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Background: The COVID-19 pandemic led to a national lockdown and the interruption of all cancer preventive services, including cervical cancer screening. We aimed to assess the COVID-19 pandemic impact on opportunistic screening participation, abnormal cytology (ASCUS+) prevalence and screening interval in 2020 and 2021 within the Public Health System of Catalonia, Spain. Methods: Individual data on cytology and HPV testing of women aged 25–65 from 2014 to 2021 were retrieved from the Information System for Primary Care Services (SISAP). Time-series regression models were used to estimate expected screening participation and abnormal cytology prevalence in 2020 and 2021. The impact was determined by comparing observed and expected values (ratios). Additionally, changes in screening interval trends between 2014 and 2021 were assessed by fitting a Piecewise linear regression model. Results: Cervical cancer screening participation decreased by 38.8% and 2.2% in 2020 and 2021, respectively, with the most significant impact on participation (-96.1%) occurring in April 2020. Among older women, participation was lower, and it took longer to recover. Abnormal cytology prevalence was 1.4 times higher than expected in 2020 and 2021, with variations by age (range=1.1–1.5). From June 2020 onwards, the screening interval trend significantly changed from an increase of 0.59 to 3.57 months per year, resulting in a median time of 48 months by December 2021. Conclusions: During the pandemic, fewer women have participated in cervical cancer screening, abnormal cytology prevalence has increased, and the screening interval is more prolonged than before. The potential cervical cancer lifetime risk implications highlight the need for organized HPV-based screening. [ABSTRACT FROM AUTHOR]

Abstract Background The role of human papillomavirus (HPV) in malignant and non-malignant genital diseases in women is well known and the corresponding epidemiological burden has been widely described. However, less is known about the role of HPV in anal, penile and head and neck cancer, and the burden of malignant and non-malignant HPV-related diseases in men. The objective of this review is to estimate the epidemiological burden of HPV-related cancers and non-malignant diseases in men in Europe. Methods The annual number of new HPV-related cancers in men in Europe was estimated using Eurostat population data and applying cancer incidence rates published by the International Agency for Research on Cancer. The number of cancer cases attributable to HPV, and specifically to HPV16/18, was calculated based on the most relevant prevalence estimates. The annual number of new cases of genital warts was calculated from the most robust European studies; and latest HPV6/11 prevalence estimates were then applied. A literature review was also performed to retrieve exhaustive data on HPV infection at all anatomical sites under study, as well as incidence and prevalence of external genital warts, recurrent respiratory papillomatosis and HPV-related cancer trends in men in Europe. Results A total of 72, 694 new cancer cases at HPV-related anatomical sites were estimated to occur each year in men in Europe. 17,403 of these cancer cases could be attributable to HPV, with 15,497 of them specifically attributable to HPV16/18. In addition, between 286,682 and 325,722 new cases of genital warts attributable to HPV6/11were estimated to occur annually in men in Europe. Conclusions The overall estimated epidemiological burden of HPV-related cancers and non-malignant diseases is high in men in Europe. Approximately 30% of all new cancer cases attributable to HPV16/18 that occur yearly in Europe were estimated to occur in men. As in women, the vast majority of HPV-positive cancer in men is related to HPV16/18, while almost all HPV-related non-malignant diseases are due to HPV6/11. A substantial number of these malignant and non-malignant diseases may potentially be prevented by quadrivalent HPV vaccination.

Cardiovascular drug toxicity is responsible for 17% of drug withdrawals in clinical phases, half of post-marketed drug withdrawals and remains an important adverse effect of several marketed drugs. Early assessment of drug-induced cardiovascular toxicity is mandatory and typically done in cellular systems and mammals. Current in vitro screening methods allow high-throughput but are biologically reductionist. The use of mammal models, which allow a better translatability for predicting clinical outputs, is low-throughput, highly expensive, and ethically controversial. Given the analogies between the human and the zebrafish cardiovascular systems, we propose the use of zebrafish larvae during early drug discovery phases as a balanced model between biological translatability and screening throughput for addressing potential liabilities. To this end, we have developed a high-throughput screening platform that enables fully automatized in vivo image acquisition and analysis to extract a plethora of relevant cardiovascular parameters: heart rate, arrhythmia, AV blockage, ejection fraction, and blood flow, among others. We have used this platform to address the predictive power of zebrafish larvae for detecting potential cardiovascular liabilities in humans. We tested a chemical library of 92 compounds with known clinical cardiotoxicity profiles. The cross-comparison with clinical data and data acquired from human induced pluripotent stem cell cardiomyocytes calcium imaging showed that zebrafish larvae allow a more reliable prediction of cardiotoxicity than cellular systems. Interestingly, our analysis with zebrafish yields similar predictive performance as previous validation meta-studies performed with dogs, the standard regulatory preclinical model for predicting cardiotoxic liabilities prior to clinical phases. [ABSTRACT FROM AUTHOR]

