Diffuse Alterations Research Articles

Malignant Perivascular epithelioid cell tumour of the uterus without TFE3 gene rearrangement: a case report

BackgroundPerivascular epithelioid cell tumours (PEComas) are soft tissue tumours. These neoplasms belong to the family of mesenchymal tumours, which include angiomyolipomas, clear-cell sugar tumours of the lung, and PEComas not otherwise specified (NOS). The probability of a perivascular epithelioid cell tumour (PEComa) occurring in the uterus is low, and the incidence, diagnosis, treatment, and outcomes of such tumours are still unclear.Case presentationA 51-year-old woman presented a 4-year history of natural menopause. An intrauterine mass was detected via ultrasound examination; the mass showed a tendency to increase but caused no symptoms. The levels of tumour markers were within the normal range. Pathological analysis of the curettage revealed perivascular epithelioid differentiation of the endometrial tumour. Consequently, a laparoscopic total hysterectomy with bilateral adnexectomy was performed. No distant metastasis was detected via whole-body positron emission computed tomography (PETCT) after the operation. Fluorescence in situ hybridization (FISH) revealed no TFE3 gene rearrangement. Next-generation sequencing of bone and soft tissue revealed negative TSC1/2 and TP53 expression. No recurrence or metastasis was observed during the 18-month follow-up period.ConclusionPEComa of the gynecologic tract is a rare and challenging entity. Diffuse HMB-45 expression, TSC alterations and TFE3 rearrangement are characteristic of uterine PEComas. Surgical resection is the first choice. Genetic testing is helpful for determining the nature of the mass and for choosing targeted therapy. Further research is needed to establish treatment protocols.

Very high-T hydration in the lower gabbro section of Semail ophiolite, Hydrous components of the lower crust at fast-spreading ridge

Totally fresh black gabbros are observed locally at the very base of the gabbro section in southern Semail ophiolite. Devoid of medium to low-temperature diffuse alteration, the black gabbros are characterized by cloudy plagioclase marked by a high density of hydrothermal inclusions below the optical microscope resolution, evolving into diopside and pargasite crystals ∼10 μm sized. They record hydration at temperature over 900 °C as shown by their major elements composition. Focused Electron Backscattered Electron Diffraction (EBSD) study of the crystalline inclusions, suggests a phase transition from diopside to amphibole, and traces consistent crystallographic relationships of diopside inclusions with their host plagioclase. The detailed geometry of the microcrack system traces a complete fluid path from inter-grain cracking, to plagioclase intra-grain network, possibly thermally-induced. The evidence of solid-state deformation overprinting the magmatic textures suggests that twinning mechanism in plagioclase controls the intra-grain diffusion of hydrous fluids. Located at the interface of the Moho Transition Zone (MTZ) and semi-brittle lithosphere, the ‘black gabbros’ record a narrow domain where focused fluid flow induces rapid cooling below the gabbro solidus at the lowest limit of the magma chamber.

Strict Avalanche Criterion of SHA-256 and Sub-Function-Removed Variants

The measure of diffusion, the property of dissipating patterns and statistical structures in cryptographic transformations, serves as a valuable heuristic for assessing the obscurity of patterns that could lead to collisions. As with many cryptographic hash functions, SHA-256 is thought to exhibit the property of diffusion. While SHA-256’s diffuse output is loosely documented, even less is known about how the diffusion rate changes across the 64 rounds in its compression function and how the algorithm’s individual sub-functions contribute to the overall diffusion. The diffusion of the unmodified compression function is initially measured using the Strict Avalanche Criterion (SAC), with the aim of understanding the alteration in diffusion across the 64 rounds of compression. The level to which sub-functions affect diffusion is subsequently measured, enabling potential prioritization of these sub-functions in future collision attacks. To accomplish this, the compression function is modified by removing sub-functions, and the diffusion of these new variants is measured. While the SAC measurements of each function eventually plateau close to the 50% target, no function, including the unmodified compression function, strictly meets the SAC, and multiple variant functions diffuse at comparatively slower rates.

