Altered Brain Glymphatic Function at Diffusion-Tensor MRI in Pre-cirrhotic Metabolic Dysfunction-Associated Fatty Liver Disease.

RATIONALE AND OBJECTIVES: To evaluate glymphatic function changes and their relationships with clinical features in patients with metabolic dysfunction-associated fatty liver disease (MAFLD), thereby facilitating early intervention before this disease progresses to cirrhosis. MATERIALS AND METHODS: A cross-sectional cohort of 46 pre-cirrhotic MAFLD patients and 30 age-, sex-, and education-matched controls was enrolled, with diffusion-tensor imaging (DTI) data, laboratory and neurocognitive scores collected. The DTI analysis along the perivascular space (DTI-ALPS) index was computed for qualifying glymphatic function. Generalized linear model and partial correlation analyses were applied to evaluate relationships between the ALPS index and clinical variables. RESULTS: MAFLD group exhibited a decreased ALPS index and increased diffusivity along the y-axis in the projection fiber compared to the controls. The altered ALPS index was associated with clock drawing test (CDT) score (3.931 [0.914, 6.947], P = 0.011) and was correlated with diastolic pressure level (r = -0.315, P = 0.033) in MAFLD group. The relationships of ALPS index with CDT score (6.263 [2.069, 10.458], P = 0.003) and diastolic pressure level (r = -0.518, P = 0.014) remained in the MAFLD with metabolic syndrome (MetS) group. Furthermore, the ALPS index was even associated with Auditory Verbal Learning Test-Immediate recall score (-23.853 [-45.417, -2.289], P = 0.030) in MAFLD with MetS group. CONCLUSION: MAFLD patients may have a glymphatic dysfunction prior to cirrhosis, and this alteration may be related to cognition and diastolic pressure. Glymphatic dysfunction has a more severe impact on cognition when MAFLD patient is accompanied by MetS.

Decreased DTI-ALPS index in delirium: a preliminary MRI study.

PURPOSE: Delirium is linked to brain abnormalities, yet the role of the glymphatic system is not well understood. This study aims to examine alterations in brain physiology in delirium by using diffusion-tensor imaging (DTI) to assess water diffusion along the perivascular space (ALPS) and to explore its correlation with clinical symptoms. METHODS: We examined 15 patients with delirium and 15 healthy controls, measuring water diffusion metrics along the x-, y-, and z-axes in both projection and association fibers to determine the DTI-ALPS index. We used a general linear model, adjusted for age and sex, to compare the DTI-ALPS index between groups. We also investigated the relationship between the DTI-ALPS index and clinical symptoms using partial correlations. RESULTS: Patients with delirium exhibited significantly lower DTI-ALPS indices compared to healthy controls (1.25 ± 0.15 vs. 1.38 ± 0.10, t = 2.903, p = 0.007; 1.27 ± 0.16 vs. 1.39 ± 0.08, 1.22 ± 0.16 vs. 1.37 ± 0.14, t = 2.617, p = 0.014; t = 2.719, p = 0.011; respectively). However, there was no significant correlation between the DTI-ALPS index and clinical symptoms. CONCLUSION: Our findings indicate a decreased DTI-ALPS index in patients with delirium, suggesting potential alterations in brain physiology that may contribute to the pathophysiology of delirium. This study provides new insights into the mechanisms underlying delirium.

Diffusion Tensor Imaging-Along the Perivascular-Space Index Is Associated with Disease Progression in Parkinson's Disease.

BACKGROUND: The glymphatic clearance pathway is a waste clearance system that allows for removal of soluble proteins such as amyloid ß (Aß) from the brain. Higher Aß levels are associated with cognitive dysfunction in Parkinson's disease (PD). Diffusion tensor imaging-along the perivascular space (DTI-ALPS) is an imaging measure proposed to indirectly measure glymphatic function. OBJECTIVES: Evaluate differences in DTI-ALPS-index between PD and healthy controls (HC) and characterize relationships between this proposed measure of glymphatic clearance, cognition, and disease severity in PD. METHODS: PD (n = 32) and HC (n = 23) participants underwent brain imaging to assess DTI-ALPS. PD participants were classified as PD-normal cognition (PD-NC; n = 20) or PD-mild cognitive impairment (PD-MCI; n = 12) based on a Level II comprehensive cognitive assessment. A subgroup of PD participants (n = 21) returned for annual assessments for up to 4 years after baseline. Longitudinal outcomes included changes in performance on the comprehensive cognitive assessment and changes in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). RESULTS: PD participants had lower DTI-ALPS-index compared to HC. PD participants classified as PD-MCI had significantly lower DTI-ALPS-index compared to PD-NC. Lower DTI-ALPS-index at baseline was associated with longitudinal cognitive decline and worse longitudinal disease severity. CONCLUSIONS: Glymphatic clearance, as measured with DTI-ALPS, has potential to serve as a marker of longitudinal disease progression. Interventions targeting glymphatic function should be explored for potential to slow cognitive decline in PD. © 2024 International Parkinson and Movement Disorder Society.

