Contribution of staphylococcal virulence factors in the pathogenesis of thrombosis.

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.

Ketamine - A New Antidepressant Drug with Anti-Inflammatory Properties.

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.

Antidepressant mechanisms of ketamine's action: NF-κB in the spotlight.

Ketamine recently approved for therapy of treatment-resistant depression shows a complex and not fully understood mechanism of action. Apart from its classical glutamatergic N-methyl-D-aspartate receptor antagonistic action, it is thought that anti-inflammatory properties of the drug are of clinical relevance due to the contribution of activated inflammatory mediators to the pathophysiology of depression and non-responsiveness of a group of patients to current antidepressant therapies. In a search of the mechanism underlying anti-inflammatory effects of ketamine, the nuclear factor kappa B transcription factor (NF-κB) has been proposed as a target for ketamine. The NF-κB forms precisely regulated protein signaling cascades enabling a rapid response to cellular stimuli. In the central nervous systems, NF-κB signaling appears to have pleiotropic but double-edged functions: on the one hand it participates in the regulation of processes that are crucial in the treatment of depression, such as neuroplasticity, neurogenesis or neuronal survival, on the other - in the activation of neuroinflammation and cell death. Ketamine has been found to reduce inflammation mediated by NF-κB, leading to decreased level of pro-inflammatory cytokines and other inflammatory or stress mediators. Therefore, this review presents recent data on the significance of the NF-κB cascade in the mechanism of ketamine's action and its future perspectives in designing new strategies for the treatment of depression.

Personality traits and health-related behaviors in medical students facing a stressful event.

Background: It is believed that personality traits have an impact on the propensity to change and maintain favorable lifestyle habits. This issue has been raised by multiple studies, however, none of them appeared to focus on population under severe psychological stress. The aim of the present study was to investigate the link between personality traits and health-related behaviors and measures such as dietary intake of specific food products, physical activity, body-mass index and the use of cigarettes in medical students facing a stressful event. Methods: The study included a cohort of third-year medical students from the Medical University of Lodz, Poland, facing a stressful subject exam during the first COVID-19-related lockdown. At baseline, personality traits were evaluated with the use of the Polish version of the Big Five Inventory-Short questionnaire. Then, consumption of selected food products was monitored with the use of seven-day electronic dietary record. Also, some other health-related data was collected (body-mass index, physical activity and the use of cigarettes). General Linear Modeling techniques, logistic regression and exploratory factor analysis were applied to analyze the data. Results: Four hundred and forty-four students completed the study. A two-factor pattern of food consumption was discovered by the exploratory factor analysis in the study group (34% of the variance explained). Higher conscientiousness, but not the other personality traits, was found to be significantly associated with generally healthier lifestyle manifested by higher consumption of vegetables, wholegrain products, fruits and nuts (adjusted beta 0.16, 95%CI 0.06 to 0.26, pη2 = 2.3%, p = 0.0015) and lower cigarette smoking (adjusted odds ratio 0.84, 95%CI 0.75 to 0.94, p = 0.0020), but insignificantly with physical activity and body-mass index. Conclusion: Severely stressed medical students expressing high conscientiousness tend to present healthier behaviors. Therefore, interventions aimed at improving lifestyle habits in students with low conscientiousness might be useful.

Deciphering psychobiotics' mechanism of action: bacterial extracellular vesicles in the spotlight.

