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Adela Voinescu,1– 3 Monica Licker,2,3 Delia Muntean,2,3 Corina Musuroi,2,3 Silvia Ioana Musuroi,1 Oana Izmendi,1,2 Silvana Vulpie,1,2 Romanita Jumanca,4 Mihnea Munteanu,5 Andrei Cosnita5 1Doctoral School “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania; 2Department of Microbiology, Multidisciplinary Research Center on Antimicrobial Resistance, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania; 3Clinical Laboratory, “Pius Brinzeu” Emergency Clinical County Hospital, Timisoara, Romania; 4Romanian and Foreign Languages Department, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania; 5Department IX, Surgery and Ophthalmology “Victor Babes” University of Medicine and Pharmacy, Timisoara, RomaniaCorrespondence: Monica Licker, Department of Microbiology, Multidisciplinary Research Center on Antimicrobial Resistance, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania, Email licker.monica@umft.roAbstract: Contact lenses (CL) have become an immensely popular means of vision correction, offering comfort to millions worldwide. However, the persistent issue of biofilm formation on lenses raises significant problems, leading to various ocular complications and discomfort. The aim of this review is to develop safer and more effective strategies for preventing and managing microbial biofilms on CL, improving the eye health and comfort of wearers. Taking these into consideration, the present study investigates the intricate mechanisms of biofilm formation, by exploring the interplay between microbial adhesion, the production of extracellular polymeric substances, and the properties of the lens material itself. Moreover, it emphasizes the diverse range of microorganisms involved, encompassing bacteria, fungi, and other opportunistic pathogens, elucidating their implications within lenses and other medical device-related infections and inflammatory responses. Going beyond the challenges posed by biofilms on CL, this work explores the advancements in biofilm detection techniques and their clinical relevance. It discusses diagnostic tools like confocal microscopy, genetic assays, and emerging technologies, assessing their capacity to identify and quantify biofilm-related infections. Finally, the paper delves into contemporary strategies and innovative approaches for managing and preventing biofilms development on CL. In Conclusion, this review provides insights for eye care practitioners, lens manufacturers, and microbiology researchers. It highlights the intricate interactions between biofilms and CL, serving as a foundation for the development of effective preventive measures and innovative solutions to enhance CL safety, comfort, and overall ocular health. Research into microbial biofilms on CL is continuously evolving, with several future directions being explored to address challenges and improve eye health outcomes as far as CL wearers are concerned.Keywords: Pseudomonas, Staphylococcus, microscopy, genetic, microbial keratitis

Oana Magiar,1 Silvana Vulpie,1,2 Corina Musuroi,1,3 Iosif Marincu,4,5 Alina Murariu,6 Mirela Turaiche,4,5 Silvia Ioana Musuroi,7 Delia Muntean,1,3,8 Monica Licker1,3,8 1Clinical Laboratory, “Pius Brînzeu” County Clinical Emergency Hospital Timisoara, Timis, Romania; 2Doctoral School, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Timis, Romania; 3Microbiology Department, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Timis, Romania; 4”Victor Babeș” Clinical Hospital of Infectious Diseases, Methodological and Infectious Diseases Research Centre Timisoara, Timis, Romania; 5Infectious Diseases Department, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Timis, Romania; 6Neurology II Department, “Pius Brînzeu” County Clinical Emergency Hospital Timisoara, Timis, Romania; 7Internal Medicine Department, Clinical Emergency Municipal Hospital, Timisoara, Romania; 8Multidisciplinary Research Centre for Antibiotic Resistance, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Timis, RomaniaCorrespondence: Silvana Vulpie, Clinical Laboratory, “Pius Brînzeu” County Clinical Emergency Hospital Timisoara, Liviu Rebreanu, No. 156, Timișoara, Timis, 300723, Romania, Tel +40 727248701, Email vulpie.silvana@umft.comAbstract: Listeria monocytogenes (LM), one of the most important foodborne pathogens, is an intracellular bacterium found in food and the environment. It causes listeriosis, a potentially severe disease, particularly for pregnant women, the elderly and immunocompromised patients, but in rare cases, it can cause invasive disease in immunocompetent adults and children. Community-acquired bacterial meningitis caused by LM is rare and difficult to diagnose. It carries a high mortality rate; therefore, it is essential to start appropriate antibiotic treatment as soon as possible. The first case of LM meningitis identified in our hospital over the last 10 years is that of a previously healthy 45-year-old man who presented in the emergency department with a 4-day history of diplopia, left eye medial deviation and left palpebral ptosis, with no history of fever, headache or gastrointestinal symptoms. Because of the atypical symptoms, a suspicion of meningitis vs cerebral aneurysm was raised during the admission process. The patient was diagnosed with LM meningitis and recovered fully after appropriate antibiotic treatment. The purpose of this article is to emphasise the possibility of LM invasive disease (in this case meningitis) occurring in previously healthy individuals and to raise awareness about the need for LM to be considered in the differential diagnosis of atypical presentations.Keywords: Listeria monocytogenes, meningitis, antibiotics, atypical clinical manifestation, immunocompetent patient

