Publications by authors named "Dejan Markovic"

90 Publications

In Vivo Intravascular Pacing Using a Wireless Microscale Stimulator.

Ann Biomed Eng 2021 Feb 3. Epub 2021 Feb 3.

Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.

Millions of patients worldwide are implanted with permanent pacemakers for the treatment of cardiac arrhythmias and conduction disorders. The increased use of these devices has established a growing clinical need to mitigate associated complications. Pacemaker leads, in particular, present the primary risks in most implants. While wireless power transfer holds great promise in eliminating implantable device leads, anatomical constraints limit efficient wireless transmission over the necessary operational range. We thereby developed a transmitter-centered control system for wireless power transfer with sufficient power for continuous cardiac pacing. Device safety was validated using a computational model of the system within an MRI-based anatomical model. The pacer was then fabricated to meet the acute constraints of the anterior cardiac vein (ACV) to enable intravascular deployment while maintaining power efficiency. Our computational model revealed the wireless system to operate at > 50 times below the tissue energy absorption safety criteria. We further demonstrated the capacity for ex vivo pacing of pig hearts at 60 beats per minute (BPM) and in vivo pacing at 120 BPM following pacer deployment in the ACV. This work thus established the capacity for wireless intravascular pacing with the potential to eliminate complications associated with current lead-based deep tissue implants.
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http://dx.doi.org/10.1007/s10439-021-02729-8DOI Listing
February 2021

Antimicrobial potential of irrigants based on essential oils of Cymbopogon martinii and Thymus zygis towards in vitro multispecies biofilm cultured in ex vivo root canals.

Arch Oral Biol 2020 Sep 16;117:104842. Epub 2020 Jul 16.

Department of Pediatric and Preventive Dentistry, University of Belgrade - Faculty of Dental Medicine, Dr Subotića 11, Belgrade, Serbia. Electronic address:

Objective: The objective was to determine the antibiofilm efficacy of Cymbopogon martinii and Thymus zygis essential oils and to estimate the disruption potential of oil-based endodontic irrigants on the multispecies biofilm formed in the root canals of extracted teeth.

Design: The essential oils were characterized (GC-MS), while their antibacterial and cytotoxic properties were detected by microdilution and MTT assays. Particles sizes and polydispersity indices were determined for the irrigants. The isolates from root canals of pediatric patients were identified (MALDI-TOF). The multispecies biofilms were formed from Streptococcus mitis, Streptococcus sanguinis and Enterococcus faecalis. Antibiofilm properties of the essential oils and irrigants were determined by crystal violet and plate counting assay. Statistical analysis was performed by one-way ANOVA.

Results: The screening of biofilm biomass revealed a disruption potential of C. martinii essential oil. The plate counting assay showed the efficacy of both oils in diminishing cell viability: high in biofilms (reduction of logCFU was 2.75-2.87) and moderate in the planktons formed above. The essential oil-based irrigants showed the same antibiofilm activity as in the control (1.5 % sodium hypochlorite) for C. martini and almost 2-fold higher for T. zygis. Successive irrigations with 1.5 % sodium hypochlorite, saline and an oil-based irrigant was more efficient for C. martini than for the control (reductions of logCFU was 1.69 and 1.14, respectively).

Conclusions: Notable activities achieved by essential oils and oil-based irrigants, particularly regarding C. martini, against the biofilm consisting of S. mitis, S. sanguinis, and E. faecalis, are expected to encourage further research in endodontics.
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http://dx.doi.org/10.1016/j.archoralbio.2020.104842DOI Listing
September 2020

Surgical Challenges of Heart Mate 3 Pump Implantation in Aneurysmally Changed Heart Ventricles.

Heart Surg Forum 2020 Jun 4;23(3):E393-E396. Epub 2020 Jun 4.

Department for Heart Transplant, LVAD and ECMO, Clinic for Cardiac surgery, Clinical Center of Serbia, Belgrade, Serbia.

We presented surgical treatment of three patients indicated for implantation of a permanent mechanical circulatory support device and with the associated left ventricular aneurysms. In order to evade the left ventricular rupture, adverse thromboembolic events and provide safe implantation of the inflow cannula, LVAD HM3 implantation together with the reconstruction of the left ventricular aneurysmal wall was performed in two patients. Regarding the third patient, LVAD implantation upon the reconstruction of the left ventricular wall was abandoned because there was no safe location for placement of the inflow cannula.
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http://dx.doi.org/10.1532/hsf.2721DOI Listing
June 2020

Clinical Performance of a Glass-Hybrid System Compared with a Resin Composite in the Posterior Region: Results of a 2-year Multicenter Study.

J Adhes Dent 2020 ;22(3):235-247

Purpose: To compare the clinical performance of a glass hybrid restorative system, EQUIA Forte, with that of a nanohybrid resin composite, Tetric EvoCeram, in two-surface class II cavities.

Materials And Methods: This multicenter, randomized controlled clinical study was conducted at four different dental schools. In total, 360 restorations were placed in patients in need of two class-II, two-surface restorations in the molar region of the same jaw. Each patient received one glass hybrid restoration (EQUIA Forte, GC) and one resin composite restoration (Tetric EvoCeram, Ivoclar Vivadent). Two independent evaluators performed a clinical evaluation of each site after 1 week (baseline), 1 year, and 2 years using the criteria of the FDI World Dental Federation (FDI-2).

Results: The estimated survival rates at the 2-year recall were 93.6% and 94.5% for EQUIA Forte and Tetric EvoCeram, respectively. There were no significant differences in the survival rates or in any of the evaluated esthetic, functional or biological properties between EQUIA Forte and Tetric EvoCeram restorations (p ˃ 0.05).

Conclusion: Both the glass-hybrid restorative system and nanohybrid resin composite showed good clinical performance in moderate to large two-surface class II restorations in a 2-year follow-up.
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http://dx.doi.org/10.3290/j.jad.a44547DOI Listing
May 2020

A Multi-Dimensional Analysis of a Novel Approach for Wireless Stimulation.

