ProsTAV, a novel blood-based test for biopsy decision management in significant prostate cancer.

BACKGROUND: Current pathways in early diagnosis of prostate cancer (PCa) can lead to unnecessary biopsy procedures. Here, we used telomere analysis to develop and evaluate ProsTAV®, a risk model for significant PCa (Gleason score >6), with the objective of improving the PCa diagnosis pathway. METHODS: This retrospective, multicentric study analyzed telomeres from patients with serum PSA 3-10 ng/mL. High-throughput quantitative fluorescence in-situ hybridization was used to evaluate telomere-associated variables (TAVs) in peripheral blood mononucleated cells. ProsTAV® was developed by multivariate logistics regression based on three clinical variables and six TAVs. The predictive capacity and accuracy of ProsTAV® were summarized by receiver operating characteristic (ROC) curves and its clinical benefit with decision curves analysis. RESULTS: Telomeres from 1043 patients were analyzed. The median age of the patients was 63 years, with a median PSA of 5.2 ng/mL and a percentage of significant PCa of 23.9%. A total of 874 patients were selected for model training and 169 patients for model validation. The area under the ROC curve of ProsTAV® was 0.71 (95% confidence interval [CI], 0.62-0.79), with a sensitivity of 0.90 (95% CI, 0.88-1.0) and specificity of 0.33 (95% CI, 0.24-0.40). The positive predictive value was 0.29 (95% CI, 0.21-0.37) and the negative predictive value was 0.91 (95% CI, 0.83-0.99). ProsTAV® would make it possible to avoid 33% of biopsies. CONCLUSIONS: ProsTAV®, a predictive model based on telomere analysis through TAV, could be used to increase the prediction capacity of significant PCa in patients with PSA between 3 and 10 ng/mL.

Cumulative incidence of SARS-CoV-2 infection in the general population of the Valencian Community (Spain) after the surge of the Omicron BA.1 variant.

Studies investigating the cumulative incidence of and immune status against SARS-CoV-2 infection provide valuable information for shaping public health decision-making. A cross-sectional study on 935 participants, conducted in the Valencian Community (VC), measuring anti-SARS-CoV-2-receptor binding domain-RBD-total antibodies and anti-Nucleocapsid (N)-IgGs via electrochemiluminescence assays. Quantitation of neutralizing antibodies (NtAb) against ancestral and Omicron BA.1 and BA.2 variants and enumeration of SARS-CoV-2-S specific-IFNγ-producing CD4+ and CD8+ T cells was performed in 100 and 137 participants, respectively. The weighted cumulative incidence was 51.9% (95% confidence interval [CI]: 48.7-55.1) and was inversely related to age. Anti-RBD total antibodies were detected in 97% of participants; vaccinated and SARS-CoV-2-experienced (VAC-ex; n = 442) presented higher levels (p < 0.001) than vaccinated/naïve (VAC-n; n = 472) and nonvaccinated/experienced (UNVAC-ex; n = 63) subjects. Antibody levels correlated inversely with time elapsed since last vaccine dose in VAC-n (Rho, -0.52; p < 0.001) but not in VAC-ex (rho -0.02; p = 0.57). Heterologous booster shots resulted in increased anti-RBD antibody levels compared with homologous schedules in VAC-n, but not in VAC-ex. NtAbs against Omicron BA.1 were detected in 94%, 75%, and 50% of VAC-ex, VAC-n and UNVAC-ex groups, respectively. For Omicron BA.2, the figures were 97%, 84%, and 40%, respectively. SARS-CoV-2-S-reactive IFN-γ T cells were detected in 73%, 75%, and 64% of VAC-ex, VAC-n and UNVAC-ex, respectively. Median frequencies for both T-cell subsets were comparable across groups. In summary, by April 2022, around half of the VC population had been infected with SARS-CoV-2 and, due to extensive vaccination, displayed hybrid immunity.

Severe Acute Respiratory Syndrome Coronavirus 2 Adaptive Immunity in Nursing Home Residents Following a Third Dose of the Comirnaty Coronavirus Disease 2019 Vaccine.

A third Comirnaty vaccine dose increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain antibody levels (median, 93-fold) and neutralizing antibody titers against Wuhan-Hu-1 (median, 57-fold), Beta (me 22-fold), Delta, (median, 43-fold), and Omicron (median, 8-fold) variants, but had less impact on S-reactive T-cell immunity in nursing home residents.

