Since December 2019, the COVID-19 virus has rapidly spread worldwide, prompting the World Health Organization (WHO) to declare it a pandemic and advocate for the widespread use of face masks to mitigate transmission. In this review, we delve into the potential impact of prolonged face mask use on temporomandibular joint (TMJ) health, an area that has garnered limited attention amidst COVID-19 research. Research has revealed that improper mask fit, and constant readjustment can lead to TMJ abnormalities. Similarly, there is a demonstrated correlation between continuous mask usage and increased incidence of headaches, temporomandibular pain, and diminished quality of life. Many studies have highlighted discomfort in the preauricular area, headaches, TMJ noises, headache, jaw pain, and muscle fatigue, as well as dermatological disorders that have been attributed to prolonged mask wear and its impact on TMJ. Our study catalyzes future research endeavors, urging a deeper exploration of the implications of long-term mask wear, not only in the context of the COVID-19 pandemic but also among occupational groups regularly exposed to extended mask use. By unraveling the complexities of TMJ health in the face of evolving preventive measures, we aim to enhance our understanding and safeguard the well-being of mask-wearers worldwide.

Cholangiocellular carcinoma (CCA) is the second most common primary liver cancer, with increasing incidence worldwide and inadequate therapeutic options. Intra- and extrahepatic bile ducts have distinctly different embryonic origins and developmental behavior, and accordingly intra- and extrahepatic CCAs (ICC vs. ECC) are molecularly different. A promising strategy in oncotherapy is targeted therapy, targeting proteins that regulate cell survival and proliferation; such as the MAPK/ERK and PI3K/AKT/mTOR signaling pathways. Inhibitors of these pathways have been tested previously in CCA cell lines. However, these cell lines could not be clearly assigned to ICC or ECC, and results indicated apoptosis induction by targeted therapeutics. We tested targeted therapeutics (selumetinib, MK2206) in three defined ICC cell lines (HuH28, RBE, SSP25). We observed cooperative effects of dual inhibition of the two pathways, in accordance with inhibition of phospho-AKT and phospho-ERK1/2 expression. Proliferation was blocked more effectively with dual inhibition than with each single inhibition, but cell numbers did not drop below baseline. Accordingly, we observed G1-phase arrest, but not apoptosis (cleaved caspase-3, AIFM1 regulation, subG1-phase) or necroptosis (phospho-MLKL). We conclude that dual inhibition of MAPK/ERK and PI3K/AKT/mTOR pathways is highly effective to block proliferation of ICC cell lines, but therapy must certainly be supplemented with standard therapies.

Student-centered active learning (SCAL) shifts the focus from the teacher to the student. Implementing SCAL requires the development of new forms of assessment beyond memorization and comprehension. This paper aims to demonstrate the effectiveness of SCAL by analyzing student performance at different cognitive levels. In flipped classrooms, students completed tasks with varying cognitive demands. The tests measured knowledge (level 1), comprehension (level 2), application (level 3) and analysis (level 4). This approach to assessment assesses not only the acquisition of content, but also skills that are critical to a health science student's future career. The results of expository learning were compared with student-centered collaborative learning in the Anatomy and Embryology I course over three academic years. Student opinions were collected through 326 anonymous Wooclap® surveys. No differences in performance were found for low cognitive level questions. However, SCAL significantly improved performance on higher cognitive level questions that required problem solving and application of knowledge. Despite the benefits of SCAL, it requires more effort from both teachers and students. The current assessment system, which measures the quality of teaching, penalizes this effort and requires teachers to believe strongly in the effectiveness of SCAL.

This study explores the role of inflammation and oxidative stress, hallmarks of COVID-19, in accelerating cellular biological aging. We investigated early molecular markers—DNA methylation age (DNAmAge) and telomere length (TL)—in blood leukocytes, nasal cells (NC), and induced sputum (IS) one-year post-infection in pauci- and asymptomatic healthcare workers (HCWs) infected during the first pandemic wave (February-May 2020), compared to COPD patients, model for "aged lung". Data by questionnaires, Work Ability Index (WAI), blood analyses, autonomic cardiac balance assessments, heart rate variability (HRV), and pulmonary function tests were collected. Elevated leukocyte DNAmAge significantly correlated with advancing age, male gender, daytime work, and an aged phenotype characterized by chronic diseases, elevated LDL and glycemia levels, medications affecting HRV, and declines in lung function, WAI, lymphocyte count, hemoglobin levels, and HRV (p<0.05). Increasing age, LDL levels, job positions involving intensive patient contact, and higher leukocyte counts collectively contributed to shortened leukocyte TL (p<0.05). Notably, HCWs exhibited accelerated biological aging in IS cells compared to both blood leukocytes (p≤0.05) and NC (p<0.001), and were biologically older than COPD patients (p<0.05). These findings suggest the need for monitoring aging in pauci- and asymptomatic COVID-19 survivors, who represent the majority of the general population.

Ovarian cancer (OC) represents a significant challenge in the realm of gynecological cancers, characterized by poor survival rates and complex etiology. In this review, we delve into the se-lected genetic, environmental, and hormonal factors underpinning OC development. We have reviewed scientific databases searching for ovarian cancer genetic and epigenetic factors. We have included studies based on their relevancy. As a result of exploring ovarian carcinogen-esis, this systematic review contains data collected from 126 various works. The role of prominent genetic players such as BRCA mutations, DNA repair mechanisms, un-derscores the intricate landscape of OC susceptibility. We explore Li-Fraumeni and Lynch syn-drome, which impart a heightened predisposition to OC development. Hormonal factors such as estrogen, progesterone, and androgens are also discussed. Environmental alterations, ranging from lifestyle influences on OC to microbiome dysbiosis and lifestyle factors such as obesity, al-cohol consumption, and physical activity intersect with genetic and epigenetic pathways, shaping the risk landscape for OC. Through a meticulous examination of current literature, this review provides a nuanced under-standing of the multifactorial nature of OC, emphasizing the need for holistic approaches to prevention, diagnosis, and treatment.

Presynaptic Ca²⁺-influx through voltage-gated Ca²⁺ channels (VGCC) is a key signal for synaptic vesicle release. Synaptic neurexins can partially determine the strength of transmission by regulating VGCCs. However, it is unknown whether neurexins modulate Ca²⁺-influx via all VGCC subtypes similarly. Here, we performed live cell imaging of synaptic boutons from primary hippocampal neurons with a Ca²⁺-indicator. We used the expression of inactive and active Cre recombinase to compare control to conditional knockout neurons lacking either all or selected neurexin variants. We found that reduced total presynaptic Ca²⁺-transients caused by the deletion of all neurexins were primarily due to the reduced contribution of P/Q-type VGCCs. The deletion of neurexin1α alone also reduced the total presynaptic Ca²⁺-influx but increased Ca²⁺-influx via N-type VGCCs. Moreover, we tested whether the decrease of Ca²⁺-influx induced by activation of cannabinoid receptor 1 (CB1-receptor) is modulated by neurexins. Unlike earlier observations emphasizing a role for β-neurexins, we found that the decrease of presynaptic Ca²⁺-transients induced by CB1-receptor activation depended more strongly on the presence of α-neurexins in hippocampal neurons. Together, our results suggest that neurexins have unique roles in the modulation of presynaptic Ca²⁺-influx through VGCC subtypes and that different neurexin variants may affect specific VGCCs.

This investigation pioneers an examination of the scarcely explored terrain of social diversity in medical education, assessing the complex impacts of socioeconomic status (SES), prior working experiences, and completed apprenticeships on a spectrum of psychological and academic facets among first-year medical students (n = 336) in an urban university setting. By utilizing a systematic and detailed approach, the study illuminates prior anatomical knowledge and various psycholog-ical constructs, marking a significant stride into a domain where knowledge remains profoundly limited. Analyses indicated that SES significantly affects financial anxiety (F(4, 331) = 17.391, p < .001) and academic behavioral confidence (F(4, 331) = 4.323, p = 0.002). Students with prior working experience reported higher self-perceived clinical experience but lower A-level grades (t(279.459) = -6.690, p < .001), competence in natural sciences (t(321.045) = -3.178, p = 0.002), and online competence (t(319.429) = -2.026, p = 0.044). Those who completed an apprenticeship showed higher resilience, academic confidence, self-efficacy, and greater concerns about balancing studies and work (t values ranging from 2.020 to 3.158, p < 0.05). Correlation analysis revealed a positive relationship between resilience (RQS) and coping with academic stress (CAS) (r = 0.632, p < .001), as well as between resilience and academic behavioral confidence (ABC) (r = 0.608, p < .001). Negative correlations were observed between resilience, coping with academic stress, academic confidence, and cognitive test anxiety (CTA) (r values from -0.235 to -0.404, p < .001). The findings emphasize the need for tailored support for students from diverse SES backgrounds and with varying expe-riences. The study highlights the value of a comprehensive approach in medical education, con-sidering the diverse backgrounds and experiences of students. Future research should explore the long-term impact of these factors on professional competencies and patient care, leveraging the diversity of the student body for a holistic educational experience.

Background: Endovascular treatment of popliteal aneurysms (PA) has increased in the last few years, quickly becoming the main treatment in many vascular centers, based on the acceptable and promising outcomes reported in the literature. However, endograft infections are the most dangerous complication as a serious local compromise and usually require open surgical conversion and device explantation to preserve the affected extremity. Case report: We reported two patients admitted to the emergency room for pain and edema in the lower leg. Both patients have undergone exclusion of ruptured PA a few years before by endovascular graft. CTA showed a significant volume of fluid-corpuscular collection related to perianeurysmal abscess collection in both cases. Blood cultures and drained material cultures were positive for Staphylococcus Capitis in the first case and S. Aureus in the second. The antibiotics prophylaxis was performed for 10 days, then, patients underwent an open surgical conversion with a complete explantation of endovascular material and a femoro-popliteal bypass using an autologous vein in the first case and biological bovine pericardium prosthesis in the other case. Furthermore, we have questioned the literature and found eight more cases described in case report article referred to popliteal graft infections by different microorganisms, mostly presenting acute limb ischemia as the first symptom and suggesting endograft explantation with open conversion and autologous vein bypass as the commonest therapeutic choice. Conclusions: Open surgical conversion of popliteal endograft infection is the best strategy to manage peripheral infection of the popliteal stent.

Background: Obesity remains a widely debated issue, often criticized for the limitations in its identification and classification. This study aims to compare two distinct systems for classifying obesity: Body Mass Index (BMI) and body fat percentage (BFP) as assessed by bioelectrical impedance analysis (BIA). By examining these measures, the study seeks to clarify how different metrics of body composition influence the identification of obesity-related risk factors. Methods: The study enrolled 1255 adults, comprising 471 males and 784 females, with a mean age of 36 ± 11.90 years. Participants exhibited varying degrees of weight status, including optimal weight, overweight, and obesity. Body composition analysis was conducted using the TANITA Body Composition Analyzer BC-418 MA III device (T5896, Tokyo, Japan), evaluating the following parameters: current weight, basal metabolic rate (BMR), adipose tissue (%), muscle mass (%), and hydration status (%). Results: Age and psychological factors like cravings, fatigue, stress, and compulsive eating were significant predictors of obesity in the BMI model but not in the BFP model. Additionally, having a family history of diabetes was protective in the BMI model (OR: 0.33) but increased risk in the BFP model (OR: 1.66). The BMI model demonstrates exceptional predictive ability (AUC=0.998). In contrast, the BFP model, while still performing well, exhibits a lower AUC (0.975), indicating slightly reduced discriminative power compared to the BMI model. Conclusions:BMI classification demonstrates superior predictive accuracy, specificity, and sensitivity. This suggests that BMI remains a more reliable measure for identifying obesity-related risk factors compared to the BFP model.

Twelve clinically healthy and sexually mature New Zealand White rabbits were studied. The non-contrast imaging included T1-weighted and T2-weighted spin echo and gradient echo sequences in transverse, sagittal and dorsal planes. Transverse MRI (Т2-weighted image) through L1 demonstrated only the right kidney. The transverse T2-weighted image through L2 showed both kidneys. The cranial part of the urinary bladder on T1-weighted transverse scans through L4 was flexed to the left. The T2-weighted sagittal image 30 mm to the right of the median plane showed the right kidney, the right ureter and the urinary bladder. The T2-weighted sagittal image 30 mm to the left of the median plane showed part of the left kidney, the left ureter and the urinary bladder. The T2-weighted sagittal image 45 mm to the left of the median plane presented the lateral part of the left kidney. The dorsal MRI image (Т2-weighted sequence) through the horizontal plane 30 mm ventral to the spine demonstrated the whole organs. The data will be useful in imaging anatomy and diagnostic studies of various pathologies of the excretory system in rabbits and other mammalian species.

The main focus of the in vitro toxicity assessment methods is on the viability of the cells, which is usually based on metabolism changes. Yet, when exposed to toxic substances, the cell triggers multiple signals in response. With this in mind, we have developed a promising cell-based toxicity method that observes various cell responses when exposed to toxic substances (either death, division or remaining viable). Based on the collective cell response, we observed and predicted the dynamics of the cell population to determine the toxicity of the toxicant. The method was tested with two different conformations: In the first conformation, we exposed a monoculture model of blood macrophages to UV light, hydrogen peroxide, nutrient deprivation, tetrabromobisphenol A, fatty acids and 5-fluorouracil. In the second, we exposed a coculture liver model consisting of hepatocytes, hepatic stellate cells, Kupffer cells and liver sinusoidal endothelial cells to rifampicin, ibuprofen and 5-fluorouracil. The method showed good accuracy compared to established toxicity assessment methods. In addition, this approach provided more representative information on the toxic effects of the compounds as it considers the different cellular responses induced by toxic agents.

