Paramedic Interventions and Adverse Patient Events during Prolonged Interfacility Ground Transport in a "Drip and Ship" Pharmacoinvasive Model of STEMI Care.

OBJECTIVE: Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for patients with ST-segment elevation myocardial infarction (STEMI). However, when primary PCI is not available in a timely fashion, fibrinolysis and early transfer for routine PCI is recommended. Prince Edward Island (PEI) is the only province in Canada without a PCI facility, and distances to the nearest PCI-capable facilities are between 290 and 374 kilometers. This results in prolonged out-of-hospital time for critically ill patients. We sought to characterize and quantify paramedic interventions and adverse patient events during prolonged ground transport to PCI facilities post-fibrinolysis. METHODS: We performed a retrospective chart review of patients presenting to any of four emergency departments (ED) on PEI during the calendar years 2016 and 2017. We identified patients through administrative discharge data and cross referenced with emergent out-of-province ambulance transfers. All included patients were managed as STEMIs in the EDs and subsequently transferred (primary PCI, pharmacoinvasive) directly from the EDs to PCI facilities. We excluded patients having STEMIs on inpatient wards and those transported by other means. We reviewed electronic and paper ED charts plus paper EMS records. We performed summary statistics. RESULTS: We identified 149 patients meeting inclusion criteria. Most patients were males (77.9%), mean age 62.1 (SD 13.8) years. The mean transport interval was 202 (SD 29.0) minutes. Thirty-two adverse events occurred during 24 transports (16.1%). There was one death, and four patients required diversion to non-PCI facilities. Hypotension was the most common adverse event (n = 13, 8.7%), and fluid bolus (n = 11, 7.4%) was the most common intervention. Three (2.0%) patients required electrical therapy. Nitrates (n = 65, 43.6%) and opioid analgesics (n = 51, 34.2%) were the most common drugs administered during transport. CONCLUSION: In a setting where primary PCI is not feasible due to distance, a pharmacoinvasive model of STEMI care is associated with a 16.1% proportion of adverse events. Crew configuration including ALS clinicians is the key in managing these events.

Paramedic Clinical Consults with a Paramedic or Nurse in an EMS Communications Center Compared to Traditional Online Physician Consults.

OBJECTIVES: In many emergency medical services (EMS) systems, a direct medical oversight physician is available to paramedics for mandatory and/or elective consultations. At the time of this study, a clinical support desk (CSD) was being implemented within the medical communications center of a provincial EMS system in addition to the physician resource. The CSD was initially staffed with a registered nurse or an advanced care paramedic. The objective of the current study was to compare CSD "peer to peer" consults versus physician consults with regards to consultation patterns, transport dispositions, and patient safety measures. METHODS: This retrospective cohort study analyzed 2 months before (September 1 to October 31, 2012) and 2 months after (September 1 to October 31, 2013) implementation of the CSD. In the before period, all clinical consults were fielded by the direct medical oversight physician. In the after period, consults were fielded by the physician, CSD or both. EMS databases were queried, and manual chart review and abstraction of audio recordings were done. Relapses back to EMS within 48 hours of non-transport were measured. RESULTS: 1621 consults were included, with 764 consults in the before period and 857 after (p = 0.02). The number of physician consults decreased from 764 before to 464 after (39.2%, p < 0.001), with the CSD taking 325 (37.9%) consults. The CSD was consulted more for police custody and trip destination. The physician was consulted more for cease resuscitation and clinical consults prior to medication administration. Overall non-transport rates were 595/764 before (77.9%), and 646/857 after (75.4%) (p = 0.2). Non-transports were 233/325 (71.7%) via the CSD, 364/464 (78.4%) via the physician, and 49/68 (72.1%) when both were involved (p = 0.07). Rate of relapse to EMS was similar before (25/524, 4.8%) and after (26/568, 4.6%) (p = 0.76), and between CSD (12/216, 5.5%) and physician consults (13/325, 4.0%) in the after period (p = 0.41). CONCLUSION: The introduction of a novel "peer-to-peer" consult program was associated with an increased total number of consults made and reduced call volume for direct medical oversight physicians. There was no change in the patient safety measure studied.