SARS-CoV-2 Delta-variant breakthrough infections in nursing home residents at midterm after Comirnaty® COVID-19 vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant breakthrough infections in nursing home residents following vaccination with Comirnaty® COVID-19 vaccine were characterized. In total, 201 participants (median age, 87 years; range, 64-100; 133 female) from two nursing homes in the Valencian community (Spain) were included. SARS-CoV-2-Spike (S) antibody responses were determined by a lateral flow immunocromatography (LFIC) assay and by quantitative electrochemiluminescent assay in LFIC-negative participants. SARS-CoV-2-S-IFNγ T cells were enumerated by flow cytometry in 10 participants. Nasopharyngeal SARS-CoV-2 RNA loads were quantified by real-time polymerase chain reaction assays. Vaccine breakthrough COVID-19 due to the Delta variant occurred in 39 residents (median age, 87 years; range, 69-96; 31 female) at a median of 6.5 months after vaccination (nine requiring hospitalization). Breakthrough infections occurred at a higher rate (p < 0.0001) in residents who had not been previously infected with SARS-CoV-2 (naïve) (33/108; 18%) than in those with prior diagnosis of SARS-CoV-2 infection (experienced) (6/93; 6.4%), and were more likely (p < 0.0001) to develop in residents who tested negative by LFIC (20/49) at 3 months after vaccination as compared to their LFIC-positive counterparts (19/142). Among LFIC-negative residents, a trend towards lower plasma anti-RBD antibody levels was noticed in those developing breakthrough infection (p = 0.16). SARS-CoV-2 RNA loads in nasopharyngeal specimens were lower in SARS-CoV-2-experienced residents (p < 0.001) and in those testing positive by LFIC (p = 0.13). The frequency of SARS-CoV-2-S-reactive T cells at 3 months was similar in LFIC-negative residents with (n = 7) or without (n = 3) breakthrough infection. Prior history of SARS-CoV-2 infection and detection of S-reactive antibodies by LFIC at 3 months is associated with a lower risk of Delta-variant breakthrough infection in nursing home residents at midterm after Comirnaty® COVID-19 vaccination.

SARS-CoV-2 Omicron BA.1 variant breakthrough infections in nursing home residents after an homologous third dose of the Comirnaty® COVID-19 vaccine: Looking for correlates of protection.

We investigated whether peripheral blood levels of SARS-CoV-2 Spike (S) receptor binding domain antibodies (anti-RBD), neutralizing antibodies (NtAb) targeting Omicron S, and S-reactive-interferon (IFN)-γ-producing CD4+ and CD8+ T cells measured after a homologous booster dose (3D) with the Comirnaty® vaccine was associated with the likelihood of subsequent breakthrough infections due to the Omicron variant. An observational study including 146 nursing home residents (median age, 80 years; range, 66-99; 109 female) evaluated for an immunological response after 3D (at a median of 16 days). Anti-RBD total antibodies were measured by chemiluminescent immunoassay. NtAb were quantified by an Omicron S pseudotyped virus neutralization assay. SARS-CoV-2-S specific-IFNγ-producing CD4+ and CD8+ T cells were enumerated by whole-blood flow cytometry for intracellular cytokine staining. In total, 33/146 participants contracted breakthrough Omicron infection (symptomatic in 30/33) within 4 months after 3D. Anti-RBD antibody levels were comparable in infected and uninfected participants (21 123 vs. 24 723 BAU/ml; p = 0.34). Likewise, NtAb titers (reciprocal IC50 titer, 157 vs. 95; p = 0.32) and frequency of virus-reactive CD4+ (p = 0.82) and CD8+ (p = 0.91) T cells were similar across participants in both groups. anti-RBD antibody levels and NtAb titers estimated at around the time of infection were also comparable (3445 vs. 4345 BAU/ml; p = 0.59 and 188.5 vs. 88.9; p = 0.70, respectively). Having detectable NtAb against Omicron or SARS-CoV-2-S-reactive-IFNγ-producing CD4+ or CD8+ T cells after 3D was not correlated with increased protection from breakthrough infection (OR, 1.50; p = 0.54; OR, 0.0; p = 0.99 and OR 3.70; p = 0.23, respectively). None of the immune parameters evaluated herein, including NtAb titers against the Omicron variant, may reliably predict at the individual level the risk of contracting COVID-19 due to the Omicron variant in nursing home residents.

