The Great Masquerade: Not All Coronary Artery Stenosis Are Created Equal.

We present the case of a 60-year-old male, with active smoking and cocaine use disorder, who reported progressive chest pain. Various anatomical and functional cardiac imaging, performed to further evaluate chest pain etiology, revealed changing severity and distribution of left main artery (LMA) stenosis, raising suspicion for vasospasm. Intracoronary nitroglycerin relieved the vasospasm, with resolution of the LMA pseudostenosis. A diagnosis of vasospastic angina (VA) led to starting appropriate medical therapy with lifestyle modification counselling. This case highlights VA, a frequently underdiagnosed etiology of angina pectoris. We discuss when to suspect VA, its appropriate work-up, and management.

Electroanalysis in Pharmacogenomic Studies: Mechanisms of Drug Interaction with DNA.

The review discusses electrochemical methods for analysis of drug interactions with DNA. The electroanalysis method is based on the registration of interaction-induced changes in the electrochemical oxidation potential of heterocyclic nitrogenous bases in the DNA molecule and in the maximum oxidation current amplitude. The mechanisms of DNA-drug interactions can be identified based on the shift in the electrooxidation potential of heterocyclic nitrogenous bases toward more negative (cathodic) or positive (anodic) values. Drug intercalation into DNA shifts the electrochemical oxidation potential to positive values, indicating thermodynamically unfavorable process that hinders oxidation of nitrogenous bases in DNA. The potential shift toward the negative values indicates electrostatic interactions, e.g., drug binding in the DNA minor groove, since this process does not interfere with the electrochemical oxidation of bases. The concentration-dependent decrease in the intensity of electrochemical oxidation of DNA bases allows to quantify the type of interaction and calculate the binding constants.

COVID-19 Vaccine Safety Technical (VaST) Work Group: Enhancing vaccine safety monitoring during the pandemic.

During the COVID-19 pandemic, candidate COVID-19 vaccines were being developed for potential use in the United States on an unprecedented, accelerated schedule. It was anticipated that once available, under U.S. Food and Drug Administration (FDA) Emergency Use Authorization (EUA) or FDA approval, COVID-19 vaccines would be broadly used and potentially administered to millions of individuals in a short period of time. Intensive monitoring in the post-EUA/licensure period would be necessary for timely detection and assessment of potential safety concerns. To address this, the Centers for Disease Control and Prevention (CDC) convened an Advisory Committee on Immunization Practices (ACIP) work group focused solely on COVID-19 vaccine safety, consisting of independent vaccine safety experts and representatives from federal agencies - the ACIP COVID-19 Vaccine Safety Technical Work Group (VaST). This report provides an overview of the organization and activities of VaST, summarizes data reviewed as part of the comprehensive effort to monitor vaccine safety during the COVID-19 pandemic, and highlights selected actions taken by CDC, ACIP, and FDA in response to accumulating post-authorization safety data. VaST convened regular meetings over the course of 29 months, from November 2020 through April 2023; through March 2023 FDA issued EUAs for six COVID-19 vaccines from four different manufacturers and subsequently licensed two of these COVID-19 vaccines. The independent vaccine safety experts collaborated with federal agencies to ensure timely assessment of vaccine safety data during this time. VaST worked closely with the ACIP COVID-19 Vaccines Work Group; that work group used safety data and VaST's assessments for benefit-risk assessments and guidance for COVID-19 vaccination policy. Safety topics reviewed by VaST included those identified in safety monitoring systems and other topics of scientific or public interest. VaST provided guidance to CDC's COVID-19 vaccine safety monitoring efforts, provided a forum for review of data from several U.S. government vaccine safety systems, and assured that a diverse group of scientists and clinicians, external to the federal government, promptly reviewed vaccine safety data. In the event of a future pandemic or other biological public health emergency, the VaST model could be used to strengthen vaccine safety monitoring, enhance public confidence, and increase transparency through incorporation of independent, non-government safety experts into the monitoring process, and through strong collaboration among federal and other partners.

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.

Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older - United States, 2024.