The Prevalence and Characteristics of Non-Transports in a Provincial Emergency Medical Services System: A Population-Based Study.

BACKGROUND: Emergency Medical Services (EMS) provide patients with out-of-hospital care, but not all patients are transported to the hospital. Non-transport represents an often undefined yet potentially significant risk for poor clinical outcomes. Few North American studies have quantified this risk. OBJECTIVE: The objectives of this study were to determine the prevalence of non-transport and 48-h adverse event (composite of relapse responses that resulted in transport or death) and to identify characteristics associated with either outcome. METHODS: An analysis of pooled cross-sectional, population-based administrative data from the provincial EMS electronic charting system in 2014 was conducted. Determination of non-transport was based on recorded call outcome. The data were searched by patient identifiers to determine the 48-h adverse event rate. Paramedic-documented patient, operational, and environmental characteristics were included in the logistic regression models. RESULTS: Of 74,293 emergency responses, 14,072 (18.9%) were non-transport and, of those, 798 (5.6%) resulted in a 48-h adverse event. The characteristics statistically significantly and independently associated with non-transport and 48-h adverse event were younger age (odds ratio [OR] 1.72; 99.9% confidence interval [CI] 1.46-2.02), nonspecific paramedic clinical impression (OR 5; 99.9% CI 4.48-5.57), more than 7 comorbidities (OR 0.47; 99.9% CI 0.42-0.53), and incident location (jail) (OR 2.88; 99.9% CI 2.22-3.74). CONCLUSIONS: This study provides an estimate of prevalence of non-transports and 48-h adverse event in a provincial mixed rural-urban EMS system. The results of this study describe the scope of non-transport and present several characteristics associated with non-transport. Future study should examine the appropriateness of EMS responses and methods to mitigate risk of adverse event after non-transport.

Modelling and DNA topology of compact 2-start and 1-start chromatin fibres.

We have investigated the structure of the most compact 30-nm chromatin fibres by modelling those with 2-start or 1-start crossed-linker organisations. Using an iterative procedure we obtained possible structural solutions for fibres of the highest possible compaction permitted by physical constraints, including the helical repeat of linker DNA. We find that this procedure predicts a quantized nucleosome repeat length (NRL) and that only fibres with longer NRLs (≥197 bp) can more likely adopt the 1-start organisation. The transition from 2-start to 1-start fibres is consistent with reported differing binding modes of the linker histone. We also calculate that in 1-start fibres the DNA constrains more torsion (as writhe) than 2-start fibres with the same NRL and that the maximum constraint obtained is in accord with previous experimental results. We posit that the coiling of the fibre is driven by overtwisting of linker DNA which, in the most compact forms - for example, in echinoderm sperm and avian erythrocytes - could adopt a helical repeat of ∼10 bp/turn. We argue that in vivo the total twist of linker DNA could be modulated by interaction with other abundant chromatin-associated proteins and by epigenetic modifications of the C-terminal tail of linker histones.

Highly disordered histone H1-DNA model complexes and their condensates.

Disordered proteins play an essential role in a wide variety of biological processes, and are often posttranslationally modified. One such protein is histone H1; its highly disordered C-terminal tail (CH1) condenses internucleosomal linker DNA in chromatin in a way that is still poorly understood. Moreover, CH1 is phosphorylated in a cell cycle-dependent manner that correlates with changes in the chromatin condensation level. Here we present a model system that recapitulates key aspects of the in vivo process, and also allows a detailed structural and biophysical analysis of the stages before and after condensation. CH1 remains disordered in the DNA-bound state, despite its nanomolar affinity. Phase-separated droplets (coacervates) form, containing higher-order assemblies of CH1/DNA complexes. Phosphorylation at three serine residues, spaced along the length of the tail, has little effect on the local properties of the condensate. However, it dramatically alters higher-order structure in the coacervate and reduces partitioning to the coacervate phase. These observations show that disordered proteins can bind tightly to DNA without a disorder-to-order transition. Importantly, they also provide mechanistic insights into how higher-order structures can be exquisitely sensitive to perturbation by posttranslational modifications, thus broadening the repertoire of mechanisms that might regulate chromatin and other macromolecular assemblies.