Analysing the human body by direct observation can lead to misinterpretation of underlying trends, whereas in vitro organ models facilitate their understanding. Likewise, in vitro organ models serve as valuable tools for assessing the toxicity of compounds. However, none of the existing models had the features we considered critical for toxicity assessment, so we developed an in vitro liver model for toxicity assessment. We used four different types of primary liver cells: Hepatic sinusoidal endothelial cells, hepatic stellate cells, Kupffer cells and hepatocytes. We cultured them in different combinations of composition and volume of cell medium, hepatocyte proportion of total cells, and addition of extracellular matrix. We added rifampicin, ibuprofen and 5-fluorouracil to this model and observed the microanatomy and physiology changes for a week with preclinical and clinical instruments. Among the different model configurations, we selected the feature combination of the in vitro model that had similar biomarker values to those measured by the clinical instruments used in clinical diagnostics. When we exposed the selected model configuration to rifampicin, ibuprofen and 5-fluorouracil, the viability of Kupffer cells and liver sinusoidal endothelial cells was significantly lower than in the untreated samples. In contrast, we observed negligible viability of hepatocytes compared to the untreated samples. We have built an in vitro liver model that resembles the liver microenvironment and we have analysed it with clinical instrumentation to facilitate the data translation. In this sense, we have established that Kupffer and LSEC cells are suitable candidates for the search for clinical diagnostic markers of liver function.

ABSTRACT Introduction: Traditional penile venous surgery and enhancement have been controversial. Based on De Novo penile fibrovascular assembly, we report on penile venous stripping (PVS) and factual penile girth enhancement (FPGE). Methods: From 2013 to 2023, 18 men underwent PVS and FPGE, all confirmed with veno-occlusive dysfunction (VOD). PVS involves the stripping of erection-related veins. FPGE was performed along the tunica albuginea bilaterally; then, the two tunic defects were repaired with a 70.0x30.0 mm venous stripe and covered with either autologous venous walls (AVW, n=10) or Surgiform (SF, n=8). The penile girth was measured, and radio-opaque contrast was used. The abridged 5-item version of the International Index of Erectile Function (IIEF-5) score and the Erection Hardness Scale (EHS) were used yearly during follow-up via the Internet. Results: The follow-up period was 5.3±1.5 years. Radiopacity was consistently enhanced. Although there was indifference between AVW and SF, there was a significant improvement (both P＜0.01) in IIEF-5 and EHS scores (9.7±2.8 vs. 20.8±2.3; 1.7±0.6 vs. 3.2±0.2, respectively). Both the diameters of the glans and penile shaft increased (28.0±2.3mm and 28.3±2.1mm vs 35.3±2.2mm and 36.3±2.1mm respectively). The satisfaction rate was 81.3% (13/16). Conclusions: This novel combination of PVS and FPGE is promising, although a larger sample size is needed for further validation.

1) Background: Several studies have shown the benefit of drawing when learning anatomy. Virtual Reality (VR) also appears to be useful to increase the understanding of the location of anatomical structures. This study aims to describe how students in an Operating Room Nursing (OR nursing) master study program perceive the benefit of active learning methods, including drawing and the use of VR. 2) Methods: We combined these two methods in a class of 29 students. 38 half-finished drawings of anatomical structures were made. The students were to complete these during lectures with guidance from the teacher. The students also attended a two-hour VR session where they were to find various anatomical structures. A paper questionnaire was applied to evaluate the teaching program. Data were analyzed statistically. 3) Results: The students highly appreciated these learning methods. They reported that drawing made them work more actively during lectures and increased their learning outcome. They also perceived that the use of VR technology increased their understanding of the location of anatomical structures. 4) Conclusion: The combination of drawing and VR technology may be of benefit to OR Nursing students when learning anatomy by both increasing student activity and learning outcomes.

The purpose of this study was to establish the association between total and segmental body composition (BC) variables and anaerobic performance and to create optimal models that best predict such performance in CrossFit® (CF) athletes. Fifty athletes, 25 males and 25 females (age: 33.26 ± 6.81 years; body mass: 72.57 ± 12.17 kg; height: 169.55 ± 8.71 cm; BMI: 25.06 ± 2.31 kg·m−2) were recruited to participate and underwent BC analysis using dual-energy X-ray absorptiometry (DXA) and an all-out laboratory test on a cycle ergometer (Wingate) to determine their anaerobic performance. The results show a significant correlation between BC values and performance, ranging from moderate (r = -0.34, p = 0.015) to near-perfect (r = 0.96, p &lt; 0.01). Furthermore, the created performance prediction models exhibited predictive capacities ranging from 19% (p = 0.017) to 93% (p &lt; 0.001). All prediction models were created using total or segmental lean mass variables, excluding others. BC and performance variables found significant differences between males and females. The findings demonstrate that BC variables are crucial indicators of anaerobic performance in CF athletes. Professionals responsible for athlete performance should use this information to monitor athletes and design training programs.

Background: Despite advances in the treatment of hepatocellular carcinoma (HCC) over the last few decades, treatment opportunities for patients with HCC remain limited. HCC is the most common form of liver cancer, accounting for approximately 90% of all cases worldwide. Moreover, apart from the current pharmacological interventions, hepatic resection and liver transplantation are the mainstay curative approaches for patients with HCC. Methods: This systematic review included phase I, II, III, and IV clinical trials (CTs) and randomized controlled trials (RCTs) on current treatments for patients with HCC in an Asian population (2013–2023). A total of 427 articles were screened, and 184 non-duplicate publications were identified. After screening titles and abstracts, 96 publications were excluded, and another 28 were excluded after full-text screening. The remaining 60 eligible RCTs/CTs were finally included. Results: Sixty clinical trials fulfilled our inclusion criteria and screened 36 drugs as monotherapy or combination therapy for HCC. Most studies used sorafenib alone or in combination with any of the treatment regimens. Lenvatinib or atezolizumab with bevacizumab was used for HCC after initial sorafenib treatment. Eighteen studies compared the efficacy of sorafenib with that of other drugs, including lenvatinib, cabozantinib, tepotinib, tigatuzumab, linifanib, erlotinib, resminostat, brivanib, tislelizumab, selumetinib, and refametinib. Conclusion: This study provides comprehensive insights into effective treatment interventions for HCC in Asian populations. The overall assessment indicated that sorafenib alone or in combination with atezolizumab and bevacizumab has been the first treatment choice in the past decade to achieve better outcomes in patients with HCC in an Asian population

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

Chronic kidney disease patients treated by hemodialysis present a high cardio-vascular morbidity and mortality. There is an imperative need for novel biomarkers in identifying and to offer possible therapeutically intervention in these patients. We performed a prospective observational cohort study on 77 patients in the period October 2021 – October 2023. We measured serum plasma levels of Interleukin 1-Beta, Galectin 3, human suppression of tumorigenicity factor 2, bone morphogenetic protein 2 and fibroblastic growth factor 23 at the inclusion. We evaluated the correlations of these biomarkers with cardiac function and structure evaluated by echocardiography. Mean age was 61.02 (±11.81) years, 45 (56.2%) males and with a dialysis vintage of 4.95 (2.4-7.8) years. Median ejection fraction was 51 (43-54 %) and more than two thirds of the patients presented valvular calcifications. Overall mortality was 22%. Interleukin 1-Beta correlated positively with ejection fraction and global longitudinal strain and negatively with left atrium diameter and left ventricle tele systolic diameter. Galectin 3 values negatively correlated with aortic valve fibrosis and mitral valve calcifications and human suppression tumorigenity factor 2 negatively correlated with mitral valve calcifications. Some of these novel biomarkers could be used to better asses the cardio-vascular disease in patients on maintenance hemodialysis.

Background: Inflammatory plays critical role in myocardial infarction as a critical process in the development of heart failure, involving the development of cardiac fibrosis. Colchicine is a well-established anti-inflammatory drug, but its scientific application in controlling post-acute myocardial infarction remodelling processes has not been established. IL-10, a key cytokine in modulating inflammatory responses, underscoring its potential as a crucial therapeutic target of colchicine. Objectives: To explore the protective role of IL-10 modulated by colchicine in myocardial healing and repair following AMI, particularly cardiac fibrosis. Materials and Methods: The predicted protein of Colchicine was assessed using WAY2DRUG PASS as probability active value. Proteins associated with Colchicine, cardiac fibrosis and acute myocardial infarction were analysed with DisGeNET and Open Target databases. Analysis and visualization of protein-protein interactions were conducted using STRING and Cytoscape. A 3T3 cell line treated with CoCl2 was used to mimic hypoxic. HIF-1α and IL-10 expression were measured by flow cytometry and analysed using a one-way ANOVA test. This observational clinical trial examined acute myocardial infarction patients undergoing immediate and delayed primary percutaneous coronary interventions. Subjects were randomized into control groups receiving placebo and intervention groups treated with Colchicine. Assessments occurred at 24 hours and five days after the intervention. IL-10 expression in the clinical trial was measured by ELISA assay and analysed using a T-test. Results: Colchicine demonstrates promising bioactivity in treating acute myocardial infarction, with notable probability active values as a tubulin antagonist (0.744), beta-tubulin antagonist (0.673), and NOS2 inhibitor (0.529). Its primary action targets IL-10, with protein-protein interactions analysis indicating interactions between IL-10 and key inflammatory mediators—IL-1β, IFN-γ, CCL2, TNF, and TGF-β1—during acute myocardial infarction and cardiac fibrosis. Hypoxic conditions in the CoCl2-induced 3T3 cell model show significantly elevated HIF-1α compared to controls (p&lt;0.0001). Acute myocardial infarction patients were predominantly from high-risk populations, with notable smoking prevalence in the early Colchicine group (72%). Hypertension prevalence was significantly different, with 67.31% in the late Colchicine group compared to 38% in the early Colchicine and 39.80% in the early placebo groups. Both early and late Colchicine groups exhibited a higher prevalence of diabetes mellitus. Colchicine use, either early or late, did not significantly alter major adverse cardiovascular events incidence compared to placebo (p&gt;0.05). However, Colchicine significantly increased IL-10 expression in CoCl2-treated cells (p&lt;0.0001) and in acute myocardial infarction patients within five days (p&lt;0.05). Conclusions: Colchicine may bolster the anti-inflammatory response post-myocardial infarction by activating IL-10 pathways in fibroblasts and in clinical settings, potentially reducing major adverse cardiovascular events. Further investigation into broader aspects of this pathway, particularly in cardiac fibroblasts, is required.

Epigenetic mechanisms, including histone post-translational modifications (PTMs), play a critical role in regulating pain perception and the pathophysiology of burn injury. However, the epigenetic regulation and molecular mechanisms underlying burn injury-induced pain remain insufficiently explored. Spinal dynorphinergic (Pdyn) neurons contribute to heat hyperalgesia induced by severe scalding-type burn injury through p-S10H3-dependent signaling. Beyond p-S10H3, burn injury may impact various other histone H3 PTMs. Double immunofluorescent staining and histone H3 protein analyses demonstrated significant hypermethylation at H3K4me1 and H3K4me3 sites and hyperphosphorylation at S10H3 within the spinal cord. By analyzing Pdyn neurons in the spinal dorsal horn, we found evidence of chromatin activation with a significant elevation in p-S10H3 immunoreactivity. We used RNA-seq analysis to compare the effects of burn injury and forma-lin-induced inflammatory pain on spinal cord transcriptomic profiles. We identified 98 DEGs for burn injury and 86 DEGs for formalin-induced inflammatory pain. A limited number of shared differentially expressed genes (DEGs) suggest distinct central pain processing mechanisms between burn injury and formalin models. KEGG pathway analysis supported this divergence, with burn injury activating Wnt signaling. This study enhances our understanding of burn injury mechanisms and uncovers converging and diverging pathways in pain models with different origins.

Keywords: retinoblastoma, RB, gastric inhibitory polypeptide receptor, GIPR, trefoil factor family peptide, TFF1, CAM, tumorigenesis, MK0893, miR5-542-5p

Corneal ulcers are a common and potentially vision-threatening condition in horses that can be challenging to treat with conventional therapies alone. This case report describes the successful treatment of a non-healing corneal ulcer in a 28-year-old Hispano-Bretón mare using the secretome derived from adipose tissue-derived mesenchymal stem cells (ASCs). Despite initial treatment with antibiotics, anti-inflammatory drugs, and surgical debridement, the corneal ulcer failed to heal properly, exhibiting persistent epithelial defects and stromal complications. As an alternative regenerative approach, the ASC secretome, a rich source of trophic factors, cytokines, and extracellular vesicles, was topically administered to the affected eye. Remarkably, within one week of secretome treatment, the clinical signs of blepharospasm and epiphora resolved, and the corneal ulcer exhibited complete re-epithelialization, regained transparency, and reduced neovascularization. No recurrence was observed during the 1.5-year follow-up period. This case highlights the potential therapeutic benefits of ASCs secretome in promoting corneal wound healing and suggests its promise as a novel cell-free therapy for treating refractory corneal ulcers in horses.

The anatomy of mature vertebrate hearts is marked by a looped design, which is roughly characterized by two components: (1), s-shaped (sigmoid) routing of the cardiac flow path(s), and (2,) bilaterally asymmetric (chiral) routing of the cardiac flow path(s). The looped heart design is regarded as a phylogenetically conserved feature among vertebrates and is thought to represent a significant determinant of the cardiac pumping function. It evolves during the embryonic period of development by a morphogenetic process called “cardiac looping”. During the past decades, remarkable progress has been made in the uncovering of the genetic, molecular, and biophysical factors contributing to cardiac looping. Thereby, a special focus was directed on the evolution of a bilaterally asymmetric (chiral) heart configuration, which is said to play a central role in the determination of the alignments and separations of the pulmonary and systemic flow paths in the multi-chambered hearts of tetrapods. In contrast to the recent progress made in uncovering of the biological driver of cardiac looping, our present knowledge about the functional consequences of cardiac looping is at an immature state. This article provides an overview and discussion of the currently available information about the looped design of vertebrate hearts and its functional implications.

Anatomy education plays a critical role in medical practice, and the level of anatomical knowledge among students and physicians significantly impacts patient care. This article presents a pilot project conducted by the University of Milan aimed at exploring the effectiveness of the Area9's Rhapsode platform, an intelligent tutoring system that uses artificial intelligence to personalize learning and collect data on mastery acquisition. The study focused on liver anatomy and employed a flipped classroom approach, incorporating adaptive learning modules and an interactive in-class session. The project's execution, outcomes and preliminary pedagogical considerations are discussed. The results demonstrated improved learning quality, positive repurposing of study time, enhanced metacognitive awareness among students, with most of students demonstrating conscious mastery of the materials and a clear understanding of their level of competence. This approach, by providing valuable insights into the potential of artificial intelligence-based adaptive learning systems in anatomy education, could address the challenges posed by limited teaching hours, shortage of anatomist and the need for individualized instruction, with recommendations for future research and the expansion of adaptive learning modules to other anatomical districts.