At its October 2023 meeting, the Advisory Committee on Immunization Practices* (ACIP) approved the Recommended Adult Immunization Schedule for Ages 19 Years or Older, United States, 2024. The adult immunization schedule, which can be found on the CDC immunization schedule website (https://www.cdc.gov/vaccines/schedules), is published annually to consolidate and summarize updates to ACIP recommendations on the vaccination of adults and to assist health care providers in implementing current ACIP recommendations. The 2024 immunization schedule includes several changes to the cover page, tables, notes, and appendix from the 2023 immunization schedule.† In addition, the 2024 adult immunization schedule includes a new addendum section that summarizes new or updated ACIP recommendations that will occur before the next annual update to the adult immunization schedule. Health care providers are advised to use the cover page, tables, notes, appendix, and addendum together to determine recommended vaccinations for patient populations.

Advisory Committee on Immunization Practices Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger - United States, 2024.

At its October 2023 meeting, the Advisory Committee on Immunization Practices* (ACIP) approved the Recommended Child and Adolescent Immunization Schedule for Ages 18 Years or Younger, United States, 2024. The child and adolescent immunization schedule, which can be found on the CDC immunization schedule website (https://www.cdc.gov/vaccines/schedules), is published annually to consolidate and summarize updates to ACIP recommendations on the vaccination of children and adolescents and to assist health care providers in implementing current ACIP recommendations. The 2024 immunization schedule includes several changes to the cover page, tables, notes, and appendix from the 2023 immunization schedule.† In addition, the 2024 child and adolescent immunization schedule includes a new addendum section to summarize new or updated ACIP recommendations that will occur before the next annual update to the child and adolescent immunization schedule. Health care providers are advised to use the cover page, tables, notes, appendix, and addendum together to identify the recommended immunizations for patient populations.

Communication and empathy of nursing students in patient care through telenursing: A comparative cross-sectional study.

BACKGROUND: Phone calls and videoconferences are the most widely used systems to interact with patients in real time. Patient care through phone calls or videoconferences is different from an in-person meeting. Interpersonal communication skills, self-confidence communication skills and empathy with the patient may be affected during phone calls or videoconferences. AIM: The objective of this study was to describe the interpersonal communication skills, self-confidence communication skills and empathy of nursing students during patient care through phone calls or videoconferences. DESIGN: A cross-sectional study. PARTICIPANTS: A total of 170 nursing students participated from the University of Almeria. The subjects were randomly assigned to the phone call group or videoconference group. METHODS: The students contacted standardised patients through phone calls or videoconferences. Questionnaires were used to assess interpersonal communication skills with patient, empathy, and self-confidence in communication skills. Data collection was carried out between March and May 2022. RESULTS: No statistically significant differences were found between self-confidence in communication skills with the patient and the type of consultation, nor were statistically significant differences found between the empathy of the nursing students and the type of consultation. The students who used videoconference reported higher patient interpersonal communication skills than the students who made phone calls. Finally, the participants who made videoconferences obtained a higher score in dimension therapeutic use of self than those who made phone calls. CONCLUSIONS: Nursing students have shown a high level of empathy and interpersonal communication skills with patients and a moderate level of self-confidence in communication skills, both when interacting with patients through phone calls and videoconferences. Finally, differences were found in interpersonal communication skills with patient and type of consultation. In particular, interpersonal communication skills with the patient are greater when the nursing students make a videoconference.

Primary processes in photophysics and photochemistry of a potential light-activated anti-cancer dirhodium complex.

Photophysics and photochemistry of a potential light-activated cytotoxic dirhodium complex [Rh2(µ-O2CCH3)2(bpy)(dppz)](O2CCH3)2, where bpy = 2,2'-bipyridine, dppz = dipyrido[3,2-a:2',3'-c]phenazine (Complex 1 or Rh2) in aqueous solutions was studied by means of stationary photolysis and time-resolved methods in time range from hundreds of femtoseconds to microseconds. According to the literature, Complex 1 demonstrates both oxygen-dependent (due to singlet oxygen formation) and oxygen-independent cytotoxicity. Photoexchange of an acetate ligand to a water molecule was the only observed photochemical reaction, which rate was increased by oxygen removal from solutions. Photoexcitation of Complex 1 results in the formation of the lowest triplet electronic excited state, which lifetime is less than 10 ns. This time is too short for diffusion-controlled quenching of the triplet state by dissolved oxygen resulting in 1O2 formation. We proposed that singlet oxygen is produced by photoexcitation of weakly bound van der Waals complexes [Rh2…O2], which are formed in solutions. If this is true, no oxygen-independent light-induced cytotoxicity of Complex 1 exists. Residual cytotoxicity deaerated solutions are caused by the remaining [Rh2…O2] complexes.

