Immunomodulatory markers and therapies for the management of infant respiratory syncytial virus infection.

INTRODUCTION: The human respiratory syncytial virus (hRSV) is one of childhood diseases' most common respiratory pathogens and is associated with lower respiratory tract infections. The peak in disease that this virus can elicit during outbreaks is often a significant burden for healthcare systems worldwide. Despite theapproval of treatments against hRSV, this pathogen remains one the most common causative agent of infant mortality around the world. AREAS COVERED: This review focuses on the key prognostic and immunomodulatory biomarkers associated with hRSV infection, as well as prophylactic monoclonal antibodies and vaccines. The goal is to catalyze a paradigm shift within the scientific community toward the discovery of novel targets to predict the clinical outcome of infected patients, as well as the development of novel antiviral agents targeting hRSV. The most pertinent research on this topic was systematically searched and analyzed using PubMed ISI Thomson Scientific databases. EXPERT OPINION: Despite advances in approved therapies against hRSV, it is crucial to continue researching to develop new therapies and to find specific biomarkers to predict the severity of infection. Along these lines, the use of multi-omics data, artificial intelligence and natural-derived compounds with antiviral activity could be evaluated to fight hRSV and develop methods for rapid diagnosis of severity.

Advancement in the development of mRNA-based vaccines for respiratory viruses.

Acute respiratory infections are the leading cause of death and illness in children under 5 years old and represent a significant burden in older adults. Primarily caused by viruses infecting the lower respiratory tract, symptoms include cough, congestion, and low-grade fever, potentially leading to bronchiolitis and pneumonia. Messenger ribonucleic acid (mRNA)-based vaccines are biopharmaceutical formulations that employ mRNA molecules to induce specific immune responses, facilitating the expression of viral or bacterial antigens and promoting immunization against infectious diseases. Notably, this technology had significant relevance during the COVID-19 pandemic, as these formulations helped to limit SARS-CoV-2 virus infections, hospitalizations, and deaths. Importantly, mRNA vaccines promise to be implemented as new alternatives for fighting other respiratory viruses, such as influenza, human respiratory syncytial virus, and human metapneumovirus. This review article analyzes mRNA-based vaccines' main contributions, perspectives, challenges, and implications against respiratory viruses.

Co-administration of recombinant BCG and SARS-CoV-2 proteins leads to robust antiviral immunity.

SARS-CoV-2 is the causative virus of COVID-19, which has been responsible for millions of deaths worldwide since its discovery. After its emergence, several variants have been identified that challenge the efficacy of the available vaccines. Previously, we generated and evaluated a vaccine based on a recombinant Bacillus Calmette-Guérin (rBCG) expressing the nucleoprotein (N) of SARS-CoV-2 (rBCG-N-SARS-CoV-2). This protein is a highly immunogenic antigen and well conserved among variants. Here, we tested the administration of this vaccine with recombinant N and viral Spike proteins (S), or Receptor Binding Domain (RBD-Omicron variant), plus a booster with the recombinant proteins only, as a novel and effective strategy to protect against SARS-CoV-2 variants. METHODS: BALB/c mice were immunized with rBCG-N-SARS-CoV-2 and recombinant SARS-CoV-2 proteins in Alum adjuvant, followed by a booster with recombinant proteins to assess the safety and virus-specific cellular and humoral immune responses against SARS-CoV-2 antigens. RESULTS: Immunization with rBCG-N-SARS-CoV-2 + recombinant proteins as a vaccine was safe and promoted the activation of CD4+ and CD8+ T cells that recognize SARS-CoV-2 N, S, and RBD antigens. These cells were able to secrete cytokines with an antiviral profile. This immunization strategy also induced robust titers of specific antibodies against N, S, and RBD and neutralizing antibodies of SARS-CoV-2. CONCLUSIONS: Co-administration of the rBCG-N-SARS-CoV-2 vaccine with recombinant SARS-CoV-2 proteins could be an effective alternative to control particular SARS-CoV-2 variants. Due to its safety and capacity to induce virus-specific immune responses, we believe the rBCG-N-SARS-CoV-2 + Proteins vaccine could be an attractive candidate to protect against this virus, especially in newborns.

Immunogenicity and Safety of a Quadrivalent Influenza Vaccine in Population Aged 3 Years and Older in Chile and the Philippines: A Phase 3, Non-Inferiority, Double-Blind, Randomized Controlled Clinical Trial.

