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1.
Open Forum Infect Dis ; 11(4): ofae132, 2024 Apr.
Article En | MEDLINE | ID: mdl-38560603

Background: Effective antiretroviral therapy (ART) has substantially reduced acquired immunodeficiency syndrome (AIDS)-related deaths, shifting the focus to non-AIDS conditions in people living with human immunodeficiency virus (HIV) (PLWH). We examined mortality trends and predictors of AIDS- and non-AIDS mortality in the Population HIV Cohort from Catalonia and Balearic Islands (PISCIS) cohort of PLWH from 1998 to 2020. Methods: We used a modified Coding Causes of Death in HIV protocol, which has been widely adopted by various HIV cohorts to classify mortality causes. We applied standardized mortality rates (SMR) to compare with the general population and used competing risks models to determine AIDS-related and non-AIDS-related mortality predictors. Results: Among 30 394 PLWH (81.5% male, median age at death 47.3), crude mortality was 14.2 per 1000 person-years. All-cause standardized mortality rates dropped from 9.6 (95% confidence interval [CI], 8.45-10.90) in 1998 through 2003 to 3.33 (95% CI, 3.14-3.53) in 2015 through 2020, P for trend = .0001. Major causes were AIDS, non-AIDS cancers, cardiovascular disease, AIDS-defining cancers, viral hepatitis, and nonhepatitis liver disease. Predictors for AIDS-related mortality included being aged ≥40 years, not being a man who have sex with men, history of AIDS-defining illnesses, CD4 < 200 cells/µL, ≥2 comorbidities, and nonreceipt of ART. Non-AIDS mortality increased with age, injection drug use, heterosexual men, socioeconomic deprivation, CD4 200 to 349 cells/µL, nonreceipt of ART, and comorbidities, but migrants had lower risk (adjusted hazard risk, 0.69 [95% CI, .57-.83]). Conclusions: Mortality rates among PLWH have significantly decreased over the past 2 decades, with a notable shift toward non-AIDS-related causes. Continuous monitoring and effective management of these non-AIDS conditions are essential to enhance overall health outcomes.

2.
Clin. transl. oncol. (Print) ; 26(2): 549-553, feb. 2024.
Article En | IBECS | ID: ibc-230199

Purpose Neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients has proven beneficial in overall survival. However, the optimal regimen is still a matter of debate. Materials and method In this retrospective analysis, we evaluate the results obtained in 42 patients treated in our center with 4 cycles of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) followed by radical cystectomy from August 2015 to October 2020. All patients had cT2 or higher non-metastatic MIBC. Clinical and pathological outcomes are reported. Results Of the 42 patients, 90.5% were men (n = 38) and the mean age was 65 years. All of them had ECOG 0–1 at diagnosis and most tumors had an initial clinical stage T2N0 (76%). Thirty-six patients (85.7%) completed 4 cycles of neoadjuvant treatment, and 21.4% required a dose reduction. The most frequent adverse event (AE) was grade 1–2 asthenia (81%), while neutropenia was the most frequent grade 3 or higher AE (38%). Complete pathological response (ypT0, ypN0) was achieved in 50% of patients (n = 21), and down-staging was observed in 57.1% (n = 24). Only one patient presented radiological progressive disease during neoadjuvant treatment (2.4%), and after a mean follow-up time of 31.5 months, 33.3% of patients experienced disease recurrence. Conclusions Neoadjuvant chemotherapy with 4 cycles of dd-MVAC is an effective regimen with high rates of pathological complete responses and down-staging along with an acceptable toxicity profile. DD-MVAC should be considered as an alternative to cisplatin and gemcitabine in patients with good clinical performance status (AU)


Humans , Male , Female , Aged , Antineoplastic Combined Chemotherapy Protocols , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Doxorubicin/administration & dosage , Neoadjuvant Therapy , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Retrospective Studies
3.
Microbiol Spectr ; 12(2): e0259423, 2024 Feb 06.
Article En | MEDLINE | ID: mdl-38230926

