The six scoring systems' prognostic value in predicting 24-hour mortality in septic patients.

OBJECTIVE: The use of scoring systems contributes to the faster identification of septic patients, especially those at a high risk of a fatal outcome. The best scoring system does not exist, so the search for the optimal one is always current. The aim of this study is to estimate the prognostic value of the six scoring systems in predicting 24-hour mortality among septic patients presented at the emergency department. PATIENTS AND METHODS: An observational retrospective study was conducted in the Emergency Triage Room (ETR) of the Emergency Center (EC) at the University Clinical Center of Serbia (UCCS) in Belgrade. Consecutive septic patients, according to the Sepsis-3 definition, with or without shock, presented to the ETR and then hospitalized in Intensive Care Units were included in the study. Mortality data within 24 h and on the 28th day were extracted from the Hospital information system or the National mortality database. Scoring systems including sequential organ failure assessment (SOFA), quick sequential organ failure assessment (qSOFA), systemic inflammatory response syndrome (SIRS), National early warning score (NEWS), sepsis patient evaluation in the emergency department (SPEED), and mortality in emergency department sepsis (MEDS) were analyzed for all patients utilizing the available data. The primary outcome of this study was death within 24 hours of triage. Receiver operating characteristic (ROC) analysis was used to determine the most effective scoring system. Lactate was then added to this system to enhance its predictive accuracy. RESULTS: Nineteen out of 120 patients included in the study (15.8%) experienced death within 24 hours of triage. The twenty-eight-day mortality rate was 55%. SOFA score demonstrated the highest predictive value for 24-hour mortality but was only moderately predictive overall, with an area under the receiver operating curve (AUC) of 0.755 (95% CI 0.625-0.885). SPEED, MEDS, and NEVS exhibited modest discriminatory power [0.673 (95% CI 0.543-0.803), 0.665 (95% CI 0.536-0.794), 0.630 (95% CI 0.528-0.724)], while SIRS and qSOFA remained insignificant in predicting 24-hour mortality. The predictive value of the SOFA score was increased by the addition of lactate (AUC 0.865, 95% CI 0.736-0.995; p=0.0081). All scores demonstrated better and satisfactory predictive power for 28-day mortality. CONCLUSIONS: SOFA, with the addition of lactate, is a complex but reliable tool for the early stratification of septic patients who are presenting at an emergency department.

Evaluation of the self-assessment knowledge regarding cardiopulmonary resuscitation in medical students at the University of Belgrade.

OBJECTIVE: Cardiopulmonary resuscitation (CPR) is a vital skill that can improve the outcome of patients with sudden cardiac arrest. To raise awareness about CPR some countries have introduced an obligatory First Aid Course (FAC), usually done parallelly to a driver's license (DL). While expected of doctors to know CPR, the curriculum of some medical schools does not seem to have enforced measures to improve that knowledge. The aim was to have students self-evaluate their current knowledge of CPR, comparing it before university and whether it improved during their studies. SUBJECTS AND METHODS: A cross-sectional study was conducted in October 2020 using an anonymous questionnaire among students at the Faculty of Medicine in Belgrade (studies in English). RESULTS: A total of 172 (66.7%) students possessed a DL, of which 39.8% felt they were ready, 45.8% felt neutral, and 14.4% felt unable to perform CPR. The total number of students that completed a FAC during their studies was 165. Analysis was performed on the ability assessment data after the first FAC during studies, comparing it to FAC for DL and assessments at the end of studies. No statistically significant difference was observed in the level of self-reported ability to perform CPR, while a statistically significant difference was found in ability assessments when comparing only the FAC for the DL, and the one after the first FAC during medical studies, with students feeling more prepared after the FAC for DL. Across the sample, 90.2% of the students wished they had more CPR training during their medical studies. CONCLUSIONS: From this study, it may conclude that students wish and need more CPR training in their curriculum.

Oxidative stress and inflammation parameters-novel biomarkers for idiopathic pulmonary fibrosis.

