Neurocognitive profile in HIV subjects on INSTI-regimen- one year follow up: Is there room for optimism?

The introduction of antiretroviral therapy (ART) has successfully changed the clinical course of people with HIV, leading to a significant decline in the incidence of HIV-related neurocognitive disorders. Integrase strand transferase inhibitors (INSTI) are recommended and preferred first-line ART for the treatment of HIV-1 infection in ART-naïve subjects. This type of therapy regimen is expected to have higher CNS penetration, which may bring more cognitive stability or even make significant cognitive improvement in people with HIV. The study aimed to follow up on neurocognitive performance in HIV subjects on two types of INSTI therapy regimens at two-time points, one year apart. The study sample consisted of 61 ART naïve male participants, of which 32 were prescribed raltegravir (RAL) and 29 dolutegravir (DTG). There was no significant difference between subsamples according to the main sociodemographic (age, education level) and clinical characteristics (duration of therapy, nadir CD4 cells level, CD4 cells count, CD8 cells, CD4/CD8 ratio). For neurocognitive assessment, six measures were used: general cognitive ability (MoCA test), verbal fluency (total sum score for phonemic and category fluency), verbal working memory (digit span forward), cognitive capacity (digit span backwards), sustained attention (Color Trail Test 1), and divided attention (Color Trail Test 2). In both therapy groups (RAL and DTG), there was no significant decrease in neurocognitive achievement on all used measures over a one-year follow-up in both therapy groups. A statistically significant interactive effect of time and type of therapy was found on the measure of divided attention-DTG group showed slight improvement, whereas RAL group showed slight decrease in performance. During the one-year follow-up of persons on INSTI-based regimen, no significant changes in cognitive achievement were recorded, which suggests that the existing therapy can have a potentially positive effect on the maintenance of neurocognitive achievement.

Additive Effect of Metabolic Syndrome on Brain Atrophy in People Living with HIV-Magnetic Resonance Volumetry Study.

With people living with HIV (PLWH) reaching the senium, the importance of aging-related comorbidities such as metabolic syndrome (MS) becomes increasingly important. This study aimed to determine the additive effect of MS on brain atrophy in PLWH. This prospective study included 43 PLWH, average age of 43.02 ± 10.93 years, and 24 healthy controls, average age of 36.87 ± 8.89 years. PLWH were divided into two subgroups: without MS and with MS, according to NCEP ATP III criteria. All patients underwent brain magnetic resonance imaging (MRI) on a 3T clinical scanner with MR volumetry, used for defining volumes of cerebrospinal fluid (CSF) spaces and white and grey matter structures, including basal ganglia. A Student's t-test was used to determine differences in brain volumes between subject subgroups. The binary classification was performed to determine the sensitivity and specificity of volumetry findings and cut-off values. Statistical significance was set at p < 0.05. PLWH presented with significantly lower volumes of gray matter, putamen, thalamus, globus pallidus, and nc. accumbens compared to healthy controls; cut-off values were: for gray matter 738.130 cm3, putamen 8.535 cm3, thalamus 11.895 cm3, globus pallidus 2.252 cm3, and nc. accumbens 0.715 cm3. The volumes of CSF and left lateral ventricles were found to be higher in PLWH with MS compared to those without MS, where, with a specificity of 0.310 and sensitivity of 0.714, it can be assumed that PLWH with a CSF volume exceeding 212.83 cm3 are likely to also have MS. This suggests that PLWH with metabolic syndrome may exhibit increased CSF volume above 212.83 cm3 as a consequence of brain atrophy. There seems to be an important connection between MS and brain volume reduction in PLWH with MS, which may add to the accurate identification of persons at risk of developing HIV-associated cognitive impairment.

Sagittal Abdominal Diameter as the Best Predictor of Metabolic Syndrome in HIV-Infected Men on Antiretroviral Therapy.