BackgroundLiving donor liver transplantation offers comparable long-term results to cadaveric donor transplantation. This study analyzes the selection process of living liver donors at a Western transplant center that utilizes both donation forms. MethodsThis retrospective analysis examined potential living donors, collecting medical data and reasons for refusal, and divided patients by indication and urgency for transplantation. ResultsFrom January 2013 to December 2023, 594 potential living donors were assessed at Jena University Hospital. Of these, 124 living donor transplants were performed. During outpatient evaluation, 357 potential donors were excluded. Subsequently, 238 individuals underwent inpatient assessment, with 100 more being excluded. Main reasons for donor refusal included medical or psychological issues (n=160), disease progression in recipients (n=90), and recipient refusal or donor withdrawal (n=54). The evaluation process showed a trend towards considering more distant relatives and acquaintances as donor candidates with increasing severity of the recipient's disease.

Cell viability refers to the proportion of living, healthy cells within a given population. This information is crucial in any cell-based research, especially in toxicology. Over the past century, numerous methods for assessing cell viability have been developed. These methods can be categorized into five main types: non-invasive cell structure damage, invasive cell structure damage, cell growth, cellular metabolism, and cell membrane potential. Each method operates on different principles and has its own advantages and disadvantages, making it essential for researchers to choose the method that best fits their experimental design. Despite the variety of cell viability methods available, most rely on indirect measurements of cell viability, which may compromise their accuracy. In this sense, there is insufficient information regarding their accuracy, highlighting the need for researchers to investigate the accuracy of both existing and future methods.

: This study focuses on optimizing chlorophyll extraction techniques and strategically placing leaf disks to enhance chlorophyll concentration in sesame (Sesamum indicum L.) leaves. Thirty sesame genotypes, categorized into light green (LG), middle green (MG), and deep green (DG) pigment groups based on leaf coloration, were selected from a larger pool of field-grown accessions. The investigation involved determining optimal SPAD value index measurements, quantifying pigment concentrations, exploring extraction solvents, and selecting suitable leaf disk positions. Significant variations in chlorophyll content were observed across genotypes, greenness categories, and leaf disk positions. The categorization of genotypes into DG, MG, and LG groups revealed a correlation between leaf appearance and chlorophyll content. The study highlighted a consistent relationship between carotenoids and chlorophyll, indicating their role in adaptation to warm environments. Examination of leaf disk positions revealed a significant chlorophyll gradient along the leaf blade, emphasizing the need for standardized protocols. Chlorophyll extraction experiments identified DMSO and 96% ethanol, particularly the later incubated for 10 minutes at 85°C, as effective choices. This recommendation considers factors like cost-effectiveness, time efficiency, safety, and environmental regulations, ensuring consistent and simplified extraction processes. For higher chlorophyll extraction, focusing on leaf tips and the 75% position along the sesame leaf blade is suggested, consistently yielding higher chlorophyll content. Our findings therefore, underscores insightful knowledge on chlorophyll gradients and encouraging for standardized protocols, that enabling researchers to refine experimental designs for precise and comparable chlorophyll measurements. Recommended solvent choices ensure reliable outcomes in plant physiology, ecology, and environmental studies.

The phenotypic manifestation of lead toxicity includes cognitive, learning, and memory decline which is associated with neuronal injuries and death and been a major challenge in public health especially in developing countries. Thus, we explore the prophylactic potentials of luteolin in prefrontal Pb intoxication. Thirty-six (36) male Wistar Rats were used for this research and di-vided into six (6) groups of six animals each and were treated orally as follows: Group 1-Normal saline (0.5ml daily for 14 days); Group 2- PbCl3 (50mg/kg of PbCl3 daily for 14 days); Group 3- luteolin (100mg/kg of LUT daily for 14 days); Group 4- luteolin and PbCl3 (50mg/kg PbCl3 and 100mg/kg LUT daily for 14 days); Group 5- PbCl3 then luteolin (50mg/kg of PbCl3 daily for 14 days followed by 100mg/kg of LUT daily for 14 days); Group 6- luteolin then PbCl3 (100mg/kg of LUT daily for 14days followed by 50mg/kg of PbCl3 daily for 14 days). We measured cerebral oxidative redox parameters, G6PDH, IL-6, acetylcholinesterase levels, and total protein profiles using ELISA and biochemical assay kits. We also examined cerebral morphology and the Nissl profile with H&E and toluidine blue staining techniques, as well as astrocytic morphology and synaptic integrity with anti-GFAP and anti-synaptophysin antibodies. As a result of Pb perturba-tion, luteolin treatment inhibits MDA, IL-6, and AChE expression while increasing antioxidant enzyme activities (SOD, GPx) and G6PDH. Furthermore, luteolin has significant prophylactic po-tential against Pb-induced neuronal injuries and modulates astrocyte actions, preserving synap-tic integrity and thus improving cognition, learning, and memory. Taken together, our findings indicate that luteolin may be a promising candidate for managing and treating Pb neural intoxi-cation.

Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new biomarkers and therapeutic targets. Telomere length (TL) and telomerase activity (TA) have gained attention in this context. Telomeres, protective nucleotide sequences at chromo-some ends, shorten with each cell division, leading to cellular aging. Telomerase, a ribonucleoprotein enzyme, counteracts this shortening by adding telomeric repeats, a process tightly regulated in normal cells but often dysregulated in cancer. This review critically evaluates the role of TL and TA in the pathogenesis of GI cancers, examining their potential as diagnostic, prognostic, and predictive biomarkers. It explores how alterations in telomere biology contribute to the initiation and progression of GI tumors and assesses the therapeutic implications of targeting telomerase. By integrating findings from diverse studies, this review aims to elucidate the intricate relationship between telomere dynamics and gastrointestinal carcinogenesis, offering in-sights into how TL and TA could be leveraged to enhance the early detection, treatment, and prognosis of GI cancers.

Peripheral nerve injury (PNI) is a complex clinical challenge affecting quality of life. Neurological recovery does not always ensure functional recovery as extracellular matrix (ECM) alterations affecting muscle function. This study evaluates hyaluronan (HA) and collagen concentration in gastrocnemius muscle and thoracolumbar fascia (TLF) in unilateral lower limb PNI rats to ex-plore systemic ECM alterations following PNI and their impacts on functional recovery. Eighteen 8-week-old male Sprague-Dawley rats were divided into experimental (n=12 with left sciatic nerve transection injury repaired by nerve conduit) and control (n=6) groups. After six weeks, motor function was evaluated. Muscle and TLF samples were analyzed for HA and collagen concentrations using Purple-Jelley HA Assay and Total-Collagen Assay kit. HA and collagen distribution was assessed using Alcian Blue and immunohistochemistry, and Picrosirius Red staining. In PNI rats, SFI and gait analysis were -87±9.12 and 1.32±0.29. Both sides of muscles showed significantly lower HA concentration than that in healthy rats (left p

Computer simulation of normal and diseased human heart activity requires a 3D anatomical model of the myocardium, including myofibres. For clinical applications, such a model has to be constructed based on routine methods of cardiac visualisation such as sonography. Symmetrical models are shown to be too rigid, so an analytical non-symmetrical model with enough flexibility is necessary. Based on previously made anatomical models of the left ventricle, we propose a new, much more flexible spline-based analytical model. The model is fully described and verified against DT-MRI data. We show a way to construct it on the basis of sonography data. To use this model in further physiological simulations, we propose a numerical method to utilise finite differences in solving the reaction-diffusion problem together with an example of scroll wave dynamics simulation.

BACKGROUND Detecting total cholesterol in dried blood spots could aid in identifying individuals with a high likelihood of familial hypercholesterolemia and could be used as a screening measure. This study aims to assess the diagnostic accuracy of dried blood spots on Whatman 903 paper cards using a manual enzymatic technique. METHODS A total of 394 samples collected as serum and dried blood spots were compared. Cholesterol was determined in serum using the automated reference method, while cholesterol on paper was measured using a manual enzymatic method. Within- and between-day diagnostic variability were analyzed. The correlation between both methods was assessed using Passing-Bablok regression and Bland-Altman plot. Internal validation of our correlation formula was performed on 149 samples, along with external validation of the formula proposed by Corso et al. RESULTS The within- and between-day coefficient of variation was found to be lower than 10.14% and 14.09%, respectively. Method comparison yielded an area under the curve of 0.976, with a standard error of 0.009. Passing-Bablok regression indicated a precision of 0.803 and an accuracy of 0.96. Internal validation precision was measured at 0.716. Regarding internal validation, calculated cholesterol with our regression line did not differ from serum cholesterol analysis, while significant differences were observed in calculated cholesterol levels using the external formula. CONCLUSIONS Total cholesterol analysis in dot blood spots demonstrates high precision and reproducibility. This method reliably enables the incorporation of this biological marker into neonatal screening for familial hypercholesterolemia detection.

Protein tyrosine phosphatase receptor type E (PTPRE) is a member of the “classical” protein tyrosine phosphatase subfamily and regulates a variety of cellular processes in a tissue-specific manner by antagonizing the function of protein tyrosine kinases. PTPRE plays a tumorigenic role in different human cancer cells, but its role in retinoblastoma (RB), the most common malignant eye cancer in children, remains to be elucidated. Etoposide resistant RB cell lines and RB patients display significant higher PTPRE expression levels compared to chemosensitive counterparts and the healthy human retina, respectively. PTPRE promotor methylation analyses revealed that PTPRE expression in RB is not regulated via this mechanism. Lentiviral PTPRE knockdown (KD) induced a significant decrease in growth kinetics, cell viability, and anchorage independent growth of etoposide resistant Y79 and WERI RB cells. Caspase-dependent apoptosis rates were significantly increased and a re-sensitization for etoposide could be observed after PTPRE depletion. In vivo chicken chorioallantoic membrane (CAM) assays revealed decreased tumor formation capacity as well as reduced tumor size and weight following PTPRE KD. Expression levels of miR631 were significantly downregulated in etoposide resistant RB cells and patients. Transient miR631 overexpression resulted in significantly decreased PTPRE levels and concomitantly decreased proliferation and increased apoptosis levels in etoposide resistant RB cells, impacts mirroring PTPRE KD effects and indicating PTPRE regulation via this miR. Additionally, PTPRE KD led to altered phosphorylation of protein kinase SGK3 and - dependent on the cell line - also AKT and ERK1/2, suggesting potential PTPRE downstream signaling pathways. In summary, these results indicate an oncogenic role of PTPRE in chemoresistant retinoblastoma.

Pathological cleavage of collagen type II (Col2) and generation of Col2 neoepitopes can be good molecular markers of progression of osteoarthritis (OA). One of such potential biomarkers is collagen type II neoepitope C2C. The aim of this study was to correlate the degree of articular cartilage damage in OA patients with C2C expression in histological samples of tissues removed during total knee replacement. Cartilage samples were obtained from 27 patients aged from 55 to 66. In each patient medial and lateral tibia plateau samples were analyzed according to the OARSI histopathology grading system. C2C expression was evaluated on histological slides by semi-quantitative analysis using ImageJ Fiji software. Spearman´s rank correlation analysis showed significant positive correlation (rho=0.289, P=0.0356) between the histological grade of tissue damage and the percentage of C2C staining. In addition, highly significant positive correlation (rho=0.388, P=0.0041) was found between osteoarthritis score (combining the histological grade of damage with the OA macroscopic stage) and the percentage of C2C staining in the samples. The C2C expression was found in all the regions of the articular cartilage (i.e. the superficial zone, mid zone, deep zone and tidemark area and the zone of calcified cartilage). Our study suggests that local expression of C2C correlates with the cartilage damage in the knee affected by OA. This further assures that C2C can be a perspective marker for evaluation of pathological processes in OA course and OA clinical trials.

The BET family of proteins is characterized by the presence of two tandem bromodomains and an extra-terminal domain. The mammalian BET family of proteins comprises Brd2, Brd3, Brd4, and Brdt, which are encoded by paralogous genes that may have been generated by repeated duplication of an ancestral gene during evolution. Bromodomains that can specifically bind acetylated lysine residues in histones serve as chromatin-targeting modules that decipher the histone acetylation code. BET proteins play a crucial role in regulating gene transcription through epigenetic interactions between bromodomains and acetylated histones during cellular proliferation and differentiation processes. On the other hand, BET proteins have been reported to mediate latent viral infection in host cells and be involved in oncogenesis. Human BRD4 is involved in multiple processes of the DNA virus life cycle, including viral replication, genome maintenance, and gene transcription through interaction with viral proteins. Aberrant BRD4 expression contributes to carcinogenesis by mediating hyperacetylation of the chromatin containing the cell proliferation-promoting genes. BET bromodomain blockade using small-molecule inhibitors gives rise to selective repression of the transcriptional network driven by c-Myc. These inhibitors are expected to be potential therapeutic drugs for a wide range of cancers. This review presents an overview of the basic roles of BET proteins and highlights the pathological functions of BET and the recent developments in cancer therapy targeting BET proteins in animal models.

Groove pancreatitis represents a chronic focal form of pancreatitis affecting the zone between the pancreatic head and the duodenal „C” loop, known as the groove area. This is a rare condition that affects the pancreatic periampullary part, including the duodenum and the common bile duct, associated usually with long-term alcohol and tobacco misuse and being more frequent in men than in women. The most common clinical symptoms of groove pancreatitis include weight loss, acute abdominal pain, nausea, and jaundice. This report is about a 66 year old woman with a history of heavy smoking, presenting with weight loss, nausea, and upper abdominal pain. Contrast enhanced computed tomography revealed the existence of a chronic pancreatitis as well as the dilatation of the main pancreatic duct, a cyst of the pancreatic head and enlargement of the biliary tract. Conservatory treatment was initiated but with no improvement of symptoms. Since there was no indication for endoscopic retrograde cholangiopancreatography, we decided to perform a pancreatoduodenectomy, as surgery appears to be the single effective treatment.