OBJECTIVE: The pathophysiological mechanisms of idiopathic pulmonary fibrosis (IPF) are not well elucidated. It is assumed that oxidative stress and inflammation are the key underlying culprits for its onset and progression. To gain deeper insight into these processes, we have evaluated several oxidative stress parameters, inflammation markers [i.e., high sensitivity C-reactive protein (hsCRP), serum amyloid A1 (SAA1)], soluble programmed cell death-ligand 1 (sPD-L1), and 25-hydroxyvitamin D [25(OH)D] in IPF patients. PATIENTS AND METHODS: Biochemistry analyses were done in 30 consecutive IPF patients and 30 age and gender-matched healthy control group (CG). RESULTS: IPF patients had significantly higher advanced oxidation protein products (p<0.001), pro-oxidant-antioxidant balance (p=0.010), total oxidative status (p<0.001), and ischemia modified albumin (p<0.001) compared to CG. Lower total antioxidant status and total sulfhydryl groups (tSGH) and significantly higher sPD-L1, hsCRP (p<0.001 for all), SAA1 proteins (p=0.014) and [25(OH)D] severe deficiency [11.0 (9.6-15.1) nmol/L] in IPF patients compared to CG were observed. Paraoxonase 1 activity and hsCRP level were lower, while tSHG and sPD-L1 were higher in IPF patients with more severe disease (i.e., II+III stage compared to I stage, p<0.05 for all). CONCLUSIONS: IPF patients are in a state of profound oxidative stress compared to healthy people. The inflammatory component of the disease was confirmed by higher hsCRP and SAA1, but lower [25(OH)D] in IPF than in healthy people. Also, higher levels of sPD-L1 in patients with IPF compared to healthy individuals suggest that sPD-L1 may have a significant role in immune response in IPF.

Polyphenol rich extracts of Geranium L. species as potential natural antioxidant and antimicrobial agents.

OBJECTIVE: Plants and plant extracts are of great scientific interest due to the chemical diversity and pharmacological properties of present bioactive molecules. The Geranium L. species are widely used in ethnomedicine. In the current study, the total phenolic and tannin content, antioxidant and antimicrobial activity of methanol extracts of eight Geranium species were investigated. MATERIALS AND METHODS: The total phenolic and tannin content were determined by the FC method. Antioxidant capacity was evaluated in FRAP, DPPH, and biochemical assays, while antimicrobial activity was examined using the broth microdilution method. RESULTS: The high total phenolic (170.64-636.32 mg GAE/g dry extract) and tannin content (37.80-414.02 mg GAE/g DE), along with significant total antioxidant (FRAP values 1.13-8.80 mmol Fe2+/g) and DPPH radical scavenging activity (SC50 values 4.24-34.52 µg/mL) were observed. The prominent antioxidant capacity was confirmed in biochemical assays (OS values -1.47 - -13.02). The extracts exhibited significant antimicrobial activity against ATTC strains (MICs dominantly in the range of 12.5-200 µg/mL) as well as against clinical isolates of E. coli (MICs mostly 50 and 100 µg/mL). The pronounced antioxidant and antimicrobial activity can be due to the high phenolic content, particularly due to the presence of hydrolyzable tannins. CONCLUSIONS: Based on the high content of polyphenols, pronounced antioxidant and antimicrobial activities, the examined extracts are promising natural antioxidant and antimicrobial agents with the potential medicinal purpose and use as a functional food.

Lactococcus lactis and Lactobacillus salivarius differently modulate early immunological response of Wistar rats co-administered with Listeria monocytogenes.