Ecological "Windows of opportunity" influence biofilm prokaryotic diversity differently in glacial and non-glacial Alpine streams.

In glacier-fed streams, the Windows of Opportunity (WOs) are periods of mild environmental conditions supporting the seasonal development of benthic microorganisms. WOs have been defined based on changes in biofilm biomass, but the responses of microbial diversity to WOs in Alpine streams have been overlooked. A two year (2017-2018) metabarcoding of epilithic and epipsammic biofilm prokaryotes was conducted in Alpine streams fed by glaciers (kryal), rock glaciers (rock glacial), or groundwater/precipitation (krenal) in two catchments of the Central-Eastern European Alps (Italy), aiming at testing the hypothesis that: 1) environmental WOs enhance not only the biomass but also the α-diversity of the prokaryotic biofilm in all stream types, 2) diversity and phenology of prokaryotic biofilm are mainly influenced by the physical habitat in glacial streams, and by water chemistry in the other two stream types. The study confirmed kryal and krenal streams as endmembers of epilithic and sediment prokaryotic α- and ß-diversity, with rock glacial streams sharing a large proportion of taxa with the two other stream types. Alpha-diversity appeared to respond to ecological WOs, but, contrary to expectations, seasonality was less pronounced in the turbid kryal than in the clear streams. This was attributed to the small size of the glaciers feeding the studied kryal streams, whose discharge dynamics were those typical of the late phase of deglaciation. Prokaryotic α-diversity of non-glacial streams tended to be higher in early summer than in early autumn. Our findings, while confirming that high altitude streams are heavily threatened by climate change, underscore the still neglected role of rock glacier runoffs as climate refugia for the most stenothermic benthic aquatic microorganism. This advocates the need to define and test strategies for protecting these ecosystems for preserving, restoring, and connecting cold Alpine aquatic biodiversity in the context of the progressing global warming.

Infection risk in patients with autoimmune cytopenias and immune dysregulation treated with mycophenolate mofetil and sirolimus.

Introduction: Autoimmune cytopenias (AICs) are a group of disorders characterized by immune-mediated destruction of blood cells. In children, they are often secondary to immune dysregulation that may require long-lasting immunosuppression. Mycophenolate mofetil and sirolimus represent two well-tolerated options to treat these disorders, often as a steroid-sparing option. However, no data are available on the infection risk for patients undergoing long-lasting treatments. Patients and methods: The rate of severe infective events was calculated in episodes per 100 persons/months at risk (p/m/r) documented by the analysis of hospitalization charts between January 2015 and July 2023 of patients treated with mycophenolate mofetil or sirolimus given for isolated AIC or AICs associated with autoimmune lymphoproliferative syndrome (ALPS)/ALPS-like syndromes in two large Italian pediatric hematology units. Results: From January 2015 to July 2023, 13 out of 96 patients treated with mycophenolate mofetil or sirolimus developed 16 severe infectious events requiring hospitalization. No patients died. Overall infection rate was 0.24 person/*100 months/risk (95% CI 0.09-0.3). Serious infectious events incidence was higher in patients with ALPS-like compared to others (0.42 versus 0.09; p = 0.006) and lower in patients who underwent mycophenolate treatment alone compared to those who started sirolimus after mycophenolate failure (0.04 versus 0.29, p = 0.03). Considering only patients who started treatment at the beginning of study period, overall cumulative hazard was 18.6% at 60 months (95% CI 3.4-31.4) with higher risk of infectious events after 5 years in ALPS-like patients (26.1%; 95% CI 3.2-43.5) compared to other AICs (4%; 95% CI 0-11.4; p = 0.041). Discussion: To the best of our knowledge, this is the first study to describe the infectious risk related to mycophenolate and sirolimus chronic treatment in patients with AICs and immune dysregulation. Our data highlight that infection rate is very low and mainly related to the underlying hematological condition. Conclusions: Mycophenolate and sirolimus represent a safe immunosuppressive therapy in AICs and immune dysregulation syndromes.

