Management of typical and atypical metastatic lung carcinoids: present and future perspectives.

Lung carcinoids are rare tumors representing 1-2% of all invasive lung malignancies. They include typical and atypical carcinoids, whose distinction is made based on the mitotic index and presence or absence of necrosis. The 10-year overall survival for stage IV typical carcinoid is 47% and 18% for atypical carcinoid, reflecting the indolent growth of these tumors. There are limited approved treatment options for them and most of the evidence comes from retrospective analyses, single-arm trials, subgroup analysis of phase II/III trials for metastatic neuroendocrine tumors and extrapolation of data from phase III trials for gastroenteropancreatic neuroendocrine tumors. Management of metastatic lung carcinoids requires a multidisciplinary standardized approach in specialized centers. Treatment should have a dual objective, control of tumor growth and control of symptoms related to hypersecretion syndromes, aiming to improve quality of life and survival. In the continuum of treatment disease, locoregional treatment options need to be considered in parallel with systemic treatments. In this paper, we review the present treatment options and their rational and we give an insight into future alternatives.

Beyond the Usual Suspects: Unraveling Spleen Mastocytosis in Hypersplenism Differential Diagnosis.

Systemic mastocytosis (SM) poses a diagnostic challenge. This hematologic disorder involves abnormal mast cell proliferation and concurrent tissue infiltration. SM clinical presentation is not uniform, with patients displaying a wide array of symptoms related to different organ infiltration and mast cell mediators. Splenomegaly, while not typical or specific to SM, might be present from an early stage to advanced stage, especially in the presence of thrombocytopenia. Early detection is crucial for optimal patient outcomes. We present an atypical case of SM with spleen involvement in a 63-year-old male patient with a history of persistent thrombocytopenia for five years. Upon splenectomy, histological findings were compatible with infiltration with mast cells. Remarkably, the patient showed improvement and did not require additional cytoreductive therapy. This case underlines the importance of recognizing this rare presentation and highlights the potential therapeutic role of splenectomy in aggressive SM.

State-dependent complexity of the local field potential in the primary visual cortex.

The local field potential (LFP) is as a measure of the combined activity of neurons within a region of brain tissue. While biophysical modeling schemes for LFP in cortical circuits are well established, there is a paramount lack of understanding regarding the LFP properties along the states assumed in cortical circuits over long periods. Here we use a symbolic information approach to determine the statistical complexity based on Jensen disequilibrium measure and Shannon entropy of LFP data recorded from the primary visual cortex (V1) of urethane-anesthetized rats and freely moving mice. Using these information quantifiers, we find consistent relations between LFP recordings and measures of cortical states at the neuronal level. More specifically, we show that LFP's statistical complexity is sensitive to cortical state (characterized by spiking variability), as well as to cortical layer. In addition, we apply these quantifiers to characterize behavioral states of freely moving mice, where we find indirect relations between such states and spiking variability.

Enhancing garlic propagation through functional biopolymer-based propagules coatings: A bio-nanotechnological strategy.

Integrating agricultural, chemical, and technological knowledge is crucial for developing bio-nanotechnologies to improve agricultural production. This study explores the innovative use of biopolymeric coatings, based on sodium alginate and sodium alginate + Laponite® (nanoclay), containing biostimulants (tryptophol and thymol) or not, on garlic cloves. These coatings were analyzed using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR-ATR), and scanning electron microscopy (SEM). Greenhouse bioassays showed improvements in garlic shoot plant biomass with both treatments: sodium alginate biopolymer and sodium alginate biopolymer plus Laponite®. In the field experiment, garlic plants treated with sodium alginate, in combination with conventional pesticide treatments, resulted in better quality garlic bulbs, where larger garlics were harvested in this treatment, reducing commercial losses. In tropical garlic crops, obtaining plants with greater initial vigor is essential. Our results highlight the potential of these bio-nanotechnological strategies to enhance garlic propagation, ensuring environmental protection and food security.

Water level regime variation is a crucial driver for taxonomic, functional, and phylogenetic diversity in seasonally flooded tropical forests.

