Effectiveness of the piezoelectric knife as a tool for nasal beak reduction in patients with chronic rhinosinusitis - a pilot study.

AIM: The aim of this study was to evaluate the safety and efficacy of the piezoelectric knife as a new tool for frontal beak surgery in patients with chronic rhinosinusitis (CRS) both in terms of imaging and perception of symptoms' outcomes. MATERIALS AND METHODS: The study involved 28 patients with CRS who underwent endoscopic sinus surgery (ESS) using a piezoelectric knife in the frontal recess region. Assessment of sinus imaging and patients' quality of life (QoL) was performed before and after surgery with the Lund-Kennedy and Lund-Mackay systems and the 22-item Sino-Nasal Outcomes Test (SNOT-22). RESULTS: Median scores on the Lund-Kennedy and Lund-Mackay systems decreased within 24 weeks after surgery with piezo knife assistance by 4 and 5 points, respectively. QoL improved with SNOT-22 scores decreasing by 35.5 points. CONCLUSIONS: ESS with the piezoelectric knife used for frontal beak reduction turned out to be a safe procedure. In the studied group of patients, the improvement was observed in terms of imaging, patients' perceptions of symptoms, and QoL outcomes. Therefore, the piezoelectric knife might be a valuable supporting tool in ESS in patients with CRS, although further observation is needed.

Healthcare resource utilisation and direct medical cost for individuals with 5q spinal muscular atrophy in Sweden.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare, progressive, neuromuscular disorder. Recent advances in treatment require an updated assessment of burden to inform reimbursement decisions. OBJECTIVES: To quantify healthcare resource utilisation (HCRU) and cost of care for patients with SMA. METHODS: Cohort study of patients with SMA identified in the Swedish National Patient Registry (2007-2018), matched to a reference cohort grouped into four SMA types (1, 2, 3, unspecified adult onset [UAO]). HCRU included inpatient admissions, outpatient visits, procedures, and dispensed medications. Direct medical costs were estimated by multiplying HCRU by respective unit costs. Average annual HCRU and medical costs were modelled for SMA versus reference cohorts to estimate differences attributable to the disease (i.e., average treatment effect estimand). The trajectory of direct costs over time were assessed using synthetic cohorts. RESULTS: We identified 290 SMA patients. Annualised HCRU was higher in SMA patients compared with reference cohorts. Highest risk ratios were observed for inpatient overnight stays for type 1 (risk ratio [RR]: 29.2; 95% confidence interval [CI]: 16.0, 53.5) and type 2 (RR: 23.3; 95% CI: 16.4,33.1). Mean annual direct medical costs per patient for each year since first diagnosis were greatest for type 1 (€114,185 and SMA-attributable: €113,380), type 2 (€61,876 and SMA-attributable: €61,237), type 3 (€45,518 and SMA-attributable: €44,556), and UAO (€4046 and SMA-attributable: €2098). Costs were greatest in the 2-3 years after the first diagnosis for all types. DISCUSSION AND CONCLUSION: The economic burden attributable to SMA is significant. Further research is needed to understand the burden in other European countries and the impact of new treatments.

The Influence of Endodontic Lesions on The Clinical Evolution of Odontogenic Sinusitis-A Cohort Study.

Endodontic disease with formation of periapical lesions (PALs) is one of the most common causes of chronic odontogenic sinusitis (ODS). It requires close collaboration between otolaryngologists and dentists, but the best sequence of management is still unknown. The aim of the present study is to clarify how radiological characteristics of teeth with PALs and previous root-canal treatment (RCT) influence the clinical evolution of the disease and to define the predictive value of its radiological and endoscopic features in determining the need for further surgical intervention. A total of 68 symptomatic patients with ODS with PALs were included in the study. The evaluation was performed by an otolaryngologist and a dentist based on a medical interview, nasal endoscopy, cold pulp testing and tomography images. Patients were prospectively followed for at least 12 months, during which nasal steroids, saline irrigations and RCT were administered. The criteria of disease improvement were: decrease of symptoms, healed sinonasal mucosa in endoscopy and radiological resolution of periapical radiolucency and sinus inflammation. Results showed that 9 (13%) patients improved after conservative treatment and 59 (87%) required further surgical intervention. Patients who improved after medical treatment and RCT were younger (p = 0.043) and had a greater distance from the top of the periapical lesion to the maxillary sinus' floor (p = 0.003). When expansion of PALs and bone destruction toward the maxillary sinus was observed on radiological imaging (p = 0.041), and when more than one tooth root was affected (p = 0.004), patients were more likely to require surgical intervention. In conclusion, the more roots that are affected and the closer the top of the PAL is to the maxillary sinus' floor, the greater the possibility of medical treatment and RCT failure. When the bone destruction extends into the maxillary sinus, patients eventually require both tooth extraction and FESS in order to resolve ODS completely.