2017 American Heart Association Focused Update on Adult Basic Life Support and Cardiopulmonary Resuscitation Quality: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

Cardiopulmonary resuscitation is a lifesaving technique for victims of sudden cardiac arrest. Despite advances in resuscitation science, basic life support remains a critical factor in determining outcomes. The American Heart Association recommendations for adult basic life support incorporate the most recently published evidence and serve as the basis for education and training for laypeople and healthcare providers who perform cardiopulmonary resuscitation.

ILCOR Scientific Knowledge Gaps and Clinical Research Priorities for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: A Consensus Statement.

Despite significant advances in the field of resuscitation science, important knowledge gaps persist. Current guidelines for resuscitation are based on the International Liaison Committee on Resuscitation 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations, which includes treatment recommendations supported by the available evidence. The writing group developed this consensus statement with the goal of focusing future research by addressing the knowledge gaps identified during and after the 2015 International Liaison Committee on Resuscitation evidence evaluation process. Key publications since the 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations are referenced, along with known ongoing clinical trials that are likely to affect future guidelines.

2017 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations Summary.

The International Liaison Committee on Resuscitation has initiated a near-continuous review of cardiopulmonary resuscitation science that replaces the previous 5-year cyclic batch-and-queue approach process. This is the first of an annual series of International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations summary articles that will include the cardiopulmonary resuscitation science reviewed by the International Liaison Committee on Resuscitation in the previous year. The review this year includes 5 basic life support and 1 pediatric Consensuses on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Each of these includes a summary of the science and its quality based on Grading of Recommendations, Assessment, Development, and Evaluation criteria and treatment recommendations. Insights into the deliberations of the International Liaison Committee on Resuscitation task force members are provided in Values and Preferences sections. Finally, the task force members have prioritized and listed the top 3 knowledge gaps for each population, intervention, comparator, and outcome question.

Evolution of a high-performance emergency health services system in Nova Scotia.

Since 1997, Emergency Health Services in Nova Scotia (NS) has evolved from a program providing prehospital care for patients in transport to a system providing integrated healthcare in both traditional (ie, ambulance) and non-traditional settings (eg, patient homes, hospital settings). This article highlights (1) the reorganization of the emergency medical service system design, (2) the strategies enabling efficient operation of this design, and (3) resultant innovations evolving from both system redesign and strategy application. Emergency Health Services has utilized a Public Utility Model (PUM) design providing prehospital healthcare, public safety, and public health responses to the population of NS. The success of the PUM has been complimented by three strategies: (1) co-leadership model operations, (2) common languages to translate evidence into practice, and (3) collaborative and integrated relationships with other regulated healthcare providers. This prehospital system design and application strategies could be applied in other sectors of community and hospital systems of care.

Chromosomal position shift of a regulatory gene alters the bacterial phenotype.

Recent studies strongly suggest that in bacterial cells the order of genes along the chromosomal origin-to-terminus axis is determinative for regulation of the growth phase-dependent gene expression. The prediction from this observation is that positional displacement of pleiotropic genes will affect the genetic regulation and hence, the cellular phenotype. To test this prediction we inserted the origin-proximal dusB-fis operon encoding the global regulator FIS in the vicinity of replication terminus on both arms of the Escherichia coli chromosome. We found that the lower fis gene dosage in the strains with terminus-proximal dusB-fis operons was compensated by increased fis expression such that the intracellular concentration of FIS was homeostatically adjusted. Nevertheless, despite unchanged FIS levels the positional displacement of dusB-fis impaired the competitive growth fitness of cells and altered the state of the overarching network regulating DNA topology, as well as the cellular response to environmental stress, hazardous substances and antibiotics. Our finding that the chromosomal repositioning of a regulatory gene can determine the cellular phenotype unveils an important yet unexplored facet of the genetic control mechanisms and paves the way for novel approaches to manipulate bacterial physiology.

Upstream binding of idling RNA polymerase modulates transcription initiation from a nearby promoter.