Pancreatic cancer is one of the most aggressive and lethal forms of cancer, with a five-year survival rate of less than 10%. Despite advances in treatment modalities, the prognosis for pancreatic cancer patients remains poor, highlighting the urgent need for innovative approaches for early diagnosis and targeted therapies. In recent years, there has been significant progress in understanding the molecular mechanisms underlying pancreatic cancer development and progression. This paper reviews the current knowledge of molecular targets for the diagnosis and treatment of pancreatic cancer.

Prolonged ethanol (EtOH) consumption is associated with male infertility with a decreased spermatogenesis rate as one cause. Defective maturation and development of sperm during their storage in the cauda epididymis and transit in the seminal vesicle can be another cause, possibly occurring before the drastic spermatogenesis disruption. Herein, we demonstrated that the cauda epididymis and seminal vesicle of rats, orally fed with EtOH under a regimen that spermatogenesis was still ongoing, showed histological damage, including lesion and decreased height of the epithelial cells, and increased collagen fibers in the muscle layer, which implicated fibrosis. Lipid peroxidation (shown by malondialdehyde (MDA) levels) was observed, indicating that reactive oxygen species (ROS) was produced along with acetaldehyde during EtOH metabolism by CYP2E1. MDA, acetaldehyde and other lipid peroxidation products could further damage cellular components of the cauda epididymis and seminal vesicle and this was supported by increased apoptosis (shown by TUNEL assay and caspase 9/caspase 3 expression) in these two tissues of EtOH-treated rats. Consequently, functionality of the cauda epididymis and seminal vesicle in EtOH-treated rats was impaired, as demonstrated by decreases in 1H NMR-analyzed metabolites (e.g., carnitine, fructose), which were important for sperm development, metabolism and survival in their lumen.

Here, we present a staged approach for an innovative repurposing of a portable infant humidicrib into a live cell growth, observation, and imaging system. Furthmore, humidicrib can support different variations of “umbilical” bioreactors, and can be used to conduct electrophysiology experiments and in situ immunohistochemistry. Modifications incorporate a closed loop carbon dioxide (CO₂) concentration control system with umbilical CO₂ and heating support for tailored bioreactors. The repurposing cost is inexpensive and allows for the continued observation and imaging of cells. This prototype unit has been used to continuously observe and image live primary neurons for up to 21 days. This demonstrates the repurposed units’ suitability for use in tissue culture based research, particularly where modifications to microscopes are required or where sensitive manipulation outside of a standard incubator is needed.

Background/Objectives Bowel endometriosis (BE) is defined as the presence of endometrial-like tissue in the muscular layer of the bowel wall. When BE does not cause severe obstruction to fecal transit, not leading to (sub)occlusive symptoms, the decision to operate becomes challenging as intestinal surgery is associated with higher complication rates and long-term bowel dysfunction. The aim of this cross-sectional study is to evaluate the quality of life (QoL) in patients with BE undergoing medical therapy or expectant management, investigating the impact of characteristics of BE nodules on QoL and intestinal function. Methods A retrospective cross-sectional analysis was conducted on 580 patients with BE who did not undergo surgery but were treated conservatively by medical therapy or expectant management between January 2017 and August 2022. The diagnosis of BE was done by transvaginal ultrasound and confirmed at double contrast barium enema. After at least one year of follow-up, QoL and intestinal function of patients were evaluated by the Endometriosis Health Profile-5 (EHP-5) questionnaire and Bowel Endometriosis Symptom score (BENS), whereas pain symptoms were assessed by the Visual Analogic Scale (VAS 0-10). Statistical analysis was performed to investigate possible associations between QoL and characteristics of bowel nodules (dimension, location, and evidence of stenosis) as well as type and length of eventual medical therapy. Results Patients with BE had a satisfying overall QoL with a mean EHP-5 score of 105.42 ± 99.98 points and VAS lower than 3 for all pain domains; additionally, they did not show a significant impartment of bowel function with mean BENS score of 4.89 ± 5.28 points. Notably, patients under medical therapy had a better QoL than patients without therapy (p

The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating muscle mass reduction seen in sarcopenia and the decline of neuronal functions characteristic of neurodegeneration. Our limited understanding of the intricate relationships within this triad hinders accurate diagnosis and effective treatment strategies. This review ana-lyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on ox-idative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sar-copenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, in-flammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can refine therapeutic strategies and yield better patient out-comes. This study emphasizes the complex interplay between vascular dysfunction, muscle de-generation, and cognitive decline, highlighting the necessity for multidisciplinary treatment ap-proaches. Advances in this domain promise improved diagnostic accuracy, more effective thera-peutic options, and enhanced preventive measures, all contributing to a higher quality of life for the elderly population.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding children are scarce. The purpose of our study is to explore the risk factor for AKD and impact of AKD following an acute kidney injury (AKI) episode in children on mortality and new-onset CKD. Methods: We retrospectively evaluated 736 children with ages between 2 and 18 years old with AKI admitted in a tertiary care hospital from the west Romania over a 9 years period. Results: AKD incidence following AKI was 17%. Patients that developed AKD were older, with higher baseline serum creatinine values, urea, C reactive protein and lower proteins, haemoglobin and sodium. They were more often exposed to sepsis, critical illness and nephrotoxic medications and presented certain susceptibilities like CKD, neoplasia, anemia, heart failure, arterial hypertension, stem cell transplant and female gender. AKI causes that increased the risk of AKD were intrinsic ones. AKD increased the overall mortality by three times. The factors that independently increased the risk of evolution towards CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: AKD is an independent risk factor for mortality and new-onset CKD in children.

Cerebral ischemic stroke poses a significant global cause of death, with ischemia-reperfusion injury contributing to neuronal cell death and tissue damage. However, significant therapeutic approaches with meaningful treatment effects for patients with ischemic stroke in actual clinical practice are lacking. This study investigated the potential neuroprotective effects of sildenafil, a phosphodiesterase-5 inhibitor, in a global cerebral ischemia model. We explored the impact of sildenafil on GFAP and AQP-4 expression, which are markers associated with astrocyte activation and water homeostasis, respectively. The immunofluorescence analysis revealed that the number of cells co-expressing the markers, which increased in the ischemia-induced group, was significantly reduced in sildenafil-treated groups, suggesting a potential mitigating effect on ischemia-induced astrocyte activation. Additionally, we conducted diverse behavioral tests, including the open-field test, novel object recognition, Barnes maze, Y-maze, and passive avoidance tests, to assess the effect of sildenafil on the cognitive function impaired by ischemia. Cognitive improvements were observed following sildenafil administration (20mg/kg) compared to the untreated group. Taken together, the results presented here suggest sildenafil's potential as a neuroprotective agent for alleviating delayed neuronal cell death and cognitive function impaired by ischemia.

The present paper describes the development of a prosthetic hand based on the human hand anatomy. The hand phalanges are printed by using 3D printed with Polylactic Acid material. One of the main contributions is the investigation on the prosthetic hand joins; the proposed design enables to create personalized joins that allow the prosthetic hand a high level of movement by increasing the degrees of freedom of the fingers. Moreover, the driven wire tendons show a progressive grasping movement, being the friction of the tendons with the phalanges very low. Another important point is the use of force sensitive resistors for simulating the hand touch pressure. These are used for the grasping stop simulating touch pressure of the fingers. Surface Electromyogram (EMG) sensors allow the user to control the prosthetic hand grasping start. Their use may provide the prosthetic hand the possibility of classification of the hand movements. The practical results included in the paper prove the importance of the soft joins for the object manipulation and to get adapted to the object surface. Finally, the force sensitive sensors allow the prosthesis to actuate with more naturalness by adding conditions and classifications to the Electromyogram sensor.

Proteins need to be located in appropriate spatiotemporal contexts to carry out their diverse biological functions. Mislocalized proteins may lead to a broad range of diseases, such as cancer and Alzheimer’s disease. Knowing where a target protein resides within a cell will give insights into tailored drug design for a disease. As the gold validation standard, the conventional wet lab uses fluorescent microscopy imaging, immunoelectron microscopy, and fluorescent biomarker tags for protein subcellular location identification. However, the booming era of proteomics and high-throughput sequencing generates tons of newly discovered proteins, making protein subcel-lular localization by wet-lab experiments a mission impossible. To tackle this concern, in the past decades, artificial intelligence (AI) and machine learning (ML), especially deep learning methods, have made significant progress in this research area. In this article, we review the latest advances in AI-based method development in three typical types of approaches, including sequence-based, knowledge-based, and image-based methods. We also elaborately discuss existing challenges and future directions in AI-based method development in this research field.

The incidence of diabetes mellitus (DM) continues to rise worldwide and one of the most serious microvascular complications is diabetic kidney disease (DKD), which is the leading cause of end-stage renal disease. Current bi-omarkers such as urinary albumin excretion rate have limitation for early detection of DKD. In our study we used ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-ESI+-MS) techniques to quantify previously analyzed metabolites, such as tryptophan, kynurenic acid, taurine, l-acetylcarnitine, glycine, and tiglylglycine. We performed the targeted analy-sis of metabolites from urine and serum samples, collected from 110 subjects. Of these, 90 patients with type 2 DM (T2DM) were divided according to the urinary albumin/creatinine ratio (UACR) into normoalbuminuria 300 mg/g groups, respectively, while 20 subjects were rep-resented by healthy controls. Through various validation methods, we identified several metabolites as potential biomarkers, such as kynurenic acid, glycine, and l-tryptophan in serum and l-acetylcarnitine, tiglylglycine, and tau-rine in urine.

Survival of Medulloblastoma (MB) depends on various factors, including the gene expression profiles of MB tumor tissues. In this study, we identified 967 MB survival related genes (SRBs) using the gene expression dataset of Cavalli et al. (2017) and the Cox proportional hazards regression model. Notably, the SRGs were over-represented on chromosomes 6 and 17, known for the abnormalities monosomy 6 and isochromosome 17 in MB. The most significant SRG was HMGA1 (high mobility group AT-hook 1), which is a known oncogene and a histone H1 competitor. High expression of HMGA1 was associated with worse survival, primarily in the Group 3γ subtype. The high expression of HMGA1 was unrelated to any known somatic copy number alteration. Most SRGs on chromosome 17p were associated with low expression in Group 4β, the MB subtype with 93% deletion of 17p and 98% copy gain of 17q. Pathway analysis showed that both chromosomes 6 and 17 included SRGs related to telomere maintenance and provide a rationale for testing telomerase inhibitors in Group 3 MBs. We conclude that HMGA1, along with other SRGs on chromosome 6 and 17 warrant further investigation as potential therapeutic targets in selected subgroups or subtypes of MB.

Cardiac dynamics are traditionally linked to a left ventricle, right ventricle and septum morphology, a topography that differs from the heart’s 5-century-old anatomic description of containing a helix and circumferential wrap architectural configuration. Torrent Guasp’s helical ventricular myocardial band (HVMB) defines this anatomy and its structure, explains why the heart’s 6 dynamic actions of narrowing, shortening, lengthening, widening, twisting and uncoiling happen. This database raises questions about deductions behind “accepted cardiac mechanics”, and its functional aspects will challenge and overturn them. These suppositions include the LV, RV, and septum description, timing of mitral valve opening, isovolumic relaxation period, reasons for torsion/twisting, untwisting, reasons for longitudinal and circumferential strain, echocardiographic sub segmentation, resynchronization, RV function dynamics, and diastolic dysfunction’s cause and unrecognized septum impairment. Torrent Guasp’s revolutionary contributions may alter future understanding of the diagnosis and treatment of cardiac disease.

Objectives: We aim to evaluate technical and clinical outcomes with E-nside stent-graft for thoraco-abdominal aortic aneurysm (TAAA) and pararenal abdominal aortic aneurysm (PAAA) endovascular treatment at our University Hospital Center. Methods: Retrospective analysis of patients electively treated by inner branched EVAR (iBEVAR) between 05/2021 and 03/2023. Demographics, procedural and clinical data were analyzed. Technical success and clinical outcomes, such as access-site related complications were reported. Perioperative and early mortality rate, freedom from aortic reintervention, Target vessels (TVs) patency and endoleak rate were evaluated during the follow-up. Technical aspects (external iliac artery diameter, iliac tortuosity, extent of aortic coverage) were retrospectively analyzed. Results: Twenty-two patients included (age 75.9±5.5; 72.7% male). Aneurism extent was Craw-ford I=4 (18.2%), III=8 (36.4%), IV=5 (22.7%), V=1 (4.5%) and PAAA=4 (18.2%). Mean aortic di-ameter was 63.5±9.9mm. The technical success 95.5% (assisted primary success 100%). The clini-cal success 86.4%. Perioperative and early freedom from all-cause mortality rate 90.9% and 90%, respectively. No case of inter-stage aortic-related mortality reported, as no permanent/temporary spinal cord ischemia (SCI). Seventy-eight out of 81 patent TVs were incorporated through a bridging stent (96.3%). TV success 95.1%. Mean external iliac artery (EIA) diameter 7.5±1.1mm. Twelve patients (six women, 100%) were considered outside the instructions for use (IFU) due to narrow iliac arteries. One access-site related complication reported. Conclusions: Our experience confirms that E-nside has promising technical and clinical success rates, as low reintervention rate, but requires a great sacrifice of healthy aorta and adequate iliac arteries that still represent a limitation, especially among women. Mid- to long-term studies and prospective registries are mandatory to evaluate long-term efficacy and safety, as a comparison between E-nside and other alternative off-the-shelf solution.