Effective communication between nursing professionals and patients after the implementation of mask-wearing requirements in the clinical setting: A cross-sectional study.

This study aimed to evaluate staff nurses' perspectives on the use of face masks in effective communication and relationship management skills with patients in the hospital setting. The study surveyed registered nurses (RNs) who work with adult patients in different hospital units. An online survey was completed by RNs who were selected by convenience sampling. RNs' communication with patients was perceived as moderately affected by the use of face masks. Statistically significant differences were found when comparing communication with years of professional experience. Participants who had over 10 years of experience reported having greater difficulty in their communication with patients when using face masks. The effect of provider-patient relationship on effective nurse-patient face-mask communication was statistically significant and negative. This study shows that some participants found face masks used in the clinical setting may affect nurse-patient communication, as well as the nurses' ability to manage their relationships with patients. The findings of this study support the need for targeted research into effective communication strategies when face mask use is needed in the healthcare setting.

Complex Regional Pain Syndrome Type I: Evidence for the CB1 and CB2 Receptors Immunocontent and Beneficial Effect of Local Administration of Cannabidiol in Mice.

Introduction: Complex regional pain syndrome type I (CRPS-I) is a debilitating neuropathic painful condition associated with allodynia, hyperalgesia, sudomotor and/or vasomotor dysfunctions, turning investigation of its pathophysiology and new therapeutic strategies into an essential topic. We aim to investigate the impact of ischemia/reperfusion injury on the immunocontent of CB1 and CB2 cannabinoid receptor isoforms in the paws of mice submitted to a chronic postischemia pain (CPIP) model and the effects of local administration of cannabidiol (CBD) on mechanical hyperalgesia. Methods: Female Swiss mice, 30-35 g, were submitted to the CPIP model on the right hind paw. Skin and muscle samples were removed at different periods for western blot analysis. Results: No changes in the immunocontent of CB1 and CB2 receptors in paw muscle tissues after ischemia-reperfusion were observed. CBD promoted an antihyperalgesic effect in both phases. AM281 reversed the effect of CBD, whereas ruthenium red abolished the late phase. Conclusion: Our results point to the possible beneficial effects of local administration of CBD in modulating CRPS-I in humans. As possible targets for CBD antihyperalgesia in this model, the contribution of cannabinoid receptor CB1, in addition to TRPM8 is suggested.

Protection of homologous and heterologous boosters after primary schemes of rAd26-rAd5, ChAdOx1 nCoV-19 and BBIBP-CorV during the omicron outbreak in adults of 50 years and older in Argentina: a test-negative case-control study.