OBJECTIVES: In this study, we aimed to evaluate the non-inferiority of a quadrivalent influenza vaccine (QIV) developed by Sinovac Biotech Co., Ltd. (Sinovac, Beijing, China) by comparing its immunogenicity and safety with a comparator QIV (Vaxigrip Tetra®) in a population aged 3 years and older in Chile and the Philippines. METHODS: A phase 3, non-inferiority, double-blind, randomized controlled, multicenter clinical trial was conducted in the southern hemisphere (SH) 2023 influenza season. Participants aged ≥ 3 years old with stable health were randomized 1:1 to receive either Sinovac QIV or comparator QIV. The co-primary outcomes were immunological non-inferiority for Sinovac QIV versus the comparator against each strain contained in the vaccines in terms of seroconversion rates (SCRs) and geometric mean titers (GMTs) of hemagglutination inhibition (HI) antibodies 28 days after final vaccination. RESULTS: A total of 2039 participants were vaccinated (1019 Sinovac QIV; 1020 comparator QIV). Sinovac QIV induced non-inferior immune responses to all four strains as compared to comparator QIV, with slightly higher GMTs than those of comparator QIV: GMT ratios (lower limit 95% confidence interval (CI)) were 1.8 (1.6) for A(H1N1), 1.4 (1.3) for A (H3N2), 1.3 (1.1) for B Victoria and 1.2 (1.1) for B Yamagata; observed seroconversion rate differences (lower limit 95% CI) were 9.6% (6.7) for A(H1N1), 7.0% (3.5) for A(H3N2), 2.4% (-0.03) for B Victoria and 6.8% (3.0) for B Yamagata. Adverse reactions were similar across the two groups and no vaccine-related serious adverse events were reported. CONCLUSIONS: The immunogenicity of Sinovac QIV was non-inferior to that of the comparator QIV in these populations aged 3 years and older, and safety was comparable.

Pseudomonas aeruginosa epidemic high-risk clones and their association with multidrug-resistant.

OBJECTIVE: In Ecuador, data on molecular epidemiology, as well as circulating clones, are limited. Therefore, this study aims to know the population structure of Pseudomonas aeruginosa by identifying clones in clinical samples in Quito-Ecuador. METHODS: A significant set (45) clinical P. aeruginosa isolates were selected, including multidrug and non-multidrug resistant isolates, which were assigned to sequence types (STs) and compared with their antibiotic susceptibility profile. The genetic diversity was assessed by applying the multilocus sequence typing (MLST) scheme and the genetic relationships between different STs were corroborated by phylogenetic networks. RESULTS: The MLST analysis identified 24 different STs and the most prevalent STs were ST-3750 and ST-253. The majority of the multidrug-resistance (MDR) isolates were included in ST-3750 and ST-253, also 3 singleton STs were identified as MDR isolates. The 21 different STs were found in non-multidrug resistance (non-MDR) isolates, and only 3 STs were found in more the one isolate. CONCLUSIONS: The population structure of clinical P. aeruginosa present in these isolates indicates a significant association between MDR isolates and the clonal types: all ST-3750 and ST-253 isolates were MDR. ST-3750 is a closely related strain to the clonal complex ST111 (CC111). ST-253 and ST111 are a group of successful high-risk clones widely distributed worldwide. The multiresistant isolates studied are grouped in the most prevalent STs found, and the susceptible isolates correspond mainly with singleton STs. Therefore, these high-risk clones and their association with MDR phenotypes are contributing to the spread of MDR in Quito, Ecuador.

Clinical and Radiological Differences between Patients Diagnosed with Acute Ischemic Stroke and Chameleons at the Emergency Room: Insights from a Single-Center Observational Study.

INTRODUCTION: Scarce data exist about clinical/radiological differences between acute ischemic strokes diagnosed in the emergency room (AISER) and stroke chameleons (SCs). We aimed at describing the differences observed in a comprehensive stroke center in Chile. METHODS: Prospective observational study of patients with ischemic stroke syndromes admitted to the emergency room (ER) of Clínica Alemana between December 2014 and October 2023. RESULTS: 1,197 patients were included; of these 63 (5.2%, 95% CI: 4.1-6.6) were SC; these were younger (p < 0.001), less frequently hypertensive (p = 0.03), and they also had lower systolic (SBP) (p < 0.001), diastolic blood pressures (DBP) (p = 0.011), and NIHSS (p < 0.001). Clinically, they presented less frequently gaze (p = 0.008) and campimetry alterations (p = 0.03), facial (p < 0.001) and limb weakness (left arm [p = 0.004], right arm (p = 0.041), left leg (p = 0.001), right leg p = 0.0029), sensory abnormalities (p < 0.001), and dysarthria (p < 0.001). Neuroradiological evaluations included less frequently large vessel occlusions (p = 0.01) and other stroke locations (p = 0.005); they also differed in their etiologies (p < 0.001). Brainstem strokes (p < 0.001) and extinction/inattention symptoms (p < 0.001) were only seen in AISER. In multivariate analysis, younger age (OR: 0.945; 95% CI: 0.93-0.96), DBP (OR: 0.97; 95% CI, 0.95-0.99), facial weakness (OR: 0.39; 95% CI: 0.19-0.78), sensory abnormities (OR: 0.16.18; 95% CI, 0.05-0.4), infratentorial location (OR: 0.36; 95% CI, 0.15-0.78), posterior circulation involvement (OR: 3.02; 95% CI, 1.45-6.3), cardioembolic (OR: 3.5; 95% CI, 1.56-7.99), and undetermined (OR: 2.42; 95% CI, 1.22-4.7; 95%) etiologies, remained statistically significant. A stepwise analysis including only clinical elements present on the patient's arrival to the ER, demonstrates that age (OR: 0.95; 95% CI: 0.94-0.97), DBP (OR: 0.97; 95% CI, 0.95-0.99), the presence of atrial fibrillation (OR: 2.22; 95% CI, 1.04-4.75, NIHSS (OR: 0.88; 95% CI, 0.71-0.89) and the presence in NIHSS of 1a level of consciousness (OR: 5.66; CI: 95% 1.8-16.9), 1b level of consciousness questions (OR: 3.023; 95% CI, 1.35-6.8), facial weakness (OR: 0.3; CI: 95% 0.17-0.8), and sensory abnormalities (OR: 0.27; 95% CI, 0.1-0.72) remained statistically significant. CONCLUSION: SC had clinical and radiological differences compared to AISER. An additional relevant finding is that neurological symptoms in a patient with atrial fibrillation, even with a negative diffusion-weighted imaging, should be carefully evaluated as a potential stroke until other causes are satisfactorily ruled out.