Diffusion tensor metrics, motor and non-motor symptoms in de novo Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons' degeneration of the substantia nigra, presenting with motor and non-motor symptoms. We hypothesized that altered diffusion metrics are associated with clinical symptoms in de novo PD patients. Fractional Anisotropy (FA) and Mean (MD), Axial (AD), and Radial Diffusivity (RD) were assessed in 55 de novo PD patients (58.62 ± 9.85 years, 37 men) and 55 age-matched healthy controls (59.92 ± 11.25 years, 34 men). Diffusion-weighted images and clinical variables were collected from the Parkinson's Progression Markers Initiative study. Tract-based spatial statistics were used to identify white matter (WM) changes, and fiber tracts were localized using the JHU-WM tractography atlas. Motor and non-motor symptoms were evaluated in patients. We observed higher FA values and lower RD values in patients than controls in various fiber tracts (p-TFCE < 0.05). No significant MD or AD difference was observed between groups. Diffusion metrics of several regions significantly correlated with non-motor (state and trait anxiety and daytime sleepiness) and axial motor symptoms in the de novo PD group. No correlations were observed between diffusion metrics and other clinical symptoms evaluated. Our findings suggest microstructural changes in de novo PD fiber tracts; however, limited associations with clinical symptoms reveal the complexity of PD pathology. They may contribute to understanding the neurobiological changes underlying PD and have implications for developing targeted interventions. However, further longitudinal research with larger cohorts and consideration of confounding factors are necessary to elucidate the underlying mechanisms of these diffusion alterations in de novo PD.

Synergistic effects of GFAP and Aβ42: Implications for white matter integrity and verbal memory across the cognitive spectrum

BackgroundPlasma glial fibrillary acidic protein (GFAP), an astrocytic biomarker, has previously been linked with Alzheimer's disease (AD) status, amyloid levels, and memory performance in older adults. The neuroanatomical pathways by which astrogliosis/astrocyte reactivity might impact cognitive outcomes remains unclear. We evaluated whether plasma GFAP and amyloid levels had a synergistic effect on fornix structure, which is critically involved in AD-associated cholinergic pathways. We also examined whether fornix structure mediates associations between GFAP and verbal memory. MethodsIn a cohort of both asymptomatic and symptomatic older adults (total n = 99), we assessed plasma GFAP, amyloid-β42 (Aβ42), other AD-related proteins, and vascular markers, and we conducted comprehensive memory testing. Tractography-based methods were used to assess fornix structure with whole brain diffusion metrics to control for diffuse alterations in brain white matter. ResultsIn individuals in the low plasma amyloid-β42 (Aβ42) group, higher plasma GFAP was associated with lower fractional anisotropy (FA; p = 0.007), higher mean diffusivity (MD; p < 0.001), higher radial diffusivity (RD; p < 0.001), and higher axial diffusivity (DA; p = 0.001) in the left fornix. These associations were independent of APOE gene status, plasma levels of total tau and neurofilament light, plasma vascular biomarkers, and whole brain diffusion metrics. In a sub-analysis of participants in the low plasma Aβ42 group (n = 33), fornix structure mediated the association between higher plasma GFAP levels and lower verbal memory performance. DiscussionHigher plasma GFAP was associated with altered fornix microstructure in the setting of greater amyloid deposition. We also expanded on our prior GFAP-verbal memory findings by demonstrating that in the low plasma Aβ42 group, left fornix integrity may be a primary white matter conduit for the negative associations between GFAP and verbal memory performance. Overall, these findings suggest that astrogliosis/astrocyte reactivity may play an early, pivotal role in AD pathogenesis, and further demonstrate that high GFAP and low Aβ42 in plasma may reflect a particularly detrimental synergistic role in forniceal-memory pathways.