IEEE Trans Biomed Eng 2020 12 19;67(12):3307-3316. Epub 2020 Nov 19.

The elimination of integrated batteries in biomedical implants holds great promise for improving health outcomes in patients with implantable devices. However, despite extensive research in wireless power transfer, achieving efficient power transfer and effective operational range have remained a hindering challenge within anatomical constraints.

Objective: We hereby demonstrate an intravascular wireless and batteryless microscale stimulator, designed for (1) low power dissipation via intermittent transmission and (2) reduced fixation mechanical burden via deployment to the anterior cardiac vein (ACV, ∼3.8 mm in diameter).

Methods: We introduced a unique coil design circumferentially confined to a 3 mm diameter hollow-cylinder that was driven by a novel transmitter-based control architecture with improved power efficiency.

Results: We examined wireless capacity using heterogenous bovine tissue, demonstrating >5 V stimulation threshold with up to 20 mm transmitter-receiver displacement and 20° of misalignment. Feasibility for human use was validated using Finite Element Method (FEM) simulation of the cardiac cycle, guided by pacer phantom-integrated Magnetic Resonance Images (MRI).

Conclusion: This system design thus enabled sufficient wireless power transfer in the face of extensive stimulator miniaturization.

Significance: Our successful feasibility studies demonstrated the capacity for minimally invasive deployment and low-risk fixation.
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http://dx.doi.org/10.1109/TBME.2020.2983443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262529PMC
December 2020

Wireless Pacing Using an Asynchronous Three-Tiered Inductive Power Transfer System.

Ann Biomed Eng 2020 Apr 23;48(4):1368-1381. Epub 2020 Jan 23.

Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.

Despite numerous advancements in pacemaker technology for the treatment of cardiac arrhythmias and conduction disorders, lead-related complications associated with these devices continue to compromise patient safety and survival. In this work, we present a system architecture that has the capacity to deliver power to a wireless, batteryless intravascular pacer. This was made possible through a three-tiered, dual-sub-system, four-coil design, which operates on two different frequencies through intermittent remote-controlled inductive power transfer. System efficiency was enhanced using coil design optimization, and validated using numerical simulations and experimental analysis. Our pacemaker design was concepted to achieve inductive power transfer over a 55 mm range to a microscale pacer with a 3 mm diameter. Thus, the proposed system design enabled long-range wireless power transfer to a small implanted pacer with the capacity for intravascular deployment to the anterior cardiac vein. This proposed stent-like fixation mechanism can bypass the multitude of complications associated with pacemaker wires while wireless power can eliminate the need for repeated procedures for battery replacement.
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http://dx.doi.org/10.1007/s10439-020-02450-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086509PMC
April 2020

How Much Country Economy Influences ECC Profile in Serbian Children-A Macro-Level Factor Analysis.

Front Public Health 2019 11;7:285. Epub 2019 Oct 11.

Department of Pediatric and Preventive Dentistry, School of Dental Medicine, University of Belgrade, Belgrade, Serbia.

Serbia has universal health coverage (UHC) for pediatric dental care and similar country distribution for dentists and physicians per 1,000 inhabitants. However, a high prevalence of early childhood caries (ECC) with wide variation across the country was observed in previous studies. This paper aimed to analyze the association between economic and healthcare country macro-level factors with ECC prevalence and treatment. The outcome variables were ECC prevalence and frequency of untreated ECC in 36- to 71-month-olds. Cross-sectional pathfinder survey on a nationally representative sample of children was conducted in order to obtain data. Independent variables included the following: gross domestic product (GDP), social and health care budget beneficiaries' expenditures, local self-government budget, unemployment rate, population density and density of physicians and dentists. Guided by the WHO's Basic Methods for Oral Health Surveys stratified cluster sample, 17 sites were randomly chosen to obtain adequate distribution of data regarding urban, peri-urban and rural areas in each analyzed statistical territorial unit. The variables were analyzed using the independent -test or Mann-Whitney test. A probability value of <0.05 was considered significant. The final sample included 864 children aged 36 to 71 months. Observed prevalence of ECC was 41.1%. Although no statistically significant difference was found, children with ECC compared to healthy children were living in parts of the country with averages of ≈122€ lower GDP per capita, ≈4€ lower social and health care expenditures per capita, 9 inhabitants per km lower population density, almost 7€ per capita lower local self-government budget and a 0.6% higher unemployment rate. Furthermore, although without a statistically significant difference, untreated ECC was associated with ≈302€ lower GDP per capita, ≈12€ lower social and health care expenditures per capita, 34 inhabitants per km lower population density, almost 20€ per capita lower local self-government budget and a 1.7% higher unemployment rate. This study, performed in a nationally representative sample of preschool children, revealed the association of economic macro-level factors with ECC prevalence and its (non-) treatment. Further research on a larger sample is necessary to confirm the results. These findings suggest that most of the public-health efforts regarding prevention and early treatment of ECC should be directed at regions with lower economic performance.
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http://dx.doi.org/10.3389/fpubh.2019.00285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798075PMC
October 2019

Primary Teeth Bite Marks Analysis on Various Materials: A Possible Tool in Children Health Risk Analysis and Safety Assessment.

Int J Environ Res Public Health 2019 07 9;16(13). Epub 2019 Jul 9.

Faculty of Technical Sciences, University of Novi Sad, 21000 Novi Sad, Serbia.

Background: All objects put into a child's mouth could be hazardous in terms of trauma and toxic substance exposure. The aims of this study were to evaluate morphological characteristics of the primary teeth bite marks inflicted on various materials and to assess material wear using experimental model.

Methods: Bite marks were analyzed on five materials: rubber, plastic, foil, wood, and silicone. In order to mimic children mouthing behavior an experimental setup has been designed using primary teeth placed in dentures and children's equipment specimens.

