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.

The focus of this article is the evaluation of the quality and the degree of community engagement in an expert-based, public-health communicative intervention for Alcohol Use Disorder (AUD). In 2023 the Canadian Alcohol Use Disorder Society collaborated with a grass-roots community health group, a regional health authority, and an academic participatory researcher to organize a working group to mount a social-marketing campaign to increase community support for AUD medical treatment in family-practice settings in a rural community in British Columbia. The partnership working group conducted a series of activities in the school system, the town council, and the community. This article covers the formative evaluation and the summative evaluation of the working group's effectiveness. The formative evaluation ("lessons learned" and "recommendations") consists of consensus evaluations of the quality of each activity using a variety of data sources. The formative evaluation followed improvement science methods and used consensus meetings to provide and reflect on formal and informal feedback. Formative results reflect the consensus of the participants in the working group and they record the reactions in the community. The summative evaluation measures evidence of community engagement found in transcribed text from meeting minutes. The summative evaluation used theory-based frameworks and text data visualization to assess the engagement dynamics of the working group. The summative evaluation helps to put the formative evaluation into perspective as communicative action. The summative evaluation validates the formative evaluation by revealing the communicative dynamics of engagement which resulted in the community’s increased capacity to understand and support Alcohol Use Disorder Treatment options. The working group and the entire intervention was seen by the participants and the public as a success and capable of replication. In a small community, it instilled new understandings and attitudes, bringing an emerging awareness of medication as an optional health mitigation strategy for Alcohol Use Disorder. Our study furthers this overall assessment by using theoretical constructs and analysis of communicative records to trace engagement characteristics of interest to researchers, societies, and community groups contemplating similar interventions in the future. The study also validates the effectiveness of communicative analysis as a measure of social-marketing for expert-based public health interventions.

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.

Background: Mental capacity is a fundamental aspect that enables patients to fully par-ticipate in various healthcare procedures. To assist healthcare professionals (HCPs) in assessing patients' capacity, especially in the mental health field, several standardized tools have been developed. These tools include the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), and the Competence Assessment Tool for Psychiatric Advance Directives (CAT-PAD). The core dimensions explored by these tools include Understanding, Appreciation, Reasoning, and Expression of a choice. Objective: This meta-analysis aimed to investigate potential differences in deci-sion-making capacity within the healthcare context among groups of patients with bi-polar disorder (BD) and schizophrenia spectrum disorder (SSD). Methods: A systematic search was conducted on Medline/Pubmed, and Scopus. Addi-tionally, Google Scholar was manually inspected, and a manual search of emerging re-views and reference lists of the retrieved papers was performed. Eligible studies were specifically cross-sectional, utilizing standardized assessment tools, and involving pa-tients diagnosed with BD and SSD. Data from the studies were independently extracted and pooled using random-effect models. Hedges g was used as a measure for outcomes. Results: Six studies were identified, with three studies using the MacCAT-CR, two studies the MacCAT-T, and one the CAT-PAD. The participants included 189 individuals with BD and 324 individuals with SSD. The meta-analysis revealed that patients with BD performed slightly better, and the difference was statistically significant, compared to patients with SSD, particularly in the domain of Appreciation (ES=0.23, 95% CI: 0.01 to 0.04, p=0.037). There was no statistically significant difference between the two groups for Understanding (ES=0.09, 95% CI: - 0.10 to 0.27, p=0.352), Reasoning (ES=0.18, 95% CI: - 0.12 to 0.47, p=0.074), and Expression of a choice (ES = 0.23, 95% CI: - 0.01 to 0.48, p=0.60). In the sensitivity analysis, furthermore, when considering only studies involving patients in symptomatic remission, the difference for Appreciation also resulted in non-significant (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). Conclusions: These findings indicate that there are no significant differences between patients with BD and SSD during remission phases, while differences are minimal during acute phases. The usefulness of standardized assessment of capacity at any stage of the illness should be considered, both for diagnostic-therapeutic phases and for research and advance directives. Further studies are necessary to understand the reasons for the overlap in capacity between the two diagnostic categories compared in this study.

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.

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.

Music has the innate potential to reach all parts of the brain, stimulates certain brain areas which are not achievable through other modalities. Music Therapy (MT) is being used for more than a century to treat individuals who needs personalized care. MT optimizes motor, speech and language responsibilities of the brain and improves cognitive performance. Pervasive developmentdisorder (PDD) is a multifaceted, neuro developmental disorder and autism spectrum disorder (ASD) comes under PDD, which is defined by deficiencies in three principal spheres: social connection with others, communicative and normal movement skills. The conventional imaging studies illustrate reduced brain area connectivity in people with ASD, involving selected parts of the brain cortex. People with ASD express much interest in musical activities which engages the brain network areas and improves communication and social skills.The main objective of this review is to analyze the potential role of MT in treating the neurological conditions, particularly ASD. Evidence based studies have reported the extensive therapeutic application of music on various part of the brain in a nonverbal child with autism through hearing or making music.Hence we hypothesized that MT intervention can improve the communication capacity in people with ASD, than customary neurorestoration therapy alone.

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.

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.

Artificial Intelligence (AI) is rapidly transforming the field of medicine, announcing a new era of innovation and efficiency. Among AI programs designed for general use ChatGPT holds a prom-inent position using an innovative language model developed by OpenAI. Thanks to the use of deep learning techniques, ChatGPT stands out as an exceptionally viable tool, renowned for gen-erating human-like responses to queries. Various medical specialties, including rheumatology, oncology, psychiatry, internal medicine, and ophthalmology, have been explored for ChatGPT in-tegration, with pilot studies and trials revealing each field's potential benefits and challenges. However, the field of genetics and genetic counseling, as well as that of rare disorders, represents an area suitable for exploration, with its complex data sets and the need for personalized patient care. In this review, we synthesize the wide range of potential applications for ChatGPT in the medical field, highlighting its benefits and limitations. We pay special attention to rare and genetic disorders, aiming to shed light on the future roles of AI-driven chatbots in healthcare. Our goal is to pave the way for a healthcare system that is more knowledgeable, efficient, and centered around patient needs.

Urea cycle disorders (UCDs) are common inborn errors of metabolism, with an incidence of one in 30,000 births. They are caused by deficiencies in any of six enzymes and two carrier proteins, the most common being Ornithine Transcarbamylase Deficiency (OTCD). OTCD results in impairment to excrete nitrogen, causing toxic buildup of ammonia with resultant encephalopathy. Hyperammonemia (HA) induces the conversion of glutamate to glutamine in the brain. Excess glutamine in the brain causes osmotic changes cerebral edema, changes in astrocyte morphology, and cell death. Acute symptoms of HA include vomiting, hyperventilation, seizures, and irritability. Long-term neurological changes include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of plasma ammonia level at presentation and duration of hyperammonemic coma. We provide a comprehensive analysis of a 16-year-old male with neonatal onset of OTCD as an example of how brain biomarkers may be useful to monitor disease course and outcome. This male presented at 8 days post natal with plasma ammonia and glutamine of 677 and 4024 micromol/L and had a missense mutation in Exon 4 (p.R129H). Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. He suffered recurrent acute hyperammonemic episodes despite compliance, triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI based disease biomarkers.

Introduction: Substance-induced psychotic disorder (SIPD) is a mental health condition linked to the use of a psychotropic substance whose pathogenesis has not been totally clarified. The present retrospective observational study has the objective to identify differences in clinical features and peripheral biomarkers in SIPD patients according to the main substance of abuse.Methods: A total sample of 218 patients was divided in 3 groups according to the type of consumed substance: alcohol, cannabis and psychostimulants. The 3 groups were compared for continuous variables by one-way analyses of variance (ANOVAs) and for qualitative variables by χ² tests. After removing alcohol-induced psychotic disorder group, the same analyses were repeated. Statistically significant variables from these latter analyses were included in a binary logistic regression model to confirm their reliability as predictors for cannabis- or psychostimulants-induced psychotic disorders. Results: Psychotic cannabis abusers were younger (p<0.01) and had an earlier age at onset (p<0.01). On the contrary, alcohol consumers resulted to have a longer duration of illness (p<0.01), more previous hospitalizations (p=0.04), more frequent medical comorbidity (p<0.01), higher mean Modified Sad Person Scale scores (p<0.01). Finally, psychostimulant abusers had more frequently a lifetime history of poly-substance use disorders (p<0.01). Binary logistic regression revealed that higher mean Brief Psychiatric Rating Scale scores (p<0.01) higher sodium (p=0.012) and haemoglobin(p=0.040) plasma levels were predictors of cannabis misuse in SIPD patients.Conclusions: Different clinical factors and biochemical parameters con be associated to SIPD according to the main substance of abuse, thus requiring a specific management by clinicians.

Limited understanding exists regarding the intricate dynamics between the levels of social inhi-bition exhibited by both wives and husbands concerning their perceived family support and de-pressive symptoms, particularly within couples who are parents of children diagnosed with au-tism spectrum disorder (ASD). This study used the actor-partner, interdependence mediation model to analyze data collected from 397 pairs of Chinese parents with children diagnosed with ASD. The findings of the study revealed significant indirect actor effects, indicating that the levels of social inhibition exhibited by both wives and husbands were associated with their own de-pressive symptoms through their respective perceptions of family support. In general, the study did not find significant partner effects, except for some indirect effect (IE) of wives on their hus-bands' depressive symptoms through the wives' perceived social support. This observation sug-gests that cultural norms and role expectations within the family context may influence these dy-namics. These results underscore the potential importance of interventions aimed at addressing social inhibition and enhancing perceived family support to alleviate depressive symptoms in this population. Additionally, interventions targeting fathers should emphasize the importance of their involvement in parenting and collaboration with their partners in caring for children with ASD. Such collaborative efforts may contribute to improved outcomes for both parents and chil-dren within families affected by ASD.

Intrinsically Disordered Proteins (IDPs) play crucial roles in signal transduction, cell differentiation, and transcriptional regulation. Many disrupted genes associated with mental disorders are identified as IDPs, and emerging evidence suggests the functional role of IDPs in neuropsychiatric disorders. However, few studies comprehensively explore the functional association between protein disorder properties and different mental diseases. To address this gap, we collected disrupted gene sets for seven mental diseases (MDD, SCZ, BP, ID, AD, ADHD, ASD) and a control gene set from normal brains using DisGeNET and GeneCards databases. The state-of-the-art predictor IUPred2A was then utilized to calculate the disorder properties , followed by a thorough comparison between the disordered proteins in mental diseases and healthy controls. Functional enrichment analysis and protein-protein interaction networks were conducted to investigate the IDPs’ functional roles in psychiatric diseases. Additionally, we demonstrated the role of IDPs in protein binding formations through a case study of alpha-synuclein using protein docking. Our findings reveal that differentially expressed proteins in mental disorders, especially in ASD and ADHD, exhibit more IDPs than those in healthy controls. IDPs in psychiatric disorders are significantly enriched in neurodevelopmental pathways and play an important role in in gene expression regulation. Our results indicate distinct functional patterns of disorder proteins among mental diseases and healthy controls. When comparing the IDPs between ASD and ADHD, we observed that IDPs in ADHD are more likely linked to the synaptic signaling and regulation, while IDPs in ASD are more tendentiously related to diverse and complex biological processes. Our work offers valuable insights into the important functions of IDPs in psychiatric disorders, enhancing our understanding of the molecular mechanisms involved in psychiatric disorders.

