Russian Journal of Infection and Immunity
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Published By Spb Raaci

2313-7398, 2220-7619

Author(s):  
Angelina Rybka

An interaction between decreasing host anti-infective defense due to long-term invasion with Opisthorchis felineus in the hepatobiliary system, duct bile colonization by microflora and revealing the endogenous mutagenesis (carcinogenesis) factor - secondary bile acids - in bile is considered in the article.  The role of organism genotype in the pathogen-related immune response to Opisthorchis felineus trematode and helminth development in the hepatobiliary system has been shown. The role of dysregulated mechanisms of tissue homeostasis in induction of compensatory chronic homeostatic proliferation and somatic cell oncogenesis is discussed. The study results evidence that disturbed functioning of the regulatory T-cells, inhibition of the NK cell effector function and very high functional activity of the memory B-cells are of great importance in imbalanced host immunobiological reactivity, caused by chronic opistorchosis invasion. Decreased host anti-infective protection causes intrahepatic bile duct infection with different bacterial species. Presence of secondary bile acids in hepatobiliary system was associated with biliary bacterial strains inhabiting intestinal tract: Proteus vulgaris*, Proteus mirabilis*, Citrobacter freundii*, Bacteroides alcaligues faecalis*, Clostridium*, Streptococcus faecalis*, Еscherichia coli* (*gut microflora). Participation of microbiota in bile acid biotransformation immediately in the duct bile has been confirmed in in vitro experiments. Experimental methods on Drosophila melanogaster and Salmonella tiphimurium strains: TA 100, TA 98 allowed to find out that bile from chronic opistorchosis patients exerts higher mutagenic activity compared with control groups. Mutational events in somatic and bacterial cells depend on the presence of secondary bile acids (deoxycholic, lithocholic) in duct bile, as well as the level of total bile acid concentration. The study data confirm the concept by Professor A.A. Shain about presence of endogenous risk factor for developing primary cholangiocellular liver cancer such as secondary bile acids in the bile of chronic opistorchosis patients. A concept of cholangiocarcinogenesis, based on mutational events, is added up with disturbance of generative cycle in tissue cells and their differentiation due to decreased kylon factor activity, as well as sensitivity threshold to it. Level of investigation and understanding of mechanisms underlying cholangiocarcinogenesis during chronic opisthorchiasis invasion will allow to develop pathogenetic approaches to correct homeostasis regulation and prevention of cholangiocarcinomas.


Author(s):  
A. F. Popov ◽  
E. V. Markelova ◽  
I. A. Komarova ◽  
A. V. Kosciuszko ◽  
M. Yu. Shchelkanov

The effect of the antiviral drug Kagocel on the levels of metalloproteinases MMP-8 and MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 in induced sputum in the treatment of community-acquired viral-bacterial pneumonia was analyzed. 60 adult patients with a confirmed diagnosis of community-acquired pneumonia and viral-bacterial etiology were included in the follow-up research work. Materials and methods. All patients were randomly divided into 2 groups: 1 group (comparison group) included 30 patients receiving Ceftriaxone monotherapy; in the 2nd group (main) - 30 people who were prescribed Ceftriaxone and the antiviral drug Kagocel as etiotropic treatment. Both groups were comparable in terms of gender, age and time of admission to the hospital. Results. During hospitalization, patients in both groups had elevated levels of MMP-8, MMP-9, TIMP-1 and TIMP-2 in induced sputum compared to the reference values. By 7 days of inpatient treatment, the level of MMP-8 continued to be significantly higher than the reference values ​​in both groups, and in patients of the 2nd group there was a decrease compared to baseline values, and in patients in the 1st group at the same time. The activity of MMP-9 during hospitalization was also high in patients of both groups compared with the level of these enzymes in healthy people. By the 7th day of therapy various indicators' changes were recorded. The level of MMP-9 in patients of the 1st group increased, and in patients of the 2nd group - on the contrary - decreased. The level of TIMP-1 decreased in patients of the 1st group below the control value, and in patients of the 2nd group - reached the reference values. The level of TIMP-2 decreased in both groups and reached the level of control values. Conclusion. Inclusion in the standard antibacterial regimen of community-acquired viral-bacterial pneumonia of the antiviral drug Kagocel reduces the level of MMR-9 and reduces the severity of the imbalance in the MMP and TIMP system by 7 days of therapy, which leads to a faster clinical recovery of patients.


