Association of viral loads of influenza A (H3N2) with age and care setting on presentation-a prospective study during the 2022-2023 influenza season in Spain.

OBJECTIVES: The aim of this study was to analyze the viral load (VL) using cycle threshold (Ct) in patients infected with influenza A (H3N2). METHODS: This prospective study was conducted during the 2022-2023 influenza season in sentinel, non-sentinel, and hospitalized patients of Castilla y León (Spain). Respiratory samples were obtained from nasopharyngeal swabs and analyzed by quantitative reverse transcription-polymerase chain reaction specific for influenza A (H3N2) to obtain the Ct value. RESULTS: A total of 1047 individuals were enrolled (174 [16.6%] sentinel, 200 [19.1%] non-sentinel, 673 [64.3%] hospitalized). The mean Ct value was lower in infants, young children, and in the elderly, with a sharp increase in the last from 65 years until 90 years. In addition, the lower Ct values were observed in non-sentinel patients and then in hospitalized patients, probably because non-sentinel are outpatients in the acute phase of the influenza infection. CONCLUSIONS: A higher VL (lower Ct value) is related to the extreme ages of life: children and the elderly. Furthermore, a higher VL is related with the care setting, being probably higher in outpatients because they are in the acute phase of the disease and slightly lower in hospitalized patients because they are attended during the post-acute phase.

Potential Effects on Elderly People From Nirsevimab Use in Infants.

Nirsevimab therapy has the potential to revolutionize infant respiratory syncytial virus (RSV) prophylaxis. But other populations suffering RSV, such the elderly or those over 60, may also be protected by using this novel antibody in the infant group. It is true that some studies link the use of nirsevimab to a reduction in the virus's ability to spread by lowering the viral load in infants as a result of the drug's long half-life. However, this protective effect may not be very significant because RSV transmission in the elderly typically comes from other elderly people or from school-aged children. Furthermore, RSV may be transmitted at any time of the year and not just during the period of nirsevimab protection due to its existence in human reservoirs. The reasons made here show that, even though nirsevimab treatment in infants may protect the elderly, this benefit would be limited and testimonial. Therefore, immunizing the elderly with currently licensed and developing vaccines should be a priority.

El uso de nirsevimab puede suponer una revolución en la prevención del virus respiratorio sincitial (VRS) en lactantes. Sin embargo, el uso de este nuevo anticuerpo en dicho grupo de edad podría proteger también a otros grupos que conviven con ellos, como por ejemplo las personas de edad avanzada o grupo de personas mayores de 60 años. Si bien es cierto que algunos estudios sugieren una disminución en la propagación del virus con el uso de nirsevimab, al reducir la carga viral en lactantes como consecuencia de la prolongada vida media del fármaco, este efecto protector podría ser de escasa relevancia, ya que la transmisión del VRS en personas de edad avanzada sucede en la mayor parte de los casos desde personas de la misma edad o desde niños en edad escolar. Adicionalmente, la presencia de VRS en reservorios humanos puede permitir que el VRS se transmita en cualquier época del año, no limitándose únicamente al periodo de protección de nirsevimab. Los argumentos aquí expuestos demuestran que, si bien el uso de nirsevimab en lactantes podría tener un efecto protector en las personas de edad avanzada, este solo sería testimonial y limitado. En consecuencia, debe priorizarse la inmunización de los pacientes de edad avanzada con las vacunas actualmente autorizadas y en desarrollo.

Dosimetric study for breathing-induced motion effects in an abdominal pancreas phantom for carbon ion mini-beam radiotherapy.

