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Izhodišča. Zasvojenost od alkohola je zelo pogosta in kompleksna bolezen. Zasvojeni od alkohola imajo veliko tveganje za pojav sopojavne psihiatrične motnje. Metode. V prvi tovrstni slovenski raziskavi smo preverili prisotnost in izraženost simptomatike najpogostejših sopojavnih duševnih motenj pri zasvojenih od alkohola. Vključili smo tri skupine moških: 101 preiskovanca, hospitaliziranega zaradi zdravljenja akutne zasvojenosti od alkohola, 100 abstinentnih preiskovancev in 97 zdravih kontrol iz skupine prostovoljnih krvodajalcev. Za oceno simptomatike smo uporabili vprašalnike AUDIT, Yale-Brownovo lestvico obsesivnosti in kompulzivnosti ter lestvico obsesivno-kompulzivnega pitja, Zungovo lestvico depresivnosti in anksioznosti, Kratko lestvico socialne fobije in Buss-Durkeejevo lestvico sovražnosti. Rezultati. V skupini preiskovancev z akutno zasvojenostjo so bili pomembno bolj izražene obsesivna (p < 0,001) in kompulzivna simptomatika (p < 0,001) ter obsesivno-kompulzivna simptomatika, vezana na pitje alkoholnih pijač (p < 0,001), kot v preostalih dveh skupinah. Pri preiskovancih z akutno zasvojenostjo so bile v primerjavi z abstinenti in zdravimi kontrolami statistično pomembno bolj izražene anksioznost (p < 0,001), depresivnost (p < 0,001) in agresivnost (p < 0,001). Zaključki. Obsesivno-kompulzivna simptomatika, anksioznost, depresivnost in agresivnost so lahko sopojavno vezane na zasvojenost od alkohola. Med zdravljenjem zasvojenosti od alkohola je zato treba pozornost usmeriti tudi na te simptome, saj tako lahko bistveno izboljšamo izid zdravljenja zasvojenosti od alkohola in zmanjšamo tveganje za relaps

The article examines the discourse of Slovenia’s official tourism brand I Feel Slovenia. It presents a study of the English version of the official website, focusing on the ways in which the text establishes connections between emotions and emotions in the construction of the brand. Special attention is paid to the role of the word green in the discourse construction of Slovenia’s official image. The study is based on the framework of evaluative language (Martin and White 1995). The analysis shows that the word green is primarily used as a value-laden term, functioning as a placeholder for different evaluative meanings. The word green ties different strands of Slovenia’s image into a holistic concept rooted in the English-language slogan I Feel Slovenia and the label Slovenia Green.

The review examines the long-term impact of community psychiatric care on improving the quality of life of people with schizophrenia. It addresses the global burden of this disorder and the need for effective community-based care strategies. A systematic literature search was conducted in databases such as CINAHL, Medline, Web of Science, Sage and ScienceDirect, with the search lasting until March 2024 and following the PRISMA guidelines. The inclusion criteria targeted studies that addressed the long-term effects of community mental health care for people aged 18 years and older with schizophrenia and included both quantitative and qualitative research designs. Studies unrelated to the research question or with significant methodological flaws were excluded. The risk of bias was assessed using GRADE and GRADECERqual, in addition to critical appraisal using the Joanna Briggs Institute (JBI) checklists. Independent screening and data extraction was performed, with results summarised by thematic analysis. In total, 11 studies met the inclusion criteria and included cross-sectional, cohort, qualitative and randomised controlled trial designs. The results showed that community psychiatric care significantly improves the quality of life, well-being and social integration of people with schizophrenia. Effective interventions identified include psychoeducation, cognitive behavioural therapy, social skills training and individualised care plans. However, challenges such as limited resources, labour shortages and social stigma, particularly in low-income neighbourhoods, were also identified. This study highlights the importance of continuous, personalised, multidisciplinary community-based care for sustainable mental health outcomes. Further research is recommended to investigate the long-term impact and strategies to overcome implementation challenges.

