Search

In modern medicine, studies devoted to the assessment of the parameters of residential infrastructure and the population's attitude towards them have become quite large-scale. Objectives: The aim of the study was to establish associations between individually perceived parameters of residential infrastructure and the main modifiable cardiovascular risk factors (hypertension, obesity, lipid and carbohydrate metabolism disorders) in one of the subjects of the Russian Federation. Methods : The epidemiological study "Study of the influence of social factors on chronic non-communicable diseases" started in 2015 and ended in 2023. The sample was formed by using the stratification method based on the assignment to a medical organization. The study included 1598 respondents aged 35 to 70 years (491 rural residents). The study of infrastructure parameters was conducted based on the subjective opinions of respondents using the neighborhood environment walkability scale (NEWS) questionnaire, divided into eight scales. Logistic regression analysis was used to identify associations between infrastructure parameters and cardiovascular risk factors; the odds ratio (OR) and 95% confidence interval were evaluated. Results : Individually perceived infrastructure parameters of the scale B, reflecting the accessibility of infrastructure facilities, were associated with hypertension [OR = 1.33], obesity [OR = 1.40], and abdominal obesity [OR = 1.59]. Elements of the social infrastructure of the scale C, describing the streets in the residential area, increased the likelihood of developing obesity [OR = 1.42] and visceral obesity [OR = 1.43]. The characteristics of the residential area, represented by the scale D that evaluates pedestrian infrastructure, were associated with all major cardiovascular risk factors (hypertension [OR = 1.65], obesity [OR = 1.62] and abdominal obesity [OR = 1.82], and disorders of lipid [OR = 1.41] and carbohydrate metabolism [OR = 1.44]). Conclusion : Social factors represented by various aspects of infrastructure have become important criteria for determining cardiovascular health. Environmental conditions affect cardiovascular risk factors through behavioral patterns that shape the respondent's lifestyle. Interventions in urban planning-increasing accessibility to infrastructure facilities for the population, developing a pedestrian-friendly urban environment, improving physical activity resources in areas, planning recreation areas, and landscaping-can become the most important concept for the prevention of cardiovascular diseases.

The aim of this study was to evaluate Cardio-Ankle Vascular Index (CAVI) and increased arterial stiffness predictors in patients with carbohydrate metabolism disorders (CMD) in the population sample of Russian Federation., Methods: 1617 patients (age 25-64 years) were enrolled in an observational cross-sectional study Epidemiology of Cardiovascular Diseases and Their Risk Factors in the Regions of the Russian Federation (ESSE-RF). The standard ESSE-RF protocol has been extended to measure the cardio-ankle vascular index (CAVI), a marker of arterial stiffness. Patients were divided into three groups: patients with type 2 diabetes mellitus ( n = 272), patients with prediabetes ( n = 44), and persons without CMD ( n = 1301)., Results: Median CAVI was higher in diabetes and prediabetes groups compared with group without CMD ( p = 0.009 and p < 0.001, respectively). Elevated CAVI (≥9.0) was detected in 16.8% of diabetes patients, in 15.9% of those with prediabetes, and in 9.0% of those without CMD ( p < 0.001). The factors affecting on CAVI did not differ in CVD groups. In logistic regression the visceral obesity, increasing systolic blood pressure (SBP) and decreasing glomerular filtration rate (GFR) were associated with a pathological CAVI in CMD patients, and age, diastolic blood pressure (DBP), and cholesterol in persons without CMD., Conclusions: the CAVI index values in the prediabetes and diabetes patients were higher than in normoglycemic persons in a population sample of the Russian Federation. Since the identified disorders of arterial stiffness in prediabetes are similar to those in diabetes, their identification is important to prevent further cardiovascular complications.