The intake of psychobiotic bacteria appears to be a promising adjunct to neuropsychiatric treatment, and their consumption may even be beneficial for healthy people in terms of mental functioning. The psychobiotics' mechanism of action is largely outlined by the gut-brain axis; however, it is not fully understood. Based on very recent studies, we provide compelling evidence to suggest a novel understanding of this mechanism: bacterial extracellular vesicles appear to mediate many known effects that psychobiotic bacteria exert on the brain. In this mini-review paper, we characterize the extracellular vesicles derived from psychobiotic bacteria to demonstrate that they can be absorbed from the gastrointestinal tract, penetrate to the brain, and carry the intracellular content to exert beneficial multidirectional action. Specifically, by regulating epigenetic factors, extracellular vesicles from psychobiotics appear to enhance expression of neurotrophic molecules, improve serotonergic neurotransmission, and likely supply astrocytes with glycolytic enzymes to favor neuroprotective mechanisms. As a result, some data suggest an antidepressant action of extracellular vesicles that originate even from taxonomically remote psychobiotic bacteria. As such, these extracellular vesicles may be regarded as postbiotics of potentially therapeutic application. The mini-review is enriched with illustrations to better introduce the complex nature of brain signaling mediated by bacterial extracellular vesicles and indicates knowledge gaps that require scientific exploration before further progress is made. In conclusion, bacterial extracellular vesicles appear to represent the missing piece of the puzzle in the mechanism of action of psychobiotics.

The Effect of Diosmin, Escin, and Bromelain on Human Endothelial Cells Derived from the Umbilical Vein and the Varicose Vein-A Preliminary Study.

In this study, we investigated the properties of human varicose vein (VV) endothelial cells (HVVEC) in comparison to the human umbilical vein endothelial cells (HUVEC). The cells were treated with three bioactive compounds with proven beneficial effects in the therapy of patients with VV, diosmin, escin, and bromelain. Two concentrations of tested drugs were used (1, 10 mg/mL), which did not affect the viability of either cell type. Escin led to a slight generation of reactive oxygen species in HUVEC cells. We observed a slight release of superoxide in HVVEC cells upon treatment with diosmin and escin. Diosmin and bromelain showed a tendency to release nitric oxide in HUVEC. Using membrane fluorescent probes, we demonstrated a reduced fluidity of HVVEC, which may lead to their increased adhesion, and, consequently, a much more frequent occurrence of venous thrombosis. For the first time, we show the mechanism of action of drugs used in VV therapy on endothelial cells derived from a VV. Studies with HVVEC have shown that tested drugs may lead to a reduction in the adhesive properties of these cells, and thus to a lower risk of thrombosis.

Gut Microbiota Metabolites Differentially Release Gliotransmitters from the Cultured Human Astrocytes: A Preliminary Report.

Butyrate and indole-3-propionic acid represent the CNS-available gut microbiota metabolites exhibiting potentially beneficial effects on human brain function and being tested as antidepressants. Astrocytes represent one of the putative targets for the gut metabolites; however, the mechanism of action of butyrate and indole-3-propionic acid is not well understood. In order to test this mechanism, a human astrocyte cell-line culture was treated with the compounds or without them, and the supernatants were collected for the analysis of ATP and glutamate gliotransmitter release with the use of luminescent and fluorescent methods, respectively. A 10-min incubation of astrocytes with 1-5 mM butyrate increased the ATP gliotransmitter release by 78% (95%CI: 45-119%), p < 0.001. The effect was found to be mediated by the cytosolic Ca2+ mobilization. Both 10-min and 24-h treatments with indole-3-propionic acid produced no significant effects on the release of gliotransmitters. The results for glutamate release were inconclusive due to a specific glutamate release pattern discovered in the tested model. This preliminary report of butyrate-induced ATP gliotransmitter release appears to provide a novel mechanistic explanation for the beneficial effect of this gut microbiota metabolite on brain function; however, the results require further evaluation in more composed models.

Diosmin and Bromelain Stimulate Glutathione and Total Thiols Production in Red Blood Cells.

