Multidrug-resistant Acinetobacter baumannii isolates pose a threat to healthcare systems worldwide. The antibacterial activity of essential oil components (EOCs)—linalool, geraniol, eugenol, citronellol, 1,8-cineole, carvacrol, and trans-anethole—was evaluated both alone and in combinations against multidrug-resistant A. baumannii clinical strains from wound infections, and against two reference strains. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of EOCs were determined using the broth microdilution method. The interactions between EOCs were investigated using the checkerboard microdilution method. Carvacrol and eugenol showed the strongest inhibitory effects against the tested strains. The MICs and MBCs of carvacrol were 1.70–3.39 mg/mL. The MICs of eugenol were 4.10–16.41 mg/mL, while the MBCs were 4.10–32.81 mg/mL. MIC/MBC analysis showed that all tested EOCs had bactericidal activity against A. baumannii in vitro; however, some required higher concentrations. Most EOC mixtures showed synergistic interactions. The combination of eugenol and carvacrol induced the strongest synergistic effect, leading to the greatest reduction in the MICs of both compounds (MIC of carvacrol decreased by 8–30-fold, while the MIC of eugenol decreased by 16–64-fold). Our results indicate that some EOCs, especially when combined, exhibit significant antibacterial activity against A. baumannii.

Background/Objectives: Skin and soft tissue infections (SSTIs) remain a major clinical challenge due to the increasing prevalence of antimicrobial resistance and biofilm-associated pathogens. Conventional antibiotics are often limited by reduced efficacy, recurrent infections, and disruption of the resident skin microbiota. Consequently, bacteriocins have emerged as promising alternative or adjunctive antimicrobial agents for the treatment of skin and wound infections. Methods: A literature review was conducted using the PubMed, Scopus, and Web of Science databases. Experimental in vitro, ex vivo, and in vivo studies investigating bacteriocins in skin and wound infection models were analyzed, with a focus on antimicrobial activity, antibiofilm efficacy, activity against antimicrobial-resistant pathogens, and formulation strategies designed to improve therapeutic performance. Results: Available evidence demonstrates that numerous bacteriocins exhibit potent antimicrobial activity against clinically relevant skin-associated pathogens, particularly Staphylococcus aureus, including methicillin-resistant strains (MRSA). Several bacteriocins also showed significant antibiofilm properties and synergistic interactions with conventional antibiotics, resulting in enhanced bacterial eradication and reduced risk of resistance development. Experimental infection models further support their therapeutic potential in wound-associated infections. Additionally, advanced delivery platforms, including hydrogels, wound dressings, nanofibers, and lipid-based nanoparticles, improved peptide stability, sustained release, and local antimicrobial efficacy. Conclusions: Bacteriocins are promising candidates for the prevention and treatment of skin and wound infections due to their antimicrobial and antibiofilm activity, low propensity for resistance development, and suitability for topical administration. However, further studies addressing formulation optimization, safety, pharmacokinetics, and clinical validation are required before bacteriocin-based therapies can enter routine clinical practice.

Staphylococcus aureus nasal carriage contributes to asymptomatic transmission in both community and healthcare settings. This study aimed to characterize S. aureus strains isolated from students of the Pomeranian Medical University in Szczecin, Poland, using phenotypic and genotypic methods. A total of 175 S. aureus strains were isolated from the nasal vestibules of 800 students between 2014 and 2015. Species identification and antimicrobial susceptibility testing were performed using standard microbiological methods, while virulence-associated genes and agr groups were analyzed using Single-PCR and Multiplex-PCR assays. Genotypic diversity was assessed by pulsed-field gel electrophoresis (PFGE). The prevalence of S. aureus nasal carriage among students was 21.9% and did not differ according to faculty or year of study. Most isolates (84.0%) were susceptible to all tested antibiotics, and no methicillin-resistant S. aureus (MRSA) strains were detected. All strains carried the hla gene, whereas hld and hlg were identified in 93.7% and 93.1% of isolates, respectively. In addition, the tst gene was detected in 22.3% of strains, while the lukS-PV/lukF-PV genes were identified in only one isolate (0.6%). The most prevalent enterotoxin genes were sep (17.1%) and sea (13.7%), whereas genes of the egc cluster, including seg, sei, and seo, were detected in 53.7% of isolates. Significant associations were observed between specific egc gene combinations and superantigen gene profiles, including increased frequencies of sec, sel, and tst genes (p < 0.001). The predominant agr type was agr-1 (49.7%), followed by agr-3 (28.6%) and agr-2 (20.0%). Strains carrying agr-1 more frequently harbored the g i m n o cluster as well as the sec, sel, and sep genes, whereas agr-3-positive isolates were significantly associated with the g i m o u and g i o u clusters and with the presence of tst, sea, and seh genes (p < 0.05). PFGE analysis demonstrated substantial genetic heterogeneity among the isolates, with no evidence of a predominant clonal lineage. These findings indicate a heterogeneous, non-epidemic population structure of S. aureus strains circulating among university students and highlight the considerable diversity and interrelationships of virulence-associated genetic profiles within this population.