Background: After primary vaccination schemes with rAd26-rAd5 (Sputnik V), ChAdOx1 nCoV-19, BBIBP-CorV or heterologous combinations, the effectiveness of homologous or heterologous boosters (Sputnik V, ChAdOx, Pfizer-BioNTech, Moderna) against SARS-CoV-2 infections, hospitalisations and deaths has been scarcely studied. Methods: Test-negative, case-control study, conducted in Argentina during omicron BA.1 predominance, in adults ≥50 years old tested for SARS-CoV-2 who had received two or three doses of COVID-19 vaccines. Outcomes were COVID-associated infections, hospitalisations and deaths after administering mRNA and vectored boosters, < or ≥60 days from the last dose. Findings: Of 422,124 individuals tested for SARS-CoV-2, 221,993 (52.5%) tested positive; 190,884 (45.2%) and 231,260 (54.8%) had received 2-dose and 3-dose vaccination schemes, respectively. The 3-dose scheme reduced infections, hospitalisations and death (OR 0.81 [0.80-0.83]; 0.28 [0.25-0.32] and 0.25 [0.22-0.28] respectively), but protection dropped after 60 days to 1.04 [1.01-1.06]; 0.52 [0.44-0.61] and 0.38 [0.33-0.45]). Compared with 2-dose-schemes, homologous boosters after primary schemes with vectored-vaccines provided lower protection against infections < and ≥60 days (0.94 [0.92-0.97] and 1.05 [1.01-1.09], respectively) but protected against hospitalisations (0.30 [0.26-0.35]) and deaths (0.29 [0.25-0.33]), decreasing after 60 days (0.59 [0.47-0.74] and 0.51 [0.41-0.64], respectively). Heterologous boosters protected against infections (0.70 [0.68-0.71]) but decreased after 60 days (1.01 [0.98-1.04]) and against hospitalisations and deaths (0.26 [0.22-0.31] and 0.22 [0.18-0.25], respectively), which also decreased after 60 days (0.43 [0.35-0.53] and 0.33 [0.26-0.41], respectively). Heterologous boosters protected against infections when applied <60 days (0.70 [0.68-0.71], p < 0.001), against hospitalisations when applied ≥60 days (0.43 [0.35-0.53], p < 0.01), and against deaths < and ≥60 days (0.22 [0.18-0.25], p < 0.01 and 0.33 [0.26-0.41], p < 0.001). Interpretation: During omicron predominance, heterologous boosters such as viral vectored and mRNA vaccines, following Sputnik V, ChAdOx1, Sinopharm or heterologous primary schemes might provide better protection against death; this effect might last longer in individuals aged ≥50 than homologous boosters. Funding: None.

Proteomic and genetic analyses of influenza A viruses identify pan-viral host targets.

Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases. Whole exome sequencing of patients who experienced severe influenza reveals several genes, including scaffold protein AHNAK, with predicted loss-of-function variants that are also identified in our proteomic analyses. Of our identified host factors, 54 significantly alter IAV infection upon siRNA knockdown, and two factors, AHNAK and coatomer subunit COPB1, are also essential for productive infection by SARS-CoV-2. Finally, 16 compounds targeting our identified host factors suppress IAV replication, with two targeting CDK2 and FLT3 showing pan-antiviral activity across influenza and coronavirus families. This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT.

Immobilization of Bacteriophages in Ex Tempore Hydrogel for the Treatment of Burn Wound Infection.

The resistance of bacteria to antibiotics is a major problem for anti-bacterial therapy. This problem may be solved by using bacteriophages-viruses that can attack and destroy bacteria, including antibiotic-resistant ones. In this article, the authors compared the efficacy of topical bacteriophage therapy and systemic antibiotic therapy in the treatment of wound infections caused by ESKAPE pathogens in patients with limited (less than 5% of the body surface) full-thickness burns. Patients in the study group (n = 30) were treated with PVA-based hydrogel dressings saturated ex tempore with a bacteriophage suspension characterized by its lytic activity against the bacteria colonizing the wound. Patients in the control group (n = 30) were treated using etiotropic systemic antibiotic therapy, and the wounds were covered with gauze bandages soaked in an aqueous solution of povidone-iodine. An assessment of the decrease in the level of bacterial contamination of the recipient wounds in both groups was conducted after 7 days, and after that, free skin grafting was performed. On day 14 after free skin grafting, patients in both groups underwent incisional biopsy. The study group demonstrated an increase in the indices of proliferative activity (Ki-67), and angiogenesis (CD-31, VEGF) in the area of engraftment of the split-thickness skin grafts. The results indicate that PVA-based hydrogel wound dressings can be used as bacteriophage carriers for local antimicrobial therapy ahead of free skin grafting.

Novel B2 mitogenomes from Continental southern Patagonia's Late Holocene: New insights into the peopling of the Southern Cone.

