Neurofilament Light Chain Levels Interact with Neurodegenerative Patterns and Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis.

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving rapid motor neuron degeneration leading to brain, primarily precentral, atrophy. Neurofilament light chains are a robust prognostic biomarker highly specific to ALS, yet associations between neurofilament light chains and MR imaging outcomes are not well-understood. We investigated the role of neurofilament light chains as mediators among neuroradiologic assessments, precentral neurodegeneration, and disability in ALS. MATERIALS AND METHODS: We retrospectively analyzed a prospective cohort of 29 patients with ALS (mean age, 56 [SD, 12] years; 18 men) and 36 controls (mean age, 49 [SD, 11] years; 18 men). Patients underwent 3T (n = 19) or 7T (n = 10) MR imaging, serum (n = 23) and CSF (n = 15) neurofilament light chains, and clinical (n = 29) and electrophysiologic (n = 27) assessments. The control group had equivalent 3T (n = 25) or 7T (n = 11) MR imaging. Two trained neuroradiologists performed blinded qualitative assessments of MR imaging anomalies (n = 29 patients, n = 36 controls). Associations between precentral cortical thickness and neurofilament light chains and clinical and electrophysiologic data were analyzed. RESULTS: We observed extensive cortical thinning in patients compared with controls. MR imaging analyses showed significant associations between precentral cortical thickness and bulbar or arm impairment following distributions corresponding to the motor homunculus. Finally, uncorrected results showed positive interactions among precentral cortical thickness, serum neurofilament light chains, and electrophysiologic outcomes. Qualitative MR imaging anomalies including global atrophy (P = .003) and FLAIR corticospinal tract hypersignal anomalies (P = .033), correlated positively with serum neurofilament light chains. CONCLUSIONS: Serum neurofilament light chains may be an important mediator between clinical symptoms and neuronal loss according to cortical thickness. Furthermore, MR imaging anomalies might have underestimated prognostic value because they seem to indicate higher serum neurofilament light chain levels.

Parietin, the Vibrant Natural Dye in Xanthoria parietina.

The use of natural dyes in several areas is regulated by current European and non-European legislation, due to various problems with synthetic dyes. The analysis revealed that the lichen studied: Xanthoria parietina has potential natural dye sources and provides bright colors for extraction solvents. Furthermore, dyed wool and toile fabric have good fastness properties in ammonia fermentation and boiling water, both with and without mordants. The sample dyes with Xanthoria parietina were characterized by several analytical techniques: high-performance liquid chromatography with diode array detection (HPLC-DAD) and electrospray ionization with tandem mass spectrometry (HPLC-ESI-Q-ToF). As compounds from Xanthoria parietina form a complex with mordants and tissues, it is impossible to identify the molecules responsible for coloring using chromatographic techniques. However, we have evaluated the dyeing power of their major molecule, parietin. To further confirm the coloring power of the isolated parietin molecule, we performed a dye test with pure parietin. Thus, CIALAB analyses have shown parietin is the molecule responsible for the coloring obtained by Xanthoria parietina. The utilization of parietin derived from lichens facilitates the development of sustainable dyes for textile coloring, presenting an environmentally friendly alternative to synthetic dyes while simultaneously enriching lichen biodiversity.

Association between brain and upper cervical spinal cord atrophy assessed by MRI and disease aggressiveness in amyotrophic lateral sclerosis.

PURPOSE: To study the relative contributions of brain and upper cervical spinal cord compartmental atrophy to disease aggressiveness in amyotrophic lateral sclerosis (ALS). METHODS: Twenty-nine ALS patients and 24 age- and gender-matched healthy controls (HC) were recruited. Disease duration and the Revised-ALS Functional Rating Scale (ALSFRS-R) at baseline, 3- and 6-months follow-up were assessed. Patients were clinically differentiated into fast (n=13) and slow (n=16) progressors according to their ALSFRS-R progression rate. Brain grey (GM) and white matter, brainstem sub-structures volumes and spinal cord cross-sectional area (SC-CSA) at C1-C2 vertebral levels were measured from a 3D-T1-weighted MRI. RESULTS: Fast progressors showed significant GM, medulla oblongata and SC atrophy compared to HC (p<0.001, p=0.013 and p=0.008) and significant GM atrophy compared to slow progressors (p=0.008). GM volume correlated with the ALSFRS-R progression rate (Rho/p=-0.487/0.007), the ALSFRS-R at 3-months (Rho/p=0.622/0.002), and ALSFRS-R at 6-months (Rho/p=0.407/0.039). Medulla oblongata volume and SC-CSA correlated with the ALSFRS-R at 3-months (Rho/p=0.510/0.015 and Rho/p=0.479/0.024). MRI measures showed high performance to discriminate between fast and slow progressors. CONCLUSION: Our study suggests an association between compartmental atrophy and disease aggressiveness. This result is consistent with the combination of upper and lower motor neuron degeneration as the main driver of disease worsening and severity in ALS. Our study highlights the potential of brain and spinal cord atrophy measured by MRI as biomarker of disease aggressiveness signature.

