Volunteering has many social, emotional and health benefits and could be an option for people with younger/early onset dementia to engage in stage/age-appropriate, personally meaningful activity within their local community. Audio data of people with young onset dementia discussing their volunteering experiences were taken from the Dementia Diaries and co-analysed. This study explored how people with dementia volunteer in the UK, the benefits and barriers, and how we can improve access to volunteering opportunities. The findings suggest that stigma is the overarching concept (or net) which influences people’s experiences of volunteering with dementia. Within the stigma net, three themes were developed that employed a lifespan approach to challenging said stigma: 1) Valuing the past, 2) Valuing the present and 3) Valuing the future, each with additional subthemes. This research contributes to the limited pool of literature that highlights the clear benefits of volunteering for people with young onset dementia, while also considering how dementia stigma can create practical and institutional barriers to accessing volunteering. Guidance is provided for how to deliver meaningful and accessible volunteering opportunities.

Alzheimer’s disease (AD) and vascular dementia (VaD) together contribute to almost 90% of all dementia cases leading to major health challenges of our time with a substantial global socioeconomic burden. While in Alzheimer’s disease, the improved understanding of Amyloid beta (Aß) mismetabolism and tau hyperphosphorylation as pathophysiological hallmarks has led to significant clinical breakthroughs, similar advances in VaD are lacking. We thus highlight here the importance of shared pathomechanisms found in AD and VaD: Endothelial damage, blood brain barrier (BBB) breakdown and hypoperfusion inducing oxidative stress, inflammation and demyelination and thus trophic uncoupling in the neurovascular unit. A dysfunctional endothelium and BBB lead to the accumulation of neurotoxic molecules and Aß through impaired clearance, which in turn leads to neurodegeneration. In this context we discuss possible neuropathological parameters, which might serve as biomarkers and thus improve diagnostic accuracy or reveal targets for novel therapeutic strategies for both forms of dementia.

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

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

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

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

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

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

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.

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.

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

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

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

Dementia, primarily caused by neurodegenerative diseases like Alzheimer’s disease (AD), affects millions worldwide, making detection and monitoring crucial. To enable these tasks, we propose encoding in-text pauses and filler words (i.e., “uh” and “um”) in text-based language models, and thoroughly evaluate their effect in performance. Additionally, we suggest using contrastive learning to improve performance in a multi-task framework. Our results demonstrated the effectiveness of our approaches in enhancing the model’s performance, achieving 87% accuracy and an 86% F1-score. Compared to the state-of-the-art, our approach has similar performance despite having significantly fewer parameters. This highlights the importance of pause and filler word encoding on the detection of dementia.

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.

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

Alzheimer's disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords GB in AD and dementia yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show Ginkgo biloba has promising potential in these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.

Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.

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

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.

Introduction: Dementia is a cognitive decline with patients often exhibit behavioural and psychological symptoms, severely affecting the quality of life and placing a heavy burden on caregivers. Acupressure has reported benefits for dementia. This study aims to critically review the available evidence for its use as a non-pharmacological therapy. Methods: Systematic search of major research databases for human clinical trials using acupressure as an intervention for dementia patients was conducted. Results were synthesised for the effects of acupressure on various outcome measures of interest for dementia.Results: Twelve clinical trials (N=973), including eight randomised control studies, were included in this review. The study sample was predominantly institutionalised residents with moderate to severe dementia. Baihui (GV20), Shenmen (HT7), Fengchi (GB20), Neiguan (PC6), Sanyinjiao (SP6), and Yingtang (EX-HN3) were the most used acupoints for intervention. Acupressure techniques employed in these clinical trials vary greatly with no standardised approach. This review finds inconsistent evidence in the effectiveness of acupressure in reducing agitation and behavioural disturbances. However, the treatment appears to improve their ease of care and reduce physical stress. Affixing acupressure devices on selected acupoints can also potentially improve psychiatric pain, anxiety, and depression. Long-term (6 months) treatment can potentially improve the cognitive function, activities of daily living, and quality of life of patients with mild to moderate dementia. The effect of acupressure on sleep disturbances remains unclear. Conclusion: More high-quality research on acupressure is needed to fill the gaps in knowledge and inform better care for dementia patients in the future.

Informal dementia home caregiving is viewed negatively and can result in caregiver depression and anxiety from burnout, potentially compromising caregiving. Solutions are unclear, as caregiving relationships are unique—caregiver creation of a graphic memoir may help to mitigate the negative dementia narrative and reduce experienced burnout. This investigation examines the writing of a graphic memoir by one informal dementia home caregiver, created with the help of a cartoon illustrator and a publisher who edited, printed, and made the graphic memoir available at the psychiatric bookstore considered the largest in North America. Mother of the illustrator and the editor and publisher of this graphic memoir, this author provides the perspective taken in this investigation. The analysis, developed by this author, represents psychoanalytic narrative research, serving as the historical method. Aided by email threads between the publisher/caregiver, publisher/printer, and publisher/bookseller, and a published interview with the dementia caregiver are answers to how writing, illustrating, and publishing the graphic memoir affected the caregiver’s narrative reconstruction and burnout. Providing an example for other informal dementia home caregivers similarly to write and illustrate a publishable graphic memoir for their positive narrative reconstruction and to help decrease their depression and anxiety from burnout is the aim.

