Tetracycline resistance of Escherichia coli isolated from water, human stool, and fish gills from the Lake Sevan basin.

The ecological state of Lake Sevan, the largest drinking water reservoir for the South Caucasus, formed under the influence of climatic and social changes. This study assesses the bacteriological quality of water in the rivers of the Lake Sevan basin and tetracycline-resistant bacteria isolated from fish and people living near the rivers of the Lake Sevan basin in Armenia in autumn 2019 and spring 2020. No differences have been shown for the tetracycline resistance of the investigated E. coli isolated from the human gut and the Masrik, Argichi, and Gavaraget Rivers. Horizontal gel electrophoresis revealed the same plasmid bands in most of the investigated E. coli with the same tetracycline resistance from the different sources of the Argichi River (obtained from people/fish/water sources where the fish were caught). The results also showed that most of the waters carried Edwardsiella spp., Erwinia spp., Morganella spp., and Proteus spp. in addition to E. coli; the coliform index did not exceed the standard level of 5 × 104 CFU mL-1 there. These findings highlight the importance of multidisciplinary studies of bacteria from "interacting" ecosystems, which might serve as a basis for the suggestion of microbial antibiotic resistance as another indicator of water pollution.

Effect of Bacillus subtilis KATMIRA1933 and Bacillus amyloliquefaciens B-1895 on the productivity, reproductive aging, and physiological characteristics of hens and roosters.

The study aims at investigating the effect of preparations of two bacilli strains on laying hens and roosters. Preparations were based on the strains Bacillus subtilis KATMIRA1933 and Bacillus amyloliquefaciens B-1895. Several groups of roosters and hens received a preparation based on either strain, or a mixture of both, from the first day to the last day of poultry in production. These preparations improved egg production, quality of sperm production, quality/hatchery of eggs, and slowed down the reproductive aging of hens. These observations were confirmed by the mathematical model proposed herein. At the molecular level, the slowing down of aging was confirmed by a decrease in the amount of mitochondrial DNA damage. Monitoring the physiological parameters of the experimental and control groups of birds showed that live weight gain in all experimental groups was higher than in the control group, and the reproductive organs of hens were more developed. There was also an improvement in the biochemical parameters of blood, the quality of the sperm of roosters, the laying of laying hens, and the morphological and biochemical parameters of the eggs. One of the most significant results is an increase in egg fertilization and a decrease in embryo death during the first 7 days of incubation.

Presence of Old Individuals in a Population Accelerates and Optimizes the Process of Selection: in silico Experiments.

One of the important components of the concept of aging-phenoptosis (programmed aging) is the notion of aging as an accelerator of evolution having the rank of subconcept. For many reasons, the main being the problematic experimental testing of evolutionary hypotheses, verification of the above-mentioned subconcept can be based primarily on analysis of the internal inconsistency of heuristic models and their correspondence to undisputedly observed facts. To illustrate the acceleration mechanism, and most importantly to structure the evolutionary process in communities that include naturally weakened individuals, V. P. Skulachev offered in 2003 a conceptual model that he later called a "fable about hares". Despite its simplicity, this model has undoubted internal logic. The natural trend in the development of conceptual models is their translation into the language of mathematics. The purpose of the present work was to create a variation of the known multi-agent model "predator-prey" that would allow us to "see" how the presence in the prey population of naturally weakened (old) members stimulates the selection of individuals with traits whose adaptive potential is not devaluated with age. The model (http://homebear.ru/PD) was developed on the Java platform, version 6, NetBeans development environment 8.2. Statistical analysis and preparation of illustrative materials were carried out using environment R, version 3.4.1. The results of numerical experiments set using our model correspond in principle to the provisions of the heuristic model of Skulachev and, consequently, confirm the absence in it of logical contradictions.

DNA-protection and antioxidant properties of fermentates from Bacillus amyloliquefaciens B-1895 and Bacillus subtilis KATMIRA1933.