In the light of the increasing resistance of bacterial pathogens to antibiotics, one of the main global strategies in applied science is development of alternative treatments, which would be safe both for the host and from the environmental perspective. Accordingly, the aim of this study was to test whether two lactic acid bacteria (LAB) strains, Lactococcus lactis BGBU1-4 and Lactobacillus salivarius BGHO1, could be applied as safe supplements for Listeria infection. Two major research objectives were set: to compare the effects of BGBU1-4 and BGHO1 on early immune response in gut tissue of Wistar rats co-administered with Listeria monocytogenes ATCC19111 and next, to test how this applies to their usage as therapeutics in acute ATCC19111 infection. Intestinal villi (IV), Peyer's patches (PP) and mesenteric lymph nodes (MLN) were used for the analysis. The results showed that BGHO1 increased the mRNA expression of innate immune markers CD14, interleukin (IL)-1ß and tumour necrosis factor (TNF)-α in PP and IV, and, in parallel, caused a decrease of listeriolysin O (LLO) mRNA expression in same tissues. In MLN of BGHO1 treated rats, LLO expression was increased, along with an increase of the expression of OX-62 mRNA and CD69, pointing to the activation of adaptive immunity. On the other hand, in BGBU1-4 treated rats, there was no reduction of LLO mRNA expression and no induction of innate immunity markers in intestinal tissue. Additionally, CD14 and IL-1ß, as well as LLO, but not OX-62 mRNA and CD69 expression, were elevated in MLN of BGBU1-4 treated rats. However, when applied therapeutically, both, BGBU1-4 and BGHO1, lowered Listeria count in spleens of infected rats. Our results not only reveal the potential of LAB to ameliorate Listeria infections, but suggest different immunological effects of two different LAB strains, both of which could be effective in Listeria elimination.

NMDA receptor-deficient mice display sexual dimorphism in the onset and severity of behavioural abnormalities.

N-methyl-d-aspartate (NMDA) receptor-deficient mice can be used to understand the role that NMDA receptors (NMDARs) play in the pathophysiology of neurodevelopmental disorders such as schizophrenia. Genetically modified mice with low levels of NR1 subunit (NR1 knockdown mice) have reduced receptor levels throughout development, and have robust abnormalities in behaviours that are relevant to schizophrenia. We traced the onset and severity of these behaviours at three developmental stages to understand when in development the underlying circuits depend on intact NMDAR function. We examined social behaviour, working memory, executive function, locomotor activity and stereotypy at 3, 6 and 12 weeks of age in NR1 knockdown mice and their wild-type littermates. We discovered that each of these behaviours had a unique developmental trajectory in mutant mice, and males showed an earlier onset and severity than females in several behaviours. Hyperlocomotion was most substantial in juvenile mice and plateaued in adult mice, whereas stereotypy progressively worsened with age. Impairments in working memory and sociability were sexually dimorphic, with deficits first detected in peri-adolescent males but only detected in adult females. Interestingly, executive function was most impaired in peri-adolescent mice of either sex. Furthermore, while juvenile mutant mice had some ability to problem solve in the puzzle box test, the same mice lost this ability when tested 4 weeks later. Our studies highlight key developmental periods for males and females in the expression of behaviours that are relevant to psychiatric disorders.

Ovarian cortex transplantation in the baboon: comparison of four different intra-abdominal transplantation sites.

BACKGROUND: Several sites have been used for ovarian cortex transplantation (OCT) in humans. The present study was designed to evaluate different intra-abdominal transplantation sites in the baboon to gain further knowledge about alternative transplantation sites in a human setting. METHODS: Autologous fresh OCTs were performed in 12 baboons (Papio anubis). Four different sites were tested: the free portion of the omentum (OMF), the portion of the omentum adjacent to the spleen (OMS), the pouch of Douglas (D) and the pelvic wall on the psoas muscle (PW). Cortex survival, follicle density, cyclicity and hormonal levels were compared between the different sites, 3 and 6 months after transplantation. RESULTS: Macroscopically, antral follicles were only found in the OMS and OMF locations, which also showed a higher proportion of follicle-containing cortex at light microscopy (OMF 71.4%, OMS 83.3% versus PW 58.8% and D 40%, P< 0.05). Higher densities of primordial [OMF: 3.54 (0-13.18) follicles/grid, OMS: 3.85 (0-8.53), PW: 0 (0-13.25), D 0 (0-1.33), P< 0.05] and primary follicles [OMF: 3.54 (0-18.52), OMS: 3.85 (0-1), PW: 0 (0-4.58), D 0 (0-0.25), P< 0.05] was also found in the omental locations. CONCLUSIONS: Omental locations provide a better site, in terms of follicle survival, for intra-abdominal OCT in the baboon compared with the pelvic wall and the D.