Results: Deciduous teeth make visible and recognizable traces when using physiological forces on all investigated materials. The most significant material loss was revealed in silicone samples, but it has been observed in all material groups, while mouthing with incisors using higher mastication forces were identified as significant predictors for material wear. There were no significant differences between type, species, and morphological-morphometric characteristics of the bite marks which are made by incisors, canines, and molars.

Conclusions: In the range of physiological bite forces, deciduous teeth lead to wear of material from which toys are made while the analysis of bite marks in children equipment could give some information regarding the risk of trauma and exposure.
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http://dx.doi.org/10.3390/ijerph16132434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651703PMC
July 2019

Evaluation of Sealant Penetration in Relation to Fissure Morphology, Enamel Surface Preparation Protocol and Sealing Material.

Oral Health Prev Dent 2019 ;17(4):349-355

Purpose: The objective was to assess the effect of fissure depth and enamel surface preparation protocols on penetration of resin-based, giomer and glass-ionomer fissure sealants.

Materials And Methods: Ninety extracted third molars were assigned into three groups according to the material used. All three groups were subsequently divided depending on tooth preparation: no pretreatment or surface preparation with 10% polyacrylic acid, 37% phosphoric acid, or self-etching adhesive. In addition, Er,Cr:YSGG laser or air abrasion were employed in all subgroups. The penetration was evaluated using scanning electron microscopy.

Results: The groups that were pretreated with an appropriate acid resulted in superior penetration of glass-ionomer and resin-based sealants when compared with other surface preparation protocols (p < 0.05). The exception was teeth treated with both air abrasion and acid etching. Both preparation protocol and fissure depth significantly affected the sealant penetration (p < 0.05), but fissure depth had a greater impact on fissure penetration than did enamel surface pretreatment.

Conclusion: All investigated materials exhibit similar properties regarding sealant penetration. Penetration of a fissure sealant is significantly influenced by the fissure depth. In regard to enamel surface preparation protocol, a pretreatment with phosphoric acid in resin-based and polyacrylic acid in glass-ionomers appears to be essential in obtaining the adequate penetration of a sealing material.
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http://dx.doi.org/10.3290/j.ohpd.a42689DOI Listing
November 2019

Transesophageal Echocardiography-Guided Thrombectomy of Level IV Renal Cell Carcinoma without Cardiopulmonary Bypass.

Braz J Cardiovasc Surg 2019 Mar-Apr;34(2):229-232

Clinic for Vascular and Endovascular Surgery, Clinical Center of Serbia, Belgrade, Serbia.

Advanced renal cell carcinoma accompanied by tumor thrombus in the venous system is present in up to 10% of cases. Extension of tumor thrombus above the diaphragm or into the right atrium represents level IV disease. Level IV tumors are typically treated with sterno-laparotomy approach with or without deep hypothermic circulatory arrest and veno-venous bypass. In this case report, the surgical technique for the resection of advanced RCC were described, with the concomitant use of transesophageal echocardiography for thrombus extraction without the veno-venous or cardiopulmonary bypass.
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http://dx.doi.org/10.21470/1678-9741-2018-0216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436781PMC
June 2019

A 0.338 cm, Artifact-Free, 64-Contact Neuromodulation Platform for Simultaneous Stimulation and Sensing.

IEEE Trans Biomed Circuits Syst 2019 02 21;13(1):38-55. Epub 2018 Dec 21.

Neuromodulation (NM) is the alteration of nervous tissue function through targeted delivery of a stimulus, such as electrical stimulation, into the affected neurological sites in the body. We present a bidirectional NM interface that features 100 mV linear input range and ability to sense data concurrent with stimulation (without blanking). The system includes a flexible 8-driver-to-64-contact custom waveform stimulator able to deliver up to 5.1 mA per driver and a 64-contact sensing unit with online blind artifact rejection unit. This artifact rejection unit removes stimulation artifacts from recorded data and allows extraction of neural biomarkers. The NM interface also features an efficient, integrated power management unit that can support various power delivery options. The proposed 64-contact interface satisfies design requirements of human-grade brain implants at unprecedented level of electronic miniaturization compared to state-of-the-art.
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http://dx.doi.org/10.1109/TBCAS.2018.2889040DOI Listing
February 2019

Nanostructured endodontic materials mixed with different radiocontrast agents-biocompatibility study.

J Mater Sci Mater Med 2018 Dec 10;29(12):190. Epub 2018 Dec 10.

School of Dental Medicine, University of Belgrade, Dr. Subotica 11, Belgrade, 11000, Serbia.

The aim of this study was to investigate the biocompatibility of nanostructured materials based on highly active calcium silicates mixed with different radiocontrast agents in comparison to MTA using in vitro and in vivo model. Morphology of materials' samples was analyzed using SEM while the phase compositions were identified by XRD. pH values of materials' suspensions were conducted by pH-meter. The cytotoxicity of materials' solutions was tested by MTT test (100, 50, 25 and 12.5 mg/ml). LDH and H-thymidine assay were utilized for biocompatibility investigations of materials' eluates (24 h, 7 day and 21 day). Eighteen Guinea pigs were used for intramuscular implantation, as teflon tubes with freshly prepared materials were placed into intramuscular pockets. All samples were composed of round and needle-like particles equally distributed with Ca/Si ratio ~2.7 at%, with the presence of hydrated calcium silicate phases. The pH values of ALBO-MPCA and ALBO-MPCA were high alkaline, while in case of MTA they were lower and continuously declined (p < 0.05). Investigated materials didn't exhibit dose-dependent effect on metabolic activity of L929 cells (p > 0.05). Significant differences in the percentage of cytotoxicity between diluted and undiluted extracts between all tested materials after 24 h and 7 day were noticed (p < 0.05). Increase in L929 cells proliferation was noticed in case of undiluted eluates of ALBO-MPCA and ALBO-MPCA after 7 day (p < 0.05). There were no statistically significant differences in the intensity of inflammatory response between investigated materials and control group after 60 day (p > 0.05). Evaluation of biocompatibility of both ALBO-MPCA and ALBO-MPCA indicate their potential clinical use.
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http://dx.doi.org/10.1007/s10856-018-6200-zDOI Listing
December 2018

Glass-ionomer fissure sealants: Clinical observations up to 13 years.

