Search

Background and Objectives: Dual amylin and calcitonin receptor agonists (DACRAs) are therapeutic candidates in the treatment of obesity with beneficial effects on weight loss superior to suppression of food intake. Hence, suggesting effects on energy expenditure by possibly targeting mitochondria in metabolically active tissue., Methods: Male rats with HFD-induced obesity received a DACRA, KBP-336, every third day for 8 weeks. Upon study end, mitochondrial respiratory capacity (MRC), - enzyme activity, - transcriptional factors, and -content were measured in perirenal (pAT) and inguinal adipose tissue. A pair-fed group was included to examine food intake-independent effects of KBP-336., Results: A vehicle-corrected weight loss (23.4 ± 2.8%) was achieved with KBP-336, which was not observed to the same extent with the food-restricted weight loss (12.4 ± 2.8%) (P < 0.001). Maximal coupled respiration supported by carbohydrate and lipid-linked substrates was increased after KBP-336 treatment independent of food intake in pAT (P < 0.01). Moreover, oligomycin-induced leak respiration and the activity of citrate synthase and β-hydroxyacetyl-CoA-dehydrogenase were increased with KBP-336 treatment (P < 0.05). These effects occurred without changes in mitochondrial content in pAT., Conclusions: These findings demonstrate favorable effects of KBP-336 on MRC in adipose tissue, indicating an increased energy expenditure and capacity to utilize fatty acids. Thus, providing more mechanistic insight into the DACRA-induced weight loss., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Aim: High-resolution respirometry in human permeabilized muscle fibers is extensively used for analysis of mitochondrial adaptions to nutrition and exercise interventions, and is linked to athletic performance. However, the lack of standardization of experimental conditions limits quantitative inter- and intra-laboratory comparisons., Methods: In our study, an international team of investigators measured mitochondrial respiration of permeabilized muscle fibers obtained from three biopsies (vastus lateralis) from the same healthy volunteer to avoid inter-individual variability. High-resolution respirometry assays were performed together at the same laboratory to assess whether the heterogenity in published results are due to the effects of respiration media (MiR05 versus Z) with or without the myosin inhibitor blebbistatin at low- and high-oxygen regimes., Results: Our findings reveal significant differences between respiration media for OXPHOS and ETcapacities supported by NADH&succinate-linked substrates at different oxygen concentrations. Respiratory capacities were approximately 1.5-fold higher in MiR05 at high-oxygen regimes compared to medium Z near air saturation. The presence or absence of blebbistatin in human permeabilized muscle fiber preparations was without effect on oxygen flux., Conclusion: Our study constitutes a basis to harmonize and establish optimum experimental conditions for respirometric studies of permeabilized human skeletal muscle fibers to improve reproducibility., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Laminin, fibronectin, and collagen IV are pivotal extracellular matrix (ECM) components. The ECM environment governs the fundamental properties of tumors, including proliferation, vascularization, and invasion. Given the critical role of cell-matrix adhesion in malignant tumor progression, we hypothesize that the concentrations of these proteins may be altered in the plasma of patients with clear cell renal cell carcinoma (ccRCC). This study aimed to evaluate the serum, urine, and tissue levels of laminin-5, collagen IV, and fibronectin among a control group and ccRCC patients, with the latter divided into stages T1-T2 and T3-T4 according to the TNM classification. We included 60 patients with histopathologically confirmed ccRCC and 26 patients diagnosed with chronic cystitis or benign prostatic hyperplasia (BPH). Collagen IV, laminin-5, and fibronectin were detected using Surface Plasmon Resonance Imaging biosensors. Significant differences were observed between the control group and ccRCC patients, as well as between the T1-T2 and T3-T4 subgroups. Levels were generally higher in plasma and tissue for fibronectin and collagen IV in ccRCC patients and lower for laminin. The ROC (Receiver operating characteristic) analysis yielded satisfactory results for differentiating between ccRCC patients and controls (AUC 0.84-0.93), with statistical significance for both fibronectin and laminin in plasma and urine. Analysis between the T1-T2 and T3-T4 groups revealed interesting findings for all examined substances in plasma (AUC 0.8-0.95). The results suggest a positive correlation between fibronectin and collagen levels and ccRCC staging, while laminin shows a negative correlation, implying a potential protective role. The relationship between plasma and urine concentrations of these biomarkers may be instrumental for tumor detection and staging, thereby streamlining therapeutic decision-making.

Carpesium macrocephalum , a species native to China, Korea, Japan, and Russia, has been used medicinally in the countries of its origin. Though mono- and sesquiterpenoids are known constituents of C. macrocephalum , the complete analysis of essential oils produced by the roots and aerial parts of the plant has not been published until now. The present study discloses considerable differences in the composition and cytotoxic activity of essential oils distilled from roots and shoots of C. macrocephalum . The GC-MS-FID analyses have led to the identification of 131 compounds in all, of which 114 were found in aerial parts and 110 in the roots of the plants. The essential oil distilled from shoots contained a mixture of nerol and thymol methyl ether (c. 26%), neryl isobutyrate (c. 12%) and linalool (c. 9%) as major constituents, whereas alantolactone (c. 29%), thymol methyl ether (c. 7%) and 2,5-dimethoxy- p -cymene (thymohydroquinone dimethyl ether, c. 7%) predominated in the essential oil obtained from the roots. The oils demonstrated weak antibacterial activity against Staphylococcus aureus and, at concentrations up to 2.08 mg/mL (oil from the aerial parts) and up to 3.38 mg/mL (oil from roots), were inactive against Gram-negative bacteria. The essential oil from the roots of the plant demonstrated strong but not selective cytotoxic activity.

Background: Myopia (also known as nearsightedness), a prevalent refractive error, occurs when parallel rays of light converge in front of the retina, resulting in blurry distance vision. Recently, there has been a marked rise in myopia among the global population. The absence of effective methods of controlling the progression of this visual defect prompts the search for new preventive and therapeutic options. The impact of diet and lifestyle on the progression of myopia is still not fully understood. Therefore, our aim was to examine how these factors might affect the advancement of myopia, based on the existing literature. Methods: This manuscript was prepared through an extensive literature review conducted from June 2022 to September 2024. We searched for pertinent research articles using reputable databases, including PubMed, Scopus, and Web of Science. We included all types of publications, with a special focus on the newest ones. Results: Despite far-reaching examination, the relationship between these factors and myopia control remains inconclusive with varying degrees of evidence supporting their roles. Conclusions: However, promoting a healthy lifestyle, particularly increasing physical activity and outdoor time, is essential. Additionally, emerging research suggests that maintaining a balanced diet is important due to the potential impact of certain nutrients on myopia development. Ophthalmologists should also guide parents on the alternative correction methods beyond single vision glasses, especially for rapidly progressing cases. With the rising prevalence of myopia in children, further research is necessary.

Lysosomal exoglycosidases, namely α-mannosidase (MAN), α-fucosidase (FUC), β-galactosidase (GAL), and β-glucuronidase (GLU), are of crucial importance in breaking down the oligosaccharide chains of multiple glycoconjugates. Those enzymes liberate monosaccharides from non-reducing ends of oligosaccharide chains. In this study, we have aimed to assess the potential utility of MAN, FUC, GAL, and GLU activities as indicators of ethanol abuse in individuals who died from ethanol intoxication, while also investigating the mechanisms underlying their deaths. The study group comprised 22 fatal ethanol-intoxicated individuals, while the control group included 30 deceased individuals whose body fluids showed no traces of alcohol. We measured the activities (pKat/mL) of MAN, FUC, GAL, and GLU in the supernatants of blood, urine, cerebrospinal fluid as well as vitreous humor. The results indicated significantly lower activities of MAN (p = 0.003), FUC (p = 0.008), GAL (p = 0.014), and GLU (p = 0.004) in the urine of individuals poisoned by ethanol as compared to the control group. Additionally, there was a significantly lower activity of MAN in the vitreous of those affected by ethyl alcohol poisoning (p = 0.016)., (© 2024. The Author(s).)