Anaesthesia in colorectal carcinoma surgery at the Clinic for Digestive Surgery from 1997 to 2007.

BACKGROUND: Colorectal cancers are one of the most present neoplasms in human population. This pathology is one of the most frequent ones at the Clinic for Digestive Surgery in Belgrade. AIM: To investigate if there were any changes in both number and structure of patients with colorectal cancers (age, gender, co-morbidity) as well as in both type and duration of surgical procedures and in providing and maintaining anaesthesia in patients with this disease. METHODS: This is a retrospective study. Research materials were anaesthesiological cards written for patients undergoing surgery in order to treat colorectal cancers at the Clinic for Digestive surgery in both 1997 and 2007. Demographics, co-morbidity, ASA score were the parameters we followed in our survey as well as the type of the resection and duration of these surgical interventions. Besides that providing and maintaining anaesthesia and balance of circulatory volume were considered too. RESULTS: The number of the colorectal surgical interventions has been increased up to 489 (13.1% of all) in 2007 comparing to the number of 379 (13.55% of all) in 1997. The percentage has remained the same because the number of all surgical procedures has been increased. The percentage of the rectal resections is increased highly significante in 2007 (50.1% in 1997; 62.6% in 2007). During the same year the duration of the operations was shortened (mean value 176.31 minutes in 1997, 157.5 minutes in 2007). In 2007 highly statistically significant is bigger amount of colloid and crystalloid infusions that were given for supplementation of circulatory volume (mean value 3294.89 ml in 2007; 2552.22 ml in 1997). On the other hand lower amount of blood was given in 2007 than in 1997 (mean value 102.76 opposite to 488.07) what is statisticly significant. The number of the patients with co-morbidities is not statisticly importantly changed in these two followed years. Anaesthesiology technique has been changed and is monitored by higher use of inhalation anesthetics. They were used more in 2007 (29.65%) for these types of surgical procedures than in 1997 when they had been used almost never. CONCLUSION: In these two followed years there have been significant changes in surgical interventions (type and duration of the operation). Surgical teams are higher specialised for the procedures they use modern technology such as stapplers have better equipment for diagnosing the illnes. The use of modern inhalation anaesthetics has been increased along with reduced amount of blood and derivates used for supplementation of circulatory volume.

Evaluation of Hypericum perforatum oil extracts for an antiinflammatory and gastroprotective activity in rats.

Oil extracts of Hypericum perforatum L. (Oleum Hyperici) were prepared in three different ways according to the prescriptions from traditional medicine. Variability of constituents and biological activity were evaluated in the obtained oil extracts. The carrageenan-induced rat paw edema test has been used for screening the antiinflammatory activity, while the indomethacin-induced rat gastric mucosa damage test was used for evaluation of gastroprotective activity. All examined oil extracts possessed antiinflammatory and gastroprotective activity. Among them, the oil extract prepared by maceration with 96% ethanol, followed by extraction with sunflower oil by heating on a water bath (extract 2), in a dose of 1.25 mL/kg p.o., exhibited the highest antiinflammatory effect (95.24 +/- 11.66%) and gastroprotective activity (gastric damage score of 0.21 +/- 0.12). The same oil extract had the highest content of quercetin and I3,II8-biapigenin (129 +/- 9 microg/mL and 52 +/- 4 microg/mL, respectively). Quercetin and I3,II8-biapigenin exhibited antiinflammatory activity similar to those of indomethacin as well as significant gastroprotective activity. The results provide evidence for the usage of Oleum Hyperici as an antiinflammatory and gastroprotective agent, which has been based previously only on ethnopharmacological claims.

Choroidal sclerosis in localized scleroderma (morphea en plaque).

