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Limited research suggests that certain viruses reactivate in severe-acute-respiratory-syndrome-coronavirus 2 infection, contributing to the development of postacute sequelae of COVID-19 (PASC). We examined 1083 infected individuals from a population-based cohort, and assessed differences in plasma immunoglobulin (Ig)G and immunoglobulin A levels against Epstein-Barr virus (EBV), cytomegalovirus, varicella zoster virus (VZV), BK polyomavirus, KI polyomavirus, WU polyomavirus (WUPyV), respiratory syncytial virus, and Adv-36 according to the severity of previous COVID-19 and PASC history. Individuals who had experienced severe COVID-19 had higher antibody responses to latent viruses. Ever PASC, active persistent PASC, and PASC with neuropsychiatric symptoms were associated with higher immnoglobulin G to EBV early antigen-diffuse, VZV, and WUPyV even among individuals without previous severe COVID-19.

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The use of plasmonic nanoparticles in performing photothermal treatments in cancer cells requires a full knowledge about their optical properties. The surface plasmon resonance is easily foreseen and measurable in colloidal suspensions, however it can be strongly modified when located inside cells. Assessing the optical behavior of plasmonic nanoparticles in cells is essential for an efficient and controlled treatment. This requires the combination of experimental data and computational models to understand the mechanisms that cause the change in their optical response. In this work, we investigate the plasmonic response of Au nanospheres (AuNSs) internalized into cancer cells (MCF-7). Experimental data are compared to the simulations provided by a 3D model based on a finite element method. We demonstrate the impact of physical parameters such as the type of NS assembly, the surrounding medium and the interparticle gap, in the photothermal efficiency of AuNSs. Results open the avenue to predict, by numerical calculations, the optical properties of plasmonic nanoparticles inside cells to minimize treatment costs and times in photothermal therapies.

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BACKGROUND AND OBJECTIVE: Papanicolaou staining has been successfully used to assist early detection of cervix cancer for several decades. We postulate that this staining technique can also be used for assisting early detection of oral cancer, which is responsible for about 300,000 deaths every year. The rational for such claim includes two key observations: (i) nuclear atypia, i.e., changes in volume, shape, and staining properties of the cell nuclei can be linked to rapid cell proliferation and genetic instability; and (ii) Papanicolaou staining allows one to reliably segment cells' nuclei and cytoplasms. While Papanicolaou staining is an attractive tool due to its low cost, its interpretation requires a trained pathologist. Our goal is to automate the segmentation and classification of morphological features needed to evaluate the use of Papanicolaou staining for early detection of mouth cancer. METHODS: We built a convolutional neural network (CNN) for automatic segmentation and classification of cells in Papanicolaou-stained images. Our CNN was trained and evaluated on a new image dataset of cells from oral mucosa consisting of 1,563 Full HD images from 52 patients, annotated by specialists. The effectiveness of our model was evaluated against a group of experts. Its robustness was also demonstrated on five public datasets of cervical images captured with different microscopes and cameras, and having different resolutions, colors, background intensities, and noise levels. RESULTS: Our CNN model achieved expert-level performance in a comparison with a group of three human experts on a set of 400 Papanicolaou-stained images of the oral mucosa from 20 patients. The results of this experiment exhibited high Interclass Correlation Coefficient (ICC) values. Despite being trained on images from the oral mucosa, it produced high-quality segmentation and plausible classification for five public datasets of cervical cells. Our Papanicolaou-stained image dataset is the most diverse publicly available image dataset for the oral mucosa in terms of number of patients. CONCLUSION: Our solution provides the means for exploring the potential of Papanicolaou-staining as a powerful and inexpensive tool for early detection of oral cancer. We are currently using our system to detect suspicious cells and cell clusters in oral mucosa slide images. Our trained model, code, and dataset are available and can help practitioners and stimulate research in early oral cancer detection.

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OBJECTIVES: The United Nations recognize the importance of balancing the needs of people and the planetary systems on which human health relies. This paper investigates the role that climate change has on human health via its influence on climate anxiety. DESIGN: We conducted an intensive longitudinal study. METHODS: Participants reported levels of climate anxiety, generalized anxiety and an array of health behaviours at 20 consecutive time points, 2 weeks apart. RESULTS: A network analysis shows climate anxiety and generalized anxiety not to covary, and higher levels of climate anxiety not to covary with health behaviours, except for higher levels of alcohol consumption at the within-participant level. Generalized anxiety showed completely distinct patterns of covariation with health behaviours compared with climate anxiety. CONCLUSIONS: Our findings imply that climate anxiety, as conceptualized and measured in the current study, is not in itself functionally impairing in terms of associations with unhealthy behaviours, and is distinct from generalized anxiety. The results also imply that interventions to induce anxiety about the climate might not always have significant impacts on health and well-being.