Maria Rus,1,2 Monica Licker,1– 3 Corina Musuroi,2 Edward Seclaman,4 Delia Muntean,1– 3 Natalia Cirlea,2 Alina Tamas,2 Silvana Vulpie,2 Florin George Horhat,1,3 Luminita Baditoiu3,5 1Department of Microbiology, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania; 2“Pius Brinzeu” County Clinical Emergency Hospital, Timisoara, Romania; 3Multidisciplinary Research Center on Antimicrobial Resistance, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania; 4Department of Biochemistry, “Victor Babeş” University of Medicine and Pharmacy, Timişoara, Romania; 5Department of Epidemiology, “Victor Babeş” University of Medicine and Pharmacy, Timişoara, RomaniaCorrespondence: Monica LickerDepartment of Microbiology, “Victor Babes” University of Medicine and Pharmacy, 2 E. Murgu, Timisoara 300041, RomaniaTel +40 0256-707513Email licker.monica@umft.roCorina MusuroiPius Brinzeu” County Clinical Emergency Hospital, No. 156 L.Rebreanu, Timisoara 300723, RomaniaTel +40745050232Email cormus1@yahoo.comBackground: Carbapenem-resistant Proteeae (CRP) is a group of multidrug-resistant (MDR) microorganisms that raise special treatment problems due to their intrinsic resistance to colistin. In this study, our aim is to provide a phenotypic and molecular characterization of the carbapenemases secreted by CRP strains isolated from inpatients from an intensive care unit (ICU) and surgical wards, as well as the identification of the risk factors involved in their acquisition.Methods: An observational, cross-sectional study was performed which included all Proteeae strains isolated in samples from inpatients on high-risk wards of the largest university hospital in Western Romania, from July 2017 to April 2019. Meropenem-resistant strains (N=65) with MIC ≥ 16 μg/mL were subjected to a singleplex PCR assay for the detection of blaNDM, blaVIM and blaCTX-M genes. The analysis of risk factors was performed by logistic regression.Results: Out of 8317 samples that were processed, 400 Proteeae strains were isolated: 64% belonging to the genus Proteus, 26.75% to the genus Providencia and 9.25% to the genus Morganella. Most CRP strains (N=56) were of MBL type, and 55 had the blaNDM gene as the prevalent gene substrate. P. stuartii was the main species that provided the circulating MDR strains. Most CRP strains came from patients admitted to ICU, being isolated mainly from bronchial aspirates and blood cultures. Multivariate analysis revealed 3 independent risk factors – mechanical ventilation> 96h (HR: 40.51 [13.65– 120.25], p < 0.001), tracheostomy (HR: 2.65 [1.14– 6.17], p = 0.024) and prolonged antibiotic therapy (HR: 1.01 [1.00– 1.02], p = 0.03).Conclusion: There is a significant increase in the incidence of CR P. stuartii strains, the MBL-blaNDM type being predominant. These strains presented various other resistance mechanisms, being often extremely difficult to treat and led to an excess of lethality of 27.16%.Keywords: carbapenem-resistant Proteeae, intensive care unit, P. stuartii

Vlad Serafim,1,2 Ajit J Shah,3 Monica Licker,4,5 Florin George Horhat,4 Silvana Vulpie,5 Corina Musuroi,4,5 Delia Muntean4,5 1Genetics Discipline, “Victor Babes” University of Medicine and Pharmacy, Timisoara 300041, Romania; 2The National Institute of Research and Development for Biological Sciences, Bucharest 060031, Romania; 3Department of Natural Sciences, Middlesex University, London NW4 4BT, UK; 4Department of Microbiology, “Victor Babes” University of Medicine and Pharmacy, Timisoara 300041, Romania; 5“Pius Brînzeu” Emergency Clinical County Hospital, Timișoara 300723, RomaniaCorrespondence: Monica LickerDepartment of Microbiology, “Victor Babes” University of Medicine and Pharmacy, 2 E. Murgu, Timisoara 300041, RomaniaTel +40 0256-707513Email licker.monica@umft.roPurpose: Several mass spectrometry-based methods for antimicrobial sensitivity testing have been described in recent years. They offer an alternative to commercially available testing systems which were considered to have disadvantages in terms of cost- and time-efficiency. The aim of this study was to develop an LC-MS/MS-based antibiotic hydrolysis assay for evaluating antimicrobial resistance (AMR) of Gram-negative bacteria.Materials and Methods: Four species of Gram-negative bacilli (Klebsiella pneumoniae, Escherichia coli, Providencia stuartii and Acinetobacter baumannii) were tested against six antibiotics from three different classes: ampicillin, meropenem, imipenem, ceftazidime, ceftriaxone and cefepime. Bacterial suspensions from each species were incubated with a mixture of the six antibiotics. Any remaining antibiotic following incubation was measured using LC-MS/MS. The results were interpreted using measurements obtained for an E. coli strain sensitive to all antibiotics and expressed as percentage of hydrolyzed antibiotic. These were subsequently compared to commercially-available system for the bacteria identification and susceptibility testing.Results: Overall, LC-MS/MS assay and commercial antimicrobial susceptibility platform results showed good agreement in terms of an organism being resistant/sensitive to an antibiotic. The time required to complete the LC-MS/MS-based hydrolysis test was under 5 h, significantly shorter that commercially available susceptibility testing platforms.Conclusion: By using a sensitive strain for results interpretation and simultaneous use of multiple antibiotics, the proposed protocol offers improved robustness and multiplexing over previously described methods for antibiotic sensitivity testing. Nevertheless, further research is needed before routine assimilation of the method, especially for strains with intermediate resistance.Keywords: antimicrobial, resistance, β-lactamases, LC-MS/MS, Gram-negative, mass spectrometry