Diosmin and bromelain are bioactive compounds of plant origin with proven beneficial effects on the human cardiovascular system. We found that diosmin and bromelain slightly reduced total carbonyls levels and had no effect on TBARS levels, as well as slightly increased the total non-enzymatic antioxidant capacity in the RBCs at concentrations of 30 and 60 µg/mL. Diosmin and bromelain induced a significant increase in total thiols and glutathione in the RBCs. Examining the rheological properties of RBCs, we found that both compounds slightly reduce the internal viscosity of the RBCs. Using the MSL (maleimide spin label), we revealed that higher concentrations of bromelain led to a significant decrease in the mobility of this spin label attached to cytosolic thiols in the RBCs, as well as attached to hemoglobin at a higher concentration of diosmin, and for both concentrations of bromelain. Both compounds tended to decrease the cell membrane fluidity in the subsurface area, but not in the deeper regions. An increase in the glutathione concentration and the total level of thiol compounds promotes the protection of the RBCs against oxidative stress, suggesting that both compounds have a stabilizing effect on the cell membrane and improve the rheological properties of the RBCs.

Mental Health of Students at Polish Universities after Two Years of the Outbreak of COVID-19.

BACKGROUND: Mental health deterioration in young adults in the aftermath of the COVID-19 pandemic is being increasingly studied. It is clear that the psychological consequences of the pandemic will be evident for many years, especially among the younger generation, who did not have time to acquire adaptive coping strategies before the outbreak of COVID-19. The purpose of this study was to assess the condition of the mental health of students at Polish universities after two years of the pandemic. The types of coping strategies used by the respondents to deal with stress were also evaluated in order to establish which of them could have a beneficial effect on the psyche of young people. METHODS: This study included 721 participants (age [years]: M = 25.7, SD = 5.3; 269 (37.2%) males) recruited using snowball sampling from students at two universities in Lodz, Poland, and full-time doctoral students from across Poland (phase I of the study was conducted in March 2019 (N = 352); phase II of the study was conducted in April 2022 (N = 369)). The following tools were used in this study: The General Health Questionnaire (GHQ-28) by D. Goldberg, the Perceived Stress Scale (PSS-10), and the Inventory for Measuring Coping with Stress (Mini-COPE) by Carver et al. Pearson's chi-square test and multivariate logistic regression were used in the statistical analysis. RESULTS: The results detailing the condition of the mental health of the subjects, as measured using GHQ-28, were significantly worse in the group surveyed after two years of the pandemic than the results of the survey conducted in March 2019 (adjusted odds ratio for GHQ-28 ≥ 5: 3.66, 95%CI 2.12-6.30, p < 0.001). Statistically significant differences were seen for each of the subscales of the GHQ-28 questionnaire. Most often, the subjects complained of anxiety symptoms and sleep disorders, in addition to somatic symptoms. The risk factors for worsening mental health included female (odds ratio 1.70, 95%CI 1.20-2.40, p = 0.003) and professional inactivity (odds ratio 1.55, 95%CI 1.04-2.31, p = 0.031). On the other hand, the ages of the people surveyed, their relationship status, whether they had children, or the type of university they attended all proved to be insignificant. The following coping strategies had a positive impact on the mental health of the respondents: positive reframing (Z = -2.951; p = 0.003) and seeking emotional support (Z = -2.351; p = 0.019). In contrast, strategies such as self-distraction (Z = 2.785; p = 0.005), denial (Z = 2.948; p = 0.003), venting (Z = 2.337; p = 0.019), self-blame (Z = 5.511; p < 0.001) and behavioral disengagement (Z = 4.004; p < 0.001) were associated with poorer mental health among the respondents. CONCLUSIONS: 1. Of the students surveyed, 33% reported elevated stress levels after two years of the COVID-19 pandemic. 2. The overall mental health of students at Polish universities, as measured by GHQ-28, was significantly worse in the group evaluated after two years of the COVID-19 pandemic, mainly in respect of anxiety symptoms and sleep disorders. 3. Female gender and professional inactivity appeared to be risk factors for the students' worsening mental health, which may be an indication of the need for further research and planning of psychotherapeutic interventions.

Genetic Diversity of Candida spp. Isolates Colonizing Twins and Their Family Members.

