Herbal medicine IMOD suppresses LPS-induced production of proinflammatory cytokines in human dendritic cells

Traditional medicines that stimulate or modulate the immune system can be used as innovative approaches to treat immunological diseases. The herbal medicine IMOD has been shown to strongly modulate immune responses in several animal studies as well as in clinical trials. However, little is known about the mechanisms of IMOD to modulate immunity. Here we have investigated whether IMOD modulates the immunological function of human dendritic cells (DCs). IMOD alone did not induce DC maturation nor production of cytokines. Notably, IMOD decreased the production of pro-inflammatory cytokines IL-6, IL-12 p70 and TNFα by LPS-activated DCs at both mRNA and protein levels in a dose dependent manner. In contrast, treatment with IMOD did not affect LPS induced-production of the anti-inflammatory cytokine IL-10. Furthermore, IMOD inhibited T cell activation/proliferation by LPS-treated DCs and skewed T-cells responses towards the T helper type 2 polarization. These data strongly indicate that IMOD has a potent immunomodulatory ability that affects TLR signaling and thereby modulates DC function. Insight into the immunomodulatory effect of herbal medicine IMOD may provide innovative strategies to affect the immune system and to help combat various disease

Accelerated Simulation Methodologies for Computational Vascular Flow Modelling

Vascular flow modelling can improve our understanding of vascular pathologies and aid in developing safe and effective medical devices. Vascular flow models typically involve solving the nonlinear Navier-Stokes equations in complex anatomies and using physiological boundary conditions, often presenting a multi-physics and multi-scale computational problem to be solved. This leads to highly complex and expensive models that require excessive computational time. This review explores accelerated simulation methodologies, specifically focusing on computational vascular flow modelling. We review reduced order modelling (ROM) techniques like zero-/one-dimensional and modal decomposition-based ROMs and machine learning (ML) methods including ML-augmented ROMs, ML-based ROMs and physics-informed ML models. We discuss the applicability of each method to vascular flow acceleration and the effectiveness of the method in addressing domain-specific challenges. When available, we provide statistics on accuracy and speed-up factors for various applications related to vascular flow simulation acceleration. Our findings indicate that each type of model has strengths and limitations depending on the context. To accelerate real-world vascular flow problems, we propose future research on developing multi-scale acceleration methods capable of handling the significant geometric variability inherent to such problems.</p

Subject-specific multiporoelastic model for exploring the risk factors associated with the early stages of Alzheimer's disease

There is emerging evidence suggesting that Alzheimer’s disease is a vascular disorder, caused by impaired cerebral perfusion, which may be promoted by cardiovascular risk factors that are strongly influenced by lifestyle. In order to develop an understanding of the exact nature of such a hypothesis, a biomechanical understanding of the influence of lifestyle factors is pursued. An extended poroelastic model of perfused parenchymal tissue coupled with separate workflows concerning subject-specific meshes, permeability tensor maps and cerebral blood flow (CBF) variability is utilised. The subject-specific datasets used in the modelling of this paper were collected as part of prospective data collection. Two cases were simulated involving male, non-smokers (control and MCI case) during two states of activity (high and low). Results showed a marginally reduced clearance of CSF/ISF, elevated parenchymal tissue displacement and CSF/ISF accumulation and drainage in the MCI case. Peak perfusion remained at 8 mm/s between the two cases

Effects of variations of flow and heart rate on intra-aneurysmal hemodynamics in a ruptured internal carotid artery aneurysm during exercise

Background: Hemodynamics is thought to play an important role in the mechanisms responsible for initiation, growth, and rupture of intracranial aneurysms. Computational fluid dynamic (CFD) analysis is used to assess intra-aneurysmal hemodynamics. Objectives: This study aimed to investigate the effects of variations in heart rate and internal carotid artery (ICA) flow rate on intra-aneurysmal hemodynamics, in an ICA aneurysm, by using computational fluid dynamics. Patients and Methods: Computed tomography angiography (CTA) was performed in a 55 years old female case, with a saccular ICA aneurysm, to create a patient-specific geometrical anatomic model of the aneurysm. The intra-aneurysmal hemodynamic environments for three states with different flow and heart rates were analyzed using patient-specific image-based CFD modeling. Results: Results showed significant changes for the three simulated states. For a proportion of the states examined, results were counterintuitive. Systolic and time-averaged wall shear stress and pressure on the aneurysm wall showed a proportional evolution with the mainstream flow rate. Conclusion: Results reinforced the pivotal role of vascular geometry, with respect to hemodynamics, together with the importance of performing patient-specific CFD analyses, through which the effect of different blood flow conditions on the aneurysm hemodynamics could be evaluated