Aging is associated with chronic, low-grade inflammation ("inflammaging"), which contributes to neuropsychiatric and neurodegenerative disorders such as depression, Alzheimer's disease, and Parkinson's disease. Conventional pharmacotherapies often provide limited benefit in older adults and are further complicated by polypharmacy and drug-drug interactions. Psilocybin, a serotonergic psychedelic acting primarily as a partial agonist at the 5-HT2A receptor and currently undergoing accelerated clinical development, has emerged as a potential multimodal therapeutic agent addressing these challenges. Acting via its active metabolite psilocin, 5-HT2A receptor-mediated signaling modulates cortical glutamatergic transmission, enhances tropomyosin receptor kinase B/brain-derived neurotrophic factor (TrkB/BDNF) pathways, and modulates neuroimmune cascades (includingnuclear factor kappa B (NF-κB), with convergent systems-level effects such as reorganization of the default mode network. Human studies report acute reductions in TNF-α with variable effects on IL-6 and CRP, consistent with an immunomodulatory profile. Pharmacokinetically, psilocybin shows properties advantageous in geriatric care: rapid onset, short half-life, and predominant phase-II glucuronidation, reducing interaction risk. Controlled studies demonstrate rapid antidepressant and anxiolytic effects in major depressive disorder, treatment-resistant depression, and existential distress, with emerging feasibility signals in neurodegeneration. Together, these findings support the hypothesis that a time-limited, mechanism-based intervention may improve mood and cognition while attenuating inflammation. This review integrates current evidence on psilocybin's neuroimmune and pharmacokinetic mechanisms relevant to aging, outlining its potential role in inflammation-related disorders and highlighting the need for targeted studies in older adults, who remain underrepresented in psychedelic research.

For many years, staphylococci have been detected mainly in infections of the skin and soft tissues, organs, bone inflammations, and generalized infections. Thromboembolic diseases have also become a serious plague of our times, which, as it turns out, are closely related to the toxic effects of staphylococci. Staphylococcus aureus, because of the presence of many different kinds of virulence factors, is capable of manipulating the host’s innate and adaptive immune responses. These include toxins and cofactors that activate host zymogens and exoenzymes, as well as superantigens, which are highly inflammatory and cause leukocyte death. Coagulases and staphylokinases can control the host’s coagulation system. Nucleases and proteases inactivate various immune defense and surveillance proteins, including complement components, peptides and antibacterial proteins, and surface receptors that are important for leukocyte chemotaxis. On the other hand, secreted toxins and exoenzymes are proteins that disrupt the endothelial and epithelial barrier as a result of cell lysis and disintegration of linking proteins, which ultimately increases the risk of thromboembolism. In this review, we discuss various virulence factors and substances that may inhibit their activity.