Author(s):  
I. V. Bazhutova ◽  
D. D. Ismatullin ◽  
A. V. Lyamin ◽  
D. A. Trunin ◽  
A. V. Zhestkov ◽  
...  

Bacteria of the genus Streptococcus are one of the most numerous and diverse representatives in the normal biocenosis of human organs and systems particularly being abundant as obligatory inhabitants of the oral cavity. All streptococci are divided into six groups: S.mitis, S.anginosus, S.salivarius, S.mutans, S.bovis and S.pyogenic groups, among which their certain number may potentially participate in the infectious process of developing periodontitis. Owing to the presence of a wide range of adhesion, invasion and colonization factors, they are capable of performing a protective function such as, e.g., colonization resistance, but they may also cause formation of a pathological process in the tooth tissues and dento-facial system. The most prominent adhesion factors are antigens I / II (Ag I / II), fibronectin, collagen, laminin, fibrinogen binding proteins, serine-rich glycoproteins, pili, protein M, proteases, C5a peptidases, and the presence of a tooth capsule. Among the complex of proteolytic enzymes, it is important to note that streptococci contain enzymes hyaluronidase and lyase, which cleave the β1,4 bond between N-acetylglucosamine and d-glucuronic acid as the components of hyaluronic acid being a part of the connective tissues. The members of the S.anginosus group are able to release chondroitin sulfatase, which destroys chondroitin sulfates as specific components in cartilage, ligaments and other connective tissue structures. The enzymes noted contribute to a deeper spread of microorganisms in host tissues. Pathological processes associated with the development of periodontitis comprise a complex problem, wherein several important elements take part, including an infectious agent, a macroorganismal response in the form of nonspecific and adaptive immunity, as well as involvement of anti-inflammatory components. A great body of studies in research literature are dedicated to describe to participation of the members within the "red, orange and green" complexes as the principal components in developing periodontitis. Whereas the "yellow" and the "purple" complex plays a more protective role by acting as antagonists while interacting with periodontopathogens, but it should not be ruled out a potential participation for some representatives, particularly S. intermedius, S. gordonii, Actinomyces odontolyticus, Actinomyces naeslundii in developing periodontal disease. Altogether, it poses a problem, which may be solved solely based on a multidisciplinary approach by inviting not only dentists and bacteriologists but also researchers of other specialties. Here we review the studies found in international and national data bases such as Scopus, Web of Science, Springer, RINC.


Author(s):  
V. S. Vakin ◽  
I. V. Amosova ◽  
E. M. Vojcekhovskaya ◽  
T. A. Timoshicheva ◽  
A. A. Vasileva ◽  
...  

Currently, the assessment of the immunogenic properties of influenza viruses as a part of influenza vaccines, is carried out by using seroprotection, seroconversion as well as the rate of increases in post-vaccination antibodies. At the same time, significant differences in the immunogenicity of vaccines related to dynamic formation of high antibody titers responsible for long-term protection of the vaccinated, are neglected.Influenza viruses such as A (H1N1) pdm09 that caused 2009-2010 pandemic continue to circulate in the population, therefore, the assessment of the immunogenic activity of vaccine viruses prepared during the pandemic period is interesting in for the methodology to prepare pandemic vaccines to be used in various groups (adults, children, elderly people).Analyzing immunogenicity of influenza vaccines used during the 2009-10 swine influenza pandemic and the post-pandemic period up to the year 2014 was carried out by applying the graphical method for assessing immunogenicity (immunographs) measured as follows: for each group of vaccinated subjects (depending on the vaccine used), an increased rate in antibody level was calculated and the graphs of immunogenicity were plotted. An increased rate of serum antibodies magnitude from vaccinated subjects and the number of sera (in%) with a given fold increase rate in antibody level from 1 to the maximum magnitude were plotted on the x- and y-axis, respectively. The proposed method for assessing immunogenicity allows to plot immunogenicity graphs regardless of the serum antibodies level found in volunteers. The assessment described above revealed a several features for developing immune response to the pandemic virus A (H1N1)pdm09 such as the lack of immune response in a substantial number of adult volunteers (25-27%%) and young children (60-70%%) after monovaccine administration. The reason for such immune response can be both an insufficient dose of vaccine-containing viral antigen and suppressed immune response caused by the influenza A(H1N1)pdm09.A study on the immunogenic properties for seasonal influenza vaccines containing the influenza A (H1N1) pdm09 virus antigen in the years 2010 - 2014 revealed a variety in emerging humoral immunity ranging from a short-term, low-frequency increase in antibodies from vaccinated children to the formation of high antibody titers in elderly.Practically, immunographic analysis of influenza vaccines particularly those derived from the influenza A (H1N1)pdm09 virus, may result in proposing recommendations to increase an antigenic load at the beginning of a pandemic cycle and/or block the suppressive properties of vaccine-contained viruses in pediatric vaccines, because escalating virus dose in the vaccine may not always be achievable in this case.


