Platelet P2Y₁₂ is an important ADP receptor that is involved in agonist-induced platelet aggregation and is a valuable target for the development of anti-platelet drugs. Here we characterise the effects of thio-analogues of uridine triphosphate (UTP) on ADP-induced platelet aggregation. Using human platelet-rich plasma we demonstrate that UTP inhibits P2Y₁₂ but not P2Y₁ receptors and antagonises 10 μM ADP-induced platelet aggregation in a concentration-dependent manner with an IC₅₀ value of ~250 μM. An 8-fold higher platelet inhibitory activity was observed with a 2-thio analogue of UTP (2S-UTP), with an IC₅₀ of 30 μM. The 4-thio analogue (4S-UTP) with an IC₅₀ of 7.5 μM was 33-fold more effective. A 3-fold decrease in inhibitory activity, however, was observed by introducing an isobutyl group at the 4S- position. A complete loss of inhibition was observed with thio-modification of the γ phosphate of the sugar moiety, which yields an enzymatically stable analogue. The interaction of UTP analogues with P2Y₁₂ receptors was verified by P2Y₁₂ receptor binding and cAMP assays. These novel data demonstrate for the first time that 2- and 4-thio analogues of UTP are potent P2Y₁₂ receptor antagonists that may be useful for therapeutic intervention.

Background: The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat Familial Chylomicronemia Syndrome (FCS). Cases of decreased platelet count are reported among patients treated with volanesorsen. The aim of the study is to evaluate platelet function and thrombin generation (TG) assessment in FCS patients receiving volanesorsen. We performed a cross-sectional study on FCS patients treated with volanesorsen. Methods: changes in PLC were assessed from baseline to Tw12 and Tw36. To assess TG, samples were processed by CAT (with PPP-reagent LOW). The results were expressed by the trombogram graphic (thrombin variation over time); lagTime; Endogenous Thormbin Potential(ETP); peak; time to reach peak(ttpeak), startTail e velocity Index. Platelet aggregation was assessed by testing different agonists using turbidimetry method. Results: Four FCS patients and 4 matched healthy controls were included in the present study. Changes in PLC at Tw12 was 30% and 34% at T36w. Thrombin generation results show values in normal range (for patients and controls respectively lagTime:10,42±4,40 and 9,25±0,99; ttPeak:14,33± 4,01 and 13,10±0,67; startTail:32,13±3,54 and 29,46±1,69; velocityIndex:20,21±3,63 and 33,05±13,21; ETP 599,80±73,47 and 900,2±210,99; peak value 76,84±1,07 and 123,30±39,45) and no significant difference between cases and controls. Platelet aggregation test showed values in range with no significant difference with healthy controls Conclusions: Our study showed for the first time that no significant changes in the general haemostasis assessed by TG and in platelet function have been observed in FCS patients receiving volanesorsen.

Methylmalonic acidemia (MMA), propionic acidemia (PA), and cobalamin C deficiency (cblC) share a defect in propionic acid metabolism. In addition, cblC is also involved in the process of homocysteine remethylation. These three diseases produce various phenotypes and complex downstream metabolic effects. In this study we used an untargeted metabolomics approach to investigate the biochemical differences and the possible connections with the pathophysiology of each disease. Untargeted urine metabolomic profiles of 21 patients (7 MMA, 7 PA, 7 cblC) were identified through statistical analysis (p<0.05; log2FC >|1|) and then used for the annotation. Annotated features were associated with different metabolic pathways potentially involved in the diseases development. Comparative statistic showed markedly different metabolomic profiles between MMA, PA and cblC, highlighting characteristic species for each disease. The most affected pathways were related to the metabolism of organic acids (MMA, PA, cblC), amino acids (MMA, PA, cblC), glycine and its conjugates (PA), transsulfuration pathway (cblC), oxidative processes (cblC) and neurosteroid hormones (cblC). The untargeted metabolomics study highlighted the presence of significant differences between the three diseases, pointing to the most relevant contrast of cblC profile compared to MMA and PA. Some new biomarkers are proposed for PA, while novel data regarding the alterations of steroid hormone profiles and biomarkers of oxidative stress were obtained for cblC disease. The elevation of neurosteroids in cblC may indicate a potential connection with the development of ocular and neuronal deterioration.

Coffee is rich in caffeine (CF), chlorogenic acid (CGA) and phenolics. Differing types of coffee beverages and brewing procedures may result in differences in total phenolic contents (TPC) and biological activities. Inflammation and increases of platelet activation and aggregation can lead to thrombosis. We focused on determining the chemical composition, antioxidant activity and inhibitory effects on agonist-induced platelet aggregation and cyclooxygenase (COX) of coffee beverages in relation to their preparation method. We prepared instant coffee and brewed coffee beverages using drip, espresso and boiling techniques. Coffee extracts were assayed for their CF and CGA contents using HPLC, TPC using colourimetry, platelet aggregation with an aggregometer and COX activity using ELISA. The findings have shown all coffee extracts, except the decaffeinated types, contained nearly equal amounts of CF, CGA and TPC. Inhibitory effects of coffee extracts on platelet aggregation differed depending on the activation pathways induced by different agonists. All espresso, drip and boiled coffee extracts caused dose dependent inhibition of platelet aggregation induced by ADP, collagen, epinephrine, and arachidonic acid (ARA). The most marked inhibition was seen at low doses of collagen or ARA. Espresso and drip extracts inhibited collagen-induced platelet aggregation more than purified caffeine or CGA. Espresso, boiled and drip coffee extracts were also a more potent inhibitors of COX-1 and COX-2 than purified caffeine or CGA. We conclude that inhibition of platelet aggregation and COX-1 and COX-2 may contribute to anti-platelet and anti-inflammatory effects of espresso and drip coffee extracts.

Refractoriness to antiseizure medications is still a major concern in the pharmacotherapy of epilepsy. For this reason, we decided to evaluate the combination of levetiracetam and cannabidiol, administered at a subthreshold dose, to limit the possible adverse effects of this phytocannabinoid. We administered levetiracetam (300 mg/kg/day, via osmotic minipumps), cannabidiol (120 mg/kg/day, injected once a day subcutaneously), or their combination for one week in epileptic rats. Saline-treated epileptic rats were the control group. Animals were monitored with video electroencephalography the week before and after the treatment. No changes were found in the controls. Levetiracetam did not significantly reduce the total seizure number or the overall seizure duration. Still, the overall number of seizures (p<0.001, Duncan’s new multiple range test) and their total duration (p<0.01) increased in the week following treatment withdrawal. Cannabidiol did not change seizures when administered as a single drug. Instead, levetiracetam combined with cannabidiol resulted in a significant reduction in the overall number and duration of seizures (p<0.05), when comparing values measured during treatment with both pre- and post-treatment values. These findings depended on changes in convulsive seizures, while non-convulsive seizures were stable. These results suggest cannabidiol determined a remarkable potentiation of levetiracetam antiseizure effects at a subthreshold dose.

In the present study we tested the effect of small molecular weight redox molecules on collagen-induced platelet aggregation. We used N-acetylcysteine amide (AD4), the amide form of N-acetylcysteine (NAC), a thiol antioxidant with improved lipophilicity and bio-availability compared to NAC, and the thioredoxin mimetics (TXM) peptides, TXM-CB3, TXM-CB13, and TXM-CB30. All compounds significantly inhibited platelet aggregation induced by collagen, with TXM-peptides and AD4 being more effective than NAC. The levels of TxB2 and 12-HETE, the main metabolites derived from the cyclooxygenase and lipoxygenase pathways following platelet activation, were significantly reduced in the presence of AD4, TXM-peptides, or NAC, when tested at the highest concentration (0.6 mM). The effect of AD4, TXM-peptides, and NAC was tested also on the clotting time (CT) of whole blood. TXM-CB3 and TXM-CB30 showed the highest increase of CT. Furthermore, two representative compounds, TXM-CB3, and NAC, showed an increase in the an-ti-oxidant free sulfhydryl groups of plasma detected by Ellman’s method, suggesting a contribution of plasma factors to the antiaggregating effects. Our results suggest that these small molecular weight redox peptides might become useful for the prevention and/or treatment of oxidative stress conditions associated with platelet activation.

HIV-associated cardiovascular diseases remain a leading cause of death in people living with HIV/AIDS (PLWHA). Although antiretroviral drugs suppress the viral load, they fail to remove the virus entirely. HIV-1 Nef protein is known to play a role in viral virulence and HIV latency. Expression of Nef protein can be detected in different organs, including cardiac tissue. Despite the established role of Nef protein in HIV-1 replication, its impact on organ function inside the human body is not clear. To understand the effect of Nef at the organ level, we created a new Nef transgenic (Nef-TG) mouse that expresses Nef protein in the heart. Our study found that Nef expression caused inhibition of cardiac function and pathological changes in the heart with increased fibrosis, leading to heart failure and early mortality. Further, we found that cellular autophagy is significantly inhibited in cardiac tissue of Nef-TG mice. Mechanistically, we found that Nef protein causes the accumulation of Bcl2 and Beclin-1 protein in the tissue, which may affect the cellular autophagy system. Additionally, we found Nef expression causes upregulation of cellular senescence marker p21, and senescence-associated -galactosidase expression. Our findings suggested that Nef-mediated inhibition of autophagy and induction of senescence markers may promote aging in the PLWHA. Our mouse model could help us to understand the effect of Nef protein on organ function during latent HIV infection.

High fat-diet (HFD) feeding is known to induce metabolic dysregulation, however less is known on its impact in promoting the hypercoagulable state. The current study aimed to evaluate platelet-monocyte aggregate (PMA) formation following short-term HFD feeding. This is particularly important for understanding the link between inflammation and the hypercoagulable state during the early onset of metabolic dysregulation. To explore such a hypothesis, mice were fed a HFD for 8 weeks, with body weights as well as insulin and blood glucose levels monitored on weekly basis during this period. Basal hematological measurements were determined and the levels of spontaneous peripheral blood PMAs were assessed using whole blood flow cytometry. The results showed that although there were no significant differences in body weights, mice on HFD displayed impaired glucose tolerance and markedly raised insulin levels. These metabolic abnormalities were accompanied by elevated baseline PMA levels as an indication of hypercoagulation. Importantly, it was evident that baseline levels of monocytes, measured using the CD14 monocyte marker were significantly decreased in HFD-fed mice when compared to controls. In summary, the current evidence shows that in addition to causing glucose intolerance, such as that identified in a prediabetic state, HFD-feeding can promote undesirable hypercoagulation, the major consequence implicated in the development of cardiovascular complications.

Cardiac autonomic neuropathy (CAN) is a severe complication of diabetes mellitus (DM) strongly linked to a nearly five-fold higher risk of cardiovascular mortality. Patients with Type 2 Diabetes Mellitus (T2DM) are a significant cohort in which these assessments have particular relevance to the increased cardiovascular risk inherent in the condition. This study aimed to explore the subtle correlation between the Ewing test, Sudoscan-cardiovascular autonomic neuropathy score, and cardiovascular risk calculated using SCORE 2 Diabetes in individuals with T2DM. The cohort consisted of 211 patients diagnosed with T2DM with overweight or obesity without established ASCVD, aged between 40 to 69 years. The prevalence of CAN in our group was 67.2%. In the study group, according SCORE2-Diabetes, four patients (1.9%) were classified with moderate cardiovascular risk, thirty-five (16.6%) with high risk, and one hundred seventy-two (81.5%) with very high cardiovascular risk. On multiple linear regression, the SCORE2-Diabetes algorithm remained significantly associated with Sudoscan CAN-score and Sudoscan Nephro-score and Ewing test score. Testing for the diagnosis of CAN in very high-risk patients should be performed because approximately 70% of them associate CAN. Increased cardiovascular risk is associated with sudomotor damage and that Sudoscan is an effective and non-invasive measure of identifying such risk.

In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated idiopathic GHD, with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. Analysis included 260 patients (173 boys, 87 girls) with isolated idiopathic GHD who completed rhGH therapy and have reassessed GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with assessment of GH therapy effectiveness. Incidence of transient GHD, even with respect to pediatric criteria was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in patients with normal IGF-1 before treatment, suggesting that diagnosis of GHD may be false positive. Further efforts should be made to avoid overdiagnosis GHD and overtreatment of the patients.

The applicability of the distance aggregation problem has attracted the interest of many authors. Motivated by this fact, in this paper we face the modular quasi-(pseudo-)metric aggregation problem. We characterize those functions that allow merging a collection of modular quasi-(pseudo-)metrics into a single one. Specifically, a description of such functions in terms of triangle triplets is given and, in addition, the relationship between modular quasi-(pseudo-)metric aggregation functions and modular (pseudo-)metric aggregation functions is discussed. Such characterizations are illustrated with appropriate examples. A few methods to construct modular quasi-(pseudo-)metrics are yielded. Several properties of modular quasi-(pseudo-)metric aggregation functions are explored and used to develop quick tests for discarding candidate functions to aggregate modular quasi-(pseudo-)metrics. Moreover, a characterization of those modular quasi-(pseudo-)metric aggregation functions that preserve modular quasi-(pseudo-)metrics is also provided. Furthermore, the relationship between modular quasi-(pseudo-)metric aggregation functions and quasi-(pseudo-)metric aggregation functions is studied in such a way that significative differences are displayed.

