Feasibility and Cardiometabolic Effects of Time-Restricted Eating in Patients with Metabolic Syndrome.

Metabolic syndrome (MetS) and a prolonged daily eating window (EW) are associated with circadian rhythm disruption and increased cardiometabolic risk. Misalignment between circadian timing system and daily rhythms of food intake adversely impacts metabolic regulatory mechanisms and cardiovascular function. Restricting the daily EW by imposing an eating-fasting cycle through time-restricted eating (TRE) can restore robust circadian rhythms, support cellular metabolism, and improve cardiometabolic health. The aim of this study was to assess a feasibility of 12-week TRE intervention with self-selected 10 h EW and effects of TRE on EW duration, cardiometabolic outcomes, daily rhythms of behavior, and wellbeing in Polish patients with MetS and EW ≥ 14 h/day. Dietary intake was monitored with a validated myCircadianClock application (mCC app). Adherence to TRE defined as the proportion of days recorded with mCC app in which participants satisfied 10-h TRE was the primary outcome. A total of 26 patients (aged 45 ± 13 years, 62% women, 3.3 ± 0.5 MetS criteria, EW 14 ± 1.5 h/day) were enrolled. Coexistence of increased waist circumference (WC) (96% of patients), elevated fasting plasma glucose (FPG) (77%), and elevated blood pressure (BP) (69%) was the most common MetS pattern (50%). TRE intervention (mean duration of 81.6 ± 12.6 days) led to reducing daily EW by 28% (p < 0.0001). Adherence to TRE was 87 ± 13%. Adherence to logging food intake on mCC app during TRE was 70 ± 27%. Post TRE, a decrease in body weight (2%, 1.7 ± 3.6 kg, p = 0.026), body mass index (BMI) (1%, 0.5 ± 1.2 kg/m2, p = 0.027), WC (2%, 2.5 ± 3.9 cm, p = 0.003), systolic BP (4%, 4.8 ± 9.0 mmHg, p = 0.012), FPG (4%, 3.8 ± 6.9 mg/dL, p = 0.037), glycated hemoglobin (4%, 0.2 ± 0.4%, p = 0.011), mean fasting glucose level from continuous glucose monitor (CGM) (4%, 4.0 ± 6.1 mg/dL, p = 0.002), and sleepiness score (25%, 1.9 ± 3.2 points, p = 0043) were observed. A significant decrease in body weight (2%), BMI (2%), WC (3%), mean CGM fasting glucose (6%), sleepiness score (27%), and depression score (60%) was found in patients with mean post-TRE EW ≤ 10 h/day (58% of total), and not in patients with EW > 10 h/day. Adherence to TRE was higher in patients with post-TRE EW ≤ 10 h/day vs. patients with EW > 10 h/day (94 ± 6% vs. 77 ± 14%, p = 0.003). Our findings indicate that 10-h TRE was feasible in the European MetS population. TRE resulted in reducing daily EW and improved cardiometabolic outcomes and wellbeing in patients with MetS and prolonged EW. Use of the mCC app can aid in implementing TRE. This pilot clinical trial provides exploratory data that are a basis for a large-scale randomized controlled trial to determine the efficacy and sustainability of TRE for reducing cardiometabolic risks in MetS populations. Further research is needed to investigate the mechanisms of TRE effects, including its impact on circadian rhythm disruption.

Protocol to generate scaffold-free, multicomponent 3D melanoma spheroid models for preclinical drug testing.

Three-dimensional (3D) models play an increasingly important role in preclinical drug testing as they faithfully mimic interactions between cancer cells and the tumor microenvironment (TME). Here, we present a protocol for generating scaffold-free 3D multicomponent human melanoma spheroids. We describe steps for characterizing models using live-cell imaging and histology, followed by drug testing and assessment of cell death through various techniques such as imaging, luminescence-based assays, and flow cytometry. Finally, we demonstrate the models' adaptability for co-cultures with immune cells.

Exploring the Link between Inflammatory Biomarkers and Head and Neck Cancer: Understanding the Impact of Smoking as a Cancer-Predisposing Factor.