There are two generic approaches to curing any medical condition. The first treats every patient for all of the known possible causes that contribute to pathogenesis; the second individualizes potentially curative therapy by identifying in each separate patient only those components of pathogenesis that are actually operative, and treating those. This article adopts the second approach for formulating a cure of Alzheimer’s dementia (AD). Components of AD’s pathogenesis are, in alphabetical order: circadian rhythm disturbances, depression, diabetes and insulin resistance, dyslipidemia, hypertension, inflammation, metabolic syndrome, mitochondrial dysfunction, nutritional deficiencies, TGF-β deficiency, underweight, vascular abnormalities, and Wnt/β-catenin deficiency. For each component, data are described that show the degree by which its prevalence is more in the patients with mild cognitive impairment (MCI) who did not revert to having normal cognition than in those who did, because the former group is the pool of patients from among which future AD may develop. Addressing only those components that are present in a particular individual, is potentially a curative strategy. Published data indicate that curative therapy requires that the number of such components to address should be ≥3. Although structural brain changes cannot be directly addressed, the impaired neural tracts result from many of the reversible causal elements, so correcting them will benefit those tract

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.

Background: This study aimed to assess the dementia literacy (DL) level of community-dwelling adults in the four cities (Hong Kong, Guangzhou, Macau and Zhuhai) of the Greater Bay Area of China and to determine the preferred mass media for receiving dementia information. Methods: A multi-city cross-sectional study with 788 community-dwelling adults completed the survey. Dementia literacy was indirectly measured by two validated scales, 30-item Alzhiemer’s Disease Knowledge Scale (ADKS) and 20-item Dementia Attitudes Scale (DAS). When the ADKS total score was <15 and DAS total score was <70, it was considered as ‘inadequate dementia literacy’. Participants were also asked to indicate whether they would like to receive dementia information via digital media or traditional media. Chi-square tests and logistic regressions were undertaken. Results: About one-third of the participants had inadequate dementia literacy. Those with young age or secondary education preferred to get dementia information from social media. But people living in public housing would like to get information from government or hospital websites. Middle-aged participants inclined to learn dementia from television or radio. Conclusion: It is worthy to conduct territory-wide public education in dementia and develop strategies according to their preferences in the types of mass media.

Badminton is one of the most popular racket sports played by children up to the elderly worldwide. Everyone can practice and play badminton as a leisure or competitive sport, regardless of age, experience, or skill level. It does not require physical contact among players and expensive equipment. Compared with closed-skill exercise (e.g., running, swimming), open-skill exercise (e.g., badminton, table tennis) has been reported to intervene more with cognitive function and prevent cognitive decline. In this review, we outline the characteristics of badminton’s beneficial effects on physical and cognitive aspects. The characteristics presented here indicate that intervention with regular badminton exercise could effectively improve cognitive function and prevent cognitive decline in the elderly.

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

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.

The most common form of mixed dementia (MixD) is constituted by abnormal protein deposits associated with Alzheimer´s disease (AD) that coexist with vascular disease. Although olfactory dysfunction is considered a clinical sign of AD-related de-mentias, little is known about the impact of this sensorial impairment in MixD at molecular level. To address this gap in knowledge, we have assessed olfactory bulb (OB) proteome-wide expression in MixD subjects (n=6) respect to neurologically intact controls (n=7). Around 9% of the quantified proteins were differentially expressed, pinpointing aberrant proteostasis involved in synaptic transmission, nucleoside monophosphate and carbohydrate metabolisms and neuron projection regeneration. In addition, net-work-driven proteomics revealed a modulation in cell-survival related pathways such as ERK, AKT and PDK1-PKC axis. Part of the differential OB protein set was not specific of MixD, being also deregulated across different tauopathies, synucleinopathies and tardopathies. However, the comparative functional analysis of OB proteome data between MixD and pure AD pathologies deciphered commonalities and differences between both related phenotypes. Finally, olfactory proteomics allowed to propose serum Prolow-density lipoprotein receptor-related protein 1 (LRP1) as a candidate marker to differentiate AD from MixD phe-notypes.

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.

: This paper presents a couple of meal monitoring systems for senile dementia patients by using electronic weight and temperature sensors. These monitoring systems enable to convey the information of the amount of meal taken by the patients in real-time via wireless communication networks onto the mobile phones of their families or nurses in charge. Thereby, the nurses can easily spot the most desperate patient to take care of while the families can have relief to see the crucial information for survival of their parents at least three times a day. Meanwhile, the senile dementia patients tend to suffer the burn of their tongues because they can hardly recognize the temperature of hot meals served and therefore avoid the burn of tongues. This phenomenon can be discarded by utilizing the meal temperature monitoring system which displays alarm to the patients when the meal temperature is above the reference. These meal monitoring systems can be easily implemented by utilizing low-cost sensor chips and Arduino UNO boards so that elder-care hospitals and nursing homes can afford to exploit them with no additional cost. Hence, we believe that the proposed monitoring systems would be a potential solution to provide a great help and relief not only for the professional nursing nurses working in elder-care hospitals and nursing homes, but also for the families of the dementia patients.

Research into the causes of neurotoxicity in Alzheimer’s Dementia (AD) has focused on neurofibrillary tangles and beta amyloid (Aβ) plaques. This paper proposes the heterodox theory that these hallmarks of AD are the visible effects, not direct causes of neuronal necrosis. Rather AD results from a combination of age-induced, disproportional decline in physiological support for aerobic metabolism, and dysregulation of the sleep cycle processes. The hypothesis is that the decimation of neurons in AD results from a combination of neurotoxicity and increased apoptosis caused by: 1. direct damage from toxic waste products of anaerobic glycolysis due to a progressive decline in the capacity of neurons to perform oxidative phosphorylation (OXPHOS) and an increased reliance on anaerobic glycolysis to meet metabolic needs; 2. impaired cellular repair and effluent release due to dysregulation of non-rapid eye movement (NREM) sleep allowing damage to cell membranes and synaptic junctions to accumulate inducing a chronic inflammatory response; 3. indirect damage from products produced by inflammatory reaction to toxic metabolites; 4. neuronal apoptosis from the AβPP-mediated pathway due to the age-induced decline of growth hormone (GH), GH-releasing hormone (GHRH) and insulin-like growth factor (IGF).