Adherence to guideline recommendations in the management of upper tract urothelial carcinoma: an analysis of the CROES-UTUC registry.

BACKGROUND: The European Association of Urology provides Clinical Practice Guideline on upper tract urothelial carcinoma (UTUC). Due to the rarity of UTUC, guidelines are necessary to help guide decision-making based on the highest quality of care evidence available. OBJECTIVES: To evaluate guideline adherence in the management of UTUC by assessing recommendations on diagnostics needed for risk classification and subsequent treatment selection; to assess predictors for the latter. PARTICIPANTS: Data from the Clinical Research Office of the Endo Urology Society UTUC-registry were included for analysis. STATISTICAL ANALYSIS: Overall compliance were evaluated by cross-tables, differences in risk groups characteristics and treatment selection were assessed by Chi-square tests, predictors for treatment selection by logistic regression analysis. RESULTS: Data from 2380 patients were included. Imaging by CT-scan had highest adherence (85%) but was low for other diagnostics (17.7-49.7%). Multivariable regression analysis showed higher odds of receiving radical nephroureterectomy in patients with large tumours (OR 5.45, 95% CI 3.77-7.87, p < 0.001), signs of invasion (OR 3.07,CI 2.11-4.46, p < 0.001), high tumour grade (OR 2.05, CI 1.38-3.05, p < 0.001) and multifocality (OR 1.76,CI 1.05-2.97, p =0.032). CONCLUSIONS: CT-imaging is the most used and most impactful decision tool for risk-stratification and treatment selection in UTUC. Due to the low compliance in most of the diagnostic recommendations, proper risk stratification is not possible in a significant group of patients raising the question whether current stratification is deemed applicable in daily practice. Established prognostic factors on survival guides decision-making regarding radical versus kidney-sparing surgery. Tumour size was the most influencing factor on treatment decision. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (ClinicalTrials.gov NCT02281188; https://clinicaltrials.gov/ct2/show/NCT02281188 ).

The effectiveness of mRNA vaccines to prevent SARS-CoV-2 infection and hospitalisation for COVID-19 according to the time elapsed since their administration in health professionals in the Valencian Autonomous Community (Spain).

The objective was to understand the effectiveness of the BNT162b2 and mRNA-1273 vaccines against SARS-CoV-2 in health professionals(HPs) in the Valencian Autonomous Community(Spain) who had completed a full vaccination regimen, both in terms of preventing infections and avoiding hospitalisations, according to the time elapsed since the vaccine administration. Case-controlled study with negative test results. HPs who had undergone at least one PCR or antigen(Ag) active infection diagnostic test(AIDT) to rule out SARS-CoV-2 infection between 25 January and 18 July 2021 were included. HPs with positive AIDT result were considered as cases and those with a negative result controls. Adjusted vaccine effectiveness(VEa) to prevent SARS-CoV-2 infection and its 95% confidence interval(95% CI) were calculated using the formula VEa = (1 - OR) × 100. The VEa for the prevention of SARS-CoV-2 infection 12 to 120 days after completing the full two-dose vaccine regimen was 91.6%(95%CI[89.6%,93.2%]) for the BNT162b2 vaccine and 95.2%(95%CI[88.3%,98.1%]) for the mRNA-1273 vaccine. After 120 days the VEa was 71.5%(95%CI[67.0%,75.5%]) for the BNT162b2 vaccine and 88.3%(95%CI[75.7,94.4%]) for the mRNA-1273 vaccine. The VEa for prevention of hospitalisation for COVID-19 for the complete two-dose regimen of mRNA vaccines (BNT162b2 and mRNA-1273) was 96.8%(95%CI[76.1%,99.6%]). The administration of the complete regimen of the BNT162b2 and mRNA-1273 vaccine against SARS-CoV-2 was highly effective for the prevention of COVID-19 cases in HPs when 12 to 120 days had elapsed since the second dose. However, said effectiveness decreased as time from the vaccine administration elapsed, although it was maintained for the prevention of hospitalisation of HPs.

Night shift work, chronotype and prostate cancer risk in the MCC-Spain case-control study.