BACKGROUND: Particle mini-beam therapy exhibits promise in sparing healthy tissue through spatial fractionation, particularly notable for heavy ions, further enhancing the already favorable differential biological effectiveness at both target and entrance regions. However, breathing-induced organ motion affects particle mini-beam irradiation schemes since the organ displacements exceed the mini-beam structure dimensions, decreasing the advantages of spatial fractionation. PURPOSE: In this study, the impact of breathing-induced organ motion on the dose distribution was examined at the target and organs at risk(OARs) during carbon ion mini-beam irradiation for pancreatic cancer. METHODS: As a first step, the carbon ion mini-beam pattern was characterized with Monte Carlo simulations. To analyze the impact of breathing-induced organ motion on the dose distribution of a virtual pancreas tumor as target and related OARs, the anthropomorphic Pancreas Phantom for Ion beam Therapy (PPIeT) was irradiated with carbon ions. A mini-beam collimator was used to deliver a spatially fractionated dose distribution. During irradiation, varying breathing motion amplitudes were induced, ranging from 5 to 15 mm. Post-irradiation, the 2D dose pattern was analyzed, focusing on the full width at half maximum (FWHM), center-to-center distance (ctc), and the peak-to-valley dose ratio (PVDR). RESULTS: The mini-beam pattern was visible within OARs, while in the virtual pancreas tumor a more homogeneous dose distribution was achieved. Applied motion affected the mini-beam pattern within the kidney, one of the OARs, reducing the PVDR from 3.78  ± $\pm$  0.12 to 1.478  ± $\pm$  0.070 for the 15 mm motion amplitude. In the immobile OARs including the spine and the skin at the back, the PVDR did not change within 3.4% comparing reference and motion conditions. CONCLUSIONS: This study provides an initial understanding of how breathing-induced organ motion affects spatial fractionation during carbon ion irradiation, using an anthropomorphic phantom. A decrease in the PVDR was observed in the right kidney when breathing-induced motion was applied, potentially increasing the risk of damage to OARs. Therefore, further studies are needed to explore the clinical viability of mini-beam radiotherapy with carbon ions when irradiating abdominal regions.

Importancia de los Centros Nacionales de Gripe en la vigilancia de virus aviares de alta patogenicidad. El momento para One-Healthes ahora / Importance of National Influenza Centers in the surveillance of highly pathogenic avian viruses. The time for One-Health is now

Desde el año 1996 el subtipo de gripe aviar de alta patogenicidad A(H5N1) ha estado casi de forma ininterrumpida causando brotes en aves salvajes y domésticas, además de casos en seres humanos con una mortalidad cercana al 50%. Sin embargo, los años de mayor circulación han sido precisamente los años posteriores a la pandemia de COVID-19, en los que se han registrado diversos casos en humanos en lugares donde nunca antes habían aparecido, además de múltiples casos en mamíferos salvajes, domésticos y peri domésticos, que entrañan cierta preocupación por el riesgo que puede suponer para el salto del virus al ser humano través de cadenas de transmisión de mayor o menor extensión. El brote actual de A(H5N1) nos muestra que el concepto One-Health debe estar más vivo que nunca para aunar esfuerzos entre profesionales de diferentes sectores de la sanidad humana, animal y medio ambiental para evitar o minimizar estos riesgos, de tal forma que los laboratorios de referencia como los Centros Nacionales de Gripe dispongan de los medios humanos y materiales para ofrecerinformación rápida y relevante en el menor tiempo posible antes emergencias de este tipo. Las herramientas de diagnóstico y seguimiento que se deben utilizar en estos casos deben estar disponibles para cualquier eventualidad, y llegar más allá de los datos básicos debe ser una premisa indispensable para poder hacer un seguimiento pormenorizado que sirva para acotar brotes, limitar la difusión de la enfermedad, y ayudar al diseño de futuras vacunas pandémicas frente a virus aviares. (AU)

Since 1996, the highly pathogenic avian influenza subtype A(H5N1) has been causing almost uninterrupted outbreaks in wild and domestic birds, as well as cases in humans with a mortality rate close to 50%. However, the years of greatest circulation have been precisely the years following the COVID-19 pandemic, in which several cases have been recorded in humans in places where they had never appeared before, in addition to multiple cases in wild, domestic and peri-domestic mammals, which raise some concern about the risk that the virus may jump to humans through chains of transmission of greater or lesser extent. The current outbreak of A(H5N1) shows us that the One-Health concept should be more alive than ever to join efforts between professionals from different sectors of human, animal and environmental health to avoid or minimize these risks, so that reference laboratories such as the National Influenza Centers have the human and material resources to provide rapid and relevant information in the shortest possible time before emergencies of this type. The diagnostic and monitoring tools to be used in these cases must be available for any eventuality, and going beyond the basic data must be an indispensable premise to be able to carry out a detailed monitoring that serves to limit outbreaks, limit the spread of the disease, and help in the design of future pandemic vaccines against avian viruses. (AU)

Linear Energy Transfer Measurements and Estimation of Relative Biological Effectiveness in Proton and Helium Ion Beams Using Fluorescent Nuclear Track Detectors.

