In-silico trial emulation to predict the cardiovascular protection of new lipid-lowering drugs: an illustration through the design of the SIRIUS programme.

Introduction: Inclisiran, an siRNA targeting hepatic PCSK9 mRNA, administered twice-yearly (after initial and 3-month doses), substantially and sustainably reduced LDL-cholesterol (LDL-C) in Phase III trials. Whether lowering LDL-C with inclisiran translates into a reduced risk of major adverse cardiovascular events (MACE) is not yet established. In-silico trials applying a disease computational model to virtual patients receiving new treatments allow to emulate large scale long-term clinical trials.

The phased Solanum okadae genome and Petota pangenome analysis of 23 other potato wild relatives and hybrids.

Potato is an important crop in the genus Solanum section Petota. Potatoes are susceptible to multiple abiotic and biotic stresses and have undergone constant improvement through breeding programs worldwide. Introgression of wild relatives from section Petota with potato is used as a strategy to enhance the diversity of potato germplasm.

Cardioprotective Signaling Pathways in Obese Mice Submitted to Regular Exercise: Effect on Oxysterols.

Exercise induces cardioprotection against myocardial infarction, despite obesity, by restoring pro-survival pathways and increasing resistance of mitochondrial permeability transition pore (mPTP) opening at reperfusion. Among the mechanisms involved in the inactivation of these pathways, oxysterols appear interesting. Thus, we investigated the influence of regular exercise on the reperfusion injury salvage kinase (RISK) pathway, oxysterols, and mitochondria, in the absence of ischemia-reperfusion.

Positive rumination can (also) interfere with sleep: A study in a non-clinical sample.

Unlabelled: It is postulated that negative ruminations perpetuate insomnia symptoms by increasing arousal. Less is known about the role of positive rumination. In this study, we set out to test the association between positive and negative ruminations and insomnia symptoms in a non-clinical sample, asking whether reappraisal and suppression moderate the relationship between rumination types and symptoms of insomnia.

Adsorption of SARS CoV-2 spike proteins on various functionalized surfaces correlates with the high transmissibility of Delta and Omicron variants.

The SARS-CoV-2 virus emerged at the end of 2019 and rapidly developed several mutated variants, specifically the Delta and Omicron, which demonstrate higher transmissibility and escalating infection cases worldwide. The dominant transmission pathway of this virus is via human-to-human contact and aerosols which once inhaled interact with the mucosal tissue, but another possible route is through contact with surfaces contaminated with SARS-CoV-2, often exhibiting long-term survival. Here we compare the adsorption capacities of the S1 and S2 subunits of the spike (S) protein from the original variant to that of the S1 subunit from the Delta and Omicron variants on self-assembled monolayers by Quartz Crystal ​Microbalance.

Self-catalytic growth of one-dimensional materials within dislocations in gold.

Dislocations in metals affect their properties on the macro- and the microscales. For example, they increase a metal's hardness and strength. Dislocation outcrops exist on the surfaces of such metals, and atoms in the proximity of these outcrops are more loosely bonded, facilitating local chemical corrosion and reactivity.

Detrimental Effect and Neutralization of Produced Water on Zirconia Nanoparticles Obtained by a Nonaqueous Sol-Gel Method.

In this work, the phase purity and size of zirconia nanocrystals samples were studied in terms of zirconium concentration, added water content, and subsequent use of a post solvothermal treatment. The progressive tetragonal-to-monoclinic transformation of zirconia sample was observed to be strongly related to the water content of the alcoholic medium. But more surprisingly, it has been shown that even under initially anhydrous conditions and for particle size below 5 nm, the phase purity of the samples was deteriorated by a side-reaction of alcohol dehydration catalyzed by the surface of the nanoparticles (NPs).

Tracking Dynamics of Spontaneous Tumors in Mice Using Photon-Counting Computed Tomography.