Night shift work has been classified as a probable human carcinogen based on experimental studies and limited human evidence on breast cancer. Evidence on other common cancers, such as prostate cancer, is scarce. Chronotype is an individual characteristic that may relate to night work adaptation. We evaluated night shift work with relation to prostate cancer, taking into account chronotype and disease severity in a population based case-control study in Spain. We included 1,095 prostate cancer cases and 1,388 randomly selected population controls. We collected detailed information on shift schedules (permanent vs. rotating, time schedules, duration, frequency), using lifetime occupational history. Sociodemographic and lifestyle factors were assessed by face-to-face interviews and chronotype through a validated questionnaire. We used unconditional logistic regression analysis adjusting for potential confounders. Subjects who had worked at least for one year in night shift work had a slightly higher prostate cancer risk [Odds Ratio (OR) 1.14; 95%CI 0.94, 1.37] compared with never night workers; this risk increased with longer duration of exposure (≥ 28 years: OR 1.37; 95%CI 1.05, 1.81; p-trend = 0.047). Risks were more pronounced for high risk tumors [D'Amico classification, Relative Risk Ratio (RRR) 1.40; 95%CI 1.05, 1.86], particularly among subjects with longer duration of exposure (≥28 years: RRR 1.63; 95%CI 1.08, 2.45; p-trend = 0.027). Overall risk was higher among subjects with an evening chronotype, but also increased in morning chronotypes after long-term night work. In this large population based study, we found an association between night shift work and prostate cancer particularly for tumors with worse prognosis.

Effectiveness of mRNA booster doses in preventing infections and hospitalizations due to SARS-CoV-2 and its dominant variant over time in Valencian healthcare workers, Spain.

OBJECTIVE: This study aimed to evaluate the effectiveness of SARS-CoV-2 mRNA vaccines in preventing infection and hospitalization among healthcare workers (HCWs) in the Valencian Community (Spain), considering vaccination timing, dose number, and predominant variant. METHODS: A test-negative case-control design estimated vaccine effectiveness against symptomatic disease and hospitalization due to SARS-CoV-2. HCWs who underwent PCR or antigen testing for SARS-CoV-2 from January 2021 to March 2022 were included. Cases had a positive diagnostic test, while controls had negative tests. Adjusted vaccine effectiveness (aVE) was calculated using the formula: aVE = (1 - Odds ratio) × 100. RESULTS: During the Delta variant's predominance, aVE against infection within 12-120 days post-second dose was 64.8 % (BNT162b2) and 59.4 % (mRNA-1273), declining to 21.2 % and 42.2 %, respectively, after 120 days. For the Omicron variant, aVE within 12-120 days post-second dose was 61.1 % (BNT162b2) and 85.1 % (mRNA-1273), decreasing to 36.7 % and 24.9 %, respectively, after 120 days. After a booster dose of mRNA-1273, aVE was 64.0 % (BNT162b2 recipients) and 65.9 % (initial mRNA-1273 recipients). Regardless of variant, aVE for hospitalization prevention after 2 doses was 87.0 % (BNT162b2) and 89.0 % (mRNA-1273). CONCLUSION: The administration of two doses of Moderna-mRNA-1273 against SARS-CoV-2 in HCWs proved to be highly effective in preventing infections and hospitalizations in the first 120 days after the second dose during the predominance of the Omicron variant. The decline in VE after 120 days since the administration of the second dose was significantly restored by the booster dose administration. This increase in VE was greater for the Pfizer vaccine. COVID-19 hospitalization prevention remained stable with both mRNA vaccines throughout the study period.

Combined Ultrahypofractionated Whole-Breast Irradiation and IORT-Boost: A Safety and Feasibility Analysis.

BACKGROUND: The current standard of local treatment for patients with localized breast cancer (BC) includes whole breast irradiation (WBI) after breast-conserving surgery (BCS). Ultrahypofractionated WBI schemes (1-week treatment) were shown not to be inferior to the standard WBI. Tumor bed boost using photon intraoperative radiotherapy (IORT) is safe and feasible in combination with standard WBI. The aim of the present study is to assess, for the first time, the feasibility and safety of combining photon IORT with ultrahypofractionated WBI. METHODS: Patients diagnosed with low-risk early BC candidates for BCS were included in this prospective study. IORT was administered at a dose of 20 Gy to the surface's applicator, and WBI was administered 3-5 weeks after surgery at a total dose of 26 Gy in five consecutive days. RESULTS: From July 2020 to December 2022, seventy-two patients diagnosed with low-risk early BC and treated in our institution were included in this prospective study. All patients completed the proposed treatment, and no severe acute or late grade 3 toxicity was observed 3 and 12 months after WBI, respectively. CONCLUSIONS: Our results confirm for the first time that the combination of ultrafractionation WBI and photon-IORT after BCS is a feasible and safe option in patients with early BC.