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We investigated the association between outdoor artificial light-at-night (ALAN) exposure and cardiometabolic risk in the GCAT study. We included 9,752 participants from Barcelona (59% women). We used satellite images (30m resolution) and estimated photopic illuminance and the circadian-regulation relevant melanopic illuminance (melanopic EDI). We explored the association between ALAN exposure and prevalent obesity, hypertension, and diabetes with logistic regressions. We assessed the relationship with incident cardiometabolic diseases ascertained through electronic health records (mean follow-up 6.5 years) with Cox proportional hazards regressions. We observed an association between photopic illuminance and melanopic EDI and prevalent hypertension, Odds ratio (OR) = 1.09 (95% CI, 1.01-1.16) and 1.08 (1.01-1.14) per interquartile range increase (0.59 and 0.16 lux, respectively). Both ALAN indicators were linked to incident obesity (hazard ratio [HR] = 1.29, 1.11-1.48 and 1.19, 1.05-1.34) and haemorrhagic stroke (HR = 1.73, 1.00-3.02 and 1.51, 0.99-2.29). Photopic illuminance was associated with incident hypercholesterolemia in all participants (HR = 1.17, 1.05-1.31) and with angina pectoris only in women (HR = 1.55, 1.03-2.33). Further research in this area and increased awareness on the health impacts of light pollution are needed. Results should be interpreted carefully since satellite-based ALAN data do not estimate total individual exposure.

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BACKGROUND: Oral cancer screening requires analysis capable of detecting changes preceding the clinical manifestation. Oral cytopathology studies as an oral cancer screening have shown promising results. This study aims to evaluate the use of cytopathology in a quali-quantitative analysis using Papanicoloau staining. METHODS: Four experimental groups were evaluated: control (CG), exposed to carcinogens (EG), potentially malignant disorder with and without epithelial dysplasia (D-OPMDG and ND-OPMDG) and oral squamous cell carcinoma (OSCCG). Oral smears were collected using a Cytobrush® and conventional exfoliative cytology. RESULTS: Oral Papanicolaou smears from 143 individuals were analysed in 8100 images. Qualitatively, non-lesional groups exhibited minimal suspected cases (20% in CG and 5% in EG), in the OPMD groups the ability to identify altered cells was low (40% in D-OPMDG and 0% in ND-OPMDG). Conversely, a notable 100% accuracy was achieved in the OSCCG. Quantitatively, a higher percentage of anucleated and a lower percentage of intermediate cells were observed in the OPMDG; a higher proportion of parabasal/suspicious cells was observed in OSCCG. The optimal threshold for improved accuracy in detecting suspected malignancies occurs when the count of parabasal/suspicious cells exceeds 8/100 cells examined. Cytomorphometric analysis revealed a higher nucleus/cytoplasm ratio (N/C) in OSCCG, with a best cutoff point indicating enhanced accuracy in discerning suspected malignancies when exceeding 17% of cells exhibiting this elevated ratio. CONCLUSION: It is possible to suggest updates in cytomorphometric and quantitative analysis in the modified Bethesda system for the oral cavity including objective criteria in the risk classification, therefore improving oral cancer screening.

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BACKGROUND: Prenatal ethylene oxide exposure may have adverse effects on fetal development. We examined the relationships between ethylene oxide hemoglobin (Hb) adduct levels and offspring's size at birth in a prospective European mother-child study. METHODS: This study included 1106 singletons from the NewGeneris project (2006-2010) with ethylene oxide Hb adducts measured in cord blood. We examined the relationships between adduct levels and offspring's size at birth among all infants and separately among infants of nonsmokers, using linear regression models for birth weight and birth head circumference and logarithmic binomial regression models for small for gestational age. We examined potential interactions between CYP2E1 single nucleotide polymorphisms in cord blood and the effects of ethylene oxide Hb adduct levels on offspring birth size. RESULTS: Higher quartiles of adduct levels as a measure of exposure were associated with decreasing birth weight and head circumference in the overall population. Compared to infants in the lowest quartile, those in the highest quartile exhibited lower birth weight (-70.73 g, 95% confidence interval = -141.16, -0.30) and reduced head circumference (-0.30 cm, 95% confidence interval = -0.58, -0.02). We observed similar, albeit less pronounced, patterns among infants of nonsmokers. There was no evidence of an association between ethylene oxide Hb adducts and risk of small for gestational age, nor consistent evidence of an interaction with CYP2E1 polymorphisms on the association between EO Hb adduct levels and offspring's size at birth. CONCLUSION: Results suggest that higher ethylene oxide Hb adduct levels in cord blood are associated with a reduction in offspring birth size.