PURPOSE: Our objective was to develop a methodology for assessing the linear energy transfer (LET) and relative biological effectiveness (RBE) in clinical proton and helium ion beams using fluorescent nuclear track detectors (FNTDs). METHODS AND MATERIALS: FNTDs were exposed behind solid water to proton and helium (4He) ion spread-out Bragg peaks. Detectors were imaged with a confocal microscope, and the LET spectra were derived from the fluorescence intensity. The track- and dose-averaged LET (LETF and LETD, respectively) were calculated from the LET spectra. LET measurements were used as input on RBE models to estimate the RBE. Human alveolar adenocarcinoma cells (A549) were exposed at the same positions as the FNTDs. The RBE was calculated from the resulting survival curves. All measurements were compared with Monte Carlo simulations. RESULTS: For protons, average relative differences between measurements and simulations were 6% and 19% for LETF and LETD, respectively. For helium ions, the same differences were 11% for both quantities. The position of the experimental LET spectra primary peaks agreed with the simulations within 9% and 14% for protons and helium ions, respectively. For the RBE models using LETD as input, FNTD-based RBE values ranged from 1.02 ± 0.01 to 1.25 ± 0.04 and from 1.08 ± 0.09 to 2.68 ± 1.26 for protons and helium ions, respectively. The average relative differences between these values and simulations were 2% and 4%. For A549 cells, the RBE ranged from 1.05 ± 0.07 to 1.47 ± 0.09 and from 0.89 ± 0.06 to 3.28 ± 0.20 for protons and helium ions, respectively. Regarding the RBE-weighted dose (2.0 Gy at the spread-out Bragg peak), the differences between simulations and measurements were below 0.10 Gy. CONCLUSIONS: This study demonstrates for the first time that FNTDs can be used to perform direct LET measurements and to estimate the RBE in clinical proton and helium ion beams.

Factors associated to the presence of headache in patients with influenza infection and its consequences: a 2010-2020 surveillance-based study.

Headache is a common symptom of influenza infection; however, its causes and consequences remain uncertain. In this manuscript, we analyzed which demographic and clinical factors were associated with the presence of headache during the course of influenza infection and whether patients with headache had a different prognosis, evaluated by need of hospitalization, sick leave or school absenteeism. The influence study (NCT05704335) was an observational study that analyzed data routinely collected from the Health Sentinel Network between 2010 and 2020. During the study period, 7832 cases were considered, among which, 5275 (67.4%) reported headache. The presence of headache was independently associated with myalgia (2.753; 95%CI: 2.456-3.087, P < 0.001), asthenia (OR: 1.958; 95%CI: 1.732-2.214, P < 0.001), shivering (OR: 1.925; 95%CI: 1.718-2.156, P < 0.001), nasopharyngeal erythema (OR: 1.505; 95%CI: 1.293-1.753, P < 0.001), fever (OR: 1.469; 95%CI: 1.159-1.861; P = 0.001), sudden onset of symptoms (OR: 1.380; 95%CI: 1.120-1.702, p = 0.004), female sex (OR: 1.134; 95%CI: 1.023-1.257, P = 0.018), and gastrointestinal symptoms (OR: 1.169; 95%CI: 1.039-1.315; P = 0.01). Patients with headache had a sex and age adjusted lower odds of being referred to the hospital (OR: 0.463; 95%CI: 0.264-0.812, P = 0.007) and a higher odd of having a sick leave and/or school absenteeism (absenteeism (OR: 1.342; 95%CI: 1.190-1.514, P < 0.001). In conclusion, the presence of headache seems associated with symptoms caused by the innate immune response. These findings support a headache pathophysiology linked with the innate immune response. Due to the potential negative consequences and its treatable nature, clinicians should systematically evaluate it and, whenever necessary, treat it too.