UNLABELLED: DNA protective and antioxidant activity of Bacillus amyloliquefaciens B-1895 and Bacillus subtilis KATMIRA1933 were evaluated by Escherichia coli-based Lux biosensors. Two biosensor strains of E. coli, MG1655 (pColD-lux) and MG1655 (pSoxS-lux), which react on DNA damage and superoxide-anion radical activity, were used. SOS-response and Sox-response were stimulated by addition of dioxidine (2,3-Quinoxalinedimethanol,1,4-dioxide) and paraquat (N,N'-dimethyl-4,4'-bipyridinium dichloride) respectively. Preparations of both Bacillus fermentates demonstrated DNA protective and antioxidant (superoxide scavenging) activity (up to 60·19%). The strain К1933 is, in general, characterized by higher DNA protective activity (28·85%), with parameters of antioxidant activity of both bacilli strains being statistically not significantly different. Sporogenous potential probiotic micro-organisms with antioxidant and DNA protective activities can become an effective tool for compensation of various negative oxidative stress processes in humans. SIGNIFICANCE AND IMPACT OF THE STUDY: In humans, oxidative stress is a cause or an important component of many serious diseases, as well as being one of the age influencing factors. Environmental stresses lead to the increase in levels of reactive oxygen species (ROS). Oxidative DNA damage is a side effect of nonspecific inflammation. These human health challenging factors trigger the search for health-promoting bacteria capable of production of antioxidants and DNA-protectors. In this study, two Bacillus strains of interest were shown to produce noticeable DNA protective and antioxidant activities.

High mortality in the first year after kidney graft failure.

BACKGROUND: The aim of our cohort study was to assess survival of the patients after kidney graft failure. METHODS: Patients starting dialysis after graft failure between January 1, 2004 and December 31, 2010 were identified from the Slovenian Renal Replacement Therapy (RRT) Registry and followed to December 31, 2011. The control group consisted of 351 incident dialysis patients, who were kidney transplant candidates. Survival data were not censored for retransplantations. RESULTS: After a median of 7.4 (interquartile range [IQR]) 0.4-13.0) years with a functioning graft and a median of 15.5 (IQR 7.8-20.7) years on RRT 82 patients started dialysis. Their mean (± standard deviation [SD]) age was 50.4 ± 12.7 years vs 49.2 ± 13.9 years for the incidental transplantation candidates (P = .49). There were sixty-one percent men (vs 64%; P = .67), and all subjects were on hemodialysis treatments. By Dec 31, 2011, 19 (23%) patients had undergone retransplantation and 27 (33%) died after a median of 1.6 (IQR 0.2-5.4) months on dialysis. The causes of death were infection (n = 15), cardio-disease-vascular (n = 6), malignancy (n = 4), or cerebrovascular (n = 2). Deceased patients were significantly older: 60.0 ± 7.9 vs 45.7 ± 12.0 years (P < .001) and more often men: (78% vs 53% P = .05). The unadjusted overall 1- and 3-year survivals rates after graft failure of 70% and 68% were significantly lower than those in the control candidate group of (98% and 93%, respectively (log-rank; P < .001). This difference remained significant upon multivariate analysis (hazard ratio [HR], 12.0; P < .001). The subgroup of 53 patients who started dialysis after chronic graft failure showed unadjusted 1- and 3-year survival rates of 82% and 80%, respectively which were still worse than the control group (P = .001), a difference that remained significant upon multivariate analysis (HR, 1.75; P < .001). CONCLUSION: After kidney graft failure patients experienced increased mortality in the first year after restarting dialysis. However, subjects who survived the first year showed good survival thereafter.

Early kidney graft size and Doppler parameters are associated with kidney graft function 1 year after transplantation.

