Browsing by Author "Dragović, Gordana (23396934400)"

The importance of oral microflora composition in HIV-infected patients is well recognized. However, no studies so far have dealt with age-related changes in periodontal pathogens occurrence in HIV+ individuals. The aim of the present study was to assess and compare temporal changes of bacteria frequency in younger (≥35 years) and older (≥50 years) HIV-infected and non-infected individuals. Bacterial DNA was isolated from buccal swabs of 30 younger and 30 older subjects in both HIV+ and HIV-groups. By means of PCR the following microorganisms were detected: Aggregatibacter actinomycetemcomitans, Eikenella corrodens, Peptostreptococcus micros, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia and Treponema denticola. Oral and periodontal examinations were performed in all subjects. The prevalence of microorganisms was significantly higher in HIV+ patients compared to controls, and their distribution showed a notable shift. The decreasing incidence in HIV-subjects was: Pi

We performed a study to identify factors related to favorable response to highly active-antiretroviral therapy (HAART) in HIV-infected women. A retrospective study was performed on 216 women who had initiated HAART from January 1, 1998 to December 31, 2012, at the HIV/AIDS Center, Belgrade, Serbia. Participants were followed-up for 8.2 ± 3.4 years. The mean age was 37 ± 9.7 years. During follow-up, it was found that 26 patients had died. Clinical AIDS at initiation of HAART was observed in 43.9% patients, while 64.8% had a CD4+ T-cell count below 200 cells/μL. Multivariate analyses revealed that the single factor independently related to a favorable response to HAART was good compliance (odds [OR] ratio for survival = 2.9, 95% confidence intervals [CI] = 1.0-8.6, p = 0.03), while a baseline CD4+ T-cell count below 100 cells/μL, hepatitis C virus coinfection, and aged 40 years and older were all associated with an unfavorable response to HAART (OR = 0.28, 95% CI = 0.15-0.52, p < 0.001; OR = 0.49, 95% CI = 0.22-0.8, p = 0.008; OR = 0.41, 95% CI = 0.21-0.79, p = 0.008, respectively). The estimated 14-year-survival was 100% in patients with sustained viral suppression, regardless of the CD4+ counts achieved (p = 0.6, log-rank). If women with advanced HIV-related immunodeficiency reach and maintain optimal viral suppression during HAART, regardless of the level of immune recovery, and if they continue to maintain this suppression for up to a mean 8 years of treatment, their prognosis may be fairly good, even in resource-limited settings. © 2014 Copyright Taylor and Francis Group, LLC.

Aim: To compare four cardiovascular disease (CVD) risk models and to assess the prevalence of eligibility for lipid lowering therapy according to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, European AIDS Clinical Society Guidelines (EACS), and European Society of Cardiology and the European Atherosclerosis Society (ESC/EAS) guidelines for CVD prevention in HIV infected patients on antiretroviral therapy. Methods: We performed a cross-sectional analysis of 254 consecutive HIV infected patients aged 40 to 79 years who received antiretroviral therapy for at least 12 months. The patients were examined at the HIV-treatment centers in Belgrade and Zagreb in the period February-April 2011. We compared the following four CVD risk models: the Framingham risk score (FRS), European Systematic Coronary Risk Evaluation Score (SCORE), the Data Collection on Adverse Effects of Anti-HIV Drugs study (DAD), and the Pooled Cohort Atherosclerotic CVD risk (ASCVD) equations. Results: The prevalence of current smoking was 42.9%, hypertension 31.5%, and hypercholesterolemia (>6.2 mmol/L) 35.4%; 33.1% persons were overweight, 11.8% were obese, and 30.3% had metabolic syndrome. A high 5-year DAD CVD risk score (>5%) had substantial agreement with the elevated (≥7.5%) 10-year ASCVD risk equation score (kappa = 0.63). 21.3% persons were eligible for statin therapy according to EACS (95% confidence intervals [CI], 16.3% to 27.4%), 25.6% according to ESC/EAS (95% CI, 20.2% to 31.9%), and 37.9% according to ACC/AHA guidelines (95% CI, 31.6 to 44.6%). Conclusion: In our sample, agreement between the high DAD CVD risk score and other CVD high risk scores was not very good. The ACC/AHA guidelines would recommend statins more often than ESC/EAS and EACS guidelines. Current recommendations on treatment of dyslipidemia should be applied with caution in the HIV infected population.