The article presents the potential of liposomal cannabidiol in the treatment of Panic Disorder, when used in integration with Complex Cognitive Psychotherapy. The advantages of the integrated treatment, developed by the Author, and based on the use of liposomal cannabidiol combined with cognitive psychotherapy, are discussed. A new and original tool is presented and described, developed, and tested for the first time by the Author and called NegEnt Panic Blocker.

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.

To explore the relevant factors that affect the efficacy of consciousness-regaining therapy (CRT)for prolonged disorder of consciousness(pDOC),a retrospective analysis was conducted on the case data of 114 patients with pDOC admitted to department of functional neurosurgery of Tianjin Huanhu Hospital from January 2019 to January 2022. Basic information on the cases,data on pDOC disease assessment, consciousness-regaining therapy methods, and efficacy evaluation were collected. A total of 114 patients were grouped and compared based on the efficacy at the end of treatment. Among them, there were 61 cases in the ineffective group and 53 cases in the effective group. There was no statistically significant difference (P&gt;0.05) between the two groups in terms of gender, age, etiology, acute cerebral herniation, emergency craniotomy surgery, emergency decompressive craniectomy, time from onset to start of consciousness-regaining therapy , and duration of consciousness-regaining therapy(P&gt;0.05). However, there were statistically significant differences (P&lt;0.05) in terms of secondary hydrocephalus, , consciousness-regaining therapy methods, CRS-R grading before treatment, and GOSE score at 6 months after treatment. Binary logistic regression analysis showed that the type of therapy (OR=0.169, 95% CI: 0.057-0.508) was a related factor affecting the efficacy of consciousness-regaining therapy (P&lt;0.05).Compared with non-invasive therapy, personalized awakening therapy using various invasive consciousness-regaining therapy methods can help improve the efficacy of therapy for pDOC.

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.

Psychosis can be defined as a combination of psychopathological symptoms including delusions and/or hallucinations without insight. Psychotic disorders may configure a primary psychiatric illness or represent the result of a functional/structural brain damage induced by substance use, neurological diseases or other medical conditions. They are multifactorial disorders in which genetic, environmental and gene-environment interaction factors contribute to the expressiveness of the symptoms. Among the environmental factors, psychotropic substances represent the most important removable facilitators of psychosis. In our study, we compared the prevalence of substance induced psychosis between a sample of patients affected by cannabis use disorder and a sample of patients affected by cocaine use disorder analyzing retrospectively the data of outpatients with no personal or family history of psychiatric illnesses.

Obsessive–compulsive disorder (OCD) is believed to follow a waxing and waning course, often according to environmental stressors. During the COVID-19 pandemic, pre-existing OCD symptoms were reported to increase and to change from checking to washing behaviors, while new-onset symptoms were predominantly of the hoarding type. In the present study, we followed the evolution of OCD symptoms, anxiety, depression, and insight of illness in forty-six OCD patients throughout the pandemic. Clinical measures were collected at four different time points before and during the COVID-19 pandemic in Italy. Within-subject comparisons were used to compare clinical scale scores across time, and correlations were examined between patients' baseline characteristics and changes in clinical scores. We found that all clinical measures increased during the first Italian lockdown, with respect to the pre-pandemic values. Anxiety decreased during the temporary elimination of restriction provisions, whereas severity of OCD symptoms and insight returned to pre-pandemic values during the second mandatory lockdown. These results were observed only in two sub-groups of patients: those taking benzodiazepines and those with shorter illness duration. Our findings suggest the need of additional clinical attention to these specific sub-groups of OCD patients in case of particularly distressing circumstances, while pointing to a possible adaptive role of their OCD symptoms when the environment requires a higher care of hygiene and extraordinary supply of essential resources.

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.

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.

The evolution of human societal dynamics over the course of decades and centuries has led to an ever-increasingly complex digital modern life, one of the hallmark of which is the need for multi-tasking, inclusive of that with media. Is there an empirical mapping between this macroscopic (digital) evolution of the human societal dynamics (in terms of multi-tasking) and the microscopic evolution of the functional molecular units within cells (i.e., proteins) and their manifold cross-talks? Multi-tasking requires a certain degree of intrinsic or adapted flexibility which is as true at the bio-molecular level. Evolutionary diversification of structure-function relationship in proteins emphasizes the functional importance of intrinsically disordered entities (IDPs/IDRs) which are highly dynamic biological soft matters. Multi-functionality is favorably supported by their fluid-like shapes and other new malleable members of the protein family. The new wealth of knowledge coming from recent research on protein intrinsic disorder, fold-switching, moonlighting, hub proteins etc. has given us new insights into protein structure – functional relationship. This has led to a paradigm shift in protein science, clearly diverging from the traditional 'one structure – one function' model applicable to enzyme classes to a more complex understanding of protein functionality. This paradigm shift has caused scientists to delve deeper into the subject, exploring various evolutionary toys and tools to fit the cumulative multi-functional demands in higher organisms. This commentary covers the different evolutionary arsenals to achieve the growing multi-functionality and argues in favor of protein intrinsic disorder as probably the sharpest weapon of all.

Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, unresponsive to nutritional support, and contributes significantly to morbidity and mortality in patients with cancer. Immune dysfunction, driven by cytokine imbalance, contributes to CAC progression. This review explores the potential relationship between CAC and anti-cancer immune response in pre-clinical and clinical studies. Pre-clinical studies showcase the involvement of cytokines like IL-1β, IL-6, IL-8, IFN-γ, TNF-α, and TGF-β, in CAC. IL-6 and TNF-α, interacting with muscle and adipose tissues, induce wasting through JAK/STAT and NF-κB pathways. Myeloid-derived suppressor cells (MDSCs) exacerbate CAC by promoting inflammation. Clinical studies confirm elevated pro-inflammatory cytokines (IL-6, IL-8, TNFα) and immune markers like neutrophil-to-lymphocyte ratio (NLR) in patients with CAC. Thus, immunomodulatory mechanisms involved in CAC may impact the anti-neoplastic immune response. Inhibiting CAC mechanisms could enhance anti-cancer therapies, notably immunotherapy. R-ketorolac, a new immunomodulator, reversed weight loss and increased survival in mice. Combining these agents with immunotherapy may benefit patients with cancer experiencing CAC. Further research is vital to understand the complex interplay between tumor-induced immune dysregulation and CAC during immunotherapy.

This paper offers an in-depth exploration of the complex relationship between seasonality and Autism Spectrum Disorder (ASD). It reviews existing research, providing a comprehensive summary of findings and highlighting the multifaceted dimensions of seasonality as an environmental factor that influences the etiology of ASD. The discussion encompasses various factors, including birth months, maternal health, dietary choices, and vitamin D deficiency, and delves into the intricate interplay of seasonality with environmental influences such as viral infections and solar radiation. The present study raises essential questions regarding the timing of environmental influences and the factors contributing to the rising prevalence of ASD. Ultimately, it underscores the need for future epidemiological research to incorporate more extensive investigations of environmental risk factors and employ advanced statistical analyses. This comprehensive overview contributes to a deeper understanding of how seasonality factors may be linked to the occurrence of ASD and its increasing prevalence, recognizing the multifaceted and diverse nature of these interactions.

The present review aimed to identify through what means neurologic injury can predispose individuals to Post-Traumatic Stress Disorder (PTSD). In recent years, comprehensive studies have helped to clarify which structures in the central nervous system (CNS) that, when damaged, lead to distinct PTSD symptoms–namely dissociative reactions or flashbacks. Our review narrowed its focus to three common neurologic injuries including traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and stroke. Beyond discussing the potential mechanisms by which neurotrauma may lead to PTSD, we summarized our current understanding of the pathophysiology of the disorder and discussed predicted associations between the limbic system and PTSD. In particular, the role of noradrenergic neuromodulatory signaling on the HPA axis as it pertains to fear memory recall needs to be further explored to better understand its effects on limbic structures in PTSD patients. This paper also described how damage to the CNS can alter the function of the limbic system and result in characteristic symptoms of PTSD like intrusive memories and acute psychological distress. Further, our review intended to draw attention to a lack of PTSD prognosis in TBI, SAH, and stroke patients who could benefit from early treatment. PTSD symptoms often compound with pre-existing issues further deteriorating health outcomes for these patients. It is ultimately our goal to clarify the relationship between neurotrauma and PTSD such that earlier diagnoses and appropriate treatment are observed in clinic.

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.

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: Clinical trails have revealed that patients with depression generally accompanied with learning and memory impairment, which critically impact on individual’s health and development. Danggui-Shaoyao-San (DSS), a famous Chinese complex prescription, significantly overcame depression and relieved cognitive disorder based on previous research and publication. However, its effectsand potential mechanism against chronic restraint stress (CRS) remained unknown. Methods: CRS animal model was established and mice were divided to six groups while they were oral administrated with Danggui-Shaoyao-San at doses of 1.25, 2.5 and 5 g/kg for 14 days. Emotional and cognitive performances were detected by behavior tests, meanwhile neural plasticity and its molecular mechanism were examined by Dil staining, western blot and immunofluorescence. Results: DSS treatment dose-dependently improved locomotion ability in open filed test, overcame depression behavior in forced swimming test and elevated plus maze test, enhanced learning and memory ability in Morris water maze test. CRS decreased number of total spines and mushroom spines, while DSS treatment dose-dependently restored these by Dil staining. Expression of BDNF and GluR1 were significantly down-regulated in CRS group, which were significantly normalized by DSS. Conclusions: DSS treatment dose-dependently reversed CRS-induced cognitive impairments by inducing structural remodeling of neurons.

Curcumin, found in the rhizome of turmeric, has extensive therapeutic promises via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown curcumin to be an effective treatment for multiple cancers. These effects are drived by curcumin's ability to induce G2/M cell cycle arrest, induction of autophagy, activation of apoptotic pathways, disruption of molecular signaling, inhibition of invasion and metastasis, and by increasing the efficacy of existing chemotherapeutics. Here we focused on the hormetic behaviour of curcumin. Frequently, low doses of toxins and other stressors not only are harmless but also activate an adaptive stress whereas high dose activates acute responses like autophagy and cell death. This phenomenon is referred to as hormesis. Many molecules that cause cell death elicite an initial autophagic step that is a cytoprotective mechanism relying on elimination of dysfunctional structures intracellular, notably by mitophagy. This phenomenon is considered as a primarily protective mechanism against stressors. At higher doses, cells undergo mitochondrial outer membrane permeabilization due to calcium release from the endoplasmic reticulum and die. Herein, we address the complex crosstalk between the induced mitochondrial biogenesis, mitochondrial destabilization accompanied by mitophagy and cell death that can also be at play.