Mapping macrostructural and microstructural brain alterations in patients with neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a rare complex neurodegenerative disorder presents with various radiological features. The study aimed to investigate the structural abnormalities in NIID using multi-shell diffusion MR. Twenty-eight patients with adult-onset NIID and 32 healthy controls were included. Volumetric and diffusion MRI measures, including volume, fractional anisotropy (FA), mean diffusivity (MD), intracellular volume fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF) of six brain structures, including cortex, subcortical GM, cerebral WM, cerebellar GM and WM, and brainstem, were obtained and compared between NIID and healthy controls. Associations between MRI measures and clinical variables were investigated. Brain lesions of NIID included corticomedullary junction lesions on DWI, confluent leukoencephalopathy, lesions on callosum, cerebellar middle peduncle, cerebellar paravermal area and brainstem, and brain atrophy. Compared to healthy controls, NIID showed extensive volume loss of all the six brain regions (all p < 0.001); lower FA in cerebral WM (p < 0.001); higher MD in all WM regions; lower ODI in cortex (p < 0.001); higher ODI in subcortical GM (p < 0.001) and brainstem (p = 0.016); lower ICVF in brainstem (p = 0.001), and cerebral WM (p < 0.001); higher ISOVF in all the brain regions (p < 0.001). Higher MD of cerebellar WM was associated with worse cognitive level as evaluated by MoCA scores (p = 0.011). NIID patients demonstrated widespread brain atrophy but heterogeneous diffusion alterations. Cerebellar WM integrity impairment was correlated with the cognitive decline. The findings of the current study offer a sophisticated picture of brain structural alterations in NIID.

Analysis of diffusion changes in cerebral tissues of Parki̇nson's patients who underwent subthalamic nucleus deep brain stimulation: Correlation of improvements in motor and neuropsychiatric symptoms

ObjectiveParkinson's disease (PD) as a neurodegenerative disorder characterized by a reduction in both the quantity and functionality of dopaminergic neurons. This succinctly highlights the central pathological feature of PD and its association with dopaminergic neuron degeneration, which underlies the motor and non-motor symptoms of the disease.This study aims to elucidate the nuances of apparent diffusion coefficient (ADC) changes in different cerebral regions by after the bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) surgery of PD, as well as to investigate their potential interactions with the motor and neuropsychiatric spectrum. MethodsPatients who underwent STN-DBS surgery for PD between 2017 and 2019 were included in this study. The results of diffusion magnetic resonance imaging (MRI), Unified Parkinson Disease Rating Scale (UPDRS) III scores, Beck and Hamilton depression tests were recorded before and at the 3rd month of postoperative stimulation. The data obtained were evaluated with the Wilcoxon signed rank test. Result of the statistical tests were within the 95 % confidence interval and p values were significant below 0.05. ResultsOur study was conducted with a total of 13 patients, 8 men and 5 women. As a result of measurements made in a total of 32 different regions, especially in the motor and neuropsychiatric areas of the brain, an increase in ADC values was found in all areas. ADC changes of eight localizations such as left corpus callosum, right corona radiata, left corona radiata, hippocampus, right insula, left superior cerebellar peduncle, left caudate nucleus and left putamen were statistically significant. UPDRS III scores improved by 57 % (p <0.05), and Beck and Hamilton depression scores by 25 % and 33 %, respectively (p> 0.05). ConclusionsThis article implicate that bilateral STN-DBS surgery potentially exerts beneficial effects on both motor and neuropsychiatric symptomatology in individuals with PD. We believe that this therapeutic mechanism is hypothesized to involve modulation of diffusion alterations within distinct cerebral tissues.

Exploring the role of the combination of FDG-PET plus whole body MRI for staging patients with high-risk smoldering myeloma: A prospective trial.

