The Effect of Short-Term Physical Activity on the Oxidative Stress in Rats with Different Stress Resistance Profiles in Cerebral Hypoperfusion.

Oxidative stress associated with chronic cerebral hypoperfusion is one of the fundamental factors leading to neurodegenerative diseases. To prevent oxidative stress, physical activity is effective. Physical exercise enables development of rehabilitation techniques that can progressively increase patients' stress resistance. We determined the oxidative stress dynamics in experimental hypoperfusion and modeled rehabilitation measures, comparing sex and stress resistance levels. The experiment was performed on 240 Wistar rats of both sexes over a period of 90 days. Based on behavioral test results obtained using the open field test, the rats were divided into active animals with predicted higher stress resistance (HSR) and passive animals with predicted lower stress resistance (LSR). TBA (thiobarbituric acid) plasma concentration of the active products (malondialdehyde-MDA), blood plasma (NO-X) concentration, and L-citrulline (LC) concentration were determined spectrophotometrically at the corresponding wave length (nm). The intensity of oxidative stress was evaluated using the chemoluminscent method to determine the blood plasma antioxidant activity on the BCL-07 biochemoluminometer. This study revealed two stages of oxidative stress: a less pronounced phase covering the first days after surgery and a main one, which starts from the month after the operation to 3 months. Female sex and a high initial level of stress resistance reduced the severity of oxidative stress. Physical activity commencing a week after the surgery resulted in "reloading" the adaptive mechanisms and slowed the onset of the main stage, leading to a decrease in the free-radical process in all studied subgroups and the greater blood plasma (NO)-X decrease in the male animals. Future neuropharmacological intervention most likely will be able to determine the pathophysiology mechanism of chronic brain hypoperfusion and potentially extending adaptive responses.

HIV and other sexually transmitted infections among female sex workers in Moscow (Russia): prevalence and associated risk factors.

To estimate the prevalence and factors associated with HIV and five other STIs among outdoor female sex workers (OSFW) and indoor FSW (IFSW). METHODS: Cross-sectional survey using respondent-driven sampling methodology. Participants answered a bio-behavioural questionnaire and were tested for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV), syphilis (lifetime contact) and Mycoplasma genitalium (MG). Weighted HIV and other STIs prevalence and 95% CIs were calculated. Weighted multivariate logistic regression was performed to identify factors associated with having at least one STI (including HIV). RESULTS: Between October 2017 and July 2018, 385 FSW participants were recruited, among whom 206 (53.5%) were IFSW and 179 (46.5%) were OFSW. The mean age was 31.4 years. Weighted HIV prevalence was 3.1% (95% CI 1.5 to 7.0). Weighted prevalence of other STIs was: 4.1% (95% CI 2.2 to 8.0) for NG, 8.8% (95% CI 5.9 to 13.0) for CT, 12.7% (95% CI 8.6 to 18.0) for TV, 13.9% (95% CI 9.9 to 19.0) for syphilis (lifetime contact) and 14.9% (95% CI 10.5 to 21.0) for MG. STI prevalence was significantly higher among OFSW for CT, TV and MG (p<0.001). In total, 43.2% of the participants had at least one HIV/STI. Factors associated with having HIV/STI were being an OFSW (OR 3.29; 95% CI 1.72 to 6.27); being registered in another Russian region (2.61 (95% CI 1.05 to 6.48)); having never been tested for HIV (2.51 (95% CI 0.98 to 6.41)) and having a low level of knowledge regarding HIV transmission (4.88 (95% CI 0.96 to 24.78)). CONCLUSION: Prevalence of HIV and STIs was high among FSW in Moscow. OFSW were more vulnerable to STIs. There is an urgent need to tailor programmes for sexual and reproductive health for FSW in Russia.

Crohn's disease of the vulva: A tough diagnosis (a case report of a 47 y.o. patient).

Extraintestinal symptoms of Crohn's disease may occur in the eye, the urinary system, on the skin, or subcutaneous fat. We report the case of a 7-year diagnostic search of isolated vulvar Crohn's disease in a 47-year-old woman. The disease is characterized by gradual formation of pronounced bilateral asymmetric labial hypertrophy.

