Nonspecific Response Research Articles

Review paper: Effect of periodontal treatment on the negative acute phase proteins in patients with periodontitis

Periodontitis is an inflammatory-infectious disease of tooth-supporting structures that results in the progressive destruction of the periodontal ligament and alveolar bone due to an imbalance between the host defense and microorganisms. Subgingival microbiota has a significant role in the initiation and progression of periodontitis, affecting the innate and acquired immune responses by the infiltration of immune cells such as monocytes and polymorphonuclear cells that are abundant under inflammatory conditions. The immune cells induce the release of proinflammatory cytokines that lead to the destruction of periodontal connective tissue and the alveolar bone. Cytokines activate hepatocytes to produce acute phase proteins as a component of the nonspecific response. These proteins are a group of proteins that increase (positive type) and decrease (negative type) under inflammatory conditions. This response is called the acute phase response (APR) that occurs after the initiation of a systemic inflammatory reaction. Nonsurgical periodontal therapy is the first stage of treatment for periodontitis. Its aim is to eliminate etiologic agents and decrease inflammation. The aim of this review article was to evaluate the effect of periodontitis as an inflammatory condition and its treatment on the concentrations of negative acute phase proteins

Dalbavancin Boosts the Ability of Neutrophils to Fight Methicillin-Resistant Staphylococcus aureus.

Polymorphonuclear leukocytes (PMNs) are the most important cell type involved in the early nonspecific host response to bacterial pathogens. Staphylococcus aureus has evolved mechanisms to evade immune responses that contribute to its persistence in PMNs, and acquired resistance to several antimicrobials. Additionally, methicillin-resistant S. aureus (MRSA) is one of the most common causes of acute bacterial skin and skin-structure infections (ABSSSIs). Dalbavancin (DBV), a lipoglycopeptide, is indicated for the treatment of ABSSSIs, and has a broad spectrum of action against most microorganisms. Here, we sought to determine the effect of DBV on the neutrophil killing of MRSA and its potential immunomodulating activity. Our results revealed that DBV boosts MRSA killing by acting on both bacteria and PMNs. DBV pre-treatment of PMNs did not change the respiratory burst or degranulation, while an increased trend in neutrophil extracellular traps-associated elastase and in the production of TNFα and CXCL8 was revealed. In parallel, DBV caused a delay in the apoptosis of MRSA-infected neutrophils. In conclusion, we demonstrated a cooperative effect between the antimicrobial properties of PMNs and DBV, thus owing to their immunomodulatory activity. In the choice of the treatment management of serious S. aureus infections, DBV should be considered as an outstanding option since it reinforces PMNs pathogen clearance capability by exerting its effect directly, not only on MRSA but also on neutrophils.

Psychological stress and cardiovascular diseases: clinical case

In the modern world, stress occupies a leading place among significant problems for humanity, being an etiological factor of about 80% of diseases. Social, physical and psychological factors can act as stressors that influence and determine the non-specific response of the body. In most cases, the nonspecific stress-induced reaction of the body is manifested by the picture of psychovegetative syndrome, an important component of which is the activation of the sympathetic nervous system. In a prolonged stress situation, psychovegetative syndrome can be a manifestation of stress-induced anxiety. Anxiety is detected in more than 25% of patients with a general somatic profile. Stress-induced reactions and anxiety can subsequently contribute to the development of psychogenic somatic pathology, including the cardiovascular pathology. Acute or chronic stress situation increases the risks of developing arterial hypertension, coronary heart disease, heart rhythm disorders. In the presence of background cardiac pathology, stress-induced reactions contribute to the deterioration of its course and reduce the effectiveness of treatment. The above indicates the need for a comprehensive assessment of the condition of patients with a general somatic profile. The active use in practical medicine of psychometric and psychodiagnostic scales for anxiety and depression is shown to assess the mental status of patients. When detecting stress-induced reactions or comorbid psychopathology, inclusion of psychotropic drugs, including antipsychotics (alimemazine), is indicated in the complex therapy. Timely administration of alimemazine in patients with a general somatic profile stops psychovegetative manifestations, has positive somatotropic effects due to the multimodal mechanism of action of the drug. In this clinical case, the use of alimemazine in a patient with hypertension, rhythm disorders and comorbid anxiety is presented.