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This research proposes designing and implementing a system to produce hydrogen, utilizing the thermal energy from the exhaust gases in a natural gas engine. For the construction of the system, a thermoelectric generator was used to convert the thermal energy from the exhaust gases into electrical power and an electrolyzer bank to produce hydrogen. The system was evaluated using a natural gas engine, which operated at a constant speed (2400 rpm) and six load conditions (20 %, 40 %, 60 %, 80 %, and 100 %). The effect of hydrogen on the engine was evaluated with fuel mixtures (NG + 10 % HEF and NG + 15 % HEF). The results demonstrate that the NG + 10 % HEF and NG + 15 % HEF mixtures allow for a decrease of 1.84 % and 2.33 % in BSFC and an increase of 1.88 % and 2.38 % in BTE. Through the NG + 15 % HEF mixture, the engine achieved an energy efficiency of 34.15 % and an exergetic efficiency of 32.84 %. Additionally, the NG + 15 % HEF mixture reduces annual CO, CO2, and HC emissions by 9.52 %, 15.48 %, and 13.39 %, respectively. The addition of hydrogen positively impacts the engine's economic cost, allowing for a decrease of 1.56 % in the cost of useful work and a reduction of 3.32 % in the cost of exergy loss. In general, the proposed system for hydrogen production represents an alternative for utilizing the residual energy from exhaust gases, resulting in better performance parameters, reduced annual pollutant emissions, and lower economic costs.

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BACKGROUND: Prostate cancer (PC) is the second most frequent tumor in men worldwide; however, its etiology remains largely unknown, with the exception of age and family history. The wide variability in incidence/mortality across countries suggests a certain role for environmental exposures that has not yet been clarified. OBJECTIVE: To evaluate the association between risk of PC (by clinical profile) and residential proximity to pollutant industrial installations (by industrial groups, groups of carcinogens, and specific pollutants released), within the context of a Spanish population-based multicase-control study of incident cancer (MCC-Spain). METHODS: This study included 1186 controls and 234 PC cases, frequency matched by age and province of residence. Distances from participants' residences to the 58 industries located in the study area were calculated and categorized into "near" (considering different limits between ≤1 km and ≤ 3 km) or "far" (>3 km). Odds ratios (ORs) and 95 % confidence intervals (95%CIs) were estimated using mixed and multinomial logistic regression models, adjusted for potential confounders and matching variables. RESULTS: No excess risk was detected near the overall industries, with ORs ranging from 0.66 (≤2 km) to 1.11 (≤1 km). However, positive associations (OR; 95%CI) were found, by industrial group, near (≤3 km) industries of ceramic (2.54; 1.28-5.07), food/beverage (2.18; 1.32-3.62), and disposal/recycling of animal waste (2.67; 1.12-6.37); and, by specific pollutant, near plants releasing fluorine (4.65; 1.45-14.91 at ≤1.5 km) and chlorine (5.21; 1.56-17.35 at ≤1 km). In contrast, inverse associations were detected near industries releasing ammonia, methane, dioxins+furans, polycyclic aromatic hydrocarbons, trichloroethylene, and vanadium to air. CONCLUSIONS: The results suggest no association between risk of PC and proximity to the overall industrial installations. However, some both positive and inverse associations were detected near certain industrial groups and industries emitting specific pollutants.