Background: Data about correlation of interleukins (IL-1 α IL-1 β IFN γ IL-2, IL-4, IL-6, IL-8, IL-10), adipocytokines (leptin, adiponectin, monocyte chemoattractant protein-1 (MCP-1), resistin, plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor alpha (TNFα), ferritin, C reactive protein (CRP) and vascular endothelial growth factor (VEGF) with homeostasis model assessment (HOMA) in HIV/AIDS patients are still limited. Therefore the aim of this study was to evaluate the possible correlations of serum levels of PAI-1, leptin and ferritin with HOMA in HIV/AIDS patients treated with combined antiretroviral therapy (cART). Methods: This cross-sectional study included 64 HIV/AIDS patients, all Caucasians, receiving cART at the HIV/AIDS Centre, Belgrade, Serbia. PAI-1, leptin, ferritin and insulin levels were measured using the Metabolic Syndrome Array I (Randox Laboratories Ltd., London, UK), while adiponectin and resistin levels were measured using Metabolic Syndrome Array II (Randox Laboratories Ltd., London, UK), interleukins (IL-1 α IL-1 β IFN γ IL-2, IL-4, IL-6, IL-8, IL-10), MCP-1, TNF-α as well as VEGF was measured using Cytokine Array I (Randox Laboratories Ltd., London, UK). Insulin resistance was determined using the homeostasis model assessment index (HOMA). Multicollinearity of independent variables in multivariate model was analyzed using Variance Inflation Factor. Results: Correlation analysis revealed significant correlations between HOMA and waist circumference, body mass index, patients’ age, number of cART combinations and triglycerides (p = 0.001, p = 0.001, p = 0.050, p = 0.044, p = 0.002, respectively). HOMA negatively correlated with levels of high density lipoprotein (HDL) (Rho = −0.282; p = 0.025). PAI-1 (Rho = 0.334; p= 0.007) and leptin (Rho = 0.492; p = 0.001) together with ferritin (Rho = 0.396, p = 0.001) positively and significantly correlated with HOMA. Levels of IL-1 α IL-1 β IFN γ IL-2, IL-4, IL-6, IL-8, IL-10, adiponectin, MCP-1, resistin, TNF-α CRP and VEGF did not significantly correlate with HOMA. Further, multiple logistic regression showed that there is a statistically significant correlation between PAI, leptin and ferritin with HOMA levels (p = 0.042; p < 0.001, p = 0.009). Conclusions: We showed significant correlation between PAI-1, leptin and ferritin, independently of each other with HOMA, in HIV/AIDS patients on cART. © 2018 Elsevier Inc.

Background: Data about correlation of interleukins (IL-1 α IL-1 β IFN γ IL-2, IL-4, IL-6, IL-8, IL-10), adipocytokines (leptin, adiponectin, monocyte chemoattractant protein-1 (MCP-1), resistin, plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor alpha (TNFα), ferritin, C reactive protein (CRP) and vascular endothelial growth factor (VEGF) with homeostasis model assessment (HOMA) in HIV/AIDS patients are still limited. Therefore the aim of this study was to evaluate the possible correlations of serum levels of PAI-1, leptin and ferritin with HOMA in HIV/AIDS patients treated with combined antiretroviral therapy (cART). Methods: This cross-sectional study included 64 HIV/AIDS patients, all Caucasians, receiving cART at the HIV/AIDS Centre, Belgrade, Serbia. PAI-1, leptin, ferritin and insulin levels were measured using the Metabolic Syndrome Array I (Randox Laboratories Ltd., London, UK), while adiponectin and resistin levels were measured using Metabolic Syndrome Array II (Randox Laboratories Ltd., London, UK), interleukins (IL-1 α IL-1 β IFN γ IL-2, IL-4, IL-6, IL-8, IL-10), MCP-1, TNF-α as well as VEGF was measured using Cytokine Array I (Randox Laboratories Ltd., London, UK). Insulin resistance was determined using the homeostasis model assessment index (HOMA). Multicollinearity of independent variables in multivariate model was analyzed using Variance Inflation Factor. Results: Correlation analysis revealed significant correlations between HOMA and waist circumference, body mass index, patients’ age, number of cART combinations and triglycerides (p = 0.001, p = 0.001, p = 0.050, p = 0.044, p = 0.002, respectively). HOMA negatively correlated with levels of high density lipoprotein (HDL) (Rho = −0.282; p = 0.025). PAI-1 (Rho = 0.334; p= 0.007) and leptin (Rho = 0.492; p = 0.001) together with ferritin (Rho = 0.396, p = 0.001) positively and significantly correlated with HOMA. Levels of IL-1 α IL-1 β IFN γ IL-2, IL-4, IL-6, IL-8, IL-10, adiponectin, MCP-1, resistin, TNF-α CRP and VEGF did not significantly correlate with HOMA. Further, multiple logistic regression showed that there is a statistically significant correlation between PAI, leptin and ferritin with HOMA levels (p = 0.042; p < 0.001, p = 0.009). Conclusions: We showed significant correlation between PAI-1, leptin and ferritin, independently of each other with HOMA, in HIV/AIDS patients on cART. © 2018 Elsevier Inc.