Wound infections pose a significant challenge in modern medicine, driven by multimorbidity, weakened immunity, microbial virulence factors, and resistance to antibiotics and antiseptics. This study aims to evaluate the antibacterial properties of carvacrol (CAR), its impact on biofilm formation, and its capacity to trigger oxidative stress in clinical strains of Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter cloacae. Carbapenemases in the studied bacteria were detected using culture on CarbaId agar. The presence of genes encoding bacterial virulence factors and carbapenemase production was confirmed using the PCR method. The antimicrobial activity of carvacrol was evaluated using the broth microdilution method. The ability of strains to form biofilm was determined using a modified crystal violet assay. Oxidative stress levels in bacterial cells in response to carvacrol treatment were measured using 2′,7′-dichlorofluorescein diacetate. Real-TimePCR was used to confirm the presence of NDM family carbapenemase genes in K. pneumoniae strains, KPC genes in E. cloacae strains, and VIM genes in P. aeruginosa strains. CAR exhibited a broad spectrum of antibacterial activity against the tested bacteria, with MIC values ranging from 125 to 1000 μg/mL. Treatment with 1/2 MIC of CAR did not significantly influence biofilm formation, except in a K. pneumoniae isolate. At 1/2 MIC, CAR induced an increase in intracellular ROS in most tested strains, with the exception of P. aeruginosa 25521221. This study provides insights into the antimicrobial efficacy of carvacrol against carbapenemase-producing pathogens isolated from wound infections—specifically P. aeruginosa, K. pneumoniae, and E. cloacae. CAR demonstrated promising bactericidal properties, likely mediated through the induction of oxidative stress, as evidenced by increased ROS generation in most studied isolates.

Background/Objectives: Growing antibiotic resistance is one of the most significant problems of current medicine. Various research efforts are focused on the search for new substances and their combinations as potential solutions to this problem. Essential oil compounds (EOCs) are considered promising candidates in this regard. However, the interactions between these natural compounds remain understudied. This study conducted a preliminary evaluation of the antimicrobial action of various commercial EOCs (1,8-cineole, eugenol, linalyl acetate, (-)-α-pinene, limonene, α-terpineol, DL-menthol, geraniol, farnesol, carvacrol, and myrcene) alone and in combination (n = 56) against methicillin-resistant Staphylococcus aureus strain (ATCC 43300). Methods: The following parameters were studied: antibacterial activity of EOCs alone and in combination using microdilution and checkerboard assays. Results: After the initial screening, geraniol, farnesol, linalyl acetate, carvacrol, (-)-α-pinene, α-terpineol, 1,8-cineole, and eugenol exhibited antibacterial activity against the tested strain and were, therefore, selected for further evaluation in the checkerboard assay. The checkerboard assay revealed 10 synergistic interactions, with farnesol demonstrating the highest number of synergistic combinations among the tested compounds. The results highlighted its high synergistic potential in combination with eugenol, linalyl acetate, (-)-α-pinene, α-terpineol, geraniol, and carvacrol. Conclusions: In conclusion, the results help elucidate the different interactions between EOCs and may be helpful in further applications of natural compounds as antimicrobial agents in wound dressings. Overall, the most promising compound was found to be farnesol.

The treatment of infections caused by Staphylococcus hominis remains a challenge, mainly due to the increasing resistance of these bacteria to antibiotics. The aim of the study was to determine antibiotic resistance in 62 strains S. hominis isolated from clinical materials, and to identify the molecular basis of resistance to antibiotics. Forty-six strains were both methicillin-resistant and harbored the mecA gene. Twenty-three of these strains had mec complex A and ccr complex AB1. Such a combination of the mec and ccr complexes does not correspond to any cassettes that have been demonstrated so far. However, over 80% of the tested strains were multidrug-resistant, of which as many as 12 were resistant to at least seven antibiotics. More than a half of strains harbored the tetK, acc(6’)-Ie aph(2’’), and ant(4’)-I genes. erm(C) was the most common resistant gene to antibiotics from the MLS group. Two strains had as many as five antibiotic resistance genes from the tested groups (erm(C), msr(A), msr(B), mph(C), lnu(A)). The presence of the vga gene encoding resistance to streptogramins A was detected in one strain. All of strains were sensitive to vancomycin. However, 11 of them had reduced sensitivity to this antibiotic and eight of them were characterized by a heterogeneous resistance profile to this antibiotic. Our results clearly shows increasing threat of S. hominis caused by their multi-resistance. Moreover, these bacteria can constitute a reservoir of resistance genes for more pathogenic bacteria.