Asymptomatic herpes simplex virus brain infection elicits cellular senescence phenotypes in the central nervous system of mice suffering multiple sclerosis-like disease.

Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease affecting the central nervous system (CNS) in animals that parallels several clinical and molecular traits of multiple sclerosis in humans. Herpes simplex virus type 1 (HSV-1) infection mainly causes cold sores and eye diseases, yet eventually, it can also reach the CNS, leading to acute encephalitis. Notably, a significant proportion of healthy individuals are likely to have asymptomatic HSV-1 brain infection with chronic brain inflammation due to persistent latent infection in neurons. Because cellular senescence is suggested as a potential factor contributing to the development of various neurodegenerative disorders, including multiple sclerosis, and viral infections may induce a premature senescence state in the CNS, potentially increasing susceptibility to such disorders, here we examine the presence of senescence-related markers in the brains and spinal cords of mice with asymptomatic HSV-1 brain infection, EAE, and both conditions. Across all scenarios, we find a significant increases of senescence biomarkers in the CNS with some differences depending on the analyzed group. Notably, some senescence biomarkers are exclusively observed in mice with the combined conditions. These results indicate that asymptomatic HSV-1 brain infection and EAE associate with a significant expression of senescence biomarkers in the CNS.

New insights into the pathogenesis of SARS-CoV-2 during and after the COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the respiratory distress condition known as COVID-19. This disease broadly affects several physiological systems, including the gastrointestinal, renal, and central nervous (CNS) systems, significantly influencing the patient's overall quality of life. Additionally, numerous risk factors have been suggested, including gender, body weight, age, metabolic status, renal health, preexisting cardiomyopathies, and inflammatory conditions. Despite advances in understanding the genome and pathophysiological ramifications of COVID-19, its precise origins remain elusive. SARS-CoV-2 interacts with a receptor-binding domain within angiotensin-converting enzyme 2 (ACE2). This receptor is expressed in various organs of different species, including humans, with different abundance. Although COVID-19 has multiorgan manifestations, the main pathologies occur in the lung, including pulmonary fibrosis, respiratory failure, pulmonary embolism, and secondary bacterial pneumonia. In the post-COVID-19 period, different sequelae may occur, which may have various causes, including the direct action of the virus, alteration of the immune response, and metabolic alterations during infection, among others. Recognizing the serious adverse health effects associated with COVID-19, it becomes imperative to comprehensively elucidate and discuss the existing evidence surrounding this viral infection, including those related to the pathophysiological effects of the disease and the subsequent consequences. This review aims to contribute to a comprehensive understanding of the impact of COVID-19 and its long-term effects on human health.

Gestational hypothyroxinemia induces ASD-like phenotypes in behavior, proinflammatory markers, and glutamatergic protein expression in mouse offspring of both sexes.

Background: The prevalence of autism spectrum disorder (ASD) has significantly risen in the past three decades, prompting researchers to explore the potential contributions of environmental factors during pregnancy to ASD development. One such factor of interest is gestational hypothyroxinemia (HTX), a frequent condition in pregnancy associated with cognitive impairments in the offspring. While retrospective human studies have linked gestational HTX to autistic traits, the cellular and molecular mechanisms underlying the development of ASD-like phenotypes remain poorly understood. This study used a mouse model of gestational HTX to evaluate ASD-like phenotypes in the offspring. Methods: To induce gestational HTX, pregnant mice were treated with 2-mercapto-1-methylimidazole (MMI), a thyroid hormones synthesis inhibitor, in the tap-drinking water from embryonic days (E) 10 to E14. A separate group received MMI along with a daily subcutaneous injection of T4, while the control group received regular tap water during the entire pregnancy. Female and male offspring underwent assessments for repetitive, anxious, and social behaviors from postnatal day (P) 55 to P64. On P65, mice were euthanized for the evaluation of ASD-related inflammatory markers in blood, spleen, and specific brain regions. Additionally, the expression of glutamatergic proteins (NLGN3 and HOMER1) was analyzed in the prefrontal cortex and hippocampus. Results: The HTX-offspring exhibited anxious-like behavior, a subordinate state, and impaired social interactions. Subsequently, both female and male HTX-offspring displayed elevated proinflammatory cytokines in blood, including IL-1ß, IL-6, IL-17A, and TNF-α, while only males showed reduced levels of IL-10. The spleen of HTX-offspring of both sexes showed increased Th17/Treg ratio and M1-like macrophages. In the prefrontal cortex and hippocampus of male HTX-offspring, elevated levels of IL-17A and reduced IL-10 were observed, accompanied by increased expression of hippocampal NLGN3 and HOMER1. All these observations were compared to those observed in the Control-offspring. Notably, the supplementation with T4 during the MMI treatment prevents the development of the observed phenotypes. Correlation analysis revealed an association between maternal T4 levels and specific ASD-like outcomes. Discussion: This study validates human observations, demonstrating for the first time that gestational HTX induces ASD-like phenotypes in the offspring, highlighting the need of monitoring thyroid function during pregnancy.