Author(s):  
L. Somova ◽  
B. Andryukov ◽  
I. Lyapun ◽  
E. Drobot ◽  
O. Ryazanova ◽  
...  

In the 2000s, with the development of scientific research on the uncultivated (dormant) state of pathogenic bacteria, the ideas about persistent, chronically recurrent infections, difficult to respond to antibiotic therapy have begun to shape. However, regarding human pseudotuberculosis (Far Eastern scarlet-like fever, FESLF), this question remains open. While analyzing the pathology of pseudotuberculosis, its clinical and epidemic manifestation as FESLF, we identified the etiopathogenetic prerequisites for the disease recurrence and development of persistent infection [3]. In this study, it was found that the strains of Yersinia pseudotuberculosis, which were in a dormant state, caused the development of a peculiar granulomatous inflammation in target organs with pronounced delayed-type hypersensitivity reactions in vivo. To reproduce the experimental infection, sexually mature white mice were inoculated with the strain 512 Y. pseudotuberculosis, serotype I sored for 10 years at the Museum of the Research Somov Institute of Epidemiology and Microbiology and transformed into a dormant state. For comparative studies, a dormant form from vegetative bacteria of the strain 512 Y. pseudotuberculosis was obtained by exposure to a large dose of kanamycin (the minimum antibiotic dose was exceeded 25 times). The infecting dose of both forms of bacteria was 108 µ/mouse. Samples of target organs (lung, liver, spleen) were collected for histological examination on days 3, 7, 10, 14, 21 and 32 after infection. Histological sections with 3-5 µm thickness were stained with hematoxylin and eosin according to standard techniques. It was established that strains of Y. pseudotuberculosis in dormant state caused in vivo development of a peculiar granulomatous inflammation due to delayed-type hypersensitivity reactions (DHR), which characterizes the protective reaction in infected host and reflects formation of local, tissue immunity in target organs. The peculiarities of granulomatous inflammation were revealed, in comparison with that of found during infection with vegetative ("wild") Y. pseudotuberculosis bacteria, namely: the granulomas were predominantly small in size, clearly delimited from the surrounding tissue, without destruction of central zone cells and formation of the so-called "granulomas with central karyorrhexis" (terminology proposed by A.P. Avtsyn) [4]; perivascular infiltrates and vasculitis consisted mainly of lymphocytes and often had a follicle-like appearance, resembling the follicles in lymphoid organs; in the lungs, a well-marked reaction of the bronchial-associated lymphoid tissue was observed, and in the spleen, a follicular hyperplasia, indicating a T-cell defense reaction, was observed. Thus, the causative agent of Y.pseudotuberculosis infection / FESLF, being in a dormant state, initiates the development of immunomorphological changes of a protective nature such as productive granulomatous inflammation with reactions of local tissue immunity in target organs and can contribute to the formation of persistent infection.


Author(s):  
E. Tikhomirova ◽  
V. Atrushkevich ◽  
E. Linnik ◽  
M. Konopleva ◽  
I. Zudina