Selecting the species to be used in lichen transplant surveys of air pollution in Tunisia.

This study was undertaken with the aim of selecting one or more lichen species that are the most suitable for transplant-based surveys of air pollution in Tunisia, in areas where the local native lichen vegetation is scanty or missing at all. To this purpose, four epiphytic (tree inhabiting) lichen species (Evernia prunastri, Flavoparmelia caperata, Parmotrema perlatum, Ramalina farinacea) were collected from the Babouch forests, a remote and unpolluted area of NW Tunisia, and analyzed for their content of potentially toxic elements (PTEs), namely Al, As, Cd, Cr, Cu, Fe, Ni, Pb, Sb, and Zn, by ICP-MS. Moreover, also the physiological status of the lichen samples was evaluated by measuring their chlorophyll content, photosynthetic efficiency, and spectral reflectance. The results indicated a remarkable contribution of airborne soil and dust particles to the total PTE content, especially for the foliose species F. caperata and P. perlatum. The fruticose lichens E. prunastri and R. farinacea had a lower and similar content of PTEs, and hence were regarded as more suitable to be used in transplant studies, since are able to detect even minimal accumulation amounts. All lichen species were healthy, as emerged from the analysis of physiological parameters.

HPLC analysis, mycochemical contents and biological activities of two edible hypogeous ascomycetes: Tirmania nivea and Terfezia boudieri.

Truffle, the hypogeous, ascomycetous macrofungus, has been recognized as a delicacy for centuries, and it is gaining elevated status in the culinary domain. The chemical composition and biological activities of aqueous extract and ground material of two desert Tunisian Tirmania nivea and Terfezia boudieri were studied for the first time. Using three assays antioxidant activity of the aqueous extract and ground material of the two truffles were investigated. Indeed, the aqueous extract and ground material of Terfezia boudieri showed the highest capacity for the DPPH scavenging test (IC50 = 0.18 mg/mL) and with regard to the chelating power of iron (IC50 = 0.22 mg/mL). At the same time, the highest capacity for iron reduction was recorded in the crude material of Tirmania nivea. Besides, the total phenolic, flavonoid, flavanol, tannin, and proanthocyanidin contents of both truffles extracts were determined. The ground material showed the best antibacterial activity for two ascomycetes against seven strains of bacteria. HPLC analysis of aqueous extracts showed that the predominant phenolic compounds in T. boudieri and T. nivea were gallic acid (33.25%) and myricetin (52.91%). Therefore, these truffles are a source of natural antioxidant and antimicrobial agents and could be used as a potential health food.

Combining sodium MRI, proton MR spectroscopic imaging, and intracerebral EEG in epilepsy.

Whole brain ionic and metabolic imaging has potential as a powerful tool for the characterization of brain diseases. We combined sodium MRI (23 Na MRI) and 1 H-MR Spectroscopic Imaging (1 H-MRSI), assessing changes within epileptogenic networks in comparison with electrophysiologically normal networks as defined by stereotactic EEG (SEEG) recordings analysis. We applied a multi-echo density adapted 3D projection reconstruction pulse sequence at 7 T (23 Na-MRI) and a 3D echo-planar spectroscopic imaging sequence at 3 T (1 H-MRSI) in 19 patients suffering from drug-resistant focal epilepsy who underwent presurgical SEEG. We investigated 23 Na MRI parameters including total sodium concentration (TSC) and the sodium signal fraction associated with the short component of T2 * decay (f), alongside the level of metabolites N-acetyl aspartate (NAA), choline compounds (Cho), and total creatine (tCr). All measures were extracted from spherical regions of interest (ROIs) centered between two adjacent SEEG electrode contacts and z-scored against the same ROI in controls. Group comparison showed a significant increase in f only in the epileptogenic zone (EZ) compared to controls and compared to patients' propagation zone (PZ) and non-involved zone (NIZ). TSC was significantly increased in all patients' regions compared to controls. Conversely, NAA levels were significantly lower in patients compared to controls, and lower in the EZ compared to PZ and NIZ. Multiple regression analyzing the relationship between sodium and metabolites levels revealed significant relations in PZ and in NIZ but not in EZ. Our results are in agreement with the energetic failure hypothesis in epileptic regions associated with widespread tissue reorganization.