Subject-specific multi-poroelastic model for exploring the risk factors associated with the early stages of Alzheimer's disease

none14siThere is emerging evidence suggesting that Alzheimer’s disease is a vascular disorder, caused by impaired cerebral perfusion, which may be promoted by cardiovascular risk factors that are strongly influenced by lifestyle. In order to develop an understanding of the exact nature of such a hypothesis, a biomechanical understanding of the influence of lifestyle factors is pursued. An extended poroelastic model of perfused parenchymal tissue coupled with separate workflows concerning subject-specific meshes, permeability tensor maps and cerebral blood flow variability is used. The subject-specific datasets used in the modelling of this paper were collected as part of prospective data collection. Two cases were simulated involving male, non-smokers (control and mild cognitive impairment (MCI) case) during two states of activity (high and low). Results showed a marginally reduced clearance of cerebrospinal fluid (CSF)/interstitial fluid (ISF), elevated parenchymal tissue displacement and CSF/ISF accumulation and drainage in the MCI case. The peak perfusion remained at 8 mm s-1 between the two cases.noneGuo L.; Vardakis J.C.; Lassila T.; Mitolo M.; Ravikumar N.; Chou D.; Lange M.; Sarrami-Foroushani A.; Tully B.J.; Taylor Z.A.; Varma S.; Venneri A.; Frangi A.F.; Ventikos Y.Guo L.; Vardakis J.C.; Lassila T.; Mitolo M.; Ravikumar N.; Chou D.; Lange M.; Sarrami-Foroushani A.; Tully B.J.; Taylor Z.A.; Varma S.; Venneri A.; Frangi A.F.; Ventikos Y

Randomized controlled trial of computerized cognitive behavioural therapy for depressive symptoms: effectiveness and costs of a workplace intervention

Background Depression and anxiety are major causes of absence from work and underperformance in the workplace. Cognitive behavioural therapy (CBT) can be effective in treating such problems and online versions offer many practical advantages. The aim of the study was to investigate the effectiveness of a computerized CBT intervention (MoodGYM) in a workplace context.Method The study was a phase III two-arm, parallel randomized controlled trial whose main outcome was total score on the Work and Social Adjustment Scale (WSAS). Depression, anxiety, psychological functioning, costs and acceptability of the online process were also measured. Most data were collected online for 637 participants at baseline, 359 at 6 weeks marking the end of the intervention and 251 participants at 12 weeks post-baseline.Results In both experimental and control groups depression scores improved over 6 weeks but attrition was high. There was no evidence for a difference in the average treatment effect of MoodGYM on the WSAS, nor for a difference in any of the secondary outcomes.Conclusions This study found no evidence that MoodGYM was superior to informational websites in terms of psychological outcomes or service use, although improvement to subthreshold levels of depression was seen in nearly half the patients in both groups

Velocity measurement in carotid artery: Quantitative comparison of time-resolved 3D phase-contrast MRI and image-based computational fluid dynamics

Background: Understanding hemodynamic environment in vessels is important for realizing the mechanisms leading to vascular pathologies. Objectives: Three-dimensional velocity vector field in carotid bifurcation is visualized using TR 3D phase-contrast magnetic resonance imaging (TR 3D PC MRI) and computational fluid dynamics (CFD). This study aimed to present a qualitative and quantitative comparison of the velocity vector field obtained by each technique. Subjects and Methods: MR imaging was performed on a 30-year old male normal subject. TR 3D PC MRI was performed on a 3 T scanner to measure velocity in carotid bifurcation. 3D anatomical model for CFD was created using images obtained from time-of-flight MR angiography. Velocity vector field in carotid bifurcation was predicted using CFD and PC MRI techniques. A statistical analysis was performed to assess the agreement between the two methods. Results: Although the main flow patterns were the same for the both techniques, CFD showed a greater resolution in mapping the secondary and circulating flows. Overall root mean square (RMS) errors for all the corresponding data points in PC MRI and CFD were 14.27% in peak systole and 12.91% in end diastole relative to maximum velocity measured at each cardiac phase. Bland-Altman plots showed a very good agreement between the two techniques. However, this study was not aimed to validate any of methods, instead, the consistency was assessed to accentuate the similarities and differences between Time-resolved PC MRI and CFD. Conclusion: Both techniques provided quantitatively consistent results of in vivo velocity vector fields in right internal carotid artery (RCA). PC MRI represented a good estimation of main flow patterns inside the vasculature, which seems to be acceptable for clinical use. However, limitations of each technique should be considered while interpreting results

The association of health literacy with adherence in older 2 adults, and its role in interventions: a systematic meta-review

