATEMENT: This study shows the moderating role of EI dimensions in the well-established relationship between body dissatisfaction and ED symptomatology. The research was conducted with a population at high risk of ED: female adolescents in the northwest of Mexico. Results showed that low Stress management EI, high Adaptability EI, and high Interpersonal EI were associated with higher levels of ED symptomatology among participants with high (but not low) body dissatisfaction. These insightful results have theoretical and practical implications.

Antibody levels to SARS-CoV-2 spike protein in mothers and children from delivery to six months later.

INTRODUCTION: Pregnant women are vulnerable to severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. Neutralizing antibodies against the SARS-CoV-2 spike (S) protein protect from severe disease. This study analyzes the antibody titers to SARS-CoV-2 S protein in pregnant women and their newborns at delivery, and six months later. METHODS: We conducted a prospective study on pregnant women with confirmed SARS-CoV-2 infection and newborns. Antibody (IgG, IgM, and IgA) titers were determined using immunoassays in serum and milk samples. An angiotensin-converting enzyme 2 (ACE2) receptor-binding inhibition assay to the S protein was performed on the same serum and milk samples. RESULTS: At birth, antibodies to SARS-CoV-2 spike protein were detected in 81.9% of mothers' sera, 78.9% of cord blood samples, and 63.2% of milk samples. Symptomatic women had higher antibody titers (IgG, IgM, and IgA) than the asymptomatic ones (P < 0.05). At six months postpartum, IgG levels decreased drastically in children's serum (P < 0.001) but remained high in mothers' serum. Antibody titers correlated positively with its capacity to inhibit the ACE2-spike protein interaction at baseline in maternal sera (R2  = 0.203; P < 0.001), cord sera (R2  = 0.378; P < 0.001), and milk (R2  = 0.564; P < 0.001), and at six months in maternal sera (R2  = 0.600; P < 0.001). CONCLUSIONS: High antibody levels against SARS-CoV-2 spike protein were found in most pregnant women. Due to the efficient transfer of IgG to cord blood and high IgA titers in breast milk, neonates may be passively immunized to SARS-CoV-2 infection. Our findings could guide newborn management and maternal vaccination policies.

Development of a formulation of potassium iodide tablets as an antidote against nuclear incidents.

Objectives: Potassium iodide (KI) is a treatment to neutralize radioactive agents that could be inhaled or ingested in nuclear incidents. The inorganic salt KI constitutes a source of iodine, which in the body acts by accumulating in the thyroid gland, producing its saturation, and thus preventing the fixation of radioactive iodine species. In Spain, the Military Defence Pharmacy Centre (CEMILFARDEF) was challenged to develop this antidote to be distributed among the population surrounding nuclear power plants, in only one new solid pharmaceutical form for oral administration, in order to replace the two pharmaceutical forms available, which are capsules for adults and oral solution for children, considered less versatile. Methods: A selection of excipients was carried out to achieve pharmacotechnical behaviour suitable for the industrial manufacture of potassium iodide in tablets, complying with the pre-established process and finished product quality parameters. The development allowed the preparation of three industrial-sized batches on which the stability of the developed formulation was studied. Results: An uncoated 65 mg double-scored potassium iodide tablet was developed using easily accessible excipients in the formulation and direct compression as the manufacturing method. The formula complied with the stability tests, with which the development carried out can respond to the eventual demand that its elaboration would entail in the event of nuclear incidents. Conclusions: The developed formulation of a 65 mg double-scored potassium iodide tablet allows the great variability of user needs, from infants to adults with a single pharmaceutical form, which additionally implies logistical benefits in distribution, stock control and appropriate renewal according expiration dates, among the population surrounding nuclear power plants and available to deployed military personnel, in the event of potential nuclear incidents.

HIV HGM biobank as a research platform for paediatric infectious diseases and COVID-19 pandemic.

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_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_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_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_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.

Progesterone elevation on the day of oocyte retrieval and live birth rate after in vitro fertilisation treatment.