Fungal infections are a growing global health concern due to the limited number of available antifungal therapies as well as the emergence of fungi that are resistant to first-line antimicrobials, particularly azoles and echinocandins. Development of novel, selective antifungal therapies is challenging due to similarities between fungal and mammalian cells. An attractive source of potential antifungal treatments is provided by ecological niches co-inhabited by bacteria, fungi, and multicellular organisms, where complex relationships between multiple organisms have resulted in evolution of a wide variety of selective antimicrobials. Here, we characterized several analogs of one such natural compound, collismycin A. We show that NR-6226C has antifungal activity against several pathogenic Candida species, including C. albicans and C. glabrata, whereas it only has little toxicity against mammalian cells. Mechanistically, NR-6226C selectively chelates iron, which is a limiting factor for pathogenic fungi during infection. As a result, NR-6226C treatment causes severe mitochondrial dysfunction, leading to formation of reactive oxygen species, metabolic reprogramming, and a severe reduction in ATP levels. Using an in vivo model for fungal infections, we show that NR-6226C significantly increases survival of Candida-infected Galleria mellonella larvae. Finally, our data indicate that NR-6226C synergizes strongly with fluconazole in inhibition of C. albicans. Taken together, NR-6226C is a promising antifungal compound that acts by chelating iron and disrupting mitochondrial functions.IMPORTANCEDrug-resistant fungal infections are an emerging global threat, and pan-resistance to current antifungal therapies is an increasing problem. Clearly, there is a need for new antifungal drugs. In this study, we characterized a novel antifungal agent, the collismycin analog NR-6226C. NR-6226C has a favorable toxicity profile for human cells, which is essential for further clinical development. We unraveled the mechanism of action of NR-6226C and found that it disrupts iron homeostasis and thereby depletes fungal cells of energy. Importantly, NR-6226C strongly potentiates the antifungal activity of fluconazole, thereby providing inroads for combination therapy that may reduce or prevent azole resistance. Thus, NR-6226C is a promising compound for further development into antifungal treatment.


Anti-Infective Agents , Mycoses , Animals , Humans , Antifungal Agents/pharmacology , Fluconazole/pharmacology , Iron , Candida , Mycoses/microbiology , Candida albicans , Anti-Infective Agents/pharmacology , Azoles/pharmacology , Candida glabrata , Iron Chelating Agents/pharmacology , Drug Resistance, Fungal , Microbial Sensitivity Tests , Mammals
4.
Clin Transl Oncol ; 26(2): 549-553, 2024 Feb.
Article En | MEDLINE | ID: mdl-37566343

PURPOSE: Neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients has proven beneficial in overall survival. However, the optimal regimen is still a matter of debate. MATERIALS AND METHODS: In this retrospective analysis, we evaluate the results obtained in 42 patients treated in our center with 4 cycles of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) followed by radical cystectomy from August 2015 to October 2020. All patients had cT2 or higher non-metastatic MIBC. Clinical and pathological outcomes are reported. RESULTS: Of the 42 patients, 90.5% were men (n = 38) and the mean age was 65 years. All of them had ECOG 0-1 at diagnosis and most tumors had an initial clinical stage T2N0 (76%). Thirty-six patients (85.7%) completed 4 cycles of neoadjuvant treatment, and 21.4% required a dose reduction. The most frequent adverse event (AE) was grade 1-2 asthenia (81%), while neutropenia was the most frequent grade 3 or higher AE (38%). Complete pathological response (ypT0, ypN0) was achieved in 50% of patients (n = 21), and down-staging was observed in 57.1% (n = 24). Only one patient presented radiological progressive disease during neoadjuvant treatment (2.4%), and after a mean follow-up time of 31.5 months, 33.3% of patients experienced disease recurrence. CONCLUSIONS: Neoadjuvant chemotherapy with 4 cycles of dd-MVAC is an effective regimen with high rates of pathological complete responses and down-staging along with an acceptable toxicity profile. DD-MVAC should be considered as an alternative to cisplatin and gemcitabine in patients with good clinical performance status.