OBJECTIVES: The main aim of this study is to discuss the migratory processes and peopling dynamics that shaped the genetic variability of populations during the settlement of the Southern Cone, through the analysis of complete mitogenomes of individuals from southern Patagonia. MATERIALS AND METHODS: Complete mitogenomes were sequenced through massively parallel sequencing from two late Holocene individuals (SAC 1-1-3 and SAC 1-1-4) buried in the same chenque at Salitroso Lake Basin (Santa Cruz province, Argentina). To evaluate matrilineal phylogenetic affinities with other haplotypes, maximum likelihood and Bayesian phylogenetic reconstructions were performed, as well as a haplotype median-joining network. RESULTS: The mitogenomes were assigned to haplogroups B2 and B2b, exhibiting an average depth of 54X and 89X (≥1X coverage of 98.6% and 100%), and a high number of nucleotide differences among them. The phylogenetic analyses showed a relatively close relationship between the haplotype found in SAC 1-1-4 and those retrieved from a Middle Holocene individual from Laguna Chica (Buenos Aires province), and from a group of individuals from the Peruvian coast. For the SAC 1-1-3, no clear affiliations to any other haplotype were established. DISCUSSION: The large divergence between the haplotypes presented in this study suggests either a highly variable founder gene pool, or a later enrichment by frequent biological contact with other populations. Our results underline the persistence of genetic signals related to the first waves of peopling in South America, suggesting that the regional settlement of the southern end of the continent has been much more complex than initially thought.

OBJETIVOS: El objetivo principal de este estudio es discutir los procesos migratorios y la dinámica de poblamiento que moldearon la variabilidad genética de las poblaciones durante el poblamiento del Cono Sur, a través del análisis de mitogenomas completos de individuos del sur de Patagonia. MATERIALES Y MÉTODOS: Se obtuvieron mitogenomas completos mediante secuenciación masiva de dos individuos del Holoceno tardío (SAC 1-1-3 y SAC 1-1-4) enterrados en el mismo chenque en la Cuenca del Lago Salitroso (provincia de Santa Cruz, Argentina). Para evaluar las afinidades matrilineales con otros haplotipos, se realizaron reconstrucciones filogenéticas de máxima verosimilitud y bayesianas, así como una red mediana de haplotipos. RESULTADOS: Los mitogenomas fueron asignados a los haplogrupos B2 y B2b, exhibiendo una profundidad de secuenciación promedio de 54X y 89X (cobertura ≥1X de 98,6% y 100%), y un elevado número de diferencias nucleotídicas entre ellos. Los análisis filogenéticos mostraron una relación relativamente estrecha entre el haplotipo encontrado en el SAC 1-1-4 y los recuperados de un individuo del Holoceno Medio de Laguna Chica (provincia de Buenos Aires), y de un grupo de individuos de la costa peruana. Para el SAC 1-1-3, no se establecieron relaciones claras con ningún otro haplotipo. DISCUSIÓN: La gran divergencia entre los haplotipos presentados en este estudio sugiere gran variabilidad en el acervo genético fundador, o bien un enriquecimiento posterior por contacto biológico frecuente con otras poblaciones. Nuestros resultados destacan la persistencia de señales genéticas relacionadas con las primeras oleadas de poblamiento de Sudamérica, lo que sugiere que el poblamiento regional del extremo sur del continente ha sido mucho más complejo de lo que se pensaba inicialmente.

Effect of an NGR Peptide on the Efficacy of the Doxorubicin Phospholipid Delivery System.

This study is a continuation of an investigation into the effect of a targeted component, a peptide with an NGR, on the properties of the previously developed doxorubicin phospholipid delivery system. The NGR peptide has an affinity for aminopeptidase N (known as the CD13 marker on the membrane surface of tumor cells) and has been extensively used to target drug delivery systems. This article presents the results of a study investigating the physical properties of the phospholipid composition with and without the peptide chain: particle size, zeta potential, stability in fluids, and dependence of doxorubicin release from nanoparticles at different pH levels (5.0, 6.5, 7.4). The cytotoxic effect of the compositions has also been shown to depend on the dose of the drug used for incubation, the presence of the targeted component in the composition, and the time of incubation time of the substances. There was a significant difference in the cytotoxic effect on HT-1080 (CD13-positive) and MCF-7 (CD13-negative) cells. Cell death pathway analysis has shown that death occurred mainly by apoptosis. We also present data on the effect of doxorubicin embedded in phospholipid nanoparticles with the targeted peptide on DNA assessed by differential pulse voltammetry, the mechanism of action being electrostatic interactions. The interactions of native dsDNA with doxorubicin encapsulated in phospholipid nanoparticles with the targeted peptide were studied electrochemically by differential pulse voltammetry. Here, we have highlighted that the targeted peptide in the doxorubicin composition moved specific interaction of the drug with dsDNA from intercalative mode to electrostatic interactions.