Aim: To assess the long-term survival in working-age patients after cerebrovascular accident (CVA) and to define basic medical and social factors determining the survival rates., Material and Methods: A continuous retrospective study included 756 working-age patients (<60 years) after CVA. The life-table method and Kaplan-Meier analysis were used to calculate a survival rate., Results: The highest risk of death was observed in the first year of CVA. One-year survival after CVA was 81.7%, falling to 74.7% at 3 years and to 57.9% at 7 years. The five-year survival was lower among men (60%) compared to women (74.5%). The figures were higher in working population compared to non-working population (78% vs. 56%, respectively). Long-term survival rate depends on the type of CVA: the five-year survival rate after unspecified stroke was 83.0%, after ischemic stroke - 69.0%, after hemorrhagic stroke - 43.0%. The direct dependence between long-term survival and patient age has been identified: older patients have worse long-term prognosis., Conclusion: The seven-year survival rate in working-age patients after cerebrovascular accident was 58%. The health and social factors affecting the long-term survival rates in working-age patients are as follows: hemorrhagic stroke, unemployment, male gender and advanced age.

Pertussis toxin (PT), a secreted virulence factor of Bordetella pertussis, ADP ribosylates mammalian G(i) proteins and plays an important early role in respiratory tract infection by this pathogen in a mouse intranasal infection model. To test the hypothesis that PT targets resident airway macrophages (AM) to promote this infection, we depleted AM by intranasal administration of liposome-encapsulated clodronate prior to bacterial inoculation. This treatment enhanced respiratory tract infection by B. pertussis, even though it also induced a rapid influx of neutrophils to the airways. Strikingly, AM depletion also enhanced infection by mutant strains deficient in PT production or activity to the same level as the wild-type infection, indicating that AM may be the primary target cells for PT in promoting infection. The enhancing effect of clodronate-liposome treatment on infection (i) was shown to be due to macrophage depletion rather than neutrophil influx; (ii) was observed for both tracheal infection and lung infection; (iii) was observed during the early and peak phases of the infection but was lost by day 14 postinoculation, during clearance of the infection; (iv) persisted for at least 1 week (prior to bacterial inoculation); and (v) was equivalent in magnitude to the effect of PT pretreatment and the effects were not additive, consistent with the idea that PT targets AM. We found that PT efficiently ADP ribosylated AM G proteins both in vitro and after intranasal administration of PT in mice and that the duration of G protein modification in vivo was equivalent to the duration of the enhancing effect of PT treatment on the bacterial infection. Collectively, these observations indicate that PT targets AM to promote early infection of the respiratory tract by B. pertussis.

Previously we found that pertussis toxin (PT), an exotoxin virulence factor produced by Bordetella pertussis, plays an important early role in colonization of the respiratory tract by this pathogen, using a mouse intranasal infection model. In this study, we examined the early role played by another exotoxin produced by this pathogen, adenylate cyclase toxin (ACT). By comparing a wild-type strain to a mutant strain (DeltaCYA) with an in-frame deletion of the cyaA gene encoding ACT, we found that the lack of ACT confers a significant peak (day 7) colonization defect (1 to 2 log(10)). In mixed-infection experiments, the DeltaCYA strain was significantly outcompeted by the wild-type strain, and intranasal administration of purified ACT did not increase colonization by DeltaCYA. These data suggest that ACT benefits the bacterial cells that produce it and, unlike PT, does not act as a soluble factor benefiting the entire infecting bacterial population. Comparison of lower respiratory tract infections over the first 4 days after inoculation revealed that the colonization defect of the PT deletion strain was apparent earlier than that of DeltaCYA, suggesting that PT plays an earlier role than ACT in the establishment of B. pertussis infection. Examination of cells in the bronchoalveolar lavage fluid of infected mice revealed that, unlike PT, ACT does not appear to inhibit neutrophil influx to the respiratory tract early after infection but may combat neutrophil activity once influx has occurred.