Recent advancements in vascular organoid (VO) and vessel-on-chip (VoC) technologies have revolutionized our approach to studying cardiovascular diseases (CVDs), offering unprecedented insights through more physiologically relevant models. VOs generated from human pluripotent stem cells exhibit remarkable self-organization capabilities, forming complex three-dimensional structures that closely mimic human blood vessel architecture and function, while VoCs engineered with groundbreaking microfluidic systems that meticulously recreate the physical and functional attributes of blood vessels. These innovative constructs serve as powerful tools for investigating vascular development, disease progression, and therapeutic efficacy. By enabling the creation of patient-specific VOs and VoCs, they pave the way for personalized medicine approaches, allowing researchers to delve into genetic variations, intricate cellular interactions, and dynamic processes with exceptional resolution. The synergy between VOs and VoCs with cutting-edge technologies such as single-cell sequencing and high-resolution imaging has further amplified their potential, unveiling novel mechanisms underlying CVDs and identifying promising therapeutic targets. Herein, we summarize different types of VOs and VoCs and present an extensive overview on the generation and applications of VOs and VoCs in CVDs. We will also highlight clinical and translational challenges and future perspectives around VOs and VoCs.

Fundus image registration plays a crucial role in the clinical evaluation of ocular diseases, such as diabetic retinopathy and macular degeneration, necessitating meticulous monitoring. The alignment of multiple fundus images enables the longitudinal analysis of patient progression, widening the visual scope, or augmenting resolution for detailed examinations. Currently, prevalent methodologies rely on feature-based approaches for fundus registration. However, certain methods exhibit high feature point density, posing challenges in matching due to point similarity. This study introduces a novel fundus image registration technique integrating U-Net for the extraction of feature points employing FIVES for its training and evaluation, a novel and large dataset for blood vessels segmentation, prioritizing point distribution over abundance. Subsequently, the method employs medial axis transform and pattern detection to obtain feature points characterized by the Fast Retina Keypoint (FREAK) descriptor, facilitating matching for transformation matrix computation. Assessment of the vessel segmentation achieves 0.7559 for Intersection Over Union (IoU), while evaluation on the Fundus Image Registration Dataset (FIRE) demonstrates the method’s comparative performance against existing methods, yielding a registration error of 0.596 for area under the curve, refining similar earlier methods and suggesting promising performance comparable to prior methodologies.

Microplastics (plastic particles &lt; 5 mm) are ubiquitous pollutants that pose the ability to carry microbiota, including pathogens. Microbial adhesion is usually a sign of pathogenicity, thus we investigated the adherent strains found on 4 mm nylon strips, which were ingested and excreted by wild fish specimens. Polymer analysis of the excreted samples shown no signs of degradation, nor have their controls, represented by the nylon strips submerged in the same water tanks. Both the ingested samples and controls presented pathogens in large numbers, revealing the fact that nylon microplastics can be physical carriers for pathogens in the aquatic environment.

Adipose tissue-derived stem cells (ADSCs) represent a subset of mesenchymal stem cells in every adipose compartment throughout the body. ADSCs can differentiate into various cell types, including chondrocytes, osteocytes, myocytes, and adipocytes. Moreover, they exhibit a notable potential to differentiate in vitro into cells from other germinal lineages, including endothelial cells and neurons. ADSCs have a wide range of clinical applications, from breast surgery to chronic wounds. Furthermore, they are a promising cell population for future tissue-engineering uses. Accumulating evidence indicates decreased proliferation and differentiation potential of ADSCs with increasing age, body mass index, diabetes mellitus, metabolic syndrome, or exposure to radiotherapy. Therefore, recent literature thoroughly investigates this cell population's senescence mechanisms and how they can hinder their possible therapeutic applications. This review will discuss the biological mechanisms and the physio-pathological causes behind ADSC senescence and how they can impact cellular functionality. Moreover, we will examine the possible strategies to invert these processes, re-establishing the full regenerative potential of this progenitor population.

Damage to peripheral arteries by the atherosclerotic process accounts for about 3% of the world's population, which puts this problem in the category of major social problems. Modified lipoproteins and cholesterol crystals are known to accumulate in the arterial intima and cause the formation of proatherogenic macrophages, foam cells, and inflammation. Defective efferocytosis of apoptotic foam cells leads to the formation of a necrotic core, a sign of failure to resolve inflammation. Resolution of inflammation is mediated by specialized pro-resorption lipid mediators, proteins and signaling gases. Improving the balance between pro-inflammatory and anti-inflammatory factors contributes to the reverse development of local atherogenesis. Active direct intervention in the reconstruction of the adventitial layer of the arterial wall using cholesterol-affinity polysaccharide hydrogels containing a cocktail of growth factors creates conditions for the formation of additional extracellular matrix and reversal of cholesterol mass from the subintimal zone. Creating concentration and electrostatic gradients in the adventitia zone using a hydrogel may be one of the effective ways to degrade early soft atherogenic plaques and locally restore the damaged structure of the vessel wall. Growing scientific interest in the previously insufficiently studied adventitia indicates its important role in angionesis and atherogenesis.

A theoretical account of development in mesocortical anatomy is derived from the free energy principle, operating in a neural field with both Hebbian and anti-Hebbian neural plasticity. An elementary structural unit is proposed, in which synaptic connections at mesoscale are arranged in paired patterns with mirror symmetry. Exchanges of synaptic flux in each pattern form coupled spatial eigenmodes, and the line of mirror reflection between the paired patterns operates as a Markov blanket, so that prediction errors in exchanges between the pairs are minimized. The theoretical analysis is then compared to the outcomes from a biological model of cortical neurodevelopment, in which neuron precursors are selected by apoptosis for cell body and synaptic connections maximizing synchrony and also minimizing axonal length. It is shown that this model results in patterns of connection with the anticipated mirror symmetries, at micro-, meso- and inter-arial scales, among lateral connections, and in cortical depth, explaining the spatial organization and functional significance of neuron response preferences, and compatible with features of both columnar and noncolumnar cortex. Multi-way interactions of mirrored representations provide a preliminary anatomically realistic model of cortical information processing.

In atherosclerosis patients, vascular endothelial dysfunction is commonly observed with damage of vascular endothelial glycocalyx, an extracellular matrix-bound to and encapsulating the endothelial cell lining the blood vessel wall. Unfavorable lifestyle; smoking and physical inactivity, also induces glycocalyx degradation. Moreover, the vascular endothelial glycocalyx is damaged by various unfavorable disease conditions like as dehydration, acute infectious disease, trauma, sepsis, ARDS, Kawasaki disease, preeclampsia, gestational diabetes mellitus, hypertension, diabetes, chronic kidney disease, atherosclerosis, stroke, dementia, microvascular angina, acute coronary syndrome, and heart failure. The vascular endothelial glycocalyx has been shown to be important not only as a physical cytoprotective barrier for vascular endothelial cells but also as a mechanism that regulates intracellular cell signaling. Therefore, vascular endothelial glycocalyx has great potential to explore new strategies for assessing the benefit conditions of our healthy vasculature.

New technologies have resulted in a better understanding of blood and lymphatic vascular heterogeneity at the cellular and molecular levels. Meanwhile, we still need to learn more about the heterogeneity of the cardiovascular and lymphatic systems between different species at the anatomical and functional levels. Even the deceptively simple question of the functions of fish lymphatic vessels has yet to be conclusively answered. The most common interpretation assumes a similar dual setup of the vasculature in zebrafish and mammals: on the one hand, there is the cardiovascular, circulatory system, and on the other hand, the lymphatic vascular system, in which the unidirectional flow is derived from surplus interstitial fluid and returned into the cardiovascular system. A competing interpretation questions the identity of the lymphatic vessels in fish as at least some of them receive their flow from arteries via specialised anastomoses, neither requiring an interstitial source for the lymphatic flow nor stipulating unidirectionality. In this alternative view, the “fish lymphatics” are a specialised subcompartment of the cardiovascular system, called the “secondary vascular system” (SVS). Many of the contradictions found in the literature appear to stem from the fact that the SVS develops in part or its entirety from an embryonic lymphatic vascular system by transdifferentiation. Future research needs to establish the extent of embryonic transdifferentiation of lymphatics into SVS blood vessels. Similarly, more insight is needed into the molecular regulation of vascular development in fish. Most fish do feature more than the five VEGF genes and three VEGF receptor genes that we know from mice or humans, and the relative tolerance of fish to whole genome and gene duplications could underlie the evolutionary diversification of the vasculature. This review discusses the key elements of the fish lymphatics versus the SVS and attempts to draw a picture coherent with the existing data, including the phylogenetic knowledge.

In diabetic foot injury prevention, no studies relate physical activity with the inflammatory response of the plantar tissues, evaluated by thermography and pressure distribution. These measurements are easy to be implemented in diabetic foot follow-up. The objective of this study was to analyze whether the plantar skin response, evaluated with thermography, after physical activity in healthy or diabetic patients, is a foot ulcer prognostic tool and to asses if there is a correlation between exercise intensity, plantar pressure and plantar thermographic response. A systematic review was carried out following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) format in the PubMed, Scopus and Web of Science databases, with no year limit during the second quarter of 2024. A total of 14 studies have been included in this review. The use of infrared thermography for early inflammatory tissue detection, plantar pressures and the monitoring of controlled physical activity, make possible to monitor changes that allow the identification of patients at risk of developing foot ulcers.

Oxidative stress constitutes a main molecular mechanism underlying cardiovascular diseases (CVDs). This pathological mechanism can be triggered by NADPH oxidases (NOXs), which produce reactive oxygen species (ROS). In fact, the different NOXs have been associated with myocardial infarction, atherothrombosis, and stroke. More specifically, we will focus on the implications of NOXs in atherothrombotic stroke. Each NOX member participates in a different way in the several stages of this disease: endothelial dysfunction, immune cell infiltration, foam cell genesis, vascular smooth muscle cells (VSMC) proliferation, and atherosclerotic plaque formation. Additionally, some NOXs are involved in plaque instability, thrombosis, ischemic stroke, and ischemia-reperfusion injury (IRI). Interestingly, the effects of NOXs in this pathology depend on the specific homologue, the cell type in which they are activated, and the stage of the disease. In this review we summarize the most up-to-date information about the implications of vascular NOXs in each of these processes. Finally, we highlight some limitations and future perspectives of the study of NOXs in CVDs.

Late-stage epithelial ovarian cancer (EOC) involves widespread dissemination of malignant disease throughout the peritoneal cavity, often accompanied by ascites. EOC metastasis relies on the formation of multicellular aggregates, called spheroids. Given that Liver Kinase B1 (LKB1) is required for EOC spheroid viability and LKB1 loss in EOC cells decreases tumor burden in mice, we investigated whether the LKB1 complex controls invasive properties of human EOC spheroids. LKB1 signalling was antagonized through CRISPR/Cas9 genetic knockout of LKB1 and/or RNAi-dependent targeting of STE20-related kinase adaptor protein (STRAD; an LKB1 activator). EOC spheroids expressing nuclear GFP (green) or mKate2 (red) constructs were embedded in Matrigel for real-time live-cell invasion monitoring. Migration and invasion were also assessed in spheroid culture using Transwell chambers, spheroid reattachment, and mesothelial clearance assays. The loss of LKB1 and STRAD signalling decreased cell invasion through Matrigel and Transwell membranes, as well as mesothelial cell clearance. In the absence of LKB1, zymographic assays identified a loss of matrix metalloproteinase (MMP) activity, whereas spheroid reattachment assays found that coating plates with fibronectin restored the invasive potential. A three-dimensional EOC organoid model demonstrated that organoid area was greatly reduced by LKB1 loss. Overall, our data indicated that LKB1 and STRAD facilitated EOC metastasis by promoting MMP activity and fibronectin expression. Given that LKB1 and STRAD are crucial for EOC metastasis, targeting LKB1 and/or STRAD could disrupt the dissemination of EOC, making inhibitors of the LKB1 pathway an alternative therapeutic strategy for EOC patients.

This review explores the challenges and emerging trends in pancreatic cancer therapy. In particular, we focus on the tumor microenvironment and the potential of immunotherapy in pancreatic cancer. We discuss novel strategies targeting the desmoplastic barrier and immunosuppressive cells to enhance immune cell infiltration and activation. Recent clinical trials, particularly those involving novel immunotherapeutic agents and tumor vaccines, are examined to understand their efficacy and limitations. This review aims to highlight the ongoing efforts to refine immunotherapy approaches for better patient outcomes.

Background: Both hypertension and carotid atherosclerosis are independent risk factors for cardiovascular disease. Understanding their combined impact could enhance risk assessment and management strategies. Hypothesis: We hypothesized that the synergistic effects of hypertension and carotid plaques would increase the risk of both cardiovascular events and all-cause mortality. Methods: A follow-up study was conducted at the Preventive Cardiology department of Vilnius University Hospital Santaros klinikos between 2012 and 2021. The study recruited participants aged 40-60 who did not have overt CVD and were part of the Lithuanian High Cardiovascular Risk primary preventive program. The study collected demographic and clinical data, including an ultrasound assessment of carotid plaque. The participants were monitored for 4-10 years for CVD events and all-cause mortality. Results: Among 6,138 participants, 954 (16%) experienced cardiovascular disease (CVD) events. The presence of carotid plaque on both sides was significantly associated with CVD events, myocardial infarction, and all-cause mortality. However, the combination of hypertension and carotid plaque did not significantly increase the risk for CVD events, stroke, or all-cause mortality. Conclusion: The combination of hypertension and carotid plaque did not significantly increase the risk of CVD events or all-cause mortality. CV events depend on the spread of the atherosclerosis process in the carotid vessels.

Objectives: Valsalva maneuver is performed during strength physical exercises, because it stabilizes the torso through increased intra-abdominal pressure. By contrast, yoga practitioners are discouraged from Valsalva. Instead, they use ujjayi breath, which consists of unstopped breathing through the narrowed glottis. Methods: This study was an observational research performed in healthy participants. The aim of this study was to evaluate veins in the groin area during different types of breathing. We examined 10 healthy people in the standing body position during: a) normal breathing b) Valsalva maneuver c) ujjayi breath. We measured the cross-sectional areas of the femoral and the great saphenous veins in the proximity to the sapheno-femoral junction. Results: In comparison with normal breathing, there were only slight dilatations of examined veins during Valsalva and ujjayi. The cross-sectional area of femoral vein increased by 7-9% during Valsalva, and 2-4% during ujjayi; cross-sectional area of the great saphenous vein increased by 17-18% during Valsalva and 15-16% during ujjayi. In all participants the terminal and preterminal valves of the great saphenous vein were competent. However, Valsalva maneuver was associated with complete closure of the terminal valve, while during ujjayi breath this valve was opening and closing, following the breathing. Conclusions: In the standing body position both Valsalva and ujjayi breath have minimal effect on cross-sectional areas of the veins in the groin. On the other hand, ujjayi breath allows for undisturbed flow through the sapheno-femoral junction, while Valsalva interrupts this flow, with blood stagnation distally from the terminal valve.