Objective: Gastrointestinal (GI) disorders are estimated to be frequent among general population. Various types of traditional and complementary therapies, primarily phytotherapy, can be used for prevention and treatment of many diseases and conditions, including GI complaints. Thus, the aim of this study was to investigate the patterns of use of medicinal herbs in treatment and prevention of GI disorders, together with their efficacy and safety. Methods: A prospective, repeated cross-sectional, descriptive study was conducted in the form of a specifically created questionnaire, filled in by consumers and/or patients in pharmacies on the territory of Autonomous Province of Vojvodina, Republic of Serbia. All data were statistically analyzed in Microsoft Excel 2007. Results: In the total number of 1137 patients, 10.4% declared themselves as consumers of phytopreparations for GI disorders. The most common diseases were constipation (44%) and dyspepsia (23%). The most frequently used preparations contained laxatives (with both anthraquinones and dietary fibers), artichoke and silymarin. Iberogast® was also frequently used. Pharmacists were the main source of recommendation for the most adequate herbal remedies. At the same time, phytopreparations were well tolerated, with no major side effects, and were evidently or presumably effective. Conclusions: Some mild and moderate GI disorders seem to be treated frequently with phytopreparatons. Various herbal remedies are well accepted by patients, and the phytopreparations seem to have favorable ratio of safety and efficacy. Further integration into conventional medicine will improve the quality of the products used and provide a rational plan of use of medicinal plants. © 2019 Elsevier Ltd

Objective: Gastrointestinal (GI) disorders are estimated to be frequent among general population. Various types of traditional and complementary therapies, primarily phytotherapy, can be used for prevention and treatment of many diseases and conditions, including GI complaints. Thus, the aim of this study was to investigate the patterns of use of medicinal herbs in treatment and prevention of GI disorders, together with their efficacy and safety. Methods: A prospective, repeated cross-sectional, descriptive study was conducted in the form of a specifically created questionnaire, filled in by consumers and/or patients in pharmacies on the territory of Autonomous Province of Vojvodina, Republic of Serbia. All data were statistically analyzed in Microsoft Excel 2007. Results: In the total number of 1137 patients, 10.4% declared themselves as consumers of phytopreparations for GI disorders. The most common diseases were constipation (44%) and dyspepsia (23%). The most frequently used preparations contained laxatives (with both anthraquinones and dietary fibers), artichoke and silymarin. Iberogast® was also frequently used. Pharmacists were the main source of recommendation for the most adequate herbal remedies. At the same time, phytopreparations were well tolerated, with no major side effects, and were evidently or presumably effective. Conclusions: Some mild and moderate GI disorders seem to be treated frequently with phytopreparatons. Various herbal remedies are well accepted by patients, and the phytopreparations seem to have favorable ratio of safety and efficacy. Further integration into conventional medicine will improve the quality of the products used and provide a rational plan of use of medicinal plants. © 2019 Elsevier Ltd

From 12-15th October 2011, the 13th European AIDS Conference/EACS took place in Belgrade, Serbia (www.eacs-conference2011.com) at the Sava Center. The conference was organized under the auspices of the European AIDS Clinical Society (EACS), a nonprofit group of European physicians, clinicians, and researchers dealing with the clinical management of HIV (www.europeanaidsclinicalsociety.org). © GERMS 2011.