Cold mountain stream chironomids (Diptera) of the genus Diamesa indicate both historical and recent climate change.

Chironomids of the genus Diamesa (Meigen, 1835, Diptera: Chironomidae) inhabit cold, oxygen-rich running waters. We have investigated the presence of Diamesa and other freshwater macroinvertebrates at 22 stream sampling sites in 3 European high mountain regions (the Central Pyrenees, the Ötztal Alps, and the Tatra Mountains) to establish suitable temperature conditions for Diamesa dominance. It has been generally accepted that their high abundance was linked to the presence of glaciers; however, we have shown that in the Tatra Mountains, where there are no glaciers, the conditions for the dominance of Diamesa species are created due to permanent snowfields, the geographical orientation of the valley and shading by the surrounding high peaks. The historical connection of Diamesa to glaciers was investigated from the paleolimnological records of subfossil chironomid assemblages from the Bohemian Forest, where glaciers disappeared before or during the Late Glacial period. As expected, water temperature seems to be the main driver of Diamesa distribution, and we determined that the relative abundance of Diamesa species was significantly higher at the sites with a mean July water temperature below 6.5 °C. The Diamesa-dominated stream communities seems to be endangered due to ongoing climate warming and this assumption is supported by our paleolimnological results from the Bohemian Forest lakes, where Diamesa has disappeared due to warming of lake inflows at the beginning of the Holocene. These findings strengthen the former suggestions that some Diamesa species could be used as an indicator for tracking recent environmental changes in vulnerable ecosystems of cold mountain streams.

Evaluation of the Glymphatic System in Schizophrenia Spectrum Disorder Using Proton Magnetic Resonance Spectroscopy Measurement of Brain Macromolecule and Diffusion Tensor Image Analysis Along the Perivascular Space Index.

BACKGROUND AND HYPOTHESIS: The glymphatic system (GS), a brain waste clearance pathway, is disrupted in various neurodegenerative and vascular diseases. As schizophrenia shares clinical characteristics with these conditions, we hypothesized GS disruptions in patients with schizophrenia spectrum disorder (SCZ-SD), reflected in increased brain macromolecule (MM) and decreased diffusion-tensor-image-analysis along the perivascular space (DTI-ALPS) index. STUDY DESIGN: Forty-seven healthy controls (HCs) and 103 patients with SCZ-SD were studied. Data included 135 proton magnetic resonance spectroscopy (1H-MRS) sets, 96 DTI sets, with 79 participants contributing both. MM levels were quantified in the dorsal-anterior cingulate cortex (dACC), dorsolateral prefrontal cortex, and dorsal caudate (point resolved spectroscopy, echo-time = 35ms). Diffusivities in the projection and association fibers near the lateral ventricle were measured to calculate DTI-ALPS indices. General linear models were performed, adjusting for age, sex, and smoking. Correlation analyses examined relationships with age, illness duration, and symptoms severity. STUDY RESULTS: MM levels were not different between patients and HCs. However, left, right, and bilateral DTI-ALPS indices were lower in patients compared with HCs (P < .001). In HCs, age was positively correlated with dACC MM and negatively correlated with left, right, and bilateral DTI-ALPS indices (P < .001). In patients, illness duration was positively correlated with dACC MM and negatively correlated with the right DTI-ALPS index (P < .05). In the entire population, dACC MM and DTI-ALPS indices showed an inverse correlation (P < .01). CONCLUSIONS: Our results suggest potential disruptions in the GS of patients with SCZ-SD. Improving brain's waste clearance may offer a potential therapeutic approach for patients with SCZ-SD.

PET/MRI multimodality imaging to evaluate changes in glymphatic system function and biomarkers of Alzheimer's disease.