Delia Muntean,1 Monica Licker,1 Ersilia Alexa,2 Iuliana Popescu,2 Calin Jianu,3 Valentina Buda,4 Cristina Adriana Dehelean,5 Roxana Ghiulai,6 Florin Horhat,1 Delia Horhat,7 Corina Danciu8 1Department of Microbiology, “Victor Babes” University of Medicine and Pharmacy, Timisoara 300041, Romania; 2Department of Food Control, Faculty of Food Processing Technology, Banat’s University of Agricultural Sciences and Veterinary Medicine “King Michael I of Romania”, Timisoara 300645, Romania; 3Department of Food Tehnologies, Faculty of Food Engineering, Banat’s University of Agricultural Sciences and Veterinary Medicine “King Michael I of Romania”, Timişoara 300645, Romania; 4Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy, Timisoara 300041, Romania; 5Department of Toxicology, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy, Timisoara 300041, Romania; 6Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy, Timisoara 300041, Romania; 7Department of ENT, “Victor Babes” University of Medicine and Pharmacy, Timisoara 300041, Romania; 8Department of Pharmacognosy, “Victor Babes” University of Medicine and Pharmacy, Timisoara 300041, RomaniaCorrespondence: Valentina Buda; Delia Horhat“Victor Babes” University of Medicine and Pharmacy, 2nd EftimieMurgu Square, Timisoara 300041, RomaniaTel +40 25 649 4804Fax +40 25 649 4804Email buda.valentina.oana@gmail.com; horhat.ioana@umft.roBackground: Bacterial multidrug resistance currently poses an increasingly serious threat, with important clinical consequences regarding treatment options. In 2017, the WHO released a global list of resistant bacteria, identifying multidrug-resistant (MDR) Gram-negative bacteria such as carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa or Acinetobacter baumannii, extended-spectrum cephalosporin-resistant Enterobacteriaceae as critical priorities for developing new strategies of treatment.Purpose: The novelty presented in this study refers to the evaluation of the volatile oil obtained from the leaves of Mentha×piperita L., on MDR strains from hospitalized patients.Material and methods: The essential oil was extracted by steam distillation and tested on six reference bacterial strains and also on the MDR strains collected from patients of the “Pius Brînzeu” Emergency Clinical County Hospital Timișoara. The in vitro antibacterial activity was evaluated by agar disk diffusion method and microdilution method.Results: Testing the antibacterial activity of peppermint oil on both reference strains and isolated MDR strains from hospitalized patients demonstrated its bactericidal effect. Minimum inhibitory concentration (MIC) was lower (20 mg/mL) for Staphylococcus aureus, Escherichia coli and Proteus mirabilis and higher (40 mg/mL) for Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii strains. Minimum bactericidal concentration (MBC) was equal to MIC, with the exception of Pseudomonas aeruginosa strains, where MBC was the double of MIC.Conclusion: The present study highlights the bactericidal activity of Mentha×piperita L. essential oil on all tested MDR or extensively drug-resistant Gram-positive and Gram-negative strains of Staphylococcus aureus, Escherichia coli, Klebsiellapneumoniae, Proteus mirabilis, Pseudomonas aeruginosa and Acinetobacter baumannii. This oil may be a therapeutic option in the near future for many infectious diseases produced by MDR bacteria.Keywords: bacterial multidrug resistance, peppermint, essential oil, bactericidal effect

