[Mineralocorticoid receptor antagonists in heart failure with preserved/mildly reduced ejection fraction: from TOPCAT to FINEARTS-HF].

Mineralocorticoid receptor antagonists (MRAs) represent one of the cornerstones of treatment for heart failure with reduced ejection fraction. Post-hoc data from the TOPCAT trial, conducted in patients with heart failure mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), suggest the possible clinical benefit of MRAs, particularly for slightly reduced ejection fraction values. The advent of non-steroidal MRAs, including finerenone, seems to represent a turning point in the treatment for HFmrEF/HFpEF.

In vivo pharmacokinetic study and PBPK modeling: Comparison between 3D-printed nanocrystals and solid dispersions.

The solubility of drugs remains one of the most challenging aspects of formulation development. Several technologies exist to enhance the properties of poorly soluble drugs, with nanocrystal (NC) and solid dispersion (SD) technologies being among the most important. This work compared NCs and SDs under identical conditions using albendazole as a model drug and 3D printing technology as the delivery method.

A high-throughput protein tagging toolkit that retains endogenous UTRs for studying gene regulation in Kinetoplastids.

Kinetoplastid parasites cause diseases that threaten human and animal health. To survive transitions between vertebrate hosts and insect vectors, these parasites rely on precise regulation of gene expression to adapt to environmental changes. Since gene regulation in Kinetoplastids is primarily post-transcriptional, developing efficient genetic tools for modifying genes at their endogenous loci while preserving regulatory mRNA elements is crucial for studying their complex biology.

lysyl-tRNA synthetase inhibitors define the interplay between solubility and permeability required to achieve efficacy.

Cryptosporidiosis is a diarrheal disease caused by infection with spp. parasites and is a leading cause of death in malnourished children worldwide. The only approved treatment, nitazoxanide, has limited efficacy in this at-risk patient population.

Post-transcriptional reprogramming by thousands of mRNA untranslated regions in trypanosomes.

Although genome-wide polycistronic transcription places major emphasis on post-transcriptional controls in trypanosomatids, messenger RNA cis-regulatory untranslated regions (UTRs) have remained largely uncharacterised. Here, we describe a genome-scale massive parallel reporter assay coupled with 3'-UTR-seq profiling in the African trypanosome and identify thousands of regulatory UTRs. Increased translation efficiency was associated with dosage of adenine-rich poly-purine tracts (pPuTs).

Sterol 14-alpha demethylase (CYP51) activity in Leishmania donovani is likely dependent upon cytochrome P450 reductase 1.

Liposomal amphotericin B is an important frontline drug for the treatment of visceral leishmaniasis, a neglected disease of poverty. The mechanism of action of amphotericin B (AmB) is thought to involve interaction with ergosterol and other ergostane sterols, resulting in disruption of the integrity and key functions of the plasma membrane. Emergence of clinically refractory isolates of Leishmania donovani and L.

[The IN-HF Registry: the history and the scientific production for the Italian cardiology community].

The Italian Network on Congestive Heart Failure (IN-CHF) project, later known as IN-HF Online, was launched in 1995 to provide the Italian cardiology community with a digital tool, standardized across the country, for managing outpatients with heart failure (HF), that enabled the creation of a database for clinical, educational and scientific purposes. During its almost three decades of activity, this observational research program has achieved highly positive scientific results. Indeed, IN-HF fostered professional relationships among individuals working in different centers, established a cultural network for the care of HF patients, periodically updated on the scientific advances, and allowed the assessment of several clinical, epidemiological, and prognostic features.

Dose regimen optimization of cephalothin for surgical prophylaxis against Staphylococcus aureus and coagulase negative staphylococci in dogs by pharmacokinetic/pharmacodynamic modeling.

First generation cephalosporins such cephalothin of cefazolin are indicated for antimicrobial prophylaxis for clean and clean contaminated surgical procedures because its antimicrobial spectrum, relative low toxicity and cost. Anesthesia and surgery could alter the pharmacokinetic behavior of different drugs administered perioperative by many mechanisms that affect distribution, metabolism or excretion processes. Intravenous administration of the antimicrobial within 30 and 60 min before incision is recommended in order to reach therapeutic serum and tissue concentrations and redosing is recommended if the duration of the procedure exceeds two half-life of the antimicrobial.

Hyperkalaemia in Cardiological Patients: New Solutions for an Old Problem.