Floodplains contribute significantly to terrestrial ecosystem service provision but are also among the most vulnerable and degraded ecosystems worldwide. Heterogeneity in floodplain properties arises from variations in river-specific flood regimes, watershed characteristics, and valley morphology, influencing seasonally flooded forests' taxonomic, functional, and phylogenetic diversity. This study addresses persisting knowledge gaps in floodplain ecology, focusing on the seasonally dry tropics. We explore the relationships between flood regime, environmental conditions, vegetation composition, functional and phylogenetic diversity, and the impact of environmental variables on above-ground biomass (AGB) and ecological strategies. The study spans six rivers in southeastern Brazil's main river basins: Rio Grande and São Francisco. We identified five eco-units in each floodplain based on flooding regimes and surveyed six plots per eco-unit. We measured trees with DBH > 5 cm and collected functional traits, along with detailed soil, climate, and water level data. We calculated plot-level floristic composition, taxonomic, functional, and phylogenetic diversity, wood density, and AGB. Functional and phylogenetic dissimilarity were analyzed, and the effects of climate, soil, and hydrological variables were quantified using generalized linear mixed models. We show how flood frequency and duration affect floristic composition across the floodplains. Taxonomic and phylogenetic diversity responded to climate, soil, and hydrological variables, while functional diversity responded primarily to hydrological variables, emphasizing the role of environmental filtering. Hydrological seasonality, soil fertility, and flood regime emerged as key factors shaping community structure and ecological strategies in the studied seasonally flooded tropical forests. Plot-level AGB responded to phosphorus but not to climate or hydrological variables. The study also highlights functional and phylogenetic dissimilarities among eco-units and basins, indicating potential climate change impacts.

Cross-cultural adaptation and reliability of the European Portuguese version of the Musculoskeletal Health Questionnaire: A methodological study.

PURPOSE: To culturally adapt the Musculoskeletal Health Questionnaire (MSK-HQ) to European Portuguese and evaluate its reliability in individuals with musculoskeletal conditions. MATERIALS AND METHODS: The study was carried out in two phases. In the first phase, the MSK-HQ was translated and culturally adapted. In the second phase, a longitudinal observational study was carried out with a convenience sample of participants with musculoskeletal conditions. Data collection began at the start of physiotherapy treatments by filling in the MSK-HQ and Numeric Pain Rating Scale (NPRS). After 4-7 days, the participants were asked to fill out the MSK-HQ once again, as well as the Patient Global Improvement Change (PGIC) scale. The data collected was used to study internal consistency, test-retest reliability, and measurement error. Floor and ceiling effects were also analysed. RESULTS: The MSK-HQ was successfully translated and adapted into European Portuguese. The second phase of the study had a sample of 191 participants. This study demonstrated high internal consistency (Cronbach's α = 0.885) and excellent test-retest reliability (ICC(2,1) = 0.908). The analysis of measurement error resulted in an SEM of 2.818 and an SDC at 7.811. No floor or ceiling effect was observed. CONCLUSIONS: The MSK-HQ-PT is a reliable instrument for measuring musculoskeletal health. Further studies on its validity and responsiveness are needed.

The arrangement of dual-species biofilms of Candida albicans and Issatchenkia orientalis can be modified by the medium: effect of Voriconazole.

Both Candida albicans and Issatchenkia orientalis have been isolated from different types of infections over the years. They have the ability to form communities of microorganisms known as biofilms. It has been demonstrated that the medium employed in studies may affect the biofilm development. The aim of this study was to investigate the arrangement of dual-species biofilms of C. albicans and I. orientalis cultivated on either RPMI-1640 or Sabouraud Dextrose Broth (SDB), as well as the inhibitory effect of Voriconazole (VRC). For the experiments performed, ATCC strains were used, and yeast-mixed suspensions were inoculated in 96-well plates with either RPMI-1640 or SDB, in the presence or absence of VRC. The results were observed by counting the number of CFU obtained from scraping off the biofilms produced and plating the content on CHROMagar Candida medium. It was observed that for all conditions tested the medium chosen affected the arrangement of dual-species biofilms: when RPMI-1640 was used, there was a prevalence of C. albicans, while the opposite was noted when SDB was used. It could be suggested that the medium and environment could regulate interactions between both yeast species, including the response to different antifungal drugs.

Ultra-diluted/dynamized doxorubicin reduces the toxicity caused by doxorubicin during the in vitro culture of pig preantral follicles enclosed in ovarian tissue.