β-defensin-2 (HBD-2) is a peptide of innate immunity that provides the first line of defenсe of the oral mucosa from the introduction of the pathobionts. Under inflammatory conditions epithelial cells and gingival fibroblasts produce HBD-2. The defective defensin secretion may play a crucial role in the development of inflammatory periodontal diseases. The study aimed to compare the levels of HBD-2 in the gingival fluid and/or the content of the periodontal pockets in patients with dental plaque-induced gingivitis (PG), aggressive periodontitis (AgP), chronic generalized periodontitis (CP) and in the periodontally healthy subjects (Control). We examined 142 patients (45.0 ± 1.03 years) from Moscow, including 11 patients with PG (35.7 ± 3.69 years), 43 patients with AgP (35.4 ± 0.84 years), 71 patients with CP (54.4 ± 0.86 years) and 17 controls (36.1 ± 2.92 years). We determined the periodontal tissues condition in all patients during the periodontal and X-ray examination. The samples of the gingival crevicular fluid and periodontal pocket content were collected by paper points from the gingival sulcus and periodontal pockets at 8 teeth of both jaws. The concentration (C) of β-defensin-2 was determined by enzyme immunoassay (ELISA Kit for Defensin Beta 2, Cloud-Clone Corp., USA). Mann-Whitney U-test (U), the Kruskal-Wallis test (H) and the Dwass-Steel-Critchlow-Fligner post hoc test (W) determined the difference significance between the parameters. We estimated the parameter relationship and its strength using the Spearmanʼs rank correlation coefficient (rS). The critical significance level was p ≤ 0.05.The present study showed that the progression of the periodontal inflammation is accompanied by a sharp decrease in the concentration of HBD-2 in patients’ samples (H = 42.8, df =3, p < 0.001). Thus, the concentration of HBD-2 in the gingival crevicular fluid of the periodontally healthy subjects (control group) ranged from 225 to 1720 pg/ml (C = 738 [477; 1114] pg/ml). In patients with PG the median value of the peptide concentration was 242 [42.5; 610] pg/ml (Cmin = 19 pg/ml, Cmax = 1000 pg/ml). In patients with periodontitis it dropped to critically low levels: CAgP = 54 [3; 195] pg/ml (Cmin = 0, Cmax = 478 pg/ml) and ССP = 25.5 [0; 125] pg/ml (Cmin = 0, Cmax = 298 pg/ml). Thus, we can consider the level of HBD-2 in the gingival crevicular fluid – a potential predictor of the development of inflammatory periodontal diseases.


Author(s):  
S. Klyueva ◽  
S. Bugorkova ◽  
T. Kashtanova

In conditions when the assessment of changes in the incidence rate cannot be used as an indicator of the effectiveness of a live plague vaccine, there is a real need to search for other, in particular, immunological correlates of the vaccine's protection. Modern concepts of the patho- and immunogenesis of plague make it possible to narrow the search for possible correlates of protection, focusing on the assessment of cellular factors of the immune response. The aim of this work is to identify the immunological correlates of protection against plague in mice immunized with Yersinia pestis EV NIIEG, and to assess the dynamics of selected markers of immunological effectiveness of vaccination in people vaccinated against plague. Experimental model - BALB / c mice, 40 individuals in each group were immunized with Y. pestis EV at doses of 2 × 102, 1 × 103, 5 × 103, 2.5 × 104 CFU, and on the 21st day they were infected with Y. pestis 231 at a dose of 400 LD50. Control group - intact animals. Immunogenicity was determined by ImD50 and calculated by the Kerber method. Volunteers - 20 people who were first vaccinated with the live plague vaccine and 20 people who were not vaccinated against the plague (comparison group). The production of cytokines in the blood was determined on an enzyme-linked immunosorbent analyzer "LAZURIT" (Dynex Technologies, USA): in mice before infection with Y. pestis 231 on the 14th and 21st days after vaccination; in humans - before vaccination, 1, 6 and 12 months after vaccination. We used commercial kits in accordance with the instructions for their use. The immunized mice showed a significant increase (2.2 times) in the induced IFN-γ production and a moderate increase in the concentration of TNF-α, IL-10 and IL-17A on the 14th day of immunogenesis. A high correlation was found between the survival rate of animals and the level of antigen- / mitogen-induced production of IFN-γ (r = 0.94, p = 0.039), both on the 14th and 21st days, as well as a noticeable relationship with the level of production of IL-10 and IL-17A on the 14th day of immunogenesis. In volunteers one month after inoculation, an increase in the indicators of mitogen-induced production of all detectable cytokines was noted, but the levels of IFN-γ, TNF-α, IL-10, IL-17A significantly increased by the 6th month of observation (p <0.05), although only for IFN-γ and IL-17A, the induced production of these cytokines remained at a sufficiently high level up to a year after inoculation. Thus, IFN-γ and IL-17A can be considered as possible informative correlates of protection of mice from Y. pestis on days 14 and 21, considering the increase in the induced production of these cytokines as adequate markers of the protective efficacy of immunization, and the assessment of the dynamics of these parameters in volunteers vaccinated with the plague live vaccine, an increase in the levels of IFN-γ and IL-17A can be considered a favorable prognostic marker of the immunological efficacy of the vaccine in the period from the 6th to the 12th month of observation.