Immune responses during COVID-19 breakthrough cases in vaccinated children and adolescents.

Background: Vaccine effectiveness against SARS-CoV-2 infection has been somewhat limited due to the widespread dissemination of the Omicron variant, its subvariants, and the immune response dynamics of the naturally infected with the virus. Methods: Twelve subjects between 3-17 years old (yo), vaccinated with two doses of CoronaVac®, were followed and diagnosed as breakthrough cases starting 14 days after receiving the second dose. Total IgGs against different SARS-CoV-2 proteins and the neutralizing capacity of these antibodies after infection were measured in plasma. The activation of CD4+ and CD8+ T cells was evaluated in peripheral blood mononuclear cells stimulated with peptides derived from the proteins from the wild-type (WT) virus and Omicron subvariants by flow cytometry, as well as different cytokines secretion by a Multiplex assay. Results: 2 to 8 weeks post-infection, compared to 4 weeks after 2nd dose of vaccine, there was a 146.5-fold increase in neutralizing antibody titers against Omicron and a 38.7-fold increase against WT SARS-CoV-2. Subjects showed an increase in total IgG levels against the S1, N, M, and NSP8 proteins of the WT virus. Activated CD4+ T cells showed a significant increase in response to the BA.2 subvariant (p<0.001). Finally, the secretion of IL-2 and IFN-γ cytokines showed a discreet decrease trend after infection in some subjects. Conclusion: SARS-CoV-2 infection in the pediatric population vaccinated with an inactivated SARS-CoV-2 vaccine produced an increase in neutralizing antibodies against Omicron and increased specific IgG antibodies for different SARS-CoV-2 proteins. CD4+ T cell activation was also increased, suggesting a conserved cellular response against the Omicron subvariants, whereas Th1-type cytokine secretion tended to decrease. Clinical Trial Registration: clinicaltrials.gov #NCT04992260.

Natural killer T cells in allergic asthma: implications for the development of novel immunotherapeutical strategies.

Allergic asthma has emerged as a prevalent allergic disease worldwide, affecting most prominently both young individuals and lower-income populations in developing and developed countries. To devise effective and curative immunotherapy, it is crucial to comprehend the intricate nature of this condition, characterized by an immune response imbalance that favors a proinflammatory profile orchestrated by diverse subsets of immune cells. Although the involvement of Natural Killer T (NKT) cells in asthma pathology is frequently implied, their specific contributions to disease onset and progression remain incompletely understood. Given their remarkable ability to modulate the immune response through the rapid secretion of various cytokines, NKT cells represent a promising target for the development of effective immunotherapy against allergic asthma. This review provides a comprehensive summary of the current understanding of NKT cells in the context of allergic asthma, along with novel therapeutic approaches that leverage the functional response of these cells.

Cost-effectiveness of intraoperative radiation therapy versus intensity-modulated radiation therapy for the treatment of early breast cancer: a disinvestment analysis.

BACKGROUND: Adjuvant radiotherapy represents a key component in curative-intent treatment for early-stage breast cancer patients. In recent years, two accelerated partial breast irradiation (APBI) techniques are preferred for this population in our organization: electron-based Intraoperative radiation therapy (IORT) and Linac-based External Beam Radiotherapy, particularly Intensity-modulated radiation therapy (IMRT). Recently published long-term follow-up data evaluating these technologies have motivated a health technology reassessment of IORT compared to IMRT. METHODS: We developed a Markov model to simulate health-state transitions from a cohort of women with early-stage breast cancer, after lumpectomy and adjuvant APBI using either IORT or IMRT techniques. The cost-effectiveness from a private health provider perspective was assessed from a disinvestment point of view, using life-years (LYs) and recurrence-free life-years (RFLYs) as measure of benefits, along with their respective quality adjustments. Expected costs and benefits, and the incremental cost-effectiveness ratio (ICER) were reported. Finally, a sensitivity and scenario analyses were performed to evaluate the cost-effectiveness using lower IORT local recurrence and metastasis rates in IORT patients, and if equipment maintenance costs are removed. RESULTS: IORT technology was dominated by IMRT in all cases (i.e., fewer benefits with greater costs). Despite small differences were found regarding benefits, especially for LYs, costs were considerably higher for IORT. For sensitivity analyses with lower recurrence and metastasis rates for IORT, and scenario analyses without equipment maintenance costs, IORT was still dominated by IMRT. CONCLUSIONS: For this cohort of patients, IMRT was, at least, non-inferior to IORT in terms of expected benefits, with considerably lower costs. As a result, IORT disinvestment should be considered, favoring the use of IMRT in these patients.