Neoadjuvant Therapy , Urinary Bladder Neoplasms , Male , Humans , Aged , Female , Cisplatin , Retrospective Studies , Deoxycytidine/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Neoplasm Invasiveness , Neoplasm Recurrence, Local/drug therapy , Urinary Bladder Neoplasms/pathology , Doxorubicin , Methotrexate , Vinblastine/adverse effects , Muscles/pathology
7.
Rev. esp. enferm. dig ; 115(12): 750-751, Dic. 2023. ilus
Article En, Es | IBECS | ID: ibc-228740

Melanoma is a cancer that frequently metastasises to the small bowel, but most cases are asymptomatic and are diagnosed postmortem. Therefore, CT and PET CT cannot detect all lesions and conventional endoscopic study only detects 10-20% of lesions. In this study, we present the case of a 68-year-old patient with a history of cutaneous melanoma and a diagnosis of intestinal melanoma. Thanks to capsule endoscopy, two lesions compatible with cutaneous melanoma metastasis to the small bowel were detected, allowing a much more effective surgical planning. Capsule endoscopy is an innovative technique that improves preoperative diagnosis, as it is able to detect bowel segments that cannot be inspected by conventional endoscopy. It also has a better resolution than conventional CT, improving sensitivity in the detection of lesions.(AU)


Humans , Male , Middle Aged , Capsule Endoscopes , Intestine, Small , Melanoma/diagnostic imaging , Endoscopy, Gastrointestinal , Intestinal Neoplasms/surgery , Inpatients , Physical Examination , Treatment Outcome
8.
Microorganisms ; 11(11)2023 Nov 03.
Article En | MEDLINE | ID: mdl-38004713

We investigated differences in mpox clinical outcomes in people with HIV (PWH) and without HIV (PWoH) and the impact of vaccination in Catalonia, Spain. We used surveillance data and the PISCIS HIV cohort. We included all confirmed mpox cases (May-December 2022). Of 2122 mpox cases, the majority had mild disease, 56% were Spanish, and 24% were from Latin America. A total of 40% were PWH, with a median CD4+T-cell of 715 cells/µL; 83% had HIV-RNA < 50 copies/mL; and 1.8% CD4+T-cell < 200 cells/µL. PWH had no increased risk for complications, except those with CD4+T-cell < 200 cells/µL. PWH with CD4+T-cell < 200 cells/µL were more likely to be from Latin America, had more generalized exanthema, and required hospitalization more frequently (p = 0.001). Diagnosis of other sexually transmitted infections (STIs) was common, both at mpox diagnosis (17%) and two years before (43%). Dose-sparing smallpox intradermal vaccination was accompanied by a sharp decrease in mpox incidence in both populations (p < 0.0001). In conclusion, unless immunosuppressed, PWH were not at increased risk of severe disease or hospitalization. Mpox is a marker of high-risk sexual behavior and was associated with high HIV and STI rates, supporting the need for screening in all mpox cases. Ethnicity disparities demonstrate the need for interventions to ensure equitable healthcare access. Dose-sparing smallpox vaccination retained effectiveness.

9.
Nat Commun ; 14(1): 5998, 2023 10 02.
Article En | MEDLINE | ID: mdl-37783731

The recent monkeypox virus (MPXV) outbreak was of global concern and has mainly affected gay, bisexual and other men who have sex with men (GBMSM). Here we assess prevalence of MPXV in high-risk populations of GBMSM, trans women (TW) and non-binary people without symptoms or with unrecognized monkeypox (Mpox) symptoms, using a self-sampling strategy. Anal and pharyngeal swabs are tested by MPXV real-time PCR and positive samples are tested for cytopathic effect (CPE) in cell culture. 113 individuals participated in the study, 89 (78.76%) were cis men, 17 (15.04%) were TW. The median age was 35.0 years (IQR: 30.0-43.0), 96 (85.02%) individuals were gay or bisexual and 72 (63.72%) were migrants. Seven participants were MPXV positive (6.19% (95% CI: 1.75%-10.64%)). Five tested positive in pharyngeal swabs, one in anal swab and one in both. Six did not present symptoms recognized as MPXV infection. Three samples were positive for CPE, and showed anti-vaccinia pAb staining by FACS and confocal microscopy. This suggests that unrecognized Mpox cases can shed infectious virus. Restricting testing to individuals reporting Mpox symptoms may not be sufficient to contain outbreaks.