Author(s):  
L. Matveeva ◽  
R. Kapkaeva ◽  
A. Chudaikin ◽  
A. Soldatova ◽  
L. Mosina ◽  
...  

A populational infection with Helicobacter (H.) pylori poses a global problem. Mucosal colonization of H. pylori in the gastroduodenal area can initiate development multiple diseases with hyper-or hypoplasia of mucosal epithelial cells secreting vascular endothelial growth factor (VEGF). The aim of the study was to assess VEGF serum level, its diagnostic and prognostic value in diseases affecting the gastroduodenal area. Material and methods. 180 patients with exacerbated chronic gastritis, gastric ulcer, duodenal ulcer as well as 30 healthy volunteers were examined after providing an informed consent. Patients were divided into groups depending on the degree of mucous contamination with H. pylori. In the subjects examined during esophagogastroduodenoscopy, a biological material was collected during targeted biopsy for microscopic and histological studies. Blood samples for immunological examination were obtained in the morning on an empty stomach from the ulnar vein in the volume of 5 ml, and the serum was isolated by centrifugation. The level of VEGF, pepsinogens, and titer of total antibodies against the H. pylori cytotoxin-associated protein were determined in the blood serum from the subjects by using the enzyme immunoassay method. The long-term prognosis was analyzed for up to 2 years. The data obtained were processed statistically. Results. Patients were found to have excessive serum VEGF levels in healthy volunteers. For gastric ulcer associated with H. pylori, 80% of cases had increased discriminatory VEGF level. In patients, direct relationships between the serum VEGF level and degree, stage of gastritis, the degree of contamination with H. pylori, the serum pepsinogens level were uncovered. Regression analysis found that patients with diseases targeting gastroduodenal area had serum VEGF level equal to or greater than 231 pg/ml in 60% of cases that correctly predicted an increase in mucosal atrophy. If the amount of VEGF ≥373 pg/ml in 91.5% of cases, then ulceration of gastric epithelium developed, whereas for ≥396 pg/ml level it was observed in 89% cases with ulceration of the intestinal epithelium. The probability of gastroduodenal bleeding at a serum VEGF level of 408 pg/ml or higher was predicted correctly in 96% of cases. Conclusion. More than 54% of patients with H. pylori-associated chronic gastritis, peptic ulcer disease had level of VEGF significantly exceeding magnitude found in healthy volunteers and the discriminatory level reflects the morphofunctional state of the stomach and duodenum. Assessing serum VEGF level in gastroduodenal diseases can be recommended for predicting development of atrophy, ulceration of the gastric and intestinal epithelium, and gastroduodenal bleeding.


Author(s):  
M. Shperling ◽  
E. Shperling ◽  
A. Kovalev ◽  
A. Vlasov ◽  
A. Polyakov ◽  
...  