Pathophysiological, immunological, and inflammatory features of long COVID.

The COVID-19 pandemic continues to cause severe global disruption, resulting in significant excess mortality, overwhelming healthcare systems, and imposing substantial social and economic burdens on nations. While most of the attention and therapeutic efforts have concentrated on the acute phase of the disease, a notable proportion of survivors experience persistent symptoms post-infection clearance. This diverse set of symptoms, loosely categorized as long COVID, presents a potential additional public health crisis. It is estimated that 1 in 5 COVID-19 survivors exhibit clinical manifestations consistent with long COVID. Despite this prevalence, the mechanisms and pathophysiology of long COVID remain poorly understood. Alarmingly, evidence suggests that a significant proportion of cases within this clinical condition develop debilitating or disabling symptoms. Hence, urgent priority should be given to further studies on this condition to equip global public health systems for its management. This review provides an overview of available information on this emerging clinical condition, focusing on the affected individuals' epidemiology, pathophysiological mechanisms, and immunological and inflammatory profiles.

Chilean consensus by expert panel using the Delphi technique for primary and secondary prevention of gastric cancer. / Estrategias para la prevención primaria y secundaria del cáncer gástrico: consenso chileno de panel de expertos con técnica Delfi.

INTRODUCTION: Gastric cancer (GC) is the first cause of cancer-related death in Chile and 6th in Latin America and the Caribbean (LAC). Helicobacter pylori (H. pylori) is the main gastric carcinogen, and its treatment reduces GC incidence and mortality. Esophageal-gastro-duodenoscopy (EGD) allows for the detection of premalignant conditions and early-stage GC. Mass screening programs for H. pylori infection and screening for premalignant conditions and early-stage GC are not currently implemented in LAC. The aim of this study is to establish recommendations for primary and secondary prevention of GC in asymptomatic standard-risk populations in Chile. METHODS: Two on-line synchronous workshops and a seminar were conducted with Chilean experts. A Delphi panel consensus was conducted over 2 rounds to achieve>80% agreement on proposed primary and secondary prevention strategies for the population stratified by age groups. RESULTS: 10, 12, and 12 experts participated in two workshops and a seminar, respectively. In the Delphi panel, 25 out of 37 experts (77.14%) and 28 out of 52 experts (53.85%) responded. For the population aged 16-34, there was no consensus on non-invasive testing and treatment for H. pylori, and the use of EGD was excluded. For the 35-44 age group, non-invasive testing and treatment for H. pylori is recommended, followed by subsequent test-of-cure using non-invasive tests (stool antigen test or urea breath test). In the ≥45 age group, a combined strategy is recommended, involving H. pylori testing and treatment plus non-invasive biomarkers (H. pylori IgG serology and serum pepsinogens I and II); subsequently, a selected group of subjects will undergo EGD with gastric biopsies (Sydney Protocol), which will be used to stratify surveillance according to the classification Operative Link for Gastritis Assessment (OLGA); every 3 years for OLGA III-IV and every 5 years for OLGA I-II. CONCLUSION: A "test-and-treat" strategy for H. pylori infection based on non-invasive studies (primary prevention) is proposed in the 35-44 age group, and a combined strategy (serology and EGD) is recommended for the ≥45 age group (primary and secondary prevention). These strategies are potentially applicable to other countries in LAC.

99mTc-AgNPs-ICG: nanoparticle for hybrid image / 99mTc-AgNPs-ICG: nanopartícula para imagem híbrida / 99mTc-AgNPs-ICG: nanopartícula para imagem híbrida

Introduction: Currently nanotechnology has radically changed the diagnosis of many human pathologies. The aim of this work is to obtain silver nanoparticles for hybrid imaging (99mTc-AgNPs-ICG) having potential clinical imaging applications. Materials and methods: We mixed 2 ml of ascorbic acid (1.7x10-4 M), 5 mCi of 99mTcO4- , 2 ml of citric acid (8.0x10-4 M) and 0.5 ml of silver nitrate (2.5x10-3 M). Solution pH was 5, and it was shaken for 20 minutes at 37º C. Afterwards, 2 µL of Indocyanine Green (1.3x10-3 M) was added (99mTc-AgNPs-ICG). Physiochemical properties of the solution were characterized by UV (λ1 = 420 nm, λ2 = 254 nm) and gamma detector. Fluorescence image, particle size and IR spectrum were evaluated. Results: Silver nanoparticles were obtained in aqueous solution a pH of 5. Their pH, color and spectrum were stable for seven days. Furthermore, the principal peak characterized by HPLC, UV and Gamma detector had similar retention times. Its UV spectrum showed an absorption band of 420 nm, which corresponds to the plasmon absorption band of these nanoparticles. The particle size was 46 nm ± 1.5 nm. The IR spectrum showed absorption bands in 3193, 2624, 1596 y 1212 cm-1. Conclusions: We describe for the first time in literature the synthesis of hybrid (radioactive and fluorescent) silver nanoparticles. Their physiochemical properties were characterized, being stable and their labelling was reproducible having potential biomedical applications.