Physiologically-Informed Gaussian Processes for Interpretable Modelling of Psycho-Physiological States.

The widespread popularity of Machine Learning (ML) models in healthcare solutions has increased the demand for their interpretability and accountability. In this paper, we propose the Physiologically-Informed Gaussian Process (PhGP) classification model, an interpretable machine learning model founded on the Bayesian nature of Gaussian Processes (GPs). Specifically, we inject problem-specific domain knowledge of inherent physiological mechanisms underlying the psycho-physiological states as a prior distribution over the GP latent space. Thus, to estimate the hyper-parameters in PhGP, we rely on the information from raw physiological signals as well as the designed prior function encoding the physiologically-inspired modelling assumptions. Alongside this new model, we present novel interpretability metrics that highlight the most informative input regions that contribute to the GP prediction. We evaluate the ability of PhGP to provide an accurate and interpretable classification on three different datasets, including electrodermal activity (EDA) signals collected during emotional, painful, and stressful tasks. Our results demonstrate that, for all three tasks, recognition performance is improved by using the PhGP model compared to competitive methods. Moreover, PhGP is able to provide physiological sound interpretations over its predictions.

Do Symptoms Correlate with the Signs in Odontogenic Sinusitis with Periapical Lesions?

INTRODUCTION: Endodontic pathology is one of the most common causes of odontogenic sinusitis, and its evaluation is challenging. Omission of periapical lesions in diagnostic process leads to recurrent sinusitis after cessation of medical therapy. METHODS: Sixty-one symptomatic patients presented with odontogenic sinusitis with periapical lesions of teeth adjacent to the maxillary sinus were included in the study. Symptoms evaluated with SNOT-22 and OHIP-14 questionnaires were compared to signs during endoscopic and radiological evaluation. RESULTS: Coexistence of odontogenic sinusitis with nasal polyps significantly decreases the quality of life, especially concerning the emotional domain (p = 0.047). Patency of ostiomeatal corresponds well with the severity of sinonasal symptoms reported with SNOT-22 (p = 0.051). Extent of maxillary sinus opacifications scored with Zinreich scale correlates positively with the presence of discharge (p = 0.001) and edema (p = 0.072) in the endoscopic Lund-Kennedy scale. Among 67 teeth with periapical lesions, 73.1% had undergone previous root canal treatment, but in 47.8% of cases, it was defined as incomplete. Endodontic status did not affect the severity of patient's complaints. CONCLUSION: In case of odontogenic sinusitis of endodontic origin, endoscopic signs correlate better than radiological with the self-reported symptoms. In order to better evaluate the severity of the disease and possible need of surgical intervention, both otolaryngologists and dental specialists should focus on extent of inflammatory lesions in the maxillary sinus.

Clinical characteristics of odontogenic sinusitis with periapical lesions.

