The effect of multiple sclerosis therapy on gut microbiota dysbiosis: a longitudinal prospective study

Gut microbiota has complex immune functions, related to different pathologies, including multiple sclerosis (MS).This study evaluated the influence of treatments on gut microbiota in people with MS (PwMS). The research comprised 60 participants, including 39 PwMS and 21 healthy controls (HC). Among the PwMS, 20 were prescribed a disease-modifying therapy (DMT), either interferon beta1a or teriflunomide, while 19 received a combination of classical DMT and an immunoglobulin Y (IgY) supplement. For each participant, two sets of gut samples were collected: one at the study's outset and another after two months. Alpha and beta diversity analyses revealed no significant differences between groups. In comparison to the HC, the MS group exhibited an increase in Prevotella stercorea and a decrease in Faecalibacterium prausnitzii. Following treatment, individuals with MS showed enrichment in Lachnospiraceae and Streptococcus. The second sample, compared to the first one, demonstrated an increase in Bifidobacterium angulatum and a decrease in Oscillospira for individuals with MS. Gut microbiota diversity in PwMS is not significantly different to HC. However, specific taxonomic changes indicate the presence of a dysbiosis state. The use of DMTs and immunoglobulin Y supplements may contribute to alterations in microbial composition, potentially leading to the restoration of a healthier microbiome

Two and Three Dimensional Blood Flow Simulations in Different Types of Blood Vessels

In this paper we present a synthesis of our results obtained on blood flow simulation in different types of blood vessels. We present first some remarks on the wall shear stress (WSS) in the case of a human abdominal aortic aneurysm (AAA), and then we concentrate on the mechanical conditions which would lead to the “rupture” of the vascular vessel with aneurysm and implicitly to a possible stroke. We also make some investigations on the Fahraeus-Lindqvist effect in arterioles. Considering an axial-symmetric reservoir full of blood and which is linked to an arteriole (with the same particular geometry), we have pointed out the concentration of the red blood cells in this arteriole towards the core of the vessel. To improve our work we have considered a real three-dimensional geometry, which is a serious jump versus our previous results, where only the axial-symmetric geometries were considered. In this respect we have reconsidered the case of a carotid artery stenosis with and without a stent

Comments on the mathematical modelling of a vertebrobasilar stenosis

In the present paper the case of a stenosis on the basilar artery is investigated. To analyze the problem CT angiography and MRI angiography were performed. To model this real case a non-Newtonian mathematical model was taken into account for the blood flow, while the vessel walls of the arteries and the arterioles were considered to have viscoelastic and elastic behavior, respectively – as we presented already in previous papers [1], [2]. Using COMSOL Multiphysics 3.3 we performed some numerical simulations to obtain some results with regard to blood velocity, blood pressure and streamlines

Non-Newtonian Mathematical Model and Numerical Simulations for the Blood Flow in Capillary Vessels

In this paper, taking into consideration the rheological Cross type non-Newtonian model, we elaborate an axial-symmetric mathematical model for the blood flow in capillary vessel with adequate numeric algorithms. We take into account the elastic and porous behavior of the vessel wall which leads to a more realistic approach of the problem. We also accept that the change of substances through these vessels complies with the Starling hypothesis. This hypothesis states that the mass debit through the capillary wall is proportional to the pressure difference between outside and inside the capillaries. The existence of a slip condition along the permeable surface is also accepted using the results of Beavers and Joseph. The numerical experiments are made using COMSOL Multiphysics 3.3. Some numerical results with respect to the velocity field, pressure variation and the wall shear stress are presented

Large caliber blood vessel pseudoaneurysm following prosthetic surgery. Mathematical model and numerical considerations

Using a non-Newtonian mathematical model for the blood flow and a generalized Maxwell model for the viscoelastic behavior of the large vessels – elaborated and presented already by us in previous papers [1], [2] we make some remarks on the wall shear stress (WSS) in the case of an artery whose vessel wall is replaced by a vascular prosthesis following a surgical intervention. Considering then a pseudoaneurysm which is located on both genuine blood vessel and prosthesis we analyze the distribution of wall shear stress and taking also into account the viscoplastic behavior of the prosthesis we try to determine the mechanical conditions which would lead to a possible “jerk” (“rupture”) of the vascular vessel in the presence of the pseudoaneurysm

Brain-Derived Neurotrophic Factor in Multiple Sclerosis Disability: A Prospective Study

Multiple sclerosis (MS) is a demyelinating central nervous system disease that leads to neurological disability. Brain-derived neurotrophic factors (BDNFs) are neurotrophins involved in neurodegenerative disorders. This study analysed the relationship between serum BDNF, neurological disability and different MS treatments. We included 63 people with MS (PwMS), with relapsing-remitting MS or clinically isolated syndrome, and 16 healthy controls (HCs). We analysed the serum levels of BDNF and MS specific disability tests (Expanded Disability Status Scale, timed 25-foot walk test, nine-hole peg test), at baseline (V0) and after one year of interferon beta1a or teriflunomide treatment (V1). Baseline BDNF values were not different between the PwMS and HCs (p = 0.85). The BDNF levels were higher in PwMS vs. HCs after treatment (p = 0.003). BDNF was not related to last-year relapses or by the disease duration (all p > 0.05). The overall values for the PwMS decreased after one year (p p > 0.05). BDNF values were not influenced by the lesion burden, active lesions, or new lesions on MRI (p > 0.05). In our cohort, the PwMS had higher BDNF levels compared to the HCs after one year of treatment. BDNF was not related to clinical or paraclinical disease severity signs