Background. During the COVID-19 pandemic, there was an increased number of the hospitalized COVID-19 positive patients suffering from type 2 diabetes mellitus (T2DM). The objective of this research was to explore factors associated with the length of hospitalization of patients with T2DM and mild form of COVID-19. Material and Methods. This retrospective cohort study involved all patients who tested positive for COVID-19 and were treated in the dedicated COVID department of the University Clinical Center (UCC) in Nis between September 10, 2021, and December 31, 2021. Upon admission, patients underwent blood tests for biochemical analysis, including blood count, kidney and liver function parameters (C-reactive protein-CRP, creatinine kinase, D-dimer), as well as glycemia and HbA1c assessments. Additionally, all patients underwent lung radiography. Univariate and multivariate regression analyses were employed to assess the impact of specific factors on the length of hospitalization among patients with T2DM. Results. Out of the total 549 COVID-19 positive patients treated, 124 (21.0%) had T2DM, while 470 (79.0%) did not have diabetes. Among patients with T2DM, men were significantly younger than women (60.6±16.8 vs. 64.2±15.3, p

Lipoprotein (a) is a highly atherogenic, lipid particle whose concentration is genetically determined, and represents an independent risk factor for cardiovascular disease. On the other hand, metabolic syndrome represents a cluster of interconnected cardiovascular risk factors (obesity, insulin resistance, arterial hypertension, dyslipidemia) that are a direct consequence of an unhealthy lifestyle. Some evidence suggests a connection between each component of metabolic syndrome and high levels of lipoprotein (a). Still, the exact mechanisms are not fully understood and may involve complex interactions between various metabolic pathways. High levels of lp(a) are associated with insulin resistance, a key feature of type 2 diabetes mellitus and obesity. Although there is no significant association between lp(a) and other lipid levels (LDL-C, HDL-C, triglycerides), studies have shown a strong synergistic effect of genetically elevated LDL-C and Lp (a) on the development of cardiovascular events. Also, there is supporting evidence that hypertensive patients with high levels of lp(a) have higher cardiovascular risk, there is no direct association between hypertension and lp (a). Treatment of metabolic syndrome is often long-term and challenging but very important to reduce the overall cardiovascular risk, especially in individuals with higher levels of Lp (a), in whom the risk of developing cardiovascular disease is much higher.

Introduction: Vitamin B1 (thiamine) deficiency (TD) after metabolic and bariatric surgery (MBS) is often insidious and, if unrecognized, can lead to irreversible damage or death. As TD symptoms are vague and overlap with other disorders, we aim to identify predictors of recurrent TD and failure to collect B1 labs. Methods: We analyzed a large sample of data from patients with MBS (n=878) to identify potential predictors of TD risk. We modeled recurrent TD and failure to collect B1 labs using classical statistical and machine learning (ML) techniques. Results: We identified clusters of labs associated with increased risk of recurrent TD: micronutrient deficiencies, abnormal blood indices, malnutrition, and fluctuating electrolyte levels (aIRR range: 1.62-4.68). Additionally, demographic variables associated with lower socioeconomic status were predictive of recurrent TD. ML models predicting characteristics associated with failure to collect B1 labs achieved 75-81% accuracy, indicating that clinicians may fail to match symptoms with the underlying condition. Conclusion: Our analysis suggests that both clinical and social factors can increase the risk of life-threatening TD episodes in some MBS patients. Identifying these indicators can help with diagnosis and treatment.

Metabolic-associated fatty liver disease (MASLD) is not only associated with traditional cardiovascular risk factors such as T2DM and obesity, but it is also an independent risk factor for the development of cardiovascular disease. MASLD has been shown to be independently related to endothelial dysfunction and atherosclerosis. MASLD is characterized by a chronic proinflammatory response that, in turn, may induce a prothrombotic state. Several mechanisms such as endothelial and platelet dysfunction, changes in the coagulation cascade, decreased fibrinolytic activity can contribute to induce the prothrombotic state. Platelets are players and addresses of metabolic dysregulation; obesity and insulin resistance are related to platelet hyperactivation. Furthermore, platelets can exert a direct effect on liver cells, particularly through the release of mediators from granules. Growing data in literature support the use of antiplatelet agent as a treatment for MASLD. The use of antiplatelets drugs seems to have potential clinical implication for the prevention of HCC patients with MASLD, since platelets contribute to fibrosis progression and cancer development. This review aims to summarize the main data on the role of platelets in the pathogenesis of MAFLD and its main complications such as cardiovascular events and the development of liver fibrosis. Furthermore, we will examine the role of antiplatelet therapy not only in the prevention and treatment of cardiovascular events but also as a possible anti-fibrotic and anti-tumor agent.

Sarcopenia is associated with clinical complications, which increase mortality. Effective sarcopenia risk screening in the elderly should be grounded in a comprehensive assessment, encompassing both nutritional status and medication use. Current screening tools, while emphasizing muscular per-formance, exhibit limited sensitivity in identifying elderly individuals at risk of sarcopenia. This cross-sectional study aimed to develop a sarcopenia risk screening tool, named Sarc-Global, with enhanced sensitivity, incorporating factors pertinent to the overall health of the elderly. Utilizing the criteria established by EWGSOP2 for diagnosing sarcopenia, we evaluated 395 communi-ty-dwelling elderly individuals. This evaluation served as a reference for assessing the efficacy of two validated questionnaires, Sarc-F and Sarc-CalF, and our newly developed Sarc-Global. Con-structed through multiple logistic regression, Sarc-Global integrates variables such as sex, age, medication use, body mass index, arm circumference, and handgrip strength – all significantly associated with sarcopenia (p

Background/aims: Prior research identified a significant association between heart disease and metabolic dysfunction-associated liver steatohepatitis (MASLD), but the mechanisms are unclear. This study aims to search predictive biomarkers for grade I left ventricular diastolic dysfunction (LVDD), an early stage of heart failure (HF), in type 2 diabetes mellitus (T2DM) patients. Methods: This single-center, prospective observational study screened 73 T2DM patients for grade 1 LVDD and MASLD using 2D echocardiography, tissue analysis, spectral color Doppler, and Fibromax. Results: The study analyzed 50 patients (mean age 58±11.3 years) with a median diabetes duration of 7 years, abdominal obesity (mean BMI 34.4±5.9 kg/m2), and a mean HbA1c of 7.9±1.5%. The prevalence of grade I LVDD, fibrosis, mild steatosis, moderate to severe liver steatosis, mild MASLD, and moderate MASLD was 54%, 44%, 14%, 80%, 43%, and 34%, respectively. Regression analysis revealed that grade 1 LVDD was positively associated with age, Fibrotest, ɑ2-macroglobulin, epicardiac adipose tissue (EAT), and negatively associated with lateral s`, E wave, E/e`, E/A, medium E`, and septal e` (p< 0.05 for all). ɑ2-macroglobulin > 1.92 g/L (AUROC= 0.782, sensitivity 70.4%, specificity 81.2%) and fibrotest score > 0.11 (AUROC 0.766, sensitivity 92.6%, specificity 56.2%) were significant predictors of grade I LVDD. Conclusion: HF is a multifaceted disorder associated with multisystem organ damage, including nonalcoholic MASLD. Although the underlying mechanisms remain unclear, innovative non-invasive biomarkers, such as ɑ2-macroglobulin or fibrotest, could concurrently indicate liver stiffness and the likelihood of grade I LVDD, an early, asymptomatic HF stage in T2DM patients.

The task of weakly supervised point cloud semantic segmentation has received widespread attention and also has been widely used in autonomous driving, robotics, and modern industries. Due to the high dimensionality and large volume of point cloud data, many technical difficulties appeal to weakly supervised semantic processing, especially segmentation. However, weakly-supervised schemes usually provide only partial labelling information of the underlying point cloud data and thus need to effectively extract local features, geometric information, and contextual relationships only using these limited labelled data for supervised learning. To improve weakly-supervised semantic segmentation, we propose a novel segmentation network through the boundary-based feature aggregation based on a K-NN algorithm with down-sampling operation, and also introduce the smoothness loss and Siamese loss for effective segmentation. The experiments on public datasets demonstrate that our presented segmentation method exceeds most of the existing fully supervised and weakly-supervised methods in terms of mIoU. Specifically, our network has high segmentation accuracy on the labels of objects with similar geometrical structures, such as ceiling, wall, floor, chair and table, reaching 91.2%, 98.8%, 83.3%, 75.3% and 80.2%, respectively. Extensive experiments also illustrate its robustness, effectiveness, and generalization of the proposed weakly supervised segmentation network.

This paper presents a biologically inspired flocking-based aggregation behaviour of a swarm of mobile robots. Aggregation behaviour is essential to many swarm systems, such as swarm robotics systems, in order to accomplish complex tasks that are impossible for a single agent. We developed a robot controller using Reynolds’ flocking rules to coordinate the movements of multiple e-puck robots during the aggregation process. To improve aggregation behaviour among these robots and address the scalability issues in current flocking-based aggregation approaches, we used a K-means algorithm to identify clusters of agents. Using the developed controller, we simulated the aggregation behaviour among the swarm of robots. Five experiments were conducted using Webots simulation software. The performance of the developed system was evaluated under a variety of environments and conditions, such as various obstacles, agent failure, different numbers of robots and arena sizes. The results of the experiments demonstrated that the proposed algorithm is robust and scalable. Moreover, we compared our proposed algorithm with another implementation of the flocking-based self-organizing aggregation behaviour based on Reynolds’ rules in a swarm of e-puck robots. Our algorithms outperformed this method in terms of cohesion performance and aggregation completion time.

Fiber aggregation in nanocomposites has an important effect on the macroscopic electrical performance. To quantitatively evaluate its effect, an index to characterize the degree of aggregation is imperative, and ideally it should have three features simultaneously, i.e., single-parametric, dimensionless and physically meaningful, applicable to different aggregation topologies, and one-to-one corresponding to material electrical properties. To this end, a new aggregation degree is proposed, which is defined as the average increased number of fibers that connect with each one when fibers aggregate from a uniformly distributed state. This index is applicable to different aggregation topologies from lump-like aggregating clusters to network-like aggregating clusters. This index is proven to only depend on the local features of aggregating clusters, and can be concisely expressed by the characteristic parameters of local structure, via geometric probability analysis and numerical validations. Further, a one-to-one linear relation between the aggregation degree and percolation threshold is established by Monte Carlo simulations, which is independent of the distribution law of the fibers. This work provides a guide to the property characterization, performance prediction and material design of nanocomposites, and also gives a physical insight into the understanding of systems with similar non-uniform distributions.

Apolipoprotein A (ApoA), an integral component of high-density lipoprotein (HDL) particles, plays a vital role in the transport and metabolism of lipids. It is implicated in both cardiovascular (CVD) and neurological diseases. In the context of CVD, ApoAs are pivotal in facilitating the reverse transport of cholesterol, mitigating inflammation, and preserving endothelial function. These char- acteristics highlight the crucial role of ApoA in averting the onset of CVDs. Moreover, ApoA has been implicated in the pathogenesis of several diseases, such as Alzheimer's disease (AD), Parkin- son's disease (PD), and multiple sclerosis (MS). Apart from its role in lipid metabolism, recent stud- ies have indicated the involvement of ApoA in neuroprotection, amyloid-beta clearance, and regu- lation of neuroinflammation. This paper addresses the research question: "How do different isoforms of Apolipoprotein A influence the development and progression of cardiovascular and neurological diseases, and what are the potential therapeutic implications of targeting ApoA in these conditions?" By providing a comprehensive review of current knowledge, this paper empha- sizes the importance of ApoA in understanding the intricate connections between cardiovascular and neurological health, suggesting that ApoA-targeted interventions may help treat diseases in both domains.

Emerging autologous cellular therapies that utilize platelet-rich plasma (PRP) applications have the potential to play adjunctive roles in a variety of regenerative medicine treatment plans. There is a global unmet need for tissue repair strategies to treat musculoskeletal (MSK) and spinal disorders, osteoarthritis (OA), and patients with chronic complex and recalcitrant wounds. PRP therapy is based on the fact that platelet growth factors (PGFs) support the three phases of wound healing and repair cascade (inflammation, proliferation, remodeling). Many different PRP formulations have been evaluated, originating from human, in vitro, and animal studies. However, recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, progress has been made in understanding PRP technology and the concepts for bioformulation, and new research directives and new indications have been suggested. In this review, we will discuss recent developments regarding PRP preparation and composition regarding platelet dosing, leukocyte activities concerning innate and adaptive immunomodulation, serotonin (5-HT) effects and pain killing. Furthermore, we discuss PRP mechanisms related to inflammation and angiogenesis in tissue repair and regenerative processes. Lastly, we will review the effect of certain drugs on PRP activity, and the combination of PRP and rehabilitation protocols.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder characterized by the development and progression of multiple renal cysts, leading to progressive renal function decline. To date, the only approved treatment for this condition is able to slow down the loss of annual renal function, without stopping the disease progression. Furthermore, this therapy is approved only for patients with rapid disease progression and its compliance is problematic because of the impact of this drug on quality of life. The recent literature suggests that cystic cells are subject to metabolic dysregulation in the glucose pathway (Warburg Effect). This finding paved the way for new lines of research targeting potential therapeutic interventions for ADPKD. In particular, this review highlights the latest studies on the use of ketosis, through ketogenic dietary interventions (daily calorie restriction, intermittent fasting, time-restricted feeding, and ketogenic diets), as a potential strategy for patients with ADPKD, and the possible involvement of microbiota in the ketogenic interventions’ effect.

Increased platelet activity is a risk factor of thrombotic events in cardiovascular patients. We studied the relationship between platelet function, platelet size and content of reticulated platelets (RP) in patients with coronary heart disease (CHD, n = 55) and acute coronary syndrome (ACS, n = 95) receiving acetylsalicylic acid + clopidogrel or ticagrelor respectively. Control group consisted of patients with risk factors for CHD, but no CHD/ACS and free of antiplatelet drugs (n = 66). Platelet function was evaluated by exposure of activated glycoprotein (GP) IIb-IIIa and P-selectin. In the control group, platelets were activated by TRAP (Thrombin Receptor Activating Peptide) 10 µM, ADP 20, 5, 2.5 µM and in CHD/ACS groups, by TRAP 10 µM, ADP 20, 5 µM (+/- epinephrine 20 µM). Platelet size was assessed by mean volume, % large forms and forward scattering. RP were stained by thiazole orange. In the control group activated GP IIb-IIIa and P-selectin correlated with platelet size and RP content after platelet activation by all agonists. Despite the decrease of platelet activity by antiplatelet drugs, most correlations (primarily for activated GP IIb-IIIa) were preserved in CHD/ACS patients. In conclusion, increased platelet size and RP content are associated with increased platelet activity and reduced efficacy of antiplatelet therapy.