Anti-Inflammatory Potential of Compounds Isolated from Tunisian Lichens Species.

The lichen's special symbiotic structure enables it to produce bioactive substances. They have historically been recognized for their aesthetic and medicinal benefits. Furthermore, in recent years, they have performed in various fields, including perfumery, dyeing, and pharmacology due to their rich secondary metabolites. From our study, four compounds were isolated from organic extracts of Parmotrema hypoleucinum, Roccella phycopsis, and Xanthoria parietina and identified by spectroscopic investigation as atranorin, (+)-iso-usnic acid, methyl orsellinate, and parietin, respectively. The anti-inflammatory effects of lichens extracts, and pure compounds were evaluated on RAW 264.7 macrophages cells at different concentrations. At 25 µg/mL all treated samples did not show any effect on cell viability. Atranorin and (+)-iso-usnic acid showed an inhibitory effect on nitric oxide (NO) levels in lipopolysaccharide (LPS)-stimulated macrophages. Nitric oxide (NO) production was measured using Griess reagent, atranorin and (+)-iso-usnic acid showed a high anti-inflammatory potential (75.99 % and 57.27 % at 25 µg/mL). On the other hand, methyl orsellinate and the organic extracts of three lichens showed good anti-inflammatory activity ranging from 29.16 % at 25 µg/mL to 86.91 % at 100 µg/mL.

Phenolic Content, Antioxidant, Antibacterial, and Anti-Acetylcholinesterase Activities of Biosynthesized and Characterized Silver Nanoparticles from Tunisian Medicinal Lichen Species.

Lichens produce a myriad of bioactive compounds that can be exploited as reducing and capping agents in the green process of synthesizing nanoparticles. In this study, we exploit a simple, environmentally safe method for synthesizing silver nanoparticles (AgNPs), using aqueous extracts of three lichen species (Lobaria pulmonaria, Ramalina farinacea, and Evernia prunastri) for the first time. Characterization showed that the three lichen species selected could be perfectly suitable as reducing agents to produce AgNPs. First, ultraviolet-visible spectroscopy confirmed the presence of metallic silver with a maximum absorbance at 425 nm. Second, Fourier transform infrared spectroscopy analysis confirmed the chemical compounds involved in reduction. Third, the elemental composition of AgNPs was illustrated by energy dispersive X-ray spectroscopy. Finally, scanning electron microscopy images displayed the size and shape of biosynthesized particles. The prepared extracts containing AgNPs showed high contents of phenolic compounds and high antioxidant activities on three assays (DPPH, ferric reducing power, and chelating power). Moreover, since bacteria are developing resistance to many common antibiotics, AgNPs produced in an environmentally safe method are an interesting replacement. The antibacterial assessment revealed more effective activity against Gram-negative than Gram-positive bacteria and a bactericidal effect against all strains tested. In this study, we present a pioneering evaluation of acetylcholinesterase inhibition by lichen-based AgNPs. The three extracts exhibited strong enzyme inhibition, with IC50 values of 3.46 ± 0.09, 3.59 ± 0.02, and 4.34 ± 0.03 mg/mL for L. pulmonaria, R. farinacea, and E. prunastri, respectively. The green approach presented would encourage the nontoxic production of AgNPs, suggesting pharmaceutical applications.

Grey-matter sodium concentration as an individual marker of multiple sclerosis severity.