Cognitive Dysfunction and Affective Mood Disorder Screening in Patients With Chronic Inflammatory Bowel Disease: Protocol for a Prospective Case-Control Study

BackgroundMild cognitive impairment (MCI) and Alzheimer’s disease (AD) might be more frequent in patients with inflammatory bowel disease (IBD), but the relationship between these 2 entities is yet to be entirely established. Certain blood biomarkers (eg, serum amyloid A [SAA] and serum homocysteine [Hcy], which increase in IBD and MCI; brain-derived neurotrophic factor [BDNF], which decreases in MCI and AD but is not clearly modified in IBD; and S100 calcium-binding protein B [S100B], which increases in the blood-brain barrier and neuronal lesions) might predict the stage of MCI or dementia or progression to a further state. The gut–brain axis (GBA) might be the key to the development of MCI in patients with IBD, along with systemic inflammation and the possible and unknown adverse effects of disease-modifying medication. ObjectiveThe aim of this study is to investigate whether GBA interactions play a role in MCI development in patients with IBD. MethodsA case-control study will be conducted on at least 100 patients diagnosed with IBD, matched with 100 healthy individual controls. The matching will include sex, age, and education. Patients will be fully examined, and a full interview and a neurological and cognitive examination will be performed. The primary clinical outcomes will be cognitive test scores (Montreal Cognitive Assessment, Trail Making Test, Digit Symbol Substitution Test, forward and backward digit span testing). Depression, stress, and anxiety screening will also be performed. Blood samples from all participants will be collected, and aliquots will be immediately stored in a biobank. Primary laboratory outcomes will include serum levels of presumed cognitive dysfunction blood biomarkers SAA, Hcy, S100B, and BDNF. Follow-up will be performed at 12, 24, 36, and 48 months. ResultsData collection started in December 2021 and is ongoing. So far, 53 patients with IBD have been recruited and 50 HC matched. Data collection should end in January 2030. Intermediary analysis will be performed in April 2024. We expect patients with IBD to have lower scores on cognitive testing and a positive correlation between disease length and cognitive impairment level. In addition, the levels of stress, anxiety, and depression should be higher in the IBD group. The serum levels of the 4 biomarkers could correlate or anticorrelate with cognitive scores and serve as predictive factors for MCI or dementia development. A higher level of education, a younger age, the absence of malabsorption, and good disease control might serve as protectors against MCI. ConclusionsGBA interactions, along with systemic inflammation and the adverse effects of medication, might be a cause of MCI and AD development in patients with IBD. Serum biomarkers could prove cheap and useful predictors of MCI development. Trial RegistrationClinicalTrials.gov NCT05760729; https://clinicaltrials.gov/study/NCT05760729 International Registered Report Identifier (IRRID)DERR1-10.2196/5054

Recent Advances on the Roles of PCSK-9 Inhibitors in the Management of Acute Ischemic Stroke Patients

Acute ischemic stroke (AIS) represents an important cause of disability and death. Since only a minor percentage of patients with AIS are eligible for acute therapy, the management of risk factors is mandatory. An important risk factor of AIS is hyperlipemia. The current guidelines recommend a strict correction of it. Statins are recommended as the first-line treatment, while proprotein convertase subtilin/kexin type 9 (PCSK-9) inhibitors are administered as a second or even third option when the goal for a low-density lipoprotein cholesterol (LDL-C) level is not achieved. PCSK-9 inhibitors effectively decrease the LDL-C levels through the inhibition of PCSK-9-LDL-receptor complex formation. The in-depth understanding of the PCSK-9 protein mechanism in the metabolism of LDL-C led to the development of effective targeted approaches. Furthermore, a better understanding of the LDL-C metabolic pathway led to the development of newer approaches, which increased the therapeutic options. This article aims to offer an overview of the PCSK-9 inhibitors and their mechanism in reducing the LDL-C levels. Moreover, we will present the main indications of the current guidelines for patients with hyperlipemia and for those who have suffered an acute ischemic stroke, as well as the importance of LDL-C reduction in decreasing the rate of a recurrence

From Gut to Brain: Uncovering Potential Serum Biomarkers Connecting Inflammatory Bowel Diseases to Neurodegenerative Diseases

Inflammatory bowel diseases (IBDs) are characterized by chronic gastrointestinal inflammation due to abnormal immune responses to gut microflora. The gut–brain axis is disrupted in IBDs, leading to neurobiological imbalances and affective symptoms. Systemic inflammation in IBDs affects the brain’s inflammatory response system, hormonal axis, and blood–brain barrier integrity, influencing the gut microbiota. This review aims to explore the association between dysregulations in the gut–brain axis, serum biomarkers, and the development of cognitive disorders. Studies suggest a potential association between IBDs and the development of neurodegeneration. The mechanisms include systemic inflammation, nutritional deficiency, GBA dysfunction, and the effect of genetics and comorbidities. The objective is to identify potential correlations and propose future research directions to understand the impact of altered microbiomes and intestinal barrier functions on neurodegeneration. Serum levels of vitamins, inflammatory and neuronal damage biomarkers, and neuronal growth factors have been investigated for their potential to predict the development of neurodegenerative diseases, but current results are inconclusive and require more studies