Head and neck cancer (HNC) is associated with significant morbidity globally, with smoking recognized as a key risk factor. This study investigates the interplay between smoking and inflammatory biomarkers in HNC development. The study involved 50 HNC patients, divided into smoking and non-smoking groups, and a control group of 30 healthy individuals. Serum levels of 48 cytokines, chemokines, growth factors, and other inflammatory markers were meticulously assessed. Significant differences in the levels of an extensive panel of inflammatory markers were observed between the patient groups and healthy controls. Elevated macrophage colony-stimulating factor (M-CSF) in both HNC groups implicated increased activity in pathways known for immunomodulation, proliferation, and angiogenesis during HNC cancerogenesis. In contrast, non-smokers with HNC demonstrated higher levels of interleukin 10 (IL-10) and interleukin 15 (IL-15), suggesting a more robust immune response. Platelet-derived growth factor BB (PDGF-BB) levels were particularly high in smokers with HNC. Smoking seems to alter the levels of crucial biomarkers in HNC, potentially affecting disease progression and responses to treatment. The data indicate that smokers may experience a more aggressive cancer phenotype, while non-smokers maintain a profile suggestive of a more active and effective immune response against HNC.

The Role of Glutathione in Selected Viral Diseases.

During inflammatory processes, immunocompetent cells are exposed to substantial amounts of free radicals and toxic compounds. Glutathione is a cysteine-containing tripeptide that is an important and ubiquitous antioxidant molecule produced in human organs. The intracellular content of GSH regulates the detoxifying capacity of cells, as well as the inflammatory and immune response. GSH is particularly important in the liver, where it serves as the major non-protein thiol involved in cellular antioxidant defense. There are numerous causes of hepatitis. The inflammation of the liver can be caused by a variety of infectious viruses. The relationship between oxidative stress and the hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis E virus (HEV) infection is not fully known. The aim of this study was to examine the relationship between hepatotropic viruses and glutathione status, including reduced glutathione (GSH) and oxidized glutathione (GSSG), as well as antioxidant enzymes, e.g., glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) in liver diseases.

Single-cell transcriptomics of NRAS-mutated melanoma transitioning to drug resistance reveals P2RX7 as an indicator of early drug response.

Treatment options for patients with NRAS-mutant melanoma are limited and lack an efficient targeted drug combination that significantly increases overall and progression-free survival. In addition, targeted therapy success is hampered by the inevitable emergence of drug resistance. A thorough understanding of the molecular processes driving cancer cells' escape mechanisms is crucial to tailor more efficient follow-up therapies. We performed single-cell RNA sequencing of NRAS-mutant melanoma treated with MEK1/2 plus CDK4/6 inhibitors to decipher transcriptional transitions during the development of drug resistance. Cell lines resuming full proliferation (FACs [fast-adapting cells]) and cells that became senescent (SACs [slow-adapting cells]) over prolonged treatment were identified. The early drug response was characterized by transitional states involving increased ion signaling, driven by upregulation of the ATP-gated ion channel P2RX7. P2RX7 activation was associated with improved therapy responses and, in combination with targeted drugs, could contribute to the delayed onset of acquired resistance in NRAS-mutant melanoma.

The Role of Oxidative Stress Enhanced by Adiposity in Cardiometabolic Diseases.

Cardiometabolic diseases (CMDs), including cardiovascular disease (CVD), metabolic syndrome (MetS), and type 2 diabetes (T2D), are associated with increased morbidity and mortality. The growing prevalence of CVD is mostly attributed to the aging population and common occurrence of risk factors, such as high systolic blood pressure, elevated plasma glucose, and increased body mass index, which led to a global epidemic of obesity, MetS, and T2D. Oxidant-antioxidant balance disorders largely contribute to the pathogenesis and outcomes of CMDs, such as systemic essential hypertension, coronary artery disease, stroke, and MetS. Enhanced and disturbed generation of reactive oxygen species in excess adipose tissue during obesity may lead to increased oxidative stress. Understanding the interplay between adiposity, oxidative stress, and cardiometabolic risks can have translational impacts, leading to the identification of novel effective strategies for reducing the CMDs burden. The present review article is based on extant results from basic and clinical studies and specifically addresses the various aspects associated with oxidant-antioxidant balance disorders in the course of CMDs in subjects with excess adipose tissue accumulation. We aim at giving a comprehensive overview of existing knowledge, knowledge gaps, and future perspectives for further basic and clinical research. We provide insights into both the mechanisms and clinical implications of effects related to the interplay between adiposity and oxidative stress for treating and preventing CMDs. Future basic research and clinical trials are needed to further examine the mechanisms of adiposity-enhanced oxidative stress in CMDs and the efficacy of antioxidant therapies for reducing risk and improving outcome of patients with CMDs.