A robust method for quantitative high-throughput analysis of proteomes by 18O labeling.

MS-based quantitative proteomics plays an increasingly important role in biological and medical research and the development of these techniques remains one of the most important challenges in mass spectrometry. Numerous stable isotope labeling approaches have been proposed. However, and particularly in the case of (18)O-labeling, a standard protocol of general applicability is still lacking, and statistical issues associated to these methods remain to be investigated. In this work we present an improved high-throughput quantitative proteomics method based on whole proteome concentration by SDS-PAGE, optimized in-gel digestion, peptide (18)O-labeling, and separation by off-gel isoelectric focusing followed by liquid chromatography-LIT-MS. We demonstrate that the off-gel technique is fully compatible with (18)O peptide labeling in any pH range. A recently developed statistical model indicated that partial digestions and methionine oxidation do not alter protein quantification and that variances at the scan, peptide, and protein levels are stable and reproducible in a variety of proteomes of different origin. We have also analyzed the dynamic range of quantification and demonstrated the practical utility of the method by detecting expression changes in a model of activation of Jurkat T-cells. Our protocol provides a general approach to perform quantitative proteomics by (18)O-labeling in high-throughput studies, with the added value that it has a validated statistical model for the null hypothesis. To the best of our knowledge, this is the first report where a general protocol for stable isotope labeling is tested in practice using a collection of samples and analyzed at this degree of statistical detail.

Androgen Receptor Signaling Inhibition in Advanced Castration Resistance Prostate Cancer: What Is Expected for the Near Future?

The androgen signaling pathway is the cornerstone in the treatment of high risk or advanced prostate cancer patients. However, in recent years, different mechanisms of resistance have been defined in this field, limiting the efficacy of the currently approved antiandrogen drugs. Different therapeutic approaches are under research to assess the role of combination therapies against escape signaling pathways or the development of novel antiandrogen drugs to try to solve the primary or acquired resistance against androgen dependent or independent pathways. The present review aims to summarize the current state of androgen inhibition in the therapeutic algorithm of patients with advanced prostate cancer and the mechanisms of resistance to those available drugs. In addition, this review conducted a comprehensive overview of the main present and future research approaches in the field of androgen receptor inhibition to overcome these resistances and the potential new drugs under research coming into this setting.

SARS-CoV-2 adaptive immunity in nursing home residents up to eight months after two doses of the Comirnaty® COVID-19 vaccine.

Burgos JS (General Directorate of Research and Healthcare Supervision, Department of Health, Valencia Government, Valencia, Spain); Meneu de Guillerna R (Vice-President Foundation Research Institute in Public Services, Valencia, Spain); Vanaclocha Luna H (General Directorate of Public Health, Department of Health, Valencia Government, Valencia, Spain); Burks DJ (The Prince Felipe Research Center-CIPF-, Valencia, Spain; Cervantes A (INCLIVA Health Research Institute, Valencia, Spain); Comas I (Biomedicine Institute of Valencia, Spanish Research Council (CSIC); Díez-Domingo J (Foundation for the promotion of health and biomedical research of the Valencian Community-FISABIO-, Valencia, Spain); Peiro S (Foundation for the promotion of health and biomedical research of the Valencian Community-FISABIO-, Valencia, Spain); González-Candelas F (CIBER in Epidemiology and Public Health, Spain; Joint Research Unit "Infection and Public Health" FISABIO-University of Valencia, Valencia, Spain; Institute for Integrative Systems Biology (I2SysBio), CSIC-University of Valencia, Valencia, Spain); Ferrer Albiach C (Fundación Hospital Provincial de Castelló); Hernández-Aguado I (University Miguel Hernández, Alicante, Spain); Oliver Ramírez N (DataPop Alliance); Sánchez-Payá J (Preventive Medicine Service, Alicante General and University Hospital, Alicante, Spain; Alicante Institute of Health and Biomedical Research (ISABIAL), Alicante, Spain; Vento Torres M (Instituto de Investigación Sanitaria La Fe); Zapater Latorre E (Fundación Hospital General Universitario de València); Navarro D (Microbiology Service, Clinic University Hospital, INCLIVA Health Research Institute, Valencia, Spain;Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain).