Despite significant advances in prenatal medicine, spontaneous miscarriage remains one of the most common and serious pregnancy complications, affecting an increasing number of women. Since many aspects of the pathogenesis of spontaneous miscarriage remain unexplained, the aim of this study has been to assess the involvement of the NLRP3 inflammasome as a potential causative factor. The concentrations of NLRP3, IL-1β, IL-18, and cytochrome C in the serum of patients after miscarriage were measured by means of the immunoenzymatic method. In the placental tissue, the expression of NLRP3, IL-1β, IL-18, and Caspase-1 as well as that of the classical apoptosis biomarkers Fas, FasL, Bcl-2, and Ca was evaluated by means of immunohistochemistry techniques. Additionally, in whole blood, the concentrations of elements crucial for pregnancy progression, such as Ca, K, Mg, and Na, were examined by means of the ICP-OES method. Significantly higher concentrations of NLRP3 and IL-18 were demonstrated in the serum of patients with miscarriage as compared to the control group. In the placental tissue samples, a higher expression of IL-1β, IL-18, and Caspase-1 proteins was noted in women who had experienced miscarriage as compared to the control group. At the same time, a significantly lower expression of FasL and Bcl-2 proteins as well as Ca deposits was observed in women after miscarriage as compared to those with a normal pregnancy outcome. Significantly lower concentrations of Ca and K were recorded in the blood of patients with spontaneous miscarriage as compared to pregnant women. The analysis of the results x indicated a greater involvement of the inflammasome in women with spontaneous miscarriage associated with oxidative-antioxidative imbalance than in the case of miscarriage related to NET formation. Our research has provided evidence for the involvement of the inflammasome in the process of spontaneous miscarriage and identifies a new direction for diagnostics that includes NLRP3 as a preventive element in prenatal care, particularly in light of the steadily declining number of pregnancies and the increasing number of reproductive failures.

Ischemic stroke (IS) is a critical medical condition that results in significant neurological deficits and tissue damage, affecting millions worldwide. Currently, there is a significant lack of reliable tools for assessing and predicting IS outcomes. The inflammatory response following IS may exacerbate tissue injury or provide neuroprotection. This review sought to summarize current knowledge on the IL-1 family's involvement in IS, which includes pro-inflammatory molecules, such as IL-1α, IL-1β, IL-18, and IL-36, as well as anti-inflammatory molecules, like IL-1Ra, IL-33, IL-36A, IL-37, and IL-38. The balance between these opposing inflammatory processes may serve as a biomarker for determining patient outcomes and recovery paths. Treatments targeting these cytokines or their receptors show promise, but more comprehensive research is essential to clarify their precise roles in IS development and progression.

(1) Background: Liver damage is an important component of acute COVID-19, and the advancement of preexisting liver disease is associated with a worse prognosis; (2) Methods: A nationwide retrospective study including 7444 patients aimed to evaluate levels of selected markers of liver damage and disease advancement and their association with mortality and mechanical ventilation (MV); (3) Results: Elevation of the following markers in multivariate models were associated with increased odds of mortality: Alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), fibrosis-4 score (FIB-4), AST-to-platelet ratio index (APRI), and decreased levels of platelet count (PLT). Elevated levels of AST, LDH, APRI, FIB-4, and the AST/ALT ratio and decreased levels of PLT were associated with increased odds of MV in multivariate models. The best predictive accuracy against mortality was achieved with FIB-4 with AUC = 0.733 (95% CI, 0.718-0.749) at the optimal cut-off point of 2.764, while against MV was achieved with LDH with AUC = 0.753 (95% CI, 0.727-0.778) at the optimal cut-off point of 449.5 IU/L. (4) Conclusions: Our study confirms that the advancement of liver damage contributes to a worse prognosis in COVID-19 patients. Markers for liver damage and the advancement of liver disease can provide predictive value in clinical practice among COVID-19 patients.

Purpose: The purpose of this study is to compare results of suture-tape augmented anterior cruciate ligament (ACL) repair (internal bracing [IB]) and ACL reconstruction (ACLR) with hamstring autograft in terms of laxity, proprioception and neuromuscular control. The hypothesis was that with strict indications IB may provide better results in proprioception and neuromuscular control., Methods: Patients with unilateral ACL injury treated with IB or ACLR with hamstring autograft were enroled in this retrospective study. Anterior tibial translation (ATT) in 30° and 90° of flexion was measured with Rolimeter. The joint position sense (JPS) test was performed in 30° and 60° of flexion using Biodex System 4Pro. The time-synchronized motion capture system and surface electromyography set were used during dynamic tasks to assess knee valgus and semitendinosus (ST) and biceps femoris (BF) activities. Comparisons between both techniques and operated versus contralateral healthy knees were performed., Results: The study groups involved 28 patients after ACLR (21.8 ± 4.8 years) and 20 patients after IB (25.8 ± 10.5 years) with the average follow-up 30 ± 18 and 28 ± 15 months, respectively. The ATT did not differ significantly between operated groups. In 30° of flexion ATT for ACLR was significantly higher in operated than in contralateral knee (5.8 ± 2.4 mm vs. 4.3 ± 1.3 mm, p  < 0.001). The JPS test and dynamic knee valgus presented no significant differences. The ACLR group presented significantly higher ST ( p  = 0.048) and BF ( p  = 0.012) activity comparing operated to contralateral knee in dynamic tasks., Conclusion: Suture-tape augmented ACL repair and ACLR with hamstring autograft yield similar results in terms of laxity, proprioception and neuromuscular control., Level of Evidence: Level III: Retrospective comparative study., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Background: Obesity is a global issue, the development of which depends on many interacting factors. Among these, hormones secreted in the gastrointestinal tract play an important role. The aim of this review was to assess the impact of these hormones on the functions of adipose tissue., Methods: The analysis was based on the latest research concerning both adipose tissue and gastrointestinal hormones., Results: It was found that these hormones can significantly affect adipose tissue, both directly and indirectly. Some hormones, when secreted in excess, can stimulate adipose tissue formation processes, while others can inhibit them. The impact of hormones depends on the location and type of adipose tissue as well as the physiological state of the body. It should also be noted that no hormone acts in isolation but in close cooperation with other factors., Conclusions: The relationship between gastrointestinal hormones and adipose tissue, and their role in obesity, is a complex and evolving field of study. Further research is necessary, particularly into the interactions between hormones and other factors, as well as their mutual interactions.

Introduction: Acute lymphoblastic leukemia is characterized by a disturbed maturation of hematopoietic stem cells (HSCs) resulting in development of a malignant clone. Despite relatively positive outcome, there are still instances of disease relapse occurring due to ineffective disease eradication or primary leukemic clone alterations. Unclear significance of stem cells in the course of ALL led us to investigate and establish crucial changes in two stem cell populations - very small embryonic-like stem cells (VSELs) and HSCs during the induction phase of treatment., Methods: In a retrospective study selected stem cells in peripheral blood and bone marrow of 60 pediatric ALL subjects and 48 healthy controls were subjected to flow cytometric analysis at 4 different time points., Results: Both VSELs and HSCs were elevated at the moment of ALL diagnosis compared to healthy controls, but profoundly decline until day 15. Further observations revealed an increase in HSCs with a concomitant depletion of VSELs until week 12. ALL patients with high HSCs showed positive correlation with bone marrow blasts at diagnosis. Patients with lower VSELs or HSCs at diagnosis had slightly improved response to applied therapy. We observed higher initial bone marrow lymphoblast values in patients with lower VSELs or higher HSCs in the high-risk group. The significance of VSELs in predicting treatment outcome can be illustrated by lower day 15 MRD level of patients with lower VSELs at diagnosis., Discussion: We found HSCs and VSELs to be valid participants in pediatric ALL with possible contribution in the neoplastic process and prediction of initial treatment outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Krętowska-Grunwald, Sawicka-Żukowska, Starosz, Krawczuk-Rybak, Moniuszko and Grubczak.)

Aim: The aim of the study was to assess the usefulness of cytokines and other soluble mediators in differentiation between severe and mild course of tick-borne encephalitis (TBE) as well as the predictor of sequalae development., Material and Methods: 122 patients (mean age 47.66 ± 14.77 years, 43 females, 79 males) with TBE were included in the study. Concentrations of 82 cytokines, growth factors, selectins, matrix metalloproteinases and other soluble mediators were measured in serum and CSF samples according to the manufacturer's instruction on a Bio-Plex 200 System using the custom made Luminex assays. Enzyme-linked immunosorbent assays for the quantitative detection of human IL-26, IL-29 IL-22, CXCL12 were performed., Results: No significant differences between serum concentrations of examined factors between group with sequelae and group with complete recovery were observed. In the CSF the concentrations of GM-CSF, Il-1α, Il-2, Il-4, Il-6, Il-12p70, Il-17A, CXCL1, CXCL6, Il-8, CCL4, CCL20, TRAIL, CD40L, MMP8 were significantly higher in patients who developed sequelae than in patients with complete recovery. For TRAIL concentration over 26.65 pg/ml in CSF the probability of sequalae development was 10.5 higher. In case of CCL20 - the concentration over 21.38 pg/ml in CSF the odds ratio was 6.429 times. For MMP-8 over 4210.54 pg/ml, the odds ratio was 11.222 times., Conclusions: TRAIL, CCL-20 and MMP-8 are promising biomarkers of prediction of the sequalae development of TBE. Pro-inflammatory cytokines IL-8, IL-1, IL-2, IL-12, IL-17A also associate well with the risk of sequelae and could be further evaluated as prognostic markers in TBE, individually or as elements of a larger model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The aim of the present study was to establish the role of platelets and activated factor XIIIa (FXIIIa) in the structuring of the fibrin network as well as to clarify the effect of network compaction on clot lysis., Methods: Turbidimetry was used for the one-stage clotting test where platelet-free plasma (PFP) is regarded as single factor-deficient plasma (platelets as lacking factor) and autologous platelet-rich plasma (PRP) as deficiency corrected plasma. Structural features of the developed and subsequently lysed fibrin network, formed under static and flow conditions, were visualized by confocal microscopy., Results: Thrombin-initiated plasma clotting revealed changes in the shape of the absorption curve, more pronounced in the presence of platelets. These changes correlate with the transformation of the fibrin scaffold during clot maturing. With the combined action of platelets, thrombin and Ca2+, plasma clotting passes through two phases: initial formation of a platelet-fibrin network (first peak in the polymerization curve), and then the compaction of fibrin, driven by FXIIIa (the second peak) which can be further modulate by the contractile action of platelets. These structural changes, mediated by platelets and FXIIIa, have been shown to determine subsequent clot lysis., Conclusions: Platelet aggregates serve as organizing centers that determine the distribution of fibrin in clot volume. The openwork structure of the platelet-transformed fibrin provides the necessary prerequisites for its timely lysis. The revealed aspects of the interaction of platelets and FXIIIa, which accompanies the maturation of a fibrin clot, may lead to new approaches in the pharmacological correction of disorders associated with both thrombotic episodes and bleeding tendency., (© 2024 The Author(s).)