Reactive attachment disorder (RAD) and disinhibited social engagement disorder (DSED) manifest in individuals facing attachment system chal-lenges, particularly observed in minors under protective measures. The lack of standardized tools for assessing these difficulties and uncertainty about the most effective instruments from a psychometric perspective prompted this study. Using the COSMIN checklist, we systematically reviewed instruments assessing RAD, adhering to PRISMA and COSMIN guidelines. Examined tools included the Disturbance Attachment Inter-view, Preschool Age Psychiatric Assessment, Relationship Patterns Questionnaire, Assessment of RAD and DSED, Development and Well-Being Assessment, and Reactive Attachment Disorder Question-naire. Of the 11 articles analyzed, results highlight a research emphasis on internal consistency, structural and construct validity, sidelining other properties. While the instruments demonstrate strong structural validity, excellent internal consistency, and generally satisfactory error measurement results, the study concludes a dearth of investigations into psychometric properties for children and adolescents under protective measures.

Mutations in the LMNA gene (encoding lamin A/C proteins) cause several human cardiac diseases, including dilated cardiomyopathies (LMNA-DCM). The main clinical risks in LMNA-DCM patients are sudden cardiac death and progressive left ventricular ejection fraction deterioration, and therefore most human and animal studies have sought to define the mechanisms through which LMNA mutations provoke cardiac alterations, with particular focus on cardiomyocytes. To investigate if LMNA mutations also cause vascular alterations that might contribute to the etiopathogenesis of LMNA-DCM, we generated and characterized Lmnaflox/floxSM22αCre mice, which constitutively lack lamin A/C in vascular smooth muscle cells (VSMCs), cardiac fibroblasts, and cardiomyocytes. Like mice with whole body or cardiomyocyte-specific lamin A/C ablation, Lmnaflox/floxSM22αCre mice recapitulated the main hallmarks of human LMNA-DCM, including ventricular systolic dysfunction, cardiac conduction defects, cardiac fibrosis, and premature death. These alterations were associated with hyperactivation of Smad3 and elevated expression of the proapoptotic protein caspase 3 in the heart. Lmnaflox/floxSM22αCre mice also exhibited perivascular fibrosis in the coronary arteries, and a switch of aortic VSMCs from the ‘contractile’ to the ‘synthetic’ phenotype. Ex vivo wire myography in isolated aortic rings revealed impaired maximum contraction capacity and an altered response to vasoconstrictor and vasodilator agents in Lmnaflox/floxSM22αCre mice. To our knowledge, our results provide the first evidence of phenotypic alterations in VSMCs that might contribute significantly to the pathophysiology of some forms of LMNA-DCM. Future work addressing the mechanisms underlying vascular defects in LMNA-DCM may open new therapeutic avenues for these diseases.

Hemodynamic relevance of differently located stenoses of the internal jugular veins remains undetermined. It particularly concerns nozzle-like strictures in the upper parts of these veins and stenotic jugular valves located at the end of this vein. This study was aimed at understanding flow disturbances caused by such stenoses. Computational fluid dynamics software, Flowsquare+, was used. We constructed 3-dimensional models of venous outflow, comprising two alternative routes: tube representing the internal jugular vein and irregular network representing the vertebral veins. At the beginning of the tube representing the internal jugular vein, differently-shaped and sized short strictures, representing nozzle-like strictures were built in. At the end of this tube, differently-shaped membranes, representing the jugular valve, were built in. With the use of computational fluid dynamics modeling, we studied how these two obstacles influenced the outflow. We found that the most relevant outflow disturbances were evoked by nozzle-like strictures in the upper part of the internal jugular vein that were either small, long or asymmetrically positioned. Very tight stenotic valves and septum-like malformed valve were equally hemodynamically relevant. These findings suggest that both upper and lower strictures of the internal jugular vein can be of clinical significance.

The formation of new blood vessels is a critical process for tumor growth and may be achieved through different mechanisms. Angiogenesis represents the first described and most studied mode of vessel formation, but tumors may also use alternative ways to secure blood supply and eventually acquire resistance to anti-angiogenic treatments. These non-angiogenic mechanisms have been described more recently and include intussusceptive microvascular growth (IMG), vascular co-option, and vasculogenic mimicry. Like solid tumors, also in lymphomas angiogenic and non-angiogenic pathways play a fundamental role in tumor growth and progression. In view of the relevant prognostic and therapeutic implications, a comprehensive understanding of these mechanisms is of paramount importance for improving the efficacy of treatment in patients with lymphoma. In this review, we summarize the current knowledge on angiogenic and non-angiogenic mechanisms involved in the formation of new blood vessels in Hodgkin’s and non-Hodgkin’s lymphomas.

Specific proteolytic cleavages turn on, modify, or turn off the activity of vascular endothelial growth factors (VEGFs). Proteolysis is most prominent among the lymph­angiogenic VEGF-C and VEGF-D, which are synthesized as precursors that need to undergo enzymatic removal of their C- and N-terminal propeptides before they can activate their receptors. The activating cleavage of VEGF-C is mediated by at least five different proteases: plasmin, ADAMTS3, prostate-specific antigen, cathepsin D, and thrombin. All of these proteases except for ADAMTS3 can also activate VEGF-D. Processing by different proteases results in distinct forms of the "mature" growth factors, which differ in affinity and receptor activation potential. The “default” VEGF-C-activating enzyme ADAMTS3 does not activate VEGF-D and therefore, VEGF-C and VEGF-D do function in different contexts. VEGF-C itself is also regulated in different contexts by different proteases. During embryonic development, ADAMTS3 activates VEGF-C. In contrast, thrombin and plasmin likely activate VEGF-C/-D during tissue injury-induced lymphangiogenesis, and PSA and cathepsin D perhaps during tumor-associated pathological lymphangio­genesis. Additionally, cathepsin D from saliva might activate latent VEGF-C/-D upon wound licking, thereby accelerating healing. Similar to tyrosine kinase receptors and VEGFs themselves, these activating proteases could be targeted to modulate angiogenesis and lymphangiogenesis in relevant diseases.

Panic disorder (PD) is characterized by recurrent and uncontrollable panic attacks associated with behavioral changes and/or persistent anxiety due to the attacks. The development of behavioral models in animals is important for the understanding of the psychobiological and behavioral bases of PD. The present article reviews the main models used in the current literature. Biobehavioral assays used in rats and mice include fear conditioning (which presents moderate predictive, face, and construct validities); the elevated T-maze (which presents good predictive validity, but low face and construct validities); electrical stimulation of the periaqueductal gray (which presents good face validity, but moderate construct validity); predator exposure models (which present good predictive and moderate construct validity); and hypercapnia-induced responses (which present moderate construct validity). These three approaches seek coherence with theories on fear as a way to increase its translational potential; thus, while the elevated T-maze is supported by the Deakin/Graeff theory, the mouse defense test battery relies on the concept of defensive distance, and periaqueductal gray stimulation is based on the functional neuroanatomy of fear. Moreover, to higher or lower degree the three models are supported by an “etho-experimental” approach, with careful observation of animal behavior as a way of discriminating different defensive strategies that model different aspects of anxiety, fear, and panic. These assays can be used, in conjunction with independent variables that attempt to simulate the vulnerabilities and stressors which lead to panic attacks, to produce true models of PD. Finally, an alternative/complementary model is proposed that uses zebrafish alarm reaction to study this disorder.

1) Background: Bipolar or manic-depressive disorder is a malign mental disease that frequently faces social stigma. Educational and thinking models are needed to increase people’s awareness and understanding of the disorder. The arts have potential to achieve this goal. 2) Methods: This paper builds on the recent use of heavy metal music as a thinking and education model. It emphasizes the artistic component of heavy metal and its potential to characterize the symptomatology during the episodes of (hypo)mania and depression and the recurrence of these episodes. Heavy metal music has diversified into subgenres that become allegorical to both the symptoms of episodes and the recurrence of bipolar cycles. 3) Results: Examples of songs are given that mirror distinct facets of the disorder. 4) Conclusion: Although the links drawn between art (music) and science (psychiatry) are inherently subjective, such connections might be used to trigger a learning process, facilitate judgment and decision-making, and induce affective reactions and memory formation in the listener. The approach may facilitate collaborative efforts and serve healthcare professionals and educators as a communication tool to aid the public’s comprehension of the disease and an associated social paradox: On one hand, bipolar disorder incurs substantial costs to society. On the other hand, it benefits from the creative artistic and scientific endeavors of bipolar individuals from which cultural and political gains may ensue.

Considering the harmful effects of cannabis on individuals with a severe mental disorder and the limited effectiveness of current interventions, this case report showcases the beneficial results of a 10-session Avatar intervention for cannabis use disorder (CUD) on a polysubstance user with a comorbid schizoaffective disorder. Virtual reality allowed the creation of an Avatar representing a person significantly related to the patient’s drug use. Avatar intervention for CUD aims to combine exposure, relational, and cognitive behavioral therapies while practicing real-life situations and learning how to manage negative emotions and cravings. Throughout therapy and later on, Mr. C managed to maintain abstinence from all substances. Also, an improvement in the severity of CUD as well as a greater motivation to change consumption, were observed after therapy. As observed by his mother, his psychiatrist, and himself, the benefits of Avatar intervention for CUD extended to other spheres of his life. The drastic results observed in this patient could be promising as an alternative to the current treatment available for people with a dual diagnosis of cannabis use disorder and psychotic disorder, which generally lack effectiveness. A single-blind randomized control trial comparing the treatment with a classical intervention in a larger sample is currently underway to evaluate whether the results are reproducible on a larger sample.

Patients with a psychotic disorder frequently report oral health problems, while mental health nurses (MHNs) seem not to be fully aware of these problems and the risk factors. Therefore, this study aims to develop supportive tools for MHNs regarding oral health to increase sensitization among MHNs and to provide MHNs with knowledge to recognize (potential) oral health problems in patients with a psychotic disorder. We used a human-centered design in which the user, MHNs as well as experts by experience, were placed in the centre of the research process. Problems and needs in MHNs working with patients with a psychotic disorder were addressed. To identify key issues of problem as well as the needs in terms of resources, we started with focus groups (n = 9). We analysed the data thematically based on context of patients and MHNs in practice regarding oral health, preferred oral health tools focused on MHN, and intended outcomes of tools. A Multi Criteria Decision Matrix was developed and analysed (n = 9) to identify the most optimal and viable solution based on established criteria and issues that are prevalent in the work of MHNs. Most promising result was the development of a brochure with an awareness screener. The brochure with awareness screener was developed as a low-fidelity prototype for MHNs regarding oral health in patients with a psychotic disorder, based on the latest scientific evidence. After testing it, the feasibility was tested through semi-structured interviews (n=19). MHNs and experts by experience were satisfied with the tool and provided recommendations for adjustments to the content. Significant augmentations to the brochure include a clinical lesson and a toothbrush with toothpaste for patients. We can conclude that a brochure with an awareness screener is feasible for MHNs. Future steps aiming to further refine and optimize care processes for oral health tools in MHNs, should take refining eligibility criteria for psychiatric populations and the language level of the target group of a tool into account.