A wide range of options for studying Candida species are available through genetic methods. Twins, particularly monozygotic ones and their families may be fitting subjects for studying those microorganisms. The question is: How specific can yeast flora be in an individual? The study aimed to analyze the strain relatedness among commensal yeasts isolated from various parts of the bodies of healthy people and to compare correlations between the genotypes of the isolates. Yeasts were isolated from 63 twins and their family members (n = 25) from the oral cavity, anus, interdigital space and navel. After species identification, Candida albicans (n = 139), C. parapsilosis (n = 39), C. guilliermondii (n = 25), C. dubliniensis (n = 11) and C. krusei (n = 9) isolates were analyzed using the random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) optimization method. The similarities between the strains were calculated based on the Dice (Sab) coefficient and are displayed graphically as dendrograms. Using cluster analysis, the following relatedness was distinguished: 13 genotypes and three unique (Un) patterns among C. albicans; 10 genotypes and four Un patterns among C. parapsilosis; three genotypes and one Un pattern among C. guilliermondii and C. dubliniensis; and three genotypes among C. krusei isolates. The presence of identical, similar or both genotypes among the strains isolated from family members shows the transmission of yeasts between ontocenoses in the same person and between individuals. The similarity between the genotypes of C. albicans, C. guilliermondii, C. dubliniensis and C. krusei was more remarkable than between the genotypes of C. parapsilosis in the strains isolated from ontocenoses of the same individual and their family members. The degrees of genetic similarity between Candida spp. strains isolated from monozygotic twins and those obtained from their relatives did not differ.

Association of polymorphic variants in GEMIN genes with the risk of depression in a Polish population.

Background: The role of miRNA in depression is widely described by many researchers. miRNA is a final product of many genes involved in its formation (maturation). One of the final steps in the formation of miRNAs is the formation of the RISC complex, called the RNA-induced silencing complex, which includes, among others, GEMIN proteins. Single-nucleotide polymorphisms (SNPs) may lead to disturbance of miRNA biogenesis and function. The objective of our research was to assess the relationship between the appearance of depression and single nucleotide polymorphisms in the GEMIN3 (rs197388) and GEMIN4 (rs7813; rs3744741) genes. Our research provides new knowledge on the genetic factors that influence the risk of depression. They can be used as an element of diagnostics helpful in identifying people at increased risk, as well as indicating people not at risk of depression. Methods: A total of 218 participants were examined, including individuals with depressive disorders (n = 102; study group) and healthy people (n = 116, control group). All the patients in the study group and the people in the control group were non-related native Caucasian Poles from central Poland. Blood was collected from study and control groups in order to assess the SNPs of GEMIN genes. Results: An analysis of the results obtained showed that in patient population, the risk of depression is almost doubled by polymorphic variants of the genes: rs197388/GEMIN3 genotype A/A in the recessive model and rs3744741/GEMIN4 genotype T/T, codominant and recessive model. The dual role of rs7813/GEMIN4 is noteworthy, where the G/A genotype in the codominant and over dominant model protects against depression.

Association of Polymorphic Variants in Argonaute Genes with Depression Risk in a Polish Population.