Phloroglucinol (PHG), an analgesic and spasmolytic drug, shows promise in preventing high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. In Wistar rats, 10 weeks of PHG treatment did not prevent HFD-induced weight gain but significantly mitigated fasting hyperglycemia, impaired insulin responses, and liver steatosis. This protective effect was not linked to hepatic lipogenesis or AMP-activated protein kinase (AMPK) activation. Instead, PHG improved mitochondrial function by reducing oxidative stress, enhancing ATP production, and increasing anti-oxidant enzyme activity. PHG also relaxed gastric smooth muscles via potassium channel activation and nitric oxide (NO) signaling, potentially delaying gastric emptying. A pilot intervention in pre-diabetic men confirmed PHG's efficacy in improving postprandial glycemic control and altering lipid metabolism. These findings suggest PHG as a potential therapeutic for NAFLD and insulin resistance, acting through mechanisms involving mitochondrial protection, anti-oxidant activity, and gastric motility modulation. Further clinical evaluation is warranted to explore PHG's full therapeutic potential.

Endometrial cancer is one of the most common malignancies in women. Sphingolipids, a group of lipids, play a key role in cancer biology. Cancer cells often exhibit abnormal redox homeostasis characterized by elevated levels of reactive oxygen species (ROS). Emerging evidence suggests that ceramides are involved in inhibiting proliferation and inducing apoptosis through ROS production. However, there is no data on the relationship between sphingolipid metabolism and oxidative status in endometrial cancer. The present study aims to assess the content of individual sphingolipids and oxidative status in healthy women and those with endometrial cancer. Sphingolipid analysis was performed using mass spectrometry. Total oxidative status (TOS) and total antioxidant capacity (TAC) were assessed colorimetrically. Our results showed a significant increase in the levels of all measured sphingolipids in cancer tissues compared to healthy endometrium. Additionally, a significant decrease in the S1P/ceramide ratio (sphingolipid rheostat) was observed in cancer patients, particularly for C14:0-Cer, C16:0-Cer, C18:1-Cer, C22:0-Cer, and C24:0-Cer. Furthermore, increased TOS and decreased TAC were found in cancer patients compared to healthy women. Significant correlations were observed between the levels of individual sphingolipids and oxidative status, with the strongest correlation noted between C22:0-Cer and TOS (r = 0.64). We conclude that endometrial cancer is characterized by profound changes in sphingolipid metabolism, contributing to oxidative dysregulation and tumor progression.

Background : Osgood-Schlatter disease (OSD) belongs to the group of sterile bone necrosis and mainly affects athletically active children. The pathogenesis of OSD is currently not fully understood, so the purpose of this study was to evaluate the concentrations of selected matrix metalloproteinases (MMPs)-MMP-2, MMP-3, MMP-7, MMP-9, MMP-10 and MMP-26 in patients diagnosed with OSD compared to patients with diseases other than sterile bone necrosis Methods : The study group included 140 patients with OSD, while the control group contained 100 patients with knee pain unrelated to sterile bone necrosis. The MMPs tested were determined by an enzyme-linked immunosorbent assay in plasma. Results : Patients with OSD had higher concentrations of MMP-2 and MMP-9 compared to the control group. The concentrations of MMP-7, MMP-10 and MMP-26 were lower in affected children. High values of diagnostic parameters-diagnostic accuracy (AC), sensitivity (SE), specificity (SP) and area under curve (AUC)-were obtained for MMP-7, MMP-9 and MMP-26. Conclusions : The collected results convince that MMP-7, MMP-9 and MMP-26 can be consider as a differential ancillary test between OSD and other knee pain and may be involved in the pathogenesis of this condition.

Context: Adipose-derived mesenchymal stem cells (ADMSCs) are progenitor cells that shape the tissue's biological properties. Objective: To examine the adipocytes differentiated from the ADMSCs of lean and obese individuals with/without a metabolic syndrome (MetSx) cytokine secretory profile, as to date, little is known on this topic. Methods: Interleukin, chemokine and growth factor levels in the culture medium were determined using the Human Cytokine kit. Results : We observed a characteristic secretory fingerprint displayed by the cells from the MetSx group and identified a set of putative markers (IL-1β, IL-6, IL-7, IL-10, IL-12, IL-13, VEGF, FGF, GM-CSF, TNF-α, IFN-γ) of the condition. Surprisingly, the concentrations of most of the molecules (except for IL-6, IFN-γ, IP-10, VEGF) decreased when compared with the cells from the lean group. We postulate that the difference stemmed from the fact that in vivo cytokines were mostly secreted by the activated monocytes/macrophages and not adipocytes per se. This may also suggest that the aforementioned upregulated cytokines (IL-6, IFN-γ, IP-10, VEGF) might have been the ones that attracted monocytes and triggered the vicious cycle of tissue inflammation. Conclusions : Our study indicated that the adipocytes newly derived from the ADMSCs of obese patients with metabolic syndrome displayed a secretory fingerprint that may be characteristic to the early stages of the condition.

Airway remodeling (AR) with chronic inflammation, are key features in asthma pathogenesis. AR characterized by structural changes in the bronchial wall is associated with a specific asthma phenotype with poor clinical outcomes, impaired lung function and reduced treatment response. Most studies focus on the role of inflammation, while understanding the mechanisms driving AR is crucial for developing disease-modifying therapeutic strategies. This review paper summarizes current knowledge on the mechanisms underlying AR, diagnostic tools, and therapeutic approaches. Mechanisms explored include the role of the resident cells and the inflammatory cascade in AR. Diagnostic methods such as bronchial biopsy, lung function testing, imaging, and possible biomarkers are described. The effectiveness on AR of different treatments of asthma including corticosteroids, leukotriene modifiers, bronchodilators, macrolides, biologics, and bronchial thermoplasty is discussed, as well as other possible therapeutic options. AR poses a significant challenge in asthma management, contributing to disease severity and treatment resistance. Current therapeutic approaches target mostly airway inflammation rather than smooth muscle cell dysfunction and showed limited benefits on AR. Future research should focus more on investigating the mechanisms involved in AR to identify novel therapeutic targets and to develop new effective treatments able to prevent irreversible structural changes and improve long-term asthma outcomes., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Varicella-Zoster Virus (VZV) is characterized by its ability to enter a dormant state within the body. When the wild or vaccine virus reactivates, it can lead to herpes zoster (HZ), which infrequently manifests as a neuroinfection., Objectives: The aim of the study was to analyze the clinical manifestations and outcomes associated with VZV reactivation in the CNS in immunocompetent children., Methods: We searched medical databases for case reports using the keywords "zoster", "meningitis", "encephalitis", and "immunocompetent". The inclusion criteria were age below 18 years, any gender, race, and ethnicity, no features or history of immunodeficiency, and confirmation of VZV reactivation through the detection of VZV DNA in the CSF. Patients were categorized into two groups: children experiencing the reactivation of the wild virus and children with the vaccine strain virus., Results: The cohort included six children hospitalized in our hospital and 49 children reported in the literature. In 37 (67%), a wild-type virus was detected, while in 18 (33%), an infection was caused by the vaccine strain. There were no differences in the clinical presentation between the two groups. A typical rash was observed in 32 (58%) children. Approximately 41 of the 55 children (75%) received antiviral treatment. Four patients experienced complications., Conclusions: Neither a history of VZV immunization nor the absence of a skin rash can definitively exclude VZV meningitis. It is important to note that any seemingly healthy child, regardless of recognized risk factors, could develop HZ meningitis.