The objective of this study was to evaluate if progesterone elevation (PE) on the day of oocyte retrieval is associated with IVF outcome. A prospective cohort study of 400 IVF-ICSI cycles, with fresh embryo transfer on day 2-3 was performed. We proposed a serum progesterone (P) level on percentile (p) 90 as a threshold.Pregnancy rates were not affected, however there were more miscarriages (25.7% vs 43.8%) and lower live birth rate (LBR) (28% vs 23.1%) in the PE group (not statistically significant). We also found a positive correlation between P levels and retrieved and mature oocytes, total embryos, and good quality embryos. This is the first study to analyse LBR based on P levels on the day of oocyte retrieval. PE is not associated with the IVF outcome, but there is a trend to lower ongoing pregnancy rate and LBR and more miscarriages. Our results also show that P levels have no negative effects on oocyte and embryo quality.Impact statementWhat is already known on this subject? The influence of PE during IVF cycle on pregnancy rates remains controversial.What do the results of this study add? This is the first study to analyse LBR based on P levels on the day of oocyte retrieval.What are the implications of these findings for clinical practice and/or further research? We demonstrated that pregnancy rates were not affected by PE at oocyte retrieval, but there is a trend to lower ongoing pregnancy rate and LBR and more miscarriages. Randomised controlled trials are needed to offer more evidence of these relationships.

More Insights on the Use of γ-Secretase Inhibitors in Cancer Treatment.

The NOTCH1 gene encodes a transmembrane receptor protein with activating mutations observed in many T-cell acute lymphoblastic leukemias (T-ALLs) and lymphomas, as well as in other tumor types, which has led to interest in inhibiting NOTCH1 signaling as a therapeutic target in cancer. Several classes of Notch inhibitors have been developed, including monoclonal antibodies against NOTCH receptors or ligands, decoys, blocking peptides, and γ-secretase inhibitors (GSIs). GSIs block a critical proteolytic step in NOTCH activation and are the most widely studied. Current treatments with GSIs have not successfully passed clinical trials because of side effects that limit the maximum tolerable dose. Multiple γ-secretase-cleavage substrates may be involved in carcinogenesis, indicating that there may be other targets for GSIs. Resistance mechanisms may include PTEN inactivation, mutations involving FBXW7, or constitutive MYC expression conferring independence from NOTCH1 inactivation. Recent studies have suggested that selective targeting γ-secretase may offer an improved efficacy and toxicity profile over the effects caused by broad-spectrum GSIs. Understanding the mechanism of GSI-induced cell death and the ability to accurately identify patients based on the activity of the pathway will improve the response to GSI and support further investigation of such compounds for the rational design of anti-NOTCH1 therapies for the treatment of T-ALL. IMPLICATIONS FOR PRACTICE: γ-secretase has been proposed as a therapeutic target in numerous human conditions, including cancer. A better understanding of the structure and function of the γ-secretase inhibitor (GSI) would help to develop safe and effective γ-secretase-based therapies. The ability to accurately identify patients based on the activity of the pathway could improve the response to GSI therapy for the treatment of cancer. Toward these ends, this study focused on γ-secretase inhibitors as a potential therapeutic target for the design of anti-NOTCH1 therapies for the treatment of T-cell acute lymphoblastic leukemias and lymphomas.

RBR-Type E3 Ligases and the Ubiquitin-Conjugating Enzyme UBC26 Regulate Abscisic Acid Receptor Levels and Signaling.