Computed tomography is a powerful medical imaging modality for longitudinal studies in cancer to follow neoplasia progression and evaluate anticancer therapies. Here, we report the generation of a photon-counting micro-computed tomography (PC-CT) method based on hybrid pixel detectors with enhanced sensitivity and precision of tumor imaging. We then applied PC-CT for longitudinal imaging in a clinically relevant liver cancer model, the Alb-R26 mice, and found a remarkable heterogeneity in the dynamics for tumors at the initiation phases.

The CO-releasing molecule CORM-3 protects adult cardiomyocytes against hypoxia-reoxygenation by modulating pH restoration.

Several studies have reported that CORM-3, a water-soluble carbon monoxide releasing molecule, elicits cardioprotection against myocardial infarction but the mechanism remains to be investigated. Numerous reports indicate that inhibition of pH regulators, the Na/H exchanger (NHE) and Na/HCO symporter (NBC), protect cardiomyocytes from hypoxia/reoxygenation injury by delaying the intracellular pH (pHi) recovery at reperfusion. Our goal was to explore whether CORM-3-mediated cytoprotection involves the modulation of pH regulation.

Brazilian network for HIV Drug Resistance Surveillance (HIV-BresNet): a survey of treatment-naive individuals.

Introduction: In Brazil, more than 487,450 individuals are currently undergoing antiretroviral treatment. In order to monitor the transmission of drug-resistant strains and HIV subtype distribution in the country, this work aimed to estimate its prevalence and to characterize the nationwide pretreatment drug resistance in individuals recently diagnosed with HIV between 2013 and 2015.

Methods: The HIV threshold survey methodology (HIV-THS, WHO) targeting antiretroviral-naive individuals with recent HIV diagnosis was utilized, and subjects were selected from 51 highly populated cities in all five Brazilian macroregions.

Potato late blight field resistance from QTL dPI09c is conferred by the NB-LRR gene R8.

Following the often short-lived protection that major nucleotide binding, leucine-rich-repeat (NB-LRR) resistance genes offer against the potato pathogen Phytophthora infestans, field resistance was thought to provide a more durable alternative to prevent late blight disease. We previously identified the QTL dPI09c on potato chromosome 9 as a more durable field resistance source against late blight. Here, the resistance QTL was fine-mapped to a 186 kb region.

K-edge imaging with the XPAD3 hybrid pixel detector, direct comparison of CdTe and Si sensors.

We investigate the improvement from the use of high-Z CdTe sensors for pre-clinical K-edge imaging with the hybrid pixel detectors XPAD3. We compare XPAD3 chips bump bonded to Si or CdTe sensors in identical experimental conditions. Image performance for narrow energy bin acquisitions and contrast-to-noise ratios of K-edge images are presented and compared.

Mean-field theory of random close packings of axisymmetric particles.

Finding the optimal random packing of non-spherical particles is an open problem with great significance in a broad range of scientific and engineering fields. So far, this search has been performed only empirically on a case-by-case basis, in particular, for shapes like dimers, spherocylinders and ellipsoids of revolution. Here we present a mean-field formalism to estimate the packing density of axisymmetric non-spherical particles.

Linking the potato genome to the conserved ortholog set (COS) markers.

Background: Conserved ortholog set (COS) markers are an important functional genomics resource that has greatly improved orthology detection in Asterid species. A comprehensive list of these markers is available at Sol Genomics Network (http://solgenomics.net/) and many of these have been placed on the genetic maps of a number of solanaceous species.

A model of hypoxia-reoxygenation on isolated adult mouse cardiomyocytes: characterization, comparison with ischemia-reperfusion, and application to the cardioprotective effect of regular treadmill exercise.

The use of in vitro experimental models of hypoxia-reoxygenation (H/R) that mimic in vivo ischemia-reperfusion represents a powerful tool to investigate cardioprotective strategies against myocardial infarction. Most in vitro studies are performed using neonatal cardiac cells or immortalized embryonic cardiac cell lines which may limit the extrapolation of the results. We developed an H/R model using adult cardiomyocytes freshly isolated from mice and compared its characteristics to the in vivo ischemia-reperfusion conditions.