Background: Accumulating data implicate interleukin (IL)-33, a proinflammatory cytokine released locally upon epithelial cell damage, in the pathogenesis of COPD. In a phase 2 study, itepekimab, a human monoclonal antibody against IL-33, reduced exacerbations and improved lung function in a subgroup analysis of former smokers with COPD with an acceptable safety profile., Methods: The study designs of AERIFY-1 and AERIFY-2 are described in this article., Discussion: The primary objective of AERIFY-1/2 (NCT04701983/NCT04751487), two phase 3 randomised, double-blind, placebo-controlled trials, is to assess the efficacy and safety of itepekimab versus placebo in a population of former smokers with moderate-to-severe COPD over up to 52 weeks. An additional secondary population of current smokers are being enrolled in AERIFY-2. These two studies will enrol patients (aged 40-85 years) with COPD and chronic bronchitis who had ≥2 moderate or ≥ 1 severe exacerbations within the previous year despite standard-of-care triple or double background therapy. All participants are required to have ≥10-pack-year smoking history, and ≥6 months since smoking cessation for former smokers. The primary end-point is the annualised rate of moderate or severe acute exacerbation of COPD. Secondary end-points include change from baseline in pre- and post-bronchodilator forced expiratory volume in 1 s, and annualised frequency of severe exacerbations. Symptomatic end-points include Evaluating Respiratory Symptoms in COPD and St. George's Respiratory Questionnaire, safety and anti-drug antibody responses., Competing Interests: Conflict of interest: K.F. Rabe reports consultancy, speaker fees’ and advisory board membership for AstraZeneca, Boehringer Ingelheim, Chiesi, Gilead, GSK, Novartis, Pearl, Sanof and Teva; and is cofounder of rnatics, Germany. Conflict of interest: F.J. Martinez has been on steering committees for Afferent/Merck, AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, GlaxoSmithKline, Nitto Pharma, Patara Pharma/Respivant Sciences, Pearl Pharmaceuticals, ProMedior/Roche, ProMetic Life Sciences, Stromedix/Biogen and Veracyte; has been an advisory board member for AstraZeneca, BioScale/ProTerrix Bio, Boehringer Ingelheim, Chiesi, CSL Behring, Gala Therapeutics, Genentech, GlaxoSmithKline, Novartis, Pearl Pharmaceuticals, Physicians Education Resource, Sunovion, Teva and Zambon; has been a consultant for Bridge Biotherapeutics, Bristol Myers Squibb and twoXR; reports continuing medical education presentation support from the Canadian Respiratory Network, Chiesi, CME Outfitters, Dartmouth University, France Foundation, Inova Fairfax, MD Magazine, Methodist Hospital, Miller Communications, National Association for Continuing Education/Haymarket, New York University, PeerView, Prime Education, Rare Diseases Healthcare Communication, Rockpointe, University of Alabama at Birmingham, UpToDate, Vindico Pharmaceuticals, WebMD/MedScape and Zambon; and has been on the data and safety monitoring board for Boehringer Ingelheim and GlaxoSmithKline. Conflict of interest: S.P. Bhatt has served on advisory boards for Boehringer Ingelheim and Regeneron, received consulting fees from Sanofi, and reports fees for continuing medical education from IntegrityCE. Conflict of interest: T. Kawayama reports support from GSK, AstraZeneca, Novartis Pharma and Healios. Conflict of interest: B.G. Cosio has served as a consultant and received speaker fees from AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Menarini, GSK, Sanofi and Teva. Conflict of interest: R.M. Mroz reports support from AstraZeneca, Boehringer Ingelheim, Chiesi, Genentech, MSD, Gilead, GSK, Novartis, Pearl Pharmaceuticals, Sanofi and Teva. Conflict of interest: M.M. Boomsma, H. Goulaouic, M. Djandji, Y. Liu, C.R. Xu and H. Staudinger are Sanofi employees and may hold stock and/or stock options in the company. Conflict of interest: M.C. Nivens, X. Soler, M.P. Kosloski and D.J. Lederer are Regeneron Pharmaceuticals Inc. employees and shareholders. Conflict of interest: N. Amin is a prior employee and shareholder for Regeneron Pharmaceuticals Inc. Conflict of interest: R.M. Abdulai is a prior employee and stock holder for Sanofi., (Copyright ©The authors 2024.)

Purpose: Upper airway (UA) surgery is commonly employed in the treatment of patients with obstructive sleep apnea (OSA). The intricate pathophysiology of OSA, variability in sites and patterns of UA collapse, and the interaction between anatomical and non-anatomical factors in individual patients may contribute to possible surgical failures. This clinical consensus statement aims to identify areas of agreement among a development group comprising international experts in OSA surgery, regarding the appropriate definition, predictive factors in patients, and management of surgical failure in OSA treatment., Methods: A clinical consensus statement (CCS) was developed using the Delphi method by a panel of 35 contributors from various countries. A systematic literature review adhering to PRISMA guidelines was conducted. A survey consisting of 60 statements was then formulated and presented to the experts., Results: Following two rounds of the Delphi process, consensus or strong consensus was achieved on 36 items, while 24 items remained without consensus. Specifically, 5 out of 10 statements reached consensus regarding on the 'Definition of Surgical Success/Failure after OSA Surgery'. Regarding the 'Predictive Factors of Surgical Failure in OSA Surgery', consensus was reached on 10 out of 13 statements. In the context of the 'Diagnostic Workup in OSA Surgery', consensus was achieved on 9 out of 13 statements. Lastly, in 'Treatment in Surgical Failure Cases', consensus was reached on 12 out of 24 statements., Conclusion: The management of OSA after surgical failure presents a significant clinical challenge for sleep specialists. This CCS provides valuable guidance for defining, preventing, and addressing surgical failures in the treatment of OSA syndrome., (© 2024. The Author(s).)

Background: Analyzing hospitalizations of patients with hepatitis C virus (HCV) infection is essential for an effective action plan to eliminate hepatitis C as a public health threat. This study aimed to explore trends in hospitalizations of patients with HCV infection and factors related to these hospitalizations. Methods: This 11-year retrospective study (2012-2022) explored trends in hospitalizations of patients with HCV infection in Poland based on data from the Nationwide General Hospital Morbidity Study. Results : The mean age of individuals was 55 years, with hospitalization rates among men and women of 15.5 and 13.7 per 100,000 population, respectively. Hospitalizations were 1.8-fold higher among urban residents. The most frequent comorbidities were digestive (24%) and cardiovascular (18%) diseases. During the studied period, the hospitalization rates significantly decreased from 31.9 per 100,000 in 2012 to 5.0 per 100,000 in 2022, with stays requiring 0-3, 4-7, and ≥8 days becoming 8-fold, 6-fold, and 4-fold less frequent, respectively. The flattening of hospitalizations was apparent across all age groups, including children. Conclusions : While significant progress has been made in managing HCV in Poland, continued efforts are required to eliminate disparities in care and to sustain the momentum toward HCV elimination, particularly through enhanced political commitment and the implementation of comprehensive national screening programs.

Purpose: The aim of this study was to analyze treatment outcomes and their predictors in children hospitalized due to varicella complicated by bacterial superinfections after pandemic of COVID-19., Methods: This retrospective study analyzed data collected in a multicenter, nationwide, observational database dedicated for children aged 0-17 years hospitalized due to bacterial complications of varicella in 9 Polish tertiary healthcare inpatient centers. The primary endpoint of this study was the treatment outcome established after the end of hospital management assessed at a 4-point scale. The secondary endpoint was defined as the necessity of surgical intervention., Results: There were 458 patients with a median age of 4 (IQR 2-6) years. After the completed treatment, 319 (69%) participants were found fully recovered; 132 (29%) had transient complications; 2 (0.5%) had persistent complications; and 1 child (0.5%) died. Multivariate analysis revealed that implementation of ibuprofen in pre-treatment management of a child with varicella was associated with a 4.07-fold (2.50-6.60) increase in risk of complications after the treatment and it was associated with 2.87 times (1.39-5.89) higher risk of surgical intervention necessity. For other pre-hospital interventions (implementation of acyclovir, antibiotics or antihistaminics) no significant impact was observed. GAS infection increased the necessity of surgical intervention by 7.51 (3.64-15.49) times., Conclusions: One-third of patients treated for bacterial complications of varicella have post-treatment complications, most of them transient. GAS infection increases the need for surgical intervention. The use of ibuprofen in the treatment of varicella significantly increases the risk of complications and the need for surgical intervention., (© 2024. The Author(s).)