Magnesium alloy stents have been extensively studied in the field of biodegradable metal stents due to their exceptional biocompatibility, biodegradability and excellent biomechanical properties. Nevertheless, the specific in vivo service environment causes magnesium alloy stents to degrade rapidly and fail to provide sufficient support for certain time. This paper presents an overview of the development history and protection strategies for magnesium alloy stents. Alloying, optimizing stent structure and preparing protective coating have improved the corrosion resistance of magnesium alloy stents. Based on the corrosion mechanism of magnesium alloy stents, as well as their deformation during use and environmental characteristics, we present some novel solution strategies aiming at reducing the corrosion rate of magnesium alloys and enhancing the comprehensive performance of magnesium alloy stents. These strategies include adapting protective coatings for the deformation of the stents, preparing rapid endothelialization coatings to enhance the service environment of the stent, and constructing coatings with self-healing functions. It is hoped that this review can help to understand the development of magnesium alloy cardiovascular stents and solve the problems related to magnesium alloy stents in clinical applications at the early implantation stage.

Several noninvasive vascular biomarkers have been suggested for improving the risk stratification for atherothrombotic events. To identify biomarkers suitable for detecting intermediate-risk individuals who might benefit from lipid-lowering treatment (L-LT) in primary prevention, the present study tested the association of plasma LDL-cholesterol with coronary artery calcification (CAC) Agatston score, high carotid and femoral intima-media thickness (IMT), low carotid distensibility and high carotid-femoral pulse-wave velocity in 260 asymptomatic individuals at intermediate cardiovascular risk and free of diabetes and L-LT. High or low vascular biomarkers were considered when their value was above the 95th or below the 5th percentile, respectively, of the distribution in the healthy or in the study population. LDL-cholesterol was independently associated with the CAC score =0 (OR 0.67; 95%CI 0.48-0.92, P=0.01), CAC score >100 (1.59; 1.08-2.39, P=0.01) and with high femoral IMT (1.89; 1.19-3.06, P<0.01), but not with other biomarkers. Our data confirm that in the presence of CAC score =0 in individuals at intermediate risk, L-LT can be avoided, while it should be used in those with CAC score >100. Femoral artery IMT could represent a useful biomarker for decision regarding L-LT, however the reference values according to sex and age should be established in a large healthy population

Coronavirus Disease 2019 (COVID-19) is the pandemic challenge of the last year. Cardiovascular involvement is one of the main characteristics of this disease. Due to endothelial damage, consequent phlogosis may increase a thrombosis risk. Cardiac injury may occur in different ways. However, an ischemic involvement of the cardiovascular system is rarely implied. In this regard, direct and indirect effects of COVID-19 are described. Nonetheless, the possible evaluation of the cardiovascular system may require different modalities. The cardiovascular evaluation may be different in emergency compared to critical care, requiring different tools for each setting. The aim of this review is to explore these modalities according to the different involvement of the cardiovascular system..

“White matter disease” identifies series of different conditions and pathological mechanisms: autoimmune, infectious, toxic-metabolic and vascular. Each of these leads to a global impairment of the neural myelination process through the secondary destruction of previously myelinated structures. To date, the imaging spectrum represents an irreplaceable tool to detect these lesions, describe their distribution patterns and stage them over time. This study aims presents a pictorial review of white matter disease, from pathology to imaging spectrum, reporting current main staging systems with greater emphasis to relationship between cerebrovascular disease and white matter hyper-intensity appearance, and the newest advances in this field.

Many lifestyle and occupational habits negatively impact on physical and mental health, increasing the risk of cardiovascular and other diseases. While larger institutions fulfill occupational health requirements to ensure their employees’ wellbeing at work, smaller business workers and entrepreneurs may neglect initial signs of stress or physical decline, putting themselves at increased risk. Early detection of compromised cardiopulmonary health or fitness has the potential to flag up indications for early interventions and reduce the risk of disease onset and progression. This case study highlights the usefulness of respiratory muscle training (RMT) in improving pulmonary and cardiovascular parameters as an early countermeasure to cardiopulmonary decline. We suggest RMT as an easily accessible, cost- and time effective opportunity to support a healthy lifestyle.

In this work, we explore the intrinsic disorder status of the three members of the synuclein family of proteins - α-, β-, and γ-synucleins. We also analyzed the peculiarities of the amino acid sequences and modeled 3D structures of the human synuclein family members to find potential effects of pathological mutations. Furthermore, we conducted a comparative sequence-based analysis of the synuclein proteins from various evolutionary distant species and evaluated their levels of intrinsic disorder using a set of commonly used bioinformatics tools. Next, we conducted a detailed functional disorder analysis of the proteins in the interactomes of the human synuclein family members using various web-based disorder analysis and prediction tools, such as RIDAO, D2P2 and FuzDrop. We identify that the interactome of human α-synuclein has relatively higher levels of intrinsic disorder, as compared to the interactomes of human β- and γ- synucleins. These observations highlight the critical importance of intrinsic disorder of human α-synuclein and its interactors in neuronal processes as compared to other proteins of the synuclein family.

Hispidulin is a natural bioactive flavonoid that has been studied for its potential therapeutic properties, including its anti-inflammatory, antioxidant, and neuroprotective effects. The aim of this study was to explore whether hispidulin could inhibit endothelial inflammation triggered by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS). The adhesion of monocytes to vascular endothelium was evaluated by in vitro and ex vivo monocyte adhesion assays. We analyze the migration of monocytes across the endothelial layer using transmigration assay. The result showed that treatment with hispidulin decreased P. gingivalis LPS-induced the adhesion of monocytes to endothelial cells and their migration by suppressing P. gingivalis LPS-triggered expression of intercellular adhesion molecule-1 (ICAM-1) through downregulating nuclear factor-қB (NF-қB). In addition, hispidulin inhibited P. gingivalis LPS-induced mitogen-activated protein kinases (MAPKs) and AKT in endothelial cells. Altogether, the results indicate that hispidulin suppresses vascular inflammation induced by P. gingivalis LPS. Mechanistically, it prevents the adhesion of monocytes to the vascular endothelium and migration and inhibits NF-қB, MAPKs, and AKT signaling in endothelial cells.

Vitamin D status may impact acute affective symptomatology and the severity of symptoms in patients with bipolar disorder (BD). Therefore, this cross-sectional study analyzed 25(OH)D, 24,25(OH)2D, and the vitamin D metabolite ratio (VMR) in BD and correlated the results with clinical affective symptomatology and functionality. The inactive precursor 25(OH)D and its principal catabolite 24,25(OH)2D were measured simultaneously with a validated liquid chromatography tandem mass-spectrometry method in 170 BD outpatients and 138 healthy controls. VMR was calculated as follows: VMR=100*(24,25(OH)2D/25(OH)D). The psychometric assessment enclosed: Beck Depression Inventory-II, Hamilton Depression Rating Scale, Young Mania Rating Scale, Global Assessment of Functioning, and number of suicide attempts. We did not find a significant difference between patients and controls in the concentrations of 25(OH)D and 24,25(OH)2D. Additionally, the VMR was comparable in both groups. The calculations for the clinical parameters showed a negative correlation between the Young Mania Rating Scale and 24,25(OH)2D (r = -.154, p = .040). Based on the small effect size and the predominantly euthymic sample, further exploitation in individuals with manic symptoms would be needed to confirm this association. In addition, long-term clinical markers, and an assessment in different phases of the disease may provide available additional insights.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause potentially life-threatening coronavirus disease (COVID-19). COVID-19 is a multisystem disease and is associated with significant respiratory distress, systemic hyper inflammation, vasculitis and multi-organ failures. SARS-CoV-2 causes deterioration of numerous systems with increasing evidence implying that COVID-19 affects endothelium and vascular function. The endothelium is important for preserving vascular tone and homeostasis. The overactivation and dysfunction of endothelial cells are significant outcomes of severity in patients with COVID-19. The Angiopoietin 1/Tie 2 pathway plays an important role in endothelium quiescence and vessel stability. The disruption of Angiopoietins/Tie balance affects vessel contact barrier and leads to vessel leakage, and this in turn causes endothelial dysfunction. Although vascular instability through SARS-CoV-2 is associated with endothelial dysfunction, it is still not understood if the virus affects Angiopoietin/Tie axis directly or via other mechanisms such as cytokine storm and/or immune response associated with the infection. This review provides an overview of the impact SARS-CoV-2 has on endothelial function and more specifically the Angiopoietin/Tie pathway.

The brain's unique characteristics make it exceptionally susceptible to oxidative stress, which arises from an imbalance between reactive oxygen species (ROS) production, reactive nitrogen species (RNS) production, and antioxidant defense mechanisms. This review explores the factors contributing to the brain vascular tone vulnerability in the presence of oxidative damage, which can be of clinical interest in critically ill patients or presenting acute brain injuries. The brain's high metabolic rate and inefficient electron transport chain in mitochondria lead to significant ROS generation. Moreover, non-replicating neuronal cells and low repair capacity increase susceptibility to oxidative insult. ROS can influence cerebral vascular tone and permeability, with a potential impact on cerebral autoregulation. Different ROS species, including superoxide and hydrogen peroxide, exhibit vasodilatory or vasoconstrictive effects on cerebral blood vessels. Reactive nitrogen species (RNS), particularly NO and peroxynitrite, also exert vasoactive effects. This review further investigates the neuroprotective effects of antioxidants, including superoxide dismutase (SOD), vitamin C, vitamin E, and the glutathione redox system. Various studies suggest that these antioxidants could be used as adjunct therapies to protect the cerebral vascular tone during high oxidative stress conditions. Nevertheless, more extensive research is required to comprehensively grasp the relationship between oxidative stress and cerebrovascular tone, as well as to explore the potential benefits of antioxidants as adjunctive therapies in critical illnesses and acute brain injuries.

Pulmonary Hypertension (PH) is a terminal disease characterized by severe pulmonary vascular remodeling. Unfortunately, targeted therapy to prevent disease progression is limited. Here, the vascular cell populations that contribute to the molecular and morphological changes of PH in conjunction with current animal models for studying vascular remodeling in PH will be examined. The status quo of epigenetic targeting for treating vascular remodeling in different PH subtypes will be dissected, while parallel epigenetic threads between pulmonary hypertension and pathogenic cancer provide insight into future therapeutic PH opportunities.

Pathologic angiogenesis is responsible for much of the vision loss that stems from several chorioretinal vascular diseases including neovascular age-related macular degeneration (nAMD), diabetic retinopathy (DR), and retinal vein occlusion (RVO). Because vascular endothelial growth factor (VEGF) serves as a pivotal angiogenic molecule, it has emerged as the primary target for therapeutic drugs. Current anti-VEGF therapy is dominated by bevacizumab, ranibizumab, and aflibercept, all of which have been available for more than a decade, but new drugs, both biosimilars (Byooviz and Cimerli) and drugs whose primary aim is to decrease treatment burden (brolucizumab, faricimab, and the ranibizumab port delivery system), have been approved. Recent failures (conbercept, abicipar, and KSI-301) emphasize the complexity of drug development and the difficulties faced by innovators. Most therapies under development, including tyrosine kinase inhibitors and gene therapy, include VEGF-A blockade as their primary function and aim to extend durability rather than increase peak efficacy. But even as many new drugs look to extend durability, cost containment with mandated use of biosimilars serves to balance the therapeutic landscape.