BACKGROUND: The aim of this study was to assess the association of various ultrasonography (US) and Doppler parameters of kidney graft as measured at 1 month posttransplant with 1-year graft function. MATERIALS AND METHODS: The study cohort included 125 adult recipients of deceased donor kidney transplantations between January 2006 and February 2009. All patients underwent an US-Doppler examination performed by a trained nephrologist at 1 month posttransplant using an Acuson-Siemens Sequoia 512. Graft length and intrarenal Doppler indices were measured at the midsegmental artery level. Relative graft size was calculated by dividing graft length with body mass index. Graft function was assessed at 1 year by estimated glomerular filtration rate (eGFR) using the 4-variable Modification of Diet in Real Disease study equation. Linear and logistic regression analyses were used to assess the relationship between US-Doppler parameters and eGFR. RESULTS: Univariate linear regression showed a significant correlation between eGFR at 1 year and graft length at 1 month (P = .009), relative graft length <0.50 cm per kg/m(2) (P = .004), resistance index >0.75 (P = .031), and end-diastolic velocity <9 cm/sec (P = .006). Logistic regression analyses showed that eGFR <60 mL/min/1.73 m(2) at 1 year was significantly associated with graft length <12 cm at 1 month (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.16-4.92; P = .017), relative graft length <0.5 cm per kg/m(2) (OR, 2.54; 95% CI, 1.20-5.35; P = .014), resistance index >0.75 (OR, 2.86; 95% CI, 1.30-6.29; P = .009), and end-diastolic velocity <9 cm/sec (OR, 2.37; 95% CI, 1.01-5.56; P = .047). CONCLUSION: In this retrospective analysis, kidney transplant recipients with greater graft length at 1 month, specifically when standardized to body size, showed better graft function at 1 year posttransplantation. Higher intrarenal diastolic blood flow and lower resistance index at 1 month were also predictive of better graft function at 1 year.

Pretransplant soluble CD30 serum concentration does not affect kidney graft outcomes 3 years after transplantation.

INTRODUCTION: An elevated serum concentration of soluble the form of CD30 (sCD30), an activation marker of mainly T(H)2-type cytokines producing T lymphocytes, has been reported as a predictive factor for acute cellular rejection episodes and poor graft outcomes in kidney transplantation. This historic cohort study investigated the association of a pretransplant sCD30 serum concentrations with kidney graft function and graft survival 3 years posttransplantation in adult recipients of deceased donor kidney grafts, treated with monoclonal anti-CD25 antibodies as an induction treatment combined with a cyclosporine (CsA)-based maintenance triple therapy. MATERIALS AND METHODS: The pretransplant sera of 296 recipients were tested for sCD30 content using a microsphere flow-cytometry assay. The estimated glomerular filtration rate (eGFR) was determined by the 4-variable Modification of Diet in Renal Disease equation. The incidences of graft loss were calculated with the use of Kaplan-Meier survival analysis and compared using the log-rank test. RESULTS: According to the distribution of the pretransplant sCD30 levels concentration ≥2700 pg/mL was defined as high (n = 146) and concentration <2700 pg/mL as low (n = 150). Three years posttransplantation, the eGFR was not significantly different in the recipients in high and low sCD30 groups (65 ± 24 vs 67 ± 21 mL/min/1.73 m(2); P = .43); there was no association between the eGFR 3 years after transplantation and the pretransplant sCD30 levels (r(2) = 0.002; P = .49). Graft survival 3 years after transplantation was also not different in the recipients in high and low sCD30 groups (P = .52). CONCLUSION: In our adult deceased-donor kidney graft recipients, the pretransplant sCD30 serum concentration was not a predictive factor of immunologic risk associated with the kidney graft function 3 years posttransplantation; neither did it affect graft survival 3 years after transplantation. The immunosuppression with anti-CD25 antibodies as an induction treatment combined with the CsA-based maintenance triple therapy could possibly be decisive for our findings.

Subclinical left ventricular echocardiographic abnormalities 1 year after kidney transplantation are associated with graft function and future cardiovascular events.