Due to the complexity of Alzheimer's disease, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted lipid nanoemulsion) are available. Versatile small molecule drug(s) targeting multiple pathways of Alzheimer's disease pathogenesis are known. By incorporating such drug(s) into the targeted LCM/ND lipid nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets cell-surface scavenger receptors (mainly SR-BI), making possible for various Alzheimer's-related cell types to be simultaneously searched out for localized drug treatment in vivo. Besides targeting cell-surface SR-BI, the proposed LCM/ND-nanoemulsion combination therapeutic(s) include a characteristic lipid-coated microbubble [LCM] subpopulation (i.e., a stable LCM suspension); such film-stabilized microbubbles are well known to substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial) ultrasound treatment, or sonoporation, if additionally desired for the Alzheimer's patient.

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

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

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.

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

Sensory processing is a crucial function of the nervous system that significantly affects a large portion of the population, particularly older individuals who may be dealing with different forms of dementia. The global population of people aged 65 or older has reached a substantial count of around 703 million, representing approximately 9% of the total global population. Within this demographic, an estimated 5-8% of those aged 60, highlighting the growing need to address sensory modulation challenges for healthy aging. Sensory diet, derived from sensory integration theory, provide a tailored approach to modulating sensory experiences and triggering neuroplastic changes in the brain. Recent neuroimaging studies have revealed intricate structural and functional alterations in the brain associated with the implementation of sensory diets. Furthermore, the integration of the Metaverse, augmented reality, and virtual reality has opened up personalized experiences, fostering cognitive stimulation and emotional well-being for individuals during aging. This article offers a comprehensive exploration of the effectiveness of sensory diets in enhancing attentional control, self-regulation, and alleviating sensory-related distress among the healthy aging and dementia population. By employing precise quantitative evaluations such as sensory processing scales and advanced neuroimaging methodologies, it presents solid evidence of the tangible impact of these interventions. Emphasizing the importance of interdisciplinary cooperation and leveraging technological advancements, the article underscores the crucial need for customized sensory diets to optimize sensory processing and improve the overall well-being of older individuals contending with sensory modulation challenges and dementia.

Young dementia carers (YDCs) rarely receive appropriate training and support. Their visibility and identification remain dangerously low and as a consequence, support initiatives being developed are failing to reach them. This study explored the success (or failure) of YDCs identification pathways as well as the barriers and enablers to their implementation. An explorative qualitative approach was followed drawing on the experiences of parents of YDCs, dementia researchers, professionals in the field of dementia/young carers and young adult carers. Data collection involved semi-structured interviews (n=17) and a participatory 2-hour workshop to discuss and critique preliminary themes as well as explore strategies to increase the visibility and identification of YDCs. Five themes were identified: A ‘whole family approach’ (as a pathway to identification); ‘Not a carer’ (self/family identification); A postcode lottery (high variability of support services); Tailored support that is ‘fit for purpose’ and the ‘power’ of peer support. Recommendations on potential initiatives and actions that can help raise awareness and increase identification success of YDCs are proposed. Our findings support the need for a broad and holistic approach to the identification of YDCs that runs alongside the development of support initiatives that are accessible and relatable. The support itself will play a role in improving subsequent identification or hindering it if not ‘fit for purpose’.

Percutaneous aortic valve replacement (TAVI) has become the treatment of choice for elderly patients with severe aortic valve stenosis because of its less invasiveness compared to surgery. However, it introduces new complications, such as vascular lesions, access site problems, paravalvular leaks, and aortic dissection. Aortic dissection after TAVI is rare but serious, occurring in 0.2% to 0.3% of cases, with both intraprocedural and late cases reported. This case study concerns a 68-year-old woman who developed Stanford B aortic dissection, external iliac artery dissection, and right common femoral artery occlusion after TAVI. Treatment included stenting of the iliac and common femoral arteries, followed by a staged procedure: debranching, thoracic endovascular aortic repair (TEVAR) and endovascular aneurysm repair (EVAR), with satisfactory results. This case, underscores the importance of vigilance in the management of TAVI-related complications to optimize patient care and outcomes.

Background: Preserving health and physical fitness is critical to ensure independent living across the lifespan. Lower levels of physical fitness are associated with age-related cognitive decline and a higher prevalence of mild cognitive impairment (MCI). Thus, this study investigates the influence of a six-month dance intervention on selected measures of physical fitness in older adults with MCI. Methods: In this randomized controlled trial 55 patients with MCI were randomized into a sportive dance training (IG; n=26; Age: 70.7 +/- 5.6 years; 62% female) or an inactive control group (CG; n=24; Age: 69.1 +/- 6.8 years; 46% female).The dance group received two 90-minute dance training sessions per week over a duration of six-months, which focused on learning dance movement patterns. During the training sessions, heartrate was measured to control exercise intensity. Physical fitness was assessed using cardiopulmonary exercise testing (CPET), lower limb functional fitness via sit-to-stand test, handgrip strength and heart rate variability (HRV). Results: We observed that the dance intervention preserved the cardiorespiratory fitness as measured by maximal oxygen uptake (VO2max) during CPET, which decreased in the CG. Furthermore, participants in the IG demonstrated increases in leg and handgrip strength although not statistically significant. HRV displayed a nonsignificant decrease following the intervention. Conclusion: The results of this randomized controlled trial suggest that sportive dance training can preserve physical fitness in older adults with MCI. Although improvements in the other parameters were statistically non-significant, likely due to the small sample size, stabilizing muscular fitness and preventing age-related decline in older adults with MCI is important for maintaining functional independence.

Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing in-creased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play im-portant roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB de-pendence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima-media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of exposure of guinea pigs to CIH (FiO2, 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter en-dothelial function or the contractile response to phenylephrine in these arteries. In contrast, CIH exposure increased the systemic arterial pressure, and enhanced the contractile response to phenylephrine while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta, without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH.

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.

This study uses explainable artificial intelligence to analyze major predictors of poor self-rated health, dementia and their comorbidity, which include various aspects of social support. Data came from the Korean Longitudinal Study of Ageing (2016-2018), with 5527 participants aged 56 or more. The dependent variables were: (1) poor self-rated health (SRH) with 5 categories (very good, good, middle, poor, very poor); (2) dementia (no, yes); and (3) their comorbidity with 4 categories (SRH very good, good or middle, dementia no; SRH very good, good or middle, dementia yes; SRH poor or very poor, dementia no; SRH poor or very poor, dementia yes). The 49 demographic, socioeconomic and health-related predictors were included. The accuracy and area under the receiver operating characteristic curve (AUC) were compared for logistic regression and the random forest. Logistic regression and the random forest registered similar AUCs with the range of 0.80-0.87. Based on random forest variable importance, 18 out of top-20 predictors were identical for SRH, dementia and their comorbidity: previous SRH, life satisfaction - health, age, body mass index, income, chronic diseases, life satisfaction - economic, life satisfaction - overall, grandchildren alive, friendship meeting, brothers/sisters alive, class identity, children alive, social activity - friendship, education, children in weekly contact, religion and drinker. However, some variations were found among the three dependent variables, i.e., previous SRH for comorbidity (1st) and SRH (1st) compared to dementia (11th), grandchildren alive for SRH (6th) and dementia (4th) compared to comorbidity (9th), chronic diseases for comorbidity (6th) compared to SRH (10th) and dementia (10th). In terms of Shapley Additive Explanation (SHAP) values, the probability of dementia is expected to decrease by 5.57% in case a predictor grandchildren alive is included to the model. This study highlights the importance of social support for the prediction of poor self-rated health, dementia and their comorbidity. Specifically, the promotion of family support and friendship activity for elders would be vital for the prevention and management of their self-rated health and dementia.

Dementia is a rising public health concern. Feeding and nutritional problems increase as the disease progresses, affecting clinical course and caregiver burden. While some guidelines advise against percutaneous endoscopic gastrostomy (PEG) and tube feeding in advanced dementia, conflicting evidence exists. This study aims evaluating nutritional status and the influence of PEG-feeding on outcome and evolution of nutritional/progonosis markers of patients with severe dementia (PWSD) who underwent gastrostomy for nutritional support. We conducted a 16-year rectrospective study on 100 PEG-fed PWSD with strong familiar support. We evaluated survival PEG-feeding period, safety, and objective nutritional/progonosis data at the gastrostomy day and after 3 months: Body Mass Index (BMI), Mid Upper Arm Circumference, Tricipital Skinfold, Mid-Arm Muscle Circumference, albumin, transferrin, total cholesterol and hemoglobin. Most patients presented low values in these nutritional/progonosis parameters. No major life-threatening PEG complications were reported. The mean survival time after gastrostomy was 27.9 months (median of 17 months). Female sex, BMI recovery at 3 months, and higher baseline hemoglobin levels were associated with a reduced risk of death and increased survival time. The study concluded that, in carefully selected PWSD with strong familiar support, PEG feeding can improve nutritional status and have a positive impact on survival.

The genetic bases of Alzheimer's disease (AD) and frontotemporal dementia (FTD) have been comprehensively studied, which is not the case for atypical cases not classified into these diagnoses. In the present study, we aim to contribute to the molecular understanding of the development of non-AD and non-FTD dementia by surveying rare pathogenic variants. The analysis was performed on 91 patients, the DNA samples of which were pooled and then subjected to whole exome sequencing. Among detected variants two are rare pathogenic and show significant difference in frequency between the analyzed pool and gnomAD Bulgarian control exomes. The rs373478202, G&gt;T, B9D1 variant, most likely present in heterozygous state; is causative for the autosomal recessive ciliopathy- Joubert syndrome, which involves specific CNS malformation. The rs148918985, C&gt;T, ASS1 variant leads to arginosuccinate enzyme deficiency and in compound heterozygosity with other rare pathogenic variant detected in the same gene causes the late-onset form of citrullinemia type I. This disorder causes high ammonia levels, which can lead to cerebral dysfunction. In conclusion, the detected rare pathogenic variants suggest that, in certain cases, the development of non-AD and non-FTD dementia can be mediated by structural alterations in neuronal cilia or by hyperammoniemia.