7569 Background: According to IMWG criteria, Smoldering Multiple Myeloma (SMM) is an asymptomatic stage characterized by M-spike &lt; 3 g/dl serum and/or bone marrow plasma cells infiltration between 10-59% in absence of myeloma-defining events and organ damage. In SMM setting, it is really important to differntiate high risk SMM (HR-SMM), in which treatment could be available thanks to clinical trials. 2016 IMWG criteria state that detection of bone lesions is mandatory for diagnosis of multiple myeloma and essential for diagnosis of SMM. It is really important to clarify in SMM the best imaging analysis in order to perform a correct diagnosis, and particularly it is necessary to define if the combination of FDG-PET/TC and WB-MRI could improve the assessment of lytic lesions and so the discrimination between high risk SMM and symptomatic MM. Methods: In our Institution we conducted a prospective trial, based on integrated new generation imaging, aiming to improve patients’ stadiation and to define its prognostic implications. From January 2021 to January 2024, we performed a prospective trial enrolling 26 consecutive newly diagnosed high risk SMM, according to IMWG, in which WB-MRI was performed according to MY-RADS criteria in combination with FDG PET-CT (median age 56; range 36-85). Results: Our comparison between WB-MRI and FDG PET-CT, showed a discordance between the two imaging modalities in 4/26 (15%) cases. In particular, in 3/26 (12%) cases WB-MRI showed bone lesions that have lead to symptomatic MM diagnosis according to IMWG criteria, while PET-CT was negative. In one case, PET-CT showed a diffuse uptake, not diagnostic for MM, while WB-MRI was negative. WB-MRI showed a 100% of accuracy in detecting SMM and MM. Therefore, WB-MRI has lead to a modification of the prognosis and treatment approach (observation in SMM vs treatment in symptomatic MM) in 3/26 patients (11%) (i.e. Figure 1, with DWI of C2 lesion). Furthermore, in 5/23 (22%) cases of confirmed SMM WB-MRI showed a slight diffuse alteration pattern of bone marrow without any overt lytic bone lesion, which could be a potential prognostic evidence. Conclusions: Our results support a fundamental role of WB-MRI in combination with FDG PET/CT in the stadiation of patients with newly diagnosed high risk SMM, which could modify prognosis and treatment, improving the differentiation with symptomatic MM. In particular, combination of WB-MRI plus FDG PET/CT could be more accurate in the detection of bone lesions than FDG PET/CT alone, being able to anticipate symptomatic MM diagnosis and consequently its treatment. Moreover, a diffuse pattern of marrow involvement could be detected in some HR-SMM patients without any overt lytic lesions: it is questionable if this group of patients is associated with a rapid progression in lytic lesions and so in symptomatic MM diagnosis. Prospective data on evolution of these patients are pending.

Choroidal hyperpermeability patterns correlate with disease severity in central serous chorioretinopathy: CERTAIN study report 2.

Choroidal vascular hyperpermeability (CVH) on indocyanine green angiography (ICGA) is a hallmark feature of central serous chorioretinopathy (CSC). We identified three distinct CVH phenotypes in CSC: uni-focal indistinct signs of choroidal hyperpermeability (uni-FISH) with one focal area of CVH, multiple areas of focal CVH (multi-FISH), and diffuse hyperpermeability covering most of the posterior pole (DISH). This report investigates the distribution of these phenotypes and their association with signs of disease chronicity. The CERTAIN study is a monocentric, retrospective study on consecutive CSC patients referred to a large tertiary referral centre that underwent ultra-widefield (UWF) and 55° ICGA. Two independent graders assessed CVH patterns based on mid- to late-phase UWF and 55° ICGA with a third grader acting as referee. Of the 167 eyes of 91 patients included in this study, 43 (26%) showed uni-FISH, 87 (52%) multi-FISH, and 34 (20%) showed DISH based on UWF ICGA. Median age (40 vs. 45 vs. 57; p < 0.001) and logMAR visual acuity (0 vs. 0 vs. 0.1, p < 0.001) differed significantly in-between groups, as did the occurrence of cystoid retinal degeneration (PCRD; 0% vs. 1% vs. 18%, p < 0.001) or diffuse atrophic RPE alterations (DARA; 0% vs. 17% vs. 29%, p < 0.001). The same was true when grading was based on 55° ICGA. The CVH patterns of uni-FISH, multi-FISH, and DISH are typical of CSC. These patterns correlate with established signs of CSC chronicity. Their predictive role in treatment response and prognosis remains to be evaluated.

Comprehensive Assessment of Ischemic Stroke in Nonhuman Primates: Neuroimaging, Behavioral, and Serum Proteomic Analysis.