The turnover of abscisic acid (ABA) signaling core components modulates the plant's response to ABA and is regulated by ubiquitination. We show that Arabidopsis (Arabidopsis thaliana) RING Finger ABA-Related1 (RFA1) and RFA4 E3 ubiquitin ligases, members of the RING between RING fingers (RBR)-type RSL1/RFA family, are key regulators of ABA receptor stability in root and leaf tissues, targeting ABA receptors for degradation in different subcellular locations. RFA1 is localized both in the nucleus and cytosol, whereas RFA4 shows specific nuclear localization and promotes nuclear degradation of ABA receptors. Therefore, members of the RSL1/RFA family interact with ABA receptors at plasma membrane, cytosol, and nucleus, targeting them for degradation via the endosomal/vacuolar RSL1-dependent pathway or 26S proteasome. Additionally, we provide insight into the physiological function of the relatively unexplored plant RBR-type E3 ligases, and through mutagenesis and biochemical assays we identified cysteine-361 in RFA4 as the putative active site cysteine, which is a distinctive feature of RBR-type E3 ligases. Endogenous levels of PYR1 and PYL4 ABA receptors were higher in the rfa1 rfa4 double mutant than in wild-type plants. UBC26 was identified as the cognate nuclear E2 enzyme that interacts with the RFA4 E3 ligase and forms UBC26-RFA4-receptor complexes in nuclear speckles. Loss-of-function ubc26 alleles and the rfa1 rfa4 double mutant showed enhanced sensitivity to ABA and accumulation of ABA receptors compared with the wild type. Together, our results reveal a sophisticated mechanism by which ABA receptors are targeted by ubiquitin at different subcellular locations, in which the complexity of the ABA receptor family is mirrored in the partner RBR-type E3 ligases.

Longitudinal plasma cytokine concentrations and recurrent wheezing after RSV bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis in young children has been associated with increased risk for developing recurrent wheezing, but the underlying mechanisms, are not completely defined. We hypothesized that RSV induces a disregulated immune response defined by a distinct cytokine profile in infants at increased risk for developing recurrent wheezing. METHODS: Previously healthy infants less than 12 months of age hospitalized with a first episode of RSV bronchiolitis were enrolled and blood samples and clinical and epidemiological data collected. A group of healthy non-infected controls were enrolled in parallel. Children were followed longitudinally and subsequent blood samples collected in RSV-infected infants at one month and at one year after hospital discharge to measure longitudinal plasma concentrations of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17 and IL1-ß. Risk of post-RSV wheezing was assessed by Poisson modelling. RESULTS: From October 2008 to March 2012 we enrolled 37 infants hospitalized with RSV bronchiolitis and 9 healthy age-matched controls. Within the RSV cohort, 17 (46%) children developed recurrent wheezing within the following 12 months. Plasma cytokine profiles measured during the acute infection were similar in children who developed recurrent wheezing versus those who did not, but lower in healthy controls vs RSV infants who subsequently developed wheezing. At one month and 12 months post-acute RSV infection, infants who developed recurrent wheezing had higher IFN-γ plasma concentrations versus those with no-wheezing (p < 0.05). Moreover, IFN-γ concentrations were identified as independent predictor of post-RSV wheezing. CONCLUSIONS: Children with RSV-associated recurrent wheezing had persistently elevated plasma concentrations of IFN-γ for a year after acute infection, suggesting that this cytokine could be used as a biomarker for risk of recurrent wheezing and possibly plays a role in the pathogenesis of this condition.

Prognostic implications of cardiac magnetic resonance feature tracking derived multidirectional strain in patients with chronic aortic regurgitation.