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Risk of depression increased in the general population after the COVID-19 pandemic outbreak. By examining the interplay between genetics and individual environmental exposures during the COVID-19 lockdown, we have been able to gain an insight as to why some individuals are more vulnerable to depression, while others are more resilient. This study, conducted on a Spanish cohort of 9218 individuals (COVICAT), includes a comprehensive non-genetic risk analysis, the exposome, complemented by a genomics analysis in a subset of 2442 participants. Depression levels were evaluated using the Hospital Anxiety and Depression Scale. Together with Polygenic Risk Scores (PRS), we introduced a novel score; Poly-Environmental Risk Scores (PERS) for non-genetic risks to estimate the effect of each cumulative score and gene-environment interaction. We found significant positive associations for PERSSoc (Social and Household), PERSLife (Lifestyle and Behaviour), and PERSEnv (Wider Environment and Health) scores across all levels of depression severity, and for PRSB (Broad depression) only for moderate depression (OR 1.2, 95% CI 1.03-1.40). On average OR increased 1.2-fold for PERSEnv and 1.6-fold for PERLife and PERSoc from mild to severe depression level. The complete adjusted model explained 16.9% of the variance. We further observed an interaction between PERSEnv and PRSB showing a potential mitigating effect. In summary, stressors within the social and behavioral domains emerged as the primary drivers of depression risk in this population, unveiling a mitigating interaction effect that should be interpreted with caution.

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Introduction: Data on medulloblastoma outcomes and experiences in low- and middle-income countries, especially in Latin America, is limited. This study examines challenges in Mexico's healthcare system, focusing on assessing outcomes for children with medulloblastoma in a tertiary care setting. Methods: A retrospective analysis was conducted, involving 284 patients treated at 21 pediatric oncology centers in Mexico. Results: High-risk patients exhibited markedly lower event-free survival than standard-risk patients (43.5% vs. 78.3%, p<0.001). Influential factors on survival included anaplastic subtype (HR 2.4, p=0.003), metastatic disease (HR 1.9, p=0.001); residual tumor >1.5cm², and lower radiotherapy doses significantly impacted event-free survival (EFS) and overall survival (OS). Platinum-based chemotherapy showed better results compared to the ICE protocol in terms of OS and EFS, which was associated with higher toxicity. Patients under 3 years old displayed notably lower OS and EFS compared to older children (36.1% vs. 55.9%, p=0.01).

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Children with autism spectrum disorder (ASD) have deficits that affect their social relationships, communication, and flexibility in reasoning. There are different types of treatment (pharmacological, educational, psychological, and rehabilitative). Currently, one way to address this problem is by using robotic systems to address the abilities that are altered in these children. The aim of this review will be to analyse the effectiveness of the incorporation of the different robotic systems currently existing in the treatment of children up to 10 years of age diagnosed with autism. A systematic review has been carried out in the PubMed, Scopus, Web of Science, and Dialnet databases, with the following descriptors: child, autism, and robot. The search yielded 578 papers, and nine were selected after the application of the PRISMA guideline. The quality of the studies was analysed with the PEDRo scale, and only those with a score between four and six were selected. From this study, the conclusion is that the use of robots, in general, improves children's behaviour in the short term, but longer-term experiences are necessary to achieve more conclusive results.

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BACKGROUND: Several studies have reported a relationship between retinal thickness and dementia. Therefore, optical coherence tomography (OCT) has been proposed as an early diagnosis method for Alzheimer's disease (AD). In this study, we performed a genome-wide association study (GWAS) aimed at identifying genes associated with retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thickness assessed by OCT and exploring the relationships between the spectrum of cognitive decline (including AD and non-AD cases) and retinal thickness. METHODS: RNFL and GCIPL thickness at the macula were determined using two different OCT devices (Triton and Maestro). These determinations were tested for association with common single nucleotide polymorphism (SNPs) using adjusted linear regression models and combined using meta-analysis methods. Polygenic risk scores (PRSs) for retinal thickness and AD were generated. RESULTS: Several genetic loci affecting retinal thickness were identified across the genome in accordance with previous reports. The genetic overlap between retinal thickness and dementia, however, was weak and limited to the GCIPL layer; only those observable with all-type dementia cases were considered. CONCLUSIONS: Our study does not support the existence of a genetic link between dementia and retinal thickness.