This study developed and evaluated plant-based mayonnaise formulations in which egg yolk was replaced with aquafaba (15–25%) and stabilized with gum tragacanth (0.3–1.0%). Formulations were prepared using canola oil and stored at 4 °C for 28 days. Aquafaba extract was characterized for total phenolic content (TPC) and total flavonoid content (TFC), while mayonnaise samples were assessed for physicochemical composition, creaming index, antioxidant activity, viscosity, texture, sensory properties, and microbiological stability. Total phenolic content (TPC) rose from 17.52 mg GAE/g at 10 µg to 135.34 mg GAE/g at 100 µg (p < 0.05), while total flavonoid content (TFC) increased from 76.95 to 192.42 mg TE/g over the same concentration range. These increases demonstrate the high antioxidant potential of aquafaba extract. The 25% aquafaba + 1% gum tragacanth formulation (T3) showed the highest protein content, viscosity, firmness, and antioxidant capacity, with improved storage stability compared to the control. FTIR analysis identified functional groups such as phenols, esters, and carboxylic acids, suggesting contributions to antioxidant activity and emulsion stability. Sensory evaluation indicated strong acceptance for T3. These results demonstrate that aquafaba combined with gum tragacanth can effectively replace egg yolk while maintaining desirable quality attributes.

Klebsiella pneumoniae is a typical opportunistic pathogen that exhibits multiple virulence factors and antibiotic resistance conditioning mechanisms. Carbapenemases are enzymes that help bacteria to exhibit the strongest resistance against antibiotics. Therefore, in routine microbiological diagnoses, it is crucial to confirm antibiotic-resistant strains, including carbapenemase-producing bacteria strains, isolated from patients. Two types of tests play an important role here: phenotypicand molecular diagnostic methods. The latter complement phenotypic tests and a mandatory procedure to confirm the detection of carbapenemases. This study aimed to evaluate the usefulness and effectiveness of tests and methods used to identify and confirm the ability of clinical K. pneumoniae strains to produce carbapenemases. The production of carbapenemases was assessed using phenotypic and genetic methods. The strains tested showed complete resistance to most beta-lactams and varying sensitivity to drugs from the quinolone carbapenem group and aminoglycosides. Among the most commonly produced carbapenemases were the metallo-beta-lactamase (NDM) family. The most accurate phenotypic method for detecting carbapenemases was the NG CARBA-5 assay, and the PCR method confirmed these results. Notably, a few inconclusive results were obtained for NDM-positive and VIM-positive strains when the disk diffusion method and CIM test were used. Further, the Carba tube assay and the RAPIDEC CARBA NP assay produced questionable results for the OXA-48 strain group. This group also generated false-negative results on Carba's CHROM ID medium.

Essential oils (EOs) and their compounds are becoming a growing interest in medical sciences. Despite their potential as antimicrobial, anxiolytic, cytotoxic, and immunosuppressive drugs, their chemical characteristics make them difficult to use in direct treatment. This article intends to summarize the current body of knowledge regarding drug delivery systems that can overcome obstacles, such as low water solubility, volatility, oxidation potential, photodegradation, and thermal instability of EO compounds. Various materials like zeolites, alginate, chitosan, cellulose nanomaterials, zein, poly (D,L-lactic-co-glycolic) acid, liposomes, nanoemulsions, and their modifications can help to mitigate these problems, but their utilization in medical settings is still lacking. The biggest issue in the utilization of natural compounds seems to be the very low number of clinical trials, which seriously impedes their usage despite favorable outcomes in/of in vitro experiments.

Infections caused by Acinetobacter baumannii are increasing worldwide. We evaluated the antibiotic resistance profile, biofilm production, and the frequency of 12 genes encoding carbapenemases and 13 virulence factors in 90 isolates from patients of three hospitals in various regions of Poland. Antibiotic resistance survey was performed using the disc-diffusion method, genes encoding resistance to carbapenems and virulence factors were detected with PCR, and biofilm formation was tested using microtiter plates. A total of 52.2% of isolates were resistant to all tested antibiotic groups (penicillins with β-lactamase inhibitors, cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and trimethoprim plus sulfamethoxazole). Among the genes encoding carbapenem resistance, the blaOXA-23 (68.9%), blaOXA-40 (83.3%), and ISAba-blaOXA-51 (18.9%) were detected. The ompA, ata, and recA genes responsible for biofilm formation, adhesion, and stress response, respectively, occurred in all isolates. Genes responsible for the production of other adhesins (bap—94.4%, espA—4.4%, chop—37.7%), biofilm formation (pbpG—90.0%), production of siderophore (basD—97.7%), toxins (lipA—92.2%, cpaA—1.1%), glycoconjugates (bfmR—84.4%), and inducing host cell death (fhaB—71.1%, abeD—93.3%) were also found. A total of 68.8% of isolates produced biofilm. The isolates from Masovia had more virulence genes than isolates from the other regions; moreover, all isolates from Masovia and West Pomerania were multidrug-resistant (MDR), including resistance to carbapenems.