Our current understanding of biology is heavily based on a small number of genetically tractable model organisms. Most eukaryotic phyla lack such experimental models, and this limits our ability to explore the molecular mechanisms that ultimately define their biology, ecology, and diversity. In particular, marine protists suffer from a paucity of model organisms despite playing critical roles in global nutrient cycles, food webs, and climate. To address this deficit, an initiative was launched in 2015 to foster the development of ecologically and taxonomically diverse marine protist genetic models. The development of new models faces many barriers, some technical and others institutional, and this often discourages the risky, long-term effort that may be required. To lower these barriers and tackle the complexity of this effort, a highly collaborative community-based approach was taken. Herein, we describe this approach, the advances achieved, and the lessons learned by participants in this novel community-based model for research. [ABSTRACT FROM AUTHOR]

Supercritical fluid extraction (SFE) was evaluated to be applied for residue analysis of 22 gas chromatography/electron capture detector-nitrogen phosphorus detector (GC/ECD-NPD) amenable pesticides in rice, wild rice and wheat. Samples were extracted with supercritical carbon dioxide at 200 atm pressure and 50°C temperature, using methanol as a static modifier. Mean recoveries obtained with the proposed SFE method at two spiking levels with four replicates per level are compared with those obtained with an ethyl acetate-based solvent extraction/gel permeation chromatography (GPC) clean up method. Both methods gave consistent high recoveries for almost all the pesticides from all the commodities with overall mean recoveries higher than 70% with relative standard deviations lower than 20%. Remarkable exceptions were captafol and dimethoate, for which low and/or non-reproducible recoveries were obtained with the SFE method. Residue levels determined with both methods in nine different incurred samples of wheat, containing some of the studied pesticides, were very similar, but, in all cases, slightly higher levels were determined with the SFE method. [ABSTRACT FROM AUTHOR]

Small fish are an excellent experimental model to screen endocrine-disrupting compounds, but current fish-based assays to detect endocrine disruption have not been standardized yet, meaning that there is not consensus on endpoints and biomarkers to be measured. Moreover, exposure conditions may vary depending on the species used as the experimental model and the endocrine pathway evaluated. At present, a battery of a wide range of assays is usually needed for the complete assessment of endocrine activities. With the aim of providing a simple, robust, and fast assay to assess endocrine-disrupting potencies for the three major endocrine axes, i.e., estrogens, androgens, and thyroid, we propose the use of a panel of eight gene expression biomarkers in zebrafish larvae. This includes brain aromatase (cyp19a1b) and vitellogenin 1 (vtg1) for estrogens, cytosolic sulfotransferase 2 family 2 (sult2st3) and cytochrome P450 2k22 (cyp2k22) for androgens, and thyroid peroxidase (tpo), transthyretin (ttr), thyroid receptor α (trα), and iodothyronine deiodinase 2 (dio2) for thyroid metabolism. All of them were selected according to their responses after exposure to the natural ligands 17β-estradiol, testosterone, and 3,3′,5-triiodo-L-thyronine (T3), respectively, and subsequently validated using compounds reported as endocrine disruptors in previous studies. Cross-talk effects were also evaluated for all compounds. [ABSTRACT FROM AUTHOR]

Through a genetic screen in zebrafish, we identified a mutant with disruption to myelin in both the CNS and PNS caused by a mutation in a previously uncharacterized gene, slc12a2b, predicted to encode a Na+, K+, and Cl− (NKCC) cotransporter, NKCC1b. slc12a2b/NKCC1b mutants exhibited a severe and progressive pathology in the PNS, characterized by dysmyelination and swelling of the periaxonal space at the axon–myelin interface. Cell-type–specific loss of slc12a2b/NKCC1b in either neurons or myelinating Schwann cells recapitulated these pathologies. Given that NKCC1 is critical for ion homeostasis, we asked whether the disruption to myelinated axons in slc12a2b/NKCC1b mutants is affected by neuronal activity. Strikingly, we found that blocking neuronal activity completely prevented and could even rescue the pathology in slc12a2b/NKCC1b mutants. Together, our data indicate that NKCC1b is required to maintain neuronal activity–related solute homeostasis at the axon–myelin interface, and the integrity of myelinated axons. [ABSTRACT FROM AUTHOR]

Supercritical fluid extraction (SFE) and the use of aminopropyl solid-phase material for "in-line" cleanup was evaluated for residue analysis of 22 GC-amenable pesticides in wild- and white-rice samples with a fat content of 1.9 and 0.4%, respectively. After optimizing the extraction conditions on glass beads as inert material and evaluating the fat amount extracted from rice by SFE, the use of Florisil, Celite, Extrelut, Hydromatrix, and an aminopropyl material as fat-retention materials for SFE "in-line" cleanup was assessed, aminopropyl being the most suitable material for this cleanup of fat. Pesticide mean recoveries obtained from rice samples, at fortification levels around 0.5 mg/kg, by means of the SFE/in-line cleanup method finally proposed (15-mL CO2 volume, 50 degrees C temperature, 200 atm pressure, 200 muL of methanol static modifier, and a 1-cm layer of aminopropyl at the bottom of the extraction vessel), ranged between 74 and 98%, except for captafol and dimethoate for which mean recoveries lower than 21% were determined.