Mpox (monkeypox) , Sexual and Gender Minorities , Male , Humans , Female , Adult , Spain/epidemiology , Homosexuality, Male , Mpox (monkeypox)/diagnosis , Mpox (monkeypox)/epidemiology , Monkeypox virus/genetics
10.
Nat Cell Biol ; 25(10): 1478-1494, 2023 Oct.
Article En | MEDLINE | ID: mdl-37749225

All eukaryotic cells require a minimal iron threshold to sustain anabolic metabolism. However, the mechanisms by which cells sense iron to regulate anabolic processes are unclear. Here we report a previously undescribed eukaryotic pathway for iron sensing in which molecular iron is required to sustain active histone demethylation and maintain the expression of critical components of the pro-anabolic mTORC1 pathway. Specifically, we identify the iron-binding histone-demethylase KDM3B as an intrinsic iron sensor that regulates mTORC1 activity by demethylating H3K9me2 at enhancers of a high-affinity leucine transporter, LAT3, and RPTOR. By directly suppressing leucine availability and RAPTOR levels, iron deficiency supersedes other nutrient inputs into mTORC1. This process occurs in vivo and is not an indirect effect by canonical iron-utilizing pathways. Because ancestral eukaryotes share homologues of KDMs and mTORC1 core components, this pathway probably pre-dated the emergence of the other kingdom-specific nutrient sensors for mTORC1.


Histones , Signal Transduction , Mechanistic Target of Rapamycin Complex 1/genetics , Mechanistic Target of Rapamycin Complex 1/metabolism , Leucine/metabolism , Histones/genetics , Histones/metabolism , Iron/metabolism , Regulatory-Associated Protein of mTOR/metabolism , Demethylation
12.
Transcription ; : 1-21, 2023 Sep 01.
Article En | MEDLINE | ID: mdl-37655806

The preservation of gene expression patterns that define cellular identity throughout the cell division cycle is essential to perpetuate cellular lineages. However, the progression of cells through different phases of the cell cycle severely disrupts chromatin accessibility, epigenetic marks, and the recruitment of transcriptional regulators. Notably, chromatin is transiently disassembled during S-phase and undergoes drastic condensation during mitosis, which is a significant challenge to the preservation of gene expression patterns between cell generations. This article delves into the specific gene expression and chromatin regulatory mechanisms that facilitate the preservation of transcriptional identity during replication and mitosis. Furthermore, we emphasize our recent findings revealing the unconventional role of yeast centromeres and mitotic chromosomes in maintaining transcriptional fidelity beyond mitosis.

13.
Sex Transm Infect ; 99(8): 541-547, 2023 12.
Article En | MEDLINE | ID: mdl-37704363

OBJECTIVES: Recent outbreaks of the mpox (monkeypox) virus have been detected in dense sexual networks of gay and bisexual men who have sex with men (GBMSM). The objective of this study is to describe and compare the epidemiological and behavioural characteristics, as well as the sexual networks, of GBMSM diagnosed with mild mpox in Spain. METHODS: A prospective case-control study was conducted in Spain from July 2022 to February 2023. The study targeted a key population of GBMSM aged 18 years or older. Study participants were categorised into cases, those who were diagnosed with mpox virus infection; and controls, those who were not diagnosed. We examined and compared the sexual network characteristics of the two groups-mpox-positive (mpox-P) and mpox-negative (mpox-N) egos-using χ2, t-test and Wilcoxon test to examine the differences between the two groups in each section. Finally, we conducted univariable and multivariable logistic regressions to determine the factors associated with mpox infection. RESULTS: Among the 105 participants, 35 (33.3%) were mpox-P. Compared with mpox-N, mpox-P respondents more frequently reported syphilis (mpox-P: 31.4%; mpox-N: 12.9%) and HIV (mpox-P: 45.7%; mpox-N: 18.6%), and mpox-P individuals to have had at least one sexual contact with a confirmed mpox case (mpox-P: 62.5%; mpox-N: 8.3%). In the egocentric network analysis, mpox-P respondents had a higher prevalence of group sex with alters (mpox-P: 18.5%; mpox-N: 8.9%) and one-time sexual partners (mpox-P: 46.1%; mpox-N: 31.7%). Multivariable logistic regressions showed that reporting stranger/client ties (adjusted OR (aOR)=10.3, 95% CI 1.39 to 76.6) with alters, being vaccinated for mpox (aOR=0.07, 95% CI 0.02 to 0.24) and tie strength heterogeneity (aOR=0.01, 95% CI 0.00 to 0.42) were associated with mpox infection. CONCLUSIONS: Our findings highlight the role of demographic, epidemiological and sexual network characteristics in the transmission of mpox virus during the outbreak in Spain. These findings have important implications for future prevention efforts.