Ischemic strokes, prevalence and impactful, underscore the necessity of advanced research models closely resembling human physiology. Our study utilizes nonhuman primates (NHPs) to provide a detailed exploration of ischemic stroke, integrating neuroimaging data, behavioral outcomes, and serum proteomics to elucidate the complex interplay of factors involved in stroke pathophysiology. We observed a consistent pattern in infarct volume, peaking at 1-month postmiddle cerebral artery occlusion (MCAO) and then stabilized. This pattern was strongly correlated to notable changes in motor function and working memory performance. Using diffusion tensor imaging (DTI), we detected significant alterations in fractional anisotropy (FA) and mean diffusivity (MD) values, signaling microstructural changes in the brain. These alterations closely correlated with the neurological and cognitive deficits that we observed, highlighting the sensitivity of DTI metrics in stroke assessment. Behaviorally, the monkeys exhibited a reliance on their unaffected limb for compensatory movements, a common response to stroke impairment. This adaptation, along with consistent DTI findings, suggests a significant impact of stroke on motor function and spatial perception. Proteomic analysis through MS/MS functional enrichment identified two distinct groups of proteins with significant changes post-MCAO. Notably, MMP9, THBS1, MB, PFN1, and YWHAZ were identified as potential biomarkers and therapeutic targets for ischemic stroke. Our results underscore the complex nature of stroke and advocate for an integrated approach, combining neuroimaging, behavioral studies, and proteomics, for advancing our understanding and treatment of this condition.

Baseline symptom-related white matter tracts predict individualized treatment response to 12-week antipsychotic monotherapies in first-episode schizophrenia

There is significant heterogeneity in individual responses to antipsychotic drugs, but there is no reliable predictor of antipsychotics response in first-episode psychosis. This study aimed to investigate whether psychotic symptom-related alterations in fractional anisotropy (FA) and mean diffusivity (MD) of white matter (WM) at the early stage of the disorder may aid in the individualized prediction of drug response. Sixty-eight first-episode patients underwent baseline structural MRI scans and were subsequently randomized to receive a single atypical antipsychotic throughout the first 12 weeks. Clinical symptoms were evaluated using the eight “core symptoms” selected from the Positive and Negative Syndrome Scale (PANSS-8). Follow-up assessments were conducted at the 4th, 8th, and 12th weeks by trained psychiatrists. LASSO regression model and cross-validation were conducted to examine the performance of baseline symptom-related alterations FA and MD of WM in the prediction of individualized treatment outcome. Fifty patients completed both clinical follow-up assessments by the 8th and 12th weeks. 30 patients were classified as responders, and 20 patients were classified as nonresponders. At baseline, the altered diffusion properties of fiber tracts in the anterior thalamic radiation, corticospinal tract, callosum forceps minor, longitudinal fasciculi (ILF), inferior frontal-occipital fasciculi (IFOF) and superior longitudinal fasciculus (SLF) were related to the severity of symptoms. These abnormal fiber tracts, especially the ILF, IFOF, and SLF, significantly predicted the response to antipsychotic treatment at the individual level (AUC = 0.828, P < 0.001). These findings demonstrate that early microstructural WM changes contribute to the pathophysiology of psychosis and may serve as meaningful individualized predictors of response to antipsychotics.

The Role of the Anterior Thalamic Nuclei in the Genesis of Memory Disorders in Alzheimer's Disease: An Exploratory Study.

Increasing evidence is demonstrating that degeneration of specific thalamic nuclei, in addition to the hippocampus, may occur in Alzheimer's disease (AD) from the prodromal stage (mild cognitive impairment - MCI) and contribute to memory impairment. Here, we evaluated the presence of macro and micro structural alterations at the level of the anterior thalamic nuclei (ATN) and medio-dorsal thalamic nuclei (MDTN) in AD and amnestic MCI (aMCI) and the possible relationship between such changes and the severity of memory impairment. For this purpose, a sample of 50 patients with aMCI, 50 with AD, and 50 age- and education-matched healthy controls (HC) were submitted to a 3-T MRI protocol with whole-brain T1-weighted and diffusion tensor imaging and a comprehensive neuropsychological assessment. At macro-structural level, both the ATN and MDTN were found significantly smaller in patients with aMCI and AD when compared to HC subjects. At micro-structural level, instead, diffusion alterations that significantly differentiated aMCI and AD patients from HC subjects were found only in the ATN, but not in the MDTN. Moreover, diffusion values of the ATN were significantly associated with poor episodic memory in the overall patients' group. These findings represent the first in vivo evidence of a relevant involvement of ATN in the AD-related neurodegeneration and memory profile and strengthen the importance to look beyond the hippocampus when considering neurological conditions characterized by memory decline.

Assessment of glymphatic dysfunction in pediatric idiopathic intracranial hypertension: insights from quantitative diffusivity and perivascular spaces analysis-a case-control study.

