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.

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.

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.

Fluorinated Analogues of Lepidilines A and C: Synthesis and Screening of Their Anticancer and Antiviral Activity.

Starting with fluorinated benzylamines, a series of 2-unsubstituted imidazole N-oxides was prepared and subsequently deoxygenated in order to prepare the corresponding imidazoles. The latter were treated with benzyl halides yielding imidazolium salts, which are considered fluorinated analogues of naturally occurring imidazolium alkaloids known as lepidilines A and C. A second series of oxa-lepidiline analogues was obtained by O-benzylation of the initially synthetized imidazole N-oxides. Both series of imidazolium salts were tested as anticancer and antiviral agents. The obtained results demonstrated that the introduction of a fluorine atom, fluoroalkyl or fluoroalkoxy substituents (F, CF3 or OCF3) amplifies cytotoxic properties, whereas the cytotoxicity of some fluorinated lepidilines is promising in the context of drug discovery. All studied compounds revealed a lack of antiviral activity against the investigated viruses in the nontoxic concentrations.

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.

Brain Network Dysfunction in Poststroke Delirium and Spatial Neglect: An fMRI Study.

BACKGROUND AND PURPOSE: Delirium, an acute reduction in cognitive functioning, hinders stroke recovery and contributes to cognitive decline. Right-hemisphere stroke is linked with higher delirium incidence, likely, due to the prevalence of spatial neglect (SN), a right-brain disorder of spatial processing. This study tested if symptoms of delirium and SN after right-hemisphere stroke are associated with abnormal function of the right-dominant neural networks specialized for maintaining attention, orientation, and arousal. METHODS: Twenty-nine participants with right-hemisphere ischemic stroke undergoing acute rehabilitation completed delirium and SN assessments and functional neuroimaging scans. Whole-brain functional connectivity of 4 right-hemisphere seed regions in the cortical-subcortical arousal and attention networks was assessed for its relationship to validated SN and delirium severity measures. RESULTS: Of 29 patients, 6 (21%) met the diagnostic criteria for delirium and 16 (55%) for SN. Decreased connectivity of the right basal forebrain to brain stem and basal ganglia predicted more severe SN. Increased connectivity of the arousal and attention network regions with the parietal, frontal, and temporal structures in the unaffected hemisphere was also found in more severe delirium and SN. CONCLUSIONS: Delirium and SN are associated with decreased arousal network activity and an imbalance of cortico-subcortical hemispheric connectivity. Better understanding of neural correlates of poststroke delirium and SN will lead to improved neuroscience-based treatment development for these disorders. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03349411.

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.

Mental Health of PhD Students at Polish Universities-Before the COVID-19 Outbreak.

BACKGROUND: A group particularly exposed to the occurrence of disorders in the sphere of the psyche are young people with a newly developing personality structure and a sense of identity. In the available literature there are few reports describing the mental health of doctoral students-a group that is affected by a particular group of stressors. The aim of the research was to assess the mental health of PhD students at Polish universities. MATERIAL AND METHODS: The Polish adaptation of the GHQ Questionnaire-28, developed by David Goldberg et al. was used in the research. PhD students from all universities associated in the National Representation of Doctoral Students were invited to take part in the research. A total of 576 completed questionnaires were received. RESULTS: It was found that depression is statistically more frequent in doctoral students who are not in any relationship with another person; anxiety/insomnia is more common in women than men and less frequently in doctoral students of general than in technical universities. CONCLUSIONS: (1) More than half of the surveyed students complain about the deterioration of mental health. The most commonly reported symptom groups are anxiety and insomnia, followed by social dysfunctions and somatic symptoms. (2) Depression is statistically more common in people who are not in any relationship with another person and anxiety and insomnia are statistically more common in women than in men and statistically less frequent in doctoral students of general universities than technical universities. (3) In view of the presented results, educating young adults in the field of self-awareness in the field of mental health seems to be particularly important.

Synthesis and Cytotoxic Activity of Lepidilines A-D: Comparison with Some 4,5-Diphenyl Analogues and Related Imidazole-2-thiones.

A straightforward access to 2-unsubstituted imidazole N-oxides with subsequent deoxygenation by treatment with Raney-nickel followed by N-benzylation opens up a convenient route to lepidilines A and C. Both imidazolium salts were used to generate in situ the corresponding imidazol-2-ylidenes, which smoothly reacted with elemental sulfur, yielding imidazole-2-thiones. These reactions were performed either under classical conditions in pyridine solutions or mechanochemically using solid Cs2CO3 as a base. The structure of lepidiline C was unambiguously confirmed by X-ray analysis of its hexafluorophosphate. An analogous protocol toward lepidilines B and D and their 4,5-diphenyl analogues is less efficient due to observed instability of the key precursors, i.e., the respective 2-methylimidazole N-oxides. Comparison of cytotoxic activity against HL-60 and MCF-7 cell lines of all lepidilines, as well as their selected structural analogues (e.g., 4,5-diphenyl derivatives and PF6 salts), revealed slightly more potent activity of the 2-methylated series, irrespectively of the type of counterion present in the imidazolium salt. Remarkably, the well-known 1,3-diadamantylimidazolium bromide (the "Arduengo salt"), known as the precursor of the first, shelf-stable NHC representative, and its adamantyloxy analogue displayed the most significant cytotoxic activity in the studied series.