Delia Muntean,1,2 Monica Licker,1,2 Florin Horhat,1 Victor Dumitrașcu,1 Dorel Săndesc,1,2 Ovidiu Bedreag,1,2 Dorina Dugăeșescu,1 Dan A Coșniță,1 Anca Krasta,2 Luminița Bădițoiu1 1Victor Babeș University of Medicine and Pharmacy, Timisoara, Romania; 2Pius Brînzeu Emergency Clinical County Hospital, Timisoara, Romania Purpose: The purpose of this study was to identify risk factors for extensively drug-resistant (XDR) Acinetobacter baumannii (AB) and XDR Proteeae association in the largest intensive care unit (ICU) in Western Romania. Materials and methods: This retrospective case-controlled study was conducted between January 2016 and December 2016 in the ICU of the “Pius Brînzeu” County Emergency Clinical Hospital of Timișoara. Data were collected, in strict confidentiality, from the electronic database of the Microbiology Laboratory and the hospital’s electronic medical records. Risk factors were investigated by logistic regression. Independent variables with P≤0.05 and OR >1 (95% CI >1) in the univariate analysis were entered into multivariate sequenced analysis. Findings: The incidence density of coinfection with XDR AB and XDR Proteeae was 5.31 cases per 1,000 patient-days. Independent risk factors for the association of XDR AB and XDR Proteeae were represented by the presence of tracheostomy and naso-/orogastric nutrition ≥ 8 days. In addition, pressure ulcers were independent predictive factors for infections with all three infection types. Previous antibiotic therapy was an independent risk factor for the acquisition of XDR-AB strains, alone or in association, while the prolonged hospitalization in the ICU, blood transfusion, and hemodialysis appear as independent risk factors for single infections. Conclusion: This association of XDR AB and XDR Proteeae may well not be limited to our hospital or our geographical area. Keywords: extensive drug resistance, ICU, infections, risk factors

Monica Licker,1,2 Teodora Sorescu,3,4 Maria Rus,5,6 Natalia Cirlea,6 Florin Horhat,1 Cristiana Jurescu,5,6 Mircea Botoca,7,8 Alin Cumpănas,7,8 Romulus Timar,3,4 Delia Muntean1,2 1Department of Microbiology, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania; 2Clinical Laboratory, “Pius Brînzeu” Emergency Clinical County Hospital, Timisoara, Romania; 3Department of Internal Medicine II, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania; 4Diabetes Clinic, “Pius Brînzeu” Emergency Clinical County Hospital, Timisoara, Romania; 5“Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania; 6“Pius Brînzeu” Emergency Clinical County Hospital, Timisoara, Romania; 7Department of Orthopaedics – Traumatology, Urology and Medical Imaging, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania; 8Urology Unit, “Pius Brînzeu” Emergency Clinical County Hospital, Timisoara, Romania Purpose: We report an outbreak of urinary tract infections (UTIs) caused by Myroides odoratimimus, which occurred in the largest clinical hospital in western Romania. Patients and methods: From June to August 2017, four strains of M. odoratimimus were isolated from the urine samples of patients hospitalized in the urology, diabetes, and surgery departments. Hospital records of all patients whose urine cultures were positive for M. ­odoratimimus were reviewed retrospectively. We also reviewed the cases reported in the literature. Results: All UTIs, except one, were hospital-acquired infections. All patients with M. odoratimimus UTIs were immunocompromised. Three patients underwent urinary catheterization with a Foley’s catheter upon admission in the emergency department and one presented for replacement of ureterostomy tubes. All Myroides isolates were resistant to almost all the tested antibiotics. Two patients were successfully treated with tigecycline and one was receiving antimicrobial treatment for another infection at the time of isolation of the microorganism. Conclusion: Although M. odoratimimus is an uncommon pathogen, clinicians should be aware of its ability to cause UTI outbreaks, especially in the immunocompromised population. Due to its multi-drug resistance, it is important to rapidly identify Myroides spp. in order to choose the best treatment regimen. Keywords: Myroides odoratimimus, urinary tract infection, resistance, outbreak

Teodora Chiţă,1,2 Bogdan Timar,1,2 Delia Muntean,1,2 Luminiţa Bădiţoiu,1,3 Florin Horhat,1,2 Elena Hogea,1 Roxana Moldovan,1,3 Romulus Timar,1,2 Monica Licker1,2 1Victor Babes University of Medicine and Pharmacy Timisoara, 2Pius Brinzeu Emergency Hospital, 3Regional Centre of Public Health, Timisoara, Romania Aim: Patients with diabetes mellitus (DM) have an increased risk of infections, especially urinary tract infections (UTIs). The aim of this study was to assess the prevalence and etiology of UTIs and identify the risk factors for their development in patients with DM. Patients and methods: In this retrospective, noninterventional study, the medical records of 2,465 adult patients with DM who were hospitalized in a Diabetes Clinic were reviewed. Data regarding the presence of UTI and possible associated risk factors were collected and their possible relation was analyzed. The study protocol and procedures were approved by the Ethics Committee of Timişoara Emergency Hospital. All data were collected and analyzed using SPSS v.17 statistical software. Results: The prevalence of UTIs in patients with DM was 12.0% (297 cases), being higher in females than in males and higher in patients with type 2 DM compared with patients with type 1 DM. In univariate logistic regression analysis, risk factors associated with UTIs were female gender, age, type 2 DM, longer duration of DM, and the presence of chronic kidney disease and coronary artery disease. Multivariate analysis identified age, duration of DM, and metabolic control (hemoglobin A1c levels) as independent risk factors for UTIs. The gram-negative bacilli from the Enterobacteriaceae family were predominant, with Escherichia coli being the most frequent of them (70.4%). Conclusion: UTIs are a frequent condition associated with DM. It is necessary to improve the care and the screening of UTIs in patients with DM to prevent the occurrence of possible associated severe renal complications. Keywords: urinary tract infections, diabetes mellitus, epidemiology, incidence