J Dent 2018 12 25;79:85-89. Epub 2018 Oct 25.

Department of Pediatric and Preventive Dentistry, Dentistry Clinic of Vojvodina, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 12, Novi Sad, Serbia.

Objectives: The aim of this study was to clinically examine the retention and caries-preventive effect of a glass-ionomer material for fissure sealing in newly erupted permanent molars.

Methods: A total of 1736 newly erupted permanent molars were sealed in 480 children aged 5-15 years. Sealants were evaluated yearly and recorded as "completely retained", "partially retained", or "completely lost". Teeth were also evaluated for presence of caries.

Results: Sealants were observed for 2-13 years. The mean follow-up time was 5 years. After one year, 69% of the sealants were fully retained and 21% were partially retained. Thereafter, the cumulative retention rate decreased. Starting from 8th year of follow-up, no "completely retained" sealant could have been observed. At the end of the 13-year follow-up period, 76% of sealants were "completely lost". On the other hand, 99% and 65% of observed occlusal surfaces were caries-free after one and 13 years, respectively. During the observation period, 62 teeth developed caries in surfaces other than occlusal. Survival rates were significantly better for second permanent molars than for first permanent molars (p < 0.001). No influence of caries risk on caries incidence has been noted.

Conclusions: Although the retention rate of the glass-ionomer material for fissure sealing was low, it appears to have prevented dental caries in 65% of newly erupted permanent molars evaluated after thirteen years of placement.

Clinical Significance: The present study reports long-term clinical performance of glass-ionomer fissure sealants in patients with low, moderate and high caries-risk. The study shows that caries risk does not influence survival of glass-ionomer sealants, which proved to be beneficial for long-term caries protection.
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http://dx.doi.org/10.1016/j.jdent.2018.10.007DOI Listing
December 2018

Successful establishment of a left ventricular assist device program in an emerging country: one year experience.

J Thorac Dis 2018 Jun;10(Suppl 15):S1743-S1750

Department for Heart Transplant, LVAD and ECMO, Hospital for Cardiac Surgery, Clinical Center of Serbia, Belgrade, Serbia.

Background: The primary goal of this study was to evaluate the outcomes of patients with end-stage heart failure (HF) who underwent continuous flow left ventricular assist device (CF-LVAD) in a developing country and to compare to those reported by more developed countries. The secondary goal was on determining factors that may be connected to improved survival.

Methods: We prospectively analyzed 47 consecutive patients who underwent CF-LVAD at our institution. After one year the survival and adverse event profiles of patients were evaluated. At 3, 6 and 12 months, the cardiac, renal and liver function outcomes were assessed.

Results: The 30-day, 6-month and 1-year survival rates were 89%, 85% and 80%, respectively. A significant improvement in dimensions and ejection fraction of left ventricle, BNP, functional capacity, blood urea nitrogen (BUN) and total bilirubin (P<0.05 for all) were noticed 3 months post-CF-LVAD implantation, and patients were stable throughout the entire first year follow up. In the group of patients with baseline renal dysfunction (RD) there were significant improvements of renal function (P=0.004), with no changes on follow up. 57% of patients exhibited some kind of adverse event, commonly in the form of bleeding. In multivariate Cox regression analysis renal failure was found to be as an independent risk factor for the overall survival (HR =13.1, P<0.001).

Conclusions: In conclusion, our data extends previous findings from centers of developed countries, that CF-LVAD is an adequate treatment option for patients suffering from end-stage HF, and encourages expansion of CF-LVAD implantation in developing countries with nascent HT program.
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http://dx.doi.org/10.21037/jtd.2018.04.147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035949PMC
June 2018

Alterations in Mesoscopic Oscillations affecting Episodic Memory following Developmental Traumatic Brain Injury.

Exp Neurol 2018 02 21;300:259-273. Epub 2017 Oct 21.

Department of Pediatric Neurology, Neurosurgery, University of California, Los Angeles, Mattel Children's Hospital UCLA, 757 Westwood Plaza, Los Angeles, CA 90095, United States. Electronic address:

Certain deficits of episodic memory among young adults are the delayed consequences of an earlier mild or moderate Traumatic Brain Injury (mTBI). We examined alterations in hippocampal Local Field Oscillations (LFOs) of equivalently-impaired juvenile rodents to identify reliable functional markers of single-incidence mTBI. Two persistent, behavior-dependent, electrophysiological markers of injury were identified in the absence of external physiological symptoms by the analysis of wirelessly-transmitted hippocampal LFOs (3-80Hz) during repeat measures of the Novel Object Recognition (NOR) paradigm. Using a new method for detecting functional network activity at a single recording site, we correlated instantaneous increases in theta frequency and gamma magnitude with injury during periods of functional network organization and dissolution, presented here as Theta Epochs (TEs) and Theta Non-Epochs (TNEs), respectively. We estimated the efficacy of networks across pairs of such sites using new metrics such as the Coherence of Theta Phase (PCOH) and Inter-Epoch Intervals (IEIs) and demonstrated that behavioral deficits observed during the NOR testing stage correspond to electrophysiological deficits recorded during the preceding NOR familiarization stage. Increased theta frequency during TNEs and increased smoothness of PCOH during TEs were found to be robust markers of injury during memory-reliant behaviors.
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http://dx.doi.org/10.1016/j.expneurol.2017.10.021DOI Listing
February 2018

The relationship between causative microorganisms and cardiac lesions caused by infective endocarditis: New perspectives from the contemporary cohort of patients.