Introducción: actualmente la nanotecnología ha cambiado radicalmente el diagnóstico de muchas patologías humanas. El objetivo de este trabajo es obtener nanopartículas de plata para imagen híbrida (99mTc-AgNPs-ICG) que tengan potenciales aplicaciones clínicas en imagen. Materiales y métodos: se mezclaron 2 ml de ácido ascórbico (1,7x10-4 M), 5 mCi de 99mTcO4- , 2 ml de ácido cítrico (8,0x10-4 M) y 0,5 ml de nitrato de plata (2,5x10-3 M). El pH de la solución fue 5, y se agitó durante 20 minutos a 37º C. A continuación, se añadieron 2 µl de verde de indocianina (1,3x10-3 M) (99mTc-AgNPs-ICG). Las propiedades fisicoquímicas de la solución se caracterizaron mediante UV (λ1 = 420 nm, λ2 = 254 nm) y detector gamma. Se evaluaron la imagen de fluorescencia, el tamaño de las partículas y el espectro IR. Resultados: se obtuvieron nanopartículas de plata en solución acuosa a un pH de 5. Su pH, color y espectro fueron estables durante siete días. Además, el pico principal caracterizado por HPLC, UV y detector Gamma tenía tiempos de retención similares. Su espectro UV mostró una banda de absorción de 420 nm, que corresponde a la banda de absorción plasmónica de estas nanopartículas. El tamaño de las partículas era de 46 nm ± 1,5 nm. El espectro IR mostró bandas de absorción en 3193, 2624, 1596 y 1212 cm-1. Conclusiones: describimos por primera vez en la literatura la síntesis de nanopartículas de plata híbridas (radioctivas y fluorescentes). Se caracterizaron sus propiedades fisicoquímicas, siendo estables y su etiquetado fue reproducible teniendo potenciales aplicaciones biomédicas.

Introdução: atualmente, a nanotecnologia mudou radicalmente o diagnóstico de muitas patologias humanas. O objetivo deste trabalho é obter nanopartículas de prata para imagens híbridas (99mTc-AgNPs-ICG) com possíveis aplicações de imagens clínicas. Materiais e métodos: misturamos 2 ml de ácido ascórbico (1,7x10-4 M), 5 mCi de 99mTcO4- , 2 ml de ácido cítrico (8,0x10-4 M) e 0,5 ml de nitrato de prata (2,5x10-3 M). O pH da solução era 5 e ela foi agitada por 20 minutos a 37º C. Em seguida, foram adicionados 2 µL de indocianina verde (1,3x10-3 M) (99mTc-AgNPs-ICG). As propriedades físico-químicas da solução foram caracterizadas por UV (λ1 = 420 nm, λ2 = 254 nm) e detector gama. A imagem de fluorescência, o tamanho das partículas e o espectro de infravermelho foram avaliados. Resultados: as nanopartículas de prata foram obtidas em solução aquosa com pH de 5. Seu pH, cor e espectro permaneceram estáveis por sete dias. Além disso, o pico principal caracterizado por HPLC, UV e detector gama teve tempos de retenção semelhantes. Seu espectro de UV mostrou uma banda de absorção de 420 nm, que corresponde à banda de absorção plasmônica dessas nanopartículas. O tamanho da partícula foi de 46 nm ± 1,5 nm. O espectro de IV mostrou bandas de absorção em 3193, 2624, 1596 e 1212 cm-1. Conclusões: descrevemos pela primeira vez na literatura a síntese de nanopartículas de prata híbridas (radioativas e fluorescentes). Suas propriedades físico-químicas foram caracterizadas, sendo estáveis e sua rotulagem foi reprodutível, com possíveis aplicações biomédicas.