The impaired drainage of cerebrospinal fluid through the glymphatic system is thought to play a role in the idiopathic intracranial hypertension (IIH) pathophysiology. Limited data exist regarding the glymphatic system's involvement in pediatric patients with IIH. Therefore, the study's objective was to quantitatively evaluate alterations in parenchymal diffusivity and magnetic resonance imaging (MRI)-visible dilated perivascular spaces (PVS) as imaging indicators of glymphatic dysfunction in pediatric patients with IIH. Patients diagnosed with IIH in 2017-2022 in a single tertiary center (Sheba Medical Center, Israel) were retrospectively reviewed. Twenty-four pediatric patients were enrolled. All patients underwent clinical 3-T brain MRI. The control group included 24 age- and gender-matched healthy subjects with a normal-appearing brain on imaging. We used automatic atlas-based diffusion-weighted imaging analysis to determine regional diffusivity of the thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, and brain stem. PVS were evaluated using a semi-quantitative rating scale on T2-weighted images. Variables were compared using the Mann-Whitney test. Multivariate analysis of covariance was used to test for differences between controls and IIH patients. No significant differences in regional brain diffusivity were observed between individuals with IIH and healthy controls (P=0.14-0.91 for various brain regions). The number of visible PVS was comparable between patients with IIH and the control group across all evaluated sites (P=0.12-0.74 for various brain regions). Pediatric IIH patients exhibited similar patterns of parenchymal diffusivity and PVS compared to age-matched controls. These findings do not support the hypothesis that the glymphatic system may play a role in the pathophysiology of pediatric IIH, although previously postulated. However, employing more sophisticated magnetic resonance (MR) techniques could enhance the sensitivity in uncovering underlying glymphatic dysfunction. Further research is warranted to validate and explore this association in larger cohorts and investigate the underlying mechanisms involved in IIH.

Current Auditory Hallucinations Are Not Associated With Specific White Matter Diffusion Alterations in Schizophrenia.

Studies have linked auditory hallucinations (AH) in schizophrenia spectrum disorders (SCZ) to altered cerebral white matter microstructure within the language and auditory processing circuitry (LAPC). However, the specificity to the LAPC remains unclear. Here, we investigated the relationship between AH and DTI among patients with SCZ using diffusion tensor imaging (DTI). We included patients with SCZ with (AH+; n = 59) and without (AH-; n = 81) current AH, and 140 age- and sex-matched controls. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were extracted from 39 fiber tracts. We used principal component analysis (PCA) to identify general factors of variation across fiber tracts and DTI metrics. Regression models adjusted for sex, age, and age2 were used to compare tract-wise DTI metrics and PCA factors between AH+, AH-, and healthy controls and to assess associations with clinical characteristics. Widespread differences relative to controls were observed for MD and RD in patients without current AH. Only limited differences in 2 fiber tracts were observed between AH+ and controls. Unimodal PCA factors based on MD, RD, and AD, as well as multimodal PCA factors, differed significantly relative to controls for AH-, but not AH+. We did not find any significant associations between PCA factors and clinical characteristics. Contrary to previous studies, DTI metrics differed mainly in patients without current AH compared to controls, indicating a widespread neuroanatomical distribution. This challenges the notion that altered DTI metrics within the LAPC is a specific feature underlying AH.

Influence of metronidazole loaded into silver nanoparticle microcapsules on efficacy of alginate gel in correction of structural and functional disorders of dental support apparatus in rats with periodontitis

Objective: To evaluate the effect of metronidazole loaded into silver impregnated alginate microcapsules on the structural and functional disorders of the dental support apparatus in periodontitis. Material and methods. The studies were carried out on 30 white male rats randomly divided into two groups. Comparison group — 15 animals with an experimental model of periodontitis, which underwent applications of a gel containing microcapsules without additional loading with active substances. The experimental group included 15 animals with periodontitis, which were subjected to applications of gel with microcapsules containing metronidazole on inflamed gums. To assess the morphological changes in the supporting apparatus of the tooth, the mandible was taken with subsequent histological examination. Results. Results. Application of a gel containing microcapsules with silver nanoparticles loaded with metronidazole on the gums of animals with periodontitis leads to partial reduction of structural disorders. Thus, local disorganization of the fibers of the circular ligament of the tooth in the experimental group was observed only 5 cases, signs of limited bone loss — in 2 cases out of 15. In the comparison group, all 15 animals showed bone resorption and in 13 of 15 cases there was diffuse fiber alteration throughout the circumferential ligament of the tooth. Conclusion. The inclusion of alginate microcapsules with silver nanoparticles metronidazole leads to a significant decrease in destructive processes occurring in the near-tooth tissues during periodontitis.