The glymphatic system is considered to play a pivotal role in the clearance of disease-causing proteins in neurodegenerative diseases. This study employed MR diffusion tensor imaging (DTI) to evaluate glymphatic system function and its correlation with brain amyloid accumulation levels measured using [11C]Pittsburgh compound-B (PiB) PET/MRI. Fifty-six patients with mild cognitive impairment and early Alzheimer's disease (AD: 70 ± 11 y) underwent [11C]PiB PET/MRI to assess amyloid deposition and were compared with 27 age-matched cognitively normal volunteers (CN: 69 ± 10y). All participants were evaluated for cognitive function using the Mini Mental State Examination (MMSE) before [11C]PiB PET/MRI. DTI images were acquired during the PET/MRI scan with several other MR sequences. The DTI analysis along the perivascular space index (DTI-ALPS index) was calculated to estimate the functional activity of the glymphatic system. Centiloid scale was applied to quantify amyloid deposition levels from [11C]PiB PET images. All patients in the AD group showed positive [11C]PiB accumulation, whereas all CN participants were negative. ALPS-index for all subjects linearly correlated with PiB centiloid, MMSE scores, and hippocampal volume. The correlation between the ALPS-index and PiB accumulation was more pronounced than with any other biomarkers. These findings suggest that glymphatic system dysfunction is a significant factor in the early stages of Alzheimer's disease.

Evaluating the glymphatic system via magnetic resonance diffusion tensor imaging along the perivascular spaces in brain tumor patients.

PURPOSE: To investigate glymphatic system function in patients with brain tumors, including both primary and secondary tumors, using diffusion tensor imaging along perivascular spaces (DTI-ALPS). METHODS: We retrospectively analyzed the MR DTI of 24 patients with unilateral brain tumors and compared them with age and sex-matched controls. We compared the DTI-ALPS index of the ipsi- and contralateral brain hemispheres. The region of interest was placed in the periventricular vessels adjacent to the lateral ventricles. Differences between sex, age, and kind of tumor (primary or brain metastasis) were evaluated. Correlations between DTI-ALPS index and age and the tumor's apparent diffusion coefficient (ADC) were also investigated. RESULTS: The DTI-ALPS index was significantly lower (p < 0.05) in the tumor-affected hemisphere (mean = 1.26 ± 0.24) than contralateral (mean = 1.43 ± 0.28). A comparison with healthy controls revealed no significant difference on the matched ipsilateral side. However, the DTI-ALPS index of the contralateral side of the patients was larger than the HC. Additionally, no statistically significant differences were found when analyzing the DTI-ALPS index vs. age, sex, and tumor entity. Additionally, we did not find a correlation between the DTI-ALPS index and patient age or tumor ADC. CONCLUSION: The decreased DTI-ALPS index in the tumor-affected hemisphere may be related to impaired glymphatic system function. However, cancer is often a systemic disease; thus, the DTI-ALPS index from the contralateral brain hemisphere may not generally be considered as a normal control. Nonetheless, the DTI-ALPS index does not only reflect diffusion in the perivascular spaces but it can also be influenced by factors such as axonal degeneration. Therefore, it does not directly reflect brain waste clearance and changes in the index should be interpreted carefully.

A comprehensive dataset of the geophilid centipedes of the south-eastern Alps (Chilopoda, Geophilomorpha, Geophilidae s.l.).

Background: Centipedes of the family Geophilidae s.l. are widespread in the Holarctic, with the south-eastern part of the European Alps standing out as one of the most investigated regions. However, retrieving the published records for this taxon, even for this region, is challenging, since most of them are sparse in the specialised literature and interpreting them is hampered by the many taxonomic and nomenclatorial changes occurred in the past and recent times. New information: We assembled and released a dataset of occurrence records of the geophilid species in the south-eastern Alps, including all the published records and many other records present in unpublished catalogues of scientific collections. For each record, we integrated information from all the sources about: locality, date of collection, the taxonomic identifications, number and sex of individuals and available sequences of molecular markers. For all the records, we estimated geographic coordinates of the locality, when not originally provided, based on the information available. We also estimated the accuracy of the position.The dataset includes 3293 records referred to 39 species, obtained since the first half of the 19th century and up to 2022; 52% of these records have been released publicly for the first time in the dataset here described.

Looking for ALPS: The value of a combined assessment of biochemical markers.