BACKGROUND: The interaction of human immunodeficiency virus (HIV), host and antiretroviral therapy causes a range of metabolic disorders that can be characterized as a metabolic syndrome (MetS) that increases the cardiovascular risk. MetS involves central obesity, which can be detected using different anthropometric parameters. OBJECTIVE: To assess the abilities of different anthropometric parameters in the prediction of MetS in HIV-infected men on ART. METHOD: The study involved 92 male participants (mean age 44.46±10.38 years), divided into two groups: with and without MetS. All subjects underwent biochemical evaluation (triglycerides, HDL-cholesterol, fasting glucose), blood pressure measurement and anthropometric assessment: body mass, body height, body mass index (BMI), body fat mass, body circumferences (chest, upper arm, forearm, waist, hip, proximal and middle thigh and calf), sagittal abdominal diameter (SAD), skinfold thicknesses (subscapular, anterior and posterior upper arm, anterior and lateral forearm, abdominal, supraspinal, thigh and calf), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), waist-to-thigh ratio (WTR), sagittal abdominal diameter-to-body height ratio (SADH), body adiposity index (BAI) and conicity index. MetS was specified according to IDF criteria. RESULTS: Subjects with MetS had statistically significant higher values of all anthropometric parameters except middle thigh circumference, calf skinfold and body height. According to ROC analysis and Binary Logistic Regression, SAD has been shown as the best predictor of MetS with a predictive value of 21.40 cm (AUC:0.91), followed by WHR with a predictive value of 0.93. CONCLUSION: Sagittal abdominal diameter is the strongest anthropometric indicator of MetS in HIV-infected patients on ART.

Influence of physical activity on endothelial function in people living with HIV.

INTRODUCTION: Decreased physical activity is a major cardiovascular risk factor that is particularly pronounced in people living with HIV (PLHIV), who are more susceptible to endothelial dysfunction and accelerated atherosclerosis than the general population due to multiple mechanisms. The aim of the present study was to analyse whether regular physical activity is capable of improving endothelial function measured by flow-mediated dilatation (FMD) in PLHIV. METHODS: We performed FMD measurement in 38 PLHIV, along with the assessment of their regular physical activity level using the International Physical Activity Questionnaire (IPAQ). RESULTS: Flow-mediated dilatation results in PLHIV were 0.31 ± 0.06 mm and 7.34% ± 1.41% for absolute and relative FMD, respectively. IPAQ results showed that the average weekly level of physical activity was 3631.1 ± 1526.7 MET-min/week, whereas the average daily sitting time was 287.3 ± 102.7 min/day. Predictors jointly accounted for 48% (adjusted value 42%) of FMD variance. Bootstrapped confidence levels revealed that physical activity had a statistically significant effect on the outcome [beta = 0.517, 2.5% confidence interval (CI) = 0.205, 97.5% CI = 0.752]. CONCLUSION: Physical activity represents a widely available and uncostly tool that is capable of improving endothelial function and overall cardiovascular health in PLHIV.

Relation of Steatosis to Neurocognitive Function in People Living with HIV.

BACKGROUND: In HIV negative population metabolic syndrome and steatosis are related to poorer neurocognitive (NC) performance. We investigated if similar relation exists in people living with HIV (PLWH). METHODS: We included male PLWH aged 20-65, with undetectable viral load for at least 6 months. Data on levels of education, anthropometric measurements, CD4 levels, ART, markers of metabolic syndrome, smoking and concurrent treatment were collected from database. Concentrations of TNF-α and IL-6 were measured. An ultrasound was used to establish the presence of steatosis, visceral fat thickness and carotid intima media thickness. An extensive NC assessment was done by an experienced neuropsychologist. Cognitive domains were defined as executive functions, divergent reasoning, visuo-constructional abilities, delayed recall and working memory and learning and were measured using a battery of 12 tests. RESULTS: 88 PLWH were included (mean age 39,9 years), 51% on PIs, 46% on NNRTI; 20,4% had metabolic syndrome, 42% patients had steatosis. Weak but statistically significant negative correlations were found between the presence of metabolic syndrome, steatosis and VFT and cognitive domains (divergent reasoning, delayed recall and working memory). Poorer perfomrance in the domains of divergent reasoning and in the working memory were found in participants with steatosis (p=0,048 and 0,033 respectively). CONCLUSION: Although the sample size was relatively small, our results show consistent correlations between the observed neurocognitive variables and metabolic parameters. As central obesity is one of the contributors to NCI, it would be one of the modifiable factors to prevent further neurocognitive decline.