Over the years there has been an increase in the development of assistive technologies (AT’s). The implementation and scaling of AT’s at care organizations remains challenging. Moreover, to date, it has been underexplored during which stages of dementia these technologies can be best implemented. Previous work has developed an infographic providing guidance on when best to introduce AT’s for people with dementia. Although this infographic is relevant, it was based solely on the experience of the authors during various national and international projects. However, over the years a wide spread of studies has been conducted in the field of dementia on the use and implementation of technology for PwD. Therefore, in this paper we will revise the current infographic based on the insight gained from existing literature and complement these by interviews with expert on the implementation of care technology

In advanced Parkinson’s disease (PD), and especially in PD related dementia (PDD), psychotic symptoms are common. One of the manifestations of psychosis in PD is delusional misidentification syndrome, a phenomenon in which the patient believes the identity of a person, object or location has been duplicated or altered. Our patient, a 75-year-old female, was diagnosed with idiopathic Parkinson’s disease at the age of 68. Recently, her cognition deteriorated and she developed the believe that she lived in a replica of her real home. The delusion resolved completely with rivastigmine patches. Also visual hallucinations improved on treatment. This suggests that the dysfunctional connections were likely to be cholinergic.

Alzheimer's disease (AD) is a complex disease involving multiple factors such as amyloid plaque formation, mitochondrial dysfunction, telomere length, and oxidative stress. As the disease began 20 years before the onset of clinical symptoms, treatment of AD after its onset is likely to be too late to have a significant effect. Therefore, prevention from an early stage is important. Twendee X®︎ (TwX, Oxicut®︎) is an antioxidant supplement consisting of eight ingredients. TwX has been proven to prevent dementia in patients with mild cognitive impairment (MCI) in a multicenter, randomized, double-blind, placebo-controlled, prospective intervention trial. To elucidate the mechanisms of TwX on brain and cellular function, TwX was administered in in vitro experiments and in a C57BL/6 old wild-type, and spontaneous hyperglycemia model with accelerated cognitive decline, and its effects on diabetes, brain autophagy, neurogenesis, and telomere length were evaluated in comparison with those of the non-treated groups. TwX protected mitochondria from oxidative stress with higher antioxidant capacity than a single antioxidant. TwX not only lowered blood glucose levels, but also suppressed reduction of brain neurogenesis and loss of autophagy. Telomeres in aged mice were significantly longer than those in non-TwX-treated mice. Development of dementia is based on many factors of brain function. TwX was suggested to prevent dementia not only by its antioxidant effects, but also by its effects on diabetes, brain neurogenesis, telomere deficiency, and energy production.

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.

Background: The psychomotor agitation of the BPSD is one of the common issues in aged care facilities, leading to the poor functional and medical consequences. Psychotropic interventions are the preferable choice of treatment. But which medication should be the prescribers first preference? This review aims to compare pharmacological interventions for psychomotor agitation, judging them according to their effectuality and justifiability profiles. This is to be achieved by retrieving information from RCTs and systematic reviews. Objectives: This review evaluates evidence from RCTs, systematic reviews, and meta-analyses of BPSD patients who had taken agitation treatments. Assessing the efficacy of antidepressants and antipsychotic treatments when compared to each other for the purpose of improving agitation outcomes. Methods: This narrative review includes RCTs and retrospective studies that were comparing one or more active ingredient medications with another or with a placebo, along with sys-tematic reviews comparing antidepressants with antipsychotics such as quetiapine, olanzapine, and risperidone. Studies extracted by searching accessing databases, such as PubMed, OVID, and Cochrane with restrictions of date from 2000 to 2021 and English language. Quality of evidence: The quality of systematic reviews was judged against AMSTAR score, and RCTs were judged according to CONSORT checklist for RCT protocols. Conclusion: There are still few studies of serotonin targeting treatment of agitation in BPSD. The SSRIs such as citalopram were associated with a reduction in symptoms of agitation, and lower risk of adverse effects compared to antipsychotics. This review also illustrates brexpiprazole as a target of multimodal neurotransmitters such as dopamine, serotonin, and norepinephrine; and dextromethorphan, OR dextromethorphan associated with bupropion or quinidine as a blockade of NMDA receptors. The outcome of this review suggests that further studies involving more dementia/Alzheimer’s participants should be conducted. Future studies are required also to assess the long-term safety and efficacy of SSRI, brexpiprazole, dextromethorphan treatments for agitation in BPSD.

Important policy developments in dementia and palliative care in nursing homes between 2010 and 2015 in Flanders, Belgium might have influenced which people die in nursing homes and how they die. We aimed to examine differences between 2010 and 2015 in the prevalence and characteristics of residents with dementia in nursing homes in Flanders, and their palliative care service use and comfort in the last week of life. We used two retrospective epidemiological studies, including 198 residents in 2010 and 183 in 2015, who died with dementia in representative samples of nursing homes in Flanders. We found a 23%-point increase in dementia prevalence (P-value<0.001), with a total of 11%-point decrease in severe to very severe cognitive impairment (P=0.04). Controlling for this difference in resident characteristics, in the last week of life, there were increases in the use of pain assessment (+20%-point; P<0.001) and assistance with eating and drinking (+10%-point; P=0.02) but no change in total comfort. The higher prevalence of dementia in nursing homes with no improvement in residents’ total comfort while dying emphasize an urgent need to better support nursing homes in improving their capacities to provide timely and high-quality palliative care services to more residents dying with dementia.

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.

The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy Body Dementia (LBD), which includes Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD). The meeting featured eight internationally known scientists from Europe and the United States and attracted over 200 scientists and physicians from academic centers, the National Institutes of Health and the pharmaceutical industry. Methods for confirming and quantifying the presence of Lewy body and Alzheimer pathology as well as novel biomarkers were discussed.