INTRODUCTION: Although the symptoms and radiographic signs may mimic rhinogenic sinusitis, odontogenic sinusitis (OS) with periapical lesions (PALs) is fundamentally an endodontic infection. It is considered to be one of the main causes of OS, especially when presented unilaterally. Despite this routine dental examination is not performed and periapical infection frequently remains undiagnosed by otolaryngologists and radiologists. MATERIAL AND METHODS: This prospective observational study covered a group of 61 patients with symptomatic OS with PAL. Assessment of quality of life was done using the 22-item Sino-Nasal Outcome Test-22 (SNOT-22) and Oral Health-Impact Profile-14 (OHIP-14). Temporal and etiological relationship between the dental cause and sinonasal complication was established among the otolaryngologist and dental specialist based on the clinical symptoms, nasal endoscopy described according to the modified Lund-MacKay scale, computed tomography (CT) scans measured and scored in compliance with Lund- Kennedy, Zinreich and Estrela scales. RESULTS: Out of 61 patients, 28 (46%) were women and 33 (54%) men. Group median age 49.1 years, ranged from 22.8 to 78.9 years. Total OHIP-14 score was 12.7 ± 11.3, with the highest value obtained in domains describing physical pain (mean 2.9 ± 2.4, median 3) in which the highest score was obtained in item 3 - painful aching in mouth and/or teeth - scored ≥2 by 52.5% of participants. Concerning dental symptoms 11.5% of patients were asymptomatic. Total SNOT-22 score was 40.7 ± 21.1, with the highest value in domains describing nasal symptoms. 23% of patients reported mild, 44.3% moderate and 32.7% severe symptoms. In the endoscopic evaluation 86.8% of cases presented discharge, 73.8% mucosal edema. In 11.5% of cases the polypoid tissues was observed in nasal cavities. The first molar tooth was the most frequently affected with an incidence of 42.6%, followed by the second molar (27.9%). In 33 (48.5%) of cases the inflammatory process caused the discontinuity of the sinus floor, which in 51.5% coexisted with total maxillary sinus opacification. 10 teeth (14.7%) had the periapical lesions with a diameter exceeding 8 mm. In case of the multi-rooted teeth, PALs were usually encountered at more than one root (57.4%). Maxillary and ethmoid sinus were affected in 54% of cases and additional frontal sinus involvement in 32.8%. In 69.6% patients, ostiomeatal complex was obstructed. CONCLUSIONS: Persistent sinonasal symptoms such as rhinorrhea, post-nasal drip and nose congestion along with dental pain may suggest endodontic nature of OS, especially after previous root-canal treatment. The bigger the PAL is in diameter and the closer to the maxillary sinus, the greater effect on its mucosal involvement and obstruction of ostiomeatal complex is observed. PALs around molar or premolar tooth apexes with coexistence of unilateral sinus opacifications should be noticed and mentioned by radiologists and evaluated by dental specialists in order to refer the patient to further treatment.

The effect of odontogenic sinusitis with periapical lesions on quality of life.

<b> Introduction:</b> Usually the symptoms presented in odontogenic sinusitis do not differ from chronic sinusitis of other origin. However, odontogenic sinusitis is considered as an independent disease which requires specific diagnostic approach and treatment. </br></br> <b>Aim:</b> The aim of the study is to define the main symptoms of odontogenic rhinosinusitis with periapical lesions and its impact on the quality of life. </br></br> <b>Material and methods:</b> The SNOT-22 and OHIP-14 questionnaires were distributed among 26 symptomatic patients suffering from odontogenic sinusitis with periapical lesions in the teeth that remain in close contact with the maxillary sinus floor. Data was collected by means of an interview and standard examination performed by an otolaryngologist and a maxillofacial surgeon. The symptoms were also objectified using nasal endoscopy and radiological studies. The acquired data was statistically analyzed. </br></br> <b>Results:</b> The total OHIP-14 score was 14.7 ± 11.3, whereas the total SNOT-22 score was 44.6 ± 18.8. Women scored significantly higher in the total SNOT-22 score as well as domains concerning nasal symptoms, quality of sleep, and emotional symptoms. The answers given in similar items were comparable between both questionnaires. </br></br> <b>Conclusions:</b> Properly diagnosed odontogenic sinusitis (OS) with periapical lesions (PAL) will improve the quality of health-care and spare the patients inadequate procedures. Standard examination should include a unified and validated question-naire concerning both sinonasal and oral symptoms. Painful aching in the mouth and discomfort during eating might help to identify the OS with PAL during a medical interview and help both ENT (ear-nose-throat) specialists and dentists to establish proper patient-oriented diagnosis and treatment.

Evaluation of apoptotic potential of glyphosate metabolites and impurities in human peripheral blood mononuclear cells (in vitro study).

Glyphosate is used for cereal, vegetable and fruit crops for reducing or inhibiting the growth of weeds as well as a desiccant for various grain crops. That is why, glyphosate has been shown to be accumulated in humans and animals through ingestion of food of both plant and animal origin. The study aimed to assessed the effect of glyphosate, its metabolites: aminomethylphosphonic acid (AMPA), methylphosphonic acid and its impurities: PMIDA, N-methylglyphosate, hydroxymethylphosphonic acid and bis(phosphonomethyl)amine on apoptosis induction in human peripheral blood mononuclear cells (PBMCs). PBMCs were exposed to the compounds studied at the concentrations ranging from 0.01 to 5 mM for 4 h. We have observed an increase in reactive oxygen species (including hydroxyl radical) and cytosolic calcium ions levels as well as reduction of transmembrane mitochondrial potential (ΔΨm) in PBMCs exposed to the compounds examined. All substances studied changed PBMCs membrane permeability, activated caspase-8, -9, -3 and caused chromatin condensation, which showed that they were capable of inducing apoptosis both via extrinsic and particularly intrinsic pathway. Generally the study demonstrated that there were no differences between apoptotic changes induced by glyphosate, its metabolites or impurities, and observed changes were provoked by high concentrations of investigated compounds.