Associations of visceral fat thickness and anthropometric measurements with non-alcoholic fatty liver disease development in male patients mono-infected with human immunodeficiency virus.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease in mono-infected (without concomitant hepatitis B and/or C virus infection) people living with human immunodeficiency virus (HIV). The proper and on time identification of at-risk HIV-positive individuals would be relevant in order to reduce the rate of progression from NAFLD into non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. OBJECTIVES: The aim of this study was to explore visceral fat thickness (VFT) and anthropometric measurements associated with the development of NAFLD in patients mono-infected with HIV and on long-standing combination antiretroviral therapy (cART). METHOD: Eighty-eight (n = 88) HIV-positive male patients, average age 39.94 ± 9.91 years, and stable on cART, were included in this prospective study. VFT was measured using ultrasonography. Anthropometric measurements included body mass index (BMI), waist-to-hip ratio (W/H), waist-to-height ratio (WHtR), waist and hip circumference (WC, HC). Differences between variables were determined using the chi-square test. The receiver operating characteristic (ROC) curve and the Youden index were used to determine optimal cut-off values of VFT and hepatic steatosis. The area under the curve (AUC), 95% confidence intervals, sensitivity and specificity are reported for the complete sample. Significance was set at p < 0.05. RESULTS: Patients with steatosis had significantly higher values of BMI, HC, WC, W/H and WHtR. The VFT was higher in patients with steatosis (p < 0.001). Specifically, VFT values above 31.98 mm and age > 38.5 years correlated with steatosis in HIV-positive patients, namely sensitivity 89%, specificity 72%, AUC 0.84 (95% CI, 0.76-0.93, p < 0.001), with the highest Youden index = 0.61. The sensitivity of the age determinant above this cut-off point was 84%, specificity 73% and AUC 0.83 (95% CI, 0.75-0.92, p < 0.001), with the highest Youden index of 0.57. CONCLUSION: In the absence of more advanced radiographic and histological tools, simple anthropometric measurements and VFT could assist in the early identification of persons at risk of hepatic steatosis in low- and middle-income regions.

Executive Functions Rating Scale and Neurobiochemical Profile in HIV-Positive Individuals.

The set of complex cognitive processes, that are necessary for the cognitive control of behavior, known as executive functions (EF), are traditionally associated with the prefrontal cortex and commonly assessed with laboratory based tests and conventional neuroimaging. In an effort to produce a more complete and ecologically valid understanding of executive functioning, the rating scales have been developed in order to assess the behavioral aspects of EF within an everyday real-world context. The main objective of this study was to examine the relationship between behavioral aspects of EF measured by rating scale and neurometabolic profile in neurologically asymptomatic HIV-positive individuals under cART, measured using multi-voxel magnetic resonance spectroscopy (mvMRS). The sample comprised 39 HIV-positive adult male participants, stable on cART and 39 healthy HIV-negative volunteers. Both groups completed the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). HIV-positive group additionally underwent long-echo three-dimensional mvMRS to determine neurobiochemical profile in the anterior cingulate gyrus (ACG) of both hemispheres. Three dominant neurometabolites were detected: N-acetyl aspartate (NAA), the neuronal marker; choline (Cho), the marker of membrane metabolism and gliosis and creatine (Cr), the reference marker. Ratios of NAA/Cr and Cho/Cr were analyzed. The initially detected significant correlations between age, current CD4, BRIEF-A subscales Inhibit, Shift, Emotional Control, Plan/Organize, Self Monitoring and ratios of NAA/Cr and Cho/Cr in the dorsal and ventral part of the ACG, were lost after the introduction of Bonferroni corrections. Also, there were no significant differences between HIV-positive and HIV-negative group on any of BRIEF-A subscales. Such results possibly imply that stable cART regimen contributes to preservation of behavioral aspects of EF in asymptomatic HIV-positive individuals. Even though a subtle deficit in some aspects of EF might exist, it would not be manifest if behavioral aspect was assessed using EF rating scale. Further explanation might be that expected HIV-related changes in neurometabolic profile of the ACG under cART are not reflected in those behavioral aspects that are measurable by EF rating scale.

Neurocognitive profile of HIV-positive adults on combined antiretroviral therapy: A single-centre study in Serbia.