J Cardiol 2018 03 18;71(3):291-298. Epub 2017 Oct 18.

Cardiology Department, Clinical Center of Serbia, Belgrade, Serbia; School of Medicine, University of Belgrade, Serbia.

Background: The etiology of infective endocarditis (IE) is changing. More aggressive forms with multiple IE cardiac lesions have become more frequent. This study sought to explore the relationship between contemporary causative microorganisms and IE cardiac lesions and to analyze the impact of multiple lesions on treatment choice.

Methods: In 246 patients hospitalized for IE between 2008 and 2015, cardiac lesions caused by IE were analyzed by echocardiography, classified according to the 2015 European Society of Cardiology guidelines and correlated with microbiological data. We defined a new parameter, the Echo IE Sum, to summarize all IE cardiac lesions in a single patient, enabling comprehensive comparisons between different etiologies and treatment strategies.

Results: Staphylococcus aureus was associated with the development of large vegetation (OR 2.442; 95% CI 1.220-4.889; p=0.012), non-HACEK bacteria with large vegetation (OR 13.662; 95% CI 2.801-66.639; p=0.001), perivalvular abscess or perivalvular pseudoaneurysm (OR 5.283; 95% CI 1.069-26.096; p=0.041), and coagulase-negative staphylococci (CoNS) with leaflet abscess or aneurysm (OR 3.451; 95% CI 1.285-9.266, p=0.014), and perivalvular abscess or perivalvular pseudoaneurysm (OR 4.290; 95% CI 1.583-11.627; p=0.004). The Echo IE Sum significantly differed between different etiologies (p<0.001), with the highest value in non-HACEK and the lowest in streptococcal endocarditis. Patients operated for IE had a significantly higher Echo IE Sum vs those who were medically treated (p<0.001).

Conclusion: None of the IE cardiac lesions is microorganism-specific. However, more severe lesions were caused by S. aureus, CoNS, and non-HACEK bacteria. The highest propensity to develop multiple lesions was shown by the non-HACEK group. Higher Echo IE Sum in patients sent to surgery emphasized the importance of multiple IE cardiac lesions on treatment choice and potential usage of Echo IE Sum in patient management.
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http://dx.doi.org/10.1016/j.jjcc.2017.08.010DOI Listing
March 2018

Kinking of the Outflow Graft, Consequent Ventricular Tachycardia, and the Need for Reoperation in a Patient with Left Ventricular Assist Device.

Heart Surg Forum 2017 08 24;20(4):E139-E141. Epub 2017 Aug 24.

Department for Heart Transplant, LVAD and ECMO, Clinic for Cardiac Surgery, Clinical Center of Serbia, Belgrade, Serbia.

Background: Left ventricular assist devices (LVAD) have become a lifesaving solution for patients awaiting heart transplantation as well as an option to support the failing hearts of non-transplant candidates as a lifelong, or destination therapy (DT). Improvements in LVAD design have enabled greater durability and broader patient applicability, but not without complications. Ventricular arrhythmias in LVAD patients were considered benign in the early days of LVADs, but today are increasingly recognized for their harmful impact on morbidity and quality of life.

Case Presentation: We describe a 53-year-old male who underwent HeartWare left ventricular assist device (HVAD) implantation. During the postoperative period, the patient experienced ventricular tachycardia (VT) during a coughing episode, later found on CT to be due to significant angulation of the outflow graft. Following reoperation to shorten the outflow graft, the patient returned to hemodynamic stability, without VT or other arrhythmias.

Conclusions: Innovative strategies in VT prevention and improved clinical outcomes in LVAD patients may be the result of better understanding of characteristics that predispose these patients to VT. This case report showed that an excessively long outflow graft with considerable kinking created significant VT, but reoperation to correct the length of the graft mitigated further VT complications.
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http://dx.doi.org/10.1532/hsf.1848DOI Listing
August 2017

Apigenin-7-O-glucoside versus apigenin: Insight into the modes of anticandidal and cytotoxic actions.

EXCLI J 2017 23;16:795-807. Epub 2017 May 23.

Department of Plant Physiology, Institute for Biological Research "Siniša Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11000 Belgrade, Serbia.

Bioactive potential of apigenin derivative apigenin-7--glucoside related to its antifungal activity on spp. and cytotoxic effect on colon cancer cells was studied and compared with bioactive potential of apigenin. Antifungal activity was tested on 14 different isolates of spp. using membrane permeability assay, measuring inhibition of reactive oxidative species and inhibition of CYP51 enzyme. Cytotoxic potential of apigenin-7--glucoside was tested on colon cancer HCT116 cells by measuring cell viability, apoptosis rate and apoptosis- and colon cancer-related gene expression. Obtained results indicated considerable antifungal activity of apigenin-7--glucoside towards all isolates. Breakdown of plasma membrane was achieved upon treatment with apigenin-7--glucoside for shorter period of time then with apigenin. Reduction of intra- and extracellular reactive oxidative species was achieved with minimum inhibitory concentrations of both compounds, suggesting that reactive oxidative species inhibition could be a mechanism of antifungal action. None of the compounds exhibited binding affinity to CYP51 protein. Besides, apigenin-7--glucoside was more effective compared to apigenin in reduction of cell's viability and induction of cell death of HCT116 cells. Treatment with both compounds resulted in chromatin condensation, apoptotic bodies formation and apoptotic genes expression in HCT116 cells, but the apigenin-7--glucoside required a lower concentration to achieve the same effect. Compounds apigenin-7--glucoside and apigenin displayed prominent antifungal potential and cytotoxic effect on HCT116 cells. However, our results showed that apigenin-7--glucoside has more potent activity compared to apigenin in all assays that we used.
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http://dx.doi.org/10.17179/excli2017-300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547395PMC
May 2017

Assessment of risk factors and preventive measures and their relations to work-related musculoskeletal pain among dentists.