HIV Infections , HIV Seropositivity , Mpox (monkeypox) , Sexual and Gender Minorities , Male , Humans , Homosexuality, Male , Case-Control Studies , HIV Infections/prevention & control
14.
EMBO Rep ; 24(8): e56525, 2023 08 03.
Article En | MEDLINE | ID: mdl-37534581

Several homeoprotein transcription factors transfer between cells and regulate gene expression, protein translation, and chromatin organization in recipient cells. ENGRAILED-1 is one such homeoprotein expressed in spinal V1 interneurons that synapse on α-motoneurons. Neutralizing extracellular ENGRAILED-1 by expressing a secreted single-chain antibody blocks its capture by spinal motoneurons resulting in α-motoneuron loss and limb weakness. A similar but stronger phenotype is observed in the Engrailed-1 heterozygote mouse, confirming that ENGRAILED-1 exerts a paracrine neurotrophic activity on spinal cord α-motoneurons. Intrathecal injection of ENGRAILED-1 leads to its specific internalization by spinal motoneurons and has long-lasting protective effects against neurodegeneration and weakness. Midbrain dopaminergic neurons express Engrailed-1 and, similarly to spinal cord α-motoneurons, degenerate in the heterozygote. We identify genes expressed in spinal cord motoneurons whose expression changes in mouse Engrailed-1 heterozygote midbrain neurons. Among these, p62/SQSTM1 shows increased expression during aging in spinal cord motoneurons in the Engrailed-1 heterozygote and upon extracellular ENGRAILED-1 neutralization. We conclude that ENGRAILED-1 might regulate motoneuron aging and has non-cell-autonomous neurotrophic activity.


Motor Neurons , Transcription Factors , Mice , Animals , Transcription Factors/genetics , Transcription Factors/metabolism , Motor Neurons/metabolism , Spinal Cord/metabolism , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Interneurons/metabolism
15.
PLoS One ; 18(3): e0282871, 2023.
Article En | MEDLINE | ID: mdl-36893204

Vaccine hesitancy is defined as a delay in acceptance of vaccines despite its availability, caused by many determinants. Our study presents the key reasons, determinants and characteristics associated with COVID-19 vaccine acceptability among students over 16 years and parents of students under 16 years and describe the COVID-19 vaccination among students in the settings of sentinel schools of Catalonia, Spain. This is a cross-sectional study that includes 3,383 students and the parents between October 2021 and January 2022. We describe the student's vaccination status and proceed a univariate and multivariate analysis using a Deletion Substitution Addition (DSA) machine learning algorithm. Vaccination against COVID-19 reached 70.8% in students under 16 years and 95.8% in students over 16 years at the end of the study project. The acceptability among unvaccinated students was 40.9% and 20.8% in October and January, respectively, and among parents was proportionally higher among students aged 5-11 (70.2%) in October and aged 3-4 (47.8%) in January. The key reason to not vaccinate themselves, or their children, were concern about side effects, insufficient research about the effect of the vaccine in children, rapid development of vaccines, necessity for more information and previous infection by SARS-CoV-2. Several variables were associated with refusal end hesitancy. For students, the main ones were risk perception and use of alternative therapies. For parents, the age of students, sociodemographic variables, socioeconomic impact related to the pandemic, and use of alternative therapies were more evident. Monitoring vaccine acceptance and refusal among children and their parents has been important to understand the interaction between different multilevel determinants and we hope it will be useful to improve public health strategies for future interventions in this population.