Human mpox is a zoonotic disease, caused by the mpox virus (MPXV), that can spread either between animals and humans or humans and humans. In 1970 the first human case of mpox was reported in Zaire, Democratic Republic of the Congo (DRC). Other notable human mpox outbreaks in non-endemic countries were identified in June 2003 in the United States, in July 2021 in Dallas (USA), and the most recent one in May 2022 in Europe in the United Kingdom (UK). During the 2022 outbreak, sexual intercourse was observed to be the most prevalent transmission method, although other means should not be ignored, such as the involvement of respiratory droplets, exposure to surfaces and skin suspected of contamination. In the context of the current mpox outbreak, we consider it important and necessary to correctly identify the virus, use the proper laboratory testing for a correct diagnosis of mpox, understand the means of prophylaxis, and apply the correct treatment, highlighting these facts being the aim of this study.

Introduction: Resistance to first-line antibiotics of the Proteeae strains within the difficult-to-treat (DTR) phenotype is a cause of limitation of therapeutic options. The study aimed to characterize these strains, to identify the factors that influence their acquisition and the predictive factors for the patient’s evolution.

The increasing resistance against classical antibiotic treatment forces the researchers to develop novel non-toxic antimicrobial agents. The aim of this study was to determine the antimicrobial properties of seven different porphyrins having distinctive hydrophobicity/hydrophilicity: P1 meso-tetra(4-methoxy-phenyl)porphyrin, P2 Zn(II)-meso-5,10,15,20-tetrapyridylporphyrin, P3 meso-tetra(p-tolyl)porphyrin, P4 5,10,15,20-tetraphenylporphyrin; P5 (5,10,15,20-tetraphenylporphinato) dichlorophosphorus(V) chloride, P6 5,10,15,20-tetrakis-(N-methyl-4-pyridyl) porphyrin-Zn(II) tetrachloride, P7 Zn(II)-5,10,15,20-meso-tetrakis-(4-aminophenyl)porphyrin. The meso-porphyrin derivatives were screened for their antimicrobial activity against six reference strains: Streptococcus pyogenes ATCC 19615, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 700603, Pseudomonas aeruginosa ATCC27853 and Candida albicans ATCC 10231. The antimicrobial activity of these samples was evaluated by the agar disk diffusion method and dilution method, with the determination of the minimum inhibitory concentration (MIC), the minimum bactericidal concentration (MBC) and the minimum fungicidal concentration (MFC). The most significant result is provided by the water-soluble P5 manifesting an obvious antimicrobial activity against Streptococcus pyogenes. On the other hand, P6 is a moderately active derivative against Streptococcus pyogenes and Escherichia coli and P7 presents moderate activity against Streptococcus pyogenes and Staphylococcus aureus. All the tested porphyrin bases, presenting hydrophobic character, have no antimicrobial activity under the investigated conditions. The common characteristics of the porphyrins that act as promising antimicrobial agents in the non-irradiated methods are: the cationic nature, the increased hydrophilicity and the presence of both amino functional groups grafted on the porphyrin ring and the coordination with Zn or phosphorus in the inner core.