Plasma metabolomics, lipidomics and cytokinomics profiling predict disease recurrence in metastatic colorectal cancer patients undergoing liver resection.

In metastatic colorectal cancer (mCRC) patients (pts), treatment strategies integrating liver resection with induction chemotherapy offer better 5-year survival rates than chemotherapy alone. However, liver resection is a complex and costly procedure, and recurrence occurs in almost 2/3rds of pts, suggesting the need to identify those at higher risk. The aim of this work was to evaluate whether the integration of plasma metabolomics and lipidomics combined with the multiplex analysis of a large panel of plasma cytokines can be used to predict the risk of relapse and other patient outcomes after liver surgery, beyond or in combination with clinical morphovolumetric criteria. Peripheral blood metabolomics and lipidomics were performed by 600 MHz NMR spectroscopy on plasma from 30 unresectable mCRC pts treated with bevacizumab plus oxaliplatin-based regimens within the Obelics trial (NCT01718873) and subdivided into responder (R) and non-R (NR) according to 1-year disease-free survival (DFS): ≥ 1-year (R, n = 12) and < 1-year (NR, n = 18). A large panel of cytokines, chemokines, and growth factors was evaluated on the same plasma using Luminex xMAP-based multiplex bead-based immunoassay technology. A multiple biomarkers model was built using a support vector machine (SVM) classifier. Sparse partial least squares discriminant analysis (sPLS-DA) and loading plots obtained by analyzing metabolomics profiles of samples collected at the time of response evaluation when resectability was established showed significantly different levels of metabolites between the two groups. Two metabolites, 3-hydroxybutyrate and histidine, significantly predicted DFS and overall survival. Lipidomics analysis confirmed clear differences between the R and NR pts, indicating a statistically significant increase in lipids (cholesterol, triglycerides and phospholipids) in NR pts, reflecting a nonspecific inflammatory response. Indeed, a significant increase in proinflammatory cytokines was demonstrated in NR pts plasma. Finally, a multiple biomarkers model based on the combination of presurgery plasma levels of 3-hydroxybutyrate, cholesterol, phospholipids, triglycerides and IL-6 was able to correctly classify patients by their DFS with good accuracy. Overall, this exploratory study suggests the potential of these combined biomarker approaches to predict outcomes in mCRC patients who are candidates for liver metastasis resection after induction treatment for defining personalized management and treatment strategies.

Pharmacogenetics of Anticancer Drugs: Clinical Response and Toxicity.

Cancer is the most challenging disease for medical professionals to treat. The factors underlying the complicated situation include anticancer drug-associated toxicity, non-specific response, low therapeutic window, variable treatment outcomes, development of drug resistance, treatment complications, and cancer recurrence. The remarkable advancement in biomedical sciences and genetics, over the past few decades, however, is changing the dire situation. The discovery of gene polymorphism, gene expression, biomarkers, particular molecular targets and pathways, and drug-metabolizing enzymes have paved the way for the development and provision of targeted and individualized anticancer treatment. Pharmacogenetics is the study of genetic factors having the potential to affect clinical responses and pharmacokinetic and pharmacodynamic behaviors of drugs. This chapter emphasizes pharmacogenetics of anticancer drugs and its applications in improving treatment outcomes, selectivity, toxicity of the drugs, and discovering and developing personalized anticancer drugs and genetic methods for prediction of drug response and toxicity.