Keywords: Vascular Malformation, Diode Laser, Angioma, Blue light, Conservative

Abstract: The septum pellucidum is a thin, translucent double-membrane structure located between the anterior horns of the lateral ventricles. This mini-review explores the gross and radiological anatomy, variations, and clinical significance of the septum pellucidum. The article elaborates on the different types of variations, including cavum septum pellucidum (CSP), cavum vergae (CV), and cavum veli interpositi (CVI). The CSP is a fluid-filled pocket located within the two leaflets of the SP. It forms during fetal development and gradually obliterates before birth. However, the fusion may be prolonged or persist into adulthood in some individuals. The CV is formed when the two commissural plates fail to fuse completely during foetal development. When associated with CSP, the CV is collectively known as the cavum septum pellucidum et vergae (CSPV). However, the isolated CV is rare. The CVI is a CSF-filled space between two tela choroidea layers and communicates with the quadrigeminal cistern, superior to the pineal gland. This article discusses the radiological features of these variations using imaging techniques such as ultrasound, magnetic resonance imaging (MRI), and computed tomography (CT). Ultrasonography is particularly useful for evaluating the SP in fetuses and infants, while MRI and CT scans provide detailed visualisation of the SP and its variations. The SP has the potential to be associated with cerebral anomalies, hydrocephalus, mental disorders, and neurological symptoms. Knowing the related anatomy and detecting variations using imaging modalities are crucial for accurately diagnosing and managing these conditions.

The impact of systemic vascular resistance (SVR) in hypertrophic (HCM) and amyloid cardio-myopathies has been seldom investigated. We studied pressure-strain loop derived myocardial work (MW) indices and SVR in patients with either sarcomere HCM or wild type transthyretin cardiac amyloidosis (ATTR), presented with heart failure and preserved left ventricular ejection fraction (HFpEF) at the outpatient cardiology units at Messina and Catania University Hospitals (Italy). Patients were in sinus rhythm and needed to have good transthoracic ultrasound imaging quality to undergo transthoracic strain-echocardiography. Other than conventional parameters, SVR and GWI (global work index) were measured. Based on cross-tabulation (a way to assess the ventricular-arterial coupling), the patients were then classified in 4 classes according to the cut-off values suggested by previous studies of 1,440 dyne/s/cm-5 for SVR (Stefadouros et al., 1973) and 1576 mm Hg% for GWI (Olsen et al., 2022). Sixty patients, 30 in each group, aged 61±16 years, 78% males, were studied. HCM were younger than ATTR patients and in a better clinical status (23% HCM vs 77% ATTR were NYHA class 3, p<0.001). Overall, 51 patients (85%) showed high SVR, of whom 21 were HCM (70%) and 30 ATTR (100%) (p<0.005). Both, SVR and GWI were impaired (the poorest class C) in 43% HCM patients (with greater left ventricular concentric hypertrophy) vs 93% of ATTR patients (in advanced NYHA class) (p<0.001). In conclusion, assessing SVR and GWI in HFpEF patients with HCM or ATTR can help clinicians to interpret the pathophysiological and clinical features of such complex diseases.

Vascular anomalies are a diverse group of abnormal blood vessel developments that can occur at birth or shortly afterward. Embolization and sclerotherapy have been utilized as a treatment option for these malformations but may cause moderate to severe pain. This study aims to evaluate the utilization of peripheral nerve blocks in opioid consumption, pain scores, and length of stay. A retrospective chart review was conducted at the UPMC Children's Hospital of Pittsburgh for all patients who underwent embolization and sclerotherapy between 2011 and 2020. Patient data was collected to compare opioid consumption, pain scores, and length of stay. Eight hundred fifty-four procedures were performed on 347 patients. The morphine milligram equivalent per kilogram mean ratio between groups was 0.9 (0.86, 0.95) with a p-value of &lt;0.001. The pain score mean ratio was –1.17 (–2.2, -0.1) and a p-value of 0.027. Length of stay had a mean ratio of 0.94 (0.4, 2) and a p-value of 0.875. By decreasing opioid consumption and postoperative pain scores, peripheral nerve blocks may have utility in patients undergoing embolization and sclerotherapy while not clinically increasing the length of stay for patients. Their use should be individualized and carefully discussed with the interventional radiologist.

Zinc (Zn) is the second most abundant metal in the human body, and is essential for the function of 10% of all proteins. As metals cannot be synthesized or degraded, they must be assimilated from diet by specialized transport proteins, which unfortunately also provide an entry route for the toxic metal pollutant cadmium (Cd). The intestinal absorption of Zn depends on the composition of food that is consumed, firstly the amount of Zn itself, and then the quantity of other food constituents such as phytate, protein and calcium (Ca). In cells, Zn is involved in regulation of intermediary metabolism, gene expression, cell growth, differentiation, apoptosis, and antioxidant defense mechanisms. Cellular influx, efflux, subcellular compartmentalization, and trafficking of Zn are coordinated by transporter proteins, the Solute-Linked Carrier 30A and 39A (SLC30A and SLC39A), known as the ZnT and the Zrt-/Irt-like protein (ZIP). Because of its chemical similarity with Zn and Ca, Cd disrupts the physiological functions of both. The concurrent induction of a Zn efflux transporter ZnT1 (SLC30A1) and metallothionein by Cd disrupts the homeostasis and reduces the bioavailability of Zn. The present review highlights the increased mortality and the severity of various diseases, including those induced by COVID-19 infections, among Cd-exposed persons and the roles of Zn and other transport proteins in the manifestation of Cd cytotoxicity. Special emphasis is given to the potential protective effects of Zn against bone, lung and heart diseases associated with Cd exposure. The difficult challenge of determining a permissible intake level of Cd is discussed in relation to the recommended dietary Zn intake levels.

Purpose. This paper aims to present a unique perspective that emphasizes the intricate interplay between energy, dietary proteins, and amino acid composition, underscoring their mutual dependence for health-related considerations. Energy and protein synthesis are fundamental to biological processes, crucial for the sustenance of life and growth of organisms. Methods and Results. We explore the intricate relationship between energy metabolism, protein synthesis, regulatory mechanisms, protein sources, amino acid availability, and autophagy, in order to elucidate how these elements collectively maintain cellular homeostasis. We underscore the vital role this dynamic interplay has in preserving cell life. Conclusion. A deeper understanding of the link between energy and protein synthesis is essential to comprehend fundamental cellular processes. This insight could have wide-ranging impact in several medical fields, such as nutrition, metabolism, and disease management.

The evolution of knowledge in biological and medical areas which made possible scientific and technological advances are attributed to anatomical studies, physiology and immunology in animals, contributing to the discovery of prophylactic measures and treatments of diseases that affect humans and animals. Currently, substitution is suggested by alternative methods that do not use laboratory animals, however in vitro methods may never be able to provide similar results to in vivo methods. Mice and rats are the most used animals in experimental researches, the anatomical, histological and genetic differences between species should be carefully evaluated, to better apply the study model and avoid unnecessary waste avoid. This study, aimed at an anatomical comparative and histological relationship between a rat´s and a mouse´s organs, is of great importance in experimental studies. For such, 30 Mus musculus (Swiss) mice and 15 Rattus norvegicus (Wistar) male and heterogenic rats, were used. All animals were kept free of pathogenic microorganisms, with the absence of surgical interventions that could cause anatomical and physiological changes. It was possible to observe significant anatomical and histological differences between spleens, brains, hearts, stomachs and intestines, livers, eyes, lungs and kidneys among species, which will serve as a basis to assist in choosing the most satisfactory research model. Few studies relate specific characteristics among laboratory animals, being restricted to a few veterinary and zoology books. The greater the organic, physiological and anatomical similarities are with the human being, the greater is the applicability of the animals in studies. However, it is not possible to lay down general rules to validate the extrapolation from one species to another.

This systematic examines research into patients diagnosed with retinal vascular occlusive diseases (RVODs) secondary to coronavirus disease 2019 (COVID-19) infection or vaccination. RVODs include central retinal vein occlusion, branch retinal vein occlusion, central retinal artery occlusion, and branch retinal artery occlusion. Previous studies have posited a possible link between RVODs and COVID-19. RVODs are of two types: retinal vein occlusion and retinal artery occlusion. These disorders develop when retinal blood vessels become clogged by thrombi or fat deposition. The retina is an important component of the visual apparatus. Its photoreceptors are stimulated by the light hitting the eye and record its pattern. The retina then relays this visual information to the brain. When retinal blood vessels become clogged, the damage can range from slightly reduced vision to complete blindness. COVID-19 causes endothelial dysfunction and increased levels of von Willebrand factor antigens in the blood. Elevation of von Willebrand factor activates the coagulation process and platelet aggregation. The treatment methods and visual prognosis in COVID-19-related RVODs do not differ from conventional RVODs. However, ophthalmologists need to be aware of the possible relationship and should consider RVODs when they encounter patients with vision loss following COVID-19 infection or vaccination.

This review provides a comprehensive analysis of the pelvic plexus and its regulation across various mammalian species, including rats, cats, dogs, and pigs. The pelvic and hypogastric nerves play crucial roles in regulating pelvic functions such as micturition, defecation, and erection. The anatomical organization of these nerves varies, forming either well-defined ganglia or complex plexuses. Despite these variations, the neurons within these structures are consistently regulated by key neurotransmitters—norepinephrine and acetylcholine. These neurons also possess receptors for testosterone and prolactin, particularly in rats, indicating the significant role of these hormones in neuronal function and development. Moreover, neuropeptides such as vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY), somatostatin (SOM), galanin (GAL), and calcitonin gene-related peptide (CGRP) are co-released with neurotransmitters to modulate pelvic functions. This review highlights the complex interplay between neurotransmitters, neuropeptides, and hormones in regulating pelvic physiology and emphasizes the importance of hormonal regulation in maintaining the functionality and health of the pelvic plexus across different species.

Leukotrienes are proinflammatory mediators that participate in the process of atherogenesis and contribute to the development of symptomatic peripheral arterial disease. The aim was to evaluate the relationship between leukotriene E4 (LTE4) and B4 (LTB4) with parameters reflecting endothelial vascular function in patients with chronic lower limb ischemia. This prospective observational study enrolled 50 consecutive patients undergoing endovascular treatment due to chronic lower limb ischemia (Rutherford 3). All participants were followed-up for one year (after 1, 3, 6 and 12 months), with a sequential assessment of urinary LTE4 and LTB4, as well as measures of endothelial and vascular function: Flow-Mediated Dilatation (FMD), Intima-Media Thickness (IMT), corrected Augmentation Index (AI75), Shear Rate (SR), Ankle-Brachial Index (ABI), Toe-Brachial Index (TBI). There was a significant relationship between LTE4 and measures of vascular function: FMD (R2 = 0.69, P&lt;0.001), IMT (R2=0.12, P&lt;0.01), AI75 (R2=0.43, P&lt;0.001), SR (R2=0.48, P&lt;0.001). Similar findings were noted for LTB4: FMD (R2=0.47, p&lt;0.001), IMT (R2=0.23, P&lt;0.001), AI75 (R2=0.61, P&lt;0.001) and SR (R2=0.33, P&lt;0.001). Alterations in parameters were significantly related: ΔLTE4 vs ΔFMD(R2=0.63, P&lt;0.001), ΔSR (R2=0.42, P&lt;0.001) and ΔLTB4 vs AI75(R2=0.40, P&lt;0.001), SR(R2=0. 29, P&lt;0.001). We conclude, that increasing concentrations of LTE4 and LTB4 are associated with impairment of vascular and endothelial function, which may lead to worse endovascular treatment clinical outcomes.

Cancer cells require substantial amounts of energy and substrates for their metabolic hyperactivity, enabling the synthesis of new cells at the expense of healthy ones. Preliminary in vitro data suggest that a mix of free essential amino acids (EAA-mix) can promote cancer cell apoptosis by enhancing autophagy. This study aimed to confirm, both in vitro and in vivo, whether EAA intake could influence the development of colon cancer in mice. We investigated changes in cancer proliferation in CT26 cells treated with EAA-mix, and in mice fed with EAA rich modified diets (EAARD) as compared to those on a standard laboratory diet (StD). CT26 cells were injected subcutaneously (s.c.) or intraperitoneally (i.p.). After 21 days, tumors were removed and measured. In vitro data corroborated that EAA-mix impairs cancer growth by inducing autophagy and apoptosis. In vivo data revealed that mice on StD developed significantly larger (s.c.) and more numerous (i.p.) cancers than those on EAARD. EAA administration appears to influence cancer cell survival with notable anti-proliferative properties.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment and memory loss. Oxidative stress (OS) has emerged as a central element in the pathophysiology of AD, linking various pathological features including amyloid-β (Aβ) plaque formation, tau hyperphosphorylation, and synaptic dysfunction. This review comprehensively examines the role of OS in AD, focusing on the mechanisms of reactive oxygen species (ROS) production, mitochondrial dysfunction, and their impact on neuronal integrity. Additionally, the review highlights recent advances in antioxidant therapy. Elevated ROS levels in the aging brain exacerbate oxidative damage to lipids, proteins, and DNA, contributing to neuronal atrophy and synaptic loss. Mitochondrial dysfunction further amplifies OS, disrupting cellular energy metabolism and promoting neurodegeneration. Despite the strong association between OS and AD, antioxidant therapies have shown inconsistent clinical outcomes. Emerging strategies targeting offer promising avenues for therapeutic intervention. This review highlights the need for a multifaceted approach in understanding and mitigating OS-related damage in AD, aiming to pave the way for more effective treatments and improved patient outcomes.