The aim of the study was to propose pharmacy-compounded oral gels as a new and alternative dosage form that is attractive to children as having a better masking taste than syrups and reducing the risk of spilling. The application and physical properties of the gels prepared with cellulose derivatives (hydroxyethylcellulose and carmellose sodium) or carbomers were evaluated. The results of the study showed the most suitable consistency, viscosity, and organoleptic properties for gels prepared with carbomer and cellulose derivatives at concentrations of 0.75% and 2.0%, respectively. The microbial stability of the gels was guaranteed by the use of methylparaben and potassium sorbate. VAL (valsartan) and CC (candesartan cilexetil) tablets, often used off-label in children, were pulverized and suspended in the hydrogel bases, resulting in final drug concentrations of 4 mg/g and 1 mg/g, respectively. There was no significant change in viscosity and consistency parameters when the pulverized tablets were added, and only small changes in viscosity and consistency were observed during 35 days of storage, especially in the gels with sodium carmellose and candesartan. On the basis of the drug assay, an expiry date of 25 °C was recommended: 35 days for valsartan and 14 days for candesartan preparations.

Recently, silver nanoparticles (NPs) have attracted significant attention for being highly desirable nanomaterials in scientific studies as a result of their extraordinary characteristics. They are widely known as effective antibacterial agents that are capable of targeting a wide range of pathogens. Their distinct optical characteristics, such as their localized surface plasmon resonance, enlarge their utilization, particularly in the fields of biosensing and imaging. Also, the capacity to control their surface charge and modify them using biocompatible substances offers improved durability and specific interactions with biological systems. Due to their exceptional stability and minimal chemical reactivity, silver NPs are highly suitable for a diverse array of biological applications. These NPs are produced through chemical, biological, and physical processes, each of which has distinct advantages and disadvantages. Chemical and physical techniques often encounter issues with complicated purification, reactive substances, and excessive energy usage. However, eco-friendly biological approaches exist, even though they require longer processing times. A key factor affecting the stability, size distribution, and purity of the NPs is the synthesis process selected. This review focuses on how essential it is to choose the appropriate synthesis method in order to optimize the characteristics and use of silver NPs.

Objectives: To better understand the Lyme borreliosis (LB) burden in Europe, we aimed to estimate the incidence of symptomatic Borrelia burgdorferi sensu lato (Bbsl) infections after adjusting public health LB surveillance data for under-detection of symptomatic Bbsl infections., Methods: Data from seroprevalence studies and estimates of the symptomatic proportion and duration of antibody detection in Bbsl-infected individuals, derived from reviews of the published literature, were used to adjust public health LB surveillance data to estimate the incidence of symptomatic Bbsl infection in nine European countries from 2018 to 2022., Results: The prevalence of anti-Bbsl antibodies ranged from 2.3% in Romania to 9.4% in Germany. Under-detection multipliers varied across surveillance systems; using 10-year duration of antibody detection, multipliers were 2.4-10.5 in countries reporting all LB cases and 54.6-722.2 in countries reporting only Lyme neuroborreliosis cases. The incidence of symptomatic Bbsl infection adjusted for under-detection was highest in Finland, Germany, Norway, Poland, and Switzerland, intermediate in the Czech Republic and Denmark, and lowest in Ireland and Romania., Conclusion: Adjustment of LB surveillance for under-detection found a high incidence of symptomatic Bbsl infection in several European countries. Differences in LB surveillance systems should be considered when comparing surveillance data between countries and when estimating LB disease burden., Competing Interests: Declarations of competing interest Frederick J. Angulo, Gordon Brestrich, Emily Colby, Andrew Vyse, L. Hannah Gould, Kate Halsby, Patrick H. Kelly, Jennifer C. Moïsi, Andreas Pilz, Madiha Shafquat, and James H. Stark are employees of Pfizer and may hold stock or stock options. Per-Eric Lindgren has been an external scientific advisor to Valneva, Pfizer, and Bavarian-Nordic A/S., (Copyright © 2024 Pfizer Inc. Published by Elsevier Ltd.. All rights reserved.)

Aims: Short-term effects of Polish smog, particularly benzo(alpha)pyrene (B(a)P), are unclear. We aimed to examine the association between short-term exposure to air pollution and ischemic stroke (IS) incidence., Methods: We conducted a retrospective population-based cohort study including an EP-PARTICLES cohort of 8 million inhabitants in the years 2011-2020 (80 million person-years of observation). Individual clinical data on emergency hospitalizations due to IS - ICD-10: I63.X was analyzed. We used quasi-Poisson models to examine municipality-specific associations between air pollutants and IS, considering various covariates., Results: We recorded 146,262 cases of IS with a dominance of females (51.8%) and people over 65 years old (77.6%). In the overall population, exposure to PM2.5, NO2, B(a)P and SO2 increased the risk of IS onset on the day of exposure by 2.4%, 1%, 0.8%, and 0.6%, respectively. Age and sex were modifying variables for PM2.5, NO2 and B(a)P exposure with more pronounced effects in non-elderly individuals and women (all pinteraction< 0.001). Residents of regions with high tobacco and alcohol consumption were more sensitive to the effects of PM2.5 and SO2. The slopes of response-effect curves were non-linear and steeper at lower concentrations., Conclusions: Exposure to air pollution may be associated with higher IS incidence, particularly posing a higher risk to non-elderly women. Harmful lifestyle habits might exacerbate its impact. Exposure to even low levels of air pollutants had negative effects., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Valve-in-Valve (ViV) transcatheter aortic valve implantation (TAVI) has emerged as a viable therapeutic option for structural valve degeneration following surgical aortic valve replacement (SAVR) or prior TAVI. However, the understanding of long-term complications and their management remains limited. Case presentation: We present the case of a 69-year-old male with a history of ViV-TAVI, who presented with symptoms of non-ST elevation myocardial infarction (NSTEMI) and transient ischemic attack (TIA). Computed tomography (CT) revealed thrombosis of the ascending aortic graft and aortic valve prosthesis. Transthoracic echocardiography (TTE) further confirmed new valve dysfunction, indicated by an increase in the aortic valve mean gradient. Treatment with low-molecular-weight heparin (LMWH) resulted in partial thrombus resolution. The multidisciplinary Heart Team opted against coronary angiography and recommended the long-term administration of vitamin K antagonists (VKAs). Follow-up CT showed the complete resolution of the thrombus. Conclusions: Thrombosis of the aortic graft and aortic valve following ViV-TAVI may be attributed to alterations in blood flow or mechanical manipulations during the TAVI procedure, yet it can be effectively managed with VKA therapy. CT is a valuable tool in coronary assessment in patients with NSTEMI and aortic valve and/or aortic graft thrombosis.

Background : Febrile seizures are a common form of convulsions in childhood, with poorly known cellular mechanisms. The objective of this pioneering study was to provide qualitative and quantitative ultrastructural research on the large neuronal perikarya in the cerebellar dentate nucleus (DN), using an experimental model of hyperthermia-induced seizures (HSs), comparable to febrile seizures in children. Methods : The study used young male Wistar rats, divided into experimental and control groups. The HSs were evoked by a hyperthermic water bath at 45 °C for 4 min for four consecutive days. Specimens (1 mm 3 ) collected from the DN were routinely processed for transmission electron microscopy studies. Results : The ultrastructure of the large neurons in the DN affected by hyperthermic stress showed variously pronounced lesions in the perikarya, including total cell disintegration. The most pronounced neuronal lesions exhibited specific morphological signs of aponecrosis, i.e., dark cell degeneration ('dark neurons'). In close vicinity to the 'dark neurons', the aponecrotic bodies were found. The findings of this qualitative ultrastructural study correspond with the results of the morphometric analysis of the neuronal perikarya. Conclusions : Our results may constitute interesting comparative material for similar submicroscopic observations on large DN neurons in HS morphogenesis and, in the future, may help to find potential treatment targets to prevent febrile seizures or reduce recurrent seizures in children.