Links between Vitamin K, Ferroptosis and SARS-CoV-2 Infection.

Ferroptosis is a recently discovered form of programmed cell death. It is characterized by the accumulation of iron and lipid hydroperoxides in cells. Vitamin K is known to have antioxidant properties and plays a role in reducing oxidative stress, particularly in lipid cell membranes. Vitamin K reduces the level of reactive oxygen species by modulating the expression of antioxidant enzymes. Additionally, vitamin K decreases inflammation and potentially prevents ferroptosis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to coronavirus disease 2019 (COVID-19) is associated with oxidant-antioxidant imbalance. Studies have shown that intensified ferroptosis occurs in various tissues and cells affected by COVID-19. Vitamin K supplementation during SARS-CoV-2 infection may have a positive effect on reducing the severity of the disease. Preliminary research suggests that vitamin K may reduce lipid peroxidation and inhibit ferroptosis, potentially contributing to its therapeutic effects in COVID-19 patients. The links between ferroptosis, vitamin K, and SARS-CoV-2 infection require further investigation, particularly in the context of developing potential treatment strategies for COVID-19.

The Role of Selected Trace Elements in Oxidoreductive Homeostasis in Patients with Thyroid Diseases.

Impaired levels of selenium (Se), zinc (Zn), copper (Cu), iron (Fe), manganese (Mn) and iodine (I) in the organism may adversely affect the thyroid endocrine system. These trace elements play a role in the fight against oxidative stress as components of enzymes. Oxidative-antioxidant imbalance is considered a possible factor in many pathological conditions, including various thyroid diseases. In the available literature, there are few scientific studies showing a direct correlation of the effect of supplementation of trace elements on slowing down or preventing the occurrence of thyroid diseases in combination with the improvement of the antioxidant profile, or through the action of these elements as antioxidants. Among the available studies, it has been shown that an increase in lipid peroxidation levels and a decrease in the overall antioxidant defense status occur during such thyroid diseases as thyroid cancer, Hashimoto's thyroiditis and dysthyroidism. In studies in which trace elements were supplemented, the following were observed: a decrease in the level of malondialdehyde after supplementation with Zn during hypothyroidism and reduction in the malondialdehyde level after Se supplementation with a simultaneous increase in the total activity status and activity of antioxidant defense enzymes in the course of autoimmune thyroiditis. This systematic review aimed to present the current state of knowledge about the relationship between trace elements and thyroid diseases in terms of oxidoreductive homeostasis.

The Impact of Exercise on Redox Equilibrium in Cardiovascular Diseases.

Cardiovascular diseases constitute the most important public health problem in the world. They are characterized by inflammation and oxidative stress in the heart and blood. Physical activity is recognized as one of the best ways to prevent these diseases, and it has already been applied in treatment. Physical exercise, both aerobic and anaerobic and single and multiple, is linked to the oxidant-antioxidant imbalance; however, this leads to positive adaptive changes in, among others, the increase in antioxidant capacity. The goal of the paper was to discuss the issue of redox equilibrium in the human organism in the course of cardiovascular diseases to systemize updated knowledge in the context of exercise impacts on the organism. Antioxidant supplementation is also an important issue since antioxidant supplements still have great potential regarding their use as drugs in these diseases.

The specificity and the affective sign of autobiographical memories in individuals with depressive disorders and alcohol use disorder. / Specyficznosc i znak afektywny wspomnien autobiograficznych u osób z zaburzeniami depresyjnymi oraz zespolem uzaleznienia od alkoholu.