The present study investigated the effect of adding allopathic doxorubicin (DOX 0.3 µg/mL), the vehicle of ultradiluted/dynamized doxorubicin (0.2 % ethanol), different dynamizations of ultradiluted/dynamized doxorubicin (DOX 6CH, DOX 12CH and DOX 30CH), both in the absence or presence of chemical stress induced by doxorubicin at 0.3 µg/mL on follicular survival and activation, antioxidant capacity of the medium, Catalase activity (CAT), production of reactive protein thiol, maintenance of type I and III collagen fibers and accumulation of lipofuscin in porcine ovarian tissue cultured in vitro for 48 hours. To do this, part of the ovarian tissue fragments was fixed for the uncultured control and the rest were cultured in: MEM (cultured control), DOX 0.3 µg/mL, Ethanol, DOX 6CH, DOX 12CH, DOX 30CH, DOX (0.3 µg/mL) + DOX 6CH, DOX (0.3 µg/mL) + DOX 12CH, DOX (0.3 µg/mL) + DOX 30CH treatments. The results showed that, in general, ultradiluted/dynamized doxorubicin (DOX 6CH, DOX 12CH and DOX 30CH) mitigated the toxic effect of allopathic doxorubicin (0.3 µg/mL) on the morphology of preantral follicles, the content of type I and III collagen fibers, and the production of lipofuscin in the tissue. However, only DOX (0.3 µg/mL) + DOX 6CH attenuated the oxidative stress induced by DOX (0.3 µg/mL), maintaining adequate CAT activity that was similar to the uncultured control. Additionally, when the three isolated ultradiluted/dynamized doxorubicin were considered, only DOX 12CH increased the reduced thiol levels compared to the uncultured control and MEM. In conclusion, supplementing the culture medium with ultradiluted/dynamized DOX (DOX 6CH, DOX 12CH and DOX 30CH) attenuated the toxicity induced by allopathic doxorubicin during the in vitro culture of pig preantral follicles enclosed in ovarian tissue.

Food chain without giants: modelling the trophic impact of bowhead whaling on little auk populations in the Atlantic Arctic.

In the Atlantic Arctic, bowhead whales (Balaena mysticetus) were nearly exterminated by European whalers between the seventeenth and nineteenth centuries. The collapse of the East Greenland-Svalbard-Barents Sea population, from an estimated 50 000 to a few hundred individuals, drastically reduced predation on mesozooplankton. Here, we tested the hypothesis that this event strongly favoured the demography of the little auk (Alle alle), a zooplanktivorous feeder competitor of bowhead whales and the most abundant seabird in the Arctic. To estimate the effect of bowhead whaling on little auk abundance, we modelled the trophic niche overlap between the two species using deterministic simulations of mesozooplankton spatial distribution. We estimated that bowhead whaling could have led to a 70% increase in northeast Atlantic Arctic little auk populations, from 2.8 to 4.8 million breeding pairs. While corresponding to a major population increase, this is far less than predicted by previous studies. Our study illustrates how a trophic shift can result from the near extirpation of a marine megafauna species, and the methodological framework we developed opens up new opportunities for marine trophic modelling.

Identification of a novel alternative splicing isoform of the Hippo kinase STK3/MST2 with impaired kinase and cell growth suppressing activities.

Mammalian Ste-20-like Kinases 1 and 2 (MST1/2) are core serine-threonine kinases of the Hippo pathway regulating several cellular processes, including cell cycle arrest and cell death. Here, we discovered a novel alternative splicing variant of the MST2 encoding gene, STK3, in malignant cells and tumor datasets. This variant, named STK3∆7 or MST2∆7 (for mRNA or protein, respectively), resulted from the skipping of exon 7. MST2∆7 exhibited increased ubiquitylation and interaction with the E3 ubiquitin-protein ligase CHIP compared to the full-length protein (MST2FL). Exon 7 in STK3 encodes a segment within the kinase domain, and its exclusion compromised MST2 interaction with and phosphorylation of MOB, a major MST1/2 substrate. Nevertheless, MST2∆7 was capable of interacting with MST1 and MST2FL. Unlike MST2FL, overexpression of MST2∆7 did not lead to increased cell death and growth arrest. Strikingly, we observed the exclusion of STK3 exon 7 in 3.2-15% of tumor samples from patients of several types of cancer, while STK3∆7 was seldomly found in healthy tissues. Our study identified a novel STK3 splicing variant with loss of function and the potential to disturb tissue homeostasis by impacting on MST2 activities in the regulation of cell death and quiescence.

The Policy of Compulsory Large-Scale Food Fortification in Sub-Saharan Africa.