COVID-19 Vaccines , COVID-19 , Child , Humans , Spain/epidemiology , Cross-Sectional Studies , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , Parents , Schools , Students , Vaccination
16.
Proc Natl Acad Sci U S A ; 120(4): e2210593120, 2023 01 24.
Article En | MEDLINE | ID: mdl-36656860

Mitotic entry correlates with the condensation of the chromosomes, changes in histone modifications, exclusion of transcription factors from DNA, and the broad downregulation of transcription. However, whether mitotic condensation influences transcription in the subsequent interphase is unknown. Here, we show that preventing one chromosome to condense during mitosis causes it to fail resetting of transcription. Rather, in the following interphase, the affected chromosome contains unusually high levels of the transcription machinery, resulting in abnormally high expression levels of genes in cis, including various transcription factors. This subsequently causes the activation of inducible transcriptional programs in trans, such as the GAL genes, even in the absence of the relevant stimuli. Thus, mitotic chromosome condensation exerts stringent control on interphase gene expression to ensure the maintenance of basic cellular functions and cell identity across cell divisions. Together, our study identifies the maintenance of transcriptional homeostasis during interphase as an unexpected function of mitosis and mitotic chromosome condensation.


Chromatin , Chromosomes , Chromatin/genetics , Chromosomes/genetics , Chromosomes/metabolism , Interphase/genetics , Mitosis/genetics , Transcription Factors/metabolism
17.
Vaccines (Basel) ; 12(1)2023 Dec 30.
Article En | MEDLINE | ID: mdl-38250857

People with HIV (PWH) may be more susceptible to SARS-CoV-2 infection and worse clinical outcomes. We investigated the disparity in SARS-CoV-2 vaccination coverage between PWH and those without HIV (PWoH) in Catalonia, Spain, assessing primary and monovalent booster vaccination coverage from December 2021 to July 2022. The vaccines administered were BNT162, ChAdOx1-S, mRNA-127, and Ad26.COV2.S. Using a 1:10 ratio of PWH to PWoH based on sex, age, and socioeconomic deprivation, the analysis included 201,630 individuals (183,300 PWoH and 18,330 PWH). Despite a higher prevalence of comorbidities, PWH exhibited lower rates of complete primary vaccination (78.2% vs. 81.8%, p < 0.001) but surpassed PWoH in booster coverage (68.5% vs. 63.1%, p < 0.001). Notably, complete vaccination rates were lower among PWH with CD4 <200 cells/µL, detectable HIV viremia, and migrants compared to PWoH (p < 0.001, all). However, PWH with CD4 < 200 cells/µL received more boosters (p < 0.001). In multivariable logistic regression analysis of the overall population, a prior SARS-CoV-2 diagnosis, HIV status, migrants, and mild-to-severe socioeconomic deprivation were associated with lower primary vaccination coverage, reflecting barriers to healthcare and vaccine access. However, booster vaccination was higher among PWH. Targeted interventions are needed to improve vaccine coverage and address hesitancy in vulnerable populations.

18.
PLoS One ; 17(11): e0277764, 2022.
Article En | MEDLINE | ID: mdl-36395191

The Sentinel Schools project was designed to monitor and evaluate the epidemiology of COVID-19 in Catalonia, gathering evidence for health and education policies to inform the development of health protocols and public health interventions to control of SARS-CoV-2 infection in schools. The aim of this study was to estimate the prevalence and incidence of SARS-CoV-2 infections and to identify their determinants among students and staff during February to June in the academic year 2020-2021. We performed two complementary studies, a cross-sectional and a longitudinal component, using a questionnaire to collect nominal data and testing for SARS-CoV-2 detection. We describe the results and perform a univariate and multivariate analysis. The initial crude seroprevalence was 14.8% (95% CI: 13.1-16.5) and 22% (95% CI: 18.3-25.8) for students and staff respectively, and the active infection prevalence was 0.7% (95% CI: 0.3-1) and 1.1% (95% CI: 0.1-2). The overall incidence for persons at risk was 2.73 per 100 person-month and 2.89 and 2.34 per 100 person-month for students and staff, respectively. Socioeconomic, self-reported knowledge, risk perceptions and contact pattern variables were positively associated with the outcome while sanitary measure compliance was negatively associated, the same significance trend was observed in multivariate analysis. In the longitudinal component, epidemiological close contact with SARS-CoV-2 infection was a risk factor for SARS-CoV-2 infection while the highest socioeconomic status level was protective as was compliance with sanitary measures. The small number of active cases detected in these schools suggests a low transmission among children in school and the efficacy of public health measures implemented, at least in the epidemiological scenario of the study period. The major contribution of this study was to provide results and evidence that help analyze the transmission dynamic of SARS-CoV-2 and evaluate the associations between sanitary protocols implemented, and measures to avoid SARS-CoV-2 spread in schools.