Background: Antiphospholipid antibodies (aPL) are a laboratory criterion for the classification of antiphospholipid syndrome (APS), and are known to cause clinical symptoms: vascular thrombosis or obstetric complications. It is suggested that aPL may be associated with thromboembolism in severe COVID-19 cases. Aim: to combine clinical data with aPL findings at 4 time points (admission, worsening, discharge, 3-month follow-up) in patients hospitalized with COVID-19 pneumonia. Methods: current and past history of thrombosis and obstetric complications; aPL determined at 4 time points: anticardiolipin (aCL), anti-β2-glycoprotein I (anti- β2GPI) and antiphosphatidylserine/prothrombin (aPS/PT) of the IgM, IgG or IgA isotypes. Results: 111 patients with COVID-19 pneumonia were enrolled. During hospitalization, 7 patients died, 3 of them due to pulmonary artery thromboembolism (none was aPL positive). Only one of the five who developed pulmonary artery thrombosis was aPL positive. Of 9/101 patients with a history of thrombosis, 5 had arterial thrombosis and none was aPL positive at admission and follow-up; 4 had venous thrombosis and one was aPL positive at all time points (newly diagnosed APS). Of these 9/101 patients, 55.6% were transiently aPL positive at discharge only, compared to 26.1% without history of thrombosis (p=0.05). Conclusions: aPL were not associated with fatal outcomes and vascular thrombosis; aPL were transiently positive in more than half of patients with a history of thrombosis.

Angiogenesis, the sprout and growth of new blood vessels from existing vasculature, is an important process of tumor development for the supply of oxygen and nutrition to cancer cells. Endothelial cell is a critical player in angiogenic process by modulating cell proliferation, cell motility, and cell morphology in the response to pro-angiogenic factors and environments provided by tumor and cancer cells. Recent in vivo and in vitro studies have revealed that gap junction of endothelial cells also participates in the promotion of angiogenesis. Pro-angiogenic factors modulate gap junction function and connexins expression in endothelial cells, whereas endothelial connexins involve in angiogenic tube formation and cell migration of endothelial cells via both gap junction channel function dependent or independent mechanisms. In particular, connexin might have the potential to regulate cell mechanics such as cell morphology, cell migration, and cellular stiffness that are dynamically changed during angiogenic processes. Here, we review the implication for endothelial gap junction and cellular mechanics in vascular angiogenesis.

We have evaluated the antihypertensive effect of several flavonoid extracts in the spontaneous hypertensive rat model (SHR). Treatments were carried out for 6 and 12 weeks in two groups of SHR rats which received Apigenin, Lemon Extract, Grapefruit + Bitter Orange (GBO) extracts and Cocoa extract. Captopril was used as a positive control in the SHR group treated for 6 weeks (SHR6) and Diosmin was used as the industry reference in the SHR group treated for 12 weeks (SHR12). Captopril and GBO extracts significantly reduced the elevated blood pressure of the SHR6 animals, but none of the extracts was effective in the SHR12 group. Apigenin, LE, GBO and captopril also ameliorated nitric oxide-dependent and independent aortic vascular relaxation and elevated plasma and urinary excretion of nitrites, only in the SHR6 group. Kidney and urinary TBARS were also significantly reduced by GBO in the SHR6 rats. Apigenin also improved vascular relaxation in the SHR12 group and all the flavonoids studied reduced urinary TBARS excretion and proteinuria. Vascular abnormalities such as lumen/wall ratio in coronary arteries and thoracic aorta were moderately improved by these treatments in the SHR6 group. In conclusion, the flavonoids included in this study, especially apigenin, LE and GBO improved vascular vasodilatory function of young adult SHRs but only the GBO-treated rats benefited from a reduction in BP. These extracts may be used as functional food ingredients with a moderate therapeutic benefit, especially in the early phases of arterial hypertension.

Schizoaffective disorder and its classification have always been a topic of discrepancy among researchers. The overlapping presentations of schizoaffective disorder, schizophrenia and psychotic bipolar disorder makes it difficult to classify and diagnose. This study is a narrative review of literatures and genetic and epidemiological research evidences, done to determine the similarities and differences between schizoaffective and psychotic bipolar disorder. Beginning from the introduction of schizoaffective disorder as "schizoaffective psychosis" by Kasanin in 1933, various researchers have proposed different views regarding the diagnosis and classifications for schizoaffective disorder. DSM-III considered schizoaffective disorder as a diagnosis of exclusion as it fails to fit the definite diagnostic criteria of schizophrenia, major affective disorders, or schizophreniform disorder. DSM-V updated the criteria of schizoaffective disorder and stated it as a life time illness rather than being an episodic disorder as in DSM-IV and hence is more reliable. However, some studies show that schizoaffective disorder patients are more like schizophrenia than mood disorder. It still remains unclear whether schizoaffective disorder is a heterogenous disease, a form of schizophrenia, a form of mood disorder or a midpoint in the continuation spectrum of schizophrenia and psychotic bipolar disease.

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

According to the World Health Organization, cardiovascular disease (CVD) is the leading cause of death among women worldwide, yet its magnitude is often underestimated. Biological and gender differences affect health, diagnosis, and healthcare in numerous ways. The lack of sex and gender awareness in health research and healthcare is an ongoing issue and affects not only research, but also treatment and outcomes. The importance of recognising the impact of both sex and gender on health and of knowing the differences between the two in healthcare is beginning to gain ground. There is more appreciation of the role that biological differences (sex) and sociocultural power structures (gender) have, and both sex and gender affect health behaviour, the development of diseases, their diagnosis, management, and long-term effects of an illness. An important issue is the knowledge and awareness of women about vascular diseases. The risk of cardiovascular events is drastically underestimated by women themselves, as well as by those around them. The purpose of this review is to draw attention to improving the medical care and treatment of women with vascular diseases.

Many assets of clinical medicine, such as clinical chemistry and diagnostic imaging, make clinical diagnosis outstanding compared to postmortem diagnosis. An assessment of functional status certainly has priority over the postmortem, cross-sectional use of diagnostic tests and laboratory equipment. In addition, the cost of these tools is sometimes steep, and their use does not always fit into a reasonable cost–benefit ratio. However, sometimes postmortem observations, such as inflammation, pulmonary edema, or infiltration and cerebral swelling, cannot be explained without implementing immunohistochemical markers for postmortem diagnosis. Introducing blood-based biomarkers in postmortem care could significantly reduce the rates of inconclusive postmortems and discrepancies in autopsy findings and clinical diagnoses. This is particularly relevant in the scope of vascular pathology, considering the great burden of vascular diseases in overall mortality. Expanding traditional autopsy with blood-based (circulating) biomarkers to avoid invasive postmortem examination would have cultural, religious, and potential economic advantages. All of the target molecules are discussed in the context of the process they up-regulate or down-regulate and which turns out to be the final cause of death. Ultimately, it is evident that further studies are needed to provide concrete validation for a combination of markers on a specific case order to reach a postmortem diagnosis with or without clinical records.

Transmembrane protein 100 (TMEM100) plays an important role in angiogenesis, vascular morphogenesis, integrity and cardiovascular development. TMEM100 is a downstream target of the BMP9/10 and BMPR2/ALK1 signaling pathways. Our recent study demonstrates TMEM100 is a lung endothelium enriched gene. Endothelial-specific deletion of Tmem100 impairs lung endothelial cells regeneration. Activation of Tmem100 signaling represents a novel strategy for lung vascular repair and regeneration. It is interesting and important to understand the roles of TMEM100 in the physiological and pathological conditions. In this review, we summarized the current knowledge of TMEM100.

Artificial Intelligence (AI) made its first appearance in 1956, and since then it has progressively introduced itself in healthcare system and patients’ information and care. AI functions can be grouped under the following headings: Machine Learning (ML), Deep Learning (DL), Artificial Neural Network (ANN), Convolutional Neural Network (CNN), Computer Vision (CV). Chronic limb-threatening ischemia (CLTI) represents the last stage of peripheral artery disease (PAD), and has increased over recent years, together with the rise in prevalence of diabetes and population ageing. Nowadays AI grants the possibility of developing new diagnostic and treatment solutions in the vascular field, given the possibility of accessing clinical, biological, and imaging data. By assessing the vascular anatomy in every patient, as well as the burden of atherosclerosis, and classifying the level and degree of disease, sizing and planning the best endovascular treatment, defining the perioperative complications risk, integrating experiences and resources between different specialties, identifying latent PAD, thus offering evidence-based solutions and guiding surgeons in the choice of the best surgical technique, AI challenges the role of the physician’s experience in PAD treatment.

A considerable number of patients with angina or myocardial ischemia have no significant coronary artery disease on invasive angiography. In recent years, several steps towards a better comprehension of the pathophysiology of these conditions, angina or ischemia with non-obstructive coronary arteries (ANOCA/INOCA) have been made. Nevertheless, several gaps in knowledge still remain. This review is intended to provide a comprehensive overview of ANOCA and INOCA with a particular focus on pathophysiology, recent diagnostic innovations, gaps in knowledge and treatment modalities.

Intrinsic disorder accounts for the flexibility of protein loops, molecular building blocks that are largely responsible for the processes and molecular functions of the living world. While loops likely represent early structural forms that served as intermediates in the emergence of protein structural domains, their origin and evolution remains poorly understood. Here, we conduct a phylogenomic survey of disorder in loop prototypes sourced from the ArchDB classification. Tracing prototypes associated with protein fold families along an evolutionary chronology revealed ancient prototypes tended to be more disordered than their derived counterparts, with ordered prototypes developing later in evolution. This highlights the central evolutionary role of disorder and flexibility. While mean disorder increased with time, a minority of ordered prototypes exist that emerged early in evolutionary history, possibly driven by the need to preserve specific molecular functions. We also revealed percolation of evolutionary constraints from higher to lower levels of organization. Percolation resulted in trade-offs between flexibility and rigidity that impacted prototype structure and geometry. Our findings provide a deep evolutionary view of the link between structure, disorder, flexibility and function, as well as insights into the evolutionary role of intrinsic disorder in loops and their contribution to protein structure and function.

Attention Deficit Hyperactivity Disorder (ADHD) it is known as a neuropsychiatric disorder. Anatomicaly components with implications in this previously mentioned disorder, are the anterior cingulate gyrus and dorsolateral prefrontal cortex (DLFPC) that are are found having a role in appearing this disease. ADHD is associated with cognitive and functional deficits that relate to diffuse abnormalities in the brain. ADHD is a specific pathology in children but may persisit to youth and also not so hard to find to adults.Till now, hard to find the curative treatment knowing ADHD as a neuropsychiatric disorder with enlarge unknown scientific points. Genetic and environmental component play an important role in diagnosis. Patients life style, a relevant history of individual geneticsand environmental factors are important in diagnosisThe management of ADHD, is also an important part togeter with future trends.