Food fortification with micronutrients was initially justified in developed countries by a lack of availability of micronutrients in staple crops, mainly due to soil exhaustion. However, in Sub-Saharan arable lands, soil fatigue is not predominant, and communities consume mostly home-grown, organic, non-processed crops. Sub-Saharan food systems are nevertheless deeply entwined with food insecurity, driver of illnesses. Family production can promote subsistence, food stability, and self-sufficiency, the main SSA setback being the vicious cycle of poverty and the lack of dietary variety, contributing to malnutrition. Poverty reduction and women's education are significant strategies for reducing child and adolescent undernourishment. Fortification of foods consumed daily by individuals makes sense and can minimize, if not entirely, eliminate deficiencies. Compulsory mass fortification of foods in Sub-Saharan Africa (SSA) with single micronutrients is, however, controversial since they work in synergy among each other and with the food matrix, for optimal absorption and metabolism. Since the causes of malnutrition are many, caused by diverse, unequal, and unjust food distribution, interrelated with political, social, cultural, or economic factors, education status of the population, season and climatic changes, and effectiveness of nutrition programs, just food fortification cannot solve the composite of all these elements. Further, compulsory fortification is excessive, unproductive, and likely harmful to human health, while many challenges remain in assessing the quality of available premixes. Furthermore, aiming at dietary diversification is the best approach of increasing trace element intake from commonly accessible and easily available food sources.

Cryopreservation and passaging optimization for Galea spixii (Wagler, 1831) adult skin fibroblast lines: A step forward in species management and genetic studies.

BACKGROUND: In vitro culture of fibroblasts is a technique based on cell isolation, physiological characterization, and cryopreservation. This technique has not been described for Galea spixii, therefore, it can be used to learn about its cellular biology and genetic diversity. OBJECTIVE: We established fibroblast lines of six G. spixii individuals from several passages (second, fifth, eighth, and tenth) and cryopreserved them. METHODS: Fibroblasts recovered from skin biopsies were identified based on morphology, immunocytochemistry, and karyotyping. The cells were analyzed for morphology, ultrastructure, viability, proliferation, metabolism, oxidative stress, bioenergetic potential, and apoptosis before and after cryopreservation. RESULTS: After the eighth passage, the fibroblasts showed morphological and karyotypic changes, although their viability, metabolism, and proliferation did not change. An increase in oxidative stress and bioenergetic potential from the fifth to the eighth passages were also observed. Post cryopreservation, cell damage with respect to the ultrastructure, viability, proliferative rate, apoptotic levels, oxidative stress, and bioenergetic potential were verified. CONCLUSION: Fibroblasts up to the tenth passage could be cultured in vitro. However, cells at the fifth passage were of better quality to be used for reproductive techniques. Additionally, optimization of the cryopreservation protocol is essential to improve the physiological parameters of these cells.

Transcriptomic Analyses Reveal That Coffea arabica and Coffea canephora Have More Complex Responses under Combined Heat and Drought than under Individual Stressors.

Increasing exposure to unfavorable temperatures and water deficit imposes major constraints on most crops worldwide. Despite several studies regarding coffee responses to abiotic stresses, transcriptome modulation due to simultaneous stresses remains poorly understood. This study unravels transcriptomic responses under the combined action of drought and temperature in leaves from the two most traded species: Coffea canephora cv. Conilon Clone 153 (CL153) and C. arabica cv. Icatu. Substantial transcriptomic changes were found, especially in response to the combination of stresses that cannot be explained by an additive effect. A large number of genes were involved in stress responses, with photosynthesis and other physiologically related genes usually being negatively affected. In both genotypes, genes encoding for protective proteins, such as dehydrins and heat shock proteins, were positively regulated. Transcription factors (TFs), including MADS-box genes, were down-regulated, although responses were genotype-dependent. In contrast to Icatu, only a few drought- and heat-responsive DEGs were recorded in CL153, which also reacted more significantly in terms of the number of DEGs and enriched GO terms, suggesting a high ability to cope with stresses. This research provides novel insights into the molecular mechanisms underlying leaf Coffea responses to drought and heat, revealing their influence on gene expression.

Inflammatory Status in Trained and Untrained Mice at Different Pollution Levels.