BACKGROUND: Autoimmune lymphoproliferative syndrome (ALPS) is a rare primary immune disorder caused by defect of the extrinsic apoptotic pathway. The current diagnostic criteria combine clinical features and typical biomarkers but have not been the object of clear international consensus. METHODS: We conducted a retrospective study on pediatric patients who were investigated for autoimmune cytopenia and/or lymphoproliferation at the CHU Sainte-Justine Hospital over 10 years. Patients were screened using the combination of TCRαß+ CD4- CD8- "double negative" (DN) T cells and soluble plasmatic FAS ligand (sFASL). RESULTS: Among the 398 tested patients, the median sFASL and DN T cells were 200 ng/mL and 1.8% of TCRαß+ T cells, respectively. sFASL was highly correlated with vitamin B12 levels. We identified five patients diagnosed with ALPS for whose sFASL and vitamin B12 levels were the more discriminating biomarkers. While ALPS diagnostic criteria had high sensibility, their predictive value remained low. CONCLUSION: sFASL level can efficiently discriminate patients with ALPS when using the appropriate thresholds. Our study highlights the need for an international consensus to redefine the place and threshold of biological biomarkers for ALPS diagnosis.

Pigmentation level of human iPSC-derived RPE does not indicate a specific gene expression profile.

Retinal pigment epithelium (RPE) cells show heterogeneous levels of pigmentation when cultured in vitro. To know whether their color in appearance is correlated with the function of the RPE, we analyzed the color intensities of human-induced pluripotent stem cell-derived RPE cells (iPSC-RPE) together with the gene expression profile at the single-cell level. For this purpose, we utilized our recent invention, Automated Live imaging and cell Picking System (ALPS), which enabled photographing each cell before RNA-sequencing analysis to profile the gene expression of each cell. While our iPSC-RPE were categorized into four clusters by gene expression, the color intensity of iPSC-RPE did not project any specific gene expression profiles. We reasoned this by less correlation between the actual color and the gene expressions that directly define the level of pigmentation, from which we hypothesized the color of RPE cells may be a temporal condition not strongly indicating the functional characteristics of the RPE.

The backs of our eyes are lined with retinal pigment epithelial cells (or RPE cells for short). These cells provide nutrition to surrounding cells and contain a pigment called melanin that absorbs excess light that might interfere with vision. By doing so, they support the cells that receive light to enable vision. However, with age, RPE cells can become damaged and less able to support other cells. This can lead to a disease called age-related macular degeneration, which can cause blindness. One potential way to treat this disease is to transplant healthy RPE cells into eyes that have lost them. These healthy cells can be grown in the laboratory from human pluripotent stem cells, which have the capacity to turn into various specialist cells. Stem cell-derived RPE cells growing in a dish contain varying amounts of melanin, resulting in some being darker than others. This raised the question of whether pigment levels affect the function of RPE cells. However, it was difficult to compare single cells containing various amounts of pigment as most previous studies only analyzed large numbers of RPE cells mixed together. Nakai-Futatsugi et al. overcame this hurdle using a technique called Automated Live imaging and cell Picking System (also known as ALPS). More than 2300 stem cell-derived RPE cells were photographed individually and the color of each cell was recorded. The gene expression of each cell was then measured to investigate whether certain genes being switched on or off affects pigment levels and cell function. Analysis did not find a consistent pattern of gene expression underlying the pigmentation of RPE cells. Even gene expression related to the production of melanin was only slightly linked to the color of the cells. These findings suggests that the RPE cell color fluctuates and is not primarily determined by which genes are switched on or off. Future experiments are required to determine whether the findings are the same for RPE cells grown naturally in the eyes and whether different pigment levels affect their capacity to protect the rest of the eye.

Dataset of a flow intermittency study: Benthic communities of 13 alpine intermittent rivers.

In the last few decades, perennial mountain streams are becoming increasingly intermittent, due to global climate change and anthropogenic pressures. This phenomenon leads to negative effects on benthic communities' biodiversity and river ecosystems functionality. However, the impact of flow intermittency in previously perennial Alpine streams is still poorly investigated. This dataset consists of all the data collected during a spring sampling campaign performed in April-May 2017 along 13 mountain streams located in the SW Italian Alps. These watercourses have been selected because it was possible to identify two different sampling sites: one perennial, where water has always been flowing throughout the years, and one intermittent, which showed flowing water during the sampling campaign but, in the last decade, has experienced summer dry phases. All the sites have been characterized defining the microhabitats in which samples were retrieved, and physico-chemical data were collected at each site. Biological sampling included benthic macroinvertebrates and diatoms. Therefore, the present dataset offers various biological, ecological and physico-chemical information regarding Alpine streams which have recently become intermittent. Potentially, it could be used for comparisons with different benthic communities present in mountain rivers worldwide which are facing drying events too. The broad range of information present in this dataset offers the possibility to examine only the perennial sites themselves, as an example of good river functionality due to continuous flowing water, or only the intermittent ones, to better understand the effects of drying events on these peculiar ecosystems.