Enhancement in chemisorption is one of the active research areas in carbon materials. To remedy the thermally degraded chemisorption at high temperatures, we report a comprehensive study of kink structures in free-standing monoatomic carbon nanowires upon heating. Our Monte Carlo simulation considers multi-monoatomic carbon chains laterally interacted by the Van der Waals force. Our study reveals that the carbon nanowires maintain their linearity regardless of chain length at low temperatures, but this is not the case at high temperatures. Disordered kink structure is observed in the short carbon chains, especially above the Peierls transition temperature. The severe kink structure might increase the possibility of attaching negatively charged atoms, thereby contributing to the development of next-generation materials for chemisorption at high temperatures. We have also provided an important inspection that any physical property of the finite-length carbon chain predicted by ab-initio calculation should reconsider the atomic rearrangement due to the thermal instability at high temperatures.

Public concern has emerged about the effects of endocrine disruptor compounds (EDCs) on neuropsychiatric disorders. Preclinical evidence suggests that exposure to EDCs is associated with the development of the major depressive disorder (MDD) and could result in neural degeneration. The interaction of EDCs with hormonal receptors is the best-described mechanism of their biological activity. However, the dysregulation of the hypothalamic-pituitary-gonadal adrenal axis has been reported and linked to neurological disorders. On the other hand, at a worldwide level and in Mexico, the incidence of MDD has recently been increasing. Of note, in Mexico, there are no clinical associations on blood levels of EDCs and the incidence of the MDD. Methodology: Thus, we quantified for the first time the serum levels of parent compounds of two bisphenols and four phthalates in patients with MDD. Results: The levels of di-ethyl-hexyl-phthalate (DEHP), butyl-benzyl-phthalate (BBP), di-n-butyl phthalate (DBP), and di-ethyl-phthalate (DEP), bisphenol A (BPA), and bisphenol S (BPS) were determined with a gas chromatograph-mass spectrometer. Results/ conclusion: We found significant differences between concentrations of BBP between controls and patients with MDD.

Introdução: Os fatores de risco vasculares são decisivos na evolução da doença aterosclerótica e a ecografia Doppler carotídea e vertebral permite acompanhar o seu aparecimento e evolução. A medida do espessamento da parede arterial permite o diagnóstico precoce da doença potencializando seu tratamento e controle dos fatores de risco vasculares. Objetivo: Analisar a presença de doença ateromatosa em indivíduos com idade > 65 anos e compreender sua transformação com fatores de risco vascular. Materiais e Métodos: Estudo observacional transversal, em indivíduos com idade > 65 anos manifestados ao ecoDoppler carotídeo entre 1º de janeiro de 2012 e 31 de dezembro de 2021. Foi calculado o índice médio-intimal, a presença de placas ateromatosas, sua repercussão hemodinâmica e fatores de risco vascular foram registrados. Resultados: Obteve-se uma amostra de 5885 indivíduos, sendo 41,8% do sexo feminino e 58,2% do sexo masculino. A média de idade foi de 76,59 anos, variando entre 65 e 98 anos (+6,69). A hipertensão arterial foi a mais prevalente 81,3%. Houve relação positiva significativa entre índice médio-intimal, idade e história pessoal de doenças cardiovasculares e cerebrovasculares (p=0,001). Na presença de placas, sexo masculino, hipertensão arterial, diabetes, dislipidemia, tabagismo e história pessoal de doenças cardiovasculares e cerebrovasculares apresentadas de forma positiva. Conclusões: Nesta amostra, fatores de risco vascular não modificáveis ​​parecem ser determinantes na presença de aumento da espessura da parede arterial. Na presença de sinais de um estágio mais avançado da doença aterosclerótica, os fatores de risco vascular modificáveis ​​​​são decisivos,

The stele concept is one of the oldest enduring concepts in plant biology. This paper reviews the concept and its foundations, and builds an argument for an updated view of steles and their evolution. The history of studies of stelar organization has generated a widely ranging array of definitions of the stele that determine the way we classify steles and construct scenarios about the evolution of stelar architecture. Because at the level of the organism biological evolution proceeds by, and is reflected in, changes in development, concepts of structure need to be grounded in development in order to be relevant in an evolutionary perspective. For the stele, most of the traditional definitions that incorporate development have viewed it as the totality of tissues that either originate from procambium – currently the prevailing view – or are bordered by a boundary layer (e.g., endodermis). A definition of the stele that would bring consensus between these perspectives recasts the stele as a structural entity of dual nature. Here, I review briefly the history of the stele concept, basic terminology related to stelar organization, and traditional classifications of the steles. I then revisit boundary layers from the perspective of histogenesis as a dynamic mosaic of developmental domains. I use classic and recent anatomical and molecular data to reaffirm and explore the importance of boundary layers for stelar organization. Drawing on data from comparative anatomy, developmental regulation, and the fossil record, I offer a model for a stele concept that integrates both the boundary layer and the procambial perspective, consistent with a dual nature of the stele. The dual stele model posits that stelar architecture is determined in the apical meristem by two major cell fate specification events: a first one that specifies a provascular domain and its boundaries, and a second event that specifies a procambial domain (which will mature into conducting tissues) from cell subpopulations of the provascular domain. If the position and extent of the developmental domains defined by the two events are determined by different concentrations of the same morphogen (most likely auxin), then the distribution of this organizer factor in the shoot apical meristem, as modulated by changes in axis size and the effect of lateral organs, can explain the different stelar configurations documented among tracheophytes. This model provides a set of working hypotheses that incorporate assumptions and generate implications that can be tested empirically. The model also offers criteria for an updated classification of steles that is in line with current understanding of plant development. In this classification, steles fall into two major categories determined by the configuration of boundary layers – boundary protosteles and boundary siphonosteles, each with subtypes defined by the architecture of the vascular tissues. Validation the dual stele model and, more generally, in-depth understanding of the regulation of stelar architecture, will necessitate targeted efforts in two areas: (i) the regulation of procambium, vascular tissue, and boundary layer specification in all extant vascular plants, considering that most of the diversity in stelar architecture is hosted by seed-free plants, which are the least explored in terms of developmental regulation; (ii) the configuration of vascular tissues and, especially, boundary layers, in as many extinct species and lineages as possible.

The release of nanomolar concentrations of nitric oxide (NO) by endothelial cells (EC), via activation of constitutive NO synthase (eNOS), represents the pre-requisite for the vaso-protective role of vascular endothelium. On the other hand, exaggerated release of NO as a consequence of activation of inducible NO synthase (iNOS), leads to endothelial dysfunction and, at the late stages, to the development of atherothrombosis. Oxidyzed LDLs (OxyLDL) represent the major candidate to trigger biomolecular processes accompanying endothelial dysfunction and vascular inflammation leading to atherosclerosis development though the pathophysiological mechanism still remains to be elucidated. Here, we summarize recent evidence suggesting that oxyLDL produce significant impairment in the balance in the eNOS/iNOS machinery, downregulating eNOS via HMGB1-TLR4-Caveolin-1 pathway. On the other hand, a sustained activation of the scavenger receptor LOX-1 leads to NFkB activation which, in turn, increases iNOS, leading to EC oxidative stress. Finally, these events are associated to reduced protective autophagic response and accelerated apoptotic EC death which activates atherosclerotic development. Taken togheter, these informations shed new light into the pathophysiological mechanisms of oxy-LDL-related impairment of EC functionality and open new perspective in atherothrombosis prevention.

Depression is the most common chronic mental illness and is characterized by low mood, insomnia, and affective disorders. However, the pathological mechanisms of depression remain unclear. Numerous studies have suggested that the ghrelin/GHSR system may be involved in the pathophysiologic process of depression. Ghrelin plays a dual role in the experimental animals, increasing depressed behavior and decreasing anxiety. By combining several neuropeptides and traditional neurotransmitter systems to construct neural networks, it modifies signals connected to depression. The present review emphasizes the role of ghrelin in neuritogenesis, astrocyte protection, inflammatory factor production, and endocrine disruption in depression. Furthermore, ghrelin/GHSR can activate multiple signaling pathways to produce antidepressant effects, including cAMP/CREB/BDNF, PI3K/Akt, Jak2/STAT3, and p38-MAPK. Given the antidepressant effects of ghrelin/GHSR1a system, it is expected to become a potential therapeutic target for the treatment of depression.

Patients with bipolar disorder (BD) experience more frequent and intense emotions in response to environmental conditions relative to healthy subjects, which leads to mood instability. The aim of this study was to investigate the time-course of emotion regulation strategies, distraction, and reappraisal, in euthymic BD patients using electroencephalography (EEG). Fourteen BD patients and 13 matched healthy controls took part in an experiment constituted of three conditions, i.e., a passive viewing of positive, negative, and neutral pictures and two regulation conditions, one with reappraisal strategy and the other with distraction strategy. Critically, ERP results indicated that during passive viewing, the Late Positive Potential (LPP) was larger in BD patients compared with healthy controls, but only for neutral pictures. During emotion regulation, LPP amplitude was reduced in distraction condition compared with viewing one, especially for negative emotions in both patients and controls. Importantly, LPP was reduced in reappraisal condition compared with passive viewing in an early time window for negative emotions and in a later time window for positive emotions in controls but not in patients. Our findings showed that the neurochronometry of emotion regulation is faster for negative than for positive emotion in controls but not in BD patients.

The study aimed to determine, through a systematic review, the relationship between Reactive Attachment Disorder (RAD) and the presence of psychopathology in children and adolescents and to determine the existence of differences about the presence of internalising and externalising psychological problems between the RAD group and groups with other disorders or with typical development. Following the PRISMA methodology, a search was carried out in the Web of Science, PubMed and Scopus databases. The search yielded 770 results, of which only 25 met the inclusion criteria. The results, indicate a relationship between the presence of RAD and/or Disinhibited social engagement disorder (DSED) with the presence of internalising and externalising problems. These difficulties are more present in children with RAD compared to children without personal difficulties, or children with DSED, children with autism, children with intellectual disabilities or children with hyperactivity. It can be concluded that the presence of RAD has negative consequences on the mental health of children and adolescents, with these being greater in the inhibited group than in the disinhibited group, and with respect to children with autism or hyperactivity.

Autism spectrum disorder (ASD) refers to the diverse range of neurodevelopmental disorders accompanying impairments in social interaction, difficulties in communication, and stereotyped or repetitive behaviors. Unlike the older term, autism, the newer term, ASD, better reflects the broad range of autistic symptoms and denotes a single diagnostic category of autism accompanied by numerous conditions. The pineal hormone melatonin is a well-known neuroprotectant and circadian entrainer. This hormone crosses the placenta and enters the fetal circulation, then conveys photoperiodic information to the fetus during pregnancy. These actions enable normal sleep patterns and circadian rhythms, followed by normal neurodevelopment. Melatonin also reduces oxidative stress, which is harmful to the central nervous system. Therefore, melatonin acts as a neuroprotectant and circadian entrainer, and may reduce the risk of neurodevelopmental disorders such as ASD.

