Impact of knowledge of HPV positivity on cervical cytology performance in latin america.

Background: Cervical cytology is recommended by WHO as a triage option in HPV-based cervical cancer screening programmes. We assessed the performance of cytology to detect CIN3+ without and with knowledge of HPV positivity.

Methods: Women were screened with cytology and HPV across ESTAMPA study centres in Latin America.

Assessing generalizability of an AI-based visual test for cervical cancer screening.

A number of challenges hinder artificial intelligence (AI) models from effective clinical translation. Foremost among these challenges is the lack of generalizability, which is defined as the ability of a model to perform well on datasets that have different characteristics from the training data. We recently investigated the development of an AI pipeline on digital images of the cervix, utilizing a multi-heterogeneous dataset of 9,462 women (17,013 images) and a multi-stage model selection and optimization approach, to generate a diagnostic classifier able to classify images of the cervix into "normal", "indeterminate" and "precancer/cancer" (denoted as "precancer+") categories.

Stilbene-pyridazinone hybrids: design, synthesis and in vitro antiplatelet activity screening.

A series of stilbene analogues, in which a phenyl ring was replaced by the pyridazin-3(2H)-one nucleus, was designed and synthesized to be explored as platelet aggregation inhibitors. The proposed stilbene-pyridazinone hybrids were successfully obtained from simple starting materials and by Wittig's reaction. Most of the target compounds displayed improved in vitro activity in comparison with the standard drug, resveratrol, highlighting as the most potent the analogues 10d and 10e, with inhibition percentages of 94.

Association of Incident Stroke Risk With an IL-18-Centered Inflammatory Network Biomarker Composite.

Background: A coordinated network of circulating inflammatory molecules centered on the pleotropic pro-atherogenic cytokine interleukin-18 (IL-18) is linked to cerebral small vessel disease. We sought to validate the association of this inflammatory biomarker network with incident stroke risk, cognitive impairment, and imaging metrics in a sample of the Framingham Offspring Cohort.

Methods: Using available baseline measurements of serum levels of IL-18, GDF (growth and differentiation factor)-15, soluble form of receptor for advanced glycation end products, myeloperoxidase, and MCP-1 (monocyte chemoattractant protein-1) from Exam 7 of the Framingham Offspring Cohort (1998-2001), we constructed a population-normalized, equally weighted log-transformed mean -score value representing the average level of each serum analyte to create an inflammatory composite score (ICS5).

Performance of cervical cytology and HPV testing for primary cervical cancer screening in Latin America: an analysis within the ESTAMPA study.

Background: Cervical cytology remains widely used as the initial tool in cervical cancer screening worldwide. WHO guidelines recommend replacing cytology with primary HPV testing to reach cervical cancer elimination goals. We assessed the performance of cytology and high-risk HPV testing to detect cervical precancer, cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) among women aged 30-64 years participating in the ESTAMPA study.

Presence of the snout beetle in Ecuador and potential invasion risk in South America.

snout beetles are a complex of at least eight cryptic species (Curculionidae: complex), native to mainland Australia and Tasmania, that defoliate trees and are considered important pests. Since the 19th century, three species of the complex have been introduced to other continents. Here, we document the presence of snout beetles in Ecuador.

Performance of standardised colposcopy to detect cervical precancer and cancer for triage of women testing positive for human papillomavirus: results from the ESTAMPA multicentric screening study.

Background: Colposcopy, currently included in WHO recommendations as an option to triage human papillomavirus (HPV)-positive women, remains as the reference standard to guide both biopsy for confirmation of cervical precancer and cancer and treatment approaches. We aim to evaluate the performance of colposcopy to detect cervical precancer and cancer for triage in HPV-positive women.

Methods: This cross-sectional, multicentric screening study was conducted at 12 centres (including primary and secondary care centres, hospitals, laboratories, and universities) in Latin America (Argentina, Bolivia, Colombia, Costa Rica, Honduras, Mexico, Paraguay, Peru, and Uruguay).

Exchange bias coupling and bipolar resistive switching at room temperature on GaSb/Mn multilayers for resistive memories applications.