INTERACTIVE ROLE OF SLEEP AND AROUSAL ON COGNITION AND BRAIN STRUCTURE IN CHRONIC PAIN PATIENTS

Abstract Chronic widespread pain (CWP) patients experience heightened arousal, insomnia complaints, poor cognition, and diffuse brain structure alterations, but interactive relationships among symptoms remain unexplored. We assessed whether physiological arousal [assessed via heart rate variability (HRV)] moderated associations between sleep and cognition/brain structure. Adults (N=42, Mage=46.2±13.7) with CWP and insomnia (difficulty falling/staying asleep) completed 14 daily sleep diaries, 5-minute Holter monitoring [HRV root mean square of successive normal heartbeats (RMSSD), low frequency/high frequency (lf/hf) computed], cognitive tasks [Stroop (processing speed/attention/inhibition), Sternberg (working memory)], and magnetic resonance imaging. Moderation analyses examined interactive associations between sleep [total sleep time (TST), wake after sleep onset, sleep onset latency (SOL)] and HRV with cognition/gray matter volume of frontal/temporal regions. SOL and lf/hf interacted in associations with working memory and attention/processing speed. Longer SOL was associated with worse Sternberg/Stroop at lowest sympathetic predominance levels. Conversely, longer SOL was associated with better Stroop at highest lf/hf. SOL and RMSSD interacted in associations with anterior cingulate, showing longer SOL associated with lower volumes at lowest arousal levels. TST and RMSSD interacted in associations with right hippocampus, with shorter TST associated with lower volume at highest/average arousal levels. Shared dynamic physiological arousal and sleep onset hyperarousal mechanisms impact cognition and neural structure in CWP. Longer SOL may only negatively impact cognition/anterior cingulate structure up to a certain arousal threshold, with shared mechanisms potentially benefitting cognition at highest arousal levels. At higher arousal, longer TST may protect against hippocampal volume reduction. Future prospective studies are needed to inform temporal characteristics.

White matter integrity in bipolar disorder investigated with diffusion tensor magnetic resonance imaging and fractal geometry

BackgroundGrowing evidence suggests the presence of white matter (WM) alterations in bipolar disorder (BD). In this study we aimed to investigate the state of WM structures, in terms of tissue integrity and morphological complexity, in BD patients compared to healthy controls (HC), in an attempt to better elucidate the microstructural changes associated with BD. MethodsWe collected a dataset of 399 Diffusion Tensor Magnetic Resonance Imaging (167 BD and 232 healthy controls) images, acquired at five different sites, which was processed with Tract-Based Spatial Statistics (TBSS) and fractal analysis. ResultsThe TBSS analysis demonstrated significantly lower FA values in the BD group. Diffusion abnormalities were primarily located in the temporo-parietal network. The Fractal Dimension (FD) analysis did not reveal consistent significant differences in the morphological complexity of WM structures between the groups. When the FD values of patients were considered individually, it is possible to notice some localized significant deviations from the healthy population. LimitationsDTI sequences have not been harmonized before acquisition, samples' sizes are heterogeneous. ConclusionsThis study, by applying both TBSS and FD analyses, allows to evaluate diffusion and structural alterations of WM at the same time. The evaluation of WM integrity from these two different perspectives could be useful to better understand the pathophysiological and morphological changes underpinning bipolar disorder.

Neuroimaging markers of Alice in Wonderland syndrome in patients with migraine with aura.