Valentina Buda,1,* Minodora Andor,2,* Carmen Cristescu,1,* Mirela Cleopatra Tomescu,2 Danina M Muntean,3 Dana Emilia Bâibâță,4,5 Diana Aurora Bordejevic,4,5 Corina Danciu,6 Olivia Dalleur,7 Dorina Coricovac,8 Zorin Crainiceanu,9 Anca Tudor,10 Ionut Ledeti,11 Lucian Petrescu4,5 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania; 2Department of Medical Semiotics, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania; 3Department of Pathophysiology, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania; 4Department of Cardiology VI, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania; 5Cardiovascular Diseases Institute, Timisoara 300310, Romania; 6Department of Pharmacognosy, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania; 7Clinical Pharmacy Research Group, Louvain Drug Research Institute, Université Catholique De Louvain, Woluwe-Saint-Lambert 1200, Bruxelles, Belgium; 8Department of Toxicology, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania; 9Department of Plastic and Reconstructive Surgery, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania; 10Department of Statistics and Biomedical Informatics, Faculty of Medicine, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania; 11Department of Physical Chemistry, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, Timisoara 300041, Romania*These authors contributed equally to this workCorrespondence: Valentina BudaCorina Danciu Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Street, Timisoara 300041, RomaniaTel +40-256-494-604Fax +40-256-494-604Email buda.valentina.oana@gmail.comBackground: Thrombospondin-1 (TSP-1) is a matricellular functional protein of the extracellular matrix. As it is not constitutively present extracellularly, its secretion is enhanced in several situations, namely injury, chronic pathology, tissue remodeling, angiogenesis, and aging. Over the last decade, TSP-1 has been reported to be involved in complex and opposing biological effects on vasculature in the context of NO signaling. Several studies have reported high patient TSP-1 plasma levels, indicating that the protein can potentially serve as a prognostic marker for pulmonary arterial hypertension.Materials and methods: Here, we aimed to quantify TSP-1 serum levels in hypertensive patients with endothelial dysfunction before and after one year of treatment with Perindopril (an antihypertensive drug with vasoprotective properties).Results: After one year of treatment, TSP-1 levels increased in hypertensive patients compared to baseline (T0: 8061.9 ± 3684.80 vs T1: 15380±5887 ng/mL, p

Introduction: Experimental acute cerebral ischemia quickly triggers circulating inflammatory cells, provoking infiltration of neutrophils and macrophages in the damaged brain region. N-3 polyunsaturated fatty acids alleviate the ischemic deterioration, however, their potential effect on bone marrow cell mobilization is less known.

A rapid, sensitive, high-throughput liquid chromatography coupled with tandem mass spectrometry method for the quantification of rivaroxaban from human plasma has been developed and validated. For the analytical separation a Zorbax SB-C18 column with isocratic flow of mobile phase composed of 0.2% formic acid in water and acetonitril (65:35, V/V) with a flow rate of 1 mL/min at a temperature of 45ºC was used. Detection of rivaroxaban was performed using positive electrospray ionization and MS/MS mode (sum of m/z 231.1; 289.2 and 318.2 from m/z 436.3). Plasma samples were prepared using single-step protein precipitation with methanol. Method validation was performed with regards to selectivity, linearity (r >0.9927), within-run and between-run precision (CV< 13.1 %) and accuracy (bias< 9.4 %) over a concentration range of 24.00 - 960.00 ng/mL plasma. Recovery was between 96.5 - 108.5% and the lower limit of quantification of rivaroxaban was 24.00 ng/mL. The developed method is simple, rapid, and selective, requires small plasma sample volumes, and was successfully applied for therapeutic drug monitoring of rivaroxaban in treated patients.

The term biofilm designates an aggregate of microorganisms belonging to one or more species which adhere to various surfaces but also to each another. These microbial communities are included and interconnected within an organic structure known as slime, composed of protein substances, polysaccharides, and DNA.

Oxidative stress appears when the amount of free radicals that are formed in a living organism exceed its spin-trapping ability. One of the most dangerous free radicals that are formed in the human body is the hydroxyl radical. It can alter several biomolecules, including the unsaturated fatty acids; this process is known as lipid peroxidation and can lead to cell necrosis and generation of several harmful byproducts including malondialdehyde, which serves also as a biomarker of oxidative stress. A new HPLC method with visible detection was developed for the detection of malondialdehyde in human serum and saliva samples. The method was verified in terms of specificity, linearity, limits of detection (0.35 ng/ml), limit of quantification (1.19 ng/ml), recovery (90.13±10.25 – 107.29±14.33) and precision (3.84±1.49% – 6.66±1.76%). An analysis time of only 1 minute was obtained and no interferences from the matrices were observed. Statistical analysis (Pearson correlation test) showed a moderate correlation (R = 0.5061, p = 0.0099) between serum and saliva concentrations (N = 25). The possibility of measuring salivary concentrations of malondialdehyde extents the applications of oxidative stress/lipid peroxidation estimations to categories of population unreachable before (pregnant women, small children, etc); repeated sample studies are also easier to make.

The rodenticide brodifacoum is highly toxic to mammals and birds, and extremely toxic to fish. It is a highly cumulative poison due to its high lipophilicity and extremely slow elimination. For this reason, it may be interesting to find similar compounds in order to enlarge the spectrum of vitamin K epoxide reductase enzyme inhibitors used today in pest control. We used the Similar Compounds search type of the Chemical Structure Search of the PubChem Compound Database to locate records that are similar to the chemical structure of brodifacoum, using pre-specified similarity thresholds. Using the threshold ≥ than 95% for the similar structures criteria, we found 14 compounds (from over 30 million entries) that meet this criteria. Two of these compounds have a better binding affinity to vitamin K epoxide reductase enzyme than brodifacoum, but the binding energy of the other 12 substances is also high, having identical or lower lipophilicity; consequently, they will eliminate faster, possibly lacking a part of the adverse effects.