Diffusion tensor imaging analysis along the perivascular space in the UK biobank.

BACKGROUND: The recently discovered glymphatic system may support the removal of neurotoxic proteins, mainly during sleep, that are associated with neurodegenerative diseases such as Alzheimer's and Parkinson's Disease. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) has been suggested as a method to index the health of glymphatic system (with higher values indicating a more intact glymphatic system). Indeed, in small-scale studies the DTI-ALPS index has been shown to correlate with age, cognitive health, and sleep, and is higher in females than males. OBJECTIVE: To determine whether these relationships are stable we replicated previous findings associating the DTI-ALPS index with demographic, sleep-related, and cognitive markers in a large sample of participants from the UK Biobank. METHODS: We calculated the DTI-ALPS index in UK Biobank participants (n = 17723). Using Bayesian and Frequentist analysis approaches, we replicate previously reported relationships between the DTI-ALPS index. RESULTS: We found the predicted associations between the DTI-ALPS index and age, longest uninterrupted sleep window (LUSWT) on a typical night, cognitive performance, and sex. However, these effects were substantially smaller than those found in previous studies. Parameter estimates from this study may be used as priors in subsequent studies using a Bayesian approach. These results suggest that the DTI-ALPS index is consistently, and therefore predictably, associated with demographics, LUWST, and cognition. CONCLUSION: We propose that the metric, calculated for the first time in a large-scale, population-based cohort, is a stable measure, but one for which stronger links to glymphatic system function are needed before it can be used to understand the relationships between glymphatic system function and health outcomes reported in the UK Biobank.

Distribution of toxigenic cyanobacteria in Alpine lakes and rivers as revealed by molecular screening.

The increasing frequency of cyanobacteria blooms in waterbodies caused by ecosystem eutrophication could endanger human health. This risk can be mitigated by effective monitoring incorporating molecular methods. To date, most molecular studies on toxigenic cyanobacteria have been limited to microcystins (MCs), disregarding other cyanotoxins, to freshwater planktic habitats while ignoring benthic habitats, and to limited geographic areas (usually one or a few specific waterbodies). In this study, we used PCR-based methods including PCR product sequencing and chemical-analytical methods (LC-MS/MS) to screen many plankton (n = 123) and biofilm samples (n = 113) originating from 29 Alpine lakes and 18 rivers for their cyanotoxin production potential. Both mcyE (indicating MC synthesis) and anaC (indicating anatoxin (ATX) synthesis) gene fragments were able to qualitatively predict MC or ATX occurrence. The abundance of mcyE gene fragments was significantly related to MC concentrations in plankton samples (R2 = 0.61). mcyE gene fragments indicative of MC synthesis were most abundant in planktic samples (65 %) and were assigned to the genera Planktothrix and Microcystis. However, mcyE rarely occurred in biofilms of lakes and rivers, i.e., 4 % and 5 %, respectively, and were assigned to Microcystis, Planktothrix, and Nostoc. In contrast, anaC gene fragments occurred frequently in planktic samples (14 % assigned to Tychonema, Phormidium (Microcoleus), and Oscillatoria), but also in biofilms of lakes (49 %) and rivers (18 %) and were assigned to the genera Phormidium, Oscillatoria, and Nostocales. The cyrJ gene fragment indicating cylindrospermopsin synthesis occurred only once in plankton (assigned to Dolichospermum), while saxitoxin synthesis potential was not detected. For plankton samples, monomictic and less eutrophic conditions were positively related to mcyE/MC occurrence frequency, while oligomictic conditions were related to anaC/ATX frequency. The anaC/ATX frequency in biofilm was related to the lake habitats generally showing higher biodiversity as revealed from metabarcoding in a parallel study.

Bilateral glymphatic dysfunction and its association with disease duration in unilateral temporal lobe epilepsy patients with hippocampal sclerosis.