Induction motors are the most numerous and significant dynamic loads in power systems. In transient voltage stability analysis, dynamic equivalent models are commonly used to simplify the representation of a group of induction motors. This paper presents an method for the grouping and aggregation of induction motors at a common bus. Firstly, grouping rules were provided for clustering induction motors into several subgroups based on the mechanical principles of rotor force and motion, and Aggregation Rules were provided for aggregating a motor subgroup into a single-unit model based on the relationship between voltage drop and power transmission in distribution networks. Secondly, guided by the grouping rules, high-speed remaining electromagnetic torque and low-speed remaining electromagnetic torque were defined as new clustering indicators, and an adaptive K-means clustering method using silhouette coefficient verification was provided to obtain the optimal motor subgroups. Thirdly, guided by the Aggregation Rules, a dynamic equivalent method was further provided to obtain the equivalent single-unit model from a motor subgroup. Lastly, a transient voltage stability simulation in a typical distribution network was presented to illustrate that the proposed clustering and equivalent methods are more reasonable, accurate, and effective than traditional methods, as the obtained model has better dynamic characteristics and can more accurately reproduce the process of voltage collapse.

Aging causes various degenerative diseases in the older adult population. Senescence, a state of permanent cell-cycle arrest accompanied by the production of various pro-inflammatory factors known as senescence-associated secretory phenotype (SASP), is considered a significant contributor to the aging process and its chronic diseases. Ample evidence showed that various stressors could induce senescence, including DNA damage, telomere shortening and damage, activation of oncogenes, and mitochondrial dysfunction. Numerous credible findings indicate that environmental agents can induce senescence, including UV radiation, a high-fat diet, heavy metal exposure, and cigarette smoke. These findings posed the possibility that many more environmental agents may induce senescence and accelerate aging but remain unidentified. Senescence also becomes more intriguing due to its promising future as a pharmacological target to blunt the detrimental effects of aging and prevent aging-related diseases, either by eliminating the senescent cells or by controlling the SASP. On the other hand, investigating senescence has become more intricate due to the need for a multi-marker approach and translation in vivo analysis. This review will discuss senescence and its biomarkers, how to identify gerontogens in vivo, and also the development of senotherapy that targets senescent cells.

Background: Metabolic flux analysis (MFA) is an indispensable tool in metabolic engineering. The simplest variant of MFA relies on an overdetermined stoichiometric model of the cell’s metabolism under the pseudo-steady state assumption, to evaluate the intracellular flux distribution. Despite its long history, the issue of model error in the overdetermined MFA, particularly misspecifications of the stoichiometric matrix, has not received much attention. Method: We evaluated the performance of statistical tests from linear least square regressions, namely Ramsey RESET test, F-test and Lagrange multiplier test, in detecting model misspecifications in the overdetermined MFA, particularly missing reactions. We further proposed an iterative procedure using the F-test to correct such an issue. Result: Using Chinese hamster ovary and random metabolic networks, we demonstrated that: (1) a statistically significant regression does not guarantee high accuracy of the flux estimates, (2) the removal of a reaction with a low flux magnitude can cause disproportionately large biases in the flux estimates, (3) the F-test could efficiently detect missing reactions, and (4) the proposed iterative procedure could robustly resolve the omission of reactions. Conclusion: Our work demonstrated that statistical analysis and tests could be used to systematically assess, detect and resolve model misspecifications in the overdetermined MFA.

Berberine (BER) is a natural alkaloid found in various Berberis species, used traditionally in herbal medicine and dietary supplements. BER exhibited various biological activities, including anti-inflammatory, antioxidant, antidiabetic, and anti-tumour properties by modulating cellular pathways and influencing gene expression. While BER shows promise in various health applications, its possible toxicity raises concerns. In 2023, EFSA issued a call for data on BER- and protoberberine (PROTBER)-containing products, to comprehensively assess its safety and potential health claims. With these premises, new data was collected by assessing: i) the phytochemical profile of BER- and PROTBER-containing preparations by newly developed HPLC-DAD method; ii) in silico and in vitro investigation of pharmacokinetics properties of BER; iii) in vitro cytotoxicity in different human cell lines and, iv) biological and molecular activities of extracts containing BER and PROTBER in in vitro human non-cancer cells. By testing 16 commercial Berberis extracts, the evidence collected showed a good qualitative reliability in terms of phytochemical profile and limited relapses on cytotoxicity even at 200 µg/ml after a 24h of exposure, while evidencing a good cellular bioavailability and cell migration inhibition. The potential for plant-drug interactions affecting CYP450 proved to be minimal. Overall, our work provides a useful overview to better elucidate potential concerns on botanicals containing BER and minor PROTBER commonly used in food supplement.

Background Corpus callosum abnormalities (CCA) are midline developmental brain malformations and are usually associated with a wide spectrum of other neurological and non-neurological abnormalities. The study aims to highlight the diagnostic role of fetal MRI to characterize heterogeneous corpus callosum abnormalities using the latest classification system. It also helps to identify associated anomalies, which have prognostic implications on the postnatal outcome. Methods In this study, retrospective data from antenatal women who underwent fetal MRI between January 2014 and July 2023 at Rush University Medical Center were evaluated for CCA and classified based on structural morphology. Patients were further assessed for associated neurological and non-neurological anomalies. Results The most frequent class of CCA was complete agenesis (79.1%), followed by hypoplasia (12.5%), dysplasia (4.2%) and hypoplasia with dysplasia (4.2%). Amongst them, 17% had isolated CCA, while the majority (83%) had complex forms of CCA associated with other CNS and non-CNS anomalies. Out of the complex CCA cases, 58% were associated with other CNS anomalies, while 8% were associated with non-CNS anomalies. 17% of cases had both. Conclusion The use of fetal MRI is valuable in the classification of abnormalities of the corpus callosum after the confirmation of a diagnosis suspected on prenatal ultrasound. This technique is an invaluable method for distinguishing between isolated and complex forms of CCA, especially in the cases of apparent isolated CCA. The use of diffusion-weighted imaging or diffusion tensor imaging in fetal neuroimaging is expected to provide further insights into white matter abnormalities in fetuses diagnosed with CCA in the future.

Asphaltene is a component of crude oil that, if mishandled, may create substantial transportation and industrial concerns. It is a solid by nature, with a diverse set of molecular compositions. Furthermore, the oil industry has identified emulsion generation and clogging precipitate as key concerns. The emulsified water droplets in the process are just what give the raw oil its increased viscosity; hence, power is squandered to transport the oil around. The information has been separated into sections based on simulation, solubilization, agglomeration, precipitation, and evidence of model chemicals in the literature. We have included research that investigates the bulk rheology and interfacial rheology of asphaltene to describe its interfacial activity more clearly.

Proteomics is the study of cellular proteome by investigating how different proteins interact with each other and the roles they play in the organism. For mRNA expression levels do not always correlate well with protein expression levels, and the study of mRNA does not consider protein posttranslational modifications (PTMs), complex formation and localization; all of which are key to protein function. Quantitative proteomics uses mass spectrometry to identify and quantify proteins so as to find differentially expressed proteins under different condition. This allows us to gain biological insights under stress or other pathological conditions. posttranslational modifications, such as lysine acetylation, succinylation and lactylation, occur after protein biosynthesis and play vital roles in protein activity and cell physiology regulation. Here we present the mass spectrometry analysis in detail to unveil protein acylase and deacylase’ roles in metabolic regulation based on PTMomics lysine acetylome and suincylome.

This review focuses on the emerging evidence for the association between estimated cardiorespiratory fitness (eCRF) and metabolic risk factors. Given the challenges associated with directly measuring cardiorespiratory fitness (CRF) in large populations, eCRF presents a practical alternative for predicting metabolic health risks. A literature search identified six relevant cohort studies from 2021 to 2024 that investigated the association of eCRF with hypertension, hyperglycemia, dyslipidemia, and obesity. The review findings highlight a consistent inverse relationship between higher eCRF and lower incidence of metabolic risks in line with CRF cohort studies. This review highlights the importance of low eCRF as a primordial indicator for metabolic risks and underscores the need for broader application. Future research directions should include exploring eCRF's predictive accuracy across diverse populations and health outcomes and testing its real-world applicability in healthcare and public health settings.

The role of astro- and microglial cells in the pathogenesis of epilepsy is currently under active in-vestigation. It is proposed that the activity of these cells may be regulated by agonists of peroxi-some proliferator-activated nuclear receptors (PPARs). The objective of this study was to investi-gate the effects of the PPAR β/δ agonist GW0742 (Fitorine) on the behavior and gene expression of astro- and microglial proteins involved in the regulation of epileptogenesis in rat brain in a lithi-um-pilocarpine model of temporal lobe epilepsy (TLE). A seven-day administration of GW0742 at a dose of 5 mg/kg/day has been shown to suppress TLE-related behavioral hyperactivity in the Open Field test and to attenuate the TLE-induced increase in gene expression and protein levels of astro- and microglial activation markers Gfap and Aif1 in the dorsal hippocampus and temporal cortex. Furthermore, GW0742 reversed the TLE-related increase in Lcn2 gene expression (a marker of the A1 phenotype of astrocytes) in the temporal cortex, the increase in the ratio of Nos2/Arg1 gene expression (markers of the M1/M2 phenotypes of microglia), and the decrease in Arg1 gene ex-pression in the dorsal hippocampus. The results suggest that GW0742 may mitigate behavioral and biochemical abnormalities in a lithium-pilocarpine model of TLE.

The first published description of intraovarian platelet-rich plasma (PRP) appeared in mid-2016, when a new experimental technique was successfully used in adult human ovaries to correct the reduced fertility potential accompanying advanced maternal age. Considering the potential therapeutic scope of intraovarian activated PRP and/or condensed platelet cytokines would likely cover both menopause treatment and infertility, the mainstream response has ranged from skeptical disbelief to welcome astonishment. Indeed, reports of restored menses in menopause (as an alternative to conventional hormone replacement therapy) and healthy term livebirths for infertility patients (either with IVF or as unassisted conceptions) after intraovarian PRP injection continue to draw notice. Yet any proper criticism of ovarian PRP applications will be difficult to rebut given the heterogenous patient screening, varied sample preparations, wide differences in platelet incubation and activation protocols, surgical/anesthesia techniques, and delivery methods. Notwithstanding these features, no adverse events have been reported thus far and ovarian PRP appears well tolerated by patients. Here, early research guiding the transition of ‘ovarian rejuvenation’ from experimental to clinical is outlined. Likely mechanisms are presented to explain results observed in both veterinary and human ovarian PRP research. Current and future challenges for intraovarian cytokine treatment are also discussed.

Eastern (EEEV) and Venezuelan (VEEV) equine encephalitis viruses (EEVs) are related, (+)ssRNA arboviruses that can cause severe, sometimes fatal, encephalitis in humans. EEVs are highly infectious when aerosolized, raising concerns for potential use as biological weapons. No licensed medical countermeasures exist; given the severity/rarity of natural EEV infections, efficacy studies require animal models. Cynomolgus macaques exposed to EEV aerosols develop fever, encephalitis, and other clinical signs similar to humans. Fever is nonspecific for encephalitis in macaques. Electrocardiography (ECG) metrics may predict onset, severity, or outcome of EEV-attributable disease. Macaques were implanted with thermometry/ECG radiotransmitters and exposed to aerosolized EEV. Data was collected continuously, and repeated-measures ANOVA and frequency-spectrum analyses identified differences between courses of illness and between pre-exposure and post-exposure states. EEEV-infected macaques manifested widened QRS-intervals in severely ill subjects post-exposure. Moreover, QT-intervals and RR-intervals decreased during the febrile period. VEEV-infected macaques suffered decreased QT-intervals and RR-intervals with fever onset. Frequency-spectrum analyses revealed differences in the fundamental frequencies of multiple metrics in the post-exposure and febrile periods compared to baseline and confirmed circadian dysfunction. Heart rate variability (HRV) analyses revealed diminished variability post-exposure. These analyses support using ECG data alongside fever and clinical laboratory findings for evaluating medical countermeasure efficacy.

Mediterranean diet, featuring sourdough bread, shows promise in managing metabolic syndrome. This study explored the effects of two sourdough breads with differing fermentation times but similar nutritional profiles on inflammation, satiety, and gut microbiota composition in adults with metabolic syndrome. The double-blind clinical trial randomized participants to consume over two-months Elias Boulanger® long fermentation (48h) sourdough bread (EBLong) or Elias Boulanger® short fermentation (2h) sourdough bread (EBShort). We assessed clinical parameters, inflammatory- and satiety-related biomarkers; and richness and abundance of gut microbiota at baseline and follow-up. 31 individuals (mean age: 67, 55.7% female) participated. EBShort was associated with reduced soluble intercellular adhesion molecule (sICAM) levels, and irrespective of the adjudicated intervention, all participants had a decrease in sICAM and diastolic pressure relative to baseline (p<0.017). At follow-up, plasminogen activator inhibitor-1 (PAI-1) levels were lower in EBShort (-744 pg/mL; 95%CI: -282 to -1210 pg/mL) compared to EBLong. High-quality sourdough bread may offer mild benefits in blood pressure and inflammation for those with metabolic syndrome, however, only EBLong was associated to reduced Enterobacteriaceae abundance. Further research is needed to understand potential benefits and mechanisms of sourdough bread in managing metabolic syndrome and improving cardiovascular health.

This work presents the results regarding the synthesis of tungsten nanoparticles (W NPs) by magnetron sputtering combined with gas aggregation (MSGA) when H2 mixed with Ar is used as working gas, the amount of H2 being increased up to 82%. The results show that up to 40% H2 in discharge the synthesis rate increases over 60 times, rapidly decreasing for over 50% H2 in discharge. The W dust is still produced in H2 dominated discharge (82%), the deposition rate being small but not negligible (20 mg/hour). The obtained WNPs are isolated, with the diameter decreasing from 50 nm to 15 nm when the amount of H2 in discharge is smaller than 41%. Over this value, the particles tend to agglomerate, forming structures similar to film-like deposits. Also, the diameter of the deposited spots on substrates is dependent on the H2 content in discharge. This allows the efficient coating of substrates with dimensions up to 26 mm by translating them in front of the MSGA cluster source exit aperture. Supplementary, for 41% H2 in discharge, the influence of synthetic air leaks (0-5%) in discharge was investigated. The deposition rate decreases rapidly (ceasing for around 4% air in discharge) and the obtained nanoparticles tend to agglomerate (at 2% air content, the dust deposit has the aspect of a near continuous film). Chemical composition investigations show a pronounced tendency of oxidation, nitridation and oxynitride formation in the presence of air leaks.