Abstract: Perihilar cholangiocarcinoma (phCC) is the most common type of cholangiocarcinoma, accounting for approximately 60 % of cases, followed by the distal and then the intrahepatic forms. There is not a staging system that allows comparation of all series and extract some conclusions to increase the long-survival rate in this dismal disease. The extension of the resection, which theoretically dependes on the type of phCC, is not closed subject. As surgery is the only known way to achieve a cure, many aggressive approachs have been adopted. Despite extended liver resections and even vascular resections, margins are positive in around one third of patients. In the past two decades, with advances in diagnostic and surgical techniques, the surgical outcomes and survival rates have gradually improved, although variability is the rule, with morbidity and mortality rates ranging from 14% to 76% and from 0% to 19%, respectively. Extended hepatectomies and portal vein resection even right hepatic artery reconstruction for the left side tumors are frequently needed. Salvage procedures when arterial reconstruction is not feasible, as well as hepatopancreatoduodenectomy, are still under evaluation too. In this article, we discuss the aggressive surgical approach to phCC focused on vascular resection. Disparate results on the surgical treatment of phCC made it impossible to reach clear-cut conclusions.

Familial Exudative Vitreoretinopathy (FEVR), Norrie disease, and persistent fetal vascular syndrome (PFVS) are extremely rare retinopathies that are clinically distinct but are unified by abnormal retinal endothelial cell function – and subsequent irregular retinal vascular development and/or aberrant inner blood-retinal-barrier (iBRB) function. The early angiogenesis of the retina and its iBRB is a delicate process that is mediated by the canonical Norrin Wnt-signaling pathway in retinal endothelial cells. Pathogenic variants in genes that play key roles within this pathway such as NDP, FZD4, TSPAN12, and LRP5, have been associated with the incidence of these retinal diseases. Recent efforts to further elucidate the etiology of these conditions have not only highlighted their multigenic nature but have also resulted in the discovery of pathological variants in additional genes such as CTNNB1, KIF11, and ZNF408, some of which operate outside of the Norrin Wnt-signaling pathway. Recent discoveries of FEVR-linked variants in two other Catenin genes (CTNND1, CTNNA1) and the Endoplasmic Reticulum Membrane Complex Subunit-1 gene (EMC1) suggest that we will continue to find additional genes that impact the neural retinal vasculature, especially in multi-syndromic conditions. The goals of this review are to briefly highlight the current understanding of the roles of their encoded proteins in retinal endothelial cells to understand the essential functional mechanisms that can be altered to cause these very rare pediatric retinal vascular diseases.

Chronic inflammatory diseases are considered the most significant cause of death worldwide. Current treatments for inflammatory diseases are limited due to the lack of understanding of the biological factors involved in early-stage disease progression. Nerve growth factor (NGF) is a neurotrophic factor directly associated with inflammatory and autoimmune diseases like osteoarthritis, multiple sclerosis, and rheumatoid arthritis. It has been shown that NGF levels are significantly upregulated at the site of inflammation and play a crucial role in developing a robust inflammatory response. However, little is known about NGF's temporal expression profile during the initial progressive phase of inflammation. This study aimed to determine the temporal expression pattern of NGF in rat skin during Adjuvant-Induced Arthritis (AIA). Sprague Dawley rats were randomly divided into control and Complete Freund's Adjuvant (CFA) treated groups. Levels of NGF were evaluated following unilateral AIA at different time points and it was found that peripheral inflammation due to AIA significantly upregulated the expression of NGF mRNA and Protein in a biphasic pattern. These results suggest that NGF signaling is crucial for initiating and maintaining peripheral neurogenic inflammation in rats during AIA.

The vomeronasal system serves as a pivotal element in mammalian sensory biology, allowing the perception of chemical signals essential for social communication via the activation of two main receptor families, V1R and V2R. The expression of V1Rs and V2Rs is linked with that of the G-protein alpha-subunits, Gαi2 and Gαo, respectively. The exploration of the evolutionary pathways of V1Rs and V2Rs across all mammalian species remains a main challenge, juxtaposing available genomic data against emerging immunohistochemical evidence. However, recent investigations, in contrast to what is predicted by the currently annotated genomic sequences, have revealed the expression of Gαo in the vomeronasal neuroepithelium of wild canids, including wolves and foxes. In the present study, the employment of a specific antibody raised against the mouse V2R2, member of the C-family of vomeronasal receptors, V2Rs, has confirmed the expression of this receptor in the fox and wolf, but it has revealed the lack of expression in the dog. This may reflect the impact of domestication on the regression of the VNS in this species, in contrast to their wild counterparts, and underscores the effects of artificial selection on sensory functions. Thus, these findings suggest a more refined chemical detection capability in wild species.

Nerve hydrodissection (HD), a technique used when treating nerve entrapments, involves using an anesthetic or solution such as saline or 5% dextrose solution to separate the nerve from the surrounding tissue, fascia, or adjacent structures. This technique aims to treat neuropathic pain, or pain caused by the nerve. Ultrasound-guided HD of peripheral nerves has gained significant attention in the medical profession and pain management fields in recent years. This is due to a number of high impact publications of randomized control trials demonstrating the efficacy and safety of this technique for the treatment of carpal tunnel syndrome. Even the 20th edition of Harrison’s Principles of Internal Medicine textbook lists injection of 5% dextrose as an alternative local treatment that does not have the side effects of corticosteroids. At present, there is no review of the current literature on this technique. This manuscript will summarize and discuss the following: 1) the different approaches to doing ultrasound-guided HD of nervous structures, 2) its usages in different clinical situations, 3) its clinical pearls, 4) the solution used, and 5) the postulated mechanisms of action.

Chronic hemodialysis (HD) patients have very high cardiovascular risk. Acute vascular changes during dialysis mediated by factors of the endothelium may have a crucial role in this. Aim: To study acute vascular changes during HD. In 29 consecutive chronic HD patients (age: 65.6±10.4 years) pre-, mid-, and post-HD plasma syndecan-1 (SDC-1) and endothelin-1 (ET-1) levels were measured. Applanation tonometry was performed before HD. SDC-1 levels increased during HD (p=0.004). Males had higher ET-1 levels. Patients were divided into 2 groups based on pulse wave velocity (PWV): PWV≥12 m/s and PWV<12 m/s. Pre-HD and mid-HD SDC-1 levels were higher in the group with PWV≥12 m/s (10.174±2.568 vs. 7.928±1.794 ng/ml, p=0.013, and 10.319±3.482 vs. 8.248±1.793 ng/ml, p=0.044, respectively). Post-HD ET-1 levels were higher in the patient group having PWV≥12 m/s (10.88±3.00 vs. 8.05±3.48 pg/l, p=0.027). Patients having PWV≥12 m/s had higher pre-HD peripheral and aortic systolic blood pressure (p<0.05). Total cholesterol correlated with the SDC-1 decrease during HD (r=0.539; p=0.008). Pre-, mid-, and post-HD SDC-1 correlated with the ultrafiltration (r=0.432, p=0.019; r=0.377, p=0.044; and r=0.401, p=0.012, respectively). SDC-1 and ET-1 contribute to vascular changes observed during HD, and they have correlations with some cardiovascular risk factors.

Glutamate functions as the major excitatory neurotransmitter for primary sensory neurons and has a crucial role in sensitizing peripheral nociceptor terminals producing sensitization. Glutaminase (GLS) is the synthetic enzyme that converts glutamine to glutamate. GLS-immunoreactivity (-ir) and enzyme activity are elevated in dorsal root ganglion (DRG) neuronal cell bodies during chronic peripheral inflammation, but the mechanism for this GLS elevation is yet to be fully characterized. It has been well established that, after nerve growth factor (NGF) binds to its high-affinity receptor tropomyosin receptor kinase A (TrkA), a retrograde signaling endosome is formed. This endosome contains the late endosomal marker Rab7GTPase and is retrogradely transported via axons to the cell soma located in DRG. This complex is responsible for regulating the transcription of several critical nociceptive genes. Here, we show that this retrograde NGF signaling mediates the expression of GLS in DRG neurons during the process of peripheral inflammation. We disrupted the normal NGF/TrkA signaling in adjuvant-induced arthritic (AIA) Sprague Dawley rats by pharmacological inhibition of TrkA or blockade of Rab7GTPase, which significantly attenuated the expression of GLS in DRG cell bodies. These results indicate that NGF/TrkA signaling is crucial for the production of glutamate and has a vital role in the development of neurogenic inflammation. In addition, our pain behavioural data suggest that Rab7GTPase can be a potential target for attenuating peripheral inflammatory pain.

Alzheimer’s disease (AD) and the therapies of AD with anti-amyloid1-42 (Aβ) monoclonal antibodies are associated with the vascular complications of brain edema, hemorrhage, and cerebral amyloid angiopathy (CAA) termed amyloid-related imaging abnormalities (ARIAs). The neuropathology of normal and AD brains demonstrates that monocyte/macrophages (MMs) are critical in successful brain clearance in healthy brain by up-loading, transporting, and degrading Aβ but fail degradation and clearance in AD patients by releasing Aβ into vessels at the blood-brain barrier, causing vasculitis and ARIAs. The naturally-formed epoxides (EpFAs) of polyunsaturated fatty acids (PUFA’s), including arachidonic, docosahexaenoic, and eicosapentaenoic fatty acids, may repair degradation of Aβ by regulating Aβ-degrading enzymes, inflammatory cytokines, and unfolded protein response (UPR) to endoplasmic reticulum stress in a homeostatic fashion. EpFAs are, however, degraded by the soluble epoxide hydrolase enzyme (sEH) but are protected by the sEH inhibitor (sEHI) TPPU. In the cultures of AD patients’ macrophages, TPPU with the epoxide EEQ, and the cGAS/STING inhibitor H-151 increased uptake of Aβ at 2 hours and degradation of Aβ at 24 hours. In conclusion, the soluble epoxide hydrolase inhibitor TPPU with omega-3 fatty acids and the cGAS/STING inhibitor H-151 increase Aβ uptake and degradation in macrophages of AD patients, and potentially enhancing Aβ clearance in the AD brain.

Introduction: ophthalmological assessment of the retinal circulation and the level of VEGF-A is currently considered a non-invasive and safe diagnostic tool to assess the peripheral microcircu-lation Objective: to study retinal hemodynamics and VEGF-A levels in patients with type 1 diabetes mellitus after pancreas transplantation Settings and Design: A prospective, single-stage, single-center, non-randomized clinical trial Methods: 79 patients (158 eyes) with type 1 diabetes mellitus and end-stage diabetic nephropathy participated in the study. Patients were divided into 3 groups: group 1, potential recipients of pancreas and kidney transplant from the waiting list; group 2, patients after kidney transplanta-tion; and group 3, patients after simultaneous pancreas and kidney transplantation. Ophthalmo-logical examination included measuring the macular hemoperfusion density. The level of VEGF-A was examined in the patients' tear by enzyme immunoassay. Results: retinal hemoperfusion density and VEGF-A concentration were expected to correlate with the severity of diabetic changes in the fundus of patients. A lower index of retinal hemoperfusion density and a high level of VEGF-A were noted in patients with proliferative ret-inopathy and macular oedema. Group 3 showed the lowest frequency of the active phase of the proliferative retinopathy and retinal macular oedema, characterized by a higher retinal hemoperfusion density in the foveal and the parafoveal zone of the macular region, and low VEGF-A concentration in tear. Conclusion: measurement of retinal hemoperfusion density and determination of tear VEGF-A concentration are informative objective methods for diagnosing the severity of diabetic changes of the fundus.

Vascular calcification (VC), is a common complication in patients with chronic kidney disease and increases mortality. Although oxidative stress is involved in the onset and progression of this disorder, the specific role of some main redox regulators such as catalase, the main scavenger of H2O2, remains unclear. In the present study, epigastric arteries of kidney transplant recipients, an in vivo model of VC and an in vitro model of VC exhibiting catalase overexpression (Cts) were analyzed. Peri-calcification areas of human epigastric arteries have increased levels of catalase and cytoplasmic rather than nuclear RUNX2. In the in vivo model, advanced aortic VC concurs with lower levels of the H2O2 scavenger, glutathione peroxidase 3 compared to controls. In an early model of calcification using vascular smooth muscle cells (VSMCs), Cts VSMCs showed the expected increase in RUNX2 total levels. However, Cts VMSC also exhibited lower percentage of the nucleus stained for RUNX2 in response to calcifying media. At this early model of VC we did not observe dysregulation of mitochondrial redox state, an increase in general redox state was observed in the cytoplasm. These in vivo and in vitro results highlight the complex role of antioxidant enzymes as catalase in the process of VC by regulation of RUNX2 location.

In this paper, the feasibility of automated and accurate in vivo measurements of vascular parameters continuously and non-invasively using ultrasound sensor is presented. Vascular parameters such as pulse wave velocity (PWV), blood pressure (BP), arterial compliance (AC) and stiffness index (SI) are affluent indicators of cardiovascular disorders and needs to be monitored non-invasively and continuously during surgeries and follow-up procedures. Cuff based or invasive catheter techniques are considered as gold standard to measure BP and are fed manually to compute AC and SI which employ imaging algorithms. In this context, a Continuous and Non-Invasive Vascular Stiffness and Arterial Compliance Screener (CaNVAS) is developed to measure said parameters continuously and non-invasively using ultrasound sensor. Acoustic waves of 5 MHz (2.2 – 10 MHz) are driven through target arterial walls, reflected echoes captured, pre-processed and frequency shift is used to calculate PWV. It is observed that PWV measured using CaNVAS varies exponentially with BP values obtained from sphygmomanometer (BPMR-120) and this relationship is used to compute instantaneous values of BP. The proposed device is validated by performing measurements on 250 subjects in pre and post exercise conditions and found to have 95% accuracy and an average of 12.5% coefficient of variation.

Hydrogels, hydrophilic polymeric compounds, have been recently put under investigation as regenerative medicine applications and delivery systems for antineoplastic drugs, particularly chemotherapeutics (anthracyclines, alkylating agents), target drugs (trastuzumab) and immunotherapies. Porosity, conductivity, biodegradability and physical states are some of the peculiarities that render hydrogels suitable for therapies implementation. Chemically-modifying agents and enzymes can be also coupled to hydrogels for pharmacokinetical parameters improvement and side effects avoidance. Cardiotoxicity is in fact one of the major issues for oncological patients after treatment efficacy. Heart failure, myocarditis and hypertension are causes of morbidity and mortality that can possibly be avoided. Specific reaching of the target tumor site has been achieved by several authors in preclinical in vivo studies but clinical studies are currently under design processes. Polydioxanone, a hydrogel-mimicking agent, is capable to interact with the elastic properties of pulmonary artery. An advantageous characteristic is that can be also reabsorbed within biological systems and can cause a remodeling process of the vessel wall. Hydrogels currently represent a strong topic of interest for researchers and probably will guide future clinical investigations and practice.