Abstract Background Fluctuations in external salinity force eukaryotic cells to respond by changes in the gene expression of proteins acting in protective biochemical processes, thus counteracting the changing osmotic pressure. The high-osmolarity glycerol (HOG) signaling pathway is essential for the efficient up-regulation of the osmoresponsive genes. In this study, the differential gene expression of the extremely halotolerant black yeast Hortaea werneckii was explored. Furthermore, the interaction of mitogen-activated protein kinase HwHog1 and RNA polymerase II with the chromatin in cells adapted to an extremely hypersaline environment was analyzed. Results A cDNA subtraction library was constructed for H. werneckii, adapted to moderate salinity or an extremely hypersaline environment of 4.5 M NaCl. An uncommon osmoresponsive set of 95 differentially expressed genes was identified. The majority of these had not previously been connected with the adaptation of salt-sensitive S. cerevisiae to hypersaline conditions. The transcriptional response in hypersaline-adapted and hypersaline-stressed cells showed that only a subset of the identified genes responded to acute salt-stress, whereas all were differentially expressed in adapted cells. Interaction with HwHog1 was shown for 36 of the 95 differentially expressed genes. The majority of the identified osmoresponsive and HwHog1-dependent genes in H. werneckii have not been previously reported as Hog1-dependent genes in the salt-sensitive S. cerevisiae. The study further demonstrated the co-occupancy of HwHog1 and RNA polymerase II on the chromatin of 17 up-regulated and 2 down-regulated genes in 4.5 M NaCl-adapted H. werneckii cells. Conclusion Extremely halotolerant H. werneckii represents a suitable and highly relevant organism to study cellular responses to environmental salinity. In comparison with the salt-sensitive S. cerevisiae, this yeast shows a different set of genes being expressed at high salt concentrations and interacting with HwHog1 MAP kinase, suggesting atypical processes deserving of further study.

Oxidative stress and neuroinflammation are involved in the pathogenesis of alcohol addiction. However, little is known regarding the effect of genetic, behavioral, psychological, and environmental sources of origin on the inflammation and oxidative stress pathways of patients with alcohol addiction. Our study aimed to evaluate the impact of selected common functional single-nucleotide polymorphisms in inflammation and oxidative stress genes on alcohol addiction, and common comorbid psychosymptomatology. Our study included 89 hospitalized alcohol-addicted patients and 93 healthy individuals, all Slovenian males. Their DNA was isolated from peripheral blood and patients were genotyped for PON1 rs705379, rs705381, rs854560, and rs662, SOD2 rs4880, GPX1 rs1050450, IL1B rs1143623, rs16944, and rs1071676, IL6 rs1800795, IL6R rs2228145, and miR146a rs2910164. Kruskal–Wallis and Mann–Whitney tests were used for the additive and dominant genetic models, respectively. Our findings suggested the involvement of IL6 rs1800795 in alcohol addiction. Moreover, our data indicated that the genetic variability of SOD2 and PON1, as well as IL1B and IL6R, may be related to comorbid psychosymptomatology, revealing a potential indirect means of association of both the oxidative stress and inflammation pathways.

The review examines the long-term impact of community psychiatric care on improving the quality of life of people with schizophrenia. It addresses the global burden of this disorder and the need for effective community-based care strategies. A systematic literature search was conducted in databases such as CINAHL, Medline, Web of Science, Sage and ScienceDirect, with the search lasting until March 2024 and following the PRISMA guidelines. The inclusion criteria targeted studies that addressed the long-term effects of community mental health care for people aged 18 years and older with schizophrenia and included both quantitative and qualitative research designs. Studies unrelated to the research question or with significant methodological flaws were excluded. The risk of bias was assessed using GRADE and GRADECERqual, in addition to critical appraisal using the Joanna Briggs Institute (JBI) checklists. Independent screening and data extraction was performed, with results summarised by thematic analysis. In total, 11 studies met the inclusion criteria and included cross-sectional, cohort, qualitative and randomised controlled trial designs. The results showed that community psychiatric care significantly improves the quality of life, well-being and social integration of people with schizophrenia. Effective interventions identified include psychoeducation, cognitive behavioural therapy, social skills training and individualised care plans. However, challenges such as limited resources, labour shortages and social stigma, particularly in low-income neighbourhoods, were also identified. This study highlights the importance of continuous, personalised, multidisciplinary community-based care for sustainable mental health outcomes. Further research is recommended to investigate the long-term impact and strategies to overcome implementation challenges. [ABSTRACT FROM AUTHOR]