On the quantum nature of magnetic phenomena in biology

The review discusses the microscopic mechanisms of the action of weak magnetic fields on organisms. Magnetobiology distinguishes between magnetoreception, i.e., the effect of a magnetic field on specialized receptors, and a nonspecific response that develops without such receptors. The nonspecific effects of weak magnetic fields are highly general and universal: they occur in all organisms. Often these effects are disguised as the result of the action of uncontrolled random factors, appear as an increased scatter of measurements, and accompanied by low reproducibility. The nature of nonspecific magnetic effects, as is shown in this review, is related to the quantum dynamics of the magnetic moments of electrons, magnetic nuclei, and, possibly, rotations of molecular groups. Among the most substantiated is the spin-chemical mechanism, first of all. Its known low sensitivity to weak magnetic fields can be increased by including spin-correlated radical pairs in the enzymes that catalyze biopolymer processes, e.g., ribosomal ones. We show that research on the effects of significantly weakened magnetic fields compared with the geomagnetic field on cellular processes has prospects for various practical applications. The mechanisms proposed to explain nonspecific effects, but turned out to be untenable, are listed.

Influence of donor complement component allotype on renal transplantation outcome

Background Improvements in clinical care and immunosuppressive medications have provided positive outcomes following kidney transplantation such as reducing acute rejection rates. Activation of the complement cascade is inevitable in kidney transplantation because of both the specific and nonspecific immunologic responses of the recipient. This study provides insights on the influence of the donor C3 allotype on renal transplant outcome (graft function). Patients and methods The present study was conducted on 50 pairs of donors and recipients of renal transplantation who fulfilled the inclusion and exclusion criteria. C3 allotypes of donor–recipient pairs were determined and divided into four genotypic groups according to the C3F allotype of the donor and the recipient. The four genotypic groups were analyzed for association with graft function and assessed by serum creatinine, blood urea, and glomerular filtration rate. Results There was a positive statistically significant difference for the group FF/FS donor into SS recipient in comparison with other genotype groups of C3 among recipients, as shown by improvement in glomerular filtration rate, serum creatinine, and blood urea. Conclusion The presence of C3 (F) allele either homozygous or heterozygous in the donor and the absence of this allele in the recipient give a better renal allograft function.

К вопросу оптимального выбора нестероидных противовоспа- лительных средств в схеме ведения пациента с катарактой

This article aims to review the up-to-date approaches to the control of a non-specific inflammatory response following cataract phacoemulsification with intraocular lens implantation. The authors highlight the key objectives of using nonsteroidal anti-inflammatory agents after cataract surgery during the entire postoperative period, primarily to control inflammatory response and pain and to reduce the risk of cystoid macular edema. The article presents a wide range of data on the outcomes of using various nonsteroidal anti-inflammatory drugs (NSAIDs) in postoperative patients. Over the past years, classical approaches to the selection of patient management schemes have been revised taking into consideration findings of the numerous multicenter trials constructed on the principles of evidence-based medicine. The authors provide rationale for the selection of an optimal anti-inflammatory drug underpinned by the clinical trial results, pharmacodynamic and pharmacokinetic parameters of NSAIDs of a new generation. The emphasis is made on the use of bromfenac in patients with cataract. In addition, the risk factors and the major strategies of prevention and treatment of macular edema following surgical procedures are reviewed, including those in patients with diabetes mellitus. Keywords: cataract surgery, cystoid macular edema, NSAID, bromfenac, diabetes mellitus, perioperative period. For citation: Morozova T.A. On the optimal selection of nonsteroidal anti-inflammatory drugs in the management scheme of cataract patients. Russian Journal of Clinical Ophthalmology. 2023;23(1):54–59 (in Russ.). DOI: 10.32364/2311-7729-2023-23-1-54-59.