OBJECTIVES: Mental disorders may disrupt autobiographical memory (AM). An example is over general memories - without details, generalized or semantic. This paper assesses the functioning of AM in a depressive episode (DEP) and alcohol use disorder (ALC). METHODS: The study compared two study groups: hospitalized patients with DEPand ALC, and two control groups: people hospitalized for gastroenterological conditions (CON) and healthy individuals (PAN) (N =39 for each group; mean age: 46.0 ± 13.6 years; no differences). The specificity of AM was examined by the Autobiographical Memory Test.Participants rated memories in terms of vividness, affective intensity and sign. RESULTS: DEP and ALC groups recalled fewer specific memories than the control groups (p <0.001 for: all, positive and negative cue words), with the lowest results in DEP. Clinical groups recalled also more negative and less positive memories (p <0.001) than the control groups, with a deficit of positive ones in DEPand an excess of negative memories in ALC. An analysis of non-specific responses revealed that the ALC group recalled more "extended" memories than the CON group (p <0.005) and more "categorical" ones than control groups (p <0.05). The DEP group remembered more "semantic associations" than the PAN group (p <0.001). CONCLUSIONS: The results confirmed the presence of OGM in both clinical groups. ALC disrupts the mechanism of generating specific memories to alesser extent than mood disorders. Moreover, subjects from the clinical groups assess their past more pessimistically than the controls, with a reduced number of positive memories in people with a depressive episode, and probably an increased number of negative ones in people with ALC.

Influence of Semiquantitative [18F]FDG PET and Hematological Parameters on Survival in HNSCC Patients Using Neural Network Analysis.

The aim of this study is to assess the influence of semiquantitative PET-derived parameters as well as hematological parameters in overall survival in HNSCC patients using neural network analysis. Retrospective analysis was performed on 106 previously untreated HNSCC patients. Several PET-derived parameters (SUVmax, SUVmean, TotalSUV, MTV, TLG, TLRmax, TLRmean, TLRTLG, and HI) for primary tumor and lymph node with highest activity were assessed. Additionally, hematological parameters (LEU, LEU%, NEU, NEU%, MON, MON%, PLT, PLT%, NRL, and LMR) were also assessed. Patients were divided according to the diagnosis into the good and bad group. The data were evaluated using an artificial neural network (Neural Analyzer version 2.9.5) and conventional statistic. Statistically significant differences in PET-derived parameters in 5-year survival rate between group of patients with worse prognosis and good prognosis were shown in primary tumor SUVmax (10.0 vs. 7.7; p = 0.040), SUVmean (5.4 vs. 4.4; p = 0.047), MTV (23.2 vs. 14.5; p = 0.010), and TLG (155.0 vs. 87.5; p = 0.05), and mean liver TLG (27.8 vs. 30.4; p = 0.031), TLRmax (3.8 vs. 2.6; p = 0.019), TLRmean (2.8 vs. 1.9; p = 0.018), and in TLRTLG (5.6 vs. 2.3; p = 0.042). From hematological parameters, only LMR showed significant differences (2.5 vs. 3.2; p = 0.009). Final neural network showed that for ages above 60, primary tumors SUVmax, TotalSUV, MTV, TLG, TLRmax, and TLRmean over (9.7, 2255, 20.6, 145, 3.6, 2.6, respectively) are associated with worse survival. Our study shows that the neural network could serve as a supplement to PET-derived parameters and is helpful in finding prognostic parameters for overall survival in HNSCC.

MiRNAs from serum-derived extracellular vesicles as biomarkers for uveal melanoma progression.