Background: Pertussis toxin (PT) is an exotoxin virulence factor produced by Bordetella pertussis, the causative agent of whooping cough. PT consists of an active subunit (S1) that ADP-ribosylates the alpha subunit of several mammalian G proteins, and a B oligomer (S2-S5) that binds glycoconjugate receptors on cells. PT appears to enter cells by endocytosis, and retrograde transport through the Golgi apparatus may be important for its cytotoxicity. A previous study demonstrated that proteolytic processing of S1 occurs after PT enters mammalian cells. We sought to determine whether this proteolytic processing of S1 is necessary for PT cytotoxicity., Results: Protease inhibitor studies suggested that S1 processing may involve a metalloprotease, and processing does not involve furin, a mammalian cell protease that cleaves several other bacterial toxins. However, inhibitor studies showed a general lack of correlation of S1 processing with PT cellular activity. A combination of replacement, insertion and deletion mutations in the C-terminal region of S1, as well as mass spectrometry data, suggested that the cleavage site is located around residue 203-204, but that cleavage is not strongly sequence-dependent. Processing of S1 was abolished by each of 3 overlapping 8 residue deletions just downstream of the putative cleavage site, but not by smaller deletions in the same region. Processing of the various mutant forms of PT did not correlate with cellular activity of the toxin, nor with the ability of the bacteria producing them to infect the mouse respiratory tract. In addition, S1 processing was not detected in transfected cells expressing S1, even though S1 was fully active in these cells., Conclusions: S1 processing is not essential for the cellular activity of PT. This distinguishes it from the processing of various other bacterial toxins, which has been shown to be important for their cytotoxicity. S1 processing may be mediated primarily by a metalloprotease, but the cleavage site on S1 is not sequence-dependent and processing appears to depend on the general topology of the protein in that region, indicating that multiple proteases may contribute to this cleavage.

Pertussis toxin (PT), a virulence factor secreted by Bordetella pertussis, contributes to respiratory tract infection and disease caused by this pathogen. By comparing a wild-type (WT) B. pertussis strain to a mutant strain with an in-frame deletion of the ptx genes encoding PT (DeltaPT), we recently found that the lack of PT confers a significant defect in respiratory tract colonization in mice after intranasal inoculation. In this study, we analyzed serum antibody responses in mice infected with the WT or DeltaPT strain and found that infection with the DeltaPT strain elicited greater responses to several B. pertussis antigens than did infection with the WT, despite the lower colonization level achieved by the DeltaPT strain. The same enhanced antibody response was observed after infection with a strain expressing an enzymatically inactive PT; but this response was not observed after infection with B. pertussis mutant strains lacking filamentous hemagglutinin or adenylate cyclase toxin, nor when purified PT was administered with the DeltaPT inoculum, indicating a specific role for PT activity in this immunosuppressive effect. In particular, there were consistent strong serum antibody responses to one or more low-molecular-weight antigens after infection with the DeltaPT strain. These antigens were Bvg independent, membrane localized, and also expressed by the closely related pathogens Bordetella parapertussis and Bordetella bronchiseptica. Two-dimensional gel electrophoresis and mass spectrometry were used to identify one of the immunodominant low-molecular-weight antigens as a protein with significant sequence homology to peptidoglycan-associated lipoprotein in several other gram-negative bacterial species. However, a serum antibody response to this protein alone did not protect mice against respiratory tract infection by B. pertussis.

In this study, we sought to determine whether pertussis toxin (PT), an exotoxin virulence factor produced exclusively by Bordetella pertussis, is important for colonization of the respiratory tract by this pathogen by using a mouse intranasal infection model. By comparing a wild-type Tohama I strain to a mutant strain with an in-frame deletion of the ptx genes encoding PT (deltaPT), we found that the lack of PT confers a significant peak (day 7) colonization defect (1 to 2 log(10) units) over a range of bacterial inoculum doses and that this defect was apparent within 1 to 2 days postinoculation. In mixed-strain infection experiments, the deltaPT strain showed no competitive disadvantage versus the wild-type strain and colonized at higher levels than in the single-strain infection experiments. To test the hypothesis that soluble PT produced by the wild-type strain in mixed infections enhanced respiratory tract colonization by deltaPT, we coadministered purified PT with the deltaPT inoculum and found that colonization was increased to wild-type levels. This effect was not observed when PT was coadministered via a systemic route. Intranasal administration of purified PT up to 14 days prior to inoculation with deltaPT significantly increased bacterial colonization, but PT administration 1 day after bacterial inoculation did not enhance colonization versus a phosphate-buffered saline control. Analysis of bronchoalveolar lavage fluid samples from mice infected with either wild-type or deltaPT strains at early times after infection revealed that neutrophil influx to the lungs 48 h postinfection was significantly greater in response to deltaPT infection, implicating neutrophil chemotaxis as a possible target of PT activity promoting B. pertussis colonization of the respiratory tract.