Angiogenesis is new blood vessel formation from existing vessels and is a critical first step in tissue repair following chronic disturbances in healing and degenerative tissues. Chronic pathoanatomic tissues are characterized by a high number of inflammatory cells, overexpression of inflammatory mediators, such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1), the presence of mast cells, T cells, reactive oxygen species, and matrix metalloproteinases, and a decreased angiogenic capacity. Multiple studies have demonstrated that autologous orthobiological cellular preparations (e.g., platelet-rich plasma [PRP]) im-prove tissue repair and regenerate tissues. There are many PRP devices on the market. Unfortunately, they differ greatly in platelet numbers, cellular composition, and bioformulation. PRP is a platelet concentrate consisting of a high concentration of platelets with or without certain leukocytes, platelet-derived growth factors (PGFs), cytokines, molecules, and signaling cells. Several PRP products have immunomodulatory capacities that can influence resident cells in a diseased microenvironment, inducing tissue repair or re-generation. Generally, PRP is a blood-derived product, regardless of its platelet number and bioformulation, and the literature indicates both positive and negative patient treatment outcomes. Strangely, the literature does not designate specific PRP preparation qualifications that can potentially contribute to tissue re-pair. Moreover, the literature scarcely addresses the impact of platelets and leukocytes in PRP on (neo)angiogenesis other than a general one-size-fits-all statement that “PRP has angiogenic capabilities.” Here, we review the cellular composition of all PRP constituents, including leukocytes, and describe the importance of platelet dosing and bioformulation strategies in orthobiological applications to initiate angiogenic pathways that re-establish microvasculature networks, facilitating the supply of oxygen and nutrients to impaired tissues.

The relationship between metabolic changes occurring in the developing internodes of sugarcane and the final yield and sugar characteristics is poorly understood. This is due to the lack of integration between phenotypic and metabolic data. To address this issue, a study was conducted where sugarcane metabolism was modelled based on the measurement of cellular components in the top internodes at two stages of crop development. The study also looked at the effects of Trinexapac-ethyl (Moddus®) on growth inhibition. The metabolome was measured using GC-analysis while LC-MS/MS was used to measure proteome changes in the developing internodes. The data was then integrated with the metabolic rates. The study revealed that the duration of internode growth is independent of the growth rate and is probably controlled by the accumulation of heat units (degree days). In contrast, sucrose and lignin accumulation is sensitive to the growth rate. Sucrose accumulation only occurs once the cell wall synthesis slow down. The data suggest that sucrose accumulation is controlled a reduction in sucrose breakdown for metabolic activity and a reduction in demand for carbon for cell wall polysaccharide synthesis. This study also found that nucleotide sugar metabolism appears to be a key regulator in regulating carbon flow during internode development.

Severe COVID-19 is frequently associated with thromboembolic complications. Increased platelet activation and platelet-leukocyte aggregate formation can amplify thrombotic responses by inducing tissue factor (TF) expression on leukocytes. Here, we characterized TF-positive extracellular vesicles (EVs) and their cellular origin in 12 patients suffering from severe COVID-19 (time course, 134 samples overall) and 25 healthy controls. EVs exposing phosphatidylserine (PS) were characterized by flow cytometry. Their cellular origin was determined by staining with anti-CD41, anti-CD45, anti-CD235a, and anti-CD105 as platelet, leukocyte, red blood cell, and endothelial markers. We further investigated the association of EVs with TF, platelet factor 4 (PF4), C-reactive protein (CRP) and high mobility group box-1 protein (HMGB-1). COVID-19 patients showed higher levels of PS-exposing EVs compared to controls. The majority of these EVs originated from platelets. A higher amount of EVs in patient samples were associated with CRP, HMGB-1, PF4, and TF, as compared to EVs from healthy donors. In COVID-19 samples, 16.5% of all CD41+ EVs displayed the leukocyte marker CD45, and 55.5% of all EV aggregates (CD41+CD45+) co-expressed TF, which reflects the interaction of platelets and leukocytes in COVID-19 on an EV level.

This review article is devoted to the colloidal properties of fullerene solutions. According to generally accepted understanding, all solvents in relations to fullerenes are divided into “good” (or “strong” or “high-solubility” ones), “poor” (usually polar) and “reactive”. Water occupies a special place, close to “poor” solvents. We have consistently considered and discussed the state of fullerenes in these systems. In "good", predominantly non-polar aromatic solvents and CS2, nonequilibrium dissolution methods lead to the formation of colloidal aggregates, whereas utilization of equilibrium methods results in the formation of molecular solutions. The latter, however, have some unusual properties; new results confirm previously expressed ideas about colloidal properties of these solutions. Both experimental and theoretical methods devoted to such systems are considered. In “poor” (polar) solvents, typical lyophobic colloidal systems appear. Both “bottom-up” and “top-down” methods of preparation are now well documented in the literature. However, some of these polar solvents dissolve fullerenes rather easily and with less energy consumption. In addition to N-methylpyrrolidin-2-one, which has been well studied for fullerenes, DMSO and DMF have now been described. These solvents can be considered a subset of poor solvents that have some features of being “reactive” at the expense of basic (“cationophilic”) properties. Room temperature ionic liquids are also used to dissolve fullerenes, but there is little experimental research. Hydrosols and aqueous suspensions of fullerenes are typical hydrophobic colloids that obey the Schulze–Hardy rule and other regularities in the presence of electrolytes. New experimental data confirm the previously obtained results. Organosols in acetonitrile and methanol are much less stable with respect to electrolytes; the difference in critical coagulation concentrations of electrolytes reaches two to three orders of magnitude. This allows us to conclude that there is an additional, so-called non-DLVO, stabilizing factor in the hydrosols. Accordingly, the value of the Hamaker constant of fullerene-fullerene interaction may be higher than that derived from coagulation data in water. Contrary to the mentioned “poor” polar solvents, the stability of fullerene sols in DMSO is even higher than in water. These results, as well as data obtained with DMF demonstrate strong solvation of fullerenes with basic solvents.

Metabolic syndrome (MetS) refers to the group of several interconnected risk factors that collectively double the risk of cardiovascular disease. Epilepsy is linked to MetS across all age groups, though its prevalence differs across various studies. This can be understood from the perspective of seizure-related metabolic abnormalities, long-term antiepileptic drugs (AEDs) use, and a more sedentary lifestyle due to epilepsy. The factors that are considered in developing MetS for patients with epilepsy (PWE) are age, residence, level of physical activity, food intake status, epilepsy subtype, epilepsy duration, current (AEDs) use, drug responsiveness status, body-mass index (BMI), total cholesterol and LDL-cholesterol levels. A deeper understanding of the epilepsy-AED-MetS connection and the exploration of lifestyle interventions hold the promise of significantly improving the overall health and well-being of PWE. Clinicians managing PWE should closely monitor various risk factors for developing MetS and consider them when selecting AED treatment.

Background/Objectives: Encouraging results reported of Platelet-Rich Plasma (PRP) treatment for knee osteoarthritis (KOA). The present retrospective study reports the efficacy and safety of a high dose of neutrophile and red blood cell-depleted PRP to treat 212 patients with KOA. Methods: 212 consecutive patients diagnosed with Kellgren-Lawrence (KL) grading 1-3 KOA chronic knee pain for at least 1 year were treated with 3 injections at 15-day intervals with a high dose of neutrophil-depleted PRP (4 billion platelets). Clinical outcomes were retrospectively recorded as a percentage of responders at 3,6, and 12-month follow-up, following the OMERACT-OARSI criteria. Pain through VAS score and WOMAC score have also been recorded. Results: 4ml of PRP containing 4X109 platelets were obtained by single spin centrifugation and injected intra-articular into each patient with no pre-activation. The overall responder rate of patients responding to OMERACT-OARSI criteria at 3,6,12 months was 68.9%, 72,7% and 70,6%. There was a significant improvement in VAS and WOMAC scores at 3-, 6- and 12-month follow-up compared to the pre-treatment value (p< 0.01). The lowest VAS score was observed at 6 months overall and in all three-grade KL groups. KL2 groups showed the best results regarding pain reduction and WOMAC score at 6 months (p< 0.01). Conclusions: a high dose of neutrophil-depleted PRP is an effective treatment for KL1-3 KOA. It provides symptomatic relief, can potentially reduce disease progression, and has sustained effects for up to 12 months.

The disruption of brain energy metabolism, leading to alterations in synaptic signaling, neural circuitry, and neuroplasticity, has been implicated in severe mental illnesses such as schizophrenia, bipolar disorder, and major depressive disorder. The therapeutic potential of ketogenic interventions in these disorders suggests a link between metabolic disturbances and disease pathology; however, the precise mechanisms underlying these metabolic disturbances and the therapeutic effects of metabolic ketogenic therapy remain poorly understood. In this study, we conducted an in silico analysis of transcriptomic data to investigate perturbations in metabolic pathways in the brain across severe mental illnesses via gene expression profiling. We also examined dysregulation of the same pathways in rodent or cell culture models of ketosis, comparing these expression profiles to those observed in the disease states. Our analysis revealed significant perturbations across all metabolic pathways, with the greatest perturbations in glycolysis, the tricarboxylic acid (TCA) cycle, and the electron transport chain (ETC) across all three disorders. Additionally, we observed some discordant gene expression patterns between disease states and ketogenic intervention studies, suggesting a potential role for ketone bodies in modulating pathogenic metabolic changes. Our findings highlight the importance of understanding metabolic dysregulation in severe mental illnesses and the potential therapeutic benefits of ketogenic interventions in restoring metabolic homeostasis. This study provides insights into the complex relationship between metabolism and neuropsychiatric disorders and lays the foundation for further experimental investigations aimed at appreciating the implications of the present transcriptomic findings as well as developing targeted therapeutic strategies.

Advanced glycation end-products (AGEs) form through non-enzymatic glycation of various proteins. Optic nerve degeneration is a frequent complication of diabetes, and retinal AGEs accumulation is strongly linked to diabetic retinopathy development. Type 2 diabetes mellitus (T2DM) is a major risk factor for Alzheimer's disease (AD), with patients often exhibiting optic axon degeneration in the nerve fiber layer. Notably, a gap exists in our understanding of how AGEs contribute to neuronal degeneration in the optic nerve within the context of both diabetes and AD. Our previous work demonstrated that glyceraldehyde (GA)-derived toxic advanced glycation end-products (TAGE) disrupt neurite outgrowth through TAGE-β-tubulin aggregation and tau phosphorylation in neural cultures. In this study, we further illustrated GA-induced suppression of optic nerve axonal elongation via abnormal β-tubulin aggregation in mouse retinas. Elucidating this optic nerve degeneration mechanism holds promise for bridging the knowledge gap regarding vision loss associated with DM and AD.

Chronic Chagas Cardiomyopathy (CCC) results from infection with the protozoan parasite Trypanosoma cruzi and is a prevalent cause of heart disease in endemic countries. We previously found that cardiac fibrosis can vary widely in C3H/HeN mice chronically infected with T. cruzi JR strain, mirroring the spectrum of heart disease in humans. In this study, we examined functional cardiac abnormalities in this host:parasite combination to determine its potential as an experimental model for CCC. We utilized electrocardiography (ECG) to monitor T. cruzi-infected mice and determine whether ECG markers could be correlated with cardiac function abnormalities. We found that the C3H/HeN:JR combination frequently displayed early onset CCC indicators, such as sinus bradycardia and right bundle branch block, as well as prolonged PQ, PR, RR, ST and QT intervals in the acute stage. Our model exhibited high levels of cardiac inflammation and enhanced iNOS expression in the acute stage, but denervation did not appear to have a role in pathology. These results demonstrate the potential of the C3H/HeN:JR host:parasite combination as a model for CCC that could be used for screening new compounds targeted at cardiac remodeling and for examining the potential of anti-parasitic drugs to prevent or alleviate CCC development and progression.

The SARS coronavirus 2 (SARS-CoV-2) is the causative agent of the 2019 coronavirus disease (COVID-19) pandemic that has executed 6.9 million people and infected over 765 million. It’s become a major worldwide health alarm and is also known to cause abnormalities in various systems, including the hematologic system. COVID-19 infection primarily affects the lower res-piratory tract and can lead to a cascade of events, including a cytokine storm, intravascular thrombosis, and subsequent complications such as arterial and venous thromboses. COVID-19 can cause thrombocytopenia, lymphopenia, and neutrophilia, which are associated with worse out-comes. Prophylactic anticoagulation is essential to prevent complication and death rate associated with the virus's effect on the coagulation system. It is crucial to recognize these complications early and promptly start therapeutic anticoagulation to improve patient outcomes. While rare, COVID-19-induced disseminated intravascular coagulation exhibits some similarities to DIC induced by sepsis. LDH, D-dimer, ferritin, and CRP biomarker are often increase in serious COVID-19 cases and poor prognosis. Understanding the pathophysiology of the disease and identifying risk factors for adverse outcomes is critical for effective management of COVID-19.

Metabolites present in the hemolymph of honey bees play a crucial role in modulating the metamorphic process within the species. However, the precise alterations in metabolite composition, along with the associated variances and regulatory pathways implicated during the larvae-to-pupae metamorphosis of honey bees, remain incompletely elucidated. In this investigation, we gathered hemolymph samples from honey bee larvae at three distinct physiological stages-feeding, prepupal, and pupae and subjected them to metabolite analysis utilizing the liquid chromatography-mass spectrometry (LC-MS) technique. Employing principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), we identified significant differential metabolites and conducted a metabolic pathway analysis on those differentially up-regulated during the prepupal and pupae stages. Notably, metabolites up-regulated in the hemolymph of prepupal stage larvae primarily governed glucose metabolism and fat digestion and absorption, while those in pupae stage larvae were involved in regulating chitin and lipopolysaccharide precursor formation, as well as the biosynthesis of phenylalanine, tyrosine, and tryptophan. These findings bear significant implications for advancing our comprehension of the metamorphic processes in honey bees.