The bacterial gene regulatory regions often demonstrate distinctly organized arrays of RNA polymerase binding sites of ill-defined function. Previously we observed a module of closely spaced polymerase binding sites upstream of the canonical promoter of the Escherichia coli fis operon. FIS is an abundant nucleoid-associated protein involved in adjusting the chromosomal DNA topology to changing cellular physiology. Here we show that simultaneous binding of the polymerase at the canonical fis promoter and an upstream transcriptionally inactive site stabilizes a RNAP oligomeric complex in vitro. We further show that modulation of the upstream binding of RNA polymerase affects the fis promoter activity both in vivo and in vitro. The effect of the upstream RNA polymerase binding on the fis promoter activity depends on the spatial arrangement of polymerase binding sites and DNA supercoiling. Our data suggest that a specific DNA geometry of the nucleoprotein complex stabilized on concomitant binding of RNA polymerase molecules at the fis promoter and the upstream region acts as a topological device regulating the fis transcription. We propose that transcriptionally inactive RNA polymerase molecules can act as accessory factors regulating the transcription initiation from a nearby promoter.

Part 3: Adult Basic Life Support and Automated External Defibrillation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

This review comprises the most extensive literature search and evidence evaluation to date on the most important international BLS interventions, diagnostics, and prognostic factors for cardiac arrest victims. It reemphasizes that the critical lifesaving steps of BLS are (1) prevention, (2) immediate recognition and activation of the emergency response system, (3) early high-quality CPR, and (4) rapid defibrillation for shockable rhythms. Highlights in prevention indicate the rational and judicious deployment of search-and-rescue operations in drowning victims and the importance of education on opioid-associated emergencies. Other 2015 highlights in recognition and activation include the critical role of dispatcher recognition and dispatch-assisted chest compressions, which has been demonstrated in multiple international jurisdictions with consistent improvements in cardiac arrest survival. Similar to the 2010 ILCOR BLS treatment recommendations, the importance of high quality was reemphasized across all measures of CPR quality: rate, depth, recoil, and minimal chest compression pauses, with a universal understanding that we all should be providing chest compressions to all victims of cardiac arrest. This review continued to focus on the interface of BLS sequencing and ensuring high-quality CPR with other important BLS interventions, such as ventilation and defibrillation. In addition, this consensus statement highlights the importance of EMS systems, which employ bundles of care focusing on providing high-quality chest compressions while extricating the patient from the scene to the next level of care. Highlights in defibrillation indicate the global importance of increasing the number of sites with public-access defibrillation programs. Whereas the 2010 ILCOR Consensus on Science provided important direction for the "what" in resuscitation (ie, what to do), the 2015 consensus has begun with the GRADE methodology to provide direction for the quality of resuscitation. We hope that resuscitation councils and other stakeholders will be able to translate this body of knowledge of international consensus statements to build their own effective resuscitation guidelines.

Part 2: Evidence Evaluation and Management of Conflicts of Interest: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

The process for evaluating the resuscitation science has evolved considerably over the past 2 decades. The current process, which incorporates the use of the GRADE methodology, culminated in the 2015 CoSTR publication, which in turn will inform the international resuscitation councils' guideline development processes. Over the next few years, the process will continue to evolve as ILCOR moves toward a more continuous evaluation of the resuscitation science.

Cardiac arrest and cardiopulmonary resuscitation outcome reports: update of the Utstein Resuscitation Registry Templates for Out-of-Hospital Cardiac Arrest: a statement for healthcare professionals from a task force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian and New Zealand Council on Resuscitation, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa, Resuscitation Council of Asia); and the American Heart Association Emergency Cardiovascular Care Committee and the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation.

