Establishing an Extracorporeal Cardiopulmonary Resuscitation Program.

Extracorporeal cardiopulmonary resuscitation (ECPR) is a complex, life-saving procedure that uses mechanical support for patients with refractory cardiac arrest, representing the pinnacle of extracorporeal membrane oxygenation (ECMO) applications. Effective ECPR requires precise patient selection, rapid mobilization of a multidisciplinary team, and skilled cannulation techniques. Establishing a program necessitates a cohesive ECMO system that promotes interdisciplinary collaboration, which is essential for managing acute cardiogenic shock and severe pulmonary failure.

Bioinformatics Study on Site-Specific Variations of Eotaxin-3, a Key Chemokine in Eosinophilic Esophagitis (EoE).

Eotaxin-3 is a key chemokine with a relevant role in eosinophilic esophagitis, a rare chronic immune/antigen-mediated inflammatory disorder. Eotaxin-3 is a potent activator of eosinophil emergence and migration, which may lead to allergic airway inflammation. We investigated, using bioinformatics tools, the protein structure and the possible effects of the known variations reported in public databases.

Emerging role of carbonyl-carbonyl interactions in the classification of beta turns.

Carbonyl-carbonyl interactions in peptides and proteins attracted considerable interest in recent years. Here, we report a survey of carbonyl-carbonyl interactions in cyclic peptides, depsipeptides, peptoids and discuss the relationship between backbone torsion angles and CO∙∙∙CO distances. In general, φ values in the range between -40° and -90° and between 40° and 90° correspond to CO∙∙∙CO distances below 3.

An automated pipeline integrating AlphaFold 2 and MODELLER for protein structure prediction.

The ability to predict a protein's three-dimensional conformation represents a crucial starting point for investigating evolutionary connections with other members of the corresponding protein family, examining interactions with other proteins, and potentially utilizing this knowledge for the purpose of rational drug design. In this work, we evaluated the feasibility of improving AlphaFold2's three-dimensional protein predictions by developing a novel pipeline (AlphaMod) that incorporates AlphaFold2 with MODELLER, a template-based modeling program. Additionally, our tool can drive a comprehensive quality assessment of the tertiary protein structure by incorporating and comparing a set of different quality assessment tools.

HINT, a code for understanding the interaction between biomolecules: a tribute to Donald J. Abraham.

A long-lasting goal of computational biochemists, medicinal chemists, and structural biologists has been the development of tools capable of deciphering the molecule-molecule interaction code that produces a rich variety of complex biomolecular assemblies comprised of the many different simple and biological molecules of life: water, small metabolites, cofactors, substrates, proteins, DNAs, and RNAs. Software applications that can mimic the interactions amongst all of these species, taking account of the laws of thermodynamics, would help gain information for understanding qualitatively and quantitatively key determinants contributing to the energetics of the bimolecular recognition process. This, in turn, would allow the design of novel compounds that might bind at the intermolecular interface by either preventing or reinforcing the recognition.

Resources and tools for rare disease variant interpretation.

Collectively, rare genetic disorders affect a substantial portion of the world's population. In most cases, those affected face difficulties in receiving a clinical diagnosis and genetic characterization. The understanding of the molecular mechanisms of these diseases and the development of therapeutic treatments for patients are also challenging.

Dipeptidyl Amino-Peptidase 3 (DPP3) as an Early Marker of Severity in a Patient Population with Cardiogenic Shock.

Dipeptidyl amino-peptidase 3 (DPP3) is an aminopeptidase that is released into circulation upon cell death. DPP3 is involved in the degradation of angiotensins, enkephalines, and endomorphines. It has been shown that circulating DPP3 (cDPP3) plasma concentration increases in cardiogenic shock (CS) patients and correlates with high mortality risk.

Standardizing macromolecular structure files: further efforts are needed.

Investigating large datasets of biological information by automatic procedures may offer chances of progress in knowledge. Recently, tremendous improvements in structural biology have allowed the number of structures in the Protein Data Bank (PDB) archive to increase rapidly, in particular those for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated proteins. However, their automatic analysis can be hampered by the nonuniform descriptors used by authors in some records of the PDB and PDBx/mmCIF files.

Early versus late tracheostomy for traumatic brain injury: a systematic review and meta-analysis.

Introduction: Tracheostomy is the most frequent bedside surgical procedure performed on patients with traumatic brain injury who require mechanical ventilation. To compare the effects of early tracheostomy vs. late tracheostomy on the duration of mechanical ventilation in patients with traumatic brain injury, we carried out a systematic review and meta-analysis.

The anesthetic management and the role of extracorporeal membrane oxygenation for giant mediastinal tumor surgery.

Mediastinal tumors are a remarkably diverse category. They include malignant and benign forms with different rates of disease progression and tissue invasion. Anesthesiologists may encounter significant difficulties in managing patients with giant mediastinal tumors due to the non-negligible occurrence of severe cardiorespiratory collapse.

An overview of bioinformatics courses delivered at the academic level in Italy: Reflections and recommendations from BITS.