In this article, we describe the case of a 70-year-old man whose diagnosis of a brain meningioma was hindered by a SARS-CoV-2 infection. The patient, who had been vaccinated twice with the AstraZeneca COVID-19 vaccine, was admitted to Temporary Hospital No. 2, University Hospital (Białystok, Poland) with a positive PCR test result for SARS-CoV-2. The patient's general condition was good, but he reported a significant reduction in visual acuity in his left eye and headaches. A series of ophthalmological examinations were conducted, but they did not clarify the cause of the significant decrease in visual acuity. During hospitalization, an abnormal light reaction of the left pupil was observed, which led to the expansion of diagnostics to include imaging studies (CT and MRI). Computed tomography and magnetic resonance imaging revealed extensive isointense areas in the anterior cranial fossa, suggesting the presence of a meningioma. The final diagnosis and clarification of the cause of the visual impairment in the left eye resulted in the patient being transferred to the neurosurgery department for surgical treatment. COVID-19 diagnosis may mask the correct interpretation of other disease symptoms. Accidentally detected asymptomatic SARS-CoV-2 infection accelerated proper ophthalmic and neurology diagnosis. In this article, we describe the case of a 70-year-old man whose diagnosis of a brain meningioma was hindered by a SARS-CoV-2 infection. The patient, who had been vaccinated twice with the AstraZeneca COVID-19 vaccine, was admitted to Temporary Hospital No. 2, University Hospital (Białystok, Poland) with a positive PCR test result for SARS-CoV-2. The patient's general condition was good, but he reported a significant reduction in visual acuity in his left eye and headaches. A series of ophthalmological examinations were conducted, but they did not clarify the cause of the significant decrease in visual acuity. During hospitalization, an abnormal light reaction of the left pupil was observed, which led to the expansion of diagnostics to include imaging studies (CT and MRI). Computed tomography and magnetic resonance imaging revealed extensive isointense areas in the anterior cranial fossa, suggesting the presence of a meningioma. The final diagnosis and clarification of the cause of the visual impairment in the left eye resulted in the patient being transferred to the neurosurgery department for surgical treatment. COVID-19 diagnosis may mask the correct interpretation of other disease symptoms. Accidentally detected asymptomatic SARS-CoV-2 infection accelerated proper ophthalmic and neurology diagnosis.

There are scientific studies indicating that the attachment of an indole moiety to the triterpene scaffold can lead to increased anticancer potential. Lipophilicity is one of the factors that may influence biological properties and is therefore an important parameter to determine for newly obtained compounds as drug candidates. In the present study, previously synthesized 3 and/or 28-indole-betulin derivatives were evaluated for lipophilicity by reversed-phase thin-layer chromatography. The experimental values of lipophilicity (logP TLC ) were then subjected to correlation analysis with theoretical values of logP, as well as for selected physicochemical and pharmacokinetic parameters and anticancer activity. A toxicity test using zebrafish embryos and larvae was also conducted. High correlation was observed between the experimental and theoretical values of lipophilicity. We presented correlation equations and statistical parameters describing the relationships between logP TLC and several physicochemical and ADME parameters. We also revealed the lack of correlation between the experimental values of lipophilicity and anticancer activity. Moreover, experiments on zebrafish have confirmed no toxicity of the tested compounds, which was consistent with the results of the in silico toxicity analysis. The results demonstrated, using the example of indole derivatives of betulin, the utility of lipophilicity values in the context of predicting the biological activity of new compounds.

Background: Anxiety disorders significantly reduce patients' quality of life. Current pharmacological treatments, primarily benzodiazepines and antidepressants, are associated with numerous side effects. Consequently, there is a continual search for alternative methods to traditional therapies that are less burdensome for patients and broaden their therapeutic options. Our objective was to determine the role of selected alternative methods in the treatment of anxiety disorders., Methods: In this review, we examined recent evidence on alternative treatments for anxiety disorders, including physical activity, mindfulness, virtual reality (VR) technology, biofeedback, herbal remedies, transcranial magnetic stimulation (TMS), cryotherapy, hyperbaric therapy, vagus nerve stimulation (VNS), 3,4-methylenedioxymethamphetamine (MDMA), electroconvulsive therapy (ECT), and eye movement desensitization and reprocessing (EMDR) therapy. For this purpose we reviewed PubMed and after initial search, we excluded works unrelated to our aim, non-orginal data and animal studies. We conducted second search to cover all minor methods., Results: We included 116 studies, which data is presented in Tables. We have investigated which methods can support treatment and which can be used as a stand-alone treatment. We assessed the risks to benefits of using alternative treatments., Conclusion: Alternative treatments significantly expand the options available to patients and clinicians, with many serving as adjuncts to traditional therapies. Among the methods presented, mindfulness has the most significant therapeutic potential.

Background: To provide competent and respectful sexual health care, a critical and comprehensive assessment of students' attitudes towards sexuality is needed, which implies using reliable and valid questionnaires., Aim: To assess whether the extended version of the Students Attitude Towards Addressing Sexual Health (SA-SH-Ext) provides different, additional information about students' attitudes towards providing sexual healthcare compared to the Sexual Attitude and Beliefs Survey (SABS), to explore SA-SH-Ext potential response patterns through latent class analysis and to assess students' attitudes towards providing sexual healthcare and evaluate the differences in their attitudes to the cultural background and sociodemographic characteristics., Design: Multicentre, descriptive, analytical, comparative, and correlational cross-sectional study at three nursing faculties., Participants: Nursing students n = 514 (Serbia n = 180, Poland n = 150 and Lithuania n = 184)., Methods: A general questionnaire for obtaining sociodemographic data, SA-SH-Ext and SABS were used as students' report measures., Results: One part of the variance of each instrument does not overlap with the other, indicating that these instruments, in addition to the shared variance, provide different, additional information. A solution with three latent classes was found in the domain of responses to the SA-SH-Ext items. The response pattern placed nursing students in the class Comfortable and prepared in some situations, and the SABS score revealed students' moderately positive attitudes towards providing sexual healthcare. Significantly more conservative attitudes were demonstrated by students from Poland, those identifying their religious affiliation as Catholic and females, while first-year students showed more positive attitudes than those in later years of study., Conclusions: The SA-SH-Ext and SABS enable a reliable and quick assessment of nursing students' comfort and competence in providing sexual healthcare. However, the differences in students' attitudes towards sexuality concerning belonging to a specific group imply a need for curriculum redesign and facilitating students to be more open to communication about sexuality with people with mental illnesses and intellectual and physical disabilities., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background/Objectives: Exploring and establishing a consensus on palatal surgery, the outcomes and follow-up after the palatal surgery, the complications of palatal surgery, and the post-operative management after palatal surgery for snoring and obstructive sleep apnea (OSA) among sleep surgeons is critical in the surgical management of patients with such conditions. Methods: Using the Delphi method, a set of statements was developed based on the literature and circulated among a panel of eight European experts. Responses included agreeing and disagreeing with each statement, and the comments were used to assess the level of consensus and to develop a revised version. The new version with the level of consensus and anonymized comments was sent to each panel member as the second round. This was repeated over a total of five rounds. Results: The final set included a total of 111 statements, 27 of which were stand-alone questions and 21 of which contained 84 sub-statements. Of the 34 statements regarding palatal surgery, consensus was achieved among all eight, seven, and six panelists for 50%, 35.3%, and 5.9% of the questions, respectively. Of the 43 statements regarding the outcomes and follow-up after the palatal surgery, consensus was achieved among all eight, seven, and six panelists for 53.5%, 23.3%, and 4.7% of the questions, respectively. Of the 24 statements regarding complications after the palatal surgery, consensus was achieved among all eight, seven, and six panelists for 91.7%, 0%, and 4.2% of the questions, respectively. Of the 10 statements regarding post-operative management after palatal surgery, consensus was achieved among all eight, seven, and six panelists for 10%, 30%, and 30% of the papers, respectively. Conclusions: This consensus provides an overview of the work of European sleep surgeons to develop a set of statements on palatal surgery for the treatment of snoring and OSA, the outcomes and follow-up, the complications, and the post-operative management of palatal surgery. We believe that this will be helpful in everyday practice. It also indicates key areas for further studies in sleep surgery.

Despite tremendous developments in the field of laboratory testing in transplantation, the rules of eligibility for corneal transplantation still do not include typing of human leukocyte antigens (HLAs) in the donor and recipient or detection of donor-specific antibodies (DSAs) in the patient. The standard use of diagnostic algorithms is due to the cornea belonging to immunologically privileged tissues, which usually determines the success of transplantation of this tissue. A medical problem is posed by patients at high risk of transplant rejection, in whom the immune privilege of the eye is abolished and the risk of transplant failure increases. Critical to the success of transplantation in patients at high risk of corneal rejection may be the selection of an HLA-matched donor and recipient, and the detection of existing and/or de novo emerging DSAs in the patient. Incorporating the assessment of these parameters into routine diagnostics may contribute to establishing immune risk stratification for transplant rejection and effective personalized therapy for patients.