The treatment of infections caused by Staphylococcus hominis remains a challenge, mainly due to the increasing resistance of these bacteria to antibiotics. The aim of the study was to determine antibiotic resistance in 62 strains S. hominis isolated from clinical materials, and to identify the molecular basis of resistance to antibiotics. Forty-six strains were both methicillin-resistant and harbored the mecA gene. Twenty-three of these strains had mec complex A and ccr complex AB1. Such a combination of the mec and ccr complexes does not correspond to any cassettes that have been demonstrated so far. However, over 80% of the tested strains were multidrug-resistant, of which as many as 12 were resistant to at least seven antibiotics. More than a half of strains harbored the tetK, acc(6’)-Ie aph(2”), and ant(4’)-I genes. erm(C) was the most common resistant gene to antibiotics from the MLS group. Two strains had as many as five antibiotic resistance genes from the tested groups (erm(C), msr(A), msr(B), mph(C), lnu(A)). The presence of the vga gene encoding resistance to streptogramins A was detected in one strain. All of strains were sensitive to vancomycin. However, 11 of them had reduced sensitivity to this antibiotic and eight of them were characterized by a heterogeneous resistance profile to this antibiotic. Our results clearly shows increasing threat of S. hominis caused by their multi-resistance. Moreover, these bacteria can constitute a reservoir of resistance genes for more pathogenic bacteria.

Ketamine is a new, potent and rapid-acting antidepressant approved for therapy of treatment-resistant depression, which has a different mechanism of action than currently-available antidepressant therapies. It owes its uniquely potent antidepressant properties to a complex mechanism of action, which currently remains unclear. However, it is thought that it acts by modulating the functioning of the glutamatergic system, which plays an important role in the process of neuroplasticity associated with depression. However, preclinical and clinical studies have also found ketamine to reduce inflammation, either directly or indirectly (by activating neuroprotective branches of the kynurenine pathway), among patients exhibiting higher levels of inflammation. Inflammation and immune system activation are believed to play key roles in the development and course of depression. Therefore, the present work examines the role of the antidepressant effect of ketamine and its anti-inflammatory properties in the treatment of depression. SIGNIFICANCE STATEMENT: The present work examines the relationship between the antidepressant effect of ketamine and its anti-inflammatory properties, and the resulting benefits in treatment-resistant depression (TRD). The antidepressant mechanism of ketamine remains unclear, and there is an urgent need to develop new therapeutic strategies for treatment of depression, particularly TRD.

Although the epidemiology and symptoms of major depressive disorder (MDD) have been well-documented, the etiology and pathophysiology of the disease have not yet been fully explained. Depression arises from intricate interplay among social, psychological, and biological factors. Recently, there has been growing focus on the involvement of miRNAs in depression, with suggestions that abnormal miRNA processing locally at the synapse contributes to MDD. Changes in miRNAs may result from altered expression and/or function of the miRNA biogenesis machinery at the synapse. The aim of our research was to assess the relationship between the occurrence of depression and single-nucleotide polymorphisms (SNP) in the following genes in the Polish population: DROSHA (rs6877842; rs10719) and XPO5 (rs11077). This study involved 200 individuals, including 100 with depressive disorders in the study group (SG) and 100 healthy people without MDD in the control group (CG). All participants were unrelated native Caucasian Poles from central Poland. Blood samples were collected to evaluate the single-nucleotide polymorphism of the genes. Findings indicated that within our patient cohort, the risk of depression is increased by polymorphic variants of the rs10719/DROSHA and rs11077/XPO5 genes and lowered by rs6877842/DROSHA. Our study sheds light on the understanding of the genetic basis of depression, which can be used in the rapid diagnosis of this disease.