Argonaute (AGO) proteins, through their key role in the regulation of gene expression, participate in many biological processes, including cell differentiation, proliferation, death and DNA repair. Accurate regulation of gene expression appears to be important for the proper development of complex neural circuits. Loss of AGO proteins is known to lead to early embryonic mortality in mice with various malformations, including anomalies of the central nervous system. Single-nucleotide polymorphisms (SNPs) of AGO genes can lead to deregulation of the processes in which AGO proteins are involved. The contribution of different SNPs in depression has been extensively studied. However, there are hardly any studies on the contribution of AGO genes. The aim of our research was to assess the relationship between the occurrence of depression and the presence of SNPs in genes AGO1 (rs636882) and AGO2 (rs4961280; rs2292779; rs2977490) in a Polish population. One hundred and one subjects in the study group were diagnosed with recurrent depressive disorder by a psychiatrist. The control group comprised 117 healthy subjects. Study participants performed the HDRS (Hamilton Depression Scale) test to confirm or exclude depression and assess severity. The frequency of polymorphic variants of genes AGO1 (rs636882) and AGO2 (rs4961280; rs2292779; rs2977490) was determined using TaqMan SNP genotyping assays and the TaqMan universal PCR master mix, no AmpErase UNG. The rs4961280/AGO2 polymorphism was associated with a decrease in depression occurrence in the codominant (OR = 0.51, p = 0.034), dominant (OR = 0.49, p = 0.01), and overdominant (OR = 0.58, p = 0.049) models. Based on the obtained results, we found that the studied patients demonstrated a lower risk of depression with the presence of the polymorphic variant of the rs4961280/AGO2 gene-genotype C/A and C/A-A/A.

Diclofenac Diminished the Unfolded Protein Response (UPR) Induced by Tunicamycin in Human Endothelial Cells.

Diclofenac belongs to the class of nonsteroidal anti-inflammatory drugs (NSAIDs), which are amongst the most frequently prescribed drugs to treat fever, pain and inflammation. Despite the presence of NSAIDs on the pharmaceutical market for several decades, epidemiological studies have shown new clinical applications of NSAIDs, and new mechanisms of their action were discovered. The unfolded protein response (UPR) activated under endoplasmic reticulum (ER) stress is involved in the pathophysiology of many diseases and may become a drug target, therefore, the study evaluated the effects of diclofenac on the tunicamycin-induced UPR pathways in endothelial cells. RT PCR analysis showed that diclofenac significantly inhibited activation of ER stress-responsive genes, i.e., CHOP/DITT3, GRP78/HSPA5 and DNAJB9. Additionally, the drug diminished the significant upregulation and release of the GRP78 protein, as evaluated using the ELISA assay, which was likely to be involved in the mechanism of the UPR activation resulting in apoptosis induction in endothelial cells. These results suggest the value of diclofenac as a factor capable of restoring the ER homeostasis in endothelial cells by diminishing the UPR.

Mechanisms of Cognitive Impairment in Depression. May Probiotics Help?

Depression is the major cause of disability globally. Apart from lowered mood and accompanying symptoms, it leads to cognitive impairment that altogether predicts disadvantaged social functioning. Reduced cognitive function in depression appears a bit neglected in the field of clinical and molecular psychiatry, while it is estimated to occur in two-thirds of depressed patients and persist in at least one third of remitted patients. This problem, therefore, requires elucidation at the biomolecular and system levels and calls for improvement in therapeutic approach. In this review study, we address the above-mentioned issues by discussing putative mechanisms of cognitive decline in depression: (1) increased oxidative stress and (2) inflammation, (3) disturbed hypothalamus-pituitary-adrenals axis, and (4) reduced monoamines functionality. Moreover, we acknowledge additional underpinnings of cognitive impairment in depressed elderly: (5) vascular-originated brain ischemia and (6) amyloid-beta plaque accumulation. Additionally, by reviewing molecular, pre-clinical and clinical evidence, we propose gut microbiota-targeted strategies as potential adjuvant therapeutics. The study provides a consolidated source of knowledge regarding mechanisms of cognitive impairment in depression and may path the way toward improved treatment options.

The Importance of Endoplasmic Reticulum Stress as a Novel Antidepressant Drug Target and Its Potential Impact on CNS Disorders.