Lewis-Acid-Catalyzed (3+2)-Cycloadditions of Donor-Acceptor Cyclopropanes with Thioketenes.

The reactivity of donor-acceptor (D-A) cyclopropanes towards thioketenes was investigated. In a (3+2)-cycloaddition using Sc(OTf)3 as a Lewis acidic catalyst, the corresponding exocyclic thioenol ethers (2-methylidene tetrahydrothiophenes) were formed in moderate to good yields. Unsymmetrical thioketenes provided E/Z mixtures at the double bond, with the Z isomer being preferred.

The role of the endoplasmic reticulum stress in depression. / Rola stresu siateczki sródplazmatycznej w depresji.

Depression is an important health problem around the world. There are several effective methods for its treatment, but it is estimated that one-third of patients with depression do not respond adequately to conventional antidepressants. There is, therefore, an urgent need to identify the biological mechanism of depression and the pharmacological action of antidepressants. The participation of broadly understood inflammatory factors in the etiology of depressive disorders no longer raises doubts. In recent years, a lot of attention has also been devoted to changes in the endoplasmic reticulum, suggesting that the so-called endoplasmic reticulum stress gives rise to many diseases. The endoplasmic reticulum stress is activated in response to the increasing amount of unfolded or improperly folded proteins in the ER. Research on the so-called endoplasmic reticulum stress inspire hope not only in the context of amore thorough understanding of the pathophysiology of diseases, but it can also be an inspiration to search for new, more effective drugs. This paper presents the connections between changes of the endoplasmic reticulum and inflammatory states and oxidative-reduction balance. Both the occurrence of inflammation and so-called oxidative stress have been confirmed in depressive disorders.

Synthesis, Selected Transformations, and Biological Activity of Alkoxy Analogues of Lepidilines A and C.

Condensation of diacetyl monooxime with formaldimines derived from alkoxyamines in glacial acetic acid at room temperature leads to corresponding 2-unsubstituted imidazole N-oxides bearing an alkoxy substituent at the N(1) atom of the imidazole ring. Subsequent O-benzylation afforded, depending on the type of alkylating agent, either symmetric or nonsymmetric alkoxyimidazolium salts considered as structural analogues of naturally occurring imidazole alkaloids, lepidilines A and C. Some of the obtained salts were tested as precursors of nucleophilic heterocyclic carbenes (NHCs), which in situ reacted with elemental sulfur to give the corresponding N-alkoxyimidazole-2-thiones. The cytotoxic activity of selected 4,5-dimethylimidazolium salts bearing either two benzyloxy or benzyloxy and 1-adamantyloxy groups at N(1) and N(3) atoms was evaluated against HL-60 and MCF-7 cell lines using the MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. Notably, in two cases of alkoxyimidazolium salts, no effect of the counterion exchange (Br- → PF6-) on the biological activity was observed.

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor-acceptor cyclopropanes.

Ferrocenyl thioketones reacted with donor-acceptor cyclopropanes in dichloromethane at room temperature in the presence of catalytic amounts of Sc(OTf)3 yielding tetrahydrothiophene derivatives, products of formal [3 + 2]-cycloaddition reactions, in moderate to high yields. In all studied cases, dimethyl 2-arylcyclopropane dicarboxylates reacted with the corresponding aryl ferrocenyl thioketones in a completely diastereoselective manner to form single products in which (C-2)-Ar and (C-5)-ferrocenyl groups were oriented in a cis-fashion. In contrast, the same cyclopropanes underwent reaction with alkyl ferrocenyl thioketones to form nearly equal amounts of both diastereoisomeric tetrahydrothiophenes. A low selectivity was also observed in the reaction of a 2-phthalimide-derived cyclopropane with ferrocenyl phenyl thioketone.

Anxiety associated with parachute jumping as the cause of blood red-ox balance impairment. / Lek zwiazany ze skokami spadochronowymi przyczyna zaburzen równowagi red-ox.

OBJECTIVES: The aim of the study was to assess the effect of anxiety associated with parachute jumps on selected redox balance parameters in regular soldiers from airborne forces. The study allows estimating whether the paratroopers exposed to high level of mental stress are simultaneously under severe oxidative stress. METHODS: The investigations were carried out on 46 professional soldiers from airborne forces divided into groups depending on the number of performed parachute jumps. Peripheral venous blood samples were obtained under fasting conditions three times for the determination of selected parameters of red-ox balance: on an ordinary working day, on the day when the jump was performed and on the day after the jump. The time of the performed determinations was to reflect the initial balance of the organism, the state at the moment of stress and its effect on the organism. RESULTS: Our investigations showed lack of differences in characteristics of the activity of antioxidant enzymes (CAT and SOD) in response to mental stress depending on the experience of the investigated group in parachuting. Decrease in GSH-Px activity was demonstrated in response to mental stress in all the investigated groups. The TBARS level was higher in more experienced parachutists. CONCLUSIONS: The analysis of changes in selected redox balance parameters may be useful for monitoring anxiety associated with parachute jumps.

Benign intramural schwannoma of the esophagus - case report.

Schwannomas of the esophagus are rare peripheral nerve tumors. A 37-year-old woman with dysphagia was found to have an intramural tumor of the upper esophagus. The lesion was revealed on computed tomography. Endoscopic ultrasound biopsy was nondiagnostic. Through right thoracotomy, the mass was enucleated from the wall of the esophagus. Benign schwannoma was diagnosed only after immunological staining examination.