ObjectiveTo address the role of translationally active HIV reservoir in chronic inflammation and non-AIDS related disorders, we first need a simple and accurate assay to evaluate viral protein expression in virally suppressed subjects.DesignWe optimized an HIV Nef enzyme-linked immunosorbent assay (ELISA) and used it to quantify plasma Nef levels as an indicator of the leaky HIV reservoir in an HIV-infected cohort.MethodsThis study accessed 134 plasma samples from a well-characterized cohort study of HIV-infected and uninfected adults in San Francisco (the SCOPE cohort). We optimized an ELISA for detection of plasma Nef in HIV-negative subjects and HIV-infected non-controllers, and evaluated its utility to quantify plasma Nef levels in a cross-sectional study of ART-suppressed and elite controller HIV-infected subjects.ResultsHere, we describe the performance of an optimized HIV Nef ELISA. When we applied this assay to the study cohort we found that plasma Nef levels were correlated with plasma HIV RNA levels in untreated disease. However, we were able to detect Nef in plasma of approximately half of subjects on ART or with elite control, despite the lack of detectable plasma HIV RNA levels using standard assays. Plasma Nef levels were not consistently associated with CD4+ T-cell count, CD8+ T-cell count, self-reported nadir CD4+ T-cell count or the CD4+/CD8+ T-cell ratio in HIV-infected subjects.ConclusionSince plasma HIV RNA levels are undetectable in virally suppressed subjects, it is reasonable to assume that viral protein expression in leaky reservoir, and not plasma virions, is the source of Nef accumulating in plasma. To examine this further, improvements of the assay sensitivity, by lowering the background through improvements in the quality of Nef antibodies, and detailed characterization of the HIV reservoirs are needed.

We investigated two functional polymorphisms in NLRP3 inflammasome genes (NLRP3 rs35829419 and CARD8 rs2043211) and their association with alcohol dependence and related anxiety, depression, obsession-compulsion, or aggression in 88 hospitalised alcohol-dependent patients, 99 abstinent alcohol-dependent participants, and 94 controls, all male Caucasian. Alcohol dependence-related psychiatric disorders were assessed with the Zung Depression and Anxiety scale, Buss-Durkee Hostility Inventory, Alcohol Use Disorders Identification Test, Brief Social Phobia Scale, Obsessive Compulsive Drinking Scale, and Yale-Brown Obsessive-Compulsive Scale. For genotyping we used the allele-specific quantitative polymerase chain reaction-based methods. The three groups differed significantly in CARD8 rs2043211 distribution (P=0.049; chi-squared=9.557; df=4). The NLPR3 rs35829419 polymorphism was not significantly associated with alcohol dependence. In hospitalised alcohol-dependent patients the investigated polymorphisms were not associated with scores indicating alcohol consumption or comorbid symptoms. In abstinent alcohol-dependent subjects homozygotes for the polymorphic CARD8 allele presented with the highest scores on the Zung Anxiety Scale (p=0.048; df=2; F=3.140). Among controls, CARD8 genotype was associated with high scores on the Obsessive Compulsive Drinking Scale (P=0.027; df=2; F=3.744). In conclusion, our results reveal that CARD8 rs2043211 may play some role in susceptibility to alcohol dependence, expression of anxiety symptoms in abstinent alcohol-dependent subjects, and in obsessive compulsive drinking in healthy controls. However, further studies with larger cohorts are required to confirm these preliminary findings.

Extremophilic organisms demonstrate the flexibility and adaptability of basic biological processes by highlighting how cell physiology adapts to environmental extremes. Few eukaryotic extremophiles have been well studied and only a small number are amenable to laboratory cultivation and manipulation. A detailed characterization of the genome architecture of such organisms is important to illuminate how they adapt to environmental stresses. One excellent example of a fungal extremophile is the halophile Hortaea werneckii (Pezizomycotina, Dothideomycetes, Capnodiales), a yeast-like fungus able to thrive at near-saturating concentrations of sodium chloride and which is also tolerant to both UV irradiation and desiccation. Given its unique lifestyle and its remarkably recent whole genome duplication, H. werneckii provides opportunities for testing the role of genome duplications and adaptability to extreme environments. We previously assembled the genome of H. werneckii using short-read sequencing technology and found a remarkable degree of gene duplication. Technology limitations, however, precluded high-confidence annotation of the entire genome. We therefore revisited the H. wernickii genome using long-read, single-molecule sequencing and provide an improved genome assembly which, combined with transcriptome and nucleosome analysis, provides a useful resource for fungal halophile genomics. Remarkably, the ∼50 Mb H. wernickii genome contains 15,974 genes of which 95% (7608) are duplicates formed by a recent whole genome duplication (WGD), with an average of 5% protein sequence divergence between them. We found that the WGD is extraordinarily recent, and compared to Saccharomyces cerevisiae, the majority of the genome's ohnologs have not diverged at the level of gene expression of chromatin structure.