From 12-15th October 2011, the 13th European AIDS Conference/EACS took place in Belgrade, Serbia (www.eacs-conference2011.com) at the Sava Center. The conference was organized under the auspices of the European AIDS Clinical Society (EACS), a nonprofit group of European physicians, clinicians, and researchers dealing with the clinical management of HIV (www.europeanaidsclinicalsociety.org). © GERMS 2011.

We appraised the relationship between the biological and the chronological age and estimated the rate of biological aging in HIV-infected patients. Two independent biomarkers, the relative telomere length and iron metabolism parameters, were analyzed in younger (,35) and older (.50) HIV-infected and uninfected patients (control group). In our control group, telomeres of younger patients were significantly longer than telomeres of older ones. However, in HIV-infected participants, the difference in the length of telomeres was lost. By combining the length of telomeres with serum iron, ferritin, and transferrin iron-binding capacity, a new formula for determination of the aging process was developed. The life expectancy of the healthy population was related to their biological age, and HIV-infected patients were biologically older. The effect of antiretroviral HIV drug therapies varied with respect to the biological aging process. IMPORTANCE This article is focused on the dynamics of human aging. Moreover, its interdisciplinary approach is applicable to various systems that are aging. Copyright © 2023 Toljić et al.

We appraised the relationship between the biological and the chronological age and estimated the rate of biological aging in HIV-infected patients. Two independent biomarkers, the relative telomere length and iron metabolism parameters, were analyzed in younger (,35) and older (.50) HIV-infected and uninfected patients (control group). In our control group, telomeres of younger patients were significantly longer than telomeres of older ones. However, in HIV-infected participants, the difference in the length of telomeres was lost. By combining the length of telomeres with serum iron, ferritin, and transferrin iron-binding capacity, a new formula for determination of the aging process was developed. The life expectancy of the healthy population was related to their biological age, and HIV-infected patients were biologically older. The effect of antiretroviral HIV drug therapies varied with respect to the biological aging process. IMPORTANCE This article is focused on the dynamics of human aging. Moreover, its interdisciplinary approach is applicable to various systems that are aging. Copyright © 2023 Toljić et al.

Aims: Lopinavir (LPV) is not a first-line regimen. According to recent WHO data, LPV usage in low- and middle-income countries accounted for approximately 52% of the adult and 23% of the paediatric protease inhibitor market in 2017. Since LPV is a substrate for the SLCO1B1 (OATP1B1) transporter, the aim of this study was to assess the impact of SLCO1B1 polymorphisms (rs11045819, rs4149032 and rs4149056) on LPV trough plasma concentrations (Ctrough) in Serbian patients. Methods: Plasma samples from 104 HIV/AIDS Caucasians were collected. LPV Ctrough was quantified using liquid-chromatography-mass spectrometry. Genotyping was carried out using real-time-PCR-based allelic discrimination. One-way analysis of variance, t test and linear regression were used for data analysis. Results: The overall mean (SD) LPV Ctrough was 5885 ± 2755 ng/mL. Significant differences were between patients with different rs11045819 genotypes: CC (LPV median Ctrough = 6072 ng/mL, interquartile range (IQR) = 4318–7617 ng/mL), CA (LPV median Ctrough = 4987 ng/mL, IQR = 4300–6295 ng/mL) and AA (LPV median Ctrough = 3648 ng/mL, IQR = 1949–4072 ng/mL) (P =.005). Significant differences were also observed according to rs4149032 genotype: CC (LPV median Ctrough = 6027 ng/mL, IQR =4548–8250 ng/mL), CT (LPV median Ctrough = 5553 ng/mL, IQR = 4300–6888 ng/mL) and TT (LPV median Ctrough = 4408 ng/mL, IQR = 3361–5233 ng/mL) (P =.007). For rs4149056 a statistically significant difference between T-homozygotes (LPV median Ctrough = 5434 ng/mL, IQR = 3855–6830 ng/mL), heterozygotes (LPV median Ctrough = 6707 ng/mL, IQR = 5088–8063 ng/mL) and C-homozygotes (LPV median Ctrough = 13906 ng/mL, IQR = 12946–14866 ng/mL) was observed (P =.002). In multivariate regression analysis, only the SLCO1B1 rs4149056 polymorphism was independently associated with higher LPV Ctrough (β = 2834.5 [1442–4226.9] ng/mL [P =.001]). Conclusions: Our results demonstrate a statistically significant influence of the SLCO1B1 rs4149056 polymorphism on higher LPV Ctrough in Caucasian HIV/AIDS patients. © 2020 The British Pharmacological Society

