Persistent dysexecutive syndrome after pneumococcal meningitis complicated by recurrent ischemic strokes: A case report.

Background: Meningitis is a possible complication of pneumococcal infection concerning acute otitis media and sinusitis. It might compromise cognitive function, both for the infection itself and the vascular events that sometimes follow the acute phase.

Case Summary: Here we describe the case of a 32-year-old female patient admitted to the emergency room due to extensive pneumococcal meningitis as a consequence of sinus outbreak.

A comparison of numerical approaches for statistical inference with stochastic models.

Unlabelled: Due to our limited knowledge about complex environmental systems, our predictions of their behavior under different scenarios or decision alternatives are subject to considerable uncertainty. As this uncertainty can often be relevant for societal decisions, the consideration, quantification and communication of it is very important. Due to internal stochasticity, often poorly known influence factors, and only partly known mechanisms, in many cases, a stochastic model is needed to get an adequate description of uncertainty.

Cognition in COVID-19 infected patients undergoing invasive ventilation: results from a multicenter retrospective study.

A growing number of scientific contributions suggest that COVID-19 infection can lead to impairment of cognition, mainly in executive functions and memory domains, even in the absence of frank neurological pathologies.The primary objective of this retrospective study is to evaluate the frequency and type of inefficiencies in a selection of cognitive tests administered to a sample of subjects who, following infection, required invasive assisted ventilation and were admitted to rehabilitation wards for the treatment of functional impairment.Fifty-seven subjects were enrolled.

Antibody binding modulates the dynamics of the membrane-bound prion protein.

Misfolding of the cellular prion protein (PrP) is associated with lethal neurodegeneration. PrP consists of a flexible tail (residues 23-123) and a globular domain (residues 124-231) whose C-terminal end is anchored to the cell membrane. The neurotoxic antibody POM1 and the innocuous antibody POM6 recognize the globular domain.

A discrete-to-continuum model of protein complexes.

On the basis of a tensor representation of protein shape, obtained by an affine decomposition of residue velocity, we show how to identify actions at continuum scale for both single proteins and their complexes in terms of power equivalence. The approach constructs and justifies a continuum modeling of protein complexes, which avoids a direct, atomistic-based, simulation of the whole complex, rather it focuses (in a statistical sense) on a single protein and its interactions with the neighbors. In the resulting setting we also prove the existence of equilibrium configurations (native states) under large strains.

On the removal of initial state bias from simulation data.

Classical atomistic simulations of biomolecules play an increasingly important role in molecular life science. The structure of current computing architectures favors methods that run multiple trajectories at once without requiring extensive communication between them. Many advanced sampling strategies in the field fit this mold.

Focused conformational sampling in proteins.

A detailed understanding of the conformational dynamics of biological molecules is difficult to obtain by experimental techniques due to resolution limitations in both time and space. Computer simulations avoid these in theory but are often too short to sample rare events reliably. Here we show that the progress index-guided sampling (PIGS) protocol can be used to enhance the sampling of rare events in selected parts of biomolecules without perturbing the remainder of the system.

Amyloid β Fibril Elongation by Monomers Involves Disorder at the Tip.

The growth of amyloid fibrils from Aβ peptide, one of the key pathogenic players in Alzheimer's disease, is believed to follow a nucleation-elongation mechanism. Fibril elongation is often described as a "dock-lock" procedure, where a disordered monomer adsorbs to an existing fibril in a relatively fast process (docking), followed by a slower conformational transition toward the ordered state of the template (locking). Here, we use molecular dynamics simulations of an ordered pentamer of Aβ42 at fully atomistic resolution, which includes solvent, to characterize the elongation process.

A molecular simulation protocol to avoid sampling redundancy and discover new states.

Background: For biomacromolecules or their assemblies, experimental knowledge is often restricted to specific states. Ambiguity pervades simulations of these complex systems because there is no prior knowledge of relevant phase space domains, and sampling recurrence is difficult to achieve. In molecular dynamics methods, ruggedness of the free energy surface exacerbates this problem by slowing down the unbiased exploration of phase space.

Protein transport across nanopores: a statistical mechanical perspective from coarse-grained modeling and approaches.

We survey the transport of proteins across nanopores in the framework of coarse-grained modeling. The advantage of a reduced complexity with respect to full-atomistic techniques lies in the possibility of massive sampling of events, thus allowing a statistical mechanical description of translocation in terms of ensemble averages. Often, protein transport through narrow channels tightly couples with unfolding pathways causing a richer phenomenology compared to unstructured polymer translocation.

Protein translocation in narrow pores: inferring bottlenecks from native structure topology.

Coarse-grained simulations of protein translocation across narrow pores suggest that the transport is characterized by long stall events. The translocation bottlenecks and the associated free-energy barriers are found to be strictly related to the structural properties of the protein native structure. The ascending ramps of the free-energy profile systematically correspond to regions of the chain denser in long range native contacts formed with the untranslocated portion of the protein.

Role of denaturation in maltose binding protein translocation dynamics.

We present a computational study on the driven transport of the Maltose Binding Protein (MBP) across nanochannels in the framework of coarse-grained modeling. The work is motivated by recent experiments on voltage-driven transport of MBP across nanopores exploring the influence of denaturation on translocation pathways. Our simplified approach allows a statistical mechanical interpretation of the process which may be convenient also to the experiments.