Obesity is a significant public health concern. GLP-1 receptor agonists (GLP1-RA), predominantly in use as a type 2 diabetes treatment, are a promising pharmacological approach for weight loss, while bariatric surgery (BS) remains a durable, but invasive, intervention. Despite observed heterogeneity in weight loss effects, the genetic effects on weight loss from GLP1-RA and BS have not been extensively explored in large sample sizes, and most studies have focused on differences in race and ethnicity, rather than genetic ancestry. We studied whether genetic factors, previously shown to affect body weight, impact weight loss due to GLP1-RA therapy or BS in 10,960 individuals from 9 multi-ancestry biobank studies in 6 countries. The average weight change between 6 and 12 months from therapy initiation was -3.93% for GLP1-RA users, with marginal differences across genetic ancestries. For BS patients the weight change between 6 and 48 months from the operation was -21.17%. There were no significant associations between weight loss due to GLP1-RA and polygenic scores for BMI or type 2 diabetes or specific missense variants in the GLP1R, PCSK1 and APOE genes, after multiple-testing correction. However, a higher polygenic score for BMI was significantly linked to lower weight loss after BS (+0.7% for 1 standard deviation change in the polygenic score, P = 1.24×10 -4 ). In contrast, higher weight at baseline was associated with greater weight loss. Our findings suggest that existing polygenic scores related to weight and type 2 diabetes and missense variants in the drug target gene do not have a large impact on GLP1-RA effectiveness. Our results also confirm the effectiveness of these treatments across all major continental ancestry groups considered.

Disturbances in pro/antioxidant balance emerge as a crucial element in bipolar disorder (BD). Some studies suggest that treatment effects on trace element concentration in BD. This study aimed to identify (a) the changes related to oxidative stress in BD and their relationship with trace elements engaged in pro/antioxidant homeostasis; (b) BD biomarkers using machine learning algorithm classification and regression tree (C&RT) analysis. 62 individuals with BD and 40 healthy individuals (HC) were included in the study. The concentration of pro/antioxidant state and concentration of selenium, zinc, arsenic in blood were assessed. We found a higher concentration of total antioxidant capacity, catalase, advanced oxidation protein products and a lower concentration of 4-hydroxynonenal (4-HNE), glutathione, glutathione peroxidase (GPx) in BD compared to HC. All examined trace elements were lower in the BD group compared to HC. A combination of two variables, 4-HNE (cut-off: ≤ 0.004 uM/mg protein) and GPx (cut-off: ≤ 0.485 U/mg protein), was the most promising markers for separating the BD from the HC. The area under the receiver operating characteristic curve values for C&RT was 90.5%. Disturbances in the pro/antioxidant state and concentration of trace elements of patients with BD may be a target for new therapeutic or diagnostic opportunity of BD biomarkers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rog, Łobejko, Hordejuk, Marciniak, Derkacz, Kiljańczyk, Matuszczak, Lubiński, Nesterowicz, Żendzian-Piotrowska, Zalewska, Maciejczyk and Karakula-Juchnowicz.)

The study assessed selected parameters of redox status in the plasma of patients suffering from high myopia (HM). Thirty-five children with mean age 13.7 ± 2.7 years with HM and 40 healthy children were included. Plasma redox status parameters were determined using colorimetric kits. The levels of retinol, α-tocopherol and coenzyme Q10 were determined with a high-performance liquid chromatograph. Negative correlations were observed between the concentrations of retinol and the axial length of the eye (r = - 0.514 p < 0.001). Increased myeloperoxidase (MPO) activity (p < 0.018), and decreased concentrations of retinol (p < 0.001) and α-tocopherol (p < 0.023) in patients with HM and the axial length of the eye > 26 mm compared to controls were established. Significantly lower retinol and α-tocopherol concentrations were found in patients with the axial length of the eye > 26 mm compared to those with the axial length of the eye ≤ 26 mm (p < 0.001, p < 0.021, respectively). Increased MPO activity in advanced stages of HM may confirm an inflammatory process in HM patients. Reduced retinol and α-tocopherol concentrations and their link to disease progression indicate a need for monitoring their levels and supplementation in children with HM., (© 2024. The Author(s).)

Depressive symptoms are highly prevalent and heterogeneous in women. Different brain structures might be associated with depressive symptoms and body composition in women with obesity/overweight and normal-/underweight, although the data is limited. The analysis included 265 women from Bialystok PLUS population study, untreated with antidepressive or antipsychotic medications. The subjects underwent brain magnetic resonance imaging and body composition analysis. Beck Depression Inventory (BDI) score was inversely associated with nucleus accumbens volume (β = -0.217, p = 0.008) in women with BMI ≥ 25 kg/m 2 , but with insula volume (β = -0.147, p = 0.027) in women with BMI < 25 kg/m 2 after adjustment for age and estimated intracranial volume (eTIV). In women with BMI ≥ 25 kg/m 2 , nucleus accumbens volume was inversely associated with the percentage of visceral fat and BDI score (β = -0.236, p = 0.012, β = -0.192, p = 0.017) after adjustment for age and eTIV. In women with BMI < 25 kg/m 2 , insula volume was positively associated with total fat-free mass and negatively with the BDI score (β = 0.142, p = 0.030, β = -0.137, p = 0.037) after adjustment for age and eTIV. Depressive symptoms might be associated with nucleus accumbens volume in overweight/obese women, while in normal-/ underweight women-with alterations in insula volume., (© 2024. The Author(s).)

Primary Hyperparathyroidism (PHPT) is characterized by excessive parathormone (PTH) secretion and disrupted calcium homeostasis. Untargeted metabolomics offers a valuable approach to understanding the complex metabolic alterations associated with different diseases, including PHPT. Plasma untargeted metabolomics was applied to investigate the metabolic profiles of PHPT patients compared to a control group. Two complementary liquid-phase separation techniques were employed to comprehensively explore the metabolic landscape in this retrospective, single-center study. The study comprised 28 female patients diagnosed following the current guidelines of PHPT diagnosis and a group of 30 healthy females as a control group. To evaluate their association with PHPT, we identified changes in plasma metabolic profiles in patients with PHPT compared to the control group. The primary outcome measure included detecting plasma metabolites and discriminating PHPT patients from controls. The study unveiled specific metabolic imbalances that may link L-amino acids with peptic ulcer disease, gamma-glutamyls with oxidative stress, and asymmetric dimethylarginine (ADMA) with cardiovascular complications. Several metabolites, such as gamma-glutamyls, caffeine, sex hormones, carnitine, sphingosine-1-phosphate (S-1-P), and steroids, were connected with reduced bone mineral density (BMD). Metabolic profiling identified distinct metabolic patterns between patients with PHPT and healthy controls. These findings provided valuable insights into the pathophysiology of PHPT., (© 2024. The Author(s).)

Breast cancer has the highest incidence rate among all malignancies worldwide. Its high mortality is mainly related to the occurrence of multidrug resistance, which significantly limits therapeutic options. In this regard, there is an urgent need to develop compounds that would overcome this phenomenon. There are few reports in the literature that selenium compounds can modulate the activity of P-glycoprotein (MDR1). Therefore, we performed in silico studies and evaluated the effects of the novel selenoesters EDAG-1 and EDAG-8 on BCRP, MDR1, and MRP1 resistance proteins in MCF-7 and MDA-MB-231 breast cancer cells. The cytometric analysis showed that the tested compounds (especially EDAG-8) are inhibitors of BCRP, MDR1, and MRP1 efflux pumps (more potent than the reference compounds-novobiocin, verapamil, and MK-571). An in silico study correlates with these results, suggesting that the compound with the lowest binding energy to these transporters (EDAG-8) has a more favorable spatial structure affecting its anticancer activity, making it a promising candidate in the development of a novel anticancer agent for future breast cancer therapy.

In the study, we aimed to investigate the activity of nanoformulations containing 5-fluorouracil and polymer-magnetic hybrids bearing membrane-penetrating and ligand-receptor-recognizing agents against colorectal cancer cells. The formation and characterization of iron oxide particles covered with polymeric shells comprising lithocholic acid and folic acid moieties are presented. The efficiency of nanoformulations combined by the simple mixing of low doses of 5-fluorouracil with the obtained hybrids was demonstrated against DLD-1 and HT-29 colon cancer cells. The most pronounced cytotoxic potential against HT-29 cells was observed in the cases of particles based on block and randomly arranged copolymers functionalized by FA motifs with depletion of viable cells by approximately 50 % compared to control cells and cells treated by 5-FU applied in free form. In the case of the DLD-1 cell line, the percentage of viable DLD-1 cells decreased by about 30 to 40% after treatment with the block and randomly arranged copolymer decorated by FA-moiety, when compared to 5-FU at the free form and the untreated control. The induction of apoptosis associated with PS-translocation was determined to be the main mechanism of their cytotoxic effects. Moreover, the safety profiles of the nanoformulations were established through hemolysis assay and the analysis of the viability of human colorectal fibroblasts. It was indicated that all tested nanoparticles met the compatibility requirements at the in vitro level. It should be emphasized that in many cases, there was a significant improvement in the compatibility of hybrids with the FA motif compared to non-functionalized hybrids with the addition of 5-FU. These findings suggest that the presence of FA might modulate the toxicity of chemotherapeutic agents., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Agnieszka Zofia Wilczewska reports financial support was provided by National Science Centre Poland. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Oxidative stress and the accompanying chronic inflammation constitute an important metabolic problem that may lead to pathology, especially when the body is exposed to physicochemical and biological factors, including UV radiation, pathogens, drugs, as well as endogenous metabolic disorders. The cellular response is associated, among others, with changes in lipid metabolism, mainly due to the oxidation and the action of lipolytic enzymes. Products of oxidative fragmentation/cyclization of polyunsaturated fatty acids (PUFAs) [4-HNE, MDA, 8-isoprostanes, neuroprostanes] and eicosanoids generated as a result of the enzymatic metabolism of PUFAs significantly modify cellular metabolism, including inflammation and the functioning of the immune system by interfering with intracellular molecular signaling. The key regulators of inflammation, the effectiveness of which can be regulated by interacting with the products of lipid metabolism under oxidative stress, are inflammasome complexes. An example is both negative or positive regulation of NLRP3 inflammasome activity by 4-HNE depending on the severity of oxidative stress. 4-HNE modifies NLRP3 activity by both direct interaction with NLRP3 and alteration of NF-κB signaling. Furthermore, prostaglandin E2 is known to be positively correlated with both NLRP3 and NLRC4 activity, while its potential interference with AIM2 or NLRP1 activity is unproven. Therefore, the influence of PUFA metabolites on the activity of well-characterized inflammasome complexes is reviewed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Atalay Ekiner, Gęgotek and Skrzydlewska.)