Plaque morphea is a superficial type of morphea (localized scleroderma) which is characterized by various fibrotic areas of the dermis without systemic features. We present a 63-year-old man with morphea en plaque. The skin on his forearms and feet was taut, thickened and hidebound with scattered telangiectatic changes. Autoantibody profile was obtained and only ANA were positive (1:80). The patient had a decreased vision in the only functional, left eye. Our case is specific because the patient negated any kind of health problem, meaning the morphea and visual deterioration were of outstanding importance for him. Choroidal sclerosis and fundus appearance was extremely impressive and, to our knowledge, this is the first report of such unique case of ocular involvement in the literature.

Adaptation and validation of a telephone questionnaire--Serbian version for case detection of rheumatoid arthritis and spondyloarthropathy (multicentric Eular study).

OBJECTIVE: To adapt and validate a telephone questionnaire for case detection of rheumatoid arthritis (RA) and spondyloarthropathies (SpA) in the Serbian population. METHODS: A questionnaire, developed by the French Society of Rheumatology and successfully tested in France, was adapted to the Serbian language using a cross-cultural adaptation process. It was validated in 150 patients: 50 with RA, 50 with SpA and 50 with degenerative rheumatic disorders. They were recruited from Institute of Rheumatology in Belgrade, hospital registry, years 2001 and 2002. The questionnaire validity was assessed in reference to clinical diagnosis and ACR 1987 and ESSG 1991 classification criteria. A logistic regression model was used for RA-control and SpA-control comparison to identify the set of items that best discriminates these groups. RESULTS: Cross-cultural adaptation of the Questionnaire was successfully achieved, verifying its equivalence with the original (semantic, idiomatic, experiential, conceptual). According to the logistic regression, two items selected for RA provided 92.1% agreement when using either clinical diagnosis or ACR classification criteria as a standard. SpA-control comparison included five items providing 96.8% agreement with clinical diagnosis and four items providing 94.1% agreement with ESSG criteria. Results of the present study are similar to those found in the French study. CONCLUSION: Validation results of the telephone questionnaire, translated and adapted to the Serbian language, confirm that it can be used as a detection tool for RA and SpA cases in the population of Serbia, whose diagnoses would have to be further confirmed.

Suppression of experimental autoimmune myocarditis by sodium fusidate (fusidin).

Fusidic acid and its sodium salt sodium fusidate (fusidin) are widely used antibiotics that possess immunomodulating properties. It has been shown that fusidin ameliorates the course of several organ-specific immunoinflammatory diseases and thus we investigated the effect of fusidin on myosin-induced experimental autoimmune myocarditis (EAM) in rats, a well-established animal model for human giant cell myocarditis and postmyocarditis dilated cardiomyopathy (DCM). Fusidin at doses of 80 mg kg(-1) was administrated i.m. to male Dark Agouti (DA) rats, either from days 0 to 10 (early treatment group), or from days 10 to 20 (late treatment group) after induction of EAM. Efficacy of fusidin treatment was determined on day 21 of EAM development. It was observed that both early and late treatment with fusidin markedly ameliorated clinical, histological and immunohistochemical signs of the disease. The treated rats had significantly decreased incidence of EAM, heart weight and heart weight/body weight ratio (Hw/Bw) compared with untreated animals. In contrast to the severe myocardial damage and cellular infiltration in the EAM rats, there was only focal infiltration of inflammatory cells in the myocardium of the treated rats. In both treated groups the mean microscopic score was markedly lower compared with vehicle-treated animals. In addition, the number of CD4+, ED1+ and OX6+ cells was significantly lower in myocardium of fusidin-treated rats than that in untreated group. The present findings suggest that fusidin exhibited both early and late therapeutical effect in EAM.

The Serbian version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Serbian language of the parentís version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Serbian CHAQ-CHQ were fully validated with 3 forward and 1 backward translations. A total of 139 subjects were enrolled: 79 patients with JIA (30% systemic onset, 28% polyarticular onset, 6% extended oligoarticular subtype, and 36% persistent oligoarticular subtype) and 60 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Serbian version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

Localization of the tetrodotoxin-resistant sodium channel NaN in nociceptors.