ИСПОЛЬЗОВАНИЕ ИНТЕГРАЛЬНЫХ ЛЕЙКОЦИТАРНЫХ ИНДЕКСОВ В ОЦЕНКЕ ВЛИЯНИЯ СТРЕССИРУЮЩИХ ФАКТОРОВ НА ГОМЕОСТАЗ КОЗ

The principle of a quantitative-qualitative approach, which reflects the activity of the organism while distinguishing its specific and non-specific adaptive responses, includes the requirement for quantitative assessment of specific changes in the body. To achieve the research objective, the resources of integral leukocyte indices (ILI) were used to assess the homeostasis of goats during castration, weaning from dams and transfer from pasture to stabling. After percutaneous castration, the index data vary significantly in a day, and in the month following the operation they slowly return to the level of the initial values. The surgical method of castration of goats acts as an unusual extreme stimulus, as it has a damaging effect on the body for a longer period of time. Changes in the blood of kids after weaning from dams were characterised by an increase in leukocytes by 36.84±2.71%, a change in the status of neutrophils, as they increased by 6.85±0.39%. The number of band immature neutrophils increased, but the presence of eosinophils decreased by 1.75±0.19 times, which is one of the indicators of the presence of a moderate stress factor. The transfer of goats to stabling leads to a sharp decrease in impulses from the skeletal muscles, which weakens the activating effect of the reticular formation of the brain on the cerebral cortex. The goat’s body is exposed to extreme stimuli, beyond the limits of everyday influences, and reacts specifically according to the nature of the activeagent. The most pronounced reaction is to open surgical castration, less so to percutaneous castration and then, in descending order: weaning of goats from dams and transfer from pasturing.

Influence of gut microbiota on resilience and its possible mechanisms.

Excessive stress leads to disruptions of the central nervous system. Individuals' responses to stress and trauma differ from person to person. Some may develop various neuropsychiatric disorders, such as post-traumatic stress disorder, major depression, and anxiety disorders, while others may successfully adapt to the same stressful events. These two neural phenotypes are called susceptibility and resilience. Previous studies have suggested resilience/susceptibility as a complex, non-specific systemic response involving central and peripheral systems. Emerging research of mechanisms underlying resilience is mostly focussing on the physiological adaptation of specific brain circuits, neurovascular impairment of the blood-brain barrier, the role of innate and adaptive factors of the immune system, and the dysbiosis of gut microbiota. In accordance with the microbiota-gut-brain axis hypothesis, the gut microbiome directly influences the interface between the brain and the periphery to affect neuronal function. This review explored several up-to-date studies on the role of gut microbiota implicated in stressful events-related resilience/susceptibility. We mainly focus on the changes in behavior and neuroimaging characteristics, involved brain regions and circuits, the blood-brain barrier, the immune system, and epigenetic modifications, which contribute to stress-induced resilience and susceptibility. The perspective of the gut-brain axis could help to understand the mechanisms underlying resilience and the discovery of biomarkers may lead to new research directions and therapeutic interventions for stress-induced neuropsychiatric disorders.

Electrodermal activity spectral and nonlinear analysis – potential biomarkers for sympathetic dysregulation in autism

Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by emotional and social deficits, which can be associated with sympathetic dysregulation. Thus, we aimed to analyze the electrodermal activity (EDA) using time, and novel spectral and nonlinear indices in ASD. The cohort consisted of 45 ASD boys and 45 age-matched controls. EDA was continuously recorded at rest. The EDA indices were evaluated by time-, spectral-, and nonlinear-domain analysis. Our results revealed increased non-specific skin conductance responses, spectral parameters in high and very-high frequency bands, approximate and symbolic information entropy indicating sympathetic overactivity in ASD vs. controls (p < 0.05, for all). Surprisingly, the nonlinear index from detrended fluctuation analysis α1 was lower in ASD vs. controls (p = 0.024) providing thus distinct information about qualitative features of complex sympathetic regulation. Concluding, the complex time, spectral, and nonlinear EDA indices revealed discrete abnormalities in sympathetic cholinergic regulation as one of the potential pathomechanisms contributing to cardiovascular complications in ASD.

Приме-нение метода мультисрезовой спиральной компьютерной томографии для оценки состояния лёгких у животных с моделированным антракозом

Occupational diseases and harmful production factors contribute to a significant disability of the working population. This article discusses some morphological aspects of changes in the lungs of experimental animals after the introduction of coal suspension into the respiratory tract. Specific and non-specific responses of lung tissue to the damage were determined. The object of the study was white outbred rats, formed according to the principle of pairs of analogues, with the separation of the experimental and control groups. On the 10th day of the experiment, the animals were withdrawn from the experiment, with a preliminary multislice computed tomography and subsequent microscopic assessment of the organization of the lung parenchyma. As a result, computed tomography revealed a pronounced reaction with the formation of emphysema in the subpleural parts of the lungs. Microscopic examination revealed non-specific types of responses to the introduction of coal dust with the formation of leukocyte infiltration in various parts of the lungs, accumulation of mucus and coal dust in the respiratory bronchioles.