Regular treadmill exercise restores cardioprotective signaling pathways in obese mice independently from improvement in associated co-morbidities.

Obesity is a major health issue that impedes the ability of preconditioning and postconditioning to protect the myocardium against infarction secondary to dysregulation of kinase signaling pathways. Moreover, exercise decreases cardiovascular mortality in obese patients but the mechanism remains to be established. Wild-type (WT) and obese (ob/ob) mice were assigned to sedentary conditions or regular treadmill exercise (1h/day, 5 days/7, 4 weeks, 4° slope, 10-30 cm/s) and underwent 30 min of coronary artery occlusion followed by 24h of reperfusion for infarct size measurement.

Conditional QTL underlying resistance to late blight in a diploid potato population.

A large number of quantitative trait loci (QTL) for resistance to late blight of potato have been reported with a "conventional" method in which each phenotypic trait reflects the cumulative genetic effects for the duration of the disease process. However, as genes controlling response to disease may have unique contributions with specific temporal features, it is important to consider the phenotype as dynamic. Here, using the net genetic effects evidenced at consecutive time points during disease development, we report the first conditional mapping of QTL underlying late blight resistance in potato under five environments in Peru.

Clinical experience with miglustat therapy in pediatric patients with Niemann-Pick disease type C: a case series.

Niemann-Pick disease type C (NP-C) is an inherited neurovisceral lysosomal lipid storage disease characterized by progressive neurological deterioration. Different clinical forms have been defined based on patient age at onset: perinatal, early-infantile (EI), late-infantile (Li), juvenile and adult. We evaluated the efficacy and tolerability of miglustat in 16 symptomatic NP-C patients, with comparative reference to one neurologically asymptomatic, untreated patient.

Subacute presentation of propionic acidemia.

Propionic acidemia is a hereditary metabolic disease caused by a deficiency of enzyme propionyl-CoA carboxylase, which is involved in the catabolism of ramified amino acids, odd-chain fatty acids, and other metabolites; the deficiency of this enzyme leads to an accumulation of toxic substances in the body. There are various forms of clinical presentation (severe neonatal, chronic intermittent, or slow and gradual). The case presented in this study was of a slow and insidious evolution form that was diagnosed when the child was 9 months old.

[Neonatal screening for hemoglobinopathies: a pilot study in Porto Alegre, Rio Grande do Sul, Brazil].

This study was conducted to establish the frequency of hemoglobinopathies among newborns undergoing screening tests for metabolic diseases at the University Hospital (Hospital de Clínicas) in Porto Alegre, Rio Grande do Sul, Brazil. Testing for abnormal hemoglobins was performed by isoelectric focusing electrophoresis on agarose gel with blood obtained by heel stick and applied to filter paper. For confirmatory testing of abnormal neonatal screening, a venopuncture blood sample was obtained from the infant and parents and then submitted to hemoglobin electrophoresis on cellulose acetate at pH 8.

Avascular necrosis of the femoral head after femoral neck fracture.

Trauma-induced avascular necrosis of the femoral head represents the most common femoral head aseptic necrosis. An alteration in blood supply to the femoral head is the cause of the vascular necrosis. Another mechanism in the genesis of femoral head necrosis is the tamponade effect.

G6PD deficiency in an unselected Brazilian population.

Data about glucose-6-phosphate dehydrogenase (G6PD) deficiency are not available in Brazil, a country characterized by a great mix of races. The disease is associated with ethnic groups. High prevalence (5 to 25%) has been reported in Africa, Asia, Middle East and the Mediterranean.

A comprehensive screening program in South Brazil.

We present the experience and figures about a screening program in South Brazil carried on in Porto Alegre, capital of the Southern Brazilian State. We present the tests performed routinely in our laboratory, the prevalence of some diseases and tests for infectious diseases to be added in the most comprehensive regional program in our country.