Work 2017 ;57(4):573-593

Department of Periodontology and Oral Medicine, School of Dental Medicine, University of Belgrade, Belgrade, Serbia.

Background: Dentists have a high prevalence of musculoskeletal (MS) pain, which is the most common symptom associated with work-related musculoskeletal disorders (WMSDs). To overcome this problem, identification of the risk factors and preventive measures for MS pain are of paramount importance to dentists in order to improve their quality of life and work.

Objectives: The aims of this study were to recognize the risk factors for MS pain and their impact on dental work, as well as to identify preventive measures of MS pain among dentists.

Methods: Self-reporting questionnaire consisting of 78 questions was exclusively developed for the study and sent to 500 working active dentists in Serbia.

Results: Response rate was 71.2% (356 dentists). The prevalence of MS pain was 82.6% among dentists. The main risk factors for MS pain were advanced age, female dentists, presence of chronic diseases, long working hours, and high frequency of treated patients. The most effective preventive measures in preventing MS pain were massage treatments and physical activities. Followed by use of ergonomically designed equipment, correct and dynamic working positions, and an adequate workflow organization.

Conclusion: The risk factors for MS pain and their impact on dental work should widely be disseminated among dentists. Importantly, proper implementation in everyday life of adequate preventive measures is essential for preventing MS pain and development of WMSDs.
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http://dx.doi.org/10.3233/WOR-172588DOI Listing
April 2018

Antimicrobial synergism and cytotoxic properties of Citrus limon L., Piper nigrum L. and Melaleuca alternifolia (Maiden and Betche) Cheel essential oils.

J Pharm Pharmacol 2017 Nov 17;69(11):1606-1614. Epub 2017 Aug 17.

Institute for Biological Research 'Siniša Stanković', University of Belgrade, Belgrade, Serbia.

Objectives: The chemical composition, antimicrobial and synergistic effect, and cytotoxic activity of Citrus limon (lemon), Piper nigrum (green pepper) and Melaleuca alternifoila (tea tree) essential oils (EOs) were investigated.

Methods: Chemical analyses of essential oils were tested by GC-FID and GC-MS spectroscopy. The antimicrobial activity assay was conducted using microdilution method against several oral bacteria and Candida spp. originating from the humans with oral disorders. The synergistic antimicrobial activity was evaluated using checkerboard method. The cytotoxicity evaluation of EOs was assessed using MTT test.

Key Findings: Limonene (37.5%) and β-pinene (17.9%) were the major compounds in C. limon oil, β-pinene (34.4%), δ-3-carene (19.7%), limonene (18.7%) and α-pinene (10.4%) in P. nigrum oil and terpinen-4-ol (38.6%) and γ-terpinene (21.7%) in M. alternifolia oil. The broad-spectrum antimicrobial activity was achieved by tested three EOs, with C. limon oil being the strongest against bacteria and M. alternifolia oil strongest against fungi. The EOs demonstrated synergism; their combined application revealed an increase in antimicrobial activity. All tested essential oils showed lower cytotoxic activity in comparison with the positive control, and the obtained results confirmed a dose-dependent activity.

Conclusions: The results of this study encourage use of tested EOs in development of a novel agent intended for prevention or therapy of corresponding oral disorders.
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http://dx.doi.org/10.1111/jphp.12792DOI Listing
November 2017

Inductively powered wireless pacing via a miniature pacemaker and remote stimulation control system.

Sci Rep 2017 07 21;7(1):6180. Epub 2017 Jul 21.

Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA.

Pacemakers have existed for decades as a means to restore cardiac electrical rhythms. However, lead-related complications have remained a clinical challenge. While market-released leadless devices have addressed some of the issues, their pacer-integrated batteries cause new health risks and functional limitations. Inductive power transfer enables wireless powering of bioelectronic devices; however, Specific Absorption Rate and size limitations reduce power efficiency for biomedical applications. We designed a remote-controlled system in which power requirements were significantly reduced via intermittent power transfer to control stimulation intervals. In parallel, the cardiac component was miniaturized to facilitate intravascular deployment into the anterior cardiac vein. Given size constraints, efficiency was optimal via a circular receiver coil wrapped into a half-cylinder with a meandering tail. The pacemaker was epicardially tested in a euthanized pig at 60 beats per minute, 2 V amplitude, and 1 ms pulse width, restoring mean arterial pressure from 0 to 37 mmHg. Power consumption was 1 mW at a range of > 3 cm with no misalignment and at 2 cm with 45° displacement misalignment, 45° x-axis angular misalignment, or 45° y-axis angular misalignment. Thus, we demonstrated a remote-controlled miniaturized pacing system with low power consumption, thereby providing a basis for the next generation of wireless implantable devices.
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http://dx.doi.org/10.1038/s41598-017-06493-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522478PMC
July 2017

A Miniaturized 0.78-mW/cm2 Autonomous Thermoelectric Energy-Harvesting Platform for Biomedical Sensors.

IEEE Trans Biomed Circuits Syst 2017 08 23;11(4):773-783. Epub 2017 May 23.

In order to use thermoelectric energy harvesters (TEHs) as a truly autonomous energy source for size-limited sensing applications, it is essential to improve the power conversion efficiency and energy density. This study presents a thin-film, array-based TEH with a surface area of 0.83 cm. The TEH autonomously supplies a power management IC fabricated in a 65-nm CMOS technology. The IC utilizes a single-inductor topology with integrated analog maximum power point tracking (MPPT), resulting in a 68% peak end-to-end efficiency (92% converter efficiency) and less than 20-ms MPPT. In an in-vivo test, a 645-μW regulated output power (effective 3.5 K of temperature gradient) was harvested from a rat implanted with our TEH, demonstrating true energy independence in a real environment while showing a 7.9 × improvement in regulated power density compared to the state-of-the-art. The system showed autonomous operation down to 65-mV TEH input.
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http://dx.doi.org/10.1109/TBCAS.2017.2684818DOI Listing
August 2017

Risk Factors for Intraoperative Hypertension during Surgery for Primary Hyperparathyroidism.