Психологический стресс и папилломавирусная инфекция. Взаимосвязь и пути решения

Stress is a non-specific response of the body to stimuli that disrupt homeostasis. Stress can suppress the immune function and therefore increase the risk of immunodeficiency disorders, including human papillomavirus (HPV) infection. Stress-induced immunosuppression is especially important for infection-related cancer since damage to cellular immunity can stimulate the development of oncogenic viral infection. A connection was established between psychosocial stress and the development of SILs (squamous intraepithelial lesions) in women (formerly known as ‘cervical intraepithelial neoplasia (CIN)’ in the International Classification of Diseases (ICD-10)). This connection ends with immune response, which, in turn, depends on the duration of exposure to stressors: a shorter duration of stress shifts specific immunity to innate immunity, and chronic stress shifts it from a Th1-type response to a Th2-type response. Against the background of cognitive behavioral therapy, the incidence of severe SILs/CIN is significantly lower than in the absence of psychological treatment. However, the use of adaptive ways of coping with stress does not exclude the need for pathogenetic (antiviral) therapy for HPV infection. One of the most demanded medications in the pharmaceutical market of Russia is inosine pranobex. It is included in the register of antiviral medications used for HPV treatment. It enhances antiviral protection against HPV, slows or stops oncogenesis in the cervix, which together contribute to a rapid virus elimination. Key words: stress, immunosuppression, human papillomavirus infection, SILs/CIN, inosine pranobex

THE INFLUENCE OF INTERNET ADDICTION ON GENERAL HEALTH AND COPING STRESS AMONG YOUNG ADULTS

Aim: Internet addiction is referred to as a form of technology addiction (such as computer addiction) and sub category of behavioural addictions (such as obsessive gambling addiction). (Griffiths, 1999). Stress is defined as “the non-specific response of the body to any demand for change”. (Hans Salye, 1936). Coping with stress is the process by which a person consciously attempts to master, minimize, or tolerate stressors and problems in life. Health is defined as a condition of complete bodily, mental, and social health, not only the absence of disease or disability. (WHO, 1948). The study aimed to investigate the influence of internet addiction on general health and coping stress among young adults. Methods: The study was conducted on 120 participants between the ages of 18 to 25, out of which 60 were females and 60 were males, through purposive sampling techniques. A social demographic questionnaire, Internet Addiction Test (IAT) (Young, 1998), Brief Cope Scale (Carver, 1982) and General Health Questionnaire (Goldberg, 1972) were used to gather information. Data were analyzed by using one way ANOVA, mean, standard deviation and Pearson product moment correlation. Result: The results shows that there is a significant difference in the level of internet addiction and coping stress among young adults across their gender. there is no significant difference in the level of general health among young adults across their gender. There is no significant relationship between internet addiction and coping stress. There is no significant relationship between internet addiction and general heath. And there is no significant relationship between general health and coping stress.

Latent herpes simplex virus type 1 reactivation increases the susceptibility of neurodegenerative diseases: intervention with traditional Chinese medicine