Background: Low health literacy is a common problem among older adults. It is often suggested to be associated with poor adherence. This suggested association implies a need for effective adherence interventions in low health literate people. However, previous reviews show mixed results on the association between low health literacy and poor adherence. A systematic meta-review of systematic reviews was conducted to study the association between health literacy and adherence in adults above the age of 50. Evidence for the effectiveness of adherence interventions among adults in this older age group with low health literacy was also explored. Methods: Eight electronic databases (MEDLINE, ERIC, EMBASE, PsycINFO, CINAHL, DARE, the Cochrane Library, and Web of Knowledge) were searched using a variety of keywords regarding health literacy and adherence. Additionally, references of identified articles were checked. Systematic reviews were included if they assessed the association between health literacy and adherence or evaluated the effectiveness of interventions to improve adherence in adults with low health literacy. The AMSTAR tool was used to assess the quality of the included reviews. The selection procedure, data-extraction, and quality assessment were performed by two independent reviewers. Seventeen reviews were selected for inclusion. Results: Reviews varied widely in quality. Both reviews of high and low quality found only weak or mixed associations between health literacy and adherence among older adults. Reviews report on seven studies that assess the effectiveness of adherence interventions among low health literate older adults. The results suggest that some adherence interventions are effective for this group. The interventions described in the reviews focused mainly on education and on lowering the health literacy demands of adherence instructions. No conclusions could be drawn about which type of intervention could be most beneficial for this population. Conclusions: Evidence on the association between health literacy and adherence in older adults is relatively weak. Adherence interventions are potentially effective for the vulnerable population of older adults with low levels of health literacy, but the evidence on this topic is limited. Further research is needed on the association between health literacy and general health behavior, and on the effectiveness of interventions

Hemodynamics of thrombus formation in intracranial aneurysms: an in-silico observational study

How prevalent is spontaneous thrombosis in a population containing all sizes of intracranial aneurysms? How can we calibrate computational models of thrombosis based on published data? How does spontaneous thrombosis differ in normo- and hypertensive subjects? We address the first question through a thorough analysis of published datasets that provide spontaneous thrombosis rates across different aneurysm characteristics. This analysis provides data for a subgroup of the general population of aneurysms, namely, those of large and giant size (>10 mm). Based on these observed spontaneous thrombosis rates, our computational modeling platform enables the first in silico observational study of spontaneous thrombosis prevalence across a broader set of aneurysm phenotypes. We generate 109 virtual patients and use a novel approach to calibrate two trigger thresholds: residence time and shear rate, thus addressing the second question. We then address the third question by utilizing this calibrated model to provide new insight into the effects of hypertension on spontaneous thrombosis. We demonstrate how a mechanistic thrombosis model calibrated on an intracranial aneurysm cohort can help estimate spontaneous thrombosis prevalence in a broader aneurysm population. This study is enabled through a fully automatic multi-scale modeling pipeline. We use the clinical spontaneous thrombosis data as an indirect population-level validation of a complex computational modeling framework. Furthermore, our framework allows exploration of the influence of hypertension in spontaneous thrombosis. This lays the foundation for in silico clinical trials of cerebrovascular devices in high-risk populations, e.g., assessing the performance of flow diverters in aneurysms for hypertensive patients

Public health interventions for Aedes control in the time of Zikavirus- A metareview on effectiveness of vector control strategies

Background: There is renewed interest in effective control measures to control Zika and dengue vectors. A synthesis of published systematic reviews with a focus on grading of intervention evidence is warranted to determine the reliability of evidence for control strategies. Methodology: We conducted a meta-review (a systematic review of systematic reviews) assessing the effectiveness of any Aedes control measure. We searched Scopus and Medline for relevant reviews through to 11 May 2016. Titles, abstracts and full texts were assessed independently for inclusion by two authors. Data extraction was performed independently in duplicate using a standardised form and validity of the evidence in each review was assessed using GRADE criteria. Findings: 13 eligible systematic reviews that investigated the effect of community interventions on entomological parameters (such as vector density) or disease incidence were included. Quality of evidence was mostly low to very low due to poor reporting of study design, observational methodologies, heterogeneity, and indirect outcomes, hindering an evidence-based recommendation. Biological controls seem to achieve better reduction of entomological indices than chemical controls, while educational campaigns can reduce breeding habitats and interrupt disease transmission cycle. Integrated control strategies may not add efficiency to educational campaigns. Conclusions: Despite decades of Aedes mosquito abatement programmes, mosquito populations are widely established and abundant, and associated with a significant disease burden. The efficiency of any control programme is dependent on local settings and resources. More good quality primary studies for the control of Aedes transmitted diseases are still required