Staphylococcus aureus, being one of the most common human pathogens, is responsible for infections in both hospital and community settings. Its virulence is attributed to its ability to evade the immune system by producing immune evasion (IE) proteins. The aim of this study was to detect the frequency of selected IE genes (spin, sbi, sea, sak, chp, scin, sep, ecb), belonging to the immune evasion cluster (IEC), and IEC types in 86 methicillin-susceptible S. aureus (MSSA) strains isolated from unrelated outpatients. In order to determine the diversity of analyzed strains, the phylogenetic relatedness was also determined. All strains were examined for the presence of IE genes using polymerase chain reaction assay. To analyze the clonal relatedness of S. aureus, pulsed-field gel electrophoresis (PFGE) was performed. All analyzed strains harbored the scn gene, followed by sbi (95.4%), ecb (91.7%), spin (89.5%), sak (83.7%), chp (67.4%), sep (67.4%) and sea (5.8%). Seventy-three (84.9%) S. aureus strains were classified into IEC types, of which, IEC type F was most commonly observed. IEC type A was not detected. PFGE results showed no association between clonal relatedness and the presence of IE genes/IEC types. In conclusion, the abundant and so diverse repertoire of genes determining invasion in analyzed strains may prove the fact that these strains are highly advanced and adapted to evade the host immune response.

The accumulation of ginsenosides (triterpenic saponins) was determined in Panax quinquefolium hairy root cultures subjected to an elicitation process using carvacrol at 5, 10, 25, 50, 100, 250, and 500 μM concentrations during 24 and 72 h exposure. This study was the first one in which carvacrol was applied as an elicitor. The content of eight ginsenosides, Rb1, Rb2, Rb3, Rc, Rd, Rg1, Rg2, and Re, was determined using HPLC analysis. Moreover, the quantitative RT-PCR method was applied to assess the relative expression level of farnesyl diphosphate synthase, squalene synthase, and dammarenediol synthase genes in the studied cultures. The addition of carvacrol (100 μM) was an effective approach to increase the production of ginsenosides. The highest content and productivity of all detected saponins were, respectively, 20.01 mg∙g−1 d.w. and 5.74 mg∙L−1∙day−1 after 72 h elicitation. The production profile of individual metabolites in P. quinquefolium cultures changed under the influence of carvacrol. The biosynthesis of most examined protopanaxadiol derivatives was reduced under carvacrol treatment. In contrast, the levels of ginsenosides belonging to the Rg group increased. The strongest effect of carvacrol was noticed for Re metabolites, achieving a 7.72-fold increase in comparison to the control. Saponin Rg2, not detected in untreated samples, was accumulated after carvacrol stimulation, reaching its maximum concentration after 72 h exposure to 10 μM elicitor.

Lactobacillus acidophilus is a probiotic bacterium that possesses numerous health-promoting properties and has significant technological applications in the fermentation of a wide range of food products and beverages. This review discusses the health benefits of L. acidophilus, including its ability to enhance immunity; promote digestive wellness; and exhibit antioxidant, antitumor, and antimicrobial properties. This review also discusses the production of bioactive peptides and extracellular polysaccharides (EPS) by L. acidophilus. Factors, such as salinity, temperature, carbon sources, and nutrient availability, influence the growth of L. acidophilus, which can affect the survival and bioactive potential of fermented products. The proteolytic effects of L. acidophilus contribute to protein breakdown, which leads to the release of bioactive peptides with various health benefits. This review also discusses the applications of L. acidophilus in the fermentation of dairy products, cereal beverages, soymilk, fruit and vegetable juices, and other functional food preparations, highlighting its potential for improving the nutritional value, organoleptic properties, and probiotic delivery of these products. This review highlights the importance of understanding and controlling fermentation conditions to maximize the growth and health-promoting benefits of L. acidophilus in various food and beverage products.

Staphylococci are responsible for many infections in humans, starting with skin and soft tissue infections and finishing with invasive diseases such as endocarditis, sepsis and pneumonia, which lead to high mortality. Patients with sepsis often demonstrate activated clotting pathways, decreased levels of anticoagulants, decreased fibrinolysis, activated endothelial surfaces and activated platelets. This results in disseminated intravascular coagulation and formation of a microthrombus, which can lead to a multiorgan failure. This review describes various staphylococcal virulence factors that contribute to vascular thrombosis, including deep vein thrombosis in infected patients. The article presents mechanisms of action of different factors released by bacteria in various host defense lines, which in turn can lead to formation of blood clots in the vessels.