Current State and Future Directions of Technology-Based Ecological Momentary Assessment and Intervention for Major Depressive Disorder: A Systematic Review.

Ecological momentary assessment (EMA) and ecological momentary intervention (EMI) are alternative approaches to retrospective self-reports and face-to-face treatments, and they make it possible to repeatedly assess patients in naturalistic settings and extend psychological support into real life. The increase in smartphone applications and the availability of low-cost wearable biosensors have further improved the potential of EMA and EMI, which, however, have not yet been applied in clinical practice. Here, we conducted a systematic review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to explore the state of the art of technology-based EMA and EMI for major depressive disorder (MDD). A total of 33 articles were included (EMA = 26; EMI = 7). First, we provide a detailed analysis of the included studies from technical (sampling methods, duration, prompts), clinical (fields of application, adherence rates, dropouts, intervention effectiveness), and technological (adopted devices) perspectives. Then, we identify the advantages of using information and communications technologies (ICTs) to extend the potential of these approaches to the understanding, assessment, and intervention in depression. Furthermore, we point out the relevant issues that still need to be addressed within this field, and we discuss how EMA and EMI could benefit from the use of sensors and biosensors, along with recent advances in machine learning for affective modelling.

Current state and future directions of technology-based ecological momentary assessments and interventions for major depressive disorder: protocol for a systematic review.

BACKGROUND: Ecological momentary assessments (EMAs) and ecological momentary interventions (EMIs) represent a novel approach for the assessment and delivery of psychological support to depressed patients in daily life. Beyond the classical paper-and-pencil daily diaries, the more recent progresses in Information and Communication Technologies (ICT) enabled researchers to bring all the needed processes together in only one device, i.e., response signaling, repeated symptom collection, information storage, secure data transfer, and psychological support delivery. Despite evidence showing the feasibility and acceptability of these techniques, EMAs are only beginning to be applied in real clinical practice, whether the development of EMIs for clinically depressed patients is still very limited. The objective of this systematic review is to provide the state of the art of technology-based EMAs and EMIs for major depressive disorder (MDD), with the aim of leading the way to possible future directions for the clinical practice. METHODS: We will conduct a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Data sources will include two bibliographic databases, PubMed and Web of Science (Web of Knowledge), supplemented by searches for unpublished or ongoing studies. Eligible studies will report data for adult (≥ 18 years old) with a primary (both current and past) diagnosis of MDD, defined by a valid criterion standard. We will consider studies adopting technology-based EMAs and EMIs for the investigation and/or assessment of depression and for the delivery of a psychological intervention. We will exclude studies adopting paper-and-pencil tools. DISCUSSION: The proposed systematic review will provide new insights on the advantages and benefits of adopting technology-based EMAs and EMIs for MDD in the traditional clinical practice, taking into consideration both clinical and technological issues. The potential of using sensors and biosensors along with machine learning for affective modeling will also be discussed.

Molecular Filters for Noise Reduction.

Living systems are inherently stochastic and operate in a noisy environment, yet despite all these uncertainties, they perform their functions in a surprisingly reliable way. The biochemical mechanisms used by natural systems to tolerate and control noise are still not fully understood, and this issue also limits our capacity to engineer reliable, quantitative synthetic biological circuits. We study how representative models of biochemical systems propagate and attenuate noise, accounting for intrinsic as well as extrinsic noise. We investigate three molecular noise-filtering mechanisms, study their noise-reduction capabilities and limitations, and show that nonlinear dynamics such as complex formation are necessary for efficient noise reduction. We further suggest that the derived molecular filters are widespread in gene expression and regulation and, particularly, that microRNAs can serve as such noise filters. To our knowledge, our results provide new insight into how biochemical networks control noise and could be useful to build robust synthetic circuits.

Critical properties of unlimited gliding: Unexpected flocking behavior driven by the exchange of information.

Inspired by albatrosses that use thermal lifts to fly across oceans we develop a simple model of gliders that serves us to study theoretical limitations of unlimited exploration of the Earth. Our studies, grounded in physical theory of continuous percolation and biased random walks, allow us to identify a variety of percolation transitions, which are understood as providing potentially unlimited movement through a space in a specified direction. We discover an unexpected phenomenon of self-organization of gliders in clusters, which resembles the flock organization of birds. This self-organization is intriguing, as it occurs thanks to exchange of information only and without any particular rules that could favor the clustering of the gliders (in contrast to the causes well known in literature, like, for example, attractive forces used in the Vicsek-type models or fitness functions used in evolutionary computation).