Many central nervous system (CNS) diseases, including major depressive disorder (MDD), are underpinned by the unfolded protein response (UPR) activated under endoplasmic reticulum (ER) stress. New, more efficient, therapeutic options for MDD are needed to avoid adverse effects and drug resistance. Therefore, the aim of the work was to determine whether UPR signalling pathway activation in astrocytes may serve as a novel target for antidepressant drugs. Among the tested antidepressants (escitalopram, amitriptyline, S-ketamine and R-ketamine), only S-ketamine, and to a lesser extent R-ketamine, induced the expression of most ER stress-responsive genes in astrocytes. Furthermore, cell viability and apoptosis measuring assays showed that (R-)S-ketamine did not affect cell survival under ER stress. Under normal conditions, S-ketamine played the key role in increasing the release of brain-derived neurotrophic factor (BDNF), indicating that the drug has a complex mechanism of action in astrocytes, which may contribute to its therapeutic effects. Our findings are the first to shed light on the relationship between old astrocyte specifically induced substance (OASIS) stabilized by ER stress and (R-)S-ketamine; however, the possible involvement of OASIS in the mechanism of therapeutic ketamine action requires further study.

Who Benefits from Fermented Food Consumption? A Comparative Analysis between Psychiatrically Ill and Psychiatrically Healthy Medical Students.

Probiotic therapies and fermented food diets hold promise for improving mental health. Although in this regard psychiatric patients appear to benefit more than healthy individuals, no research has been performed to directly evaluate this hypothesis. The present study examined a cohort of medical students facing a stressful event, and some of the students reported suffering from chronic psychiatric diseases. The amount of fermented food consumption was calculated with the use of seven-day dietary records, while depressive and anxiety symptoms were assessed with the use of the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7, respectively. In psychiatrically healthy medical students under psychological stress (n = 372), higher fermented food consumption was associated with more depressive and anxiety symptoms. In contrast, psychiatrically ill medical students (n = 25, 6.3% of all the participants) were found to present a negative association between the amount of fermented food consumed and the severity of depressive symptoms (adjusted ß -0.52, 95% CI -0.85 to -0.19, p = 0.0042); however, this relationship was insignificant for anxiety symptoms (adjusted ß -0.22, 95% CI -0.59 to 0.15, p = 0.22). A significant interaction was found between the consumption of fermented food and psychiatric diagnosis in predicting depressive symptoms (p = 0.0001), and a borderline significant interaction for anxiety symptoms (p = 0.053). In conclusion, psychiatrically ill people, but not healthy ones, may benefit from fermented food consumption in terms of alleviation of depressive symptoms. Our findings require cautious interpretation and further investigation.

Association Between Consumption of Fermented Food and Food-Derived Prebiotics With Cognitive Performance, Depressive, and Anxiety Symptoms in Psychiatrically Healthy Medical Students Under Psychological Stress: A Prospective Cohort Study.

Background: Gut microbiota-based therapeutic strategies, such as probiotic and prebiotic preparations, may benefit mental health. However, commonly consumed fermented and prebiotic-containing foods have not been well-tested. The aim of the present study was to determine whether consumption of fermented food and food-derived prebiotics is associated with cognitive performance, depressive, and anxiety symptoms in psychiatrically healthy medical students under psychological stress. Methods: The study protocol with data analysis plan was prospectively registered. Food consumption was evaluated with a 7-day dietary record. Cognitive performance was modeled with academic examination performance in relation to subject knowledge. Pre-exam depressive and anxiety symptoms were assessed with the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7, respectively. Results: In total, 372 medical students (22.7 ± 1.1 years of age, 66% female) completed the study. No relationship was observed between cognitive performance under stress and either fermented food (adjusted ß 0.02, 95% CI -0.07-0.11, p = 0.63) or food-derived prebiotics consumption (adjusted ß -0.00, 95% CI -0.09-0.09, p = 0.99). High intake of fermented food was associated with more severe depressive (adjusted ß 0.11, 95% CI 0.01-0.20, p = 0.032) and anxiety symptoms under stress (adjusted ß 0.13, 95% CI 0.04-0.22, p = 0.0065); however, no such link was observed for food-derived prebiotics (adjusted ß 0.03, 95% CI -0.07-0.13, p = 0.50 and -0.01, 95% CI -0.11-0.08, p = 0.83, for depression and anxiety, respectively). Conclusions: Under psychological stress in medical students, consumption of fermented food and food-derived prebiotics appears to be not associated with cognitive performance. High intake of fermented food, but not food-derived prebiotics, may be associated with severity of depressive and anxiety symptoms. The safety of fermented food in this regard therefore requires further clarification.