Introduction. This retrospective study aimed to compare the risk factors for vascular calcification (VC) between pre-hemodialysis (HD) and prevalent HD adult patients while investigating associations with calcification biomarkers. Methods. Baseline data from 30 pre-HD and 85 HD patients were analyzed, including iPTH, vitamin D, FGF23, fetuinA, sclerostin, and VC scores (Adragao method). Multivariable linear regression identified VC predictors. Results: The prevalence of VC was similar in both groups, but HD patients had more pronounced VC scores ≥6. Pre-HD patients were older, with higher prevalence of Balkan endemic nephropathy, hypertension, and less frequent use of calcium phosphate binders. Both groups exhibited similar patterns of hyperphosphatemia, low vitamin D, and iPTH levels. In HD group normal phosphate was significantly common in patients with VC, whereas hyperphosphatemia was significantly common in patients without VC. Fetuin-A levels were higher in pre-HD patients, while FGF23 was elevated in HD patients. In pre-HD patients, male gender was associated with reduced VC risk, while in HD patients, malignancies and serum phosphate levels were negative VC predictors. Conclusion: Effective monitoring and tailored treatment of VC in CKD are still focused on phosphate regulation. Besides, mineral disturbances, hormones and biomarkers regulation, and patient-specific variables need to be considered.

(1) Background: Thrombophilia is a tendency towards hypercoagulability, and it is increased by pregnancy, peaking around delivery. Research question: does thrombophilia stimulate the in-flammatory state of the patient, already suppressed by pregnancy? (2) Methods: Eighty thrombo-philia patients admitted for delivery between 1/10/2017 and 1/12/2021 were prospectively stud-ied, together with eighty age- and para-matched control patients. Patients were admitted for de-livery at term by means of cesarean section. The inflammation indexes from the complete blood count values analysis during both the 24 hours before and after labor—extracted from the hospi-tal’s medical records—were calculated and then correlated with uterine involution. (3) Results: Except for the PLR, most of the numerous inflammation indexes studied were not significantly different in treated thrombophilia patients, before and after delivery, compared to non-thrombophilia patients. Only when we split the patients, based on the uterine haematometra in the first 24-48 hours postpartum, we found out that the few treated thrombophilia patients with haematometra (14 with haematometra out of 79 with treated thrombophilia) had elevated SII and AISI antepartum. In pregnant patients treated for thrombophilia, MLR is higher in pa-tients without the Rh factor than in those with the Rh factor. In non-thrombophilia patients, MCVL and NLPR increased with age and before labor, while SII and AISI increased with age postpartum. (4) Conclusions: Thrombophilia did not stimulate the inflammatory state of the pa-tient, already suppressed by pregnancy.

Prosthetic infections are associated with high morbidity, mortality, and relapse rates making them still a serious problem for implantology. Staphylococcus aureus is one of the most common bacterial pathogens causing prosthetic infections. In response to the increasing rate of bacterial resistance to commonly used antibiotics, the work proposed a method of combating pathogenic microorganisms by modifying the surface of synthetic polymeric biomaterials using proteolytic enzyme inhibitors (serine protease inhibitors - 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride and puromycin). While using techniques based on immobilization of biologically active molecules, it is important to monitor changes occurring on the surface of the modified biomaterial, where spectroscopic techniques (e.g. FTIR) are ideal. The ATR-FTIR measurements demonstrated that the immobilization of both inhibitors caused large structural changes on the surface of the tested vascular prostheses (polyester or polytetrafluoroethylene) and showed that they were covalently bonded to the surface of the biomaterials. Next, the bactericidal and antibiofilm activities of the tested serine protease inhibitors were determined using the CLSM microscopic technique with fluorescent staining. During LIVE/DEAD analyses, a significant decrease in the formation of Staphylococcus aureus biofilm after exposure to selected concentrations of native inhibitors (0.02-0.06 mg/mL for puromycin and 0.2-1 mg/mL for 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride was demonstrated.

Consumption of high amounts of ethanol is a risk factor for development of cardiovascular diseases such as arterial hypertension. The hypertensive state induced by ethanol is a complex multi-factorial event, and oxidative stress is a pathophysiological hallmark of vascular dysfunction associated with ethanol consumption. Increasing levels of reactive oxygen species (ROS) in the vasculature triggers important processes underlying vascular injury, including accumulation of intracellular Ca2+ ions, reduced bioavailability of nitric oxide (NO), activation of mitogen-activated protein kinases (MAPKs), endothelial dysfunction, and loss of the anticontractile effect of perivascular adipose tissue (PVAT). The enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase plays a central role in vascular ROS generation in response to ethanol. Activation of the renin-angiotensin-aldosterone system (RAAS) is an upstream mechanism which contributes to NADPH oxidase stimulation, overproduction of ROS and vascular dysfunction. This review discusses the mechanisms of vascular dysfunction induced by ethanol, detailing the contribution of ROS to these processes. Data examining the association between neuroendocrine changes and vascular oxidative stress induced by ethanol are also reviewed and discussed. These issues are of paramount interest to public health as ethanol contributes to blood pressure elevation in the general population, and it is linked to cardiovascular conditions and diseases.

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

Introduction: Ehlers-Danlos syndromes (EDS) constitute a rare entity of genetic disorders, affecting the collagen of all types all. Herein, we describe a case of vascular type of EDS, with coexisting segmental absence of intestinal musculature, while performing simultaneously a narrative review of the existing literature. Case Presentation: A 23-year-old male patient with a history of multiple abdominal operations due to recurrent bowel perforations and the presence of high-output enterocutaneous fistula was admitted to our surgical department for further evaluation and treatment. After detailed diagnostic testing, the diagnosis of vascular type of EDS (vEDS) was made and a conservative therapeutic approach was adopted. In addition, a comprehensive review of the international literature was carried out by applying the appropriate search terms. Results: The diagnosis of vEDS was molecularly confirmed by means of genetic testing. The patient was treated conservatively, with parenteral nutrition and supportive methods. Thirty-four cases of bowel perforation in vEDS have been reported so far. Interestingly, this case is the second one ever to report with co-existence of vEDS with Segmental Absence of Intestinal Musculature. Conclusions: Establishing the diagnosis of vEDS promptly is of vital significance in order to ensure that patients receive appropriate treatment. Due to initial non-specific clinical presentation, EDS should always be included in the differential diagnoses of young patients with unexplained perforations of the gastrointestinal tract.

Branching patterns are ubiquitous in nature, consequently over the years many researchers have tried to characterize the complexity of their structures. Due to their hierarchical nature and resemblance to fractal trees, they are often thought to have fractal properties, however their non-homogeneity (i.e., lack of strict self-similarity) is often ignored. In this paper we review and examine the use of the box-counting and sandbox methods to estimate the fractal dimensions of branching structures. We highlight the fact that these methods rely on an assumption of self-similarity that is not present in branching structures due to their non-homogeneous nature. Looking at the local slopes of the log-log plots used by these methods reveals the problems caused by the non-homogeneity. Finally, we examine the role of the canopies (endpoints or limit points) of branching structures in the estimation of their fractal dimensions.

Background: Takayasu Arteritis (TAK) increases vascular stiffness and arterial resistance. Hypertension and atherosclerosis lead to similar changes. We investigated possible differences in cardiovascular remodeling between these diseases and whether the differences are correlated with immune cell expression. Methods: Patients with active TAK arteritis were compared with age- and sex-matched hypertensive and atherosclerotic patients. In a subpopulation of TAK patients, Treg/Th17 cells were measured before (T0) and after 18 months (T18) of infliximab treatment. Echocardiogram, supraaortic Doppler ultrasound, and lymphocytogram were performed in all patients. Histological and immunohistochemical evaluation of the vessel wall was performed to compare the in vivo results. Results: TAK patients have increased aortic valve dysfunction and diastolic dysfunction. These data have been associated with uric acid levels. A significant increase in aortic stiffness was also noted and associated with peripheral T lymphocyte levels. CD3+CD4+ cell infiltrates were detected in the vessel wall samples of these patients. They had a lower mean percentage of Tregs at T0 than controls, but levels increased significantly at T18. Opposite results were found in Th17 cells. Finally, TAK patients were found to have an increased risk of atherosclerotic cardiovascular disease (ASCVD). Conclusion: Our data suggest that different pathogenic mechanisms of vessel damage, including atherosclerosis, underlie TAK patients compared with control subjects. The increased risk of ASCVD in TAK patients correlates directly with the degree of inflammatory cell infiltration in the vessel wall. Infliximab restores the normal frequency of Tregs/Th17 in TAK patients and allows a possible reduction of steroids and immunosuppressants.

The lack of suitable autologous grafts and poor compliance of existing prostheses have prompted the study of novel materials for vascular graft design. Polyurethanes (PUs) were used in the past because they have high compliance and properties that are similar to those of native tissue. In this work, the mechanical properties of a group of PUs in two states (non-hydrated and hydrated) were studied using uniaxial tensile tests, strain sweep tests, and multi-step creep recovery tests. Additionally, a hyper-elastic model based on the Mooney–Rivlin strain density function was fitted and used to model the performances of the PUs under physiological pressure and geometry conditions. The tensile tests revealed a softening phenomenon after hydration, which could potentially reduce patient discomfort and risk of vascular trauma. The ultimate strength values after hydration were similar to those reported for other vascular conduits. The strain sweep showed a strong strain dependency of the modulus indicating non-linear viscoelasticity. In the creep-recovery tests, increasing the polyethylene glycol(PEG) content enhanced the viscous flow, while the elastic behavior was enhanced with the largest concentration of polycaprolactone diol (PCL). On the other hand, under simulated physiological conditions, the compliance of the PUs showed a cyclic behavior with the time and pressure but was not affected by the radii and thickness variation, which could increase the graft compliance and geometry mismatch. Nevertheless, the compliance could be tuned using the material composition. This paper studied the biomechanics of a group of materials under simulated physiological conditions (Temperature, hydration, and pressure) to select those that could perform better for further vascular graft design.

Toll-like receptor 5 ligand, flagellin, and Vascular Adhesion Protein-1 (VAP-1) are involved in non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether VAP-1 mediates flagellin-induced hepatic fat accumulation. The effects of flagellin on adipocyte VAP-1 expression were first studied in vitro. Then, flagellin (100 ng/mouse) or saline was intraperitoneally injected to C57BL/6J WT and C57BL/6-Aoc3^-/- (VAP-1 KO) mice on high-fat diet twice a week every two weeks for 10-weeks. After that, the effects on inflammation, insulin signaling, and metabolism were studied in liver and adipose tissues. Hepatic fat was quantified histologically and biochemically. Because flagellin challenge increased VAP-1 expression in human adipocytes, we used VAP-1 KO mice to determine whether VAP-1 regulates the inflammatory and metabolic effects of flagellin in vivo. In mice, VAP-1 mediated flagellin-induced inflammation, leukocyte infiltration and lipolysis in visceral adipose tissue. Consequently, increased release of glycerol led to hepatic steatosis in WT but not KO mice. Flagellin-induced hepatic fibrosis was not mediated by VAP-1. VAP-1 KO mice harbored more inflammation-related microbes than WT, while flagellin did not affect the gut microbiota. Our results suggest that by acting on visceral adipose tissue, flagellin increased leukocyte infiltration that induced lipolysis. Further, the released glycerol participated in hepatic fat accumulation. In conclusion, the results describe that gut microbial flagellin through VAP-1 induced hepatic steatosis.