OBJECTIVE: In this study, the diffusion tensor imaging along perivascular space analysis (DTI-ALPS) technique was utilized to evaluate the functional changes in the glymphatic system of the bilateral hemispheres in patients with unilateral temporal lobe epilepsy (TLE) accompanied by hippocampal sclerosis (HS). The aim was to gain insights into the alterations in the glymphatic system function in TLE patients. METHODS: A total of 61 unilateral TLE patients with HS and 53 healthy controls (HCs) from the Department of Neurosurgery at Xiangya Hospital were included in the study. All subjects underwent DTI using the same 3 T MR Scanner, and the DTI-ALPS index was calculated. Differences in the DTI-ALPS index between TLE patients and HCs were evaluated, along with the correlation between the DTI-ALPS index of TLE and clinical features of epilepsy. These features included age, age of onset, seizure duration, and neuropsychological scores. RESULTS: Compared to the bilateral means of the HCs, both the ipsilateral and contralateral DTI-ALPS index of the TLE patients were significantly decreased (TLE ipsilateral 1.41 ± 0.172 vs. HC bilateral mean: 1.49 ± 0.116, p = 0.006; TLE contralateral: 1.42 ± 0.158 vs. HC bilateral mean: 1.49 ± 0.116, p = 0.015). The ipsilateral DTI-ALPS index in TLE patients showed a significant negative correlation with disease duration (r = -0.352, p = 0.005). CONCLUSIONS: The present study suggests the presence of bilateral dysfunctions in the glymphatic system and also highlight a laterality feature in these dysfunctions. Additionally, the study found a significant negative correlation between the ipsilateral DTI-ALPS index and disease duration, underscoring the significance of early effective interventions and indicating potential for the development of innovative treatments targeting the glymphatic system.

Glymphatic System Dysfunction Underlying Schizophrenia Is Associated With Cognitive Impairment.

BACKGROUND AND HYPOTHESIS: Despite the well-documented structural and functional brain changes in schizophrenia, the potential role of glymphatic dysfunction remains largely unexplored. This study investigates the glymphatic system's function in schizophrenia, utilizing diffusion tensor imaging (DTI) to analyze water diffusion along the perivascular space (ALPS), and examines its correlation with clinical symptoms. STUDY DESIGN: A cohort consisting of 43 people with schizophrenia and 108 healthy controls was examined. We quantified water diffusion metrics along the x-, y-, and z-axis in both projection and association fibers to derive the DTI-ALPS index, a proxy for glymphatic activity. The differences in the ALPS index between groups were analyzed using a 2-way ANCOVA controlling for age and sex, while partial correlations assessed the association between the ALPS index and clinical variables. STUDY RESULTS: People with schizophrenia showed a significantly reduced DTI-ALPS index across the whole brain and within both hemispheres (F = 9.001, P = .011; F = 10.024, P = .011; F = 5.927, P = .044; false discovery rate corrected), indicating potential glymphatic dysfunction in schizophrenia. The group by cognitive performance interaction effects on the ALPS index were not observed. Moreover, a lower ALPS index was associated with poorer cognitive performance on specific neuropsychological tests in people with schizophrenia. CONCLUSION: Our study highlights a lower ALPS index in schizophrenia, correlated with more pronounced cognitive impairments. This suggests that glymphatic dysfunction may contribute to the pathophysiology of schizophrenia, offering new insights into its underlying mechanisms.

Comparative analysis of glymphatic system alterations in multiple sclerosis and neuromyelitis optica spectrum disorder using MRI indices from diffusion tensor imaging.