This work present structural, morphological, magnetic, and electrical properties of GaSb/Mn multilayer deposited via DC magnetron sputtering at room temperature and at 423 K. The samples are characterized by forming layers of 3, 6 and 12 periods of the GaSb/Mn structure. Through XRD patterns, it was possible to stablish the formation of GaSb, MnGa, and MnSb phases.

Joint optimization of land carbon uptake and albedo can help achieve moderate instantaneous and long-term cooling effects.

Both carbon dioxide uptake and albedo of the land surface affect global climate. However, climate change mitigation by increasing carbon uptake can cause a warming trade-off by decreasing albedo, with most research focusing on afforestation and its interaction with snow. Here, we present carbon uptake and albedo observations from 176 globally distributed flux stations.

Novel Phthalazin-1(2H)-One Derivatives Displaying a Dithiocarbamate Moiety as Potential Anticancer Agents.

Nowadays, cancer disease seems to be the second most common cause of death worldwide. Molecular hybridization is a drug design strategy that has provided promising results against multifactorial diseases, including cancer. In this work, two series of phthalazinone-dithiocarbamate hybrids were described, compounds -, which display the dithiocarbamate scaffold at N2, and compounds , in which this moiety was placed at C4.

Implementing HPV testing in 9 Latin American countries: The laboratory perspective as observed in the ESTAMPA study.

Background: Replacement of cytology screening with HPV testing is recommended and essential for cervical cancer elimination. HPV testing for primary screening was implemented in 12 laboratories within 9 Latin American countries, as part of the ESTAMPA cervical cancer screening study. Our observations provide information on critical operational aspects for HPV testing implementation in diverse resource settings.

Performance of visual inspection of the cervix with acetic acid (VIA) for triage of HPV screen-positive women: results from the ESTAMPA study.

VIA is recommended for triage of HPV-positive women attending cervical screening. In the multicentric ESTAMPA study, VIA performance for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among HPV-positive women was evaluated. Women aged 30-64 years were screened with HPV testing and cytology and referred to colposcopy if either test was positive.

Physical exercise training as preceding treatment to cognitive behavioral therapy in mild to moderate major depressive disorder: A randomized controlled trial.

Background: Many patients with major depressive disorder (MDD) remain untreated or do not respond to cognitive behavioral therapy (CBT). Physical exercise shows antidepressive effects and may serve as an effective augmentation treatment. However, research on combining exercise with CBT is sparse in MDD and underlying mechanisms of exercise are not well understood to date.

Daily tenofovir disoproxil fumarate/emtricitabine and hydroxychloroquine for pre-exposure prophylaxis of COVID-19: a double-blind placebo-controlled randomized trial in healthcare workers.

Objectives: To assess the effect of hydroxychloroquine (HCQ) and Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as pre-exposure prophylaxis on COVID-19 risk.

Methods: EPICOS is a double-blind, placebo-controlled randomized trial conducted in Spain, Bolivia, and Venezuela. Healthcare workers with negative SARS-CoV-2 IgM/IgG test were randomly assigned to the following: daily TDF/FTC plus HCQ for 12 weeks, TDF/FTC plus HCQ placebo, HCQ plus TDF/FTC placebo, and TDF/FTC placebo plus HCQ placebo.

Novel Pyridazin-3(2)-one-Based Guanidine Derivatives as Potential DNA Minor Groove Binders with Anticancer Activity.

Novel aryl guanidinium analogues containing the pyridazin-3(2)-one core were proposed as minor groove binders (MGBs) with the support of molecular docking studies. The target dicationic or monocationic compounds, which show the guanidium group at different positions of the pyridazinone moiety, were synthesized using the corresponding silyl-protected pyridazinones as key intermediates. Pyridazinone scaffolds were converted into the adequate bromoalkyl derivatives, which by reaction with ,'-di-Boc-protected guanidine followed by acid hydrolysis provided the hydrochloride salts - in good yields.