Prevalence of Ureaplasma spp. and Mycoplasma hominis in healthy women and patients with flora alterations.

The objective was to estimate the prevalence of Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum in healthy women and patients with altered vaginal microflora. Vaginal samples from 2594 unselected female patients were divided into normal, bacterial vaginosis (BV), and aerobic vaginitis (AV) groups and tested for U. parvum, U. urealyticum and M. hominis. Normal flora was detected in 1773 patients (68.4%), BV in 754 patients (29.1%), and AV in 67 patients (2.6%). In the control group, 771 (43.5%) patients were U. parvum positive, 104 (5.9%) were U. urealyticum positive, and 158 (8.9%) were M. hominis positive. In the BV group, those bacteria were detected in 452 (59.9%), 102 (13.5%), and 202 (26.8%) patients, respectively (P < 0.001); in the AV group, those were detected in 16 (23.9%), 3 (4.5%), and 4 (6.0%) patients, respectively (P < 0.001; 0.63 and 0.40, respectively). This study demonstrated that mycoplasmas may be a marker or a symbiont of the BV flora but not AV flora.

Bacterial infection-triggered acute-on-chronic liver failure is associated with increased mortality.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is characterized by an acute deterioration of liver function in patients with cirrhosis in combination with recently defined organ failures. Our aim was to independently validate the prognostic value of the recently established EASL-CLIF-Consortium definition of ACLF and to identify new predictors of short-term mortality. METHODS: Patients with cirrhosis and the International Classification of Diseases, Tenth Revision diagnosis of (sub)acute liver failure were retrospectively categorized according to the EASL-CLIF-Consortium definition. Logistic regression analyses were performed to identify clinical and epidemiological predictors of 30- and 90-day mortality. RESULTS: From 2008 to 2015, 257 patients were included. Overall, 173 (67%) patients met the EASL criteria for ACLF (grade 1: n = 43 [25%], grade 2: n = 52 [30%], grade 3: n = 79 [45%]). Mortality within 30 days in patients without ACLF was 3.6%, and 18.6%, 37.3% and 62.0% in patients with ACLF grades 1, 2 and 3 respectively. Outcome of patients with bacterial infection-triggered ACLF was distinct from non-infection-triggered ACLF (71.6% vs 33.8% 30-day survival, P < .001), and infection-triggered ACLF was independently associated with increased mortality (odds ratio [OR] = 4.28, P < .001). Pneumonia was a particularly frequent infection and burdened with high mortality. In addition, infections with multidrug-resistant organisms were frequent and independently associated with mortality (P = .030, OR = 4.41), as was glycopeptide antibiotic therapy as initial empirical antibiotic therapy (P = .005). CONCLUSIONS: This study confirmed the EASL-CLIF-Consortium definition of ACLF as strong predictor of mortality in patients with acute decompensation of cirrhosis. However, we have observed a remarkably higher mortality in infection-triggered ACLF compared to other precipitating events.

Prevalence of macrolide and fluoroquinolone resistance-mediating mutations in Mycoplasma genitalium in five cities in Russia and Estonia.

BACKGROUND AND OBJECTIVE: Resistance in the sexually transmitted bacterium Mycoplasma genitalium to all recommended therapeutic antimicrobials have rapidly emerged. However, to date, internationally reported resistance surveillance data for M. genitalium strains circulating in Eastern Europe are entirely lacking. The aim of this study was to estimate the prevalence of macrolide and fluoroquinolone resistance-associated mutations in M. genitalium in four cities in Russia and one in Estonia, 2013-2016. MATERIALS AND METHODS: Consecutive urogenital samples found positive for M. genitalium during diagnostic testing were retrospectively analyzed for resistance-associated mutations in the 23S rRNA and parC genes using pyrosequencing and conventional Sanger sequencing, respectively. RESULTS: In total, 867 M. genitalium positive samples from 2013-2016 were analyzed. Macrolide resistance-associated mutations were detected in 4.6% of the samples from Russia (0.7-6.8% in different cities) and in 10% of the samples from Estonia. The mutations A2059G and A2058G were highly predominating in both Russia and Estonia, accounting together for 90.9% of the cases positive for nucleotide substitutions in the 23S rRNA gene. The rates of possible fluoroquinolone resistance-associated mutations were 6.2% in Russia (2.5-7.6% in different cities) and 5% in Estonia. The mutations S83I and S83N were the most frequent ones in Russia (24.4% each), whereas D87N highly predominated in Estonia (83.3% of all fluoroquinolone resistance-associated mutations). Approximately 1% of the samples in both countries harbored both macrolide and possible fluoroquinolone resistance-associated mutations, with A2058G and S83I being the most frequent combination (37.5%). CONCLUSIONS: The prevalence of macrolide and fluoroquinolone resistance-associated mutations in M. genitalium was 4.6% and 6.2%, respectively, in Russia, and 10% and 5%, respectively, in Estonia. Despite the relatively low rates of macrolide and fluoroquinolone resistance in these countries, antimicrobial resistance surveillance and testing for resistance-associated mutations in M. genitalium positive cases would be valuable.