Before the global spotlight ascended upon nationwide efforts to codify into law that Black Lives Matter, specifically, police accountability against the use of excessive force against unarmed civilians, qualified immunity has silently flourished throughout America. Created to shield police officers and other government officials for the actions they engage on the job, this long-standing judicial doctrine continues to proliferate a culture of near-zero accountability when police officers engage in misconduct, which for communities of color, oftentimes results in deadly outcomes against unarmed civilians. This article will first revisit the development and legacy of qualified immunity, followed by analyzing its universal defense from police unions, then shifting to a data-rich illustration of disciplinary data highlighting the systemically designed outcomes of qualified immunity via the New York Police Department, before providing concluding thoughts. Ultimately, this article asserts that the retrogressive outcomes of police disciplinary inquiries, especially with respect to communities of color, is operating as designed, whereas efforts to review and revisit its structure and practices threaten a longstanding culture of disregard and near-zero accountability. [ABSTRACT FROM AUTHOR]

Abstract Human plasma is a complex fluid, increasingly used for extracellular vesicle (EV) biomarker studies. Our aim was to find a simple EV-enrichment method for reliable quantification of EVs in plasma to be used as biomarker of disease. Plasma of ten healthy subjects was processed using sedimentation rate- (sucrose cushion ultracentrifugation—sUC) and size- (size exclusion chromatography—SEC) based methods. According to nanoparticle tracking analysis (NTA), asymmetrical flow field-flow fractionation coupled to detectors (AF4-UV-MALS), miRNA quantification, transmission electron microscopy and enzyme-linked immunosorbent assay, enrichment of EVs from plasma with sUC method lead to high purity of EVs in the samples. High nanoparticle concentrations after SEC resulted from substantial contamination with lipoproteins and other aggregates of EV-like sizes that importantly affect downstream EV quantification. Additionally, sUC EV-enrichment method linked to quantification with NTA or AF4-UV-MALS is repeatable, as the relative standard deviation of EV size measured in independently processed samples from the same plasma source was 5.4% and 2.1% when analyzed by NTA or AF4-UV-MALS, respectively. In conclusion, the sUC EV-enrichment method is compatible with reliable measurement of concentration and size of EVs from plasma and should in the future be tested on larger cohorts in relation to different diseases. This is one of the first studies using AF4-UV-MALS to quantify EVs in blood plasma, which opens new possible clinical utility for the technique.

Sensing and responding to changes in NaCl concentration in hypersaline environments is vital for cell survival. In this paper, we identified and characterized key components of the high-osmolarity glycerol (HOG) signal transduction pathway, which is crucial in sensing hypersaline conditions in the extremely halotolerant black yeast Hortaea werneckii and in the obligate halophilic fungus Wallemia ichthyophaga. Both organisms were isolated from solar salterns, their predominating ecological niche. The identified components included homologous proteins of both branches involved in sensing high osmolarity (SHO1 and SLN1) and the homologues of mitogen-activated protein kinase module (MAPKKK Ste11, MAPKK Pbs2, and MAPK Hog1). Functional complementation of the identified gene products in S. cerevisiae mutant strains revealed some of their functions. Structural protein analysis demonstrated important structural differences in the HOG pathway components between halotolerant/halophilic fungi isolated from solar salterns, salt-sensitive S. cerevisiae, the extremely salt-tolerant H. werneckii, and halophilic W. ichthyophaga. Known and novel gene targets of MAP kinase Hog1 were uncovered particularly in halotolerant H. werneckii. Molecular studies of many salt-responsive proteins confirm unique and novel mechanisms of adaptation to changes in salt concentration.

Oxidative stress and neuroinflammation are involved in the pathogenesis of alcohol addiction. However, little is known regarding the effect of genetic, behavioral, psychological, and environmental sources of origin on the inflammation and oxidative stress pathways of patients with alcohol addiction. Our study aimed to evaluate the impact of selected common functional single-nucleotide polymorphisms in inflammation and oxidative stress genes on alcohol addiction, and common comorbid psychosymptomatology. Our study included 89 hospitalized alcohol-addicted patients and 93 healthy individuals, all Slovenian males. Their DNA was isolated from peripheral blood and patients were genotyped for PON1 rs705379, rs705381, rs854560, and rs662, SOD2 rs4880, GPX1 rs1050450, IL1B rs1143623, rs16944, and rs1071676, IL6 rs1800795, IL6R rs2228145, and miR146a rs2910164. Kruskal–Wallis and Mann–Whitney tests were used for the additive and dominant genetic models, respectively. Our findings suggested the involvement of IL6 rs1800795 in alcohol addiction. Moreover, our data indicated that the genetic variability of SOD2 and PON1, as well as IL1B and IL6R, may be related to comorbid psychosymptomatology, revealing a potential indirect means of association of both the oxidative stress and inflammation pathways. [ABSTRACT FROM AUTHOR]