99mTc-AgNPs-ICG: nanopartícula para imagen híbrida / 99mTc-AgNPs-ICG: nanoparticle for hybrid image / 99mTc-AgNPs-ICG: nanopartícula para imagem híbrida

Introducción: actualmente la nanotecnología ha cambiado radicalmente el diagnóstico de muchas patologías humanas. El objetivo de este trabajo es obtener nanopartículas de plata para imagen híbrida (99mTc-AgNPs-ICG) que tengan potenciales aplicaciones clínicas en imagen. Materiales y métodos: se mezclaron 2 ml de ácido ascórbico (1.7 x10-4 M), 5 mCi de 99mTcO4-, 2 ml de ácido cítrico (8.0 x 10-4 M) y 0.5 ml de nitrato de plata (2.5 x 10-3 M). El pH de la solución fue 5, y se agitó durante 20 minutos a 37º C. A continuación, se añadieron 2 µl de verde de indocianina (1.3 x 10-3 M) (99mTc-AgNPs-ICG). Las propiedades fisicoquímicas de la solución se caracterizaron mediante UV (λ1 = 420 nm, λ2 = 254 nm) y detector gamma. Se evaluaron la imagen de fluorescencia, el tamaño de las partículas y el espectro IR. Resultados: se obtuvieron nanopartículas de plata en solución acuosa a un pH de 5. Su pH, color y espectro fueron estables durante siete días. Además, el pico principal caracterizado por HPLC, UV y detector Gamma tenía tiempos de retención similares. Su espectro UV mostró una banda de absorción de 420 nm, que corresponde a la banda de absorción plasmónica de estas nanopartículas. El tamaño de las partículas era de 46 nm ± 1,5 nm. El espectro IR mostró bandas de absorción en 3193, 2624, 1596 y 1212 cm-1. Conclusiones: describimos por primera vez en la literatura la síntesis de nanopartículas de plata híbridas (radioactivas y fluorescentes). Se caracterizaron sus propiedades fisicoquímicas, siendo estables y su etiquetado fue reproducible teniendo potenciales aplicaciones biomédicas.

Introduction: Currently nanotechnology has radically changed the diagnosis of many human pathologies. The aim of this work is to obtain silver nanoparticles for hybrid imaging (99mTc-AgNPs-ICG) having potential clinical imaging applications. Materials and methods: We mixed 2 ml of ascorbic acid (1.7x10-4 M), 5 mCi of 99mTcO4-, 2 ml of citric acid (8.0 x 10-4 M) and 0.5 ml of silver nitrate (2.5 x 10-3 M). Solution pH was 5, and it was shaken for 20 minutes at 37º C. Afterwards, 2 µL of Indocyanine Green (1.3 x 10-3 M) was added (99mTc-AgNPs-ICG). Physiochemical properties of the solution were characterized by UV (λ1 = 420 nm, λ2 = 254 nm) and gamma detector. Fluorescence image, particle size and IR spectrum were evaluated. Results: Silver nanoparticles were obtained in aqueous solution a pH of 5. Their pH, color and spectrum were stable for seven days. Furthermore, the principal peak characterized by HPLC, UV and Gamma detector had similar retention times. Its UV spectrum showed an absorption band of 420 nm, which corresponds to the plasmon absorption band of these nanoparticles. The particle size was 46 nm ± 1.5 nm. The IR spectrum showed absorption bands in 3193, 2624, 1596 y 1212 cm-1. Conclusions: We describe for the first time in literature the synthesis of hybrid (radioactive and fluorescent) silver nanoparticles. Their physiochemical properties were characterized, being stable and their labelling was reproducible having potential biomedical applications.

Introdução: Atualmente, a nanotecnologia mudou radicalmente o diagnóstico de muitas patologias humanas. O objetivo deste trabalho é obter nanopartículas de prata para imagens híbridas (99mTc-AgNPs-ICG) com possíveis aplicações de imagens clínicas. Materiais e métodos: Misturamos 2 ml de ácido ascórbico (1.7 x 10-4 M), 5 mCi de 99mTcO4-, 2 ml de ácido cítrico (8.0 x 10-4 M) e 0.5 ml de nitrato de prata (2.5 x 10-3 M). O pH da solução era 5 e ela foi agitada por 20 minutos a 37º C. Em seguida, foram adicionados 2 µL de indocianina verde (1,3x10-3 M) (99mTc-AgNPs-ICG). As propriedades físico-químicas da solução foram caracterizadas por UV (λ1 = 420 nm, λ2 = 254 nm) e detector gama. A imagem de fluorescência, o tamanho das partículas e o espectro de infravermelho foram avaliados. Resultados: As nanopartículas de prata foram obtidas em solução aquosa com pH de 5. Seu pH, cor e espectro permaneceram estáveis por sete dias. Além disso, o pico principal caracterizado por HPLC, UV e detector gama teve tempos de retenção semelhantes. Seu espectro de UV mostrou uma banda de absorção de 420 nm, que corresponde à banda de absorção plasmônica dessas nanopartículas. O tamanho da partícula foi de 46 nm ± 1,5 nm. O espectro de IV mostrou bandas de absorção em 3193, 2624, 1596 e 1212 cm-1. Conclusões: Descrevemos pela primeira vez na literatura a síntese de nanopartículas de prata híbridas (radioativas e fluorescentes). Suas propriedades físico-químicas foram caracterizadas, sendo estáveis e sua rotulagem foi reprodutível, com possíveis aplicações biomédicas.

