Determinism and boundedness of self-assembling structures.

Self-assembly processes are widespread in nature and lie at the heart of many biological and physical phenomena. The characteristics of self-assembly building blocks determine the structures that they form. Two crucial properties are the determinism and boundedness of the self-assembly. The former tells us whether the same set of building blocks always generates the same structure, and the latter whether it grows indefinitely. These properties are highly relevant in the context of protein structures, as the difference between deterministic protein self-assembly and nondeterministic protein aggregation is central to a number of diseases. Here we introduce a graph theoretical approach that can determine the determinism and boundedness for several geometries and dimensionalities of self-assembly more accurately and quickly than conventional methods. We apply this methodology to a previously studied lattice self-assembly model and discuss generalizations to a wide range of other self-assembling systems.

Nondeterministic self-assembly with asymmetric interactions.

We investigate general properties of nondeterministic self-assembly with asymmetric interactions, using a computational model and DNA tile assembly experiments. By contrasting symmetric and asymmetric interactions we show that the latter can lead to self-limiting cluster growth. Furthermore, by adjusting the relative abundance of self-assembly particles in a two-particle mixture, we are able to tune the final sizes of these clusters. We show that this is a fundamental property of asymmetric interactions, which has potential applications in bioengineering, and provides insights into the study of diseases caused by protein aggregation.

Nondeterministic self-assembly of two tile types on a lattice.

Self-assembly is ubiquitous in nature, particularly in biology, where it underlies the formation of protein quaternary structure and protein aggregation. Quaternary structure assembles deterministically and performs a wide range of important functions in the cell, whereas protein aggregation is the hallmark of a number of diseases and represents a nondeterministic self-assembly process. Here we build on previous work on a lattice model of deterministic self-assembly to investigate nondeterministic self-assembly of single lattice tiles and mixtures of two tiles at varying relative concentrations. Despite limiting the simplicity of the model to two interface types, which results in 13 topologically distinct single tiles and 106 topologically distinct sets of two tiles, we observe a wide variety of concentration-dependent behaviors. Several two-tile sets display critical behaviors in the form of a sharp transition from bound to unbound structures as the relative concentration of one tile to another increases. Other sets exhibit gradual monotonic changes in structural density, or nonmonotonic changes, while again others show no concentration dependence at all. We catalog this extensive range of behaviors and present a model that provides a reasonably good estimate of the critical concentrations for a subset of the critical transitions. In addition, we show that the structures resulting from these tile sets are fractal, with one of two different fractal dimensions.

A one-dimensional statistical mechanics model for nucleosome positioning on genomic DNA.

The first level of folding of DNA in eukaryotes is provided by the so-called '10 nm chromatin fibre', where DNA wraps around histone proteins (∼10 nm in size) to form nucleosomes, which go on to create a zig-zagging bead-on-a-string structure. In this work we present a one-dimensional statistical mechanics model to study nucleosome positioning within one such 10 nm fibre. We focus on the case of genomic sheep DNA, and we start from effective potentials valid at infinite dilution and determined from high-resolution in vitro salt dialysis experiments. We study positioning within a polynucleosome chain, and compare the results for genomic DNA to that obtained in the simplest case of homogeneous DNA, where the problem can be mapped to a Tonks gas. First, we consider the simple, analytically solvable, case where nucleosomes are assumed to be point-like. Then, we perform numerical simulations to gauge the effect of their finite size on the nucleosomal distribution probabilities. Finally we compare nucleosome distributions and simulated nuclease digestion patterns for the two cases (homogeneous and sheep DNA), thereby providing testable predictions of the effect of sequence on experimentally observable quantities in experiments on polynucleosome chromatin fibres reconstituted in vitro.

Preoperative evaluation in infants and children: recommendations of the Italian Society of Pediatric and Neonatal Anesthesia and Intensive Care (SARNePI).

BACKGROUND: The preoperative assessment involves the process of evaluating the patient's clinical condition, which is intended to define the physical status classification, eligibility for anesthesia and the risks associated with it, thus providing elements to select the most appropriate and individualized anesthetic plan. The aim of this recommendation was provide a framework reference for the preoperative evaluation assessment of pediatric patients undergoing elective surgery or diagnostic/therapeutic procedures. METHODS: We obtained evidence concerning pediatric preoperative evaluation from a systematic search of the electronic databases MEDLINE and Embase between January 1998 and February 2012. We used the format developed by the Italian Center for Evaluation of the Effectiveness of Health Care's scoring system for assessing the level of evidence and strength of recommendations. RESULTS: We produce a set of consensus guidelines on the preoperative assessment and on the request for preoperative tests. A review of the existing literature supporting these recommendations is provided. In reaching consensus, emphasis was placed on the level of evidence, clinical relevance and the risk/benefit ratio. CONCLUSION: Preoperative evaluation is mandatory before any diagnostic or therapeutic procedure that requires the use of anesthesia or sedation. The systematic prescription of complementary tests in children should be abandoned, and replaced by a selective and rational prescription, based on the patient history and clinical examination performed during the preoperative evaluation.