The advent of combined antiretroviral therapy (cART) has prolonged the life expectancy of HIV + individuals and decreased the incidence of HIV-associated dementia. However, milder forms of neurocognitive impairment remain common and are often associated with poor daily functioning and lower medication adherence. This paper presents a research aimed at exploring the cognitive status differences between HIV + subjects (N = 39) on cART therapy and a group of demographically comparable healthy subjects (N = 39) in Serbia. The significance of differences between the HIV + group and the healthy control group in performance in six cognitive domains was tested using the multivariate analysis of variance. Results showed a lower performance of the HIV + group in the domains of attention/working memory, and learning. HIV-related clinical variables were not significantly associated with cognitive performance. An older age in HIV + patients was significantly related to a lower performance in all six cognitive domains, as opposed to healthy subjects, implying a synergistic interaction between HIV and aging, resulting in accentuated cognitive difficulties. Our findings suggest that even with the absence of a subjective experience of cognitive deficits and with a good basic control of the illness, a certain degree of cognitive deficit can be observed in the tested group.

Neuroendocrine disorder in chronic fatigue syndrome

Background/aim: Neuroendocrine disorders are considered a possible pathogenetic mechanism in chronic fatigue syndrome (CFS). The aim of our study was to determine the function of the hypothalamic-pituitary-adrenal axis (HPA) and thyroid function in women of reproductive age suffering from CFS. Materials and methods: The study included 40 women suffering from CFS and 40 healthy women (15-45 years old). Serum levels of cortisol (0800 and 1800 hours), ACTH, total T4, total T3, and TSH were measured in all subjects. The Fibro Fatigue Scale was used for determination of fatigue level. Results: Cortisol serum levels were normal in both groups. The distinctively positive moderate correlation of morning and afternoon cortisol levels that was observed in healthy women was absent in the CFS group. This may indicate a disturbed physiological rhythm of cortisol secretion. Although basal serum T4, T3, and TSH levels were normal in all subjects, concentrations of T3 were significantly lower in the CFS group. Conclusion: One-time hormone measurement is not sufficient to detect hormonal imbalance in women suffering from CFS. Absence of a correlation between afternoon and morning cortisol level could be a more representative factor for detecting HPA axis disturbance.

Non-cirrhotic Portal Hypertension Associated with Didanosine and Streptococcus agalactiae Infection: A Case Report.

BACKGROUND: Non-Cirrhotic Portal Hypertension (NCPH) is a rare but potentially fatal liver disorder described in patients treated with anti-retroviral therapy for Human Immunodeficiency Virus (HIV). In particular, the most important predisposing factor to its development has been identified as prolonged exposure to Didanosine (ddI). The clinical entity of NCPH is characterized by an increase in portal pressure due to pre- or intra-hepatic causes, in absence of liver cirrhosis. However, the exact pathogenesis remains poorly understood, and due to its rarity, the diagnosis is often delayed. OBJECTIVE: We herein report a case in which ddI administration, with concomitant spontaneous bacterial peritonitis by Streptococcus agalactiae, has induced NCPH in a HIV male patient. CONCLUSION: NPCH should be suspected when HIV patient with an history of ddI treatment presents liver decompensation.

Prediction of brain atrophy using three drug scores in neuroasymptomatic HIV-infected patients with controlled viremia

ABSTRACTBACKGROUND: Despite potent antiretroviral therapy, HIV still causes brain damage. Better penetration into the CNS and efficient elimination of monocyte/macrophages reservoirs are two main characteristics of an antiretroviral drug that could prevent brain damage. The aim of our study was to assess efficacy of three antiretroviral drug scores to predict brain atrophy in HIV-infected patients.METHODS:A cross sectional study consisting of 56 HIV-infected patients with controlled viremia, who had no clinically evident neurocognitive impairment. All patients had MRI of the head. A typical T2 transversal slice was analyzed and ventricles-brain ratio (VBr) as an overall brain atrophy index was calculated. Three antiretroviral drug scores were used and correlated with VBr: 2008 and 2010 CNS penetration effectiveness scores (SCPE2008 and SCPE2010) and the recently established monocyte efficacy (SME) score. A p-value <0.05 was considered significant.RESULTS:SCPE2010 was significantly associated with VBr in both univariate (r = -0.285, p = 0.033) and multivariate (ß = -0.299, p = 0.016) regression models, while SCPE2008 was not (r = -0.141, p = 0.300 and ß = -0.156,p = 0.214). SME was associated with VBr in multivariate model only (r = -0.297, p = 0.111 andß = -0.406, p = 0.029). Age and reported duration of HIV infection were also significant predictors of overall brain atrophy in multivariate regression models.CONCLUSIONS:Although based on similar type of research, SCPE2010 is a superior drug score compared to SCPE2008. SME is an efficient drug score in determining brain damage. Both SCPE2010 and SME scores should be taken into account in preventive strategies of brain atrophy and neurocognitive impairment in HIV-infected patients.