Early estimates of nirsevimab immunoprophylaxis effectiveness against hospital admission for respiratory syncytial virus lower respiratory tract infections in infants, Spain, October 2023 to January 2024.

The monoclonal antibody nirsevimab was at least 70% effective in preventing hospitalisations in infants with lower respiratory tract infections (LRTI) positive for respiratory syncytial virus (RSV) in Spain (Oct 2023-Jan 2024), where a universal immunisation programme began late September (coverage range: 79-99%). High protection was confirmed by two methodological designs (screening and test-negative) in a multicentre active surveillance in nine hospitals in three regions. No protection against RSV-negative LRTI-hospitalisations was shown. These interim results could guide public-health decision-making.

Impact on the time elapsed since SARS-CoV-2 infection, vaccination history, and number of doses, on protection against reinfection.

SARS-CoV-2 reinfections have been frequent, even among those vaccinated. The aim of this study is to know if hybrid immunity (infection + vaccination) is affected by the moment of vaccination and number of doses received. We conducted a retrospective study in 746 patients with a history of COVID-19 reinfection and recovered the dates of infection and reinfection and vaccination status (date and number of doses). To assess differences in the time to reinfection(tRI) between unvaccinated, vaccinated before 6 months, and later; and comparing one, two or three doses (incomplete, complete and booster regime) we performed the log-rank test of the cumulative incidence calculated as 1 minus the Kaplan-Meier estimator. Also, an adjusted Cox-regression was performed to evaluate the risk of reinfection in all groups. The tRI was significantly higher in those vaccinated vs. non-vaccinated (p < 0.001). However, an early incomplete regime protects similar time than not receiving a vaccine. Vaccination before 6 months after infection showed a lower tRI compared to those vaccinated later with the same regime (adj-p < 0.001). Actually, early vaccination with complete and booster regimes provided lower length of protection compared to vaccinating later with incomplete and complete regime, respectively. Vaccination with complete and booster regimes significantly increases the tRI (adj-p < 0.001). Vaccination increases the time it takes for a person to become reinfected with SARS-CoV-2. Increasing the time from infection to vaccination increases the time in which a person could be reinfected and reduces the risk of reinfection, especially in complete and booster regimes. Those results emphasize the role of vaccines and boosters during the pandemic and can guide strategies on future vaccination policy.

A Monte Carlo study on the secondary neutron generation by oxygen ion beams for radiotherapy and its comparison to lighter ions.

Objective.To study the secondary neutrons generated by primary oxygen beams for cancer treatment and compare the results to those from primary protons, helium, and carbon ions. This information can provide useful insight into the positioning of neutron detectors in phantom for future experimental dose assessments.Approach.Mono-energetic oxygen beams and spread-out Bragg peaks were simulated using the Monte Carlo particle transport codesFLUktuierende KAskade, tool for particle simulation, and Monte Carlo N-Particle, with energies within the therapeutic range. The energy and angular distribution of the secondary neutrons were quantified.Main results.The secondary neutron spectra generated by primary oxygen beams present the same qualitative trend as for other primary ions. The energy distributions resemble continuous spectra with one peak in the thermal/epithermal region, and one other peak in the fast/relativistic region, with the most probable energy ranging from 94 up to 277 MeV and maximum energies exceeding 500 MeV. The angular distribution of the secondary neutrons is mainly downstream-directed for the fast/relativistic energies, whereas the thermal/epithermal neutrons present a more isotropic propagation. When comparing the four different primary ions, there is a significant increase in the most probable energy as well as the number of secondary neutrons per primary particle when increasing the mass of the primaries.Significance.Most previous studies have only presented results of secondary neutrons generated by primary proton beams. In this work, secondary neutrons generated by primary oxygen beams are presented, and the obtained energy and angular spectra are added as supplementary material. Furthermore, a comparison of the secondary neutron generation by the different primary ions is given, which can be used as the starting point for future studies on treatment plan comparison and secondary neutron dose optimisation. The distal penumbra after the maximum dose deposition appears to be a suitable location for in-phantom dose assessments.