1) Background: we have evaluated the antihypertensive effect of several flavonoid extracts in a rat model of arterial hypertension caused by chronic administration (6 weeks) of the nitric oxide synthesis inhibitor, L-NAME. 2) Methods: Sprague Dawley rats received L-NAME alone or L-NAME plus flavonoid-rich vegetal extracts (Lemon, Grapefruit + Bitter Orange, and Cocoa) or purified flavonoids (Apigenin and Diosmin) for 6 weeks. 3) Results: L-NAME treatment resulted in a marked elevation of blood pressure, and treatment with Apigenin, Lemon Extract, and Grapefruit + Bitter Orange extracts significantly reduced the elevated blood pressure of these animals. Apigenin and some of these flavonoids also ameliorated nitric oxide-dependent and independent aortic vasodilation and elevated nitrite urinary excretion. End-organ abnormalities such as cardiac infarcts, hyaline arteriopathy and fibrinoid necrosis in coronary arteries and aorta were improved by these treatments, reducing the end-organ vascular damage. 4) Conclusions: the flavonoids included in this study, specially apigenin, may be used as functional food ingredients with potential therapeutic benefit in arterial hypertension.

(1) Background: Gamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters with beneficial effects including sedative property. However, despite various clinical trials, scientific evidence regarding the impact of orally ingested GABA, whether natural or synthesized through biological pathways, on sleep is not clear.; (2) Methods: The present study work evaluated GABA-A biding affinity of GABALAGEN(GBL), a low-molecular-weight collagen infused with GABA, through receptor binding assays. The sedative effects of GBL were investigated through electroencephalography (EEG) analysis in the electro foot shock (EFS) stress-induced sleep animal model and then we examined the expression orexin, GABAA receptor in the brain region using immunohistochemistry.; (3) Results: We found that on the binding assay, GBL displayed high affinity to GABAA receptor (IC50 value, 31.5µg/mL)). Also, after treatment of GBL, percent of total time of REM and NREM were significantly and dose-dependently increased compared to the Con group. Consistent with behavioral results, the GBL-treated groups showed that the expression of GABAA receptor immune-positive cells in the VLPO were markedly and dose-dependently increased compared to the Con group. Also, the GBL-treated groups showed that the expression of orexin immune-reactive cells in the LH were significantly decreased compared to the Con group.; (4) Conclusions: In conclusion, GBL showed efficacy and potential to be used as an anti-stress therapy to treat sleep deprivation through antagonism of GABA receptors and consequent inhibition of orexin activity.

With more than half of U.S. adults reporting alcohol consumption the last 30 days and nearly 6% reporting heavy drinking, alcohol imposes a significant socioeconomic burden. While there are a host of current medications approved to treat alcoholism, they have limited effectiveness and lack support from both providers and patients. Semaglutide, a medication originally developed for obese type 2 diabetics, may offer a distinctly new approach. A survey to assess the impact of semaglutide on alcohol consumption and desire was designed and distributed in semaglutide-user Facebook and Reddit groups. Of those who had reported drinking before starting semaglutide, 21% of respondents (N= 121) ceased drinking altogether, and 88·4% of respondents (N=538) reported a reduction in their desire to consume alcohol after commencing their medication. Respondents also shared further personal accounts of decreased occurrences of compulsive or "addictive" behaviors beyond a reduction in the desire to consume alcohol. Considering the growing number of reports detailing experiences such as these, combined with our survey results indicating a reduction in both frequency and quantity of alcohol consumption, we strongly recommend conducting scientifically rigorous investigations and clinical trials to explore the potential of semaglutide for addressing conditions associated with alcohol use.

The passion of bodybuilding athletes for a symmetric, lean, heavily muscled body leads them to carry out exhausting exercise programs and restrictive eating regimens, sometimes resulting in disordered eating behaviors. This study investigates potential exacerbators on the development of disordered eating in bodybuilding and strength athletes. The study involved 103 Cypriot bodybuilding athletes of both sexes, performing at three levels: professional, recreational and strength athletes. The Eating Attitude Test 26 (EAT-26) and The Three Factor Eating Questionnaire (TFEQ-R21) were used to evaluate disordered eating and eating behaviors respectively. The current study was performed under the auspices of the Hellenic Center of Education & Treatment of Eating Disorders (KEADD). The degree of deviation between the perceived ideal body weight and the actual body weight was associated with increased risk of eating disorder. Athletes who desired a lower body weight recorded higher scores on EAT-26 overall, and the subscales of dieting and bulimia. Cognitive restraint and emotional eating scales of TFEQ-R21 were more pronounced in the non-professional athletes. The emotional eating score was higher in women. There is a need for appropriate sport-specific, gender-specific preventive intervention to deescalate the risk of eating disorder, in both professional and non-professional bodybuilding athletes.

Background: Post-traumatic stress disorder (PTSD) is a common debilitating psychiatric condition for which pharmacological therapy is not always solvable. Various treatments have been suggested for these patients. Deep brain stimulation (DBS) is currently under investigation for patients affected by PTSD. 2) Methods: We review the neurocircuitry and up to date clinical concepts that may be of relevance for the implementation of DBS in posttraumatic stress disorder (PTSD). 3) Results: The role of DBS in treatment-refractory PTSD patients has been investigated relying on both preclinical and clinical studies. 4) Conclusions: DBS for PTSD is in its preliminary phases and likely to provide hope to patients with medical refractory PTSD following the results of randomized controlled studies.

Proteomic analysis revealed the preservation of many proteins in the “Heslington brain” (which is at least 2,600-year-old brain tissue uncovered within the skull excavated in 2008 from a pit in Heslington, Yorkshire, England). Five of these proteins (“main proteins”), heavy, medium, and light neurofilament proteins (NFH, NFM, and NFL), glial fibrillary acidic protein (GFAP), and myelin basic (MBP) protein are engaged in the formation non-amyloid protein aggregates, such as intermediate filaments and myelin sheath. We used a wide spectrum of bioinformatics tools to evaluate the prevalence of functional disorder in several related sets of proteins, such as “main proteins” and their 44 interactors, as well as all other protein identified in the Heslington brain. These analyses revealed that all five “main proteins”, half of their interactors and almost one third of the Heslington brain proteins are expected to be mostly disordered. Furthermore, most of the remaining proteins are expected to contain sizable disordered regions. This is in contrary the expected substantial (if not complete) elimination of the disordered proteins from the Heslington brain. Therefore, it seems that the intrinsic disorder of NFH, NFM, NFL, GFAP, and MBP, their interactors and many other proteins might play a crucial role in preserving the Heslington brain by forming tightly folded brain protein aggregates, in which different parts are glued together via the disorder-to-order transitions.

Obsessive-Compulsive Disorder (OCD) is a mental health condition marked by recurrent intrusive thoughts or sensations that compel individuals to perform repetitive behaviors or mental acts. Obsessions and compulsions significantly disrupt daily life and cause considerable distress. Early identification and intervention improve long-term outcomes. This study aimed to evaluate the ability of four advanced artificial intelligence models (ChatGPT-3.5, ChatGPT-4, Claude, and Bard) to accurately recognize OCD compared to human professionals and to assess recommended therapies and stigma attributions. This study was conducted during March 2024 utilizing 12 vi-gnettes. Each vignette depicted a client, either a young adult or a middle-aged male or female, attending an initial therapy session. Each vignette was evaluated ten times, resulting in 480 evaluations. The results were compared with those of a human sample of 514 psychotherapists, as reported by Canavan. Significant differences were found. AI models demonstrated higher OCD recognition rates and confidence levels than human professionals and showed 100% confidence in recognition, compared to 87% among psychotherapists. AI models also recommended evi-dence-based interventions more frequently, with ChatGPT-3.5 and Claude at 100%, ChatGPT-4 at 90%, and Bard at 60%, compared to 61.9% among psychotherapists. Additionally, AI models ex-hibited significantly lower stigma and danger estimations, though both AI and psychotherapists demonstrated high willingness to treat the described cases. The findings suggest that AI models surpass human professionals in recognizing OCD and recommending evidence-based treatments while also demonstrating lower stigma. These results highlight the potential of AI tools to enhance OCD diagnosis and treatment in clinical settings.

Brain-Computer Interface (BCI) systems can assist physically challenged people to interact with their surroundings and improve the quality of their lives. Decoding human thoughts is a powerful technique that can assist paralyzed people who have lost their speech production ability. Speaking is a combined process involving synchronizing the brain and the oral articulators. This paper proposed a high-accuracy brain wave pattern recognition based on inner speech using a novel feature extraction method. Only eight EEG electrodes were used in this study, and they were set on selected spots on the scalp. Support Vector Machine (SVM) was employed to decode the recorded EEG dataset into four internally spoken words which are: Up, Down, Left, and Right. The proposed approach achieved overall classification accuracy that ranges between 96.20% to 97.5%. In addition, more performance evaluation metrics were estimated to test the reliability of classifying the EEG-based inner speech data, and we obtained 97.61%, 97.50%, and 97.73% for F1-score, recall, and precision respectively. Furthermore, the Area Under Curve of the Receiver Operating Characteristic (AUC-ROC) proved the strength of the proposed approach for classifying the specified inner speech commands by achieving a macro-average amount of 99.32%. The inner speech classification method using electroencephalography proposed in this work can clinically help improve communication for patients with problems including speech disorder, mutism, cognitive development, executive function, and psychopathology.

Movement disorders can be associated with various drugs and systemic diseases, posing diagnostic challenges for clinicians. This review explores the spectrum of movement disorders associated with pharmacological agents and medical conditions. Drug-induced movement disorders encompass a broad range of conditions resulting from exposure to medications that affect several neurotransmitters. Neuroleptic medications can lead to tardive dyskinesia, characterized by involuntary, repetitive movements. Antipsychotics and antiemetics, including metoclopramide, may induce acute dystonic reactions. Other drugs, such as dopamine receptor-blocking agents, can contribute to drug-induced parkinsonism. Beyond medications, movement disorders can also arise secondary to systemic diseases. Metabolic disorders like Wilson's disease, characterized by copper accumulation, may manifest as chorea or dystonia. Inflammatory conditions such as rheumatoid arthritis and systemic lupus erythematosus can result in secondary movement disorders due to autoimmune-mediated processes affecting the central nervous system. Movement disorders linked to drugs or systemic diseases often necessitate a thorough clinical evaluation, including detailed medication histories and comprehensive systemic assessments. Neuroimaging, laboratory investigations, and, in some cases, cerebrospinal fluid analyses and electrodiagnostic studies help in establishing accurate diagnoses. Management involves addressing the underlying cause, modifying medications, and employing symptomatic treatments.