OBJECTIVE: Quantification of brain injury in patients with variable disability despite similar disease duration may be relevant to identify the mechanisms underlying disability in multiple sclerosis (MS). We aimed to compare grey-matter sodium abnormalities (GMSAs), a parameter reflecting neuronal and astrocyte dysfunction, in MS patients with benign multiple sclerosis (BMS) and non-benign multiple sclerosis (NBMS). METHODS: We identified never-treated BMS patients in our local MS database of 1352 patients. A group with NBMS was identified with same disease duration. All participants underwent 23Na magnetic resonance imaging (MRI). The existence of GMSA was detected by statistical analysis. RESULTS: In total, 102 individuals were included (21 BMS, 25 NBMS and 56 controls). GMSA was detected in 10 BMS and 19 NBMS (11/16 relapsing-remitting multiple sclerosis (RRMS) and 8/9 secondary progressive multiple sclerosis (SPMS) patients) (p = 0.05). On logistic regression including the presence or absence of GMSA, thalamic volume, cortical grey-matter volume and T2-weighted lesion load, thalamic volume was independently associated with BMS status (odds ratio (OR) = 0.64 for each unit). Nonetheless, the absence of GMSA was independently associated when excluding patients with significant cognitive alteration (n = 7) from the BMS group (OR = 4.6). CONCLUSION: Detection of GMSA in individuals and thalamic volume are promising to differentiate BMS from NBMS as compared with cortical or whole grey-matter atrophy and T2-weighted lesions.

Anodal tDCS of contralesional hemisphere modulates ipsilateral control of spinal motor networks targeting the paretic arm post-stroke.

OBJECTIVE: The role of ipsilateral motor cortex efferent pathways in the transmission of voluntary command to spinal motor nuclei remains controversial in humans. In healthy subjects, their implication in cortical control is hidden by predominant role of crossed corticospinal tract. However, evidence from electrophysiological and imaging studies suggest that ipsilateral tracts may contribute to functional recovery after unilateral brain damage. This randomized-sham control study aims to explore to what extent ipsilateral tracts from the undamaged hemisphere may strengthen corticospinal control onto spinal motor networks following stroke. METHODS: Anodal transcranial direct current stimulation (tDCS) was combined with monosynaptic H-reflex method to evaluate the variations of reciprocal inhibition (RI) in wrist flexors in 21 stroke participants. RESULTS: Anodal tDCS decreased RI in wrist flexors in stroke participants in both arms. tDCS unmasks an ipsilateral control from the undamaged hemisphere onto spinal motor networks controlling affected arm muscles in stroke participants. In the unaffected (contralateral) arm, effects in stroke participants were opposite to those induced in healthy subjects. CONCLUSIONS: Stimulation of the undamaged cortex in stroke participants induces modulation of ipsilateral motor networks controlling the hemiparetic side. SIGNIFICANCE: Rehabilitation could leverage stimulation of the undamaged hemisphere to enhance motor recovery post stroke.

Cerebellar pathology and disability worsening in relapsing-remitting multiple sclerosis: A retrospective analysis from the CombiRx trial.

BACKGROUND AND PURPOSE: Cerebellar damage is a valuable predictor of disability, particularly in progressive multiple sclerosis. It is not clear if it could be an equally useful predictor of motor disability worsening in the relapsing-remitting phenotype. AIM: We aimed to determine whether cerebellar damage is an equally useful predictor of motor disability worsening in the relapsing-remitting phenotype. METHODS: Cerebellar lesion loads and volumes were estimated using baseline magnetic resonance imaging from the CombiRx trial (n = 838). The relationship between cerebellar damage and time to disability worsening (confirmed disability progression [CDP], timed 25-foot walk test [T25FWT] score worsening, nine-hole peg test [9HPT] score worsening) was tested in stagewise and stepwise Cox proportional hazards models, accounting for demographics and supratentorial damage. RESULTS: Shorter time to 9HPT score worsening was associated with higher baseline Expanded Disability Status Scale (EDSS) score (hazard ratio [HR] 1.408, p = 0.0042) and higher volume of supratentorial and cerebellar T2 lesions (HR 1.005 p = 0.0196 and HR 2.211, p = 0.0002, respectively). Shorter time to T25FWT score worsening was associated with higher baseline EDSS (HR 1.232, p = 0.0006). Shorter time to CDP was associated with older age (HR 1.026, p = 0.0010), lower baseline EDSS score (HR 0.428, p < 0.0001) and higher volume of supratentorial T2 lesions (HR 1.024, p < 0.0001). CONCLUSION: Among the explored outcomes, single time-point evaluation of cerebellar damage only allows the prediction of manual dexterity worsening. In clinical studies the selection of imaging biomarkers should be informed by the outcome of interest.