InfluenCEF study: Clinical phenotype and duration of headache attributed to influenza infection.

INTRODUCTION: Headache is a frequent symptom of infections. We aimed to characterize the clinical phenotype and duration of headache attributed to influenza infection. METHODS: Prospective cohort study done in 53 primary care centers between January and April 2023. Patients were included if they had a confirmed influenza diagnosis, were older than 15 years and had a new-onset headache. Patients' demographics, prior medical history, headache phenotype and duration, associated symptoms and patients' outcomes were assessed. The International Classification of Headache Disorders criteria for headache attributed to a systemic viral infection, migraine and tension-type headache were assessed. RESULTS: Of the 478 patients 75 fulfilled eligibility criteria. The mean age was 43, 56% were men, and 27% had a prior headache history. The headache phenotype was a bilateral headache (52%), with frontal topography (48%), pressing quality (61%), moderate intensity, rhinorrhea (79%), nasal congestion (76%), and photophobia (59%). All patients fulfilled headache attributed to acute systemic viral infection criteria, 43% fulfilled migraine criteria and 31% tension-type headache criteria. The median duration of the headache was four (Inter-quartile range: two-six) days. CONCLUSION: The clinical phenotype of headache attributed to influenza infection was similar to other infections, with more pronounced cranial autonomic symptoms. The headache was an early symptom and was self-limited within a few days.Trial Registration: The study protocol is registered in ClinicalTrial.gov (NCT05704335).

A phantom to simulate organ motion and its effect on dose distribution in carbon ion therapy for pancreatic cancer.

Objective. Carbon ion radiotherapy is a promising radiation technique for malignancies like pancreatic cancer. However, organs' motion imposes challenges for achieving homogeneous dose delivery. In this study, an anthropomorphicPancreasPhantom forIon-beamTherapy (PPIeT) was developed to simulate breathing and gastrointestinal motion during radiotherapy.Approach. The developed phantom contains a pancreas, two kidneys, a duodenum, a spine and a spinal cord. The shell of the organs was 3D printed and filled with agarose-based mixtures. Hounsfield Units (HU) of PPIeTs' organs were measured by CT. The pancreas motion amplitude in cranial-caudal (CC) direction was evaluated from patients' 4D CT data. Motions within the obtained range were simulated and analyzed in PPIeT using MRI. Additionally, GI motion was mimicked by changing the volume of the duodenum and quantified by MRI. A patient-like treatment plan was calculated for carbon ions, and the phantom was irradiated in a static and moving condition. Dose measurements in the organs were performed using an ionization chamber and dosimetric films.Main results. PPIeT presented tissue equivalent HU and reproducible breathing-induced CC displacements of the pancreas between (3.98 ± 0.36) mm and a maximum of (18.19 ± 0.44) mm. The observed maximum change in distance of (14.28 ± 0.12) mm between pancreas and duodenum was consistent with findings in patients. Carbon ion irradiation revealed homogenous coverage of the virtual tumor at the pancreas in static condition with a 1% deviation from the treatment plan. Instead, the dose delivery during motion with the maximum amplitude yielded an underdosage of 21% at the target and an increased uncertainty by two orders of magnitude.Significance. A dedicated phantom was designed and developed for breathing motion assessment of dose deposition during carbon ion radiotherapy. PPIeT is a unique tool for dose verification in the pancreas and its organs at risk during end-to-end tests.

The Impact of the COVID-19 Pandemic on Influenza Vaccination Attitudes and Actions in Spain's Adult Population.