Evaluation and subsequent optimizations of the quantitative AmpliSens Florocenosis/Bacterial vaginosis-FRT multiplex real-time PCR assay for diagnosis of bacterial vaginosis.

Traditional microscopy-based methods for diagnosis of bacterial vaginosis (BV) are underutilized in many settings, and molecular techniques may provide opportunities for rapid, objective, and accurate BV diagnosis. This study evaluated the quantitative AmpliSens Florocenosis/Bacterial vaginosis-FRT multiplex real-time PCR (Florocenosis-BV) assay. Vaginal samples from a previous study including unselected female subjects (n = 163) and using Amsel criteria and 454 pyrosequencing for BV diagnosis were examined with the Florocenosis-BV test and additionally tested for the presence and quantity of Gardnerella vaginalis clades 3 and 4. The Florocenosis-BV assay demonstrated 100% and 98% sensitivity compared with the Amsel criteria and 454 pyrosequencing, respectively, with 91% specificity. The modified Florocenosis-BV assay (detecting also G. vaginalis clades 3 and 4) resulted in 100% sensitivity vs the Amsel criteria and 454 pyrosequencing with specificity of 86% and 88%, respectively. Further optimizations of thresholds for the quantitative parameters used in the kit resulted in 99-100% accuracy vs Amsel criteria and 454 pyrosequencing for selected parameters. The Florocenosis-BV assay is an objective, accurate, sensitive, and specific method for BV diagnosis; however, the performance of the test can be further improved with some minor optimizations.

Evaluation of the new AmpliSens multiplex real-time PCR assay for simultaneous detection of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis.

In this study, we performed an evaluation of the new CE-marked multiplex real-time AmpliSens N.gonorrhoeae/C.trachomatis/M.genitalium/T.vaginalis-MULTIPRIME-FRT PCR assay compared to APTIMA tests, i.e., APTIMA COMBO 2 assay, APTIMA Trichomonas vaginalis assay (FDA-approved), and two different APTIMA Mycoplasma genitalium assays (research use only; one of them only used for discrepancy analysis). Vaginal swabs (n = 209) and first-void urine (FVU) specimens from females (n = 498) and males (n = 554), consecutive attendees (n = 1261) at a dermatovenerological clinic in Sweden, were examined. The sensitivity of the AmpliSens PCR assay for detection of C. trachomatis (6.3% prevalence), M. genitalium (5.7% prevalence), N. gonorrhoeae (0.3% prevalence), and T. vaginalis (0.08% prevalence) was 97.5% (95% confidence interval (CI): 91.2-99.6%), 81.9% (95% CI: 70.7-89.7%), 100% (95% CI: 40.2-100%) and 100% (95% CI: 16.5-100%), respectively. The specificity of the AmpliSens PCR assay was 100% (95% CI: 99.6-100%) for all agents. The analytical sensitivity and specificity for N. gonorrhoeae detection was excellent, i.e., 55 international gonococcal strains detected and 135 isolates of 13 non-gonococcal Neisseria species were negative. In conclusion, the multiplex real-time AmpliSens N.gonorrhoeae/C.trachomatis/M.genitalium/T.vaginalis-MULTIPRIME-FRT PCR assay demonstrated high sensitivity and excellent specificity for the detection of C. trachomatis, N. gonorrhoeae, and T. vaginalis, and excellent specificity but suboptimal sensitivity for M. genitalium detection.