The term dehumanisation refers to the ways in which a person is perceived to be less than human or treated as if they are less than human. It involves treating a person as if they are a child or infant, like an animal or non-living object, or as if they are dead, or any other way in which someone fails to be treated like a human being with an adult identity. Dehumanisation is widespread in dementia care; it is a major obstacle to person-centred care and has poor outcomes for people with dementia. This article proposes a new model of dehumanisation. The New Model presents a new way of describing dehumanisation that has been synthesised from current understanding about the phenomenon and reflects what is presently known about the subject. The model aims to summarise existing theories and models of dehumanisation and make dehumanisation theory accessible to students and trainees in healthcare. This article describes the new model, discusses existing models and theories in the literature, and explores the potential role of the new model in solutions for reducing dehumanisation in dementia care.

Context: A clinical video telehealth (CVT) program was implemented improve access and quality of dementia care to patients and their caregivers in rural areas. The program was offered as part of an established dementia clinic/geriatric primary care clinic in collaboration with five community-based outpatient clinics (CBOC’s) affiliated with the Tennessee Valley Healthcare System (TVHS) in middle Tennessee. Telehealth support was provided by a physician – social worker team visit. Methods: Telehealth training and equipment were provided to clinic personnel, functioning part-time with other collateral clinical duties. Patients and caregivers were referred by primary care providers and had an average of 1 to 2 CVT encounters originating at their local CBOC lasting 20 to 30 minutes. Clinical characteristics and outcomes of patients and caregivers receiving CVT support were collected by retrospective electronic medical record (EMR) review. Results: Over a 3-year period 45 CVT encounters were performed on patient-caregiver pairs, followed for a mean of 15 (1-36) months. Some 80% patients had dementia confirmed and 89% of these had serious medical comorbidities, took an average of 8 medications, and resided at a distance of 103 (76-148) miles from the medical center. Dementia patients included 33% with late stage dementia, 25% received additional care from a mental health provider, 23% took antipsychotic medications, 19% transitioned to a higher level of care, and 19% expired an average of 10.2 months following consultation. Caregiver distress was present in 47% of family members. Consult recommendations included 64% community-based long-term care services and supports (LTSS), 36% medications, and 22% further diagnostic testing. Acceptance of the CVT encounter was 98%, with 8770 travel miles saved. Conclusion: CVT is well received and may be helpful in providing dementia care and supporting dementia caregivers to obtain LTSS for high-need older adults in rural areas.

Dementia is a public health priority, in which memory impairments are prevalent and affects an individual’s daily activities. Research has tried to find ways to support memory problems of individuals with dementia. Self reference effect (SRE) has been shown to benefit memory in healthy, non-dementia group. The study aimed to investigate if SRE will improve memory performance of individuals with dementia. We used ecologically valid Ownership Procedure and the Remember/Know Paradigm to examine the Self-Reference Effect (SRE) on memory. It was hypothesised that participants living with dementia will perform differently in the recall of items that were self-referentially encoded compared to items other-referentially encoded and that the memory will be different in control participants than in those that live with dementia. The research found that self-referential processes did not have effect on memory in individuals with dementia. We suggest that impaired self-awareness may have contributed to the lack of this effect. However, we had a small sample size and these findings should be treated with caution.

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.

Detecting and evaluating pain in people with cognitive impairment, especially dementia, is a challenge. Their ability to accurately report pain and comprehend related questions decreases the reliability of their self-report. This has contributed to the fact that pain is underdiagnosed and undertreated in this population, which can lead to involuntary ageism. The design and assessment of this training capsule under the context of the European COST-Action TD1005 responds to the need for education and training in "Pain Assessment In Cognitive Impairment, especially dementia" and the development of the internationally agreed observational PAIC15 scale. The 3-hour capsule, intended for healthcare workers and caregivers, consists of theoretical-practical levels: 1) basic concepts and challenges in pain in aging, cognitive impairment/dementia, 2) available scales and PAIC15, 3) video presentation of clinical cases illustrating a 3×2 matrix of situations (rest, transfer and experimental pain) and stages of disease (mild and moderate). The objectives focused on training the ability to observe, detect, and assess the signs of pain using PAIC15 and its feasibility. The pre-post analysis in a Master educational setting showed agreement with the results obtained in the Spanish national survey on 1) scarce knowledge of observational tools and their use, and 2) uncertainty in the identification of signs of pain and feasibility in moderate/severe scenarios. The capsule improved the ability to identify and evaluate the pain items, especially facial expressions, and their confidence on observational tools. Debriefings highlighted the relevance of observational scales in dementia and the gain obtained using the new observational instrument.

As a result of an increasing population of aged people in sub-Saharan Africa, dementia is predicted to surge up to 90% by 2030. This review is set to assess the prevalence of dementia, for 65+ aged population in sub-Saharan states and particularly in Tanzania. Subsequently, the review will identify the possible risks factors – age, gender, level of education, cardiovascular problems, diabetes and mild cognitive impairment – and will lay out the challenges of reducing the dementia burden in Tanzania. Additionally, the review explores the current approaches in solving dementia disorders, including a general view of the public understanding of dementia. Also, the review recognises the gaps in government funding to mental health, a barrier to service access and the need for further research on Alzheimer’s and other dementias. Lastly, the review links the sustainable development goals (SDGs) addressed and appreciate the impact of the coronavirus pandemic on the fight against dementia.

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.