Hyperkalaemia is one of the most common electrolyte disorders in patients with cardiovascular disease (CVD). The true burden of hyperkalaemia in the real-world setting can be difficult to assess, but in population-based cohort studies up to 4 in 10 patients developed hyperkalaemia. In addition to drugs interfering with potassium metabolism and food intake, several conditions can cause or worsen hyperkalaemia, such as advanced age, diabetes, and chronic kidney disease.

[Pulmonary hypertension associated with left heart diseases: pathophysiology, diagnosis, treatment].

Pulmonary hypertension (PH) is a common complication of diseases affecting the left heart, mostly found in patients suffering from heart failure. Left atrial hypertension is the initial driver of post-capillary PH. However, several mechanisms may lead in a subset of patients to structural changes in the pulmonary vessels with development of a pre-capillary component.

Risk factors for clinical stages of COVID-19 amongst employees of the International Committee of the Red Cross (ICRC) worldwide over a period of 12 months.

Background: Essential workers carry a higher risk of SARS-CoV-2 infection and COVID-19 mortality than individuals working in non-essential activities. Scientific studies on COVID-19 risk factors and clinical courses for humanitarian aid workers (HAW) specifically are lacking. The nature of their work brings HAW in proximity to various populations, therefore potentially exposing them to the virus.

Calcium-phosphate homeostasis and insulin resistance in men.

Background And Aims: Data on P homeostasis in insulin resistance (IR) are still conflicting. We investigated calcium-phosphate homeostasis parameters in men with/without IR.

Methods And Results: 177 volunteers (aged 61.

Characterization of the major surface glycoconjugates of Trypanosoma theileri.

Trypanosoma theileri maintains a long-term extracellular infection with a low parasitaemia in bovids. The surface of this parasite is predicted to be decorated with several surface molecules including membrane surface proteases (MSPs), trans-sialidases and T. theileri putative surface proteins (TTPSPs).

Competition among variants is predictable and contributes to the antigenic variation dynamics of African trypanosomes.

Several persistent pathogens employ antigenic variation to continually evade mammalian host adaptive immune responses. African trypanosomes use variant surface glycoproteins (VSGs) for this purpose, transcribing one telomeric VSG expression-site at a time, and exploiting a reservoir of (sub)telomeric VSG templates to switch the active VSG. It has been known for over fifty years that new VSGs emerge in a predictable order in Trypanosoma brucei, and differential activation frequencies are now known to contribute to the hierarchy.

3D-Printed Gastroretentive Tablets Loaded with Niclosamide Nanocrystals by the Melting Solidification Printing Process (MESO-PP).

Niclosamide (NICLO) is a recognized antiparasitic drug being repositioned for . The present work aimed to formulate NICLO nanocrystals (NICLO-NCRs) to produce a higher dissolution rate of the active ingredient and to incorporate these nanosystems into a floating solid dosage form to release them into the stomach slowly. For this purpose, NICLO-NCRs were produced by wet-milling and included in a floating Gelucire l3D printed tablet by semi-solid extrusion, applying the Melting solidification printing process (MESO-PP) methodology.

Visualisation of proteome-wide ordered protein abundances in .

is a protozoan parasite and etiological agent of human and animal African trypanosomiasis. It has a complex life cycle, but the most studied cellular types are the cultivated bloodstream- and procyclic-forms. These correspond to the replicating, mammalian host bloodstream-dwelling, slender trypomastigotes and tsetse vector midgut-dwelling procyclic lifecycle stages, respectively.

[Heart failure with improved ejection fraction: practical guidance for the clinician].

Heart failure with improved ejection fraction (HFimpEF) represents a nosological entity that has recently been recognized and has little evidence from the literature. Available data indicate an increasing incidence of this patient group, consistent with the progressive improvement and implementation of medical therapy of heart failure with reduced ejection fraction (HFrEF). Furthermore, it is important to underline that the therapy itself should not be suspended after ejection fraction recovery, to avoid the recurrence of worse systolic dysfunction and patient outcomes.

Decreased low-density lipoprotein receptor-related protein 1 expression in pro-inflammatory monocytes is associated with subclinical atherosclerosis.

Subclinical atherosclerosis (SCA) occurs in asymptomatic individuals. Blood peripheral monocytes are involved in the development of atherosclerosis. Circulating monocytes acquire pro-inflammatory profiles, and they are involved in the early stages of atherosclerosis development.