1H-MR Spectroscopy in Traumatic Brain Injury

Traumatic brain injury (TBI) is a common cause of neurological damage and disability. Conventional imaging (CT scan or MRI) is highly sensitive in detecting lesions and provides important clinical information regarding the need for acute intervention. However, abnormalities detected by CT scan or conventional MRI have limited importance in the classification of the degree of clinical severity and in predicting patients' outcome. This can be explained by the widespread microscopic tissue damage occurring after trauma, which is not observable with the conventional structural imaging methods. Advances in neuroimaging over the past two decades have greatly helped in the clinical care and management of patients with TBI. The advent of newer and more sensitive imaging techniques is now being used to better characterize the nature and evolution of injury and the underlying mechanisms that lead to progressive neurodegeneration, recovery or subsequent plasticity. This review will describe the role of proton magnetic resonance spectroscopic (MRS), an advanced MRI technique as related to its use in TBI. Proton MRS is a noninvasive approach that acquires metabolite information reflecting neuronal integrity and function from multiple brain regions and allows to assess clinical severity and to predict disease outcome

Identification of new non-carboxylic acid containing inhibitors of aldose reductase

Non-carboxylic acid containing bioisosteres of (5-arylidene-2,4-dioxothiazolidin-3-yl)acetic acids, which are active as aldose reductase (ALR2) inhibitors, were designed by replacing the carboxylic group with the trifluoromethyl ketone moiety. The in vitro evaluation of the ALR2 inhibitory effects of these trifluoromethyl substituted derivatives led to the identification of two inhibitors effective at low micromolar doses. It was further confirmed that a carboxylic chain on N-3 of the thiazolidinedione scaffold is a determining requisite to obtain the highest efficacy levels; however, it is not essential for the interaction with the target enzyme and it can be replaced by different polar groups, thus obtaining less ionised or unionised inhibitors

Cognitive decline in rheumatoid arthritis: Insight into the molecular pathogenetic mechanisms

Cognitive decline refers to a deterioration of intellectual and learning abilities and related memory problems, and is often associated with behavioral alterations, which prevents sufferers from carrying out the most common daily activities, such as maintaining normal productive interpersonal relationships, communicating, and leading an autonomous life. Numerous studies have highlighted the association between cognitive decline and autoimmune disorders, including rheumatoid arthritis (RA). RA is a chronic, inflammatory, autoimmune disease that involves systems and organs other than the bones and joints, with varying severity among patients. Here, we review the studies investigating the link between cognitive decline and RA, focusing on the main molecular pathogenetic mechanisms involved. The emerging body of data suggests that clinical, psychological, and biological factors may contribute to the pathogenesis of cognitive decline in RA, including cardiovascular complications, chronic pain, depression, inflammatory factors, changes in hormone levels, drug side effects, and genetics. Further studies are warranted in order to fully clarify the basis underlying the association between cognitive decline and RA and to find new possible diagnostic strategies and therapeutic targets for RA patients

Hypertensive crisis in acute cerebrovascular diseases presenting at the emergency department: A narrative review

Hypertensive crisis, defined as an increase in systolic blood pressure >179 mmHg or diastolic blood pressure >109 mmHg, typically causes end-organ damage; the brain is an elective and early target, among others. The strong relationship between arterial hypertension and cerebrovascular diseases is supported by extensive evidence, with hypertension being the main modifiable risk factor for both ischemic and hemorrhagic stroke, especially when it is uncontrolled or rapidly increasing. However, despite the large amount of data on the preventive strategies and therapeutic measures that can be adopted, the management of high BP in patients with acute cerebrovascular diseases presenting at the emergency department is still an area of debate. Overall, the outcome of stroke patients with high blood pressure values basically depends on the occurrence of hypertensive emergency or hypertensive urgency, the treatment regimen adopted, the drug dosages and their timing, and certain stroke features. In this narrative review, we provide a timely update on the current treatment, debated issues, and future directions related to hypertensive crisis in patients referred to the emergency department because of an acute cerebrovascular event. This will also focus greater attention on the management of certain stroke-related, time-dependent interventions, such as intravenous thrombolysis and mechanic thrombectomy