The New Pharmacological Chaperones PBXs Increase α-Galactosidase A Activity in Fabry Disease Cellular Models.

Fabry disease is an X-linked multisystemic disorder caused by the impairment of lysosomal α-Galactosidase A, which leads to the progressive accumulation of glycosphingolipids and to defective lysosomal metabolism. Currently, Fabry disease is treated by enzyme replacement therapy or the orally administrated pharmacological chaperone Migalastat. Both therapeutic strategies present limitations, since enzyme replacement therapy has shown low half-life and bioavailability, while Migalastat is only approved for patients with specific mutations.

Pyridazinones containing dithiocarbamoyl moieties as a new class of selective MAO-B inhibitors.

A novel class of potential MAO-B inhibitors was designed and synthesized in good yield by combining the pyridazinone moiety with the dithiocarbamate framework, two relevant pharmacophores for drug discovery. The biological results obtained for the different pyridazinone/dithiocarbamate hybrids (compounds 8-14) indicated that most of them reversibly and selectively inhibit the hMAO-B in vitro with IC values in the µM range and exhibit not significant cellular toxicity. The analogues 9a, 11a, 12a, 12b and 12b, which present the dithiocarbamate fragment derivatized with a piperidin-1-yl or pyrrolidin-1-yl group and placed at C3 or C4 of the diazine ring, were the most attractive compounds of these series.

Molecular phylogeny of Neotropical Parrot Snakes (Serpentes: Colubrinae: Leptophis) supports underestimated species richness.

Tetrapod taxa with broad geographic distributions across the Neotropics are often composed of multiple evolutionary lineages. In this paper, we present the most complete phylogeny of Leptophis to date and assess morphology-based species limits within the broadly distributed green parrot snake Leptophis ahaetulla sensu lato, which occurs from Mexico to Argentina. Although L.

Targeted replacement of full-length CFTR in human airway stem cells by CRISPR-Cas9 for pan-mutation correction in the endogenous locus.

Cystic fibrosis (CF) is a monogenic disease caused by impaired production and/or function of the CF transmembrane conductance regulator (CFTR) protein. Although we have previously shown correction of the most common pathogenic mutation, there are many other pathogenic mutations throughout the CF gene. An autologous airway stem cell therapy in which the CFTR cDNA is precisely inserted into the CFTR locus may enable the development of a durable cure for almost all CF patients, irrespective of the causal mutation.

Three new species of frogs of the genus (Anura, Strabomantidae) with a redefinition of the species group.

A new phylogeny for the species group is presented, its species content reviewed, and three new species described from the eastern slopes of the Ecuadorian Andes. Our phylogeny includes, for the first time, samples of , , and . The morphology of hyperdistal subarticular tubercles is also assessed among 21 species of .

"We have already heard that the treatment doesn't do anything, so why should we take it?": A mixed method perspective on Chagas disease knowledge, attitudes, prevention, and treatment behaviour in the Bolivian Chaco.

Background: Chagas disease (CD) is highly endemic in the Bolivian Chaco. The municipality of Monteagudo has been targeted by national interventions as well as by Médecins Sans Frontières to reduce infection rates, and to decentralize early diagnosis and treatment. This study seeks to determine the knowledge and attitudes of a population with increased awareness and to identify remaining factors and barriers for sustained vector control, health care seeking behaviour, and access, in order to improve future interventions.

Novel coumarin-pyridazine hybrids as selective MAO-B inhibitors for the Parkinson's disease therapy.

The 3-pyridazinylcoumarin scaffold was previously reported as an efficient core for the discovery of reversible and selective inhibitors of MAO-B, a validated drug target for PD therapy which also plays an important role in the AD progress. Looking for its structural optimization, novel compounds of hybrid structure coumarin-pyridazine, differing in polarizability and lipophilicity properties, were synthesized and tested against the two MAO isoforms, MAO-A and MAO-B (compounds 17a-f and 18a-f). All the designed compounds selectively inhibited the MAO-B isoenzyme, exhibiting many of them IC values ranging from sub-micromolar to nanomolar grade and lacking neuronal toxicity.