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BACKGROUND: The FACEmemory® online platform comprises a complex memory test and sociodemographic, medical, and family questions. This is the first study of a completely self-administered memory test with voice recognition, pre-tested in a memory clinic, sensitive to Alzheimer's disease, using information and communication technologies, and offered freely worldwide. OBJECTIVE: To investigate the demographic and clinical variables associated with the total FACEmemory score, and to identify distinct patterns of memory performance on FACEmemory. METHODS: Data from the first 3,000 subjects who completed the FACEmemory test were analyzed. Descriptive analyses were applied to demographic, FACEmemory, and medical and family variables; t-test and chi-square analyses were used to compare participants with preserved versus impaired performance on FACEmemory (cut-off = 32); multiple linear regression was used to identify variables that modulate FACEmemory performance; and machine learning techniques were applied to identify different memory patterns. RESULTS: Participants had a mean age of 50.57 years and 13.65 years of schooling; 64.07% were women, and 82.10% reported memory complaints with worries. The group with impaired FACEmemory performance (20.40%) was older, had less schooling, and had a higher prevalence of hypertension, diabetes, dyslipidemia, and family history of neurodegenerative disease than the group with preserved performance. Age, schooling, sex, country, and completion of the medical and family history questionnaire were associated with the FACEmemory score. Finally, machine learning techniques identified four patterns of FACEmemory performance: normal, dysexecutive, storage, and completely impaired. CONCLUSIONS: FACEmemory is a promising tool for assessing memory in people with subjective memory complaints and for raising awareness about cognitive decline in the community.

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BACKGROUND: SARS-CoV2 induces flu-like symptoms that can rapidly progress to severe acute lung injury and even death. The virus also invades the central nervous system (CNS), causing neuroinflammation and death from central failure. Intravenous (IV) or oral dexamethasone (DXM) reduced 28 d mortality in patients who required supplemental oxygen compared to those who received conventional care alone. Through these routes, DMX fails to reach therapeutic levels in the CNS. In contrast, the intranasal (IN) route produces therapeutic levels of DXM in the CNS, even at low doses, with similar systemic bioavailability. AIMS: To compare IN vs. IV DXM treatment in hospitalized patients with COVID-19. METHODS: A controlled, multicenter, open-label trial. Patients with COVID-19 (69) were randomly assigned to receive IN-DXM (0.12 mg/kg for three days, followed by 0.6 mg/kg for up to seven days) or IV-DXM (6 mg/d for 10 d). The primary outcome was clinical improvement, as defined by the National Early Warning Score (NEWS) ordinal scale. The secondary outcome was death at 28 d between IV and IN patients. Effects of both treatments on biochemical and immunoinflammatory profiles were also recorded. RESULTS: Initially, no significant differences in clinical severity, biometrics, and immunoinflammatory parameters were found between both groups. The NEWS-2 score was reduced, in 23 IN-DXM treated patients, with no significant variations in the 46 IV-DXM treated ones. Ten IV-DXM-treated patients and only one IN-DXM patient died. CONCLUSIONS: IN-DMX reduced NEWS-2 and mortality more efficiently than IV-DXM, suggesting that IN is a more efficient route of DXM administration.

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BACKGROUND: Some researchers have suggested that zinc (Zn) could reduce the risk of prostate cancer (PC). However, research from observational studies on the relationship between PC risk and biomarkers of Zn exposure shows conflicting results. OBJECTIVES: To evaluate the association between toenail Zn and PC, considering tumour extension and aggressiveness, along with a gene-environment approach, exploring the interaction of individual genetic susceptibility to PC in the relationship between toenail Zn and PC. METHODS: In MCC-Spain study we invited all incident PC cases diagnosed in the study period (2008-2013) and recruited randomly selected general population controls. In this report we included 913 cases and 1198 controls with toenail Zn determined by inductively coupled plasma mass spectrometry. To measure individual genetic susceptibility, we constructed a polygenic risk score based on known PC-related single nucleotide polymorphisms. The association between toenail Zn and PC was explored with mixed logistic and multinomial regression models. RESULTS: Men with higher toenail Zn had higher risk of PC (OR quartile 4 vs.1: 1.41; 95% CI: 1.07-1.85). This association was slightly higher in high-grade PC [(ISUP≤2 Relative risk ratio (RRR) quartile 4 vs.1: 1.36; 1.01-1.83) vs. (ISUP3-5 RRR quartile 4 vs.1: 1.64; 1.06-2.54)] and in advanced tumours [(cT1-cT2a RRR quartile 4 vs.1: 1.40; 95% CI: 1.05-1.89) vs. (cT2b-cT4 RRR quartile 4 vs.1: 1.59; 1.00-2.53)]. Men with lower genetic susceptibility to PC were those at higher risk of PC associated with high toenail Zn (OR quartile 4 vs.1: 2.18; 95% CI: 1.08-4.40). DISCUSSION: High toenail Zn levels were related to a higher risk for PC, especially for more aggressive or advanced tumours. This effect was stronger among men with a lower genetic susceptibility to PC.

