The PPARγ2 Pro12Ala variant is protective against progression of nephropathy in people with type 2 diabetes

Cross-sectional studies suggest the association between diabetic nephropathy and the PPARγ2 Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 (PPARγ2). Prospective data are limited to microalbuminuria and no information on renal function is available to date. The present study evaluates the association between the Pro12Ala polymorphism of PPARγ2 and the progression of albuminuria and decay in glomerular filtration rate (GFR) in type 2 diabetes

Diagnostic contribution of Magnetic Resonance Imaging in an atypical presentation of Motor Neuron Disease

Motor neuron disease (MND) is a neurodegenerative disease determining progressive and relentless motor deterioration involving both upper and lower motor neurons (UMN and LMN); several variants at onset are described. Here we describe a case of MND presenting as pure spastic monoparesis in which magnetic resonance imaging (MRI) gave a substantial contribution in confirming the diagnosis and assessing the severity of UMN involvement. An isolated pyramidal syndrome, with complete absence of LMN signs, is a rare phenotype in the context of MND (less than 4% of total cases), especially if restricted to only one limb. Several other elements made this case an unusual presentation of MND: the late age of onset (8th decade), the subacute evolution of symptoms (raising the suspicion of an ischemic or inflammatory, rather than degenerative, etiology), the patient’s past medical history (achalasia, erythema nodosum), the increase of inflammatory indices. Conventional MRI showed no focal lesions that could explain the clinical features; therefore, we used advanced MR sequences. Diffusion tensor imaging (DTI) evaluation evidenced bilateral impairment of corticospinal tract (CST) diffusion metrics, with clear right-left asymmetry, pointing to a neurodegenerative etiology, which clinically appeared less likely at that time. Magnetic resonance spectroscopy (MRS) showed a significant reduction of NAA/Cho + Cr ratio in the motor cortex (MC), further supporting the hypothesis of UMN degeneration. In conclusion, in this particular case of MND, whose nosographic framing has not been fully defined, advanced MRI techniques with DTI and MRS proved to be of great usefulness in confirming a diffuse UMN involvement, possibly at a more advanced stage than its clinical expression

Il rischio cardiovascolare nel diabete mellito tipo 2

È noto a tutti che il diabete mellito tipo 2 (DM2) è una patologia cronica associata ad un aumento nell’incidenza di eventi cardiovascolari (CV) e ad un’aumentata mortalità cardiovascolare. Nonostante i grandi avanzamenti negli ultimi anni nella terapia e nella prevenzione delle malattie cardiovascolari (MCV), esse rappresentano tutt’ora la prima causa di morte nei pazienti affetti da DM2 ed il rischio di manifestare MCV è più elevato da 2 a 4 volte rispetto alla popolazione generale. Il diabete tipo 2 ha un’ampia diffusione in tutto il mondo; la sua prevalenza è notevolmente aumentata negli ultimi decenni e probabilmente continuerà a crescere nel prossimo futuro, rappresentando uno dei principali problemi di salute in tutto il mondo, anche a causa dell’elevato rischio di morte da causa cardiovascolare ad esso associato. Considerando l'epidemia globale di DM2 e di conseguenza il numero crescente di pazienti con DM2 ad alto rischio cardiovascolare, sono urgentemente necessarie strategie efficaci volte alla riduzione del rischio cardiovascolare. La gestione della malattia cardiovascolare (CVD) si pone quindi come un obiettivo ineludibile di cura e, possibilmente, di efficace prevenzione nel DM2

Polyphenol-rich diets improve glucose metabolism in people at high cardiometabolic risk: a controlled randomised intervention trial

Dietary polyphenols and long chain n-3 polyunsaturated fatty acids (LCn3) are associated with lower cardiovascular risk. This may relate to their influence on glucose metabolism and diabetes risk. We evaluated the effects of diets naturally rich in polyphenols and/or LCn3 of marine origin on glucose metabolism in people at high cardiometabolic risk

The effects of biochar and its combination with compost on lettuce (Lactuca sativa L.) growth, soil properties, and soil microbial activity and abundance