Seasonal influenza is an acute respiratory infection caused by the influenza virus which constitutes a significant public health issue associated with high morbidity and mortality. The aim of this study was to investigate changes in attitudes, perceptions, and practices regarding influenza vaccination in the Spanish adult population during the COVID-19 pandemic, as well as their vaccination intentions, with special attention paid to those over 65 years old and in high-risk groups. To this end, a cross-sectional study was conducted through 2219 telephone interviews, and the results were compared with results obtained a year earlier. Regarding the reasons for deciding to get vaccinated in the 2022/23 season, a significant increase was observed in vaccine confidence (36.7% vs. 42.8%), social responsibility (32.5% vs. 43.8%), and in awareness of the importance of vaccination due to COVID-19 (21.7% vs. 25.4%). Advanced age (OR 2.8, 95% CI 2.0-3.9), belonging to high-risk groups (OR 2.7, 95% CI 2.0-3.7), and prior vaccination (OR 25.3, 95% CI 19.5-32.7) emerged as significant predictors for the intent to receive the influenza vaccine in the 2022/23 season. Continuously observing shifts in perceptions and behaviors related to influenza immunization is crucial to pinpoint factors that may influence the willingness to receive the vaccine and, in this way, design public health strategies that achieve a greater acceptance of it.

Nuevos y viejos aspectos de la gripe / Old and new aspects of influenza

La gripe es una enfermedad infecciosa clásica que, a través de la continua variación que experimentan los virus que la producen, nos impone nuevos retos que debemos solventar con la mayor celeridad posible. La pandemia de COVID-19 ha modificado sustancialmente el comportamiento de la gripe y de otros virus respiratorios, y en los próximos años tendremos que convivir con un nuevo patógeno que probablemente interactuará con los existentes bajo un prisma que de momento no alcanzamos a vislumbrar. Sin embargo, los conocimientos previos a la pandemia nos permiten focalizar en los aspectos que se deben modificar para que la gripe sea un reto asumible a futuro. En esta revisión se hace hincapié en los aspectos más relevantes de la epidemiología, la carga de enfermedad, el diagnóstico y la prevención mediante vacunas, y cómo fluyen las tendencias científicas y clínicas en dichos aspectos desde lo anteriormente conocido a los retos futuros (AU)

Influenza is a classic infectious disease that, through the continuous variation of the viruses that produce it, imposes new challenges that we must solve as quickly as possible. The COVID-19 pandemic has substantially modified the behavior of influenza and other respiratory viruses, and in the coming years we will have to coexist with a new pathogen that will probably interact with existing pathogens in a way that we cannot yet glimpse. However, knowledge prior to the pandemic allows us to focus on the aspects that must be modified to make influenza an acceptable challenge for the future. In this review, emphasis is placed on the most relevant aspects of epidemiology, disease burden, diagnosis, and vaccine prevention, and how scientific and clinical trends in these aspects flow from the previously known to future challenges (AU)

Long-term influenza antibodies profiles in previously vaccinated and non-vaccinated adults.

The aim of this work is to describe the dynamics of influenza antibodies after vaccination in adults. We conducted a case-cohort serological study in the automobile manufacturing plants of the Renault España S.A. group in Valladolid and Palencia (Spain), including 550 workers (66.9%) previously vaccinated against influenza (group V), and 272 (33.1%) never vaccinated (group NV). A pre-vaccination serum sample was collected, another after 30-40 days and another after 6 months. The dynamics of antibodies were analyzed. A lower seroprotection of NV before vaccination was observed, but an antibody response between 2 and 4 times higher than in V was assessed. After 6 months, antibodies declined in both groups until equalize. Antibodies titers decrease with age, and no differences were found among underlying pathologies. Adults never vaccinated against influenza had lower seroprotection than those previously vaccinated, but influenza vaccination produces a more intense serological response in them, acquiring significantly higher antibody titers than those previously vaccinated. The antibodies, although in lower titers, persist and equalize among both groups at least 6 months after vaccination, which allows the individual to be protected during the entire circulation of the influenza virus in the same season.