The role of sativex in robotic rehabilitation in individuals with multiple sclerosis rationale, study design, and methodology

Introduction: Currently, none of the available multiple sclerosis (MS) disease-modifying medications has been shown to stop or reverse gait disability. Recently, the nabiximols has been tested for the treatment of spasticity and walking impairment in MS. Nabiximols (trade name Sativex) is an oromucosal spray formulation containing 1:1 fixed ratio of delta-9-tetrahydrocannabinol and cannabidiol derived from cloned Cannabis sativa L. plant. Method and analysis: A single-center, prospective, parallel design, single-blind trial will be conducted at the IRCCS Neurolesi "Bonino-Pulejo" (Italy) involving MS patients affected by spasticity and undergoing a Robotic Rehabilitation training. The aim of the study is to clarify the role of Sativex coupled to a robotic neurehabilitation training in MS patients in improving motor outcomes, by means of clinical, kinematic, and neurophysiological measures. Patients will be randomly divided in 2 groups: one taking only an oral antispastic drug and the other with Sativex in add-on. After 1 month, we will evaluate the response to Sativex (responder patients' amelioration >20% at MRS score) enrolling into the study the first 20 patients with a good response to Sativex, whereas other 20 noresponder individuals will continue their antispastic drug. All the 40 subjects, were divided into 2 groups (A: Sativex + Lokomat Training, and B: other antispastic+Lokomat Training), will perform a neurorobotic-assisted gait training (each session will last at least 45 minutes, 3 times per week, for a total of 20 sessions). All the patients will undergo a complete physical and neurological examination at baseline, at the end of the robotic training (T1), and 30 days after the end of the neurorehabilitation training (T2)

Automatic Algorithm for Segmentation of Atherosclerotic Carotid Plaque

Background Carotid atherosclerosis is one of the major causes of stroke. The determination of the intima-media thickness, the identification of carotid atherosclerotic plaque, and the classification of the different stenoses are considered as important parameters for the assessment of atherosclerotic diseases. The aim of this work is to segment the plaques and to allow a better comprehension of carotid atherosclerosis. Methods We considered 44 subjects, 22 with and 22 without the presence of plaques in the carotid axis, and we applied the snake algorithm. Results The resulting interclass correlation coefficients (ICCs) were significant for all 3 parameters (mean echogenicity: ICC1 = .78 [95%CI: .55-0.90]; perimeter: ICC2 = .81 [95%CI: .61-0.92]; area: ICC3 = .89 [95%CI: .75-0.95]). The diagnostic accuracy was 82%, with an appropriate cutoff value of 224.5, sensitivity of 79%, and specificity of 85%. Conclusions In this study, we developed an automatic method to identify the carotid plaque. Our results showed that an automatic system of image segmentation could be used to identify, characterize, and measure atherosclerotic carotid plaques

Profiling of inhibitory immune checkpoints in glioblastoma: Potential pathogenetic players

Glioblastoma (GBM) represents the most frequent glial tumor, with almost 3 new cases per 100,000 people per year. Despite treatment, the prognosis for GBM patients remains extremely poor, with a median survival of 14.6 months, and a 5‑year survival less than 5%. It is generally believed that GBM creates a highly immunosuppressive microenvironment, sustained by the expression of immune‑regulatory factors, including inhibi‑ tory immune checkpoints, on both infiltrating cells and tumor cells. However, the trials assessing the efficacy of current immune checkpoint inhibitors in GBM are still disappointing. In the present study, the expression levels of several inhibitory immune checkpoints in GBM (CD276, VTCN1, CD47, PVR, TNFRSF14, CD200, LGALS9, NECTIN2 and CD48) were characterized in order to evaluate their potential as prognostic and eventually, therapeutic targets. Among the investigated immune checkpoints, TNFRSF14 and NECTIN2 were identified as the most promising targets in GBM. In particular, a higher TNFRSF14 expression was associated with worse overall survival and disease‑free survival, and with a lower Th1 response