Background: The increasing prevalence of severe obesity among children and adolescents poses a significant challenge for pediatricians and general practitioners. This study aimed to investigate the relationships between biochemical results, anthropometry, blood pressure measurements and bioimpedance analysis (BIA)-derived parameters, to identify potential cardiometabolic complications associated with severe obesity. Methods: The study included 347 children (162 boys, 185 girls) aged 0-19 years, meeting criteria for severe obesity based on BMI thresholds for different age groups. Patients were recruited in four pediatric endocrinology centers in Poland (Zabrze, Cracow, Rzeszow, Szczecin). Each participant underwent anthropometric measurements, pubertal stage assessment, blood pressure measurement, biochemical and hormonal tests and BIA. Results: BMI showed significant associations with fat mass percentage (FM%) and waist-to-height ratio (WHtR), but not waist-to-hip ratio (WHR). The relationship between BMI and FM% was stronger in girls and prepubertal children. Metabolic syndrome (MetS) Z-score showed a strong positive correlation with BMI in pubertal children. Negative correlation between HDL and triglycerides was observed only in boys. Prepubertal children exhibited more significant correlations despite a smaller sample size and shorter duration of obesity. Conclusions: Considering multiple parameters beyond BMI alone provides a better understanding of cardiometabolic risks associated with severe obesity in children. MetS Z-score was not a reliable indicator of increased cardiometabolic risk in younger children. Early-onset severe obesity was associated with a higher risk of metabolic complications. Early intervention is crucial to mitigate metabolic complications in this population.

Amyloids result from the aggregation of several unrelated proteins, due to either specific mutations or promoting intra- or extra-cellular conditions. Structurally, they are rich in intermolecular β-sheets and are the causative agents of several diseases, both neurodegenerative and systemic. It is believed that the most toxic species are small aggregates, referred to as oligomers, rather than the final fibrillar assemblies. Their mechanisms of toxicity are mostly mediated by aberrant interactions with the cell membranes, with resulting derangement of membrane-related functions. Much effort is being put in the search for natural antiamyloid agents, and/or in the development of synthetic molecules. Actually, it is well documented that the prevention of amyloid aggregation results in several cytoprotective effects. Here, we portray the state of the art in the field. Several natural compounds are effective antiamyloid agents, notably tetracyclines and polyphenols. They are generally non-specific, as documented by their partially overlapping mechanisms, and the capability to interfere with the aggregation of several unrelated proteins. Among rationally designed molecules, we mention the prominent examples of β-breakers peptides, whole antibodies and fragments thereof, and the special case of drugs contrasting transthyretin aggregation. In this framework, we stress the pivotal role of the computational approaches. When combined with biophysical methods, in several cases they have helped clarify in detail the protein/drug modes of interaction, which make it plausible that more effective drugs will be developed in the future.

Hematological malignancies refer to a heterogeneous group of neoplastic conditions of lymphoid and hematopoietic tissues classified in leukemias, Hodgkin and non-Hodgkin lymphomas and multiple myeloma, according to their presumed cell of origin, genetic abnormalities, and clinical features. Metabolic adaptation and immune escape, which influence various cellular functions including proliferation and survival of hematological malignant tumor cells, are major aspects of these malignancies that lead to therapeutic drug resistance. Targeting specific metabolic pathways is emerging as novel therapeutic strategy in hematopoietic neoplasms, particularly in acute myeloid leukemia and multiple myeloma. In this context, CD147, also known as Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) or Basigin, is one target-candidate involved in reprogramming metabolism in different cancer cells, including hematological malignant tumor cells. CD147 overexpression significantly contributes to the metabolic transformation of these cancer cells, by mediating signaling pathway, growth, metastasis and metabolic reprogramming, through its interaction, direct or not, with various membrane proteins related to metabolic, regulation including monocarboxylated transporters, integrins, P-glycoprotein and Glucose Transporter 1. This review explores the metabolic functions of CD147 and its impact on the tumor microenvironment, influencing the progression and neoplastic transformation in leukemias, myeloma and lymphomas. Furthermore, we highlight new opportunities for the development of targeted therapies against CD147, potentially improving the treatment of hematologic malignancies.

Thrombosis is the pathological clot formation under abnormal hemodynamic conditions, which can result in vascular obstruction, causing ischemic strokes and myocardial infarction. Thrombus growth under moderate to low shear (<1000 s^-1) relies on platelet activation and coagulation. Thrombosis at elevated high shear rates (>10,000 s-1) is predominantly driven by unactivated platelet binding and aggregating mediated by von Willebrand factor (VWF), while platelet activation and coagulation are secondary in supporting and reinforcing the thrombus. Given the molecular and cellular level information it can access, multiscale computational modelling informed by biology can provide new pathphysiological mechanisms that are otherwise not accessible experimentally, holding promise for novel first-principle-based therapeutics. In this review, we summarize the key aspects of platelet biorheology and mechanobiology, focusing on the molecular and cellular scale events and how they build up to thrombosis through platelet adhesion and aggregation in the presence or absence of platelet activation. In particular, we highlight recent advancements in multiscale modeling of platelet biorheology and mechanobiology and how they can lead to better prediction and quantification of thrombus formation, exemplifying the exciting paradigm of digital medicine.

In the past thirty years, childhood obesity rates have risen significantly worldwide, affecting over 340 million children in affluent nations. This surge is intricately tied to metabolic disorders, notably insulin resistance, type 2 diabetes mellitus (T2DM), and the continually evolving spectrum of metabolic-associated (dysfunction) steatotic liver disease (MASLD). This review underscores the alarming escalation of childhood obesity and delves comprehensively into the evolving and dynamic changes of nomenclature surrounding diverse conditions of hepatic steatosis, from the initial recognition of non-alcoholic fatty liver disease (NAFLD) to the progressive evolution into MASLD. Moreover, it emphasizes the crucial role of pediatric endocrinologists in thoroughly and accurately investigating MASLD onset in children with T2DM where each condition influences and exacerbates the progression of the other. The review critically highlights the inadequacies of current screening strategies and diagnosis, stressing the need for a paradigm shift. A proposed solution involves the integration of hepatic magnetic resonance imaging assessment in the diagnostic arsenal for children showing insufficient glycaemic control and weight loss post-T2DM diagnosis, thereby complementing conventional liver enzyme testing. This holistic approach aims to significantly enhance diagnostic precision, fostering improved outcomes in this vulnerable high-risk pediatric population.

The long-term use of fertilizers and pesticides in conventional cultivation has resulted in a decrease in soil productivity and vegetable yields in greenhouses. However, only a limited number of studies have explored the impacts of organic cultivation on greenhouse soil. Specifically, there is a scarcity of research examining the alterations in soil aggregate mediated organic carbon and microbial communities, which are known to enhance soil productivity. This study investigated the properties of soil aggregates, including the levels of organic carbon fractions, microbial community, and enzyme activity with the three aggregate classes microaggregates (&lt;0.25 mm), small macroaggregates (2-0.25 mm) and large macroaggregates (&gt;2 mm). These investigations were conducted under three different cultivation methods in a greenhouse: conventional cultivation (CC), integrated cultivation (IC), and organic cultivation (OC) in greenhouse. The results showed that (1) OC and IC promoted the formation of small macro-aggregates and enhanced aggregate stability compared to CC, (2) SOC in the three size fractions of OC increased by 98.99%-92.06% compared to CC; EOC increased by 98.47%-117.59%; POC increased by 138.59%-208.70%; MBC increased by 104.71%-230.61%; DOC increased by 21.93%-40.90%, respectively; (3) Organic cultivation significantly increased enzyme activity in all three particle size aggregates and increased the relative abundance of bacteria in micro-aggregates as well as the relative abundance of fungi in small macro-aggregates. Structural equation model (SEM) analysis revealed that organic farming practices fostered the development of smaller macro-aggregates, elevated microbial and enzyme activities within soil aggregates, and facilitated the conversion of soil nutrients and carbon sequestration. consequently, this led to an increase in soil organic carbon content and improved vegetable yield in greenhouse environments. In conclusion, the soil carbon content and vegetable yield are enhanced through long-term organic cultivation in greenhouses, primarily by increasing the proportion of small macro-aggregates.

Rat is one of the most commonly used model animals for biological research. The organs and systems of human being are somewhat similar to that of rat in structure as well as functions, making it a valuable choice for research experimentation in biological sciences. A number of studies have been conducted to evaluate the potential risks and toxicity of different elements on the physiology and histology of rats. There is need to address certain environmental factors affecting rats condition during experimentation. Reproduction along with its pathologies is under investigation on larger scale throughout the world, being central for the existence of a species. These studies focus on the major factors that influence reproductive function. Review of literature clearly indicated the unwanted consequences of over nutrition, malnutrition, high or low temperature, non-enriched housing, improper handling, intense or poor light exposure and environmental pollution on histology and hormonal profile of reproductive system of rats.

Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from serosal surface of abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1-WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within 3 years. The dismal survival makes DSRCT an orphan disease with urgent need of new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors have been evaluated in small studies. Recent works using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials.

Genome-wide association studies (GWAS) have successfully revealed numerous susceptibility loci for obesity. PREDATORR study (2014) shows that in Romania, 34,6% of adults aged 20-79 y/o are overweight, 31,4% are obese with a high risk of cardiometabolic complications, a number that puts almost 67% of Romania's population in the abnormal weight group. Our study aims to investigate the current staus of genetic foundation in metabolic disease associated with obesity, applied to a pilot group of patients specifically examining the impact of known polymorphisms and their haplotype of six food intake-regulating genes: leptin (LEP), leptin receptor (LEP-R), serotonin receptor (5HTR2A), ghrelin (GHRL), neuropeptide Y (NPY) and fat-mass and obesity-associated (FTO) with the following polymorphisms: LEP A-2548G, LEPR A-223G, 5HTR2A G-1439A, GHRL G-72T, NPY T-29063C, FTO A-T and body mass index (BMI). A notable link between the LEP-2548 rs7799039 gene's AG genotype and the risk of obesity was observed, particularly pronounced in males aged 40-49, with an approximately sevenfold increased likelihood of obesity. The 5HTR2A rs6311 AA genotype was associated with a higher BMI, not statistically significant. The FTO rs9939609 gene's AA genotype emerged as a significant predictor of obesity risk. Besides these significant findings, no substantial associations were observed with the LEPR, 5HTR2A, GHRL and NPY genes. Haplotype association analysis showed a suggestive indication of GRGMLA (rs7799039, rs1137101, rs6311, rs696217, rs16139, rs9939609 sequence) haplotype with susceptibility effect towards obesity predisposition. Linkage disequilibrium (LD) analysis showed statistically significant associations between LEP and LEPR gene (p = 1e-04), LEP and GHRL gene (p = 0.0047), GHRL and FTO gene (p=0.03). The outcomes of this study, to our knowledge, one of the very few on the Romanian population, aimed to be a starting point for further research on the targeted interventional strategies to reduce cardiometabolic risks.

Alzheimer’s disease is associated with prion-like aggregation of the amyloid β (Aβ) peptide and the subsequent accumulation of misfolded neurotoxic aggregates in the brain. Therefore, it is critical to clearly identify the factors that trigger the cascade of Aβ misfolding and aggregation. Numerous studies have pointed out the association between microorganisms and their virulence factors and Alzheimer’s disease; however, their exact mechanisms of action remain unclear. Recently, we discovered a new pathogenic role of bacterial extracellular DNA, triggering the formation of misfolded Tau aggregates. In this study, we investigated the possible role of DNA extracted from different bacterial and eukaryotic cells in triggering Aβ aggregation in vitro. Interestingly, we found that the extracellular DNA of some, but not all, bacteria is an effective trigger of Aβ aggregation. Furthermore, the acceleration of Aβ nucleation and elongation can vary based on the concentration of the bacterial DNA and the bacterial strain from which this DNA had originated. Our findings suggest that bacterial extracellular DNA might play a previously overlooked role in the Aβ protein misfolding associated with Alzheimer’s disease pathogenesis. Moreover, it highlights a new mechanism of how distantly localized bacteria can remotely contribute to protein misfolding and diseases associated with this process. These findings might lead to the use of bacterial DNA as a novel therapeutic target for the prevention and treatment of Alzheimer’s disease.

Extracellular vesicles (EVs) present a great potential for the development of new treatments in the biomedical field. To be used as therapeutics, many different sources have been used for EVs obtention, while only few studies have addressed the use of platelet derived EVs (pEVs). In fact, pEVs have been shown to intervene in different healing responses, thus some studies have evaluated their regenerative capability in wound healing or hemorrhagic shock. Even more, pEVs have proven to induce cellular differentiation, enhancing musculoskeletal or neural regeneration. However, the obtention and characterization of pEVs is widely heterogeneous and differs from the recommendations of the International Society for Extracellular Vesicles. Therefore, in this review, we aim to present the main advances in the therapeutical use of pEVs in the regenerative medicine field while highlighting the isolation and characterization steps followed. The main goal of this review is to portray the studies performed in order to enhance the translation of the pEVs research into feasible therapeutical applications.

Aim: In the present work we have studied the role of platelets and microvesicles in patients with severe hemophilia A (HA) treated under the regimen of prophylaxis. We have analyzed whether the administration of coagulation factor FVIII modifies this hemorrhagic phenotype in a cohort of 16 patients with diagnosis of severe HA, who were on prophylactic treatment with recombinant FVIII. Methods: Blood tests were performed before (72h without FVIII, baseline sample) and after 15 minutes of FVIII infusion. As a control group, 15 healthy subjects were studied. Platelet aggregation was determined by closure time, optical aggregation, impedance aggregation and flow cytometry. We also studied the expression of the platelet activation markers P-selectin, CD63, platelet-tissue factor, formation of platelet-leukocyte aggregates and tissue factor exposure. The total number of platelet and endothelial microvesicles were also analyzed by flow cytometry, as well as platelet cytosolic Ca²⁺ mobilization. Results: We found no significant differences in platelet function in patients with severe HA in prophylactic treatment before and after FVIII infusion. After FVIII administration, patients presented fewer endothelial microvesicles, indicating that the treatment does not increase one of the possible thrombotic risk markers of these patients. The total amount of plasma microvesicles and the platelet microvesicles were decreased in patients with HA compared to the control group. Conclusions: Our results do not support any effect of FVIII on platelet function in patients with severe HA treated under the regime of prophylaxis.