Does the lichenicolous fungus Heterocephalacria bachmannii affect the antimicrobial potential of its host Cladonia foliacea?

The effects of the lichenicolous fungus Heterocephalacria bachmannii on the antimicrobial potential of the lichen Cladonia foliacea demonstrated that the extracts investigated have antimicrobial potential against gram-positive and negative bacteria, and yeast, and inhibit the germination of fungal spores. Inhibition activity varied considerably depending on the extract, the bacterial species, and the absence or presence of H. bachmannii; unparasitised C. foliacea has a higher antimicrobial activity. Methanol and acetone extracts of C. foliacea alone have higher inhibition diameters than C. foliacea with H. bachmannii against Enterobacter cloacae; the methanol extract of C. foliacea showed the best inhibition (250 µg/ml). C. foliacea also has a high lysozyme potential against Streptococcus agalactiae and Staphylococcus aureus. Fungal hyphae of Alternaria alternata were more affected by the methanol extract from C. foliacea.

Altered anterior default mode network dynamics in progressive multiple sclerosis.

BACKGROUND: Modifications in brain function remain relatively unexplored in progressive multiple sclerosis (PMS), despite their potential to provide new insights into the pathophysiology of the disease at this stage. OBJECTIVES: To characterize the dynamics of functional networks at rest in patients with PMS, and the relation with clinical disability. METHODS: Thirty-two patients with PMS underwent clinical and cognitive assessment. The dynamic properties of functional networks, retrieved from transient brain activity, were obtained from patients and 25 healthy controls (HCs). Sixteen HCs and 19 patients underwent a 1-year follow-up (FU) clinical and imaging assessment. Differences in the dynamic metrics between groups, their longitudinal changes, and the correlation with clinical disability were explored. RESULTS: PMS patients, compared to HCs, showed a reduced dynamic functional activation of the anterior default mode network (aDMN) and a decrease in its opposite-signed co-activation with the executive control network (ECN), at baseline and FU. Processing speed and visuo-spatial memory negatively correlated to aDMN dynamic activity. The anti-couplings between aDMN and auditory/sensory-motor network, temporal-pole/amygdala, or salience networks were differently associated with separate cognitive domains. CONCLUSION: Patients with PMS presented an altered aDMN functional recruitment and anti-correlation with ECN. The aDMN dynamic functional activity and interaction with other networks explained cognitive disability.

Mycochemical Contents and Biological Activities of Three Wild Mushrooms from Tunisia.

The objective of the current study was to compare the mycochemical composition and biological activities of two extracts (aqueous extracts and ground materials prepared with the QUENCHER approach) of three wild Basidiomy-cetes, Agaricus vaporarius, Lactarius deliciosus, and Lycoperdon pyriforme, collected from a region located in the north of Tunisia. Mycochemical analysis in terms of total phenolic compounds, flavonoids, flavanols, proanthocyanidins, and tannin contents were determined. In addition, the antioxidant activities of the mushrooms were evaluated using three assays (2,2-di-phenyl-1-picrylhydrazyl free radical scavenging, ferric reducing antioxidant power assay, and metal chelating assay). Their antimicrobial activities were assessed against seven bacterial species. The obtained data revealed the presence of significant differences between secondary metabolites and the biological activities of the different tested extracts. Extracts of Basidiomy-cetes prepared with the QUENCHER approach had higher total phenolic content and antimicrobial activity against the evaluated strains. Antioxidant activity showed that the water extract had the greatest activity. The water extracts were analyzed with high-performance liquid chromatography, and the results showed that these three wild macromycetes contain a wide variety of antioxidant compounds in addition to many other bioactive compounds of nutritional and therapeutic interest.

Increased Sodium Concentration in Substantia Nigra in Early Parkinson's Disease: A Preliminary Study With Ultra-High Field (7T) MRI.