Chemical reaction network designs for asynchronous logic circuits.

Chemical reaction networks (CRNs) are a versatile language for describing the dynamical behaviour of chemical kinetics, capable of modelling a variety of digital and analogue processes. While CRN designs for synchronous sequential logic circuits have been proposed and their implementation in DNA demonstrated, a physical realisation of these devices is difficult because of their reliance on a clock. Asynchronous sequential logic, on the other hand, does not require a clock, and instead relies on handshaking protocols to ensure the temporal ordering of different phases of the computation. This paper provides novel CRN designs for the construction of asynchronous logic, arithmetic and control flow elements based on a bi-molecular reaction motif with catalytic reactions and uniform reaction rates. We model and validate the designs for the deterministic and stochastic semantics using Microsoft's GEC tool and the probabilistic model checker PRISM, demonstrating their ability to emulate the function of asynchronous components under low molecular count.

Programming discrete distributions with chemical reaction networks.

We explore the range of probabilistic behaviours that can be engineered with Chemical Reaction Networks (CRNs). We give methods to "program" CRNs so that their steady state is chosen from some desired target distribution that has finite support in [Formula: see text], with [Formula: see text]. Moreover, any distribution with countable infinite support can be approximated with arbitrarily small error under the [Formula: see text] norm. We also give optimized schemes for special distributions, including the uniform distribution. Finally, we formulate a calculus to compute on distributions that is complete for finite support distributions, and can be compiled to a restricted class of CRNs that at steady state realize those distributions.

PRISM-games: verification and strategy synthesis for stochastic multi-player games with multiple objectives.

PRISM-games is a tool for modelling, verification and strategy synthesis for stochastic multi-player games. These allow models to incorporate both probability, to represent uncertainty, unreliability or randomisation, and game-theoretic aspects, for systems where different entities have opposing objectives. Applications include autonomous transport, security protocols, energy management systems and many more. We provide a detailed overview of the PRISM-games tool, including its modelling and property specification formalisms, and its underlying architecture and implementation. In particular, we discuss some of its key features, which include multi-objective and compositional approaches to verification and strategy synthesis. We also discuss the scalability and efficiency of the tool and give an overview of some of the case studies to which it has been applied.

Factors affecting one-year survival after radical cystectomy: A prospective study.

INTRODUCTION: Survival after radical cystectomy (RC) is affected by various factors. Significance of preoperative health status and its influence on treatment outcome is uncertain. The aim of the study was to prospectively evaluate overall survival, cause of death and the role of comorbidities in mortality during the first 12 months following RC. MATERIAL AND METHODS: All patients who underwent RC between January 2014 and May 2016 for T1-T4 bladder cancer in a single center were prospectively followed. Stage and comorbidities were explored as predictors of overall survival (OS). Patient status was assessed for at least 12 months. RESULTS: Follow-up was available for 25 men and 19 women at the mean age 67. Median time of follow-up for survivors was 16 months. Six-month and 1-year OS was 84% and 77%. Out of 11 deaths, 8 were related to cancer progression and 3 patients died for other causes. All deaths apart from one occurred in the first year after surgery. One-year OS was affected mostly by tumor stage: 95% for pT1-2 vs. 62.5% for pT3-4; p = 0.01. Worse outcome was found in patients ≥72 years old, (44% vs. 86%; p = 0.02) and among women (63% vs. 88%; p = 0.07). When patients who died were compared to survivors the following distribution of comorbidities was found: diabetes mellitus - 30.0% vs. 11.8%, p = 0.3; history of stroke - 30.0% vs. 2.9%, p = 0.1; thyroid disease - 30.0% vs. 11.8%, p = 0.3. CONCLUSIONS: Majority of patients died because cystectomy was performed too late. History of stroke, diabetes mellitus, and thyroid diseases should be assessed as possible risk factors in larger studies.

DNA damage and methylation induced by glyphosate in human peripheral blood mononuclear cells (in vitro study).