Aims: Lopinavir (LPV) is not a first-line regimen. According to recent WHO data, LPV usage in low- and middle-income countries accounted for approximately 52% of the adult and 23% of the paediatric protease inhibitor market in 2017. Since LPV is a substrate for the SLCO1B1 (OATP1B1) transporter, the aim of this study was to assess the impact of SLCO1B1 polymorphisms (rs11045819, rs4149032 and rs4149056) on LPV trough plasma concentrations (Ctrough) in Serbian patients. Methods: Plasma samples from 104 HIV/AIDS Caucasians were collected. LPV Ctrough was quantified using liquid-chromatography-mass spectrometry. Genotyping was carried out using real-time-PCR-based allelic discrimination. One-way analysis of variance, t test and linear regression were used for data analysis. Results: The overall mean (SD) LPV Ctrough was 5885 ± 2755 ng/mL. Significant differences were between patients with different rs11045819 genotypes: CC (LPV median Ctrough = 6072 ng/mL, interquartile range (IQR) = 4318–7617 ng/mL), CA (LPV median Ctrough = 4987 ng/mL, IQR = 4300–6295 ng/mL) and AA (LPV median Ctrough = 3648 ng/mL, IQR = 1949–4072 ng/mL) (P =.005). Significant differences were also observed according to rs4149032 genotype: CC (LPV median Ctrough = 6027 ng/mL, IQR =4548–8250 ng/mL), CT (LPV median Ctrough = 5553 ng/mL, IQR = 4300–6888 ng/mL) and TT (LPV median Ctrough = 4408 ng/mL, IQR = 3361–5233 ng/mL) (P =.007). For rs4149056 a statistically significant difference between T-homozygotes (LPV median Ctrough = 5434 ng/mL, IQR = 3855–6830 ng/mL), heterozygotes (LPV median Ctrough = 6707 ng/mL, IQR = 5088–8063 ng/mL) and C-homozygotes (LPV median Ctrough = 13906 ng/mL, IQR = 12946–14866 ng/mL) was observed (P =.002). In multivariate regression analysis, only the SLCO1B1 rs4149056 polymorphism was independently associated with higher LPV Ctrough (β = 2834.5 [1442–4226.9] ng/mL [P =.001]). Conclusions: Our results demonstrate a statistically significant influence of the SLCO1B1 rs4149056 polymorphism on higher LPV Ctrough in Caucasian HIV/AIDS patients. © 2020 The British Pharmacological Society

Background The role of interleukins in the pathogenesis of lipodystrophy in HIV/AIDS-patients is still not understood. The aim of this study was to evaluate the relationship between serum levels of interleukins between HIV/AIDS-patients with or without lipodystrophy, as well as between different subgroups of lipodystrophy (lipoatrophy, lipohypertrophy, mixed-fat-redistribution) and patients without lipodystrophy. Methods Cross-sectional study of 66 HIV/AIDS patients, all Caucasians. Serum levels of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10) were measured using Cytokine-Array-1 on Evidence Investigator, Biochip Array Technology. The associations between interleukins and anthropometric and metabolic variables were estimated by Spearman-correlation. Analysis of covariance with bootstrapping method (ACBM) was used to examine relationship between interleukins and lipodystrophy categories adjusted for confounding variables. Results The lipodystrophy was observed in 29 (44%) patients, while 15 (52%) had lipoatrophy, 4 (14%) lipohypertrophy and 10 (34%) patients had mixed fat redistribution. There were 37 (56%) patients without lipodystrophy. Significantly lower levels of IL-4 and IL-10 were observed in lipodystrophy vs. non-lipodystrophy (p = 0.008; p = 0.027, respectively). No differences were found relating IL-1α, IL-1β, IL-2, IL-6 and IL-8 levels in lipodystrophy vs. non-lipodystrophy. In patient subgroup with lipoatrophy, significantly lower levels of IL-4 and IL-10 were found when compared to non-lipodystrophy (p = 0.043; p = 0.031, respectively). In lipohypertrophy subgroup significantly lower levels of IL-4 were found when compared to non-lipodystrophy (p = 0.003). In order to estimate the correlation of IL-4 and IL-10 and the presence of lipodystrophy, ACBM showed that correlation of IL-4 levels in patients with lipodystrophy remains statistically significant (p = 0.004) in all types of lipodystrophy: lipoatrophy, lipohypertrophy and mix-fat-redistribution (p = 0.027; p = 0.009; p = 0.017, respectively) after adjustment for age, BMI. Conclusions IL-4 and IL-10 levels were significantly lower in lipodystrophy vs. non-lipodystrophy. According to our knowledge, we showed for the first time significant correlation between IL-4 levels and lipodystrophy development in HIV/AIDS patients. © 2017