Uveal melanoma (UM) is a rare type of malignancy that originates from melanocytes in the choroid, iris and the eye's ciliary body. Biomarkers for early detection and progression of UM, especially the molecular traits governing the development of metastasis, are still not available in clinical practice. One extensively studied components of liquid biopsies are extracellular vesicles. Due to their unique molecular cargo, they can contribute to early cancer development and at the same time carry markers for disease onset and progression. For characterisation of the miRNA profiles present in circulating serum-derived exosomes of patients with diagnosed primary and metastatic UM, we have analyzed the miRNA cargos using next-generation sequencing followed by RT-qPCR validation in a cohort of patients (control n = 20; primary n = 9; metastatic n = 11). Nine miRNAs differentiating these patient groups have been established. We show that hsa-miR-144-5p and hsa-miR-191-5p are the most promising biomarker candidates, allowing the categorization of patients into local and advanced UM. Additionally, the comparison of miRNA expression levels in exosomes derived from UM patients with those derived from healthy donors revealed that hsa-miR-191-5p, -223-3p, -483-5p, -203a has the potential to be used as an early marker for the presence of UM. This pilot study reveals that miRNAs extracted from circulating exosomes could be exploited as potential biomarkers in UM diagnosis and, more importantly, for indicating metastatic spread.

Prognostic Roles of BRAF, KIT, NRAS, IGF2R and SF3B1 Mutations in Mucosal Melanomas.

BACKGROUND: The prognostic value of commonly recurrent mutations remains unclear in mucosal melanomas. METHODS: Clinicopathologic parameters of 214 cases of mucosal melanomas diagnosed in 1989-2020 in several clinical institutions were analyzed. NRAS, KIT, BRAF, IGF2R and SF3B1 mutational analyses by Sanger sequencing and next generation sequencing-based assay were performed in a subset of cases. RESULTS: Of the triple (BRAF, NRAS, NF1)-negative cases, APC, KIT and KRAS are detected mainly in sinonasal, vulvovaginal and anorectal melanomas, respectively. NRAS, KIT, BRAF, IGF2R and SF3B1 mutations are detected in 19% (37/198), 22% (44/197), 12% (25/201), 16% (22/138) and 15% (20/133) of cases, respectively. In univariate analyses, advanced stage (p = 0.016), 65 years or older (p = 0.048) and presence of ulceration (p = 0.027) are significantly correlated with worse overall survival (OS), respectively. NRAS mutation significantly correlates with worse OS (p = 0.028) and worse melanoma-specific survival (MSS) (p = 0.03) for all cases of mucosal melanomas. In multivariate analyses, NRAS mutation remains as an independent predictor of worse OS (p = 0.036) and worse MSS (p = 0.024). CONCLUSION: NRAS mutation is a predictor of worse survival, independent of stage in mucosal melanomas. The significance of frequently mutated IGF2R in mucosal melanomas remains unclear.

Characteristics of Selected Adipokines in Ascites and Blood of Ovarian Cancer Patients.

Ovarian cancer is one of the most common malignancies among women worldwide. The course of the disease is often latent and asymptomatic in the early stages, but as it develops, metastasis occurs, accompanied by accumulation of ascites in the peritoneal cavity. The ascites fluid constitutes a specific microenvironment influencing the processes of carcinogenesis. In ascites, signaling is mediated by various cytokines that control tumor cell proliferation, progression, metastasis, and chemoresistance. Adipokines, secreted into ascites and also appearing in blood, may be markers of ongoing processes related to the development of neoplastic disease. Moreover, a significant influence of adipocyte lipids on the growth of tumors, for which they are one of energy sources, is observed. Adiponectin, interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemotactic protein-1 (MCP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1), discussed in the present review, were found to mediate the effects of omentum metastasis through homing, migration and invasion of ovarian cancer cells. Further research on those adipokines seem to be a natural consequence, allowing for a better understanding of the mechanisms of neoplastic disease and determination of the treatment procedure.

Disruption of RING and PHD Domains of TRIM28 Evokes Differentiation in Human iPSCs.