Impacts of biochar application in combination with organic fertilizer, such as compost, are not fully understood. In this study, we tested the effects of biochar amendment, compost addition, and their combination on lettuce plants grown in a soil poor in nutrients; soil microbiological, chemical, and physical characteristics were analyzed, together with plant growth and physiology. An initial screening was also done to evaluate the effect of biochar and compost toxicity, using cress plants and earthworms. Results showed that compost amendment had clear and positive effects on plant growth and yield and on soil chemical characteristics. However, we demonstrated that also the biochar alone stimulated lettuce leaves number and total biomass, improving soil total nitrogen and phosphorus contents, as well as total carbon, and enhancing related microbial communities. Nevertheless, combining biochar and compost, no positive synergic and summative effects were observed. Our results thus demonstrate that in a soil poor in nutrients the biochar alone could be effectively used to enhance soil fertility and plant growth and biomass yield. However, we can speculate that the combination of compost and biochar may enhance and sustain soil biophysical and chemical characteristics and improve crop productivity over time

ATP-evoked intracellular Ca2+ transients shape the ionic permeability of human microglia from epileptic temporal cortex

BACKGROUND: Intracellular Ca2+ modulates several microglial activities, such as proliferation, migration, phagocytosis, and inflammatory mediator secretion. Extracellular ATP, the levels of which significantly change during epileptic seizures, activates specific receptors leading to an increase of intracellular free Ca2+ concentration ([Ca2+]i). Here, we aimed to functionally characterize human microglia obtained from cortices of subjects with temporal lobe epilepsy, focusing on the Ca2+-mediated response triggered by purinergic signaling.METHODS: Fura-2 based fluorescence microscopy was used to measure [Ca2+]i in primary cultures of human microglial cells obtained from surgical specimens. The perforated patch-clamp technique, which preserves the cytoplasmic milieu, was used to measure ATP-evoked Ca2+-dependent whole-cell currents.RESULTS: In human microglia extracellular ATP evoked [Ca2+]i increases depend on Ca2+ entry from the extracellular space and on Ca2+ mobilization from intracellular compartments. Extracellular ATP also induced a transient fivefold potentiation of the total transmembrane current, which was completely abolished when [Ca2+]i increases were prevented by removing external Ca2+ and using an intracellular Ca2+ chelator. TRAM-34, a selective KCa3.1 blocker, significantly reduced the ATP-induced current potentiation but did not abolish it. The removal of external Cl- in the presence of TRAM-34 further lowered the ATP-evoked effect. A direct comparison between the ATP-evoked mean current potentiation and mean Ca2+ transient amplitude revealed a linear correlation. Treatment of microglial cells with LPS for 48h did not prevent the ATP-induced Ca2+ mobilization but completely abolished the ATP-mediated current potentiation. The absence of the Ca2+-evoked K+ current led to a less sustained ATP-evoked Ca2+ entry, as shown by the faster Ca2+ transient kinetics observed in LPS-treated microglia.CONCLUSIONS: Our study confirms a functional role for KCa3.1 channels in human microglia, linking ATP-evoked Ca2+ transients to changes in membrane conductance, with an inflammation-dependent mechanism, and suggests that during brain inflammation the KCa3.1-mediated microglial response to purinergic signaling may be reduced

Gradient of microstructural damage along the dentato‐thalamo‐cortical tract in Friedreich ataxia

Objective: The dentato-thalamo-cortical tract (DTT) is the main cerebellar efferent pathway. Degeneration of the DTT is a core feature of Friedreich ataxia (FRDA). However, it remains unclear whether DTT disruption is spatially specific, with some segments being more impacted than others. This study aimed to investigate microstructural integrity along the DTT in FRDA using a profilometry diffusion MRI (dMRI) approach. Methods: MRI data from 45 individuals with FRDA (mean age: 33.2 ± 13.2, Male/Female: 26/19) and 37 healthy controls (mean age: 36.5 ± 12.7, Male/Female:18/19) were included in this cross-sectional multicenter study. A profilometry analysis was performed on dMRI data by first using tractography to define the DTT as the white matter pathway connecting the dentate nucleus to the contralateral motor cortex. The tract was then divided into 100 segments, and dMRI metrics of microstructural integrity (fractional anisotropy, mean diffusivity and radial diffusivity) at each segment were compared between groups. The process was replicated on the arcuate fasciculus for comparison. Results: Across all diffusion metrics, the region of the DTT connecting the dentate nucleus and thalamus was more impacted in FRDA than downstream cerebral sections from the thalamus to the cortex. The arcuate fasciculus was minimally impacted. Interpretation: Our study further expands the current knowledge about brain involvement in FRDA, showing that microstructural abnormalities within the DTT are weighted to early segments of the tract (i.e., the superior cerebellar peduncle). These findings are consistent with the hypothesis of DTT undergoing anterograde degeneration arising from the dentate nuclei and progressing to the primary motor cortex