Cardiovascular events (CVE) are the leading cause of mortality in kidney transplant recipients. Increased left ventricular mass (LVM) is a risk factor for CVE. This study investigated the associations of LVM with impaired kidney graft function expressed as lower glomerular filtration rate (GFR) at 1 year after transplantation and future CVE beyond 1 year. The prospective study cohort included 68 nondiabetic recipients of a kidney transplant between January 2004 and December 2005 who underwent a transthoracic echocardiographic investigation at 1 year after transplantation. LVM and left ventricular hypertrophy (LVH) were assessed using 2-dimensional M-mode echocardiography. GFR was estimated (eGFR) by the 4-variable Modification of Diet in Renal Disease formula. Cox proportional hazards analysis was used to estimate cardiac CVE (angina pectoris, acute myocardial infarct, coronary angioplasty or bypass surgery, or sudden cardiac death) hazard ratios (HRs) for patients with LVH versus control subjects with no LVH at 1 year after transplantation. All patients had normal systolic function (ejection fraction >50%) with no symptoms or signs of heart failure. LVH was present in 44 patients (65%). LVM and incidence of LVH were increased in 28 patients with eGFR <60 mL/min/1.73 m(2) compared with 40 patients with eGFR ≥60 mL/min/1.73 m(2) (248 ± 61 g and 86% vs 210 ± 46 g and 50%, respectively; P < .01). After a median follow-up of 4.5 years, there were 18 (26.5%) cardiac CVE. The incidence of CVE was higher in patients with LVH than in patients with no LVH at 1 year after transplantation (36.4% vs 8.3%; P = .020). In adjusted analyses, LVH was associated with an increased risk for future CVE (HR, 4.69; 95% confidence interval, 1.02-21.5; P = .037). In kidney transplant recipients, a lower eGFR at 1 year after transplantation was associated with greater LVM and higher incidence of LVH. Presence of LVH was associated with an increased risk for future CVE.

Does pretransplant soluble CD30 serum concentration affect deceased-donor kidney graft function 3 years after transplantation?

Elevated serum concentrations of soluble CD30 molecule (sCD30) have been related to acute cellular rejection and poor graft outcomes in kidney transplantation. This historical cohort study investigated the association of pretransplant sCD30 serum concentrations with kidney graft function expressed as estimated glomerular filtration rate (GFR) at 3 years after transplantation. Pretransplant sera from 176 adult deceased-donor kidney graft recipients were tested for sCD30 content using a commercially available automated enzyme-linked immunosorbent assay. The immunosuppression consisted of induction therapy with monoclonal anti-CD25 antibodies and a maintenance regimen of cyclosporine (CsA)-based therapy. GFR was estimated (eGFR) by the four-variable Modification of Diet in Renal Disease (MDRD) Study equation. According to the distribution of pretransplant sCD30 levels (median 66.7 U/mL; interquartile range, 46.6 to 98.6 U/mL), a concentration of 66 U/mL or higher was defined as high (n = 89) and below 66 U/mL as low (n = 87). Three years after transplantation, eGFR was not significantly different among recipients in high versus low sCD30 groups (69 +/- 23 mL/min/1.73m2 vs 66 +/- 21 mL/min/1.73m2; P = .327) and there was no correlation between eGFR and pretransplant sCD30 levels (r2 = 0.001; P = .73). Upon multivariate regression analysis, donor age, recipient body mass index at transplantation, and acute rejection episodes were independent variables affecting eGFR at 3 years after transplantation. This study showed that pretransplant sCD30 serum concentrations were not associated with deceased-donor kidney graft function at 3 years after transplantation. The immunosuppression with anti-CD25 antibodies and a triple CsA-based maintenance regimen could possibly be decisive for our findings.

Left ventricular mass is associated with ventricular repolarization heterogeneity one year after renal transplantation.