A conformational rearrangement of the SARS-CoV-2 host protein sigma-1 is required for antiviral activity: insights from a combined in-silico/in-vitro approach.

The development of effective drugs to treat coronavirus infections remains a significant challenge for the scientific community. Recent evidence reports on the sigma-1 receptor (S1R) as a key druggable host protein in the SARS-CoV-1 and SARS-CoV-2 interactomes and shows a potent antiviral activity against SARS-CoV-2 for the S1R antagonist PB28. To improve PB28 activity, we designed and tested a series of its analogues and identified a compound that is fourfold more potent against SARS-CoV-2 than PB28 itself. Interestingly, we found no direct correlation between S1R affinity and SARS-CoV-2 antiviral activity. Building on this, we employed comparative induced fit docking and molecular dynamics simulations to gain insights into the possible mechanism that occurs when specific ligand-protein interactions take place and that may be responsible for the observed antiviral activity. Our findings offer a possible explanation for the experimental observations, provide insights into the S1R conformational changes upon ligand binding and lay the foundation for the rational design of new S1R ligands with potent antiviral activity against SARS-CoV-2 and likely other viruses.

Interaction of Doxorubicin Embedded into Phospholipid Nanoparticles and Targeted Peptide-Modified Phospholipid Nanoparticles with DNA.

The interactions of dsDNA with new targeted drug delivery derivatives of doxorubicin (DOX), such as DOX embedded into phospholipid nanoparticles (NPhs) and DOX with the NGR targeted peptide-modified NPhs were studied electrochemically by differential pulse voltammetry technique. Screen-printed electrodes (SPEs), modified with stable fine dispersions of carbon nanotubes (CNTs), were used for quantitative electrochemical investigations of direct electrochemical oxidation of guanine, adenine, and thymine heterocyclic bases of dsDNA, and their changes in the presence of DOX nanoderivatives. Analysing the shifts of peak potentials of nucleobases in the presence of drug, we have shown that the doxorubicin with NGR targeted peptide changed the mode of interaction in DNA-drug complexes from intercalative to electrostatic. Binding constants (Kb) of DNA-drug complexes were calculated in accordance with adenine, guanine, and thymine oxidation signals. Based on our experiments, we have proven that the surface modification of a drug delivery system with NGR targeted peptide dramatically changed the mechanism of interaction of drug with genetic material. DNA-mediated drug toxicity was calculated based on the concentration-dependent "response" of heterocyclic nucleobases on drug influence. DOX, DOX-loaded phospholipid nanoparticles (NPhs), and DOX with NGR addressed peptide-modified NPhs were moderately toxic in the concentration range of 0.5-290 µM.

Safety and immunogenicity of a SARS-CoV-2 Gamma variant RBD-based protein adjuvanted vaccine used as booster in healthy adults.

A Gamma Variant RBD-based aluminum hydroxide adjuvanted vaccine called ARVAC CG was selected for a first in human clinical trial. Healthy male and female participants (18-55 years old) with a complete COVID-19-primary vaccine scheme were assigned to receive two intramuscular doses of either a low-dose or a high-dose of ARVAC CG. The primary endpoint was safety. The secondary objective was humoral immunogenicity. Cellular immune responses were studied as an exploratory objective. The trial was prospectively registered in PRIISA.BA (Registration Code 6564) and ANMAT and retrospectively registered in ClinicalTrials.gov (NCT05656508). Samples from participants of a surveillance strategy implemented by the Ministry of Health of the Province of Buenos Aires that were boosted with BNT162b2 were also analyzed to compare with the booster effect of ARVAC CG. ARVAC CG exhibits a satisfactory safety profile, a robust and broad booster response of neutralizing antibodies against the Ancestral strain of SARS-CoV-2 and the Gamma, Delta, Omicron BA.1 and Omicron BA.5 variants of concern and a booster effect on T cell immunity in individuals previously immunized with different COVID-19 vaccine platforms.