In Italian universities, bioinformatics courses are increasingly being incorporated into different study paths. However, the content of bioinformatics courses is usually selected by the professor teaching the course, in the absence of national guidelines that identify the minimum indispensable knowledge in bioinformatics that undergraduate students from different scientific fields should achieve. The Training&Teaching group of the Bioinformatics Italian Society (BITS) proposed to university professors a survey aimed at portraying the current situation of bioinformatics courses within undergraduate curricula in Italy (i.

Regional Cerebral Oxygen Saturation to Predict Favorable Outcome in Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis.

Objective: This systematic review and meta-analysis aimed to investigate the role of regional cerebral oxygen saturation (rSO) in predicting survival and neurologic outcomes after extracorporeal cardiopulmonary resuscitation (ECPR).

Design: The study authors performed a systematic review and meta-analysis of all available literature.

Setting: The authors searched relevant databases (Pubmed, Medline, Embase) for studies measuring precannulation rSO in patients undergoing ECPR and reporting mortality and/or neurologic outcomes.

In Silico Analysis of the Effects of Omicron Spike Amino Acid Changes on the Interactions with Human Proteins.

The SARS-CoV-2 variant Omicron is characterized, among others, by more than 30 amino acid changes occurring on the spike glycoprotein with respect to the original SARS-CoV-2 spike protein. We report a comprehensive analysis of the effects of the Omicron spike amino acid changes in the interaction with human antibodies, obtained by modeling them into selected publicly available resolved 3D structures of spike-antibody complexes and investigating the effects of these mutations at structural level. We predict that the interactions of Omicron spike with human antibodies can be either negatively or positively affected by amino acid changes, with a predicted total loss of interactions only in a few complexes.

Molecular dynamics analysis of the structural properties of the transglutaminases of and .

The microbial transglutaminase (TGase) from (MTGase) is widely used for industrial applications. However, in the last decades, TGases from other bacteria have been described. We focused our attention on TGase, from (KalbTGase), recently characterized as more selective than MTGase and proposed for applications in drug delivery.

Computational methods to assist in the discovery of pharmacological chaperones for rare diseases.

Pharmacological chaperones are chemical compounds able to bind proteins and stabilize them against denaturation and following degradation. Some pharmacological chaperones have been approved, or are under investigation, for the treatment of rare inborn errors of metabolism, caused by genetic mutations that often can destabilize the structure of the wild-type proteins expressed by that gene. Given that, for rare diseases, there is a general lack of pharmacological treatments, many expectations are poured out on this type of compounds.

Investigating the Effects of Amino Acid Variations in Human Menin.

Human menin is a nuclear protein that participates in many cellular processes, as transcriptional regulation, DNA damage repair, cell signaling, cell division, proliferation, and migration, by interacting with many other proteins. Mutations of the gene encoding menin cause multiple endocrine neoplasia type 1 (MEN1), a rare autosomal dominant disorder associated with tumors of the endocrine glands. In order to characterize the structural and functional effects at protein level of the hundreds of missense variations, we investigated by computational methods the wild-type menin and more than 200 variants, predicting the amino acid variations that change secondary structure, solvent accessibility, salt-bridge and H-bond interactions, protein thermostability, and altering the capability to bind known protein interactors.

Simulation of the Interactions of Arginine with Wild-Type GALT Enzyme and the Classic Galactosemia-Related Mutant p.Q188R by a Computational Approach.

Classic galactosemia is an inborn error of metabolism associated with mutations that impair the activity and the stability of galactose-1-phosphate uridylyltransferase (GALT), catalyzing the third step in galactose metabolism. To date, no treatments (including dietary galactose deprivation) are able to prevent or alleviate the long-term complications affecting galactosemic patients. Evidence that arginine is able to improve the activity of the human enzyme expressed in a prokaryotic model of classic galactosemia has induced researchers to suppose that this amino acid could act as a pharmacochaperone, but no effects were detected in four galactosemic patients treated with this amino acid.

Analysis of the Structure-Function-Dynamics Relationships of GALT Enzyme and of Its Pathogenic Mutant p.Q188R: A Molecular Dynamics Simulation Study in Different Experimental Conditions.

The third step of the catabolism of galactose in mammals is catalyzed by the enzyme galactose-1-phosphate uridylyltransferase (GALT), a homodimeric enzyme with two active sites located in the proximity of the intersubunit interface. Mutations of this enzyme are associated to the rare inborn error of metabolism known as classic galactosemia; in particular, the most common mutation, associated with the most severe phenotype, is the one that replaces Gln188 in the active site of the enzyme with Arg (p.Gln188Arg).

Performance of Web tools for predicting changes in protein stability caused by mutations.

Background: Despite decades on developing dedicated Web tools, it is still difficult to predict correctly the changes of the thermodynamic stability of proteins caused by mutations. Here, we assessed the reliability of five recently developed Web tools, in order to evaluate the progresses in the field.

Results: The results show that, although there are improvements in the field, the assessed predictors are still far from ideal.