Owing to environmental and lifestyle changes in modern society, physical and mental stress is on the rise among the population in attempting to compensate for the changes. Stress, defined as a series of non-specific responses to abnormal internal and external stimuli, has long been recognized to increase susceptibility to various diseases, including neurodegenerative diseases (NDs). Herpes simplex virus type 1 (HSV-1), a neurotropic herpes virus, establishes latent infections in the trigeminal ganglia for the lifetime of the host. Upon reactivation, the latent HSV-1 enters the lytic cycle, which not only causes a substantial production of reactive oxygen species (ROS) in the neurons, but also induces glial cells to produce inflammatory mediators, eventually resulting in neuronal damage and occurrence of NDs. Remarkably, both physical and psychological stress are common stimuli leading to latent HSV-1 reactivation. Acyclovir is a classic antiviral drug for the treatment of HSV-1 infection and recurrence, but acyclovir cannot reverse neuronal damage caused by HSV-1 reactivation. Recent studies have shown that traditional Chinese medicine (TCM) has advantages in the treatment of NDs. In addition, TCM is thought to prevent latent HSV-1 reactivation and NDs, which may involve regulation of the neuro-endocrine-immune network, treatment of emotional disorders, and modulation of oxidative stress. Understanding the mechanism underlying stress-induced reactivation of latent HSV-1 and the potential consequences of NDs is needed. TCM may be a promising alternative therapy for related diseases.

Molecular and cellular features of femoral head avascular necrosis: in vivo study

Aim. To study the molecular and cellular features of femoral head avascular necrosis in the rat model.Materials and Methods. Femoral head avascular necrosis was surgically induced in 8 rats with the 4-week follow-up. Then, the animals have been euthanised, and we performed gross, radiological, and histological examination of avascular and intact contralateral femoral heads. Systemic inflammation was assessed using enzyme-linked immunosorbent assay, and pro-inflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor α). The proteomic profile of healthy and necrotic femoral heads was interrogated using sodium dodecyl sulfate polyacrylamide gel electrophoresis and ultra-high performance liquid chromatography-tandem mass spectrometry with ion mobility (TimsToF Pro).Results. Aseptic necrosis of the femoral head was successfully induced in all rats. Serum levels of pro-inflammatory cytokines (interleukin-1β and interleukin-6) were higher in rats with femoral head avascular necrosis as compared with healthy rats. Among the major proteins revealed at proteomic profiling were those involved in maintaining bone tissue homeostasis, calcium phosphate metabolism, angiogenesis, hematopoiesis, cell-cell interactions, chaperones, cartilage matrix proteins, collagen synthesis, and lipid metabolism. In bones with avascular necrosis, we have also found proteins regulating the inflammatory response and oxidative stress. Sodium dodecyl sulfate polyacrylamide gel electrophoresis indicate that the development of avascular osteonecrosis was accompanied by an overexpression of oxidative stress proteins, anaerobic glycolysis, and non-specific inflammatory response along with the downregulation of molecules responsible for angiogenesis, chondrogenesis, calcium phosphate metabolism, collagen synthesis, and cartilage matrix.Conclusion. Femoral head avascular necrosis is accompanied by non-specific inflammation, oxidative stress, and lipid peroxidation all presumably developed because of hypoxia and together contributing to bone destruction.

Observations of nemaline bodies in muscle biopsies of critically ill patients infected with SARS-CoV-2.

Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who have been admitted to the intensive care unit (ICU) often face months of physical disability after discharge. To optimize recovery, it is important to understand the role of musculoskeletal alterations in critically ill patients infected with SARS-CoV-2. The main aim of the present study was to describe the presence and morphology of nemaline bodies found in the skeletal muscle tissue from critically ill patients infected with SARS-CoV-2. In n = 7 patients infected with SARS-CoV-2, ultrastructural characteristics of vastus lateralis muscle obtained on days 1-3 and days 5-8 following ICU admission were investigated in more detail with electron microscopy. Those muscle biopsies consistently showed variable degrees of myofiber necrosis and myofibrillar disorganization. In 4/7 (57%) patients on days 5-8, the Z-line material accumulated into nemaline bodies with a typical lattice-like appearance at higher magnification, similar to that found in nemaline myopathy. This study is the first to describe the disintegration of myofibrils and the accumulation of Z-line material into nemaline bodies in the skeletal muscle tissue obtained from critically ill coronavirus disease-19 patients following ICU admission, which should be interpreted primarily as a non-specific pathological response of extreme myofibrillar disintegration associated with myofiber necrosis.