Background The role of interleukins in the pathogenesis of lipodystrophy in HIV/AIDS-patients is still not understood. The aim of this study was to evaluate the relationship between serum levels of interleukins between HIV/AIDS-patients with or without lipodystrophy, as well as between different subgroups of lipodystrophy (lipoatrophy, lipohypertrophy, mixed-fat-redistribution) and patients without lipodystrophy. Methods Cross-sectional study of 66 HIV/AIDS patients, all Caucasians. Serum levels of interleukins (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10) were measured using Cytokine-Array-1 on Evidence Investigator, Biochip Array Technology. The associations between interleukins and anthropometric and metabolic variables were estimated by Spearman-correlation. Analysis of covariance with bootstrapping method (ACBM) was used to examine relationship between interleukins and lipodystrophy categories adjusted for confounding variables. Results The lipodystrophy was observed in 29 (44%) patients, while 15 (52%) had lipoatrophy, 4 (14%) lipohypertrophy and 10 (34%) patients had mixed fat redistribution. There were 37 (56%) patients without lipodystrophy. Significantly lower levels of IL-4 and IL-10 were observed in lipodystrophy vs. non-lipodystrophy (p = 0.008; p = 0.027, respectively). No differences were found relating IL-1α, IL-1β, IL-2, IL-6 and IL-8 levels in lipodystrophy vs. non-lipodystrophy. In patient subgroup with lipoatrophy, significantly lower levels of IL-4 and IL-10 were found when compared to non-lipodystrophy (p = 0.043; p = 0.031, respectively). In lipohypertrophy subgroup significantly lower levels of IL-4 were found when compared to non-lipodystrophy (p = 0.003). In order to estimate the correlation of IL-4 and IL-10 and the presence of lipodystrophy, ACBM showed that correlation of IL-4 levels in patients with lipodystrophy remains statistically significant (p = 0.004) in all types of lipodystrophy: lipoatrophy, lipohypertrophy and mix-fat-redistribution (p = 0.027; p = 0.009; p = 0.017, respectively) after adjustment for age, BMI. Conclusions IL-4 and IL-10 levels were significantly lower in lipodystrophy vs. non-lipodystrophy. According to our knowledge, we showed for the first time significant correlation between IL-4 levels and lipodystrophy development in HIV/AIDS patients. © 2017

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In recent years mathematical modeling has become a valuable tool in the analysis of infectious disease dynamics at both individual and population level. Mathematical models allow us to extrapolate from current information about the natural history of a disease, therapy/intervention outcome, state and progress of an outbreak, to predict the future and, most importantly, to quantify the uncertainty in these predictions, thus, increasingly gaining the ability to perform as a link between basic science, clinical medicine and public health. © GERMS 2012.

In recent years mathematical modeling has become a valuable tool in the analysis of infectious disease dynamics at both individual and population level. Mathematical models allow us to extrapolate from current information about the natural history of a disease, therapy/intervention outcome, state and progress of an outbreak, to predict the future and, most importantly, to quantify the uncertainty in these predictions, thus, increasingly gaining the ability to perform as a link between basic science, clinical medicine and public health. © GERMS 2012.

[No abstract available]