Med Princ Pract 2017 10;26(4):381-386. Epub 2017 Apr 10.

Objective: To investigate the incidence and identify risk factors for the occurrence of intraoperative hypertension (IOH) during surgery for primary hyperparathyroidism (pHPT).

Subjects And Methods: The study included 269 patients surgically treated between January 2008 and January 2012 for pHPT. IOH was defined as an increase in systolic blood pressure ≥20% compared to baseline values which lasted for 15 min. The investigated influence were demographic characteristics, surgical risk score related to physical status (based on the American Society of Anesthesiologists [ASA] classification), comorbidities, type and duration of surgery, and duration of anesthesia on IOH occurrence. The investigated factors were obtained from the patients' medical history, anesthesia charts, and the daily practice database. Logistic regression analysis was done to determine the predictors of IOH.

Results: Of the 269 patients, 153 (56.9%) had IOH. Based on the univariate analysis, age, body mass index, ASA status, duration of anesthesia, and preoperative hypertension were risk factors for the occurrence of IOH. Multivariate analysis showed that independent predictors of IOH were a history of hypertension (OR = 2.080, 95% CI: 1.102-3.925, p = 0.024) and age (OR = 0.569, 95% CI: 0.360-0.901, p = 0.016).

Conclusion: In this study, a high percentage (56%) of the patients developed IOH during surgery for pHPT, which indicates that special attention should be paid to these patients, especially to the high-risk groups: older patients and those with a history of hypertension. Further, this study showed that advanced age and hypertension as a coexisting disease prior to parathyroid surgery were independent risk factors for the occurrence of IOH.
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http://dx.doi.org/10.1159/000475597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768112PMC
June 2018

Biocompatibility Investigation of New Endodontic Materials Based on Nanosynthesized Calcium Silicates Combined with Different Radiopacifiers.

J Endod 2017 Mar;43(3):425-432

Clinic for Pediatric and Preventive Dentistry, School of Dentistry, University of Belgrade, Belgrade, Serbia.

Introduction: The aim of this article was to analyze biocompatibility and bioactivity of new endodontic materials on the basis of nanosynthesized calcium silicates (ALBO-MPCA and ALBO-MPCA) combined with different radiopacifiers in comparison with MTA.

Methods: Morphology of the samples was studied by scanning electron microscopy, and the pH and ion release analysis were also assessed. Biocompatibility of materials' eluates (24-hour, 7-day, and 21-day) was conducted by using MTT test. Twelve New Zealand white rabbits were used for intraosseous implantation. Four calvarial defects per animal were created and filled with freshly prepared investigated materials.

Results: Samples mostly consisted of agglomerates built up from nanoparticles, preferably spherical and rod-like. There was no significant difference among pH values of materials' eluates after 24 hours (P > .05). The amount of calcium and aluminum ion release decreased, whereas the amount of magnesium and bismuth (ALBO-MPCA, MTA) and barium (ALBO-MPCA) increased during 21-day period. The metabolic activity of cells increased after the extraction time, except in case of undiluted elutes of ALBO-MPCA and ALBO-MPCA (21-day). Histologic analysis of the samples revealed newly formed bone tissue with moderate inflammation for all investigated materials, which subsided during 90-day period to mild. Both MTA and ALBO-MPCA were in direct contact with the newly formed bone tissue. After 90 days, statistically significant difference in hard tissue formation was observed in comparison of MTA and ALBO-MPCA with control group (P < .05).

Conclusions: Experimental materials ALBO-MPCA and ALBO-MPCA possess both biocompatibility and bioactivity. Because ALBO-MPCA provokes favorable biological response, it is especially good candidate for further clinical investigations.
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http://dx.doi.org/10.1016/j.joen.2016.10.041DOI Listing
March 2017

A Brief History of Carotid Artery Surgery and Anesthesia.

J Anesth Hist 2016 10 28;2(4):147-150. Epub 2016 Sep 28.

School of Medicine, University of Belgrade, Serbia; Center for Endocrine Surgery, Clinical Center of Serbia, Belgrade.

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http://dx.doi.org/10.1016/j.janh.2016.09.005DOI Listing
October 2016

Unmet oral health needs among persons with intellectual disability.

Res Dev Disabil 2016 Dec 30;59:370-377. Epub 2016 Sep 30.

Dentistry Clinic of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia.

The aim of this study was to examine the factors affecting oral health status among intellectually disabled individuals in Serbia. The sample population was categorized according to age, sex, living arrangements, general health and the level of intellectual disability (ID). The diagnosis of dental caries was performed using the DMFT/dmft criteria. The oral hygiene and gingival health were assessed with the plaque index (Silness&Löe) and gingival index (Löe&Silness), respectively. Descriptive analysis, step-wise and logistic regression were performed to analyze related influential factors for caries presence, number of extracted teeth, teeth restored, the oral hygiene level and the extent of gingival inflammation. Odds ratios for caries were significantly higher among adult persons with ID, in persons with co-occurring developmental disorders (DDS) and increased with the level of ID. Group with DDS was associated with a 1.6 times greater odds of untreated decay, while the institutionalization was associated with 2.4 times greater odds of untreated decay. Institutionalization and co-occurring disabilities have been found to be significantly associated with a higher probability of developing gingivitis. Targeting oral health services to individuals with ID are encouraged and may help to reduce overall negative effect on oral and general health associated with delayed treatments, chronic dental pain, emergency dental care, tooth loss and advanced periodontal disease.
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http://dx.doi.org/10.1016/j.ridd.2016.09.020DOI Listing
December 2016

Sensitivity of clinical isolates of Candida to essential oils from Burseraceae family.

EXCLI J 2016 19;15:280-9. Epub 2016 Apr 19.