Atmospheric pollution can be defined as a set of changes that occur in the composition of the air, making it unsuitable and/or harmful and thereby generating adverse effects on human health. The regular practice of physical exercise (PE) is associated with the preservation and/or improvement of health; however, it can be influenced by neuroimmunoendocrine mechanisms and external factors such as air pollution, highlighting the need for studies involving the practice of PE in polluted environments. Herein, 24 male C57BL/6 mice were evaluated, distributed into four groups (exposed to a high concentration of pollutants/sedentary, exposed to a high concentration of pollutants/exercised, exposed to ambient air/sedentary, and exposed to ambient air/exercised). The exposure to pollutants occurred in the environmental particle concentrator (CPA) and the physical training was performed on a treadmill specially designed for use within the CPA. Pro- and anti-inflammatory markers in blood and bronchoalveolar lavage (BALF), BALF cellularity, and lung tissue were evaluated. Although the active group exposed to a high concentration of pollution showed a greater inflammatory response, both the correlation analysis and the ratio between pro- and anti-inflammatory cytokines demonstrated that the exercised group presented greater anti-inflammatory activity, suggesting a protective/adaptative effect of exercise when carried out in a polluted environment.

Zinc/Magnesium Ferrite Nanoparticles Functionalized with Silver for Optimized Photocatalytic Removal of Malachite Green.

Water pollution is a major environmental challenge. Due to the inefficiency of conventional wastewater treatment plants in degrading many organic complex compounds, these recalcitrant pollutants end up in rivers, lakes, oceans and other bodies of water, affecting the environment and human health. Semiconductor photocatalysis is considered an efficient complement to conventional methods, and the use of various nanomaterials for this purpose has been widely explored, with a particular focus on improving their activity under visible light. This work focuses on developing magnetic and photoactive zinc/magnesium mixed ferrites (Zn0.5Mg0.5Fe2O4) by sol-gel and solvothermal synthesis methods, which are two of the most important and efficient methods used for the synthesis of ferrite nanoparticles. The nanoparticles (NPs) synthesized by the sol-gel method exhibited an average size of 14.7 nm, while those synthesized by the solvothermal method had an average size of 17.4 nm. Both types possessed a predominantly cubic structure and demonstrated superparamagnetic behavior, reaching a magnetization saturation value of 60.2 emu g-1. Due to the high recombination rate of electrons/holes, which is an intrinsic feature of ferrites, surface functionalization with silver was carried out to enhance charge separation. The results demonstrated a strong influence of adsorption and of the deposition of silver. Several optimization steps were performed during synthesis, allowing us to create efficient catalysts, as proved by the almost full removal of the dye malachite green attaining 95.0% (at a rate constant of 0.091 min-1) and 87.6% (at a rate constant of 0.017 min-1) using NPs obtained by the sol-gel and solvothermal methods, respectively. Adsorption in the dark accounted for 89.2% of the dye removal for nanoparticles prepared by sol-gel and 82.8% for the ones obtained by the solvothermal method. These results make mixed zinc/magnesium ferrites highly promising for potential industrial application in effluent photoremediation using visible light.

Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies.

Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a leading blood-stage malaria vaccine antigen target, currently in a phase 2b clinical trial as a full-length soluble protein/adjuvant vaccine candidate called RH5.1/Matrix-M. We identify that disordered regions of the full-length RH5 molecule induce non-growth inhibitory antibodies in human vaccinees and that a re-engineered and stabilized immunogen (including just the alpha-helical core of RH5) induces a qualitatively superior growth inhibitory antibody response in rats vaccinated with this protein formulated in Matrix-M adjuvant. In parallel, bioconjugation of this immunogen, termed "RH5.2," to hepatitis B surface antigen virus-like particles (VLPs) using the "plug-and-display" SpyTag-SpyCatcher platform technology also enables superior quantitative antibody immunogenicity over soluble protein/adjuvant in vaccinated mice and rats. These studies identify a blood-stage malaria vaccine candidate that may improve upon the current leading soluble protein vaccine candidate RH5.1/Matrix-M. The RH5.2-VLP/Matrix-M vaccine candidate is now under evaluation in phase 1a/b clinical trials.

Unveiling the molecular landscape of cognitive aging: insights from polygenic risk scores, DNA methylation, and gene expression.