Tetrodotoxin-resistant sodium currents contribute to the somal and axonal sodium currents of small diameter primary sensory neurons, many of which are nociceptive. NaN is a recently described tetrodotoxin-resistant sodium channel expressed preferentially in IB4-labeled dorsal root ganglion (DRG) neurons. We employed an antibody raised to a NaN specific peptide to show that NaN is preferentially localized along axons of IB4-positive unmyelinated fibers in the sciatic nerve and in axon terminals in the cornea. NaN immunoreactivity was also found at some nodes of Ranvier of thinly myelinated axons of the sciatic nerve, where it was juxtaposed to Kv1.2 potassium channel immunoreactivity. This distribution of NaN is consistent with a role for NaN sodium channels in nociceptive transmission.

Retention of metal ceramic crowns cemented with resin cements: effects of preparation taper and height.

This study investigated the effect of varying crown preparation taper and height on the retention of metal ceramic crowns cemented with resin cements. In part 1, 32 extracted molars were divided into four groups. All groups received complete-veneer crown preparations, two with a 12-degree wall angle and two with a 35-degree wall angle. Crowns were cemented with zinc phosphate and dentin-bonded resin cements. After 24 hour water storage at 37 degrees C, the crowns were separated in tension. Crowns cemented with zinc phosphate were cleaned and recemented with another dentin-bonded resin cement and after similar storage, the crowns were separated. Mean separation forces of resin-cemented crowns were higher than those of crowns cemented with zinc phosphate cement. Mean separation force of 35-degree crowns cemented with one dentin-bonded resin cement was found to be significantly higher than for the 12-degree crowns cemented with zinc phosphate cement. In part II, 32 extracted molars were divided into two groups of complete-veneer crown preparations (group I preparations were 3 mm high and group II were 5 mm high). Crowns for all teeth were cast and cemented with zinc phosphate. After 48 hours' water storage at 37 degrees C, the crowns were separated in tension. Crowns and teeth were then cleaned and each group was subdivided into 2 equal subgroups. In one subgroup of teeth with 3 mm and in one with 5 mm high preparations, the crowns were recemented with one of the two resin cement systems and the other two subgroups were recemented with the other resin cement. After 48-hour water storage, the crowns were separated. Mean separation forces of the resin-cemented crowns were greater than those of crowns cemented with zinc phosphate. Also, mean separation force of 3 mm crowns cemented with one resin cement was significantly greater than the 5 mm crowns cemented with zinc phosphate. Cohesive dentin fracture on separation was observed with some resin-cemented crowns but never with crowns cemented with zinc phosphate.

Retention of paraposts cemented with dentin-bonded resin cements.

The main purpose of this study was to assess the retention of Paraposts cemented with dentin-bonded resin cements in single-rooted teeth with elliptical canals. Forty-two mandibular premolars and canines were used in this study. The crowns of these teeth were removed 1 mm above the cementoenamel junction and the root canals instrumented to a depth of 8 mm to receive size 5 Paraposts. Prepared teeth were divided into six equal groups. Each group was assigned to a different cementation system at random. The six cementation systems used were: Fleck's Cement, Universal Post Cementation Kit, Prisma Universal Bond 3/Biomer, Scotchbond 2/Resiment, All-Bond 2/All-Bond C & B Cement, and Scotchbond Multi-Purpose/Resiment. Following post cementation, the teeth were stored in water at 37 degrees C for 24 hours, after which the posts were subjected to uniaxial tensile force on a testing machine until post separation occurred. Paraposts cemented with Prisma Universal Bone 3/Biomer or with Scotchbond Multi-Purpose/Resiment had significantly greater separation forces than posts cemented with any of the other cementation systems. Adhesive failure of the posts occurred in all of the specimens of the resin cement groups, whereas cohesive failure of the cement occurred in the majority of the specimens of the zinc phosphate cement group. The effects of thermocycling and post length (5 mm versus 8 mm) on the retention of Paraposts cemented with dentin-bonded resin cements were also investigated. Neither thermocycling nor post length had a significant effect on post separation force.