OBJECTIVE: The glymphatic system is a glial-based perivascular network that promotes brain metabolic waste clearance. Glymphatic system dysfunction has been observed in both multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), indicating the role of neuroinflammation in the glymphatic system. However, little is known about how the two diseases differently affect the human glymphatic system. The present study aims to evaluate the diffusion MRI-based measures of the glymphatic system by contrasting MS and NMOSD. METHODS: This prospective study included 63 patients with NMOSD (n = 21) and MS (n = 42) who underwent DTI. The fractional volume of extracellular-free water (FW) and an index of diffusion tensor imaging (DTI) along the perivascular space (DTI-ALPS) were used as indirect indicators of water diffusivity in the interstitial extracellular and perivenous spaces of white matter, respectively. Age and EDSS scores were adjusted. RESULTS: Using Bayesian hypothesis testing, we show that the present data substantially favor the null model of no differences between MS and NMOSD for the diffusion MRI-based measures of the glymphatic system. The inclusion Bayes factor (BF10) of model-averaged probabilities of the group (MS, NMOSD) was 0.280 for FW and 0.236 for the ALPS index. CONCLUSION: Together, these findings suggest that glymphatic alteration associated with MS and NMOSD might be similar and common as an eventual result, albeit the disease etiologies differ. PRACTITIONER POINTS: Previous literature indicates important glymphatic system alteration in MS and NMOSD. We explore the difference between MS and NMOSD using diffusion MRI-based measures of the glymphatic system. We show support for the null hypothesis of no difference between MS and NMOSD. This suggests that glymphatic alteration associated with MS and NMOSD might be similar and common etiology.

[Glymphatic dysfunction and sleep disorders: indirect effects on Alzheimer's disease]. / Glimfaticheskaya disfunktsiya i narusheniya sna: oposredovannoe vliyanie na bolezn' Al'tsgeimera.

Modern research raises the question of the potentially significant role of glymphatic dysfunction in the development of neurodegeneration and pathological aging. The exact molecular mechanisms are not yet fully understood, but there is ample evidence of a link between sleep deprivation and decreased clearance of ß-amyloid and other neurotoxin proteins that are associated with the development of neurodegenerative diseases, particularly Alzheimer's disease. The review analyzes current scientific information in this area of research, describes the latest scientific discoveries of the features of the glymphatic system, and also illustrates studies of markers that presumably indicate a deterioration in the glymphatic system. The relationship between sleep deprivation and pathophysiological mechanisms associated with neurodegenerative diseases is considered, and potential targets that can be used to treat or delay the development of these disorders are noted.

Tectonic architecture of the northern Dora-Maira Massif (Western Alps, Italy): field and geochronological data.

High-pressure and ultra-high-pressure metamorphic terrains display an internal architecture consisting of a pile (or stack) of several coherent tectonic thrust sheets or units. Their identification is fundamental for understanding the scale and mechanisms active during subduction and exhumation of these crustal slices. This study investigates the geometry of the northern Dora-Maira Massif and the kinematics of the major tectonic boundaries, combining field and geochronological data. The tectonic stack of the northern Dora-Maira Massif comprises the following units. The lowermost unit (the Pinerolo Unit) is mainly characterized by Upper Carboniferous fluvio-lacustrine (meta-)sediments. The Pinerolo unit is overthrust by a pre-Carboniferous basement. The latter is subdivided in two tectonic units (the Chasteiran and Muret Units) with different Alpine metamorphism (ultra-high-pressure and high-pressure, respectively). The pre-Carboniferous basement of the Muret Unit is thicker than previously thought for two main reasons. Firstly, some paragneisses, traditionally assumed to be Carboniferous and/or Permian in age, display detrital zircon ages indicating a main source at about 600 Ma. Secondly, three samples of the Granero Orthogneiss, previously assumed to be a Permian intrusive body, have provided zircon U-Pb ages of 447 ± 1 Ma, 456 ± 2 Ma and 440 ± 2 Ma, indicating a late Ordovician or early Silurian age for the protoliths. The uppermost unit (the Serre Unit) comprises porphyritic (meta-) volcanic and volcaniclastic rocks dated to the Permian (271 ± 2 Ma), on top of which remnants of the Mesozoic cover is preserved. Detailed mapping of an area about 140 km2 shows that (i) the ultra-high pressure Chasteiran Unit is localized at the boundary between the Pinerolo and Muret Units, (ii) the Granero Orthogneiss may be considered as the mylonitic sole of the Muret Unit, characterized by a top-to-W sense of shear, and (iii) the contact between the Muret and Serre Units displays ductile-to brittle structures (La Fracho Shear Zone), indicating a top-to-the-NW displacement of the hangingwall with respect to the footwall. A final episode of brittle faulting, cutting across the nappe stack (the Trossieri Fault), indicates an extensional stage in the core of the Alpine belt, as previously documented in more external zones. This work provides a necessary and robust basis before an accurate discussion of processes acting during continental subduction of the Dora-Maira Massif may be understood. Supplementary Information: The online version contains supplementary material available at 10.1186/s00015-024-00459-2.