Pathophysiology of idiopathic Parkinson's disease (iPD) is complex and still misunderstood. At a time when treatments with disease-modifying potential are being developed, identification of early markers of neurodegeneration is essential. Intracerebral sodium accumulation could be one of them. Indeed, it may be in relation to the mitochondrial dysfunction that early exists in iPD. For the first time, we used brain sodium (23Na) MRI to explore sodium concentration changes that have already been reported to be related to neurodegeneration in other diseases. We prospectively included 10 iPD patients (mean age 52.2 ± 5.9 years-old) with motor symptoms that started <36 months before inclusion and 12 healthy subjects (mean age 53 ± 6.4 years-old). Patients were scanned in OFF medication state by using proton (1H) and 23Na MRI at 7T. We then extracted quantitative Total Sodium Concentration (TSC) from five regions of interest known to be early impaired in iPD [substantia nigra (SN), putamen, caudate nucleus, pallidum, thalamus] and in one region supposed to be relatively spared in the first stages of the disease [cortical gray matter (neocortex)]. Potential atrophy in these structures was also investigated with 1H MRI. Relative to healthy subjects, iPD patients showed higher TSC in the SN (43.73 ± 4.64 vs. 37.72 ± 5.62, p = 0.006 after Bonferroni correction). A trend of increase in sodium concentrations was found within the pallidum (45.80 ± 4.19 vs. 41.07 ± 4.94, p = 0.017), putamen (48.65 ± 4.58 vs. 43.66 ± 5.04, p = 0.041) and the cortical gray matter (56.34 ± 3.92 vs. 50.81 ± 5.50, p = 0.021). No significant brain atrophy was found in patients compared to controls. Thus, alteration of sodium homeostasis in the SN in the absence of atrophy could be considered as a potential early marker of cellular dysfunction in iPD.

An optimized MP2RAGE sequence for studying both brain and cervical spinal cord in a single acquisition at 3T.

Magnetization Prepared 2 Rapid Acquisition Gradient Echo (MP2RAGE) is a T1 mapping technique that has been used broadly on brain and recently on cervical spinal cord (cSC). The growing interest for combined investigation of brain and SC in numerous pathologies of the central nervous system such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and traumatic injuries, now brings about the need for optimization with regards to this specific investigation. This implies large spatial coverage with high spatial resolution and short acquisition time, high CNR and low B1+ sensitivity, as well as high reproducibility and robust post-processing tools for T1 quantification in different regions of brain and SC. In this work, a dedicated protocol (referred to as Pr-BSC) has been optimized for simultaneous brain and cSC T1 MP2RAGE acquisition at 3T. After computer simulation optimization, the protocol was applied for in vivo validation experiments and compared to previously published state of the art protocols focusing on either the brain (Pr-B) or the cSC (Pr-SC). Reproducibility and in-ROI standard deviations were assessed on healthy volunteers in the perspective of future clinical use. The mean T1 values, obtained by the Pr-BSC, in brain white, gray and deep gray matters were: (mean ± in-ROI SD) 792 ± 27 ms, 1339 ± 139 ms and 1136 ± 88 ms, respectively. In cSC, T1 values for white matter corticospinal, posterior sensory, lateral sensory and rubro/reticulospinal tracts were 902 ± 41 ms, 920 ± 35 ms, 903 ± 46 ms, 891 ± 41 ms, respectively, and 954 ± 32 ms for anterior and intermediate gray matter. The Pr-BSC protocol showed excellent agreement with previously proposed Pr-B on brain and Pr-SC on cSC, with very high inter-scan reproducibility (coefficients of variation of 0.52 ± 0.36% and 1.12 ± 0.62% on brain and cSC, respectively). This optimized protocol covering both brain and cSC with a sub-millimetric isotropic spatial resolution in one acquisition of less than 8 min, opens up great perspectives for clinical applications focusing on degenerative tissue such as encountered in MS and ALS.

Gait and cognitive abnormalities are associated with regional cerebellar atrophy in elderly fallers - A pilot study.