Dementia, characterized by cognitive decline beyond age-related expectations, poses a formidable global health challenge. With an estimated 55 million individuals affected worldwide and 10 million new cases annually, dementia profoundly impacts memory, comprehension, language, and behavior. Then, the global diabetes population increased from 108 million in 1980 to 422 million in 2014, with a more rapid rise in prevalence observed in low- and middle-income countries compared to high-income countries. Individuals with diabetes have an increased risk of cognitive problems, including a higher likelihood of developing dementia, Alzheimer's disease, and vascular dementia, especially in older age. Managing diabetes through diet, physical activity, medication, and consistent screening and treatment for complications can prevent or delay its consequences.Globally ranking as the seventh leading cause of death, dementia's societal implications are substantial. The chapter delves into Mild Cognitive Impairment (MCI), a precursor to dementia, emphasizing its global epidemiological trends. Neuroimaging, particularly Functional Near-Infrared Spectroscopy (fNIRS), emerges as a non-invasive diagnostic tool, surpassing traditional imaging methods' portability. The chapter investigates the effects of non-invasive electrical stimulation on neurovascular tissues, shedding light on its impact including potential to address metaboreflex related reduced exercise tolerance. Furthermore, the chapter presents a clinical trial (ClinicalTrials.gov NCT04626453 and NCT04812288) examining the effects of a 2-month exercise program on cognitive function and muscular oxidative capacity in older adults with type 2 diabetes. The study's design, individualized exercise regimens to address muscle mechanoreflex and metaboreflex responses, and their physiological changes during exercise are discussed, offering insights into the interplay between exercise tolerance, cognition, and vascular health. The findings contribute to tailored and effective interventions for cognitive well-being. Here, our exploration extends to the application of transcranial electrical stimulation (tES) in optimizing exercise performance, with a focus on its various forms, including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS). A physiological modeling approach based on the neurovascular unit (NVU) is employed, revealing potential avenues for also treating vascular dementia (often noted to have a strong association with type 2 diabetes) through tACS, guided by human-in-the-loop approaches. Here, modal analysis for control is applied to assess the NVU model's characteristic dynamics under tACS, providing a comprehensive understanding of neurovascular coupling modes.In summary, this chapter synthesizes diverse facets in type 2 diabetes comorbidity and cognitive decline, ranging from global impact and diagnostic criteria to innovative interventions like exercise and transcranial electrical stimulation. The multidisciplinary approach integrates epidemiology, clinical trials, and physiological modeling, contributing valuable insights into the holistic management of cognitive health and neurovascular function.

A recent report from the American Heart Association in 2018 shows that over 103 million American adults have hypertension. The angiotensin-converting enzyme (ACE) (EC 3.4.15.1) is a dipeptidyl carboxylase that, when inhibited, can reduce blood pressure through the renin-angiotensin system. ACE inhibitors are used as a first-line medication to be prescribed to treat hypertension, chronic kidney disease, heart failure among others. It has been suggested that ACE inhibitors can reduce the symptoms in mouse models. Despite the benefits of ACE inhibitors, previous studies also have suggested that alterations in the ACE gene are risk factors for Alzheimer’s disease (AD) and other neurological diseases. In mice, overexpression of ACE in the brain reduces symptoms of the AD-model systems. Thus, we find opposing effects of ACE on health. To clarify the effects, we dissect the functions of ACE as follows: (1) angiotensin-converting enzyme that hydrolyzes angiotensin I to make angiotensin II in the renin-angiotensin system; (2) amyloid-degrading enzyme that can hydrolyze beta-amyloid and reduce amyloid toxicity. The efficacy of the ACE inhibitors is well established in humans, while the knowledge specific to AD remains to be open for further research. We provide an overview of ACE and inhibitors that link a wide variety of age-related comorbidities from hypertension to Alzheimer’s disease to aging. ACE also serves as an example of the middle-life crisis theory that assumes deleterious events during the midlife, leading to age-related later events.

Neurodegenerative diseases of protein misfolding affect humans and animals. In humans, these diseases include Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Western Pacific amyotrophic lateral sclerosis and Parkinsonism-dementia complex (ALS/PDC). Mineral exposure may be important in the pathogenesis of protein misfolding cascades. The possible association of bentonite, montmorillonite, and mineral risk factors with Alzheimer’s disease, Parkinson’s disease, ALS, and Western Pacific ALS/PDC is analyzed and discussed.

Once considered relatively benign, superficial vein thrombosis (SVT) of the lower limbs is often linked to deep vein thrombosis (DVT) or pulmonary embolism (PE). Treatment goals include alleviating local symptoms and preventing SVT from recurring or extending into DVT or PE. Fondaparinux 2.5 mg once daily for 45 days is the treatment of choice for most patients with SVT. Potential alternatives include intermediate-dose low-molecular-weight heparin or the direct oral factor Xa inhibitor rivaroxaban. Despite these treatment options, significant gaps remain, including the role of systemic or topical anti-inflammatory agents alone or combined with anticoagulants, and the optimal duration of anticoagulation for patients at varying risk levels. Additionally, the efficacy and safety of factor Xa inhibitors other than rivaroxaban, management of upper extremity SVT, and optimal treatment for SVT near the sapheno-femoral or sapheno-popliteal junctions are not well understood. This narrative review aims to summarize current evidence on anticoagulant treatment for SVT, highlight key unmet needs in current approaches, and discuss how ongoing studies may address these gaps.

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.