Determinarea concentraţiilor in vivo ale monoxidului de azot (NO) este necesară pentru identificarea condiţiilor patologice în care producţia endogenă a acestui compus este redusă sau pentru identificarea unor agenţi care pot genera in vivo acest compus. Instabilitatea crescută a oxidului de azot îl face extrem de greu de determinat. Ionii nitrat şi nitrit (produşi de oxidare ai NO) sunt de obicei determinaţi ca sumă prin reducerea nitratului la nitrit şi determinarea nitritulu ca un biomarker al NO în studii experimentale pe om și animale de experienţă. În lucrarea de faţă s-a evaluat utilitatea testului NOx în detectarea unei eliberări de moment a unor cantităţi crescute de NO.

The present paper focuses on the development of the composite materials in the automotiv industry by making a comparative analysis between a 3D model of the part and a real part made by a composite material, measuring the part using the point cloud. The aim is to obtain a high modeling and a more clear visualization of the composite material part.

The intense urbanization process Romania has known during the industrialization period of the 1960-70s led to an exponential shortage in urban housing. Similar to other countries, but more specifically to the former Eastern block, Romanian state-financed collective dwellings were erected starting from standardized projects of Reinforced Concrete Large Prefabricated Panels (RCLPP) blocks of flats, generating nowadays a particular built stock of identical buildings and several apartment types, widespread throughout the entire country. These buildings currently house 60% of the urban population of Romania that own 96% of the apartments, as opposed to the European trends regarding the number of owner-occupied barely reaching 60%. Even though at not even half of their intended lifespan, the collective dwellings do not satisfy basic comfort conditions such as cooling and ventilation, being in an urge of retrofitting and upgrading. Individually applicable cooling systems undertaken by the owners have proved to be acceptable, but did not, however, contribute to a decrease in the overall energy consumption of the buildings. The present paper analyses the individual cooling systems being currently applied in Romanian apartments as opposed to a global-holistic system on block level, in terms of energy consumption and efficiency, flexibility of owner controlled indoor microclimate. The results show the potential of introducing renewable energy sources as viable alternatives for the existing systems.

The paper makes an in-sight analysis of four actual steel-intensive envelope solutions existing on the market adaptable to steel structural systems. The solutions enable flexible modular construction, fast fabrication and erection times and easy disassembling. The analyses consider the heat transfer analysis including phase shift, amplitude attenuation and temperature amplitude ratio and the energy balance analysis. Considering the sustainability approach, the study is completed by an environmental impact analysis on Life-Cycle, by considering the production and end-of life stages. Although the selected systems from similar thermal resistances, the results show a certain variation of analysed parameters such as amplitude attenuation and temperature amplitude ratio (TAV). The energy balance analysis shows that the heating, solar gain and hot water preparation are responsible for the supplied energy. The emitted house energy break-down is almost equally shared among transmission, ventilation and sewage energies. The Life-Cycle Assessment (LCA) analysis proves that the end-of-life of the systems play an important role in the environmental impact of analysed systems, reversing the initial ranking of systems.

Ephedra alata Decne. belongs to the Ephedraceae family. It is a species of Ephedra that grows mostly in the desert. Today, the main importance of Ephedra species in the medical field is due to the presence of the alkaloids derived from phenyl-alanine, which act on the sympathetic nervous system as a sympathomimetic. The aim of this study was to conduct a phytochemical characterization of the hydroalcoholic extract of the aerial part of Ephedra alata Decne., which is indigenous to Tunis, that involves the total phenolic content, individual phenolic content, and antioxidant activity as well as a biological screening for the evaluation of the antimicrobial, antifungal, antiproliferative, pro-apoptotic, and cytotoxic potential against the MCF-7 breast cancer cell line. The results show that the hydroalcoholic extract contains polyphenolic phytocompounds (156.226 ± 0.5 mgGAE/g extract) and elicits antioxidant activity (7453.18 ± 2.5 μmol Trolox/g extract). The extract acted as a bacteriostatic agent against all tested bacterial strains, but was bactericidal only against the Gram-positive cocci and Candida spp. In the set experimental parameters, the extract presents antiproliferative, pro-apoptotic, and cytotoxic potential against the MCF-7 human breast cancer cell line.