OBJECTIVES: To investigate cerebellar lobule atrophy patterns in elderly fallers (EFs) and their association with gait and cognitive performance. BACKGROUND: Cognitive impairments, gait, and balance deficits are major risk factors for falls in older adults, however, their neural fingerprints remain poorly understood. Recent evidence from neuroimaging studies highlight the role of the cerebellum in both sensorimotor and cognitive networks, suggesting that it may contribute to fall risk. METHODS: Fourteen EFs (mean age ± SD = 78 ± 1.5 yrs.) and 20 healthy controls (HCs) (mean age ± SD = 69.6 ± 1.3 yrs.) underwent a 3 T MRI scan obtaining 3D T1-weighted images, cognitive, and gait assessments. Cerebellar lobule segmentation was performed, and the obtained cerebellar lobules volumes were adjusted for intracranial volume (ICV). The relationship between lobules volumes, gait, and cognitive performance scores was assessed using hierarchical multiple linear regression adjusted for age and gender. RESULTS: EFs exhibited lower cerebellar volumes in the posterior cerebellum, lobules V, VI, VIIB, VIIIA, VIIIB, and Crus II, and significantly higher volumes in the anterior cerebellum and lobule IV (p = 0.018 and p = 0.046) compared to HCs. In EFs, lobule V, VI, VIIB, VIIIA, VIIIB, and anterior cerebellum volumes were found to be independent predictors of usual walking (UW) gait speed, dual-task (DT) gait speed, mini Best, MOCA, CTTa, and CTTb (p < 0.05). CONCLUSIONS: The observed patterns of cerebellar lobule atrophy and their associations with motor and cognitive performance scores suggest that cerebellar atrophy contributes to the pathophysiology of fall risk in EFs.

Lichenochemical Screening and Antioxidant Capacity of Four Tunisian Lichen Species.

The phenolic composition and antioxidant capacity of four Tunisian lichen species, Cladonia rangiformis, Flavoparmelia caperata, Squamarina cartilaginea and Xanthoria parietina, were determined in order to provide a better understanding of their lichenochemical composition. Powdered material of F. caperata was the richest in total phenolic content (956.68 µg GAE g-1 DW) and S. cartilaginea in proanthocyanidin content (77.31 µg CE g-1 DW), while the acetone extract of X. parietina showed the highest flavonoid content (9.56 µg CE g-1 DW). The antioxidant capacity of all lichen extracts and crude material was evaluated by DPPH. scavenging, iron-chelating, and iron-reducing powers. Results showed that methanol extracts of S. cartilaginea had the highest DPPH. antioxidant capacity (IC50 =0.9 µg mL-1 ) and the highest iron-reducing power was attributed to the acetone extract of this species. All extracts of all species were further screened by Fourier-transform infrared spectroscopy (FT-IR) and nuclear resonance spectroscopy (NMR); results showed an abundance of phenols, aromatic compounds, and fatty acids. Overall, our results showed that the investigated species are a rich source of potentially bioactive compounds with valuable properties.

Depression is associated with disconnection of neurotransmitter-related nuclei in multiple sclerosis.

BACKGROUND: Depression is frequently associated with multiple sclerosis (MS). However, the biological background underlying such association is poorly understood. OBJECTIVE: Investigating the functional connections of neurotransmitter-related brainstem nuclei, along with their relationship with white matter (WM) microstructure, in MS patients with depressive symptomatology (MS-D) and without depressive symptomatology (MS-nD). METHODS: Combined resting-state functional magnetic resonance imaging (fMRI) and diffusion-weighted MRI (dMRI) study on 50 MS patients, including 19 MS-D and 31 MS-nD patients, along with 37 healthy controls (HC). Main analyses performed are (1) comparison between groups of raphe nuclei (RN)-related functional connectivity (FC); (2) correlation between RN-related FC and whole brain dMRI-derived fractional anisotropy (FA) map; and (3) comparison between groups of FA in the RN-related WM area. RESULTS: (1) RN-related FC was reduced in MS-D when compared to MS-nD and HC; (2) RN-related FC positively correlated with FA in a WM cluster mainly encompassing thalamic/basal ganglia regions, including the fornix; and (3) FA in such WM area was reduced in MS-D. CONCLUSION: Depressive symptomatology in MS is specifically associated to a functional disconnection of neurotransmitter-related nuclei, which in turn may be traced to a distinct spatial pattern of WM alterations mainly involving the limbic network.

Cerebellar volume loss in radiologically isolated syndrome.

Radiologically isolated syndrome (RIS), in which asymptomatic demyelinating-appearing lesions are detected incidentally on MRI, can be a pre-clinical form of multiple sclerosis (MS). In this study, we measured cerebellar volumes on 3D T1-weighted 3T MR images in 21 individuals with RIS and 38 age- and sex-matched healthy controls (HC). Normalized cerebellar white matter volume and the anterior cerebellar gray matter volume were significantly decreased in RIS compared to HC (p = 0.003 and p = 0.005, respectively). Our findings support reports of regional brain atrophy in RIS prior to the development of a seminal attack related to inflammatory demyelination.