Treatment of COVID-19-associated pneumonia in the overwhelming majority of cases is accompanied by empirical prescription of antibiotic therapy. According to a number of studies carried out, the addition of a bacterial infection in this disease is noted less often than in other viral pneumonias, in particular, caused by the influenza virus. In addition, the occurrence of leukocytosis in response to therapy with glucocorticosteroids (GCS) is often perceived as an attachment of bacterial flora and is the reason for initiating antibiotic therapy. Therefore, an urgent task is the correct interpretation of leukocytosis in response to GCS therapy in COVID-19. The purpose of the work was to study the dynamics of changes in the number of leukocytes, neutrophils and monocytes of venous blood in patients with moderate COVID-19 with systemic use of GCS. Also we aimed to determine the differences in these indicators between the group of patients with indirect signs of bacterial infection and the group of patients receiving GCS. We analyzed the indicators of the complete blood count of 154 patients in the temporary infectious diseases hospital in the “PATRIOT” Park of the Moscow region with confirmed moderate form of COVID-19. The comparison group (1) consisted of 128 patients without clinical signs of bacterial infection and leukocytosis on admission, who were prescribed GCS therapy. The control group (2) consisted of 26 people who, upon admission, showed signs of a bacterial infection - a cough with purulent sputum in combination with neutrophilic leukocytosis. The dynamics of cells in venous blood was assessed in patients of group (1) before the start, 3 and 6 days after the start of GCS therapy. We also compared the number of leukocytes, neutrophils and monocytes between patients with developed leukocytosis from group (1) in response to GCS therapy and group (2). As a result of the study, an increase in the number of leukocytes, neutrophils and monocytes was revealed according to the data of the complete blood count test in patients of the group (1) on days 3 and 6 of GCS therapy. All patients with developed leukocytosis (103 people) had no clinical signs of bacterial infection. In patients with developed leukocytosis from group (1), an increase in the number of monocytes was revealed (0.90 (0.84; 1.02) on day 3 of GCS and 0.94 (0.87; 1.26) on day 6 of GCS) compared with group (2) (0.61 (0.50; 0.71)), p <0.001. The number of leukocytes and neutrophils did not differ between the groups. The appearance of monocytosis when taking GCS may be due to the presence of macrophage activation syndrome in the pathogenesis of COVID-19 and, therefore, increased activation of monocytes. The use of GCS in this case leads to inhibition of the migration of monocytes to the inflammation area and to the stimulation of the production of their anti-inflammatory pool (M2 cells) by the bone marrow. This fact causes an increase in the number of monocytes in the peripheral blood. Monocytosis in response to GCS therapy can be a differential diagnostic criterion between glucocorticoid-induced leukocytosis and the addition of a bacterial infection. This may be one of the factors influencing the decision to prescribe antibiotic therapy, and may also be a criterion for the effectiveness of GCS immunosuppressive therapy in COVID-19, which requires further study.


Author(s):  
O. V. Smirnova ◽  
V. V. Tsukanov ◽  
A. A. Sinyakov ◽  
O. L. Moskalenko ◽  
N. G. Elmanova ◽  
...  

The aim of our study was to evaluate the clinical-anamnestic, serological, immunological and biochemical tests used for early diagnostics of gastric cancer associated with Helicobacter pylori infection in the adult population of the Krasnoyarsk Territory.Materials and methods: The control group consisted of 104 apparently healthy blood donors, the comparison group – 97 patients with chronic atrophic gastritis as well as a group of patients with early gastric cancer comprising 98 subjects. Assessment of monocyte and neutrophil spontaneous and induced chemiluminescence (CL) was carried out on a 36-channel biochemiluminometer "BLM - 3607". Phagocytosis was measured by using a Beckman Coulter FC 500 flow cytometer. A Varyan Cary Eclipse spectrofluorometer was used to study lipid peroxidation and factors of the antioxidant defense system.Results and discussion: While studying the phagocytic arm of immunity, it was found that all patients with early gastric cancer were reported to have parameters of the maximum intensity for neutrophil spontaneous CL from 17831 c.u. and lower, whereas induced CL reached at least 30,000 c.u.. Phagocytic activity of neutrophilic granulocytes in patients with early gastric cancer was 36% or less. While studying the indicators of monocytes, it was found that spontaneous and induced CL decreased from 454 c.u. and 1186 c.u., respectively, in the patients with early gastric cancer. Monocytic activity in early gastric cancer was 34% or less. In the study of lipid peroxidation, an antioxidant defense in patients with chronic atrophic gastritis and gastric cancer had increased malondialdehyde (MDA) level. Patients with gastric cancer had decreased activity of the enzyme catalase (CAT), whereas subjects with chronic atrophic gastritis had reduced glutathione peroxidase (GPO) level. In contrast, patients with early gastric cancer were featured with increased GPO activity. We have proposed coefficients for assessing the factors of the AOD system in patients: the ratio for superoxide dismutase to catalase activity (SOD / CAT) as well as the ratio for superoxide dismutase to glutathione peroxidase activity (SOD / GPO).Conclusion: During the study, threshold values of parameters were obtained for assigning groups at high risk of developing early gastric cancer, which can be used for screening in adult population.


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