Orofaryngeální forma tularemie s kožními projevy: Sweetův syndrom

The authors present a case report of a patient with unilateral tonsillitis and severe non-specific inflammatory response not responding to anti- biotic therapy. Along with persistent local and systemic symptoms, the patient also developed skin exanthema and cervical lymphadenopathy. The definitive dia gnosis of oropharyngeal tularemia was confirmed after several weeks, based on serological and histological findings. Finally, the targeted antibiotic therapy led to rapid symptom resolution. The authors describe an unusual combination of the diagnoses, which resulted in a prolonged and initially unsuccessful therapy. Symptoms resembling to tonsillitis, which persist despite the use of antibiotics, should lead to reconsideration of suspected diagnosis. Key words tularemia – Sweet’s syndrome – lymphadenopathy – tonsillitis

Effect of ticagrelor and prasugrel on remote myocardial inflammation in patients with acute myocardial infarction with ST-elevation: a CMR T1 and T2 mapping study.

Acute myocardial ischaemia triggers a non-specific inflammatory response of remote myocardium through the increase of plasma concentrations of acute-phase proteins, which causes myocardial oedema. As ticagrelor has been shown to significantly decrease circulating levels of several pro-inflammatory cytokines in patients after acute myocardial infarction with ST-elevation (STEMI), we sought to investigate a potential suppressive effect of ticagrelor over prasugrel on cardiac magnetic resonance (CMR) T1 and T2 values in remote myocardium. Ninety STEMI patients were prospectively included and randomised to receive either ticagrelor or prasugrel maintenance treatment after successful primary percutaneous coronary intervention. Patients underwent CMR after 2-7 days. The protocol included long and short axis cine imaging, T1 mapping, T2 mapping and late gadolinium enhancement imaging. After excluding 30 patients due to either missing images or insufficient quality of the T1 or T2 maps, 60 patients were included in our analysis. Of those, 29 patients were randomised to the ticagrelor group and 31 patients to the prasugrel group. In the remote myocardium, T1 values did not differ between groups (931.3 [919.4-950.4] ms for ticagrelor vs. 932.6 [915.5-949.2] ms for prasugrel (p = 0.94)), nor did the T2 values (53.8 ± 4.6 ms for ticagrelor vs. 53.7 ± 4.7 ms for prasugrel (p = 0.86)). Also, in the infarcted myocardium, T1 and T2 values did not differ between groups. In revascularised STEMI patients, ticagrelor maintenance therapy did not show superiority over prasugrel in preventing early remote myocardial inflammation as assessed by CMR T1 and T2 mapping.

Central and peripheral nervous system responses to chronic and paced hyperventilation in anxious and healthy subjects

The aim of the present study was to examine self-report, peripheral nervous system, and central nervous system correlates of naturally-occurring, chronic hyperventilation (HV, assessed by hypocapnia or low resting state low end-tidal CO2), and to examine the additional effect of acute, experimentally-induced HV in anxious and healthy participants. By identifying the biomarkers of anxiety-related chronic HV and examining responses to acute HV, we hope to identify meaningful, mechanistic targets for further treatment development. Seventy anxious patients and 34 healthy control participants completed electroencephalogram (EEG) and peripheral nervous system recording at baseline and following a paced breathing task. Diagnosis x baseline hypnocapnia group analyses indicated that anxious/hypocapnic patients exhibited greater nonspecific skin conductance response amplitude than did anxious/normocapnic patients, and the anxious group reported greater HV-related symptoms and anxiety sensitivity than did the control group. However, no EEG abnormalities were noted as a function of anxiety group or baseline hypocapnia status. Following paced HV, anxious patients (but not controls) exhibited an increase in left-frontal alpha 1 power. Hypocapnic, but not normocapnic, participants exhibited an increase in skin conductance levels. Anxious patients reported an increase in negative cognitive appraisals of HV symptoms, and anxious/hypocapnic participants reported an increase in affective responses to HV. Thus, chronic HV is associated with greater arousal, and increased self-reported and physiological sensitivity to paced HV. Patients who chronically hyperventilate appear to be more sensitive to respiratory distress, responding with higher levels of anxiety and poorer tolerance of the physiological sensations accompanying acute HV.