COVID-19 , Child , Humans , COVID-19/epidemiology , Prevalence , Incidence , Seroepidemiologic Studies , Cross-Sectional Studies , Spain/epidemiology , SARS-CoV-2 , Schools
19.
Environ Pollut ; 313: 120109, 2022 Nov 15.
Article En | MEDLINE | ID: mdl-36155148

Air pollution exposure during early-life is associated with altered brain development, but the precise periods of susceptibility are unknown. We aimed to investigate whether there are periods of susceptibility of air pollution between conception and preadolescence in relation to white matter microstructure and brain volumes at 9-12 years old. We used data of 3515 children from the Generation R Study, a population-based birth cohort from Rotterdam, the Netherlands (2002-2006). We estimated daily levels of nitrogen dioxide (NO2), and particulate matter (PM2.5 and PM2.5absorbance) at participants' homes during pregnancy and childhood using land-use regression models. Diffusion tensor and structural brain images were obtained when children were 9-12 years of age, and we calculated fractional anisotropy and mean diffusivity, and several brain structure volumes. We performed distributed lag non-linear modeling adjusting for socioeconomic and lifestyle characteristics. We observed specific periods of susceptibility to all air pollutants from conception to age 5 years in association with lower fractional anisotropy and higher mean diffusivity that survived correction for multiple testing (e.g., -0.85 fractional anisotropy (95%CI -1.43; -0.27) per 5 µg/m3 increase in PM2.5 between conception and 4 years of age). We also observed certain periods of susceptibility to some air pollutants in relation to global brain and some subcortical brain volumes, but only the association between PM2.5 and putamen survived correction for multiple testing (172 mm3 (95%CI 57; 286) per 5 µg/m3 increase in PM2.5 between 4 months and 1.8 year of age). This study suggested that conception, pregnancy, infancy, toddlerhood, and early childhood seem to be susceptible periods to air pollution exposure for the development of white matter microstructure and the putamen volume. Longitudinal studies with repeated brain outcome measurements are needed for understanding the trajectories and the long-term effects of exposure to air pollution.


Air Pollutants , Air Pollution , White Matter , Air Pollution/adverse effects , Brain/diagnostic imaging , Child , Child, Preschool , Environmental Exposure/adverse effects , Female , Humans , Nitrogen Dioxide , Particulate Matter/analysis , Pregnancy , White Matter/chemistry , White Matter/diagnostic imaging
20.
Pharmacogenomics ; 23(11): 627-638, 2022 Jul.
Article En | MEDLINE | ID: mdl-35880554

Background: The aim of this study was to evaluate the impact of certain single-nucleotide polymorphisms (SNPs) in cabazitaxel activity and toxicity in patients with metastatic castration-resistant prostate cancer (mCRPC). Patients & methods: 56 SNPs in five genes (CYP3A4, CYP3A5, ABCB1, TUBB1 and CYP2C8) were genotyped in 67 mCRPC patients and their correlation with outcomes analyzed. Results:TUBB1-rs151352 (hazard ratio: 0.52) and CYP2C8-rs1341164 (hazard ratio: 0.53) were associated with better overall survival, and CYP2C8-rs1058932 with biochemical progression (odds ratio: 6.60) in multivariate analysis. ABCB1-rs17327624 correlated with severe toxicity ≥grade 3 (odds ratio: 8.56) and CYP2C8-rs11572093 with asthenia (odds ratio: 8.12). Conclusion: Genetic variants in mCRPC patients could explain different outcomes with cabazitaxel. Nonetheless, the small sample size and the high number of SNPs analyzed mean that the results are only hypothesis-generating and require further validation.


Antineoplastic Agents , Prostatic Neoplasms, Castration-Resistant , Taxoids , Humans , Male , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , ATP Binding Cassette Transporter, Subfamily B/genetics , Cytochrome P-450 CYP2C8/genetics , Cytochrome P-450 CYP3A/genetics , Polymorphism, Single Nucleotide , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/pathology , Taxoids/adverse effects , Taxoids/therapeutic use , Treatment Outcome , Tubulin/genetics
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