TRIM28, a multi-domain protein, is crucial in the development of mouse embryos and the maintenance of embryonic stem cells' (ESC) self-renewal potential. As the epigenetic factor modulating chromatin structure, TRIM28 regulates the expression of numerous genes and is associated with progression and poor prognosis in many types of cancer. Because of many similarities between highly dedifferentiated cancer cells and normal pluripotent stem cells, we applied human induced pluripotent stem cells (hiPSC) as a model for stemness studies. For the first time in hiPSC, we analyzed the function of individual TRIM28 domains. Here we demonstrate the essential role of a really interesting new gene (RING) domain and plant homeodomain (PHD) in regulating pluripotency maintenance and self-renewal capacity of hiPSC. Our data indicate that mutation within the RING or PHD domain leads to the loss of stem cell phenotypes and downregulation of the FGF signaling. Moreover, impairment of RING or PHD domain results in decreased proliferation and impedes embryoid body formation. In opposition to previous data indicating the impact of phosphorylation on TRIM28 function, our data suggest that TRIM28 phosphorylation does not significantly affect the pluripotency and self-renewal maintenance of hiPSC. Of note, iPSC with disrupted RING and PHD functions display downregulation of genes associated with tumor metastasis, which are considered important targets in cancer treatment. Our data suggest the potential use of RING and PHD domains of TRIM28 as targets in cancer therapy.

The Analysis of Inflammation-Related Proteins in a Cargo of Exosomes Derived from the Serum of Uveal Melanoma Patients Reveals Potential Biomarkers of Disease Progression.

BACKGROUND: Uveal melanoma (UM) is the most common intraocular tumour in adults with a poor prognosis and extremely high mortality rate due to the development of metastatic disease. However, despite relatively good knowledge about the histological and genetic risk factors for metastasis development, there is no specific biomarker that would allow early detection of UM progression. Recently, exosomes and their molecular cargo have been widely studied in the search for potential biomarkers in several cancers. The purpose of this study was to analyze the inflammation-related protein cargo of exosomes derived from the serum of primary and metastatic UM patients and healthy donors. METHODS: The exosomes were isolated from the serum of primary and metastatic UM patients and healthy donors. Using multiplex immunoassay technology, we analyzed the concentration of 37 inflammation-related proteins in obtained exosomes. RESULTS: The analysis of protein cargo showed several molecules related to inflammation, such as interferon-gamma, interleukin 2, 22 and 12(p40), Pentraxin-3, TNFSF13B and TNFSF8 which were significantly enriched in metastatic UM exosomes. We showed a significant correlation between the disease stage and the concentration of these inflammation-related proteins from exosomal cargo. CONCLUSIONS: Based on the obtained results, we propose the panel of exosomal proteins for early detection of uveal melanoma progression into metastatic disease.

The involvement of small heat shock protein in chemoresistance in ovarian cancer - in vitro study.

Ovarian cancer is the most deadly gynecologic malignancy worldwide. Although the primary response to chemotherapy is high, the majority of patients will develop resistance against applied treatment. In this study, we focused on resistance to cisplatin, a first-line drug used for the treatment of ovarian cancer. The mechanism of the resistance development process is widely described, but there is a lack of information about the involvement of members of small heat shock proteins (HSPs) and their transport via exosomes. In this study, we used two cell lines: A2780 and SKOV3, and their cisplatin-resistance variants: A2780 CDDP and SKOV3 CDDP. We have shown that the expression of three small HSPs (HSPB5, HSPB6, and HSPB8) in cisplatin-resistant cell lines differs from their sensitive counterparts. Further, we isolated exosomes and determined the small HSPs in their cargo. In A2780 WT we observed a low amount of HSPB5 and HSPB6. We did not observe the expression of small HSPs in the SKOV3 cell line in both sensitive and resistant variants. Our data suggest the involvement of small HSPs in drug resistance of ovarian cancer and their presence is not related to exosomal transport. Analysis of the biological consequences of the imbalance of small HSPs expression in cisplatin resistance needs further investigation.

Merkel Cell Carcinoma of Unknown Primary: Immunohistochemical and Molecular Analyses Reveal Distinct UV-Signature/MCPyV-Negative and High Immunogenicity/MCPyV-Positive Profiles.