The aim of the study was to conduct of relationship of acute-phase proteins (APPs) with the severity of COVID-19 defined by National Institutes of Health and according to the criteria of MEWS scale, with the presence of a cytokine storm, oxygen therapy and patient survival. We enrolled 96 patients with COVID-19 and 30 healthy people. The samples were taken on the day of admission and after 9 days on average. Not only commonly used APPs such as CRP, procalcitonin and ferritin and also rarely assayed proteins such as transferrin, haptoglobin, α1-acid glycoprotein and α1-antitrypsin, were tested in the study. The levels of APPs depends on the severity of COVID-19 disease, on the presence of cytokine storm and used oxygen therapy. The greatest APPs changes occurred in the most advanced form of the disease, with the presence of a cytokine storm and the most intense oxygen therapy. The results obtained from MEWS scale were not consistent with National Institutes of Health scores. Studies in the second samples showed the quenching of the acute phase reactions and the effectiveness of oxygen therapy. Only two of the examined APPs i.e. procalcitonin and transferrin, differed between surviving and non-surviving patients, and these two predispose to the role of prognostic factors in Covid-19. In conclusion, the concentration of not all acute-phase proteins depends on the severity of COVID-19 disease, presence of cytokine storm, the used of oxygen therapy and only some of them (procalcitonin and transferrin) are related to the survival outcomes. Of the newly tested acute-phase proteins, only transferrin shows significance as a marker of disease severity and mortality in COVID-19 disease., (© 2024. The Author(s).)

The term "revolving door patients" refers to those who are frequently rehospitalized for relapse. This phenomenon can be explained by a multitude of factors, including a lack of medical and/or social support. On the basis of a review of various modalities of psychiatric treatment, such as long-acting injectables, assisted outpatient treatment, and telehealth, it is clear that a major underlying issue among people with psychiatric diseases who lack insight into their mental and physical health is medication nonadherence. Therefore, we propose a mobile delivery program (MDP) in which health care professionals deliver medications and care to psychiatric patients in their own homes. The target patient population for MDP is patients with medication nonadherence, frequent emergency department visits, and missed appointments. Patients with mental illnesses, especially schizophrenia, are disproportionately represented among the homeless and incarcerated populations. By implementing MDP, we can help break the cycle of incarceration for patients with mental illnesses and homelessness. In addition, the cost of transportation and salaries for the mobile delivery team would be considerably lower than the billions of dollars spent each year due to relapses, emergency department visits, inpatient admissions, and crime leading to long-term stays in correctional facilities. This model has the potential to reduce relapse, improve functioning, and reduce excess morbidity and mortality. Substantial cost savings for health services can, in turn, be expected., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The goal of the study was to identify markers of organ function used in daily routines that could potentially aid in the overall evaluation of the cardiovascular system in patients with right-ventricle heart failure due to pulmonary arterial hypertension (PAH) and left-ventricle heart failure. We analyzed correlations between parameters from right heart catheterization (RHC), cardiopulmonary exercise test (CPET), and selected laboratory parameters of thyroid, liver, kidneys function and iron homeostasis., Patients and Methods: A retrospective analysis included 107 patients (mean age 57.6 ​± ​16.2; 34.6 ​% women), comprising 57 patients with PAH (mean age 54.0 ​± ​18.2; 49.1 ​% women) and 50 patients with heart failure with reduced ejection fraction (HFrEF) ​< ​40 ​% (mean age 61.6 ​± ​12.7; 18 ​% women). All patients underwent CPET. Each patient in the PAH group had RHC performed. Fifteen patients from the HFrEF group underwent RHC, which confirmed the suspicion of pulmonary hypertension (HFrEF-SPH)., Results: CPET and laboratory parameters' analysis showed strong correlations between ventilation/carbon dioxide production (VE/VCO 2 ) slope and NT-proBNP in HFrEF without secondary PH and HFrEF-SPH groups. In the PAH group, VE/VCO 2 slope correlated with liver and thyroid function but also with morphological parameters of red-cell system. Analysis of correlations between laboratory and hemodynamic parameters revealed significant correlations between pulmonary arterial pressure, pulmonary vascular resistance (PVR) and red-cell parameters, especially strong with fT4 in the PAH group., Conclusions: In HFrEF-SPH patients, laboratory parameters strongly correlated with pulmonary pressures and pulmonary capillary wedge pressure (PCWP)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Inflammation plays a crucial role in the development of atherosclerotic plaques. Pentraxin 3 (PTX3) is produced at the site of inflammation and has been identified as a specific marker of atherosclerosis, vascular inflammation, and progression of the coronary artery disease (CAD). The aim of the study was to establish if PTX3 has potential relations with classical markers of cardiovascular risk, and if PTX3 may act as an independent risk factor of CAD occurrence and advancement., Materials and Methods: The study included 98 patients with stable CAD confirmed in coronary angiography (CAD group) (median age 65 interquartile range [IQR] 61-72 years; 72 ​% men). The control group consisted of 40 patients without CAD., Results: The CAD group had significantly higher PTX3 concentration compared to the control group. There was a correlation with age, male gender, lipid profile and intima-media thickness. There was no correlation between PTX3 concentration and the number of coronary vessels with significant atherosclerotic lesions and the advancement of atherosclerotic lesions on the Gensini scoring scale. The cut-off point was determined for 0.89 ​ng/ml for the exclusion of angiographically significant atherosclerotic lesions., Conclusions: Patients with CAD have significantly higher concentration of PTX3. There was no correlation between PTX3 and the advancement of angiographically significant atherosclerotic lesions in coronary arteries. Low PTX3 concentration may serve as an indicator for the absence of atherosclerosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Undernutrition and inflammatory processes are predictors of early mortality in the elderly and require a rapid and accurate diagnosis. Currently, there are laboratory markers for assessing nutritional status, but new markers are still being sought. Recent studies suggest that sirtuin 1 (SIRT1) has the potential to be a marker for undernutrition. This article summarizes available studies on the association of SIRT1 and undernutrition in older people. Possible associations between SIRT1 and the aging process, inflammation, and undernutrition in the elderly have been described. The literature suggests that low SIRT1 levels in the blood of older people may not be associated with physiological aging processes, but with an increased risk of severe undernutrition associated with inflammation and systemic metabolic changes.

Research on the markers of autoimmune response in multiple sclerosis (MS) is still of great importance. The aim of our study was the evaluation of plasma 20S constitutive proteasome, 20S immunoproteasome, and cathepsin S concentrations as potential biomarkers of a relapsing-remitting type of MS (RRMS). Surface plasmon resonance imaging (SPRI) biosensors were used for the evaluation of protein concentrations. Plasma 20S constitutive proteasome, 20S immunoproteasome, and cathepsin S concentrations were significantly higher in RRMS patients compared to the control group. All three parameters were characterized by excellent usefulness in differentiating MS patients from healthy individuals (AUC equal to or close to 1.000). The plasma concentration of analyzed parameters was not correlated with severity of disability in the course of RRMS (EDSS value), the number of years from the first MS symptoms, the number of years from MS diagnosis, or the number of relapses within the 24-month observational period. Our study has shown that plasma concentrations of 20S constitutive proteasome, 20S immunoproteasome, and cathepsin S have promising potential in differentiating RRMS patients from healthy individuals. All of the analyzed parameters were found to be independent of the time of MS relapse and the severity of neurological symptoms. Hence, their potential as highly sensitive and independent circulating markers of RRMS suggests a stronger association with immunological activity (inflammatory processes) than with the severity of the disease., (© 2024 The Author(s). Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)