Prediction of brain atrophy using three drug scores in neuroasymptomatic HIV-infected patients with controlled viremia.

BACKGROUND: Despite potent antiretroviral therapy, HIV still causes brain damage. Better penetration into the CNS and efficient elimination of monocyte/macrophages reservoirs are two main characteristics of an antiretroviral drug that could prevent brain damage. The aim of our study was to assess efficacy of three antiretroviral drug scores to predict brain atrophy in HIV-infected patients. METHODS: A cross sectional study consisting of 56 HIV-infected patients with controlled viremia, who had no clinically evident neurocognitive impairment. All patients had MRI of the head. A typical T2 transversal slice was analyzed and ventricles-brain ratio (VBr) as an overall brain atrophy index was calculated. Three antiretroviral drug scores were used and correlated with VBr: 2008 and 2010 CNS penetration effectiveness scores (ΣCPE2008 and ΣCPE2010) and the recently established monocyte efficacy (ΣME) score. A p-value <0.05 was considered significant. RESULTS: ΣCPE2010 was significantly associated with VBr in both univariate (r=-0.285, p=0.033) and multivariate (ß=-0.299, p=0.016) regression models, while ΣCPE2008 was not (r=-0.141, p=0.300 and ß=-0.156, p=0.214). ΣME was associated with VBr in multivariate model only (r=-0.297, p=0.111 and ß=-0.406, p=0.029). Age and reported duration of HIV infection were also significant predictors of overall brain atrophy in multivariate regression models. CONCLUSIONS: Although based on similar type of research, ΣCPE2010 is a superior drug score compared to ΣCPE2008. ΣME is an efficient drug score in determining brain damage. Both ΣCPE2010 and ΣME scores should be taken into account in preventive strategies of brain atrophy and neurocognitive impairment in HIV-infected patients.

Multivitamin mineral supplementation in patients with chronic fatigue syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS) is characterized by medically unexplained persistent or reoccurring fatigue lasting at least 6 months. CFS has a multifactorial pathogenesis in which oxidative stress (OS) plays a prominent role. Treatment is with a vitamin and mineral supplement, but this therapeutic option so far has not been properly researched. MATERIAL AND METHODS: This prospective study included 38 women of reproductive age consecutively diagnosed by CDC definition of CFS and treated with a multivitamin mineral supplement. Before and after the 2-month supplementation, SOD activity was determined and patients self-assessed their improvement in 2 questionnaires: the Fibro Fatigue Scale (FFS) and the Quality of Life Scale (SF36). Results There was a significant improvement in SOD activity levels; and significant decreases in fatigue (p=0.0009), sleep disorders (p=0.008), autonomic nervous system symptoms (p=0.018), frequency and intensity of headaches (p=0.0001), and subjective feeling of infection (p=0.0002). No positive effect on quality of life was found. CONCLUSIONS: Treatment with a vitamin and mineral supplement could be a safe and easy way to improve symptoms and quality of life in patients with CFS.

Adaptation of marine plankton to environmental stress by glycolipid accumulation.

A systematic investigation of non-phosphorus containing glycolipids (GL) was conducted in the northern Adriatic Sea during two years at two stations with different nutrient loads. GL concentration varied both spatially and temporally, with values of 1.1-21.5 µg/L and 0.4-44.7 µg/L in the particulate and the dissolved fraction, respectively. The highest concentrations were measured during summer in surface waters and at the more oligotrophic station, where GL yields (% of total lipids) were often higher than 20% and 50% in the particulate and dissolved fractions, respectively. To obtain more insight into factors governing GL accumulation autotrophic plankton community structure (pico-, nano- and microplankton fractions), chlorophyll a, heterotrophic bacteria and nutrient concentrations were measured together with hydrographic parameters and sunlight intensity. During the investigated period smaller autotrophic plankton cells (pico- and followed by nanoplankton) prevailed in abundance over larger cells (microplankton), which were found in large numbers in freshened surface samples. Several major findings resulted from the study. Firstly, during PO4 limitation, particularly at the oligotrophic station, enhanced glycolipid instead of phospholipid accumulation takes place, representing an effective phosphate-conserving mechanism. Secondly, results suggest that at seawater temperatures >19 °C autotrophic plankton considerably accumulate GL, probably to achieve thermal stability. Thirdly, high sunlight intensities seem to influence increased GL accumulation; GL possibly plays a role in cell mechanisms that prevent/mitigate photooxidation. And finally, substantial accumulation of GL detected in the dissolved fraction could be related to the fact that GL do not contain biologically relevant elements, like phosphorus, which makes them an unattractive substrate for enzyme activity. Therefore, substantial portion of CO2 could be removed from the atmosphere in P-limited regions during summer via its capture by plankton and conversion to GL.