Dementia education and training for workforce development is becoming increasingly important in bridging knowledge gaps among health and social care practitioners in the UK and internationally. Dementia Education for Workforce Excellence (DEWE) was developed during the COVID-19 pandemic blending both synchronous and asynchronous instruction and delivered across three different contexts: care homes, home care, and nurse education within the UK and India. This study aimed to evaluate DEWE using mixed methods with online survey data analyzed descriptively and interview data analyzed thematically. Integration of survey and interview data aimed toward a comprehensive evaluation of this novel approach for dementia workforce development. Thirty-four social care practitioners and nurse educators completed the online survey demonstrating high-level learner satisfaction; learning gains; behavioral change, and motivation to share new knowledge. Four key themes developed from the analysis of interviews (n=9) around participants’ pursuit of new knowledge; delivery modes in DEWE; learning gains and impact of DEWE; and adaptations for future program implementation. Findings suggest DEWE is an innovative resource that promotes person- and relationship-centered dementia care across all stages of one’s dementia journey. Cultural adaptations are recommended for international delivery to ensure contextual alignment and maximum impact.

Abstract Forensic institutions throughout the country house patients with severe psychiatric illness and history of criminal violations. Improved medical care, hygiene, and nutrition led to unmatched longevity in this population which previously lived on average 15 to 20 years shorter than the public at large. On the other hand, longevity has contributed to increased prevalence of age-related diseases, including neurodegenerative disorders, which complicate clinical management. Forensic institutions, originally intended for the treatment of younger individuals, are ill-equipped for the growing number of older offenders. Moreover, as antipsychotic drugs became available in 1950s and 1960s, we are observing the first generation of forensic detainees who had aged on dopamine blockers. Although the consequences of long-term treatment with these agents are unclear, schizophrenia-associated gray matter loss, may contribute to the development of early dementia. Taken together, increased lifespan and subsequent cognitive deficit observed in long-term psychiatric institutions brought forth questions and dilemmas unencountered by the previous generations of clinicians, such as: 1. Does the presence of neurocognitive dysfunction justify antipsychotic dose reduction or discontinuation despite a lifelong history of schizophrenia and violent behavior? 2. Should neurolipidomic interventions become the standard of care in elderly individuals with lifelong schizophrenia and dementia? 3. Can patients with schizophrenia and dementia meet the Dusky standard and stand trial? 4. Should neurocognitive disorders in elderly with lifelong schizophrenia be treated differently than age-related neurodegeneration? In this article, we describe strategies for potentially slowing the development of neurocognitive disorders in forensic patients with chronic mental illness by adopting a three-prong strategy: 1. Approaching lifelong psychosis from microbial and immunological perspective. 2. Identify modifiable risk factors for age-related diseases in forensic institutions. 3. Utilizing novel receptor-independent treatments for chronic psychosis.

Frontal Temporal Dementia (FTD) is a neurological disorder known to have less therapeutic options. So far only a few biomarkers are available for FTD that can be used as potential comorbidity targets. To this end, in the present study we aim to identify potential biomarkers or susceptible genes for FTD that show comorbidities with diseases such as COVID-19 and Breast Cancer. Gene expression Omnibus datasets containing FTD expression profiles from African American and white ethnicity background were included in our study. In FTD samples of GSE193391 dataset, we identified 305 DEGs with 168 genes being up-regulated and 137 genes being down-regulated. We conducted comorbidity analysis for COVID-19 and Breast cancer followed by analysis of potential drug interactions, pathogenicity, analysis of genetic variants and functional enrichment analysis. Resulting genes AKT3, GFAP, ADCYAP1R1, VDAC1, and C4A showed significant transcriptomic alterations in FTD and significant comorbidity status with COVID-19 and Breast cancer. Functional pathway analysis revealed that these comorbid genes were significantly enriched in the pathways such as glioma, JAK/STAT signaling, systematic lupus erythematosus, neurodegeneration-multiple diseases and neuroactive ligand-receptor interaction. Overall, from these results, we concluded that these genes could be recommended as potential therapeutic targets for the treatment of comorbidities in FTD.

Age-in-place can reduce the progress of dementia syndrome and improve the quality of life of the sufferers and their families. This work proposes an innovative information home support system to be established at the houses of people suffering from dementia. The main innovation of the system are its transparent character that overcomes the need for training of the sufferer, as well as the exploitation of a well-known technique for dementia, namely music therapy. It addresses the need of people suffering from dementia as well as their familiars to be recognized by them and have better interaction and collaboration. The system offers a ubiquitous recognition system, just by using smart devices like smart-phones or smart-wristbands. When a familiar person is detected in the house, then a sound file is reproduced on smart speakers placed in the house, in order to trigger the memory, based on the principles of music therapy. The system reproduced the appropriate time at 100% of the cases and the benefits of music therapy are evident daily. To the best of the authors' knowledge, this is the first system of its kind ever reported in the literature.

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.

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.

Because of an often complicated and difficult-to-access care system, help-seeking for people with suspected dementia can be stressful. Difficulty in help-seeking may contribute to carer burden, in addition to other known stressors in dementia care. This study examined the relationship between perceived help-seeking difficulty and carer burden, and the barriers contributing to perceived difficulty. We interviewed 110 carers accessing a community-based dementia assessment service for suspected dementia of a family member for their perceived difficulty, delays, and barriers in help-seeking, and carers burden in terms of role strain, self-criticism, and negative emotions. Linear regression models showed that perceived help-seeking difficulty is associated with carer self-criticism, while carer role strain and negative emotions are associated with symptom severity of the person with dementia but not help-seeking difficulty. Inadequate knowledge about symptoms, service accessibility, and affordability together explained more than half of the variance in perceived help-seeking difficulty (Nagelkerke R2 = .56). Public awareness about symptoms, support in navigating service, and financial support may reduce perceived difficulty in help-seeking, which in turn may reduce carer self-criticism during the early course of illness.

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.