Early protective effect of a ("pan") coronavirus vaccine (PanCoVac) in Roborovski dwarf hamsters after single-low dose intranasal administration.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the danger posed by human coronaviruses. Rapid emergence of immunoevasive variants and waning antiviral immunity decrease the effect of the currently available vaccines, which aim at induction of neutralizing antibodies. In contrast, T cells are marginally affected by antigen evolution although they represent the major mediators of virus control and vaccine protection against virus-induced disease. Materials and methods: We generated a multi-epitope vaccine (PanCoVac) that encodes the conserved T cell epitopes from all structural proteins of coronaviruses. PanCoVac contains elements that facilitate efficient processing and presentation of PanCoVac-encoded T cell epitopes and can be uploaded to any available vaccine platform. For proof of principle, we cloned PanCoVac into a non-integrating lentivirus vector (NILV-PanCoVac). We chose Roborovski dwarf hamsters for a first step in evaluating PanCoVac in vivo. Unlike mice, they are naturally susceptible to SARS-CoV-2 infection. Moreover, Roborovski dwarf hamsters develop COVID-19-like disease after infection with SARS-CoV-2 enabling us to look at pathology and clinical symptoms. Results: Using HLA-A*0201-restricted reporter T cells and U251 cells expressing a tagged version of PanCoVac, we confirmed in vitro that PanCoVac is processed and presented by HLA-A*0201. As mucosal immunity in the respiratory tract is crucial for protection against respiratory viruses such as SARS-CoV-2, we tested the protective effect of single-low dose of NILV-PanCoVac administered via the intranasal (i.n.) route in the Roborovski dwarf hamster model of COVID-19. After infection with ancestral SARS-CoV-2, animals immunized with a single-low dose of NILV-PanCoVac i.n. did not show symptoms and had significantly decreased viral loads in the lung tissue. This protective effect was observed in the early phase (2 days post infection) after challenge and was not dependent on neutralizing antibodies. Conclusion: PanCoVac, a multi-epitope vaccine covering conserved T cell epitopes from all structural proteins of coronaviruses, might protect from severe disease caused by SARS-CoV-2 variants and future pathogenic coronaviruses. The use of (HLA-) humanized animal models will allow for further efficacy studies of PanCoVac-based vaccines in vivo.

Old and new aspects of influenza. / Nuevos y viejos aspectos de la gripe.

Influenza is a classic infectious disease that, through the continuous variation of the viruses that produce it, imposes new challenges that we must solve as quickly as possible. The COVID-19 pandemic has substantially modified the behavior of influenza and other respiratory viruses, and in the coming years we will have to coexist with a new pathogen that will probably interact with existing pathogens in a way that we cannot yet glimpse. However, knowledge prior to the pandemic allows us to focus on the aspects that must be modified to make influenza an acceptable challenge for the future. In this review, emphasis is placed on the most relevant aspects of epidemiology, disease burden, diagnosis, and vaccine prevention, and how scientific and clinical trends in these aspects flow from the previously known to future challenges.

Group 1 and group 2 hemagglutinin stalk antibody response according to age.

Objective: Antibodies elicited by seasonal influenza vaccines mainly target the head of hemagglutinin (HA). However, antibodies against the stalk domain are cross-reactive and have been proven to play a role in reducing influenza disease severity. We investigated the induction of HA stalk-specific antibodies after seasonal influenza vaccination, considering the age of the cohorts. Methods: A total of 166 individuals were recruited during the 2018 influenza vaccine campaign (IVC) and divided into groups: <50 (n = 14), 50-64 (n = 34), 65-79 (n = 61), and ≥80 (n = 57) years old. Stalk-specific antibodies were quantified by ELISA at day 0 and day 28 using recombinant viruses (cH6/1 and cH14/3) containing an HA head domain (H6 or H14) from wild bird origin with a stalk domain from human H1 or H3, respectively. The geometric mean titer (GMT) and the fold rise (GMFR) were calculated, and differences were assessed using ANOVA adjusted by the false discovery rate (FDR) and the Wilcoxon tests (p <0.05). Results: All age groups elicited some level of increase in anti-stalk antibodies after receiving the influenza vaccine, except for the ≥80-year-old cohort. Additionally, <65-year-old vaccinees had higher group 1 antibody titers versus group 2 before and after vaccination. Similarly, vaccinees within the <50-year-old group showed a higher increase in anti-stalk antibody titers when compared to older individuals (≥80 years old), especially for group 1 anti-stalk antibodies. Conclusion: Seasonal influenza vaccines can the induction of cross-reactive anti-stalk antibodies against group 1 and group 2 HAs. However, low responses were observed in older groups, highlighting the impact of immunosenescence in adequate humoral immune responses.

Optically stimulated luminescence detectors for dosimetry and LET measurements in light ion beams.