Treatment efficacy, treatment failures and selection of macrolide resistance in patients with high load of Mycoplasma genitalium during treatment of male urethritis with josamycin.

BACKGROUND: Azithromycin has been widely used for Mycoplasma genitalium treatment internationally. However, the eradication efficacy has substantially declined recent decade. In Russia, josamycin (another macrolide) is the recommended first-line treatment for M. genitalium infections, however, no data regarding treatment efficacy with josamycin and resistance in M. genitalium infections have been internationally published. We examined the M. genitalium prevalence in males attending an STI clinic in Moscow, Russia from December 2006 to January 2008, investigated treatment efficacy with josamycin in male urethritis, and monitored the M. genitalium DNA eradication dynamics and selection of macrolide resistance in M. genitalium during this treatment. METHODS: Microscopy and real-time PCRs were used to diagnose urethritis and non-viral STIs, respectively, in males (n = 320). M. genitalium positive patients were treated with recommended josamycin regimen and treatment efficacy was monitored using quantitative real-time PCR. Macrolide resistance mutations were identified using sequencing of the 23S rRNA gene. RESULTS: Forty-seven (14.7%) males were positive for M. genitalium only and most (85.1%) of these had symptoms and signs of urethritis. Forty-six (97.9%) males agreed to participate in the treatment efficacy monitoring. All the pre-treatment M. genitalium specimens had wild-type 23S rRNA. The elimination of M. genitalium DNA was substantially faster in patients with lower pre-treatment M. genitalium load, and the total eradication rate was 43/46 (93.5%). Of the six patients with high pre-treatment M. genitalium load, three (50%) remained positive post-treatment and these positive specimens contained macrolide resistance mutations in the 23S rRNA gene, i.e., A2059G (n = 2) and A2062G (n = 1). CONCLUSIONS: M. genitalium was a frequent cause of male urethritis in Moscow, Russia. The pre-treatment M. genitalium load might be an effective predictor of eradication efficacy with macrolides (and possibly additional antimicrobials) and selection of macrolide resistance. Additional in vivo and in vitro data are crucial to support the recommendation of using josamycin as first-line treatment for M. genitalium infections in Russia. It would be valuable to develop international M. genitalium management guidelines, and quantitative diagnostic PCRs determining also M. genitalium load and resistance mutations (for macrolides and ideally also moxifloxacin) should ideally be recommended.

Utility of microscopic techniques and quantitative real-time polymerase chain reaction for the diagnosis of vaginal microflora alterations.

OBJECTIVE: The aim of the study was to evaluate the diagnostic value of Nugent score, wet mount microscopy, and polymerase chain reaction (PCR) test developed in Russia for bacterial vaginosis (BV) diagnosis. MATERIALS AND METHODS: One hundred Caucasian women were enrolled in this study. Three vaginal samples were taken from each participant: 1 for PCR analysis, 1 for Nugent score evaluation, and 1 for wet mount microscopy. The smears for microscopy were air-dried and sent to Femicare, Tienen, Belgium, for blinded analysis by microscopy. Multiplex real-time PCR was performed using primers and probes targeting Gardnerella vaginalis, Atopobium vaginae, Lactobacillus species, and total quantity of bacterial DNA (16SrRNA gene). RESULTS: Agreement among the 3 methods was 72 (73.5%) of 98 samples. Agreement between Nugent score and PCR results was 77 (78.6%) of 98 samples; between wet mount microscopy and PCR, 81 (82.65%) of 98 samples; between wet mount microscopy and Nugent score, 84 (85.7%) of 98 samples. The sensitivity and specificity of the methods studied were as follows: 75% (21/28) and 97.1% (68/70) for Nugent score, 96.4% (27/28) and 94.3% (66/70) for wet mount microscopy, 92.8% (26/28) and 85.7% (60/70) for PCR, respectively. CONCLUSIONS: This study demonstrated that wet mount microscopy is a superior method for BV diagnosis. The PCR test under study showed a high sensitivity and can be used for discrimination between normal flora and BV.