Determining the HIV-1 reservoir size in infected individuals is of great importance for improvement of their treatment. Plasma trans-activation response element (TAR) RNA has been suggested as one of the possible biomarkers. TAR RNA is produced during non-processive transcription in HIV-1 productively infected and latent T cells. Here, plasma samples and paired exosome samples of 55 subjects from the observational SCOPE cohort were analysed for the presence of TAR RNA. First, a PCR-based assay was optimized, which provided 100% specificity and 100% sensitivity in differentiating HIV-1 infected non-controllers from uninfected individuals. Next, TAR RNA was detected in the plasma of 63% of aviremic HIV-1–infected patients, who were either treated with antiretroviral therapy or were elite controllers. Although TAR RNA levels did not correlate with patient gender, age, CD4 levels, CD8 levels, they tended to correlate with CD4/CD8 ratio (P = 0.047). This study is the first to investigate plasma TAR RNA in a relatively large cohort of HIV-1–infected patients. We additionally show that the TAR RNA molecules in the plasma of aviremic patients are not limited to exosomes.

Modern approaches to management of medical conditions are based on a holistic view, taking into account bidirectional connections between physical and mental health. The current pharmacologically focused model has so far provided modest benefits in addressing the burden of poor mental health. Convincing data suggest that diet quality and select nutrient-based supplements might influence a range of neurochemical modulatory activities, improving the management of mental disorders. Examples of these nutrient-based supplements include omega-3 fatty acids, S-adenosyl methionine, N-acetyl cysteine, zinc, B vitamins (including folic acid), and vitamin D. The traditional Mediterranean diet is considered to be the most beneficial diet in our region. Based on the results of preclinical studies, we are increasingly aware of the role of intestinal microbiota in the pathogenesis and potential treatment of mental disorders. Bidirectional signalling between the brain and the gut microbiome involving vagal neurocrine and endocrine signalling mechanisms influences mental and physical wellbeing. These findings suggest that using prebiotics, probiotics or in the strict sense psychobiotics, as well as incorporating fermented foods in the diet, could have a potential role in the management of mental disorders. As of now, we lack sufficient evidence to implement recommendations for dietary supplements in treatment guidelines, however, this might change in light of emerging data from contemporary research studies, at least for certain indications.

To address the role of translationally active HIV reservoir in chronic inflammation and non-AIDS related disorders, we first need a simple and accurate assay to evaluate viral protein expression in virally suppressed subjects.We optimized an HIV Nef enzyme-linked immunosorbent assay (ELISA) and used it to quantify plasma Nef levels as an indicator of the leaky HIV reservoir in an HIV-infected cohort.This study accessed 134 plasma samples from a well-characterized cohort study of HIV-infected and uninfected adults in San Francisco (the SCOPE cohort). We optimized an ELISA for detection of plasma Nef in HIV-negative subjects and HIV-infected non-controllers, and evaluated its utility to quantify plasma Nef levels in a cross-sectional study of ART-suppressed and elite controller HIV-infected subjects.Here, we describe the performance of an optimized HIV Nef ELISA. When we applied this assay to the study cohort we found that plasma Nef levels were correlated with plasma HIV RNA levels in untreated disease. However, we were able to detect Nef in plasma of approximately half of subjects on ART or with elite control, despite the lack of detectable plasma HIV RNA levels using standard assays. Plasma Nef levels were not consistently associated with CD4+ T-cell count, CD8+ T-cell count, self-reported nadir CD4+ T-cell count or the CD4+/CD8+ T-cell ratio in HIV-infected subjects.Since plasma HIV RNA levels are undetectable in virally suppressed subjects, it is reasonable to assume that viral protein expression in leaky reservoir, and not plasma virions, is the source of Nef accumulating in plasma. To examine this further, improvements of the assay sensitivity, by lowering the background through improvements in the quality of Nef antibodies, and detailed characterization of the HIV reservoirs are needed.