Autologous platelet-rich plasma (PRP) preparations are prepared at point of care. Centrifugation cellular density separation sequesters a fresh unit of blood into three main fractions: a platelet-poor plasma (PPP) fraction, a stratum rich in platelets (platelet concentrate) and, bioformulation dependent, also leukocyte and erythrocyte fractions. The employment of autologous platelet concentrates facilitates the biological potential to accelerate and support in numerous cellular activities that can lead to tissue repair, tissue regeneration, wound healing, and ultimately functional structural repair. Normally, after PRP preparation the PPP fraction is discarded. One of the less well known, but equally important features of PPP is that particular growth factors (GFs) are not abundantly present in PRP, as they reside outside the platelet alpha granules. Precisely, insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) are mainly present in the PPP fraction. In addition to their roles as angiogenesis activators, these plasma-based GFs are also known to inhibit inflammation, fibrosis, and they promote keratinocyte migration and support in tissue repair and wound healing. Additionally, PPP is known for the presence of exosomes and other macrovesicles, exerting cell-cell communication and cell signaling. Newly developed ultrafiltration technologies incorporate PPP processing methods by eliminating in a fast and efficient manner plasma water, cytokines, molecules, and plasma proteins with a molecular mass (weight) less than the pore size of the fibers. Consequently, a viable and viscous protein concentrate of functional, total proteins, like fibrinogen, albumin, and alpha-2-macroglobulin is created. Consolidating a small volume of high platelet concentrate with a small volume of highly concentrated protein-rich PPP creates a protein rich platelet concentrate (PRPC) biological preparation. After the activation of proteins, mainly fibrinogen, the PRPC matrix retains and facilitates interactions between invading resident cells, like macrophages, fibroblast, and mesenchymal stem cells (MSCs), and the embedded concentrated PRP cells and molecules. The administered PRPC biologic will ultimately undergo fibrinolysis, leading to a sustained release of concentrated cells and molecules that have been retained in the PRPC matrix until the matrix is dissolved. We will discuss the unique biological and tissue reparative and regenerative properties of PRPC matrix.

The aim of this study was to compare the effect of using L-PRF in patients undergoing impacted lower third molar surgery with either primary or secondary closure techniques. Methods: This prospective, randomised, double-blind, split-mouth clinical trial was conducted in patients with bilateral lower impacted third molars of similar position. Primary closure was performed in group 1 and secondary closure in group 2. Group 1 closure technique was applied to one side of the patients and group 2 closure technique was applied to the other side at different times. Nine pa-tients were excluded from the study due to alveolitis and failure to attend regular control visits out of the 45 patients evaluated. Results: Of the 36 patients included in the study, 23 were female and 13 were male and the mean age was 22.42±3.36 years. The secondary closure group had lower VAS scores at hour 6 (p

Hundreds of thousands of people living along the Yatsushiro Sea coast have been exposed to methylmercury from the contaminated water of the Chisso factory in Minamata. Methylmercury causes neurological deficits in the cerebrum and cerebellum, with symptoms of ataxia, dysarthria, and visual field constriction in severe cases, but the most common symptom of a milder disorder is somatosensory disturbance due to parietal lobe damage. We investigated the characteristics of the somatosensory disturbances in detail by studying subjective complaints, neurological findings, and quantitative sensory tests in 197 residents (63.2 ± 10.7 years old) from contaminated areas exposed to methylmercury from seafood and 130 residents (63.7 ± 9.3 years old) from control areas. The most commonly affected sensory modalities were superficial peripheral touch and pain in the extremities, followed by two-point discrimination and deep senses, and in the most severe cases, full-body sensory dysfunction and impairment of all sensory submodalities. Although the severity of the sensory submodalities correlated with each other, there was almost no correlation between the severity of these submodalities and indices of peripheral nerve conduction studies, suggesting that the primary cause of the sensory deficits was damage to the central nervous system. The health effects of chronic methylmercury toxicosis can be elucidated by a detailed examination of sensory deficits.

Marfan syndrome is an autosomal dominant genetic connective tissue disorder that results from mutations in the fibrillin-1 gene located on chromosome band 15q 15–21. Fibrillin, a glycoprotein, is widely expressed throughout the body and contribute to elasticity and force-bearing capacity of connective tissue. In the eye, fibrillin is a key constituent of the ciliary zonules, which suspend the crystalline lens in place. The zonular defect leads to ectopia lentis that is hallmark of Marfan ocular abnormalities and occurs in 60 to 80% of cases. Other less common ocular features of Marfan syndrome are increased axial length, astigmatism, and flat cornea. Visual function in Marfan syndrome could be affected in several ways: ectopia lentis, refractive error, amblyopia, retinal detachment, cataract, and glaucoma. Management of subluxated lens starts with correction of refractive error with eyeglasses in mild cases. In more severe cases, especially when lens bisects the pupil, complete correction of refractive error is impossible without removing subluxated lens. The best method for visual rehabilitation after lens extraction is still debated. Aphakic Artisan implantation at the time of subluxated lens removal results in good visual outcomes with acceptable safety profile. Studies with longer term follow up and larger sample populations are needed to evaluate the safety of this procedure in patients with Marfan syndrome.

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene. CDD is characterized by a broad spectrum of clinical manifestations, including early-onset refractory epileptic seizures, intellectual disability, hypotonia, visual disturbances, and autism-like features. The Cdkl5 knockout (KO) mouse recapitulates several features of CDD, including autistic-like behavior, impaired learning and memory, and motor stereotypies. These behavioral alterations are accompanied by diminished neuronal maturation and survival, reduced dendritic branching and spine maturation, and marked microglia activation. There is currently no cure or effective treatment to ameliorate the symptoms of the disease. Aerobic exercise is known to exert multiple beneficial effects in the brain, not only by increasing neurogenesis, but also by improving motor and cognitive tasks. To date, no studies have analyzed the effect of physical exercise on the phenotype of a CDD mouse model. In view of the positive effects of voluntary running on the brain of mouse models of various human neurodevelopmental disorders, we sought to determine whether voluntary daily running, sustained over a month, could improve brain development and behavioral defects in Cdkl5 KO mice. Our study showed that long-term voluntary running improved hyperlocomotion and impulsivity behaviors, and memory performance of Cdkl5 KO mice. This is correlated with increased hippocampal neurogenesis, neuronal survival, spine maturation, and inhibition of microglia activation. These behavioral and structural improvements were associated with increased BDNF levels. Given the positive effects of BDNF on brain development and function, the present findings support the positive benefits of exercise as an adjuvant therapy for CDD.

: Background: A wide variety of coils are available for vascular embolization. This study aims to evaluate the safety and efficacy of a new Prestige coil. Method: Retrospective analysis of a multicentre registry data collected between February 2022 and November 2022. The choice of the embolization agent used was left at the investigator’s discretion to treat peripheral vascular anomalies. Patients for whom at least one Prestige coil was used were included in Series 1. All other patients were included in Series 2. Efficacy and safety were evaluated. Patients were followed up for one month. Results: 220 patients were included, 110 in each series. Patients were 149 men (67.7%) and 71 women (32.3%), of median age 62.5 years [IQR: 35.8-73], similar in the two series. The complete occlusion of the targeted vessel was reported in 96.4% (N=106/110) in Series 1 and in 99.7% (N=109/110) in Series 2. 4 patients experienced non-serious adverse events (1.8%, N=4/220): 1 back pain, 1 vomiting in Series 1, 1 off-target embolization and 1 puncture site hematoma in Series 2. 16 patients (7.2%, N=16/220) were lost to follow up. Improvement of the patient’s general state at one month was reported in 79.0% (N=83/105) in Series 1 and in 74.7% (N=74/99) in Series 2. 10 deaths occurred, 5 in Series 1 (4.8 %, N=5/105) and 5 in Series 2 (5.1%, N=5/99). They all concerned critically ill patients embolized for emergent arterial bleeding. Conclusion: the 1-month follow-up showed that the Prestige coils, alone or in combination, are efficient and safe.

The increasing prevalence of Metabolic Syndrome (MetS), a serious condition associated with elevated risks of cardiovascular diseases, stroke, and type 2 diabetes, underscores the urgent need for effective diagnostic tools. This research carefully examines the effectiveness of 16 diverse machine learning (ML) models in predicting MetS, a multifaceted health condition linked to increased risks of heart disease and other serious health complications. Utilizing a comprehensive, unpublished dataset of imbalanced blood test results, spanning from 2017 to 2022, from the Laboratory Information System of the General Hospital of Amfissa, Greece, our study embarks on a novel approach to enhance MetS diagnosis. By harnessing the power of advanced ML techniques, we aim to predict MetS with greater accuracy using non-invasive blood test data, thereby reducing the reliance on more invasive diagnostic methods. Central to our methodology is the application of the Borda count method, an innovative technique employed to refine the dataset. This process prioritizes the most relevant variables, as determined by the performance of the leading ML models, ensuring a more focused and effective analysis. Our selection of models, encompassing a wide array of ML techniques, allows for a comprehensive comparison of their individual predictive capabilities in identifying MetS. This study not only illuminates the unique strengths of each ML model in predicting MetS but also reveals the expansive potential of these methods in the broader landscape of health diagnostics. The insights gleaned from our analysis are pivotal in shaping more efficient strategies for the management and prevention of Metabolic Syndrome, thereby addressing a significant concern in public health.

Candida albicans is an opportunistic fungus that becomes pathogenic and problematic under certain biological conditions. C.albicans may cause painful and uncomfortable symptoms, as well as deaths in immunocompromised patients. Therefore, early detection of c.albicans is essential. However, conventional detection methods are costly, slow and inaccessible to women in remote or developing areas. To address these concerns, we have developed a wearable and discrete naked-eye detectable, colorimetric platform for c.albicans detection. With some modification, this platform is designed to be directly adhered to existing feminine hygiene pads. Our platform is rapid, inexpensive, user-friendly, disposable and only requires three steps: i) addition of vaginal fluid onto sample pads; ii) addition of gold nanoparticle gel and running buffer, and iii) naked eye detection. Our platform is underpinned by selective thiolated aptamer-based recognition of 1,3-β-D glucan molecules- a hallmark of c.albicans cell walls. In the absence of c.albicans, wearable sample pads turn bright pink. In the presence of c. albicans, the wearable pads turn dark blue due to significant nanoparticle target-induced aggregation. We demonstrate naked eye colorimetric detection of 4.4 ×106 c.albicans cells per ml. We believe that this proof-of-concept platform has the potential to have a significant impact on women’s health, globally.

Abiotic stress, especially drought stress poses a significant threat to the terrestrial plant growth, development, and productivity. Although mulberry have great genetic diversity and extensive stress tolerant traits in agroforestry systems, only a few reports offer preliminary insight into biochemical responses of mulberry leaves under drought conditions. In this study, we performed a comparative metabolomic and transcriptomic analysis on the “drooping mulberry” (Morus alba var. Pendula Dippel) under PEG-6000-simulated drought stress. Our research revealed that drought stress significantly enhanced flavonoid accumulation and up-regulated the expression of phenylpropanoid biosynthetic genes. Furthermore, the activities of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) content were elevated. In vitro enzyme assays and fermentation tests indicated the involvement of flavonol synthase/flavanone 3-hydroxylase (XM_010098126.2) and anthocyanidin 3-O-glucosyltransferase 5 (XM_010101521.2) in the biosynthesis of flavonol aglycones and glycosides, respectively. The recombinant MaF3GT5 protein was found to recognize kaempferol, quercetin, and UDP-glucose as substrates, but not 3-/7-O-glucosylated flavonols and UDP-rhamnose. MaF3GT5 is capable of forming 3-O- and 7-O-monoglucoside, but not di-O-glucosides, form kaempferol. This implies its role as a flavonol 3, 7-O-glucosyltransferase. The findings from this study provided insights into the biosynthesis of flavonoids and could have substantial implications for the future diversified utilization of mulberry.

The gastrointestinal tract is colonized by trillions of different microorganisms, named the gut microbiota, which is key to degrade undigested food such as dietary fibers. The fermentation of these food components leads to the production of short-chain fatty acids (SCFA) acetate, propionate, and butyrate, which exploit several beneficial roles for the host’s health. Their production and absorption happen in different ways in the human intestine and depend on the type of dietary fiber reaching the gut and the microorganisms involved in the fermentation. The supplementation of SCFAs, mostly butyrate, in treating gastrointestinal, metabolic, cardiovascular, and gut-brain-related diseases has been reported in the medical literature. This review aims to give an overview of the production and absorption dynamics of acetate, propionate, and butyrate in the human gut, with a final focus on the role played by these SCFAs on gastrointestinal and metabolic health and the present therapeutic implications.

Aim: The purpose of this study was to collect prevalence data of Hypomineralized Second Primary Molars (HSPM) and Molar Incisor Hypomineralization (MIH) among pediatric patients treated by dental practitioners in Northern Italy and assess the practitioners’ awareness of these conditions. Methods: A cross-sectional pilot study was conducted using a structured online questionnaire administered through Google Forms. The survey comprised 10 single-choice questions addressing the prevalence of opacities affecting molars and an index of HSPM and MIH in caries-free children aged 6-9 years, categorized by percentage. Results: A total of 315 dentists participated in the survey, yielding a response rate of 31.5%. The majority of respondents (59%) reported HSPM prevalence in 1-25% of their patients, while 18% observed no opacity in any of their patients. MIH was observed in HSPM patients in 1-25% and 25-50% of cases, as reported by 44% and 31% of respondents, respectively. Among non-HSPM patients, MIH was observed in 1-25% of children (reported by 74% of respondents). Conclusion: The findings from this pilot survey show substantial agreement with existing prevalence data on HSPM and MIH reported in the literature. The co-occurrence rate of HSPM and MIH defects supports the hypothesis of HSPM potentially serving as a predictor of MIH. The study underscores a significant need to enhance awareness of these defects for early diagnosis and effective management. Additionally, there is a call for the promotion of standardized diagnostic protocols to obtain more accurate epidemiological data.

(1) Introduction: The COVID-19 pandemic presented unique challenges for patients and healthcare providers, especially for those working with obesity and related health problems. E-health has emerged as a crucial tool for the follow-up of users undergoing bariatric surgery during this period, allowing remote monitoring of users' health status and providing access to virtual consultation with health professionals. This study aims to analyze the impact of the use of telemedicine during the COVID-19 pandemic on the results of bariatric surgery and user satisfac-tion with this follow-up. (2) Method: Observational study with retrospective data collection. The variables were divided into several groups: health data, associated comorbidities, quality of life, quality of sleep and satisfaction with telemedicine monitoring. (3) Results: Surgery significantly affected weight loss, in general more than 75% loss of excess weight. Comorbidities, like the qual-ity of life, were reversed over time, with 50% of subjects maintaining excellent levels. Although most users were satisfied with the monitoring, the variables had no relationship. (4) Conclusions: The follow-up assured by telemedicine did not alter the results of bariatric surgery, which may allow us to infer that it may be an option to consider for regular monitoring of the post-bariatric surgery process.

Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder characterized by cognitive decline and neuronal loss, representing a most challenging health issue. We present a computational analysis of transcriptomic data of AD tissues vs. healthy controls, focused on elucidation of functional roles played by long non-coding RNAs (lncRNAs) throughout the AD progression. We first assembled our own lncRNA transcripts from the raw RNA-Seq data generated from 527 samples of dorsolateral prefrontal cortex, resulting in the identification of 31,574 novel lncRNA genes. Based on co-expression analyses between mRNAs and lncRNAs, a co-expression network is constructed. Maximal subnetworks with dense connections are identified as functional clusters. Pathway enrichment analyses are conducted over mRNAs and lncRNAs in each cluster, which serve as the basis for the inference of functional roles played by lncRNAs involved in each of the key steps in an AD development model that we have previously build based on transcriptomic data of protein-encoding genes. Detailed information is presented about the functional roles by lncRNAs in activities related to stress response, reprogrammed metabolism, cell-polarity, and development. Our analyses have also revealed that lncRNAs have discerning power in distinguishing between AD samples of each stage and healthy controls. This study represents the first of its kind.

Introduction: Although aging is a natural phenomenon, in recent years it has accelerated. One key factor implicated in the aging process is oxidative stress. Oxidative stress play also role in frailty (frail) and metabolic syndrome (MetS). Methods: 66 elderly persons (65 years old and older) with no acute or severe chronic disorders were assessed: waist circumference (WC), arterial blood pressure, glycemia, glycated hemoglobin (HbA1c), plasma lipids and activity of erythrocyte superoxide dismutase (SOD-1). Patients were classified as NonMetS-Nonfrail (n=19), NonMetS-frail (n=20), MetS-Nonfrail (n=17), and MetS-frail (n=10). Results: There were no significant differences in superoxide dismutase activity among investigated elderly groups. However, the data suggests that MetS individuals, both frail and nonfrail, have higher risk factors for cardiovascular disease compared to NonMetS individuals. The correlations analyses of SOD-1 and other metabolic indices suggest that SOD-1 levels may be influenced by age, total cholesterol, HDL cholesterol, and fasting glucose levels in certain groups of seniors. Conclusions: Aging is associated with decreased antioxidant enzyme SOD-1 activity with glucose alteration in frailty syndrome as well as with lipids disturbances in metabolic syndrome.

Plant biomass could become a new world-class "currency" because almost everything can be made of it: fuels, foods, feeds, constructing materials, furniture, etc. Currently, growing biomass for energy needs is particularly relevant in so complicated socioeconomical situation. There are important its productivity and the lowest possible ecological footprint. Can increasing crop biodiversity address these challenges? A field experiment was started at the Vytautas Magnus University Agricultural Academy in 2020-2022. Maize, hemp and faba bean were grown as single, binary and ternary crops to determine its effect on soil properties. Studies have shown that most intercrops failed to stabilize soil aggregate composition, NPK levels and pH, and enzyme urease activity. Binary maize-hemp and the ternary crops reduced the amount of the main macroelements in the soil the most because of the highest yields, which were removed from the fields. Regardless of the ecological services provided by faba beans, biomass removal leads to degradation of most soil properties and making the soil vulnerable to erosion. In the future, the cultivation of such multicrops should be investigated under conditions of more abundant fertilization or the effect of green manure should be used by increasing the number of fast- and short-growing interior plant species in the cultivation.

Current prenatal genetic evaluation showed a significantly increase in non-invasive screening and the reduction of invasive diagnostic procedures. To evaluate the diagnostic efficacy on detecting common aneuploidies, structural chromosomal rearrangements and pathogenic copy number variants (pCNV), we performed a retrospective analysis on a case series initially analyzed by aneuvysion fluorescence in situ hybridization (FISH) and karyotyping then followed by array comparative genomic hybridization (aCGH). Of the 386 cases retrieved from the past decade, common aneuploidies were detected in 137 cases (35.5%), other chromosomal structural rearrangements were detected in four cases (1%), and pCNV were detected in five cases (1.3%). The relative frequencies for common aneuploidies suggested a under detection of sex chromosome aneuploidies. Approximately 9.5% of cases with common aneuploidies showed a mosaic pattern. Inconsistent results between FISH and karyotyping were noted in cases with pseudo-mosaicism introduced by culture artifact or variable cellular proliferation from cells with mosaic karyotypic complements under in vitro cell culture. Based on findings from this case series, cell-based FISH and karyotyping should be performed to detect common aneuploidies, structural chromosomal abnormalities, and mosaic pattern. DNA-based aCGH and reflex FISH should be performed to detect and confirm genomic imbalances and pCNV. Practice points to ensure the diagnostic accuracy and efficacy were summarized.

On a bleak therapeutic landscape unchanged since the 1980’s, IVF with egg donation still stand as the lone medical answer to diminished reserve and premature ovarian insufficiency. Intraovarian platelet-rich plasma (PRP) crossed the horizon in 2016 as hopeful answer to these intertwined problems. The once remote mirage of platelet cytokine effects on gene regulation or telomere stabilization is now in sharper focus, and current work is clarifying how PRP corrects oxidative stress, rectifies tissue hypoxia, downregulates apoptosis, and enhances cellular metabolism. Not yet ready for routine use, this investigational treatment does offer one point of general agreement: How intraovarian PRP results should be classified—Patients are either responders or non-responders. From this, it is intriguing that no published PRP protocol has reported a supranormal ovarian rebound or hyperstimulation effect. This could be explained by baseline age-related ovarian conditions prevalent among poor responders, but since dysregulated or malignant transformations are also absent in other tissue contexts following autologous PRP treatment, the contribution of some platelet product which intrinsically delimits regenerative action cannot be discounted. Here we summarize results with recent experimental and clinical platelet research, framing those most likely to help advance reproductive endocrinology practice.

Human Platelet lysate, a hemoderivative product rich in growth factors, holds significant promise in tissue engineering and regenerative medicine. However, its practical utility in liquid or gel form is hampered by challenges such as limited stability and handling difficulties. This study aimed to engineer dry and porous aerogels from platelet lysate hydrogel using an environmen-tally friendly supercritical CO2-based shaping process customized for tissue engineering appli-cations. The resulting aerogels demonstrated remarkable mechanical robustness and improved manageability. Notably, they exhibited a high-water absorption capacity. Moreover, these aer-ogels exhibited a sustained and favourable biological response in-vitro. They demonstrated the ability to release functional growth factors, sustaining cellular metabolic activity similar to that of conventional culture conditions, even after prolonged storage. Furthermore, they supported the adhesion and proliferation of murine fibroblasts (BALB-3T3) and the migration of Human Um-bilical Vein Endothelial Cells (HUVEC). In addition to serving as excellent matrices for cell culture, these proposed aerogels also function as efficient growth factor delivery systems. This multi-functional capability positions them as promising candidates for various tissue regeneration strategies. Importantly, the elaborated aerogels can be conveniently stored and considered as ready-to-use products, enhancing their practicality and applicability in regenerative medicine

The objective of this study was to investigate the transcriptomic profiling of differentially ex-pressed genes between a commercial layer breed and an indigenous Indian breed. RNA was ex-tracted from NDV-infected and uninfected embryo lung tissue samples of Aseel, Kadaknath, and White Leghorn chickens. RNA-Seq was performed, and reads were aligned to the chicken refer-ence genome (Galgal7). A total of 594 genes were significantly differentially expressed, with 264 upregulated and 330 downregulated in infected embryos. Highly overexpressed genes in infect-ed conditions included C8A, FGG, PIT54, FETUB, APOC3, FGA, SPIA1, AvBD13, APOH, AMBP, TTR, PLA2G12B. Additionally, 29 novel transcripts and 20 lncRNAs were upregulated. White Leghorn embryos showed distinct expression patterns for CAV1 and GATA3, while Kadaknath healthy embryos had higher levels of CYTB, HBBA, ND4, ND4L, and ND5, indicating breed uniqueness. The analysis revealed significant gene involvement through Gene Ontology and KEGG pathways, highlighting alterations in gene expression related to immune function, me-tabolism, cell cycle, nucleic acid processes, and mitochondrial activity due to NDV infection. ALDOB, PRPS2, XDH, DCK2, and TK1 genes, which were involved in several metabolic path-ways, clearly displayed an altered expression pattern in the infected embryo. Additionally, ALB, TLR4, TLR2, TLR21, IL1R2, IL22RA2, HSP90AA, HSPB9(p60), and HSPB8 were significantly up-regulated in infected lung samples, while CXCR4, CXCL14, GATA3, IL17REL, and IL22RA1 were downregulated. Notably, higher expression of HSPs in Kadaknath suggests heat tolerance. This research provides insights into the genetic differences between commercial and local breeds and reveals the impact of NDV infection on metabolic processes, potentially identifying candidate genes for breed improvement.

Riboflavin transporter deficiency (RTD) is a childhood-onset neurodegenerative disorder characterized by sensorineural deafness and motor neuron degeneration. Since riboflavin plays key functions in biological oxidation-reduction reactions, energy metabolism pathways involving flavoproteins are affected in RTD. We recently generated iPSC lines from affected individuals as an in vitro model of the disease and documented mitochondrial impairment in these cells dramatically impacting cell redox status. In the present work, we extend our study to motor neurons (MNs), i.e., the cell type mostly affected in patients with RTD. Altered intracellular distribution of mitochondria was detected by confocal microscopic analysis, following immunofluorescence for superoxide dismutase 2 (SOD2), as a dual mitochondrial and antioxidant marker, and βIII Tubulin, as neuronal marker. We demonstrate significantly lower SOD2 levels in RTD MNs, as compared to their healthy counterparts. Mitochondrial ultrastructural abnormalities were also assessed by Focused Ion Beam/Scanning Electron Microscopy. Moreover, we investigated the effects of combination treatment using riboflavin and N-acetylcysteine, which is a widely employed antioxidant. Overall, our findings further support the potential of patient specific RTD models, and provide evidence of mitochondrial alterations in RTD-related iPSC-derived MNs, emphasizing oxidative stress involvement in this rare disease. We also provide new clues for possible therapeutic strategies, aimed at correcting mitochondrial defects, based on the use of antioxidants.

Abstract: The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this workflow we predicted the capacity of cells to sustain SARS-CoV-2 virion production in patients and found a tissue-wide induction of metabolic pathways that support viral replication. Expanding our analysis to influenza A and dengue viruses, we identified metabolic targets and inhibitors for potential broad-45 spectrum antiviral treatment. These targets were highly enriched for known interaction partners of all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed SARS-CoV-2 and dengue virus replication. Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, dengue virus, respiratory syncytial virus, and influenza A with high selectivity indices. In vivo, phenformin showed antiviral activity against SARS-CoV-2 in a Syrian hamster model. Our work establishes host metabolism as druggable for broad-spectrum antiviral strategies, providing invaluable tools for pandemic preparedness.

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.

The human gastrointestinal gut contains about 100 trillion of microorganisms including up to 5000 different types of bacteria called the "gut microbiome". Alterations in the composition of gut microorganisms (dysbiosis) can cause threatening for life diseases. This present seeks to evaluate if finally diet and more specifically functional foods affect the intestinal microbiome, and if obesity and the metabolic syndrome (Mets) are associated with the intestinal microbiome. This systematic review was accomplished according to PRISMA guidelines mostly using the key words functional foods, microbiome, obesity, Mets, Mediterranean diet. The search was carried out of recent scien-tific articles from the databases Pubmed, Scopus, and Google Scholar. The most studies discussed in this review showed a potential therapeutic effect of the Mediterranean diet rich in beneficial nutrients, on body weight, fat deposition, in correlation with modulation of the synthesis of gut microbiome. This literature review demonstrates a possible relationship between the metabolites of the microflora, the endotoxemia, obesity and Mets. The role of probiotics, prebiotics, and polyphe-nols in the prevention of obesity and Mets is of high importance in promoting healthy aging. The future challenge is to understand how different dietary patterns can regulate the composition of the gut microflora and whether these changes could be long-term.

Background and objective: Analysis of inflammatory biomarkers, along with the neutrophil/lymphocyte ratio (NLR) or platelets/lymphocyte ratio (PLR), supports the connection between inflammation and carcinogenesis. Methods: We conducted a retrospective observational study at the Clinical County Hospital Mureș, including patients with lung cancer. The parameters analyzed included: histopathological type (NSCLC - squamous cell carcinoma or adenocarcinoma; SCLC), molecular mutations (EGFR, ALK, PD-L1), parameters from the complete blood count, inflammatory parameters and associated comorbidities. Results: 380 patients were included: 115 patients in the cancer group and 265 patients in the control group. Among patients in the lung cancer group, 88 were diagnosed with NSCLC (44 adenocarcinomas, 44 squamous cell carcinomas) and 27 with SCLC. Both NLR and PLR were significantly higher in cancer patients than in the control group (5,30 versus 2,60, p&lt;0,001; 217 versus 136, p&lt; 0.001, respectively). NLR and PLR differs between men and women (p = 0.005, respectively p=0.056). C-reactive protein was not correlated with either NLR (p-value: 0.0669) or PLR (p-value: 0.6733) in lung cancer patients. Conclusion: The NLR and PLR values ​​may serve as new predictive biomarkers for the diagnostic of disease in patients with lung cancer, especially those with NSCLC.

Acoustic Radiation Forced Impulse (ARFI) is an ultrasound integrated method, measuring stiff-ness by point shear wave elastography. To evaluate the diagnostic performance of ARFI of the liver and of the spleen, combined with spleen dimension and platelet count, in predicting clinical events in cirrhosis, a prospective and cross-sectional study was conducted between February 2017 and February 2021. The following ratio scores with ARFI measurements were performed: ALSDP (ARFI Liver-Spleen Diameter-to-Platelets ratio score), ASSDP (ARFI Spleen-Spleen Diam-eter-to-Platelets ratio score), ASSAP (ARFI Spleen-Spleen Area-to-Platelets ratio score), ALSAP (ARFI Liver-Spleen Area-to-Platelets ratio score). In 100 enrolled subjects, spleen ARFI, ASSDP, ASSAP, were significantly associated with high-risk oesophageal varices (HRVs) in the prospec-tive short- and long-term follow-up and in the cross-sectional study (p 0.7). ARFI-ratio scores can predict, in cirrhotic patients, the risk of developing HVRs in short and long-term period.