An Investigation of Corticospinal Tract Microstructural Integrity in ARSACS Using a Profilometry MRI Analysis: Results From the PROSPAX Study

Background: Spasticity represents a core clinical feature of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) patients. Nonetheless, its pathophysiological substrate is poorly investigated. We assessed the microstructural integrity of the corticospinal tract (CST) using diffusion MRI (dMRI) via profilometry analysis to understand its possible role in the development of spasticity in ARSACS. Materials and Methods: In this multi-center prospective study, data of 37 ARSACS (M/F = 21/16; 33.4 ± 12.4 years) and 29 controls (M/F = 13/16; 42.1 ± 17.2 years) acquired within the PROSPAX consortium were collected from January 2021 to October 2022 and analyzed. Differences in terms of global CST microstructural integrity were probed, as well as a possible spatial distribution of the damage along the tract via profilometry analysis. Possible correlations between clinical severity, including the Spastic Paraplegia Rating Scale (SPRS), were also tested. Results: A significant global involvement of the CST was found in ARSACS compared to controls (all tests with p < 0.001), with a spatially defined pattern of more pronounced microstructural integrity loss occurring right below and above the pons, a structure that was also confirmed to be thickened in these patients (p < 0.001). A bilateral negative correlation emerged between the microstructural integrity of the CST and clinical indices of spasticity expressed via SPRS (p = 0.02 for both CSTs). Conclusion: A clinically meaningful microstructural involvement of CST is present in ARSACS patients, with a spatially defined pattern of damage occurring right below and above a thickened pons. An evaluation of the microstructure of this bundle might serve as a possible biomarker in this condition

Conventional MRI-Based Structural Disconnection and Morphometric Similarity Networks and Their Clinical Correlates in Multiple Sclerosis

BACKGROUND AND OBJECTIVES: Although multiple sclerosis (MS) can be conceptualized as a network disorder, brain network analyses typically require advanced MRI sequences not commonly acquired in clinical practice. Using conventional MRI, we assessed cross-sectional and longitudinal structural disconnection and morphometric similarity networks in people with MS (pwMS), along with their relationship with clinical disability. METHODS: In this longitudinal monocentric study, 3T structural MRI of pwMS and healthy controls (HC) was retrospectively analyzed. Physical and cognitive disabilities were assessed with the expanded disability status scale (EDSS) and the symbol digit modalities test (SDMT), respectively. Demyelinating lesions were automatically segmented, and the corresponding masks were used to assess pairwise structural disconnection between atlas-defined brain regions based on normative tractography data. Using the Morphometric Inverse Divergence method, we computed morphometric similarity between cortical regions based on FreeSurfer surface reconstruction. Using network-based statistics (NBS) and its extension NBS-predict, we tested whether subject-level connectomes were associated with disease status, progression, clinical disability, and long-term confirmed disability progression (CDP), independently from global lesion burden and atrophy. RESULTS: We studied 461 pwMS (age = 37.2 ± 10.6 years, F/M = 324/137), corresponding to 1,235 visits (mean follow-up time = 1.9 ± 2.0 years, range = 0.1-13.3 years), and 55 HC (age = 42.4 ± 15.7 years; F/M = 25/30). Long-term clinical follow-up was available for 285 pwMS (mean follow-up time = 12.4 ± 2.8 years), 127 of whom (44.6%) exhibited CDP. At baseline, structural disconnection in pwMS was mostly centered around the thalami and cortical sensory and association hubs, while morphometric similarity was extensively disrupted (pFWE < 0.01). EDSS was related to frontothalamic disconnection (pFWE < 0.01) and disrupted morphometric similarity around the left perisylvian cortex (pFWE = 0.02), while SDMT was associated with cortico-subcortical disconnection in the left hemisphere (pFWE < 0.01). Longitudinally, both structural disconnection and morphometric similarity disruption significantly progressed (pFWE = 0.04 and pFWE < 0.01), correlating with EDSS increase (ρ = 0.07, p = 0.02 and ρ = 0.11, p < 0.001), while baseline disconnection predicted long-term CDP (accuracy = 59% [58-60], p = 0.03). DISCUSSION: Structural disconnection and morphometric similarity networks, as assessed through conventional MRI, are sensitive to MS-related brain damage and its progression. They explain disease-related clinical disability and predict its long-term evolution independently from global lesion burden and atrophy, potentially adding to established MRI measures as network-based biomarkers of disease severity and progression