Lipid and protein oxidation in female patients with chronic fatigue syndrome.

INTRODUCTION: Chronic fatigue syndrome (CFS) is a widely recognized problem, characterized by prolonged, debilitating fatigue and a characteristic group of accompanying symptoms, that occurs four times more frequently in women than in men. The aim of the study was to determine the existence of oxidative stress and its possible consequences in female patients with CFS. MATERIAL AND METHODS: Twenty-four women aged 15-45 who fulfilled the diagnostic criteria for CFS with no comorbidities were recruited and were age matched to a control group of 19 healthy women. After conducting the routine laboratory tests, levels of the lipid oxidation product malondialdehyde (MDA) and protein oxidation protein carbonyl (CO) were determined. RESULTS: The CFS group had higher levels of triglycerides (p = 0.03), MDA (p = 0.03) and CO (p = 0.002) and lower levels of HDL cholesterol (p = 0.001) than the control group. There were no significant differences in the levels of total protein, total cholesterol or LDL cholesterol. CONCLUSIONS: The CFS group had an unfavorable lipid profile and signs of oxidative stress induced damage to lipids and proteins. These results might be indicative of early proatherogenic processes in this group of patients who are otherwise at low risk for atherosclerosis. Antioxidant treatment and life style changes are indicated for women with CFS, as well as closer observation in order to assess the degree of atherosclerosis.

Cystatin C in pre-eclampsia.

OBJECTIVE: To evaluate diagnostic value of cystatin C serum levels as alternative marker of renal function in pre-eclamsia (PE) and compare it with the traditional markers of renal function, creatinine and uric acid. In order to investigate the possible influence of inflammation on biochemical markers of renal function, serum levels of high sensitive CRP were measured (hsCRP). METHODS: In this prospective study markers of kidney function were investigated in two groups of pregnant women: one with PE (n = 32) and the other of healthy pregnant women (n = 60). Serum cystatin C levels were measured as well as levels of traditional renal markers creatinin and uric acid and levels of high sensitive C-reactive protein. RESULTS: Serum levels of cystatin C, creatinine and uric acid were significantly higher in the PE group than in the control group. Serum levels of hsCRP were higher in approximately the same number of patients with PE (50%) as in normal pregnancies (40%), without significant differences in CRP values between the two groups of patients. CONCLUSIONS: Cystatin C serum level may have significant role as a marker of pre-eclampsia specially when used in combination with uric acid levels.

Thiobarbituric acid reactive substances as marker of oxidative stress in pregnancies with pre-eclampsia.

Pre-eclampsia is characterized by increased lipid peroxidation and diminished antioxidant capacity. The aim of the study was to establish concentration of thiobarbituric acid reactive substances as a marker of lipid peroxidation in normal pregnancies and in pregnancies complicated with pre-eclampsia, and to estimate the possibility of using thiobarbituric acid reactive substances as a screening method for development of pre-eclampsia. The study was conducted at the Department of Obstetrics and Gynaecology, Clinical Centre of Vojvodina. The study included 57 singleton pregnancies, gestation > or = 24 weeks, of which 29 were healthy pregnancies and 28 were with pre-eclampsia, defined as systolic arterial pressure of > or = 90 mmHg, diastolic of > or = 145 mmHg, and 24h proteinuria of > or = 300 mg. Thiobarbituric acid reactive substances concentrations evaluated by malondialdehyde equivalent standards (OxiSelect TBARS Assay Kit (malondialdehyde Quantitation), Cell Biolabs' OxiSelect) showed that oxidative stress was more evident in the group with pre-eclampsia, though not statistically significant (p = 0.107). There was no correlation ofthiobarbituric acid reactive substance levels with gestation in either group. The differences between the level of thiobarbituric acid reactive substance concentrations in pre-eclampsia and healthy pregnancies indicate the possibility of using thiobarbituric acid reactive substances as a screening tool for the development of pre-eclampsia. Further studies with larger numbers of patients are needed in order to come to final conclusions.

Chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is defined by a profound, debilitating fatigue, lasting for at least 6 months and resulting in a substantial reduction of occupational, personal, social and educational status. CFS is a relatively poorly recognized clinical entity, although everyday experience shows that there are many patients with CFS symptoms. The incidence and prevalence of CFS remain unknown in most countries; however, the working population is most affected with predominantly female patients in generative period. Although, CFS was first mentioned four centuries ago, mysterious aethiopathogensis of CFS still intrigues scientists as hundreds of studies are still published every year on the subject. About 80 different aetiological CFS factors are mentioned, which can be classified into five basic groups: genetics, immunology, infectious diseases, endocrinology and neuropsychiatry-psychology. Even today the condition is passed established based on the diagnosis by exclusion of organic and psychiatric disorders, which demands a multidisciplinary approach. As the syndrome is often misdiagnosed and mistreated, self-medication is not uncommon in CFS patients'. In addition, such patients usually suffer for years tolerating severe fatigue. Thus, at the moment there are three priorities regarding CFS; understanding pathogenesis, development of diagnostic tests and creating efficient treatment program.

Fever of unknown origin in elderly patients.

INTRODUCTION: Causes of fever of unknown origin are different. It is considered that it can be caused with over 200 different clinical entities. Aetiological causes differ according to different categories of age. Febricity in the elderly is at most the result of autoimmune processes, malignancies, bacterial infections and vasculitis. OBJECTIVE: The aim of this study was to determine the most common characteristics of fever, the most common laboratory, bacterial and viral tests and to analyze applied therapy in patients with unknown febrile state, and to affirm final diagnosis in elderly patients, as well as younger than 65 years old, and to define outcome of disease in both groups of patients. METHODS: Research comprised 100 patients who had been treated at the Infectious Disease Clinic of the Clinical Centre of Vojvodina in Novi Sad, during a three-year period, and in whom fever of unknown origin had been diagnosed. Patients were divided into two homogenous groups of 50 people. The first one (S) consisted of patients older than 65 years, and the second, control group (K) was constituted of patients younger than the age of 65. All of them were chosen by random sample method. RESULTS: Average results of standard laboratory parameters of infection were obtained, such as erythrocyte sedimentation rate (ESR), fibrinogen, CRP, and especially leukocyte, and those were significantly higher in the group of elderly patients. The cause had not been found in 10% of elderly patient group, and in the younger group, not even in the third of patients. Among known causative agents dominant were infections, usually of respiratory and urinary tract, in both tested groups. Even 28% of the elderly had sepsis, and 10% endocarditis. Malignant diseases were more frequent in group of the elderly patients, and immune i.e. systematic disorders were evenly noticed in both groups of patients. CONCLUSION: Despite advanced studies in medicine, and existence of modern diagnostic procedures, fever of unknown origin is still today differential diagnostic problem.

AFM imaging of extracellular polymer release by marine diatom Cylindrotheca closterium (Ehrenberg) Reiman & J.C. Lewin.

Extracellular polysaccharide production by marine diatoms is a significant route by which photosynthetically produced organic carbon enters the trophic web and may influence the physical environment in the sea. This study highlights the capacity of atomic force microscopy (AFM) for investigating diatom extracellular polysaccharides with a subnanometer resolution. Here we address a ubiquitous marine diatom Cylindrotheca closterium, isolated from the northern Adriatic Sea, and its extracellular polymeric substance (EPS) at a single cell level. We applied a simple procedure for AFM imaging of diatom cells on mica under ambient conditions (in air) to achieve visualization of their EPS with molecular resolution. The EPS represents a web of polysaccharide fibrils with two types of cross-linking: fibrils association forming junction zones and fibril-globule interconnections with globules connecting two or more fibrils. The fibril heights were 0.4-2.6 nm while globules height was in the range of 3-12 nm. Polymer networks of native gel samples from the Northern Adriatic and the network formed by polysaccharides extracted from the C. closterium culture share the same features regarding the fibril heights, pore openings and the mode of fibril association, proving that the macroscopic gel phase in the Northern Adriatic can be formed directly by the self-assembly of diatom released polysaccharide fibrils.