Immunological response against SARS-CoV-2 following full-dose administration of Comirnaty® COVID-19 vaccine in nursing home residents.

OBJECTIVES: The current study was aimed at examining SARS-CoV-2 immune responses following two doses of Comirnaty® COVID-19 vaccine among elderly people in nursing homes. METHODS: A prospective cohort study in a representative sample from nursing homes in Valencia (n = 881; males: 271, females 610; median age, 86 years) recruited residents using a random one-stage cluster sampling approach. A lateral flow immunochromatography device (LFIC) (OnSite COVID-19 IgG/IgM Rapid Test; CTK BIOTECH, Poway, CA, USA) was used as the front-line test for detecting SARS-CoV-2-Spike (S)-specific antibodies in whole blood obtained using a fingerstick. Residents returning negative LFIC results underwent venipuncture and testing for presence of SARS-CoV-2-S-reactive antibodies and T cells using the Roche Elecsys® Anti-SARS-CoV-2 S (Roche Diagnostics, Pleasanton, CA, USA), the LIAISON® SARS-CoV-2 TrimericS IgG assay (Diasorin S.p.A, Saluggia, Italy) and by flow cytometry, respectively. RESULTS: The SARS-CoV-2-S antibody detection rate in nursing home residents was 99.6% (283/284) and 98.3% (587/597) for SARS-CoV-2 recovered and naïve residents, respectively, within a median of 99 days (range 17-125 days) after full vaccination. Three out of five residents lacking SARS-CoV-2-S antibodies had detectable S-reactive CD8+ and/or CD4+ T cells. In addition, 50/50 and 40/50 participants with detectable SARS-CoV-2 antibodies also had SARS-CoV-2-S-reactive interferon-γ-producing CD4+ and CD8+ T cells, respectively. DISCUSSION: The Comirnaty® COVID-19 vaccine is highly immunogenic in nursing home residents.

Clinical and Novel Biomarkers in Penile Carcinoma: A Prospective Review.

Penile carcinoma is a rare urological neoplasia in men compared to other more common tumors, such as prostate, kidney, or bladder tumors. However, this neoplasm continues to affect a large number of patients worldwide, with developing countries presenting the highest incidence and mortality rates. Important risk factors such as the human papilloma virus, a factor affecting a large number of patients, have been described; however, few studies have evaluated screening programs in populations at risk for this disease, which severely affects the quality of life of older men. The management of these patients is usually complex, requiring surgical interventions that are not without risk and that have a great impact on the functionality of the male reproductive system. In addition, in cases of disseminated disease or with significant locoregional involvement, patients are evaluated by multidisciplinary oncological committees that can adjust the application of aggressive neoadjuvant or adjuvant chemotherapy on numerous occasions without clear improvement in survival. Chemotherapy regimens are usually aggressive, and unlike in other urological neoplasms, few advances have been made in the use of immunotherapy in these patients. The study of serological and histological biomarkers may help to better understand the underlying pathophysiology of these tumors and select patients who have a higher risk of metastatic progression. Similarly, the analysis of molecular markers will improve the availability of targeted therapies for the management of patients with disseminated disease that would benefit prognosis. Therefore, the purpose of this article is to summarize the main advances that have occurred in the development of serological and histological markers and their therapeutic implications in patients diagnosed with penile carcinoma, explaining the limitations that have been observed and analyzing future perspectives in the management of this disease.

Side effects during the week after first dose vaccination with four Covid-19 vaccines. Results of the ProVaVac Survey Study with 13,837 people in Spain.