BACKGROUND: Aging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive alterations, though the precise mechanisms remain largely unknown. This study aimed to investigate the impact of polygenic risk scores (PRS) for WM integrity, together with age-related DNA methylation, and gene expression alterations, on cognitive aging in a cross-sectional healthy aging cohort. The PRSs were calculated using genome-wide association study (GWAS) summary statistics for magnetic resonance imaging (MRI) markers of WM integrity, including WM hyperintensities, fractional anisotropy (FA), and mean diffusivity (MD). These scores were utilized to predict age-related cognitive changes and evaluate their correlation with structural brain changes, which distinguish individuals with higher and lower cognitive scores. To reduce the dimensionality of the data and identify age-related DNA methylation and transcriptomic alterations, Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was used. Subsequently, a canonical correlation algorithm was used to integrate the three types of omics data (PRS, DNA methylation, and gene expression data) and identify an individual "omics" signature that distinguishes subjects with varying cognitive profiles. RESULTS: We found a positive association between MD-PRS and long-term memory, as well as a correlation between MD-PRS and structural brain changes, effectively discriminating between individuals with lower and higher memory scores. Furthermore, we observed an enrichment of polygenic signals in genes related to both vascular and non-vascular factors. Age-related alterations in DNA methylation and gene expression indicated dysregulation of critical molecular features and signaling pathways involved in aging and lifespan regulation. The integration of multi-omics data underscored the involvement of synaptic dysfunction, axonal degeneration, microtubule organization, and glycosylation in the process of cognitive aging. CONCLUSIONS: These findings provide valuable insights into the biological mechanisms underlying the association between WM coherence and cognitive aging. Additionally, they highlight how age-associated DNA methylation and gene expression changes contribute to cognitive aging.

COVID-19 Vaccine Effectiveness in Autumn and Winter 2022 to 2023 Among Older Europeans.

Importance: In the context of emerging SARS-CoV-2 variants or lineages and new vaccines, it is key to accurately monitor COVID-19 vaccine effectiveness (CVE) to inform vaccination campaigns. Objective: To estimate the effectiveness of COVID-19 vaccines administered in autumn and winter 2022 to 2023 against symptomatic SARS-CoV-2 infection (with all circulating viruses and XBB lineage in particular) among people aged 60 years or older in Europe, and to compare different CVE approaches across the exposed and reference groups used. Design, Setting, and Participants: This case-control study obtained data from VEBIS (Vaccine Effectiveness, Burden and Impact Studies), a multicenter study that collects COVID-19 and influenza data from 11 European sites: Croatia; France; Germany; Hungary; Ireland; Portugal; the Netherlands; Romania; Spain, national; Spain, Navarre region; and Sweden. Participants were primary care patients aged 60 years or older with acute respiratory infection symptoms who were recruited at the 11 sites after the start of the COVID-19 vaccination campaign from September 2022 to August 2023. Cases and controls were defined as patients with positive and negative, respectively, reverse transcription-polymerase chain reaction (RT-PCR) test results. Exposures: The exposure was COVID-19 vaccination. The exposure group consisted of patients who received a COVID-19 vaccine during the autumn and winter 2022 to 2023 vaccination campaign and 14 days or more before symptom onset. Reference group included patients who were not vaccinated during or in the 6 months before the 2022 to 2023 campaign (seasonal CVE), those who were never vaccinated (absolute CVE), and those who were vaccinated with at least the primary series 6 months or more before the campaign (relative CVE). For relative CVE of second boosters, patients receiving their second booster during the campaign were compared with those receiving 1 booster 6 months or more before the campaign. Main Outcomes and Measures: The outcome was RT-PCR-confirmed, medically attended, symptomatic SARS-CoV-2 infection. Four CVE estimates were generated: seasonal, absolute, relative, and relative of second boosters. CVE was estimated using logistic regression, adjusting for study site, symptom onset date, age, chronic condition, and sex. Results: A total of 9308 primary care patients were included, with 1687 cases (1035 females; median [IQR] age, 71 [65-79] years) and 7621 controls (4619 females [61%]; median [IQR] age, 71 [65-78] years). Within 14 to 89 days after vaccination, seasonal CVE was 29% (95% CI, 14%-42%), absolute CVE was 39% (95% CI, 6%-60%), relative CVE was 31% (95% CI, 15% to 44%), and relative CVE of second boosters was 34% (95% CI, 18%-47%) against all SARS-CoV-2 variants. In the same interval, seasonal CVE was 44% (95% CI, -10% to 75%), absolute CVE was 52% (95% CI, -23% to 82%), relative CVE was 47% (95% CI, -8% to 77%), and relative CVE of second boosters was 46% (95% CI, -13% to 77%) during a period of high XBB circulation. Estimates decreased with time since vaccination, with no protection from 180 days after vaccination. Conclusions and Relevance: In this case-control study among older Europeans, all CVE approaches suggested that COVID-19 vaccines administered in autumn and winter 2022 to 2023 offered at least 3 months of protection against symptomatic, medically attended, laboratory-confirmed SARS-CoV-2 infection. The effectiveness of new COVID-19 vaccines against emerging SARS-CoV-2 variants should be continually monitored using CVE seasonal approaches.