Intravenous Thrombolysis in Patients 90 Years or Older with Moderate to Severe Acute Ischemic Stroke Increases Ambulation at Discharge and Is Safe: A Prospective Cohort Study from a Single Center in Santiago, Chile.

INTRODUCTION: The World Health Organization predicts that the global population aged 60 years and older will double by 2050, leading to a significant rise in the public health impact of acute ischemic stroke (AIS). Existing stroke guidelines do not specify an upper age limit for the administration of intravenous thrombolysis (IVT), although some suggest a relative exclusion criterion in patients aged ≥80 in the 3-4.5-h window. Many physicians avoid treating these patients with IVT, argumenting high risk and little benefit. Our aim was to investigate the efficacy and safety of IVT treatment in patients with non-minor AIS aged ≥90, admitted to our institution. The primary efficacy endpoint was the ability to walk at discharge (mRS 0-3), and the primary safety endpoints were death and symptomatic intracranial hemorrhagic transformation (sIHT) at discharge. METHODS: Patients with AIS aged ≥90 admitted to our center from January 2003 to December 2022 were included. They were selected if had an NIHSS ≥5, were previously ambulatory (prestroke mRS score 3 or less), and arrived within 6 h from symptom onset. Those treated or not with IVT were compared with univariate analysis. RESULTS: The mean age was 93.2 (2.4) years, and 51 (73.9%) were female. The admission mRS and NIHSS were 1 (IQR 0-2) and 14 (IQR 7-22), respectively. Thrombolyzed patients had a shorter time from symptom onset to door and lower glycemia on admission. IVT was associated with a higher proportion of patients achieving mRS 0-3 at discharge (p = 0.03) and at 90 days (p = 0.04). There were no differences between groups in the risk of death (p = 0.55) or sIHT (p = 0.38). CONCLUSION: In this small sample, ambulatory patients aged ≥90 with moderate or severe AIS treated with IVT had increased odds of being able to walk independently at discharge than those not treated, without safety concerns.

A molecular perspective for the development of antibodies against the human respiratory syncytial virus.

The human respiratory syncytial virus (hRSV) is the leading etiologic agent causing respiratory infections in infants, children, older adults, and patients with comorbidities. Sixty-seven years have passed since the discovery of hRSV, and only a few successful mitigation or treatment tools have been developed against this virus. One of these is immunotherapy with monoclonal antibodies against structural proteins of the virus, such as Palivizumab, the first prophylactic approach approved by the Food and Drug Administration (FDA) of the USA. In this article, we discuss different strategies for the prevention and treatment of hRSV infection, focusing on the molecular mechanisms against each target that underly the rational design of antibodies against hRSV. At the same time, we describe the latest results regarding currently approved therapies against hRSV and the challenges associated with developing new candidates.

Natural Killer T Cell Diversity and Immunotherapy.

Invariant natural killer T cells (iNKTs), a type of unconventional T cells, share features with NK cells and have an invariant T cell receptor (TCR), which recognizes lipid antigens loaded on CD1d molecules, a major histocompatibility complex class I (MHC-I)-like protein. This interaction produces the secretion of a wide array of cytokines by these cells, including interferon gamma (IFN-γ) and interleukin 4 (IL-4), allowing iNKTs to link innate with adaptive responses. Interestingly, molecules that bind CD1d have been identified that enable the modulation of these cells, highlighting their potential pro-inflammatory and immunosuppressive capacities, as required in different clinical settings. In this review, we summarize key features of iNKTs and current understandings of modulatory α-galactosylceramide (α-GalCer) variants, a model iNKT cell activator that can shift the outcome of adaptive immune responses. Furthermore, we discuss advances in the development of strategies that modulate these cells to target pathologies that are considerable healthcare burdens. Finally, we recapitulate findings supporting a role for iNKTs in infectious diseases and tumor immunotherapy.

Different Safety Pattern of an Inactivated SARS-CoV-2 Vaccine (CoronaVac®) According to Age Group in a Pediatric Population from 3 to 17 Years Old, in an Open-Label Study in Chile.

During the COVID-19 pandemic, the importance of vaccinating children against SARS-CoV-2 was rapidly established. This study describes the safety of CoronaVac® in children and adolescents between 3- and 17-years-old in a multicenter study in Chile with two vaccine doses in a 4-week interval. For all participants, immediate adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were registered throughout the study. In the safety subgroup, AEs were recorded 28 days after each dose. COVID-19 surveillance was performed throughout the study. A total of 1139 individuals received the first and 1102 the second dose of CoronaVac®; 835 were in the safety subgroup. The first dose showed the highest number of AEs: up to 22.2% of participants reported any local and 17.1% systemic AE. AEs were more frequent in adolescents after the first dose, were transient, and mainly mild. Pain at the inoculation site was the most frequent AE for all ages. Fever was the most frequent systemic AE for 3-5 years old and headache in 6-17 years old. No SAEs or AESIs related to vaccination occurred. Most of the COVID-19 cases were mild and managed as outpatients. CoronaVac® was safe and well tolerated in children and adolescents, with different safety patterns according to age.