Utstein-style guidelines contribute to improved public health internationally by providing a structured framework with which to compare emergency medical services systems. Advances in resuscitation science, new insights into important predictors of outcome from out-of-hospital cardiac arrest, and lessons learned from methodological research prompted this review and update of the 2004 Utstein guidelines. Representatives of the International Liaison Committee on Resuscitation developed an updated Utstein reporting framework iteratively by meeting face to face, by teleconference, and by Web survey during 2012 through 2014. Herein are recommendations for reporting out-of-hospital cardiac arrest. Data elements were grouped by system factors, dispatch/recognition, patient variables, resuscitation/postresuscitation processes, and outcomes. Elements were classified as core or supplemental using a modified Delphi process primarily based on respondents' assessment of the evidence-based importance of capturing those elements, tempered by the challenges to collect them. New or modified elements reflected consensus on the need to account for emergency medical services system factors, increasing availability of automated external defibrillators, data collection processes, epidemiology trends, increasing use of dispatcher-assisted cardiopulmonary resuscitation, emerging field treatments, postresuscitation care, prognostication tools, and trends in organ recovery. A standard reporting template is recommended to promote standardized reporting. This template facilitates reporting of the bystander-witnessed, shockable rhythm as a measure of emergency medical services system efficacy and all emergency medical services system-treated arrests as a measure of system effectiveness. Several additional important subgroups are identified that enable an estimate of the specific contribution of rhythm and bystander actions that are key determinants of outcome.

Impact of a Novel Collaborative Long-Term Care -EMS Model: A Before-and-After Cohort Analysis of an Extended Care Paramedic Program.

To compare system and clinical outcomes before and after an extended care paramedic (ECP) program was implemented to better address the emergency needs of long-term care (LTC) residents. Data were collected from emergency medical services (EMS), hospital, and ten LTC facility charts for two five-month time periods, before and after ECP implementation. Outcomes include: number of EMS patients transported to emergency department (ED) and several clinical, safety, and system secondary outcomes. Statistics included descriptive, chi-squared, t-tests, and ANOVA; α = <0.05. 413 cases were included (before: n = 136, 33%; after n = 277, 67%). Median patient age was 85 years (IQR 77-91 years) and 292/413 (70.7%) were female. The number of transports to ED before implementation was 129/136 (94.9%), with 147/224 (65.6%) after, p < 0.001. In the after period, fewer patients seen by ECP were transported: 58/128 (45.3%) vs. 89/96 (92.7%) of those not seen by ECP, p < 0.001. Hospital admissions were similar between phases: 39/120 (32.5%) vs. 56/213 (29.4%), p = NS, but in the after phase, fewer ECP patients were admitted vs. non-ECP: 21/125 (16.8%) vs. 35/88 (39.8%), p < 0.001. Mean EMS call time (dispatch to arrive ED or clear scene) was shorter before than after: 25 minutes vs. 57 minutes, p < 0.001. In the after period, calls with ECP were longer than without ECP: 1 hour, 35 minutes vs. 30 minutes, p < 0.001. The mean patient ED length-of-stay was similar before and after: 7 hours, 29 minutes compared to 8 hours, 11 minutes; p = NS. In the after phase, ED length-of-stay was somewhat shorter with ECPs vs. no ECPs: 7 hours, 5 minutes vs. 9 hours, p = NS. There were zero relapses after no-transport in the before phase and three relapses from 77 calls not transported in the after phase (3/77, 3.9%); two involved ECP (2/70, 2.8%). Reductions were observed in the number of LTC patients transported to the ED when the ECP program was introduced, with fewer patients admitted to the hospital. EMS calls take longer with ECP involved. The addition of ECP to the LTC model of care appears to be beneficial and safe, with few relapse calls identified.

Structural insights into the mechanism of negative regulation of single-box high mobility group proteins by the acidic tail domain.

The Drosophila and plant (maize) functional counterparts of the abundant vertebrate chromosomal protein HMGB1 (HMG-D and ZmHMGB1, respectively) differ from HMGB1 in having a single HMG box, as well as basic and acidic flanking regions that vary greatly in length and charge. We show that despite these variations, HMG-D and ZmHMGB1 exist in dynamic assemblies in which the basic HMG boxes and linkers associate with their intrinsically disordered, predominantly acidic, tails in a manner analogous to that observed previously for HMGB1. The DNA-binding surfaces of the boxes and linkers are occluded in "auto-inhibited" forms of the protein, which are in equilibrium with transient, more open structures that are "binding-competent." This strongly suggests that the mechanism of auto-inhibition may be a general one. HMG-D and ZmHMGB1 differ from HMGB1 in having phosphorylation sites in their tail and linker regions. In both cases, in vitro phosphorylation of serine residues within the acidic tail stabilizes the assembled form, suggesting another level of regulation for interaction with DNA, chromatin, and other proteins that is not possible for the uniformly acidic (hence unphosphorylatable) tail of HMGB1.