Ventricular repolarization heterogeneity (VRH) is associated with the risk of arrhythmia and cardiac death. This study investigated the association between VRH and left ventricular mass (LVM) in renal transplant recipients 1 year after transplantation. Echocardiography and 5-min 12-lead electrocardiogram were recorded and GFR was estimated (eGFR) in 68 nondiabetic patients. Beat-to-beat QT interval variability algorithm was used to calculate SDNN-QT and rMSSD-QT indices of VRH. To quantify QT interval variability relative to heart rate fluctuations, QTRR index was calculated. Left ventricular hypertrophy (LVH) was present in 44 patients (65%). LVM and incidence of LVH were increased in 28 patients with eGFR <60 mL/min/1.73 m(2) compared with 40 patients with eGFR > or =60 mL/min/1.73 m(2) (248 +/- 61 g and 86% vs. 210 +/- 46 g and 50%, respectively; p < 0.01). A direct correlation was found between LVM and SDNN-QT (R = 0.47, R(2)= 0.23; p < 0.001), rMSSD-QT (R = 0.27; R(2)= 0.10; p = 0.034), and QTRR (R = 0.55; R(2)= 0.31; p < 0.001) indices. In conclusion, greater LVM is associated with increased VRH in renal transplant recipients, providing a link with the high risk of arrhythmia and cardiac death, specifically in patients with decreased graft function.

Basiliximab versus daclizumab combined with triple immunosuppression in deceased donor renal graft recipients.

In this prospective, randomized, open-label, single-center study, we compared the efficacy and safety of two anti-interleukin-2 receptor monoclonal antibodies among adult recipients of at least 1 HLA-mismatched deceased donor renal grafts. Eligible patients were randomized to induction with either basiliximab or daclizumab. Both groups received cyclosporine microemulsion (CsA Neoral), mycophenolate mofetil, and methylprednisolone. An intent-to-treat analysis of 1-year data assessed the incidence of acute rejection episodes, the renal graft function, the safety, and the patient and graft survivals. Among 127 patients, six (10.0%) and seven (11.5%) patients experienced biopsy-confirmed acute rejection at 12 months, in the basiliximab and the daclizumab groups, respectively. Two renal grafts were lost in the basiliximab and six in the daclizumab cohort, one of them due to rejection. One basiliximab and two daclizumab patients died. Hospital treatment was required for 25 and 33 infections in basiliximab and daclizumab groups, respectively. One basal cell carcinoma of skin was detected. One hypersensitivity reaction was observed with daclizumab. At 12 months, serum creatinine was 101+/-28 micromol/L with basiliximab and 109+/-41 micromol/L with daclizumab. Patient survival was 98.4% with basiliximab and 96.7% with daclizumab, and graft survival was 96.8% versus 90.8%, respectively. No significant differences were observed between the groups. Basiliximab or daclizumab combined with triple therapy was an efficient and safe immunosuppression strategy, demonstrated with low incidence of acute rejection episodes, an acceptable adverse event profile, excellent graft function, and high survival rates in adult recipients within the first year after deceased donor renal transplantation.

Effective immunoprophylaxis with basiliximab plus triple therapy in renal transplantation: five-year single-center experience.

We studied prospectively the efficacy and safety of basiliximab combined with triple immunosuppression in adult recipients of > or = 1 HLA-mismatched deceased donor renal grafts. All studied patients received equal immunosuppressive drugs: 20 mg infusion of basiliximab on day 0 and on day 4, cyclosporine microemulsion (Neoral), mycophenolate mofetil, and methylprednisolone. An analysis of 1-year data assessed the incidence of acute rejection episodes, safety of this therapy, renal graft function, and patient and graft survivals. One hundred seventy-two patients were studied. The HLA-antigen mismatches were 2.9 +/- 0.9 (mean +/- SD), and the cold ischemia time was 22.0 +/- 7.5 hours. Fifty-three (31.5%) patients experienced delayed graft function. At 12 months, 5 (3.0%) patients experienced acute rejection. Six renal grafts were lost, but not from rejection. Two patients died. Sixty-six infections required treatment in the hospital. One carcinoma of cervix (in situ) and two basal cell carcinomas of skin were detected. Hypersensitivity reactions and cytokine-release syndrome were not observed. At 12 months, serum creatinine was significantly higher (119 +/- 46 micromol/L; P < .001) in patients with delayed graft function than in patients with immediate graft function (99 +/- 26 micromol/L). Patient and graft survivals were 98.8% and 97.1%, respectively. Basiliximab combined with this triple therapy was an efficient and safe immunosuppression strategy, demonstrated with very low incidence of acute rejections, an acceptable adverse event profile, excellent graft function, and high short-term survival rates in adult recipients of deceased donor renal transplant.