BACKGROUND: In 2021, four vaccines against Covid-19 (BNT162b2, mRNA-1273, ChAdOx1nCoV-19, and JNJ-78436735) were employed in the region of Valencia, Spain. We conducted a survey to identify real-world, self-reported frequency and severity of side effects during the week after vaccination. METHODS: Survey data was obtained from April 19, 2021, to October 6, 2021, at three different moments in time: day one, day three and day seven after vaccination. Answers were linked to individual-level, personal and clinical information. Respondents were stratified by the vaccine they received and reported effects were presented over time and stratified by severity. We compared our results per vaccine with the frequencies stated in each Summary of Product Characteristics (SmPC). We used binomial logistic models to identify associations between respondent characteristics and side effects. RESULTS: No symptoms were reported by 1,986 respondents (14.35 %), 6,254 informed exclusively mild symptoms (45.20 %), 3,444 up to moderate symptoms (24.89 %), and 2,153 people (15.56 %) notified also severe symptoms. Among the latter, the more frequent were extreme tiredness (7.0 %), and nausea or vomiting (7.1 %). The reported frequency of facial paralysis (0.4 %) was much higher than reflected in SmPCs. Female sex, younger age, previous positive Active Infection Diagnostic Test, chronicity, and vaccination with other than the BNT162b2 vaccine were associated to an increased risk of side effects (p < 0.001). CONCLUSIONS: Side effects after vaccination are common in the real-world. However, they are principally mild, and their frequency declines after a few days. Providing patients with dependable, beforehand information about side effects may improve outcomes and reinforce vaccination programs.

Kainate administered to adult zebrafish causes seizures similar to those in rodent models.

Glutamate is the major excitatory neurotransmitter of the central nervous system in vertebrates. Excitotoxicity, caused by over-stimulation of the glutamate receptors, is a major cause of neuron death in several brain diseases, including epilepsy. We describe here how behavioural seizures can be triggered in adult zebrafish by the administration of kainate and are very similar to those observed in rodent models. Kainate induced a dose-dependent sequence of behavioural changes culminating in clonus-like convulsions. Behavioural seizures were suppressed by DNQX (6,7-dinitroquinoxaline-2,3-dione) dose-dependently, whilst MK-801 (a non-competitive NMDA receptor antagonist) had a lesser effect. Kainate triggers seizures in adult zebrafish, and thus this species can be considered as a new model for studying seizures and subsequent excitotoxic brain injury.

Synergic effect of salinity and zinc stress on growth and photosynthetic responses of the cordgrass, Spartina densiflora.

Spartina densiflora is a C(4) halophytic species that has proved to have a high invasive potential which derives from its physiological plasticity to environmental factors, such as salinity. It is found in coastal marshes of south-west Spain, growing over sediments with between 1 mmol l(-1) and 70 mmol l(-1) zinc. A glasshouse experiment was designed to investigate the synergic effect of zinc from 0 mmol l(-1) to 60 mmol l(-1) at 0, 1, and 3% NaCl on the growth and the photosynthetic apparatus of S. densiflora by measuring chlorophyll fluorescence parameters and gas exchange, and its recovery after removing zinc. Antioxidant enzyme activities and total zinc, sodium, calcium, iron, magnesium, manganese, phosphorus, potassium, and nitrogen concentrations were also determined. Spartina densiflora showed the highest growth at 1 mmol l(-1) zinc and 1% NaCl after 90 d of treatment; this enhanced growth was supported by the measurements of net photosynthetic rate (A). Furthermore, there was a stimulatory effect of salinity on accumulation of zinc in tillers of this species. Zinc concentrations >1 mmol l(-1) reduced growth of S. densiflora, regardless of salinity treatments. This declining growth may be attributed to a decrease in A caused by diffusional limitation of photosynthesis, owing to the modification of the potassium/calcium ratio. Also, zinc and salinity had a marked overall effect on the photochemical (photosystem II) apparatus, partially mediated by the accumulation of H(2)O(2) and subsequent oxidative damage. However, salinity favoured the recovery of the photosynthetic apparatus to the toxic action of zinc, and enhanced the nutrient uptake.

Same pollution sources for climate change might be hyperactivating the NLRP3 inflammasome and exacerbating neuroinflammation and SARS mortality.

We have reviewed a considerable amount of recent scientific papers relating inflammation caused by air pollution with chronic and severe medical conditions. Furthermore, there are evidences relating organ inflammation caused by not only outdoor long-term but also short-term inhaled radioisotopes contained in high polluted air or in household natural radioactive background aerosols, in addition to SARS-COV-2 attached to bioaerosols, which are related with a worst evolution of severe acute respiratory syndrome patients. Reactive oxygen species (ROS) production induced by the interaction with environmental ionizing radiation contained in pollution is pointed out as a critical mechanism that predispose mainly to elder population, but not excluding young subjects, presenting previous chronic conditions of lung inflammation or neuroinflammation, which can lead to the most serious consequences.