BACKGROUND: Merkel cell carcinomas of unknown primary (MCC-UPs) are defined as deep-seated tumors without an associated cutaneous tumor. Although the distinction has important clinical implications, it remains unclear whether these tumors represent primary tumors of lymph nodes or metastatic cutaneous primaries. METHODS: We compared the immunohistochemical profiles of four groups of MCCs (Merkel cell polyomavirus (MCPyV)-positive UP, MCPyV-negative UP, MCPyV-positive known primary (KP), and MCPyV-negative KP) using B-cell and pre-B-cell markers, cell cycle regulating proteins, follicular stem cell markers, and immune markers, and performed next generation and Sanger sequencing. RESULTS: Virus-positive and virus-negative MCC-UPs exhibited an immunoprofile similar to virus-positive and virus-negative primary cutaneous MCCs, respectively. MCC-UP tumors (both virus-positive and -negative) were immunogenic with similar or even higher tumoral PD-L1 expression and intratumoral CD8 and FoxP3 infiltrates in comparison to MCPyV-positive cutaneous tumors. In addition, similar to primary cutaneous MCCs, MCPyV-negative MCC-UPs exhibited UV signatures and frequent high tumor mutational burdens, whereas few molecular alterations were noted in MCPyV-positive MCC-UPs. CONCLUSIONS: Our results showed distinct UV-signatures in MCPyV-negative tumors and high immunogenicity in MCPyV-positive tumors. Although additional studies are warranted for the MCPyV-positive cases, our findings are supportive of a cutaneous metastatic origin for MCPyV-negative MCC-UP tumors.

Pilot Clinical Trial of Time-Restricted Eating in Patients with Metabolic Syndrome.

Metabolic syndrome (MetS) and erratic eating patterns are associated with circadian rhythm disruption which contributes to an increased cardiometabolic risks. Restricting eating period (time-restricted eating, TRE) can restore robust circadian rhythms and improve cardiometabolic health. We describe a protocol of the Time-Restricted Eating on Metabolic and Neuroendocrine homeostasis, Inflammation, and Oxidative Stress (TREMNIOS) pilot clinical trial in Polish adult patients with MetS and eating period of ≥14 h/day. The study aims to test the feasibility of TRE intervention and methodology for evaluating its efficacy for improving metabolic, neuroendocrine, inflammatory, oxidative stress and cardiac biomarkers, and daily rhythms of behavior for such population. Participants will apply 10-h TRE over a 12-week monitored intervention followed by a 12-week self-directed intervention. Changes in eating window, body weight and composition, biomarkers, and rhythms of behavior will be evaluated. Dietary intake, sleep, activity and wellbeing will be monitored with the myCircadianClock application and questionnaires. Adherence to TRE defined as the proportion of days recorded with app during the monitored intervention in which participants satisfied 10-h TRE is the primary outcome. TREMNIOS will also provide an exploratory framework to depict post-TRE changes in cardiometabolic outcomes and behavior rhythms. This protocol extends previous TRE-related protocols by targeting European population with diagnosed MetS and including long-term intervention, validated tools for monitoring dietary intake and adherence, and comprehensive range of biomarkers. TREMNIOS trial will lay the groundwork for a large-scale randomized controlled trial to determine TRE efficacy for improving cardiometabolic health in MetS population.

Incidence of genes encoding vanA/vanB vancomycin resistance in rectal swabs of patients with diagnosed cancer, on the day of admission to hospital, in a non-epidemic period.

INTRODUCTION: Rapid diagnosis is important for preventing infections due to vancomycin-resistant enterococci. AIM: To evaluate the status of gastrointestinal colonisation with strains containing vanA/vanB genes in oncological patients. MATERIAL AND METHODS: A total of 167 samples of rectal swabs taken from 161 patients (mean age: 63, range: 29-93 years) were examined, including 113 patients from surgical wards (70.2%) and 48 patients from non-surgical wards (29.8%), with diagnosed cancer. The tests were carried out within 24 h of admitting the patient to the department, using the Cepheid Xpert vanA/vanB test, with a CE marked GeneXpert® Instrument Systems analyser. Samples with positive vanB gene results were additionally seeded on chromogenic media. RESULTS: The presence of the vanA gene was found in 2.7% and 6.3% of the examined patients, respectively, from the surgical and non-surgical departments, which accounted for 3.7% of all the patients examined. The presence of the vanB gene was detected in 21.1% of the patients, but in no case was there any growth of vancomycin-resistant enterococci on the chromogenic medium. CONCLUSIONS: Patients admitted to non-surgical wards were more often colonised with vanA/vanB genes than were patients admitted to surgical wards, but the differences were not statistically significant.