Reversal of rocuronium induced neuromuscular block with sugammadex or neostigmine: a large observational study.

BACKGROUND: This 'real-life' study aimed to analyze the time from the start of neostigmine or sugammadex administration to recovery to a train of four ratio (TOFr) of 0.9 in a real-life in patients receiving rocuronium. The secondary aims were to assess the proportion of patients: presenting TOFr < 0.9 after 5, 10, and 20 min from reversal agent administration, receiving opioids for intraoperative analgesia and extubated in the post-anesthesia care unit (PACU). METHODS: This was a multisite, prospective, nonrandomized, observational real-life study. Reversal agent was administered at either T2 reappearance or at a post-tetanic count of 1 or 2. Drugs dosages were free according to each investigator's usual practice. RESULTS: Three hundred fifty-nine patients were enrolled onto the study. Time from reversal administration to TOFr to 0.9 is significantly faster in the sugammadex group than in the neostigmine group (shallow block: 2.2 vs. 6.9 min, respectively; P < 0.0001; deep block: 2.7 vs. 16.2 min, respectively; P < 0.0001). The number of patients with TOFr < 0.9 at 5, 10, and 20 min post-reversal agent administration was higher in the neostigmine than in the sugammadex group. Just five patients did not receive opioids. All patients were extubated in the operative room except for a single patient in the sugammadex group who was extubated following PACU admission. CONCLUSIONS: This real-life study confirms that reversal time is faster in patients receiving sugammadex than in those receiving neostigmine. TOFr < 0.9 20 min after reversal was only present in patients treated with neostigmine.

A probable case of nitroprusside intoxication.

This article describes the clinical history of a patient admitted to the Emergency Room after severe infrascapular pain unaffected by breathing or postural changes. After thoracic CT a type B aortic dissection was diagnosed. On admission to the CCU, the patient's blood pressure was still high (210/120 mmHg). Sodium nitroprusside (1 microg/kg/min drip) was initiated. As blood pressure remained high after 24 h, the infusion rate was increased gradually up to 18 microg/kg/min. In the evening of the following day the patient was transferred to the operating room because acute renal failure (BUN 108 mg/dL, Cr 4.00 mg/dL) occurred and arterial pressure was still high (180/60 mmHg). A thoracic endoprosthesis was then inserted. During this procedure the patient was relaxed and his blood pressure was satisfactory (140/80 mmHg) without drugs. In order to further lower blood pressure and afterload before positioning the second prosthetic segment within the aortic arch, 1 microg/kg/min nitroprusside drip was continued. A few minutes initiation of the drip an abrupt rise in blood pressure (systolic 200 mmHg) was observed, which had to be controlled before continuing the procedure. Increased nitroprusside infusion and repeated boluses of 10 mg urapidil (3-4 boluses with an interval of 15 min) and 30 microg clonidine were unsuccessful. After 15 min with an increased nitroprusside infusion rate, the patient showed psychomotor agitation and O2 his saturation dropped to 91% while arterial pH was 7.2 and lactate concentration was 3.5 mmol/L. Nitroprusside infusion was discontinued, while 0.1 microg/kg/min fenoldopam (started when the patient arrived in the operating room) was continued without improvement. In order to complete the procedure, general anaesthesia with sevflurane (2 MAC) in air (FiO2= 40%) was induced. After successful reduction in blood pressure the procedure was completed. In the postoperative course the patient was admitted to the ICU.

[Isolated persistent left superior vena cava. Detection of cause during central venous catheterization]. / Vena cava superiore sinistra persistente isolata. Riscontro occasionale in corso di cateterismo venoso centrale.

The Authors report the causal discovery of isolated persistent left superior vena cava (IPLSVC) during a central venous incannulation with a Groshong's catheter, in a patient undergoing bone marrow transplant. After a short introduction about the IPLSVC ontogenesis, they stress the need for fluoroscopy during the central venous incannulation. The Authors conclude that the possibility of angiocardiography has been very helpful, in this case, for diagnosis and prognosis.

[Atracurium, vecuronium and pancuronium. Results of a polygraphic study]. / Atracurio, vecuronio e pancuronio. Risultati di uno studio poligrafico.

The Authors have studied three nondepolarizing muscle relaxants widely used: pancuronium v/s atracurium and vecuronium. The Train of Four was used to detect the magnitude of the neuromuscular blockade. The intubation follows 90 minutes after administration of the drugs and for each patient the Authors valued: 1) the T1 and TR values at intubation; 2) the onset-time; 3) the duration of neuromuscular blockade; 4) the recovery time. Furthermore, the degree of neuromuscular blockade was clinically checked both at the time of induction and at recovery. The results of the present study show, in accordance with the literature, that all three drugs tested are capable of obtaining complete muscle relaxation. Atracurium and vecuronium particularly allow an adequate intubation at the adopted doses (0.6 mg/kg and 0.1 mg/kg respectively) with a relatively short onset-time (medium values 136" in the group of atracurium and 146" in the group of vecuronium) and a restoration time faster than pancuronium.