Objective.This work investigates the use of Al2O3:C and Al2O3:C,Mg optically stimulated luminescence (OSL) detectors to determine both the dose and the radiation quality in light ion beams. The radiation quality is here expressed through either the linear energy transfer (LET) or the closely related metricQeff, which depends on the particle's speed and effective charge. The derived LET andQeffvalues are applied to improve the dosimetry in light ion beams.Approach.OSL detectors were irradiated in mono-energetic1H-,4He-,12C-, and16O-ion beams. The OSL signal is associated with two emission bands that were separated using a pulsed stimulation technique and subjected to automatic corrections based on reference irradiations. Each emission band was investigated independently for dosimetry, and the ratio of the two emission intensities was parameterized as a function of fluence- and dose-averaged LET, as well asQeff. The determined radiation quality was subsequently applied to correct the dose for ionization quenching.Main results.For both materials, theQeffdeterminations in1H- and4He-ion beams are within 5 % of the Monte Carlo simulated values. Using the determined radiation quality metrics to correct the nonlinear (ionization quenched) detector response leads to doses within 2 % of the reference doses.Significance.Al2O3:C and Al2O3:C,Mg OSL detectors are applicable for dosimetry and radiation quality estimations in1H- and4He-ions. Only Al2O3:C,Mg shows promising results for dosimetry in12C-ions. Across both materials and the investigated ions, the estimatedQeffvalues were less sensitive to the ion types than the estimated LET values were. The reduced uncertainties suggest new possibilities for simultaneously estimating the physical and biological dose in particle therapy with OSL detectors.

Impact of COVID-19 on Adherence to Treatment in Patients with HIV.

In patients with human immunodeficiency virus (HIV), adherence to treatment is affected by the adverse effects of treatment, the presence of additional comorbidities, the complexity of dosage, and family and community support. However, one recent circumstance that was likely to have influenced therapeutic adherence was the COVID-19 pandemic and the applied containment measures. An observational retrospective study of a sample of patients with HIV was conducted to establish the relationship between sociodemographic, clinical, and pharmacological variables and therapeutic adherence before and after the pandemic. Adherence was measured using the validated simplified medication adherence questionnaire (SMAQ) and medication possession rate. A statistical analysis was performed to determine the mean, standard deviation, and median of the quantitative variables and the frequencies of the qualitative variables, and the relationship between the dependent and independent variables was analysed using the chi-squared test and Student's t-test. No statistically significant differences were found between treatment adherence measured before and 22 months after the start of the pandemic. Sex, occupation, treatment regimen, viral load levels, and COVID-19 disease status did not influence adherence during either period. However, the age of patients with HIV had an impact on adherence during both periods (p = 0.008 and p = 0.002, respectively), with the age group under 45 years being less adherent. In addition, experiencing adverse drug reactions (ADRs) was shown to have an impact on adherence before the pandemic (p = 0.006) but not afterwards. The COVID-19 pandemic was not shown to have an impact on the degree of adherence to antiretroviral treatment in patients with HIV. Instead, adherence was influenced by patient age and ADR occurrence; therefore, measures must be taken in this regard. The SMAQ demonstrated sensitivity in assessing adherence.

Effect of Nonconstituent Additive Ions on the Controlled Crystallization of Lanthanide-Based Preyssler Polyoxometalates.

Preyssler-type polyoxometalates (POMs) encapsulating lanthanide ions have been shown to provide ideal examples of single-molecule magnets and spin-qubits. However, the advances in this area are limited by the quality and size of the crystals. In this work, the role of additives ions in the crystallization of these POMs from aqueous solutions has been investigated. More specifically, we have studied the influence of Al3+, Y3+, and In3+ on the crystallization process of K12[MP5W30O110] (where M = Gd and Y). The results show that the concentration of these ions in the solution plays an important role in controlling the crystallization rate of the grown POM crystals leading to a significant increase in their size, while showing very little or no tendency to be incorporated into the structure. This has allowed us to obtain pure Gd or Y crystals, as well as diluted magnetic crystals formed by the diamagnetic Y3+ POM doped with the magnetic Gd3+ ion.