This study aimed to assess the utility of echocardiography-measured epicardial adipose tissue (EAT) thickness (EATT) as an independent predictor for coronary artery disease (CAD), examining its correlation with oxidative stress levels in epicardial tissue and the complexity of the disease in patients undergoing open-heart surgery. This study included a total of 25 patients referred for cardiac surgery with 14 in the CAD group and 11 in the non-CAD group. Epicardial fat was sampled from patients subjected to open-heart surgery . EATT was higher in the CAD group compared to the non-CAD group (8.15 ± 2.09 mm vs. 5.12 ± 1.8 mm, p  = 0.001). The epicardial reactive oxygen species level was higher in the CAD group compared to the non-CAD group (21.4 ± 2.47 nmol H 2 O 2 /g tisssue/h vs. 15.7 ± 1.55 nmol H 2 O 2 /g tisssue/h, p  < 0.001). EATT greater than 6.05 mm was associated with CAD, with a sensitivity of 86% and specificity of 73%. Echocardiographically measured EATT is a significant, independent predictor of CAD. Its relationship with increased EAT oxidative stress levels suggests a potential mechanistic link between EATT and CAD pathogenesis. These findings highlight the importance of EATT as a diagnostic tool in assessing the complexity of CAD in patients undergoing cardiac surgery., Competing Interests: The authors declare no conflict of interest.

Infections represent a major complication for burn-injured patients. The aim of this study was to highlight the changes in the incidence and antimicrobial resistance of bacterial strains isolated from burn patients, at the end of the COVID-19 pandemic, in relation to the antibiotics used during the pandemic. A comparative analysis of the demographic data and the microorganisms identified in the clinical samples of two groups of burn patients admitted to a university hospital in Romania was carried out. The first group consisted of 48 patients and the second of 69 patients, hospitalized in January-August 2020 and 2023, respectively. The bacterial species with the highest incidence were S. aureus , A. baumannii , Pseudomonas spp. The significant changes between 2023 and 2020 are reflected in the increase in the frequency of non-fermentative Gram-negative bacteria, especially S. maltophilia , and the increase in antimicrobial resistance of Pseudomonas and Klebsiella spp. Klebsiella spp. did not change in frequency (7%), but there was a significant increase in the incidence of K. pneumoniae strains with pan-drug resistant behaviour to antibiotics (40%), including colistin. The phenomenon can be explained by the selection of specimens carrying multiple resistance genes, as a result of antibiotic treatment during the COVID-19 period. The post-pandemic antimicrobial resistance detected in burn patients indicates the need for permanent surveillance of the resistance trends, primarily due to the limited therapeutic options available for these patients.

Melatonin is commonly found in various fruits, juices, and some fermented beverages. Its concentration in wine is influenced by soil properties, climatic factors, and yeast activity. Even if it is found in fermented beverages in relatively low proportions, melatonin still holds significant nutritional value, giving anti-aging properties, anti-inflammatory actions, and antidepressant effects. In this context, this article focuses on evaluating the impact of different Saccharomyces and non-Saccharomyces yeast species on the formation of melatonin and its contribution to wines' total antioxidant capacity. Considering that the antioxidant activity of wine is usually related to the content of phenolic compounds, ten such compounds were analyzed. The evaluation of bioactive compounds was performed using high-performance liquid chromatography (HPLC) coupled with mass spectrometry. The total antioxidant capacity of wine samples was evaluated by the ABTS + method. The administration of bâtonnage products increased the efficiency of non- Saccharomyces yeasts. The mixtures of Saccharomyces and non- Saccharomyces yeasts generated higher values for melatonin. The results confirm a significant impact from the grape variety and the specific yeast strains on the melatonin concentration. Also, a strong dependence between antioxidant activity and melatonin levels was observed. Given the limited existing studies on the presence of melatonin in wines, new perspectives are needed for future exploration and understanding.

Olea europaea L. is the most valuable species of the Olea type, and its products offer a wide range of therapeutical uses. The olive tree has been extensively studied for its nourishing qualities, and the "Mediterranean diet", which includes virgin olive oil as a key dietary component, is strongly associated with a reduced risk of cardiovascular disease and various malignancies. Olive leaves, a by-product in the olive harvesting process, are valued as a resource for developing novel phytomedicines. For this purpose, two ethanolic extracts obtained from Olivae folium from Spain (OFS) and Greece (OFG) were investigated. Our findings contribute to a wider characterization of olive leaves. Both extracts displayed important amounts of phenolic compounds and pentacyclic triterpenes, OFG having higher concentrations of both polyphenols, such as oleuropein and lutein, as well as triterpenes, such as oleanolic acid and maslinic acid. The antioxidant capacity is similar for the two extracts, albeit slightly higher for OFG, possibly due to metal polyphenol complexes with antioxidant activity. The extracts elicited an antimicrobial effect at higher doses, especially against Gram-positive bacteria, such as Streptococcus pyogenes . The extract with lower inorganic content and higher content of polyphenols and triterpenic acids induced a strong anti-radical capacity, a selective cytotoxic effect, as well as antimigratory potential on A375 melanoma cells and antiangiogenic potential on the CAM. No irritability and a good tolerability were noted after evaluating the extracts on the in vivo Hen's Egg Test-Chorioallantoic Membrane (HET-CAM). Therefore, the present data are suggestive for the possible use of the two types of olive leaf products as high-antioxidant extracts, potentially impacting the healthcare system through their use as antimicrobial agents and as anticancer and anti-invasion treatments for melanoma.