Utilizing lignocellulosic biosourced platforms, we synthesized novel cyanostilbene (CS) deriva-tives featuring the 3,4-dimethoxyphenyl moiety. These derivatives were investigated for their emission properties in both solution and solid states. The two simple CS derivatives exhibit very weak luminescence in solution but significant luminescence in the solid state, indicating distinct Aggregation-Induced Emission (AIE) characteristic. Furthermore, combining these two CS units, without conjugation and with quasi perpendicular orientation, results in Dual-State Emission (DSE) fluorophore showing luminescence both in solution and solid states. X-ray crys-tallography studies on the solid-state compounds reveal a structure-emission relationship, demonstrating that the colour emission correlates with the conformations adopted by the mol-ecules in the solid state, which influence the type of stacking.

The expression "metabolic reprogramming" is more and more encountered in the literature since the mid-1990s. It seems to encompass several notions depending on the author, but the lack of a clear definition allows it to be used as a "catch-all" expression. With the increased interest in metabolism, and more specifically, in the Warburg effect in cancer research, it seems appropriate to discuss this expression and related concepts in detail.

Milk and dairy foods are naturally rich sources of a wide range of nutrients, and when consumed according to recommended intakes contribute essential nutrients across all stages of the life cycle. Since then, seminal studies recommendations with respect to intake of saturated fat have been consistent and clear; limit total fat intake to 30% or less total dietary energy, with a specific recommendation for intake of saturated fat to less than 10% of total dietary energy. However, recent work has re-opened the debate on intake of saturated fat in particular, with suggestions that recommended intakes be considered not at a total fat intake within the diet, but at a food specific level. A large body of evidence exists examining the impact of dairy consumption on markers of metabolic health, both at a total dairy intake and also at a food level, with mixed findings to date, but suggests that the impact of saturated fat intake on health differs both across food groups and even between foods within the same good group such as dairy. Milk and dairy foods contain a range of nutrients and bioactive components in different levels, housed within very different food structures. The interaction of the overall food structure and the nutrients describes the concept of the ‘food matrix effect’ which has been well documented for dairy foods. Studies show that nutrients from different dairy food sources can have different effects on health and for this reason, they should be considered individually rather than grouped as a single food category in epidemiological research. This review examines the current evidence from randomised controlled trials and meta-analyses, with respect to dairy, milk, yoghurt and cheese on aspects of metabolic health, and summarises some of the potential mechanisms for these findings.

Due to the uniqueness of the underwater environment, traditional data aggregation schemes face many challenges. Most existing data aggregation solutions do not fully consider node trustworthiness, which may result in the inclusion of falsified data sent by malicious nodes during the aggregation process, thereby affecting the accuracy of the aggregated results. Additionally, because of the dynamically changing nature of the underwater environment, current solutions often lack sufficient flexibility to handle situations such as node movement and network topology changes, significantly impacting the stability and reliability of data transmission. To address the aforementioned issues, this paper proposes a secure data aggregation algorithm based on a trust mechanism. By dynamically adjusting the number and size of node slices based on node trust values and transmission distances, the proposed algorithm effectively reduces network communication overhead and improves the accuracy of data aggregation. Due to the variability in the number of node slices, even if attackers intercept some slices, it is difficult for them to reconstruct the complete data, thereby ensuring data security.

Centralized/Cloud Radio Access Networks (C-RAN) are deployed in converged fixed-mobile networks to exploit the flexibility coming from joint application of Network Function Virtualization (NFV) and Software Defined Networking (SDN). In this context, optical links connecting C-RAN nodes, possibly based on the Ethernet standards, may carry traffic with different requirements in terms of latency and throughput. This paper considers the problem of traffic aggregation on C-RAN optical Ethernet links with latency control for fronthaul traffic and throughput capability for backhaul traffic. Integrated hybrid nework technique is applied to show how time transparency can be enforced for Ethernet encapsulated Common Public Radio Interface (CPRI) traffic while allowing statistical multiplexing of backhaul traffic. Simulation results show the effectiveness of segmentation of backhaul traffic to allow exploitation of the available bandwidth even with high capacity CPRI options.

Activated platelets are involved in blood coagulation by exposing phosphatidylserine (PS), which serves as a substrate for assembling coagulation complexes. Platelets accelerate fibrin formation and thrombin generation, two final reactions of the coagulation cascade. We investigated the effects of antiplatelet drugs on platelet impact in these reactions and platelet ability to expose PS. Washed human platelets were incubated with acetylsalicylic acid (ASA), ticagrelor, ASA in combination with ticagrelor, ruciromab (glycoprotein IIb-IIIa antagonist) or prostaglandin E1 (PGE1). Platelets were not activated or activated by collagen, sedimented in multiwell plates and plasma was added after supernatant removal. Fibrin formation (clotting) was monitored in a recalcification assay by light absorbance and thrombin generation in a fluorogenic test. PS exposure was assessed by annexin V staining using flow cytometry. Ticagrelor (alone and in combination with ASA), ruciromab and PGE1, but not ASA prolonged the lag phase and decreased the maximum rate of plasma clotting, and decreased the peak and maximum rate of thrombin generation. Inhibition was observed when platelets were not treated with exogenous agonists (activation by endogenous thrombin) and pretreated with collagen. Ticagrelor (alone and in combination with ASA), ruciromab and PGE1, but not ASA decreased PS exposure on washed platelets activated by thrombin and by thrombin + collagen. PS exposure on activated platelets in whole blood was lower in patients with acute coronary syndrome receiving ticagrelor + ASA in comparison with donors free of medications. These results indicate that antiplatelet drugs are able to suppress platelet coagulation activity not only in vitro but also after administration to patients.

Inherited platelet disorders (IPDs) are rare diseases featured by low platelet count and/or defective platelet function. Patients have variable bleeding diathesis and sometimes additional features that can be congenital or acquired. Identification of an IPD is desirable to avoid misdiagnosis of immune thrombocytopenia and use of improper treatments. Diagnostic tools include platelet function studies and genetic testing. The latter can be challenging as the correlation of its outcomes with phenotype is not easy. The immune-morphological evaluation of blood smear (by light- and immunofluorescence microscopy) represents a reliable method to phenotype subjects with suspected IPD. It is relatively cheap, not excessively time-consuming, and applicable to shipped samples. In some forms, it can provide diagnosis by itself, as for MYH9-RD, or in addition to other first-line tests as aggregometry or flow cytometry. In regard to genetic testing, it can guide specific sequencing. Since only minimal amounts of blood are needed for preparation of blood smears, it can be used to further characterize thrombocytopenia in pediatric patients and even newborns. In principle it is based on visualizing alterations in the distribution of proteins, which result from specific genetic mutations, by using monoclonal antibodies. It can be applied to identify deficiencies in membrane proteins, disturbed distribution of cytoskeletal proteins, and alpha as well as delta granules. On the other hand mutations associated with impaired signal transduction are difficult to identify by immunofluorescence of blood smears. This review summarizes technical aspects and the main diagnostic patterns achievable by this method.

Head trauma or any traumatic injury can cause damage to parts of the brain. The most important part regulating the body are the hormones and the two centers of brain which are main ones for this regulation are the most prone to getting injured. The hypothalamus and pituitary regulate a lot many functions and the loss of these organs can cause Adrenal Insufficiency, SIADH, Diabetes Insipidus, and many more.

Weight loss solutions are on the rise, and there is growing interest in natural alternatives to the pharmaceuticals in the market, which are not devoid of relevant side effects. To this end, the objective of the current study is to assess the effects of a botanical-based blend comprised of lemon verbena and hibiscus extracts in weight management, body fat, appetite, lipid, and glucose profiles, in an overweight population, for 90 days. As a result, the volunteers presented significant weight loss in absence of diet, which coincided with decreased body fat. Body fat was assessed by anthropometry, electrical bioimpedance and DEXA scan. Cholesterol levels were also significantly decreased. Satiety assessment revealed that the product contributed to increased feeling of fullness and satisfaction after a meal, compared to the placebo group, which could contribute to the weight loss observed. Blood glucose and blood pressure levels remained unchanged, which was expected as the volunteers were normoglycemic and their blood pressure was in the healthy range. In conclusion, daily supplementation of a botanical-based blend contributes to weight loss in overweight individuals, in absence of diet, while not affecting other parameters that are in the healthy range. This product could be a candidate alternative or add-on to other weight loss products, as part of a healthy lifestyle.

Neurodegenerative diseases, including Alzheimer's, Huntington's, Parkinson’s, and Amyotrophic Lateral Sclerosis, involve neuron degeneration linked to the misfolding of amyloidogenic proteins, resulting in β-sheet-enriched aggregates. This phenomenon disrupts the normal folding of proteins critical for cellular function. Genetic mutations, proteolytic cleavage, oxidative stress, and aging contribute to misfolding. Parkinson's disease (PD) is closely tied to alpha-synuclein (αS) misfolding, with A53T mutation and Lewy bodies (LB) in PD brains pivotal to understanding the disease mechanism. Other synuclein homologues (βS, γS) further contribute to synucleinopathies. Mutants (A30P, A53T, E46K, H50Q, and G51D) underscore αS&#39;s role in PD development. This concise review focuses on molecular and pathological aspects of neurodegenerative diseases, emphasizing αS in PD. The integration of genetic, structural, and mechanistic insights highlights the disorders. complexity, paving the way for future therapeutic strategies targeting protein misfolding and aggregation.

Populational aging is marked by chronic non-communicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarity, IL-1β levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

Fake news detection has become a significant topic based on the fast-spreading and detrimental effects of such news. Many methods based on deep neural networks learn clues from claim content and message propagation structure or temporal information, which have been widely recognized. However, such models (i) ignore the fact that information quality is uneven in propagation, which makes semantic representations unreliable. (ii) Most models do not fully leverage spatial and temporal structure in combination. (iii) Finally, internal decision-making processes and results are non-transparent and unexplained. In this study, we develop a trust-aware evidence reasoning and spatiotemporal feature aggregation model for more interpretable and accurate fake news detection. Specifically, we first design a trust-aware evidence reasoning module to calculate the credibility of posts based on a random walk model to discover high-quality evidence. Next, from the perspective of spatiotemporal structure, we design an evidence-representation module to capture the semantic interactions granularly and enhance the reliable representation of evidence. Finally, a two-layer capsule network is designed to aggregate the implicit bias in evidence while capturing the false portions of source information in a transparent and interpretable manner. Extensive experiments on two benchmark datasets indicate that the proposed model can provide explanations for fake news detection results, as well as can achieve better performance, boosting 3.5% in F1-score on average.

The Roma population constitutes the largest ethnic minority in Europe, however, data regarding the prevalence of non- communicable diseases are still scarce in the medical literature. The aim of this study was to assess the clinical and metabolic particularities of a Roma population with diabetes, in comparison with a group of Romanian Caucasians. We conducted an observational, transversal study and evaluated 808 adult patients with diabetes mellitus, from a tertiary hospital providing diabetes care, aged between 18 and 89 years old, of whom the majority were men (52.84%). Most of them had type 2 diabetes mellitus (T2DM), reaching 95.1% the Caucasian group and 87.8% among the Roma patients. 81.1% of the Caucasian patients had hypertension, approximately 15% higher than the Roma group, while more than half of the patients in both groups had obesity. There were no differences concerning myocardial infarction, however, the number of patients with history of stroke was 2.1 times higher in the Roma group compared to Caucasians. Chronic kidney disease was present in 22.1% of the Roma patients, 33.25% had retinopathy, and 72.7% presented polyneuropathy. The prevalence of cardiovascular risk factors, cardiovascular disease and microvascular complications among the study Roma population are quite significant, underscoring the importance of ethnic disparities in approaching healthcare management strategies.

Succinate is proposed to be a mediator of muscle exercise-induced adaptations. We studied metabolic health and changes of muscle mass in 6-month-old male mice after 12 weeks of feeding regular diet (RD, 13.4 kcal% fat, 66.8 kcal% carbohydrate, 29.8 kcal% protein), high fat diet (HFD, 60 kcal% fat, 20 kcal% carbohydrates, 20 kcal% protein) and ketogenic diet (KD, 80 kcal% fat, &lt;1 kcal% carbohydrates, 20 kcal% protein) with or without 2% succinate supplements (SUS) in drinking water (n=8-12 per group). Functional overloading of the plantaris muscle (PL) was induced in a group of mice by denervation of the gastrocnemius and soleus muscles at week 6 of feeding different diets. HFD induced the greatest (p &lt; 0.001) increase in body and fat mass. HFD and KD lead to significant (p &lt; 0.01) impairment in glucose tolerance compared to RD. SUS blunted (p &lt; 0.01) initial surge in energy intake when mice were switched from RD to HFD, but did not influence any measures of metabolic health after 12 weeks of the study. Functional overloading lead to ~25% increase in PL mass which was not affected by diet or SUS. In conclusion, SUS does not have a long-term effect on metabolic health or muscle mass.

Musculoskeletal disorders are increasingly prevalent worldwide, causing significant socioeconomic burdens and diminished quality of life. Notably, patellar chondropathy (PC) is among the most widespread conditions affecting the joint structures, resulting in profound pain and disability. Hyaluronic acid (HA) and platelet-rich plasma (PRP) have emerged as reliable, effective, and minimally invasive alternatives. Continuous research spanning from laboratory settings to clinical applications demonstrate the numerous advantages of both products. These encompass lubrication, anti-inflammation, and stimulation of cellular behaviors linked to proliferation, differentiation, migration, and the release of essential growth factors. Cumulatively, these benefits support the rejuvenation of bone and cartilaginous tissues, which are otherwise compromised due to the prevailing degenerative and inflammatory responses characteristic of tissue damage. While existing literature delves into the physical, mechanical, and biological facets of these products, as well as their commercial variants and distinct clinical uses, there is limited discussion on their interconnected roles. We explore basic science concepts, product variations, and clinical strategies. This comprehensive examination provides physicians with an alternative insight into the pathophysiology of PC as well as biological mechanisms stimulated by both HA and PRP that contribute to tissue restoration.