High systolic blood pressure and increased blood pressure variability after the onset of ischemic stroke are associated with poor clinical outcomes. One of the key determinants of blood pressure is arteriolar size, determined by vascular smooth muscle tone and vasodilatory and vasoconstrictor substances that are released by the endothelium. The aim of this study is to outline alterations in vasomotor function in isolated peripheral arteries following ischemic stroke. The reactivity of thoracic aortic segments from male C57BL/6 mice to dilators and constrictors was quantified using wire myography. Acetylcholine induced endothelium-dependent vasodilation was impaired after ischemic stroke (LogIC50 Sham=-7.499, LogIC50 Stroke=-7.350, P=0.0132, n= 19, 31 respectively). Vasodilatory responses to SNP were identical in isolated aortas in sham and stroke groups. Phenylephrine induced vasoconstriction was impaired in aortas isolated from stroke animals in comparison to sham counterparts (Sham LogEC50= -6.652 vs Stroke LogEC50=-6.475, P< 0.001). Our study demonstrates that 24 hours post-ischemic stroke, peripheral vascular responses are impaired in remote arteries. Aortas from stroke animals exhibited reduced vasoconstrictor and endothelium-dependent vasodilator responses, while endothelium-independent vasodilatory responses were preserved. Since both vasodilatory and vasoconstrictor responses of peripheral arteries are impaired following ischemic stroke, our findings might explain increased blood pressure variability following ischemic stroke.

Alzheimer’s Disease (AD) is a debilitating neurodegenerative disease characterized by the accumulation of extracellular amyloid-β peptides (Aβ) within the cerebral parenchyma and vasculature, the latter termed cerebral amyloid angiopathy (CAA). This study utilized confocal imaging to investigate heparan sulfate (HS) within the cerebrovasculature and its potential associations with CAA, gender, and ApoE4 genotype. Our investigation revealed elevated levels of HS in the cerebrovasculature of AD patients with severe CAA. Additionally, these patients exhibited higher colocalization of HS with Aβ in the cerebrovasculature, including both endothelial and vascular smooth muscle cell compartments. Intriguingly, a reversal in the polarized expression of HS within the cerebral vasculature was detected in AD patients with severe CAA, suggesting a potential role in CAA development. Furthermore, male patients exhibited lower levels of both parenchymal and cerebrovascular HS. Additionally, ApoE4 carriers displayed heightened cerebrovascular Aβ expression and a tendency of elevated cerebrovascular HS levels in AD patients with severe CAA. Overall, these findings shed light on the intricate interplay between HS, Aβ, ApoE, and vascular pathology in AD, underscoring the potential roles of cerebrovascular HS in CAA development and AD pathology. Further exploring the underlying mechanisms may present novel therapeutic avenues for AD treatment.

Mesentery was discovered as a new organ in 2017. It is a continuous membranous tissue from the duodenojejunal flexure to the anorectal junction. It has distinct anatomy, physiology, and disease states. Primary mesenteropathies include vascular and non-vascular diseases. Some of them are common, and some of them are rarely seen in clinical practice. Secondary mesenteropathies occur when infection or malignancy in another organ spreads to the mesentery. Each entity has specific diagnostic and treatment protocols.

Memory decline is considered a normal part of aging, while the relationship between melatonin deficiency and cognitive function is complex and not fully understood. The present study investigated the role of melatonin deficiency functioning as a hormone at different ages on working and short-term recognition and spatial memory in rats. An age-related decline in memory function was tested in the Y-maze, the object recognition test, and the radial arm maze. Aging was associated with reduced expression of brain-derived neurotrophic factor (BDNF) throughout the hippocampus, whereas pinealectomy exacerbated this process specifically in the CA3 region of 3- and 14-month-old rats. The region-specific reduced expression of the extracellular signal-regulated kinase (ERK)1/2 and pERK1/2 was observed in young adult rats with pinealectomy. However, in middle-aged rats, the expression of these signaling molecules was either downregulated or upregulated in different hippocampal regions. The reduced ratio of pCREB/CREB in the frontal cortex and hippocampus was associated with memory impairment in young adult and middle-aged melatonin-deficient rats, whereas old rats were unaffected. Our study provides insights into the molecular pathways involved in age-related memory changes associated with melatonin deficiency, highlighting the importance of the BDNF / ERK1/2 / CREB pathway in the hippocampus and suggesting a critical period for intervention.

The objective of this study was to evaluate the genetic effects involved on pepper fruit post-harvest water loss, and correlated to morphology traits. Fruits of eight landraces of C. baccatum, and their 28 hybrids, were evaluated in a randomized complete block design. Analysis of variance, diallel analysis, phenotypic and genotypic correlation were performed to compare fruit water loss (WL), width (FW), length (FL), total soluble solids (TSS), dry matter content (DMC), pericarp thickness (PT), cuticle thickness (CT), and exocarp thickness (ET). WL varied from 14 to 68% during storage. Non-additive effects played more important role than additive, including CT, EP and TSS. Effective strategies to reduce WL should be achieved by repeated backcrosses followed by selection in segregating populations (SP). Therefore, the selection of hybrids should follow high specific combining ability traits. Selecting fruits with higher CT and lower TSS values are indirectly selecting fruits with lower WL. Varieties with low WL can be breed using landraces 04 and 58 as parents or by the hybrid 04 x 44 in open lines in SP. Brazilian C. baccatum landraces are a source of genetic variability, and the SP emerging from crossing lines with reduced WL should develop new ways for conventional breeding.

Rationale: Post-hepatectomy liver failure (PHLF) remains a significant risk for patients undergoing partial hepatectomy (PHx). Reliable prognostic markers and treatments to enhance liver regeneration are lacking. Plasma nanoparticles, including lipoproteins, exosomes, and extracellular vesicles (EVs), can reflect systemic and tissue-wide proteostasis and stress, potentially aiding liver regeneration. However, their role in PHLF is still unknow. Methods: Our study included 9 patients with hepatocellular carcinoma (HCC) undergoing PHx: 3 patients with PHLF, 3 patients undergoing the Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS) procedure and three matched controls without complications after PHx. Patient plasma was collected before (PRE), 1 and 5 days (POD1, POD5) after PHx. EVs were isolated by ultracentrifugation and extracted proteins subjected to quantitative mass spectrometry using a super-SILAC mix prepared from primary and cancer cell-lines. Results: We identified 2625 and quantified 2570 proteins in EVs in PHx patients. Among these, 53 proteins were significantly upregulated and 32 were downregulated in patients with PHLF compared to those without PHLF. Furthermore, 110 proteins were upregulated and 78 were downregulated in PHLF compared to patients undergoing ALPPS. The EV-proteomic signature in PHLF indicates significant disruptions in protein translation, proteostasis, intracellular vesicle biogenesis, as well as alterations in proteins involved in extracellular matrix (ECM) remodeling, metabolic and cell cycle pathways, present already before PHx. Conclusion: Longitudinal proteomic analysis of EV´s circulating in human patient plasma undergoing PHx uncovers proteomic signatures associated with PHLF which reflect dying hepatocytes and endothelial cells and are present before PHx already. Our results support EVs as potential biomarkers and therapeutic targets for liver regeneration and failure.

Background: Endometriosis is a female chronic inflammatory disease in which endometrial tissue develops outside the uterine cavity. It is a complex pathology, that significantly contributes to morbidity in premenopausal women, leading to chronic pain, infertility, and subfertility negatively impacting the physical, and emotional well-being and overall quality of life. The public health burden of endometriosis remains elusive and challenging to determine, and this uncertainty can lead to inadequate healthcare services and treatments. Objective: To estimate the incidence and prevalence of endometriosis in Italy using the hospital discharge records database. Population-based retrospective study. Nationwide between 2011 and 2020. Methods: From the National Hospital Discharge Database were selected all admissions with a diagnosis of endometriosis (ICD-9-CM, codes 617.x), supported by the presence of a procedure code of laparoscopy or any other surgical procedure allowing direct visualisation of the lesions. Main outcomes measures Incidence and prevalence of endometriosis were estimated for the entire 2010-2020 period and by individual year, analysing the time trend and variability in different geographical areas of Italy. Results: A total of 134,667,646 women aged 15–50 years with one or more hospitalisations for endometriosis in all Italian hospitals. The incidence of endometriosis in Italy during this period was 0.839 per 1000 women (CI95% 0.834-0.844), exhibiting a statistically significant decreasing trend over the years. A discernible north-south gradient was observed, with higher rates documented in the northern regions. The prevalence rate stood at 14.0 per 1000 during the same period, and a similar north-south geographical gradient was identifiable in the prevalence rates as well. Conclusions: The utilization of national-level hospital data enables the generation of incidence and prevalence data for endometriosis without variations in methods and definitions, facilitating the evaluation of temporal trends and regional comparisons. Understanding and quantifying this phenomenon is essential for appropriate healthcare planning in various Italian regions.

Collisional mountain belts commonly develop intramontane basins from mechanical and isostatic subsidence during orogenic development. These frequently display a relict top surface, evidencing a change interval from basin infilling to erosion often via capture or overspill. Such surfaces provide markers that inform on orogenic growth patterns via climate and base level interplay. Here, we describe the top surface from the Sorbas Basin, a key intramontane basin within the Betic Cordillera (SE Spain). The surface is fragmentary comprising high elevation hilltops and discontinuous ridges developed onto the variably deformed final basin infill outcrop (Gochar Formation). We reconstruct surface configuration using DEM interpolation and apply ¹⁰Be/²⁶Al cosmonuclides to assess surface formation timing. The surface is a degraded Early Pleistocene erosional pediment developed via autogenic switching of alluvial fan streams under stable dryland climate and base level conditions. Base level lowering since the Middle Pleistocene focused headwards incision up interfan drainages, culminating in fan head capture and fan morphological preservation within the abandoned surface. Post abandonment erosion has lowered the basin surface by 31 m (average) and removed ~5.95 km³ of fill. Regional basin comparisons reveal a phase of Early Pleistocene surface formation, marking landscape stability following the most recent Pliocene-Early Pleistocene mountain building. Post-surface erosion rate quantification is low and in accordance with ¹⁰Be denudation rates typical of the low uplift Betic Cordillera.

Omentin is an adipokine mainly produced by visceral fat tissue, and it has two isoforms: omentin-1 and omentin-2. Omentin-1 is predominantly secreted by visceral adipose tissue, deriving specially from the stromal vascular fraction cells of white adipose tissue (WAT). Levels of omentin-1 are also expressed in other WAT depots, like epicardial adipose tissue. Omentin-1 exerts several beneficial effects in glucose homeostasis in obesity and diabetes. In addition, research has suggested that omentin may have atheroprotective (protective against the development of atherosclerosis) and anti-inflammatory effects, potentially contributing to cardiovascular health. This review highlights the potential therapeutic targets of omentin-1 in metabolic-related disorders.

Photon-counting Computed Tomography (PCCT) is a promising cardiovascular-imaging technique. Using detectors that count the number and energy of photons in multiple bins, PCCT offers several advantages over conventional CT, including a higher image quality, reduced contrast agent volume, radiation doses, and artifacts. Although PCCT is well established for cardiac imaging in assessing coronary artery disease, its application in vascular imaging remains limited. This review summarizes the available literature and provides an overview of the current use of PCCT for the diagnosis of vascular conditions. Of the 13 records selected in the initial search, 7 articles were included in the present review: 6 cohort studies and 1 case report. This review synthesized the available literature on PCCT in vascular imaging, focusing mainly on endoleaks detection and characterization after endovascular aneurysm repair (EVAR), contrast dose volume, and radiation exposure reduction, particularly in patients with chronic kidney disease and in those requiring follow-up CT.

Mammography is the gold standard for breast cancer screening and diagnostic imaging; however, there is an unmet clinical need for complementary methods to detect lesions not characterized by mammography. Far-infrared 'thermogram' breast imaging can map the skin temperature, and signal inversion with components analysis can be used to identify the mechanisms of thermal image generation of the vasculature using dynamic thermal data. This work focuses on using dynamic infrared breast imaging to identify the thermal response of the stationary vascular system and the physiologic vascular response to a temperature stimulus affected by vasomodulation. The recorded data is analyzed by converting the diffusive heat propagation into a virtual wave and identifying the reflection using component analysis. Clear images of passive thermal reflection and thermal response to vasomodulation were obtained. Validation of this proposed paradigm through further clinical exploration may demonstrate clinical utility for the IR modality in diagnostic imaging, offering a potential solution to the current unmet clinical need.

Term vascular dysfunctional refers to a wide spectrum of vascular abnormalities including pathogenesis of tumors, their proliferation and leading to malfunctioned conditions. The treatment of most of the vascular anomalies including peripheral arterial disease and cardiac disease is multi factor procedure which include the embolic therapy, laser-based treatments and coagulation are all plating important role in managing the disease associated with vascular breakdown. The research proposal defines the treatment and diagnosis procedures involved in treatment of vascular abnormalities with a deep emphasis on techniques, efficiency and complications resulted from various other procedure and use of mapping and sequencing techniques based on genetics of variants of selected genes PIk3CA which will ultimately be more effective.

Background: During anatomy (topographic) chair, we prepared an anatomic piece of an older female pelvis (unknown causa mortis). Here, we present an anatomic piece prepared by medical students that helped us to better understand hypertrophic bladder pathophysiology. Methods: A traditional corpse dissection guided by an assistant professor. Results: Corpse dissection enhanced our personal experience during the medical course. It also helped us to better visualize how big a hypertrophic urinary bladder can become as the etiologic cause is not taken care. Conclusions: Despite virtual and 3D anatomy lessons, we believe corpse dissection must remain as a teaching strategy that can help to build a new generation of surgeons as well as honor the History of Medicine.