A small multigene hydroxyproline-O-galactosyltransferase family functions in arabinogalactan-protein glycosylation, growth and development in Arabidopsis.

BACKGROUND: Arabinogalactan-proteins (AGPs) are ubiquitous components of cell walls throughout the plant kingdom and are extensively post translationally modified by conversion of proline to hydroxyproline (Hyp) and by addition of arabinogalactan polysaccharides (AG) to Hyp residues. AGPs are implicated to function in various aspects of plant growth and development, but the functional contributions of AGP glycans remain to be elucidated. Hyp glycosylation is initiated by the action of a set of Hyp-O-galactosyltransferase (Hyp-O-GALT) enzymes that remain to be fully characterized. RESULTS: Three members of the GT31 family (GALT3-At3g06440, GALT4-At1g27120, and GALT6-At5g62620) were identified as Hyp-O-GALT genes by heterologous expression in tobacco leaf epidermal cells and examined along with two previously characterized Hyp-O-GALT genes, GALT2 and GALT5. Transcript profiling by real-time PCR of these five Hyp-O-GALTs revealed overlapping but distinct expression patterns. Transiently expressed GALT3, GALT4 and GALT6 fluorescent protein fusions were localized within Golgi vesicles. Biochemical analysis of knock-out mutants for the five Hyp-O-GALT genes revealed significant reductions in both AGP-specific Hyp-O-GALT activity and ß-Gal-Yariv precipitable AGPs. Further phenotypic analysis of these mutants demonstrated reduced root hair growth, reduced seed coat mucilage, reduced seed set, and accelerated leaf senescence. The mutants also displayed several conditional phenotypes, including impaired root growth, and defective anisotropic growth of root tips under salt stress, as well as less sensitivity to the growth inhibitory effects of ß-Gal-Yariv reagent in roots and pollen tubes. CONCLUSIONS: This study provides evidence that all five Hyp-O-GALT genes encode enzymes that catalyze the initial steps of AGP galactosylation and that AGP glycans play essential roles in both vegetative and reproductive plant growth.

Gene order and chromosome dynamics coordinate spatiotemporal gene expression during the bacterial growth cycle.

In Escherichia coli crosstalk between DNA supercoiling, nucleoid-associated proteins and major RNA polymerase σ initiation factors regulates growth phase-dependent gene transcription. We show that the highly conserved spatial ordering of relevant genes along the chromosomal replichores largely corresponds both to their temporal expression patterns during growth and to an inferred gradient of DNA superhelical density from the origin to the terminus. Genes implicated in similar functions are related mainly in trans across the chromosomal replichores, whereas DNA-binding transcriptional regulators interact predominantly with targets in cis along the replichores. We also demonstrate that macrodomains (the individual structural partitions of the chromosome) are regulated differently. We infer that spatial and temporal variation of DNA superhelicity during the growth cycle coordinates oxygen and nutrient availability with global chromosome structure, thus providing a mechanistic insight into how the organization of a complete bacterial chromosome encodes a spatiotemporal program integrating DNA replication and global gene expression.

Integration of syntactic and semantic properties of the DNA code reveals chromosomes as thermodynamic machines converting energy into information.

Understanding genetic regulation is a problem of fundamental importance. Recent studies have made it increasingly evident that, whereas the cellular genetic regulation system embodies multiple disparate elements engaged in numerous interactions, the central issue is the genuine function of the DNA molecule as information carrier. Compelling evidence suggests that the DNA, in addition to the digital information of the linear genetic code (the semantics), encodes equally important continuous, or analog, information that specifies the structural dynamics and configuration (the syntax) of the polymer. These two DNA information types are intrinsically coupled in the primary sequence organisation, and this coupling is directly relevant to regulation of the genetic function. In this review, we emphasise the critical need of holistic integration of the DNA information as a prerequisite for understanding the organisational complexity of the genetic regulation system.