The Alice in Wonderland syndrome (AIWS) is a transient neurological disturbance characterized by sensory distortions most frequently associated with migraine in adults. Some lines of evidence suggest that AIWS and migraine might share common pathophysiological mechanisms, therefore we set out to investigate the common and distinct neurophysiological alterations associated with these conditions in migraineurs. We conducted a case-control study acquiring resting-state fMRI data from 12 migraine patients with AIWS, 12 patients with migraine with typical aura (MA) and 24 age-matched healthy controls (HC). We then compared the interictal thalamic seed-to-voxel and ROI-to-ROI cortico-cortical resting-state functional connectivity between the 3 groups. We found a common pattern of altered thalamic connectivity in MA and AIWS, compared to HC, with more profound and diffuse alterations observed in AIWS. The ROI-to-ROI functional connectivity analysis highlighted an increased connectivity between a lateral occipital region corresponding to area V3 and the posterior part of the superior temporal sulcus (STS) in AIWS, compared to both MA and HC. The posterior STS is a multisensory integration area, while area V3 is considered the starting point of the cortical spreading depression (CSD), the neural correlate of migraine aura. This interictal hyperconnectivity might increase the probability of the CSD to directly diffuse to the posterior STS or deactivating it, causing the AIWS symptoms during the ictal phase. Taken together, these results suggest that AIWS in migraineurs might be a form of complex migraine aura, characterized by the involvement of associative and multisensory integration areas.

Widespread intra-axonal signal fraction abnormalities in bipolar disorder from multicompartment diffusion MRI: Sensitivity to diagnosis, association with clinical features and pharmacologic treatment.

Despite diffusion tensor imaging (DTI) evidence for widespread fractional anisotropy (FA) reductions in the brain white matter of patients with bipolar disorder, questions remain regarding the specificity and sensitivity of FA abnormalities as opposed to other diffusion metrics in the disorder. We conducted a whole-brain voxel-based multicompartment diffusion MRI study on 316 participants (i.e., 158 patients and 158 matched healthy controls) employing four diffusion metrics: the mean diffusivity (MD) and FA estimated from DTI, and the intra-axonal signal fraction (IASF) and microscopic axonal parallel diffusivity (Dpar) derived from the spherical mean technique. Our findings provide novel evidence about widespread abnormalities in other diffusion metrics in BD. An extensive overlap between the FA and IASF results suggests that the lower FA in patients may be caused by a reduced intra-axonal volume fraction or a higher macromolecular content in the intra-axonal water. We also found a diffuse alteration in MD involving white and grey matter tissue and more localised changes in Dpar. A Machine Learning analysis revealed that FA, followed by IASF, were the most helpful metric for the automatic diagnosis of BD patients, reaching an accuracy of 72%. Number of mood episodes, age of onset/duration of illness, psychotic symptoms, and current treatment with lithium, antipsychotics, antidepressants, and antiepileptics were all significantly associated with microstructure abnormalities. Lithium treatment was associated with less microstructure abnormality.

Pathological ultrastructural alterations of myelinated axons in normal appearing white matter in progressive multiple sclerosis

Multiple sclerosis (MS) pathophysiology includes inflammation, demyelination and neurodegeneration, but the exact mechanisms of disease initiation and progression are unknown. A major feature of lesions is lack of myelin, which increases axonal energy demand and requires adaptation in number and size of mitochondria. Outside lesions, subtle and diffuse alterations are observed in normal appearing white matter (NAWM) and normal appearing grey matter (NAGM), including increased oxidative stress, reduced axon density and changes in myelin composition and morphology. On an ultrastructural level, only limited data is available on alterations in myelinated axons. We generated large scale 2D scanning transmission electron microscopy images (‘nanotomy’) of non-demyelinated brain tissue of control and progressive MS donors, accessible via an open-access online repository. We observed a reduced density of myelinated axons in NAWM, without a decrease in cross-sectional axon area. Small myelinated axons were less frequently and large myelinated axons were more frequently present in NAWM, while the g-ratio was similar. The correlation between axonal mitochondrial radius and g-ratio was lost in NAWM, but not in NAGM. Myelinated axons in control GM and NAGM had a similar g-ratio and radius distribution. We hypothesize that axonal loss in NAWM is likely compensated by swelling of the remaining myelinated axons and subsequent adjustment of myelin thickness to maintain their g-ratio. Failure of axonal mitochondria to adjust their size and fine-tuning of myelin thickness may render NAWM axons and their myelin more susceptible to injury.Graphical