Cross-Reactive Results in Serological Tests for Borreliosis in Patients with Active Viral Infections.

Currently, serological tests for Lyme disease (LD), routinely performed in laboratories following the European Concerted Action on Lyme Borreliosis recommendations as part of two-stage diagnostics, are often difficult to interpret. This concerns both the generation of false positive and negative results, which frequently delay the correct diagnosis and implementation of appropriate treatment. The above problems result from both morphological and antigenic variability characteristics for the life strategy of the spirochete Borrelia burgdorferi sensu lato, a complicated immune response, and imperfections in diagnostic methods. The study aimed to check the reactivity of sera from 69 patients with confirmed infection with Epstein-Barr virus (EBV), cytomegalovirus (CMV) and BK virus (BKV) with Borrelia antigens used in serological tests: indirect immunofluorescence (IIFT), enzyme-linked immunosorbent (ELISA) and immunoblot (IB). In the group of patients infected with EBV, the highest percentage of positive/borderline anti-Borrelia IgM and IgG results was obtained in the following tests: IIFT (51.9% for IgM, 63.0% for IgG), ELISA (22.2% for IgM, 29.6% for IgG) and IB (11.1% for IgM, 7.4% for IgG). In the group of CMV-infected patients, the highest percentage of positive/borderline anti-Borrelia IgM results were obtained in the following tests: IB (23.1%), IIFT (15.4%) and ELISA (7.7%), while in the IgG class in the IIFT (15.4%), IB (11.5%) and ELISA (3.9%) tests. In the group of patients infected with BKV, the highest percentage of positive/borderline anti-Borrelia IgM results was obtained in the following tests: IIFT (25.0%), IB (25.0%) and ELISA (3.9%), and in the IgG class in the tests: IB (50.0%), IIFT (6.2%) and ELISA (6.2%). The native flagellin (p41) and OspC proteins were the most frequently detected Borrelia antigens in all studied groups of patients in both classes of antibodies. Similar to other authors, the study confirmed the fact that serological tests used in the diagnosis of LD have a high potential to generate false positive results in patients with active viral infections, which may be related to cross-reacting antibodies appearing during the most common polyclonal activation of T/B lymphocytes, activated by viral superantigens.

Cellular Response to Unfolded Proteins in Depression.

Despite many scientific studies on depression, there is no clear conception explaining the causes and mechanisms of depression development. Research conducted in recent years has shown that there is a strong relationship between depression and the endoplasmic reticulum (ER) stress. In order to restore ER homeostasis, the adaptive unfolded protein response (UPR) mechanism is activated. Research suggests that ER stress response pathways are continuously activated in patients with major depressive disorders (MDD). Therefore, it seems that the recommended drugs should reduce ER stress. A search is currently underway for drugs that will be both effective in reducing ER stress and relieving symptoms of depression.

Ketamine-New Possibilities in the Treatment of Depression: A Narrative Review.

The SARS-CoV-2 coronavirus epidemic has led to an increase in the number of people with depression. Symptoms related to the mental sphere (mainly depression and anxiety) may be experienced by one third of the worldwide population. This entails the need for the effective and rapid treatment of depressive episodes. An effective drug seems to be s-ketamine, which was accepted in March 2019 by the Food and Drug Administration (FDA) for the treatment of drug-resistant depression. This drug provides a quick antidepressant effect with maximum effectiveness achieved after 24 h. It also appears to reduce the occurrence of suicidal thoughts. However, research into undesirable effects, especially in groups of people susceptible to psychotic episodes or those who use alcohol or psychoactive substances, is necessary.