Glyphosate is a very important herbicide that is widely used in the agriculture, and thus the exposure of humans to this substance and its metabolites has been noted. The purpose of this study was to assess DNA damage (determination of single and double strand-breaks by the comet assay) as well as to evaluate DNA methylation (global DNA methylation and methylation of p16 (CDKN2A) and p53 (TP53) promoter regions) in human peripheral blood mononuclear cells (PBMCs) exposed to glyphosate. PBMCs were incubated with the compound studied at concentrations ranging from 0.1 to 10 mM for 24 h. The study has shown that glyphosate induced DNA lesions, which were effectively repaired. However, PBMCs were unable to repair completely DNA damage induced by glyphosate. We also observed a decrease in global DNA methylation level at 0.25 mM of glyphosate. Glyphosate at 0.25 mM and 0.5 mM increased p53 promoter methylation, while it did not induce statistically significant changes in methylation of p16 promoter. To sum up, we have shown for the first time that glyphosate (at high concentrations from 0.5 to 10 mM) may induce DNA damage in leucocytes such as PBMCs and cause DNA methylation in human cells.

Stochastic analysis of Chemical Reaction Networks using Linear Noise Approximation.

Stochastic evolution of Chemical Reactions Networks (CRNs) over time is usually analyzed through solving the Chemical Master Equation (CME) or performing extensive simulations. Analysing stochasticity is often needed, particularly when some molecules occur in low numbers. Unfortunately, both approaches become infeasible if the system is complex and/or it cannot be ensured that initial populations are small. We develop a probabilistic logic for CRNs that enables stochastic analysis of the evolution of populations of molecular species. We present an approximate model checking algorithm based on the Linear Noise Approximation (LNA) of the CME, whose computational complexity is independent of the population size of each species and polynomial in the number of different species. The algorithm requires the solution of first order polynomial differential equations. We prove that our approach is valid for any CRN close enough to the thermodynamical limit. However, we show on four case studies that it can still provide good approximation even for low molecule counts. Our approach enables rigorous analysis of CRNs that are not analyzable by solving the CME, but are far from the deterministic limit. Moreover, it can be used for a fast approximate stochastic characterization of a CRN.

The Impact of Glyphosate, Its Metabolites and Impurities on Viability, ATP Level and Morphological changes in Human Peripheral Blood Mononuclear Cells.

The toxicity of herbicides to animals and human is an issue of worldwide concern. The present study has been undertaken to assess toxic effect of widely used pesticide-glyphosate, its metabolites: aminomethylphosphonic acid (AMPA) and methylphosphonic acid and its impurities: N-(phosphonomethyl)iminodiacetic acid (PMIDA), N-methylglyphosate, hydroxymethylphosphonic acid and bis-(phosphonomethyl)amine on human peripheral blood mononuclear cells (PBMCs). We have evaluated the effect of those compounds on viability, ATP level, size (FSC-A parameter) and granulation (SSC-A parameter) of the cells studied. Human peripheral blood mononuclear cells were exposed to different concentrations of glyphosate, its metabolites and impurities (0.01-10 mM) for 4 and 24 h. It was found that investigated compounds caused statistically significant decrease in viability and ATP level of PBMCs. The strongest changes in cell viability and ATP level were observed after 24 h incubation of PBMCs with bis-(phosphonomethyl)amine, and particularly PMIDA. Moreover, all studied compounds changed cell granularity, while PMIDA and bis-(phosphonomethyl)amine altered PBMCs size. It may be concluded that bis-(phosphonomethyl)amine, and PMIDA caused a slightly stronger damage to PBMCs than did glyphosate. Changes in the parameters studied in PBMCs were observed only at high concentrations of the compounds examined, which clearly shows that they may occur in this cell type only as a result of acute poisoning of human organism with these substances.

Modelling DNA origami self-assembly at the domain level.

We present a modelling framework, and basic model parameterization, for the study of DNA origami folding at the level of DNA domains. Our approach is explicitly kinetic and does not assume a specific folding pathway. The binding of each staple is associated with a free-energy change that depends on staple sequence, the possibility of coaxial stacking with neighbouring domains, and the entropic cost of constraining the scaffold by inserting staple crossovers. A rigorous thermodynamic model is difficult to implement as a result of the complex, multiply connected geometry of the scaffold: we present a solution to this problem for planar origami. Coaxial stacking of helices and entropic terms, particularly when loop closure exponents are taken to be larger than those for ideal chains, introduce interactions between staples. These cooperative interactions lead to the prediction of sharp assembly transitions with notable hysteresis that are consistent with experimental observations. We show that the model reproduces the experimentally observed consequences of reducing staple concentration, accelerated cooling, and absent staples. We also present a simpler methodology that gives consistent results and can be used to study a wider range of systems including non-planar origami.