Institute for Biological Research "Siniša Stankovic", University of Belgrade, Bulevar Despota Stefana 142, 11000, Belgrade, Serbia.

The aim of this study was to investigate the chemical composition and antifungal activity of four commercial essential oils from the Burseraceae family - two Boswellia carterii Flueck oils, Canarium luzonicum (Blume) A. Gray oil, and Commiphora myrrha (Nees) Engl oil, against most common Candida spp. recovered from the human oral cavity. The essential oil samples were analyzed by GC-FID and GC/MS. The analysis showed that major essential oils' components were α-pinene (23.04 % and 31.84 %), limonene (45.62 %) and curzerene (34.65 %), respectively. Minimum inhibitory (MIC) and minimum fungicidal (MFC) concentrations were determined using a microdilution standardized technique. All tested Candida spp. clinical isolates and ATCC strains showed susceptibility to tested essential oils in a dose dependent manner. The strongest antifungal activity was shown by essential oil of B. carterii, sample 2; the average MIC values ranged from 1.25 to 1.34 mg/ml, and MFC values ranged from 2.50 to 3.75 mg/ml, depending on the fungus. This study supports the possible use of essential oils from the Bursecaceae family in reduction and elimination of Candida spp. populations in patients with oral cavity fungal infections.
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http://dx.doi.org/10.17179/excli2014-621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908663PMC
June 2016

Hyomental distance in the different head positions and hyomental distance ratio in predicting difficult intubation.

Bosn J Basic Med Sci 2016 Aug 14;16(3):232-6. Epub 2016 Jun 14.

School of Medicine, University of Belgrade.

The hyomental distance ratio (HMDR) is the ratio between the hyomental distance (HMD) (the distance between the hyoid bone and the tip of the chin) at the extreme of head extension (HMDe) and the one in the neutral position (HMDn). The objective of the study was to examine the predictive value, sensitivity, and specificity of HMDe, HMDn, and HMDR in predicting difficult endotracheal intubation (DI). A prospective study included 262 patients that underwent elective surgical operations. The following parameters were observed as possible predictors of DI: HMDR, HMDe, HMDn, Mallampati score, and body mass index (BMI). The cut-off points for the DI predictors were HMDe <5.3 cm, HMDn ≤5.5 cm, and HMDR ≤1.2. The assessment that DI existed was made by the anesthesiologist while performing laryngoscopy by applying the Cormack-Lehane classification. DI was present in 13 patients (5%). No significant difference was observed in the frequency of DI with regard to the sex, age, and BMI of the patients. Our research indicated HMDR as the best predictor of DI with a sensitivity of 95.6% and specificity of 69.2%. HMDR can be used in the everyday work of anesthesiologists because HMDR values ≤1.2 may reliably predict DI.
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http://dx.doi.org/10.17305/bjbms.2016.1217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978117PMC
August 2016

Extraordinary biological properties of a new calcium hydroxyapatite/poly(lactide-co-glycolide)-based scaffold confirmed by in vivo investigation.

Biomed Tech (Berl) 2017 May;62(3):295-306

.

This study examined the potential of a new porous calcium hydroxyapatite scaffold covered with poly (lactide-co-glycolide) (PLGA) as a bone substitute, identifying its advantages over Geistlich Bio-Oss®, considered the gold standard, in in vivo biofunctionality investigations. Structural and morphological properties of the new scaffold were analyzed by scanning electron and atomic force microscopy. The biofunctionality assays were performed on New Zealand white rabbits using new scaffold for filling full-thickness defects of critical size. The evaluated parameters were: the presence of macrophages, giant cells, monoocytes, plasma cells, granulocytes, neoangiogenesis, fibroplasia, and the percentage of mineralization. Parallel biofunctionality assays were performed using Geistlich Bio-Oss®. The appearance of bone defects 12 weeks after the new scaffold implantation showed the presence of a small number of typical immune response cells. Furthermore, significantly reduced number of capillary buds, low intensity of fibroplasia and high degree of mineralization in a lamellar pattern indicated that the inflammation process has been almost completely overcome and that the new bone formed was in the final phase of remodeling. All biofunctionality assays proved the new scaffold's suitability as a bone substitute for applications in maxillofacial surgery. It showed numerous biological advantages over Geistlich Bio-Oss® which was reflected mainly as a lower number of giant cells surrounding implanted material and higher degree of mineralization in new formed bone.
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http://dx.doi.org/10.1515/bmt-2015-0164DOI Listing
May 2017

PREDICTORS OF DIFFICULT AIRWAY MANAGEMENT IN THYROID SURGERY: A FIVE-YEAR OBSERVATIONAL SINGLE-CENTER PROSPECTIVE STUDY.

Acta Clin Croat 2016 Mar;55 Suppl 1:9-18

Difficult tracheal intubation (DI) is more common in thyroid than in other surgical branches due to thyromegaly. Proper preoperative airway evaluation is necessary in order to reduce the potential numerous complications. The study examined the incidence of DI in thyroid surgery and the influence of tracheal dislocation and other risk factors on DI. A prospective study was conducted on 2379 patients who underwent thyroidectomy at the Center for Endocrine Surgery, Clinical Center of Serbia, from 2007 to 2012. Patients were divided into groups with (n = 162) and without DI (n = 2217). Besides tracheal dislocation, another 13 risk factors contained in 13 screening tests and three additional factors of gender, age and diagnosis were defined. The incidence of DI in our study was 6.81%. The presence of tracheal dislocation was statistically significant, but not an independent predictor of DI. The diagnosis, large circumference and small neck length, previous DI, recessive mandible, tooth characteristics and oral anomalies were the most significant and independent predictors of DI. Neck circumference and small neck length had highest sensitivity. Previous DI had highest specificity. Thyromegaly, if causing tracheal dislocation and/or stenosis, represents a significant DI predictor, not individually, but in combination with other factors.
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March 2016