OBJECTIVE: Speckle-tracking echocardiography (STE) deformation parameters detect latent LV dysfunction in chronic aortic regurgitation (AR) and are associated with outcomes. The aim of the study was to evaluate cardiac magnetic resonance (CMR) feature tracking (FT) deformation parameters in asymptomatic patients with AR and implications in outcomes. METHODS: Fifty-five patients with AR and 54 controls were included. Conventional functional CMR parameters, aortic regurgitant volume, and fraction were assessed. CMR-FT analysis was performed with a dedicated software. Clinical data was obtained from hospital records. A combined endpoint included all-cause mortality, cardiovascular mortality, aortic valve surgery, or cardiovascular hospital admission due to heart failure. RESULTS: Left ventricular (LV) mechanics is impaired in patients with significant AR. Significant differences were noted in global longitudinal strain (GLS) between controls and AR patients (- 19.1 ± 2.9% vs - 16.5 ± 3.2%, p < 0.001) and among AR severity groups (- 18.3 ± 3.1% vs - 16.2 ± 1.6% vs - 15 ± 3.5%; p = 0.02 for AR grades I-II, III, and IV). In univariate and multivariate analyses, circumferential strain (GCS) and global radial strain (GRS) but not GLS were associated with and increased risk of the end point with a HR of 1.26 (p = 0.016, 1.04-1.52) per 1% worsening for GCS and 0.90 (p = 0.012, 0.83-0.98) per 1% worsening for GRS. CONCLUSIONS: CMR-FT myocardial deformation parameters are impaired in patients with AR not meeting surgical criteria. GLS decreases early in the course of the disease and is a marker of AR severity while GCS and GRS worsen later but predict a bad prognosis, mainly the need of aortic valve surgery. KEY POINTS: • CMR feature tracking LV mechanic parameters may be reduced in significant chronic AR with normal EF. • LV mechanics, mainly global longitudinal strain, worsens as AR severity increases. • LV mechanics, specially global radial and circumferential strain, is associated with a worse prognosis in AR patients.

The clinical relevance of the microbiome when managing paediatric infectious diseases-Narrative review.

In recent years, the field of infectious diseases has been hit by the overwhelming amount of information generated while the human microbiome is being disentangled. Based on the interaction between the microbiota and the immune system, the implications regarding infectious diseases are probably major and remain a challenge. AIMS: This review was conceived as a comprehensive tool to provide an overview of the available evidence regarding the influence of the microbiome on infectious diseases in children. METHODS: We present the main findings aroused from microbiome research in prevention, diagnosis and treatment of infectious disease under a paediatric perspective, to inform clinicians of the potential relevance of microbiome-related knowledge for translation to clinical practice. RESULTS AND CONCLUSION: The evidence shown in this review highlights the numerous research gaps ahead and supports the need to move forward to integrating the so-called microbiome thinking into our routine clinical practice.

The Role of BMP Signaling in Female Reproductive System Development and Function.

Bone morphogenetic proteins (BMPs) are a group of multifunctional growth factors that belong to the transforming growth factor-ß (TGF-ß) superfamily of proteins. Originally identified by their ability to induce bone formation, they are now known as essential signaling molecules that regulate the development and function of the female reproductive system (FRS). Several BMPs play key roles in aspects of reproductive system development. BMPs have also been described to be involved in the differentiation of human pluripotent stem cells (hPSCs) into reproductive system tissues or organoids. The role of BMPs in the reproductive system is still poorly understood and the use of FRS tissue or organoids generated from hPSCs would provide a powerful tool for the study of FRS development and the generation of new therapeutic perspectives for the treatment of FRS diseases. Therefore, the aim of this review is to summarize the current knowledge about BMP signaling in FRS development and function.

G2-S16 Polyanionic Carbosilane Dendrimer Can Reduce HIV-1 Reservoir Formation by Inhibiting Macrophage Cell to Cell Transmission.

Human immunodeficiency virus (HIV-1) is still a major problem, not only in developing countries but is also re-emerging in several developed countries, thus the development of new compounds able to inhibit the virus, either for prophylaxis or treatment, is still needed. Nanotechnology has provided the science community with several new tools for biomedical applications. G2-S16 is a polyanionic carbosilane dendrimer capable of inhibiting HIV-1 in vitro and in vivo by interacting directly with viral particles. One of the main barriers for HIV-1 eradication is the reservoirs created in primoinfection. These reservoirs, mainly in T cells, are untargetable by actual drugs or immune system. Thus, one approach is inhibiting HIV-1 from reaching these reservoir cells. In this context, macrophages play a main role as they can deliver viral particles to T cells establishing reservoirs. We showed that G2-S16 dendrimer is capable of inhibiting the infection from infected macrophages to healthy T CD4/CD8 lymphocytes by eliminating HIV-1 infectivity inside macrophages, so they are not able to carry infectious particles to other body locations, thus preventing the reservoirs from forming.