Follow-up of kidney graft recipients with cyclosporine-associated hemolytic-uremic syndrome and thrombotic microangiopathy.

The study was based on 462 patients who underwent kidney transplantation from 1986 through 2004. Cyclosporine (CsA)-related thrombotic microangiopathy (TMA) was observed in 15 (3.3%) patients. The donor ages ranged from 9 to 51 years and cold ischemia times from 12 to 31 hours. Hemolytic-uremic syndrome (HUS) developed 2 weeks after transplantation in 14 patients and later in 1 subject. Histopathologic examination demonstrated glomerular-type TMA in 3 patients, a mixed type (glomerular and vascular) in 11 patients, and a nonspecific mesangial widening with tubulointerstitial lesions in 1 patient. Follow-up biopsies revealed resolution of TMA in 4 patients and chronic vascular TMA in 1 patient. Six patients with mixed-type TMA needed transient hemodialysis. No patient with the glomerular-type TMA needed dialysis (P = .103), and 14 of 15 had good resolution of graft function after CsA dose reduction or temporary discontinuation or continuation of optimal dose. Only 1 graft with mixed-type TMA was lost due to irreversible HUS. The mean glomerular filtration rate (GFR), predicted by the Nankivell equation, was 76 +/- 13 mL/min and 80 +/- 27 mL/min at 1 month after discharge for glomerular- and mixed-type TMA, respectively (P > .05). GFRs 1 year after HUS were 82 +/- 12 and 87 +/- 21 mL/min for the glomerular and the mixed types, respectively (P > .05). We concluded that the mixed-type TMA was associated with a more severe early clinical course than the glomerular-type TMA. The 1-year prognosis was good in the majority of patients, with no significant differences between those with the glomerular- and mixed-type TMA.

Shape of the left ventricle and its computer modelling.

A simple computer program was made to draw different left ventricle shapes in order to support the theory of elongation and to get a visual presentation of the shape of the left ventricle. Experimental data, obtained from echocardiography and Simpson's rule, were used for this program. The results yielded different shapes under different physiological circumstances, indicating the sensitivity of the method. It was concluded that these figures (shapes) support the use of elongation as a shape index.

Elongation as a new shape index for the left ventricle.

OBJECTIVES: This study was done to quantify the shape of the left ventricle (LV). It was proposed that the shape of the LV is intimately related to its performance and that its elongation (ELO) is a sensitive measure of this performance. The performance was tested against classical cardiovascular parameters. METHODS: Using echocardiography and Simpson's rule, the endocardial surface area of the LV was calculated noninvasively with a simple experimental-mathematical model at enddiastole and endsystole. ELO as shape index was derived from the endocardial surface area of the LV with a simple formula. The endocardial surface area of the LV and ELO were determined in volunteers, in patients with mild heart failure and in patients with severe heart failure. RESULTS: The normal value of endocardial surface area of LV at enddiastole is 138.3 cm2 while the normal value at endsystole is 99 cm2. The endocardial surface area of the LV is significantly bigger in patients with mild heart failure than in volunteers (p < 0.01) while the parameters ELO, ejection fraction and Doppler measurements are similar. The normal values of ELO at diastole and systole are 12 and 25 respectively. The value of ELO at endsystole is lower only in patients with severe heart failure. This means a more spherical shape and poor systolic function of the LV. CONCLUSION: ELO is usefull as quantitative and qualitative index of left ventricular shape. ELO could be integrated and applied with new diagnostic tools such three-dimensional and contrast echocardiography.