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Metal nanocrystals (NCs) display unique physicochemical features that are highly dependent on nanoparticle dimensions, anisotropy, structure, and composition. The development of synthesis methodologies that allow us to tune such parameters finely emerges as crucial for the application of metal NCs in catalysis, optical materials, or biomedicine. Here, we describe a synthetic methodology to fabricate hollow multimetallic heterostructures using a combination of seed-mediated growth routes and femtosecond-pulsed laser irradiation. The envisaged methodology relies on the coreduction of Ag and Pd ions on gold nanorods (Au NRs) to form Au@PdAg core-shell nanostructures containing small cavities at the Au-PdAg interface. The excitation of Au@PdAg NRs with low fluence femtosecond pulses was employed to induce the coalescence and growth of large cavities, forming multihollow anisotropic Au@PdAg nanostructures. Moreover, single-hollow alloy AuPdAg could be achieved in high yield by increasing the irradiation energy. Advanced electron microscopy techniques, energy-dispersive X-ray spectroscopy (EDX) tomography, X-ray absorption near-edge structure (XANES) spectroscopy, and finite differences in the time domain (FDTD) simulations allowed us to characterize the morphology, structure, and elemental distribution of the irradiated NCs in detail. The ability of the reported synthesis route to fabricate multimetallic NCs with unprecedented hollow nanostructures offers attractive prospects for the fabrication of tailored high-entropy alloy nanoparticles.

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Luminescence nanothermometry allows measuring temperature remotely and in a minimally invasive way by using the luminescence signal provided by nanosized materials. This technology has allowed, for example, the determination of intracellular temperature and in vivo monitoring of thermal processes in animal models. However, in the biomedical context, this sensing technology is crippled by the presence of bias (cross-sensitivity) that reduces the reliability of the thermal readout. Bias occurs when the impact of environmental conditions different from temperature also modifies the luminescence of the nanothermometers. Several sources that cause loss of reliability have been identified, mostly related to spectral distortions due to interaction between photons and biological tissues. In this work, we unveil an unexpected source of bias induced by metal ions. Specifically, we demonstrate that the reliability of Ag2S nanothermometers is compromised during the monitoring of photothermal processes produced by iron oxide nanoparticles. The observed bias occurs due to the heat-induced release of iron ions, which interact with the surface of the Ag2S nanothermometers, enhancing their emission. The results herein reported raise a warning to the community working on luminescence nanothermometry, since they reveal that the possible sources of bias in complex biological environments, rich in molecules and ions, are more numerous than previously expected.

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BACKGROUND AND AIMS: A gonadotropin-releasing hormone (GnRH)-based therapeutic vaccine candidate against hormone-sensitive prostate cancer has demonstrated its safety and signs of efficacy in phase I/II trials. In this study, we characterized the isotype/subclass profiles of the anti-GnRH humoral response generated by the vaccination and analyzed its association with patients' clinical outcomes. METHODS: The immunoglobulin isotypes and IgG subclasses of the antibody responses of 34 patients included in a randomized, open, prospective phase I/II clinical trial were characterized. Every patient included in the study had a diagnosis of locally advanced prostate adenocarcinoma at stages 3 and 4 and received immunization with the vaccine candidate. Additionally, serum testosterone and prostate specific antigen (PSA) concentrations, serving as indicators of tumor response, were determined. The type of anti-GnRH antibody response was correlated to the time elapsed until the first biochemical recurrence in patients and the outcome of the disease. RESULTS: All patients developed strong and prolonged anti-GnRH antibody responses, resulting in a short- to mid-term decrease in serum testosterone and PSA levels. Following immunizations, anti-GnRH antibodies of the IgM/IgG and IgG1/IgG3 subclasses were observed. Following radiotherapy, the humoral response switched to IgG (IgG1/IgG4). Patients who experienced a short-term biochemical relapse were characterized by significantly higher levels of anti-GnRH IgG titers, particularly IgG1 and IgG4 subclasses. These characteristics, along with a high response of specific IgM antibodies at the end of immunizations and the development of anti-GnRH IgA antibody responses following radiotherapy, were observed in patients whose disease progressed, compared to those with controlled disease. CONCLUSION: The nature of the humoral response against anti-GnRH, induced by vaccination may play a key role in activating additional immunological mechanisms. Collectively, these mechanisms could contribute significantly to the regulation of tumor growth.

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