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Fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) are commonly used as MRI biomarkers of white matter microstructure in diffusion MRI studies of neurodevelopment, brain aging, and neurologic injury/disease. Some of the more frequent practices include performing voxel-wise or region-based analyses of these measures to cross-sectionally compare individuals or groups, longitudinally assess individuals or groups, and/or correlate with demographic, behavioral or clinical variables. However, it is now widely recognized that the majority of cerebral white matter voxels contain multiple fiber populations with different trajectories, which renders these metrics highly sensitive to the relative volume fractions of the various fiber populations, the microstructural integrity of each constituent fiber population, and the interaction between these factors. Many diffusion imaging experts are aware of these limitations and now generally avoid using FA, AD or RD (at least in isolation) to draw strong reverse inferences about white matter microstructure, but based on the continued application and interpretation of these metrics in the broader biomedical/neuroscience literature, it appears that this has perhaps not yet become common knowledge among diffusion imaging end-users. Therefore, this paper will briefly discuss the complex biophysical underpinnings of these measures in the context of crossing fibers, provide some intuitive “thought experiments” to highlight how conventional interpretations can lead to incorrect conclusions, and suggest that future studies refrain from using (over-interpreting) FA, AD and RD values as standalone biomarkers of cerebral white matter microstructure.

Hepatic steatosis is a multifactorial condition that is often observed in obese patients and is a prelude to non-alcoholic fatty liver disease. Here, we combine shotgun sequencing of fecal metagenomes with molecular phenomics (hepatic transcriptome and plasma and urine metabolomes) in two well-characterized cohorts of morbidly obese women recruited to the FLORINASH study. We reveal molecular networks linking the gut microbiome and the host phenome to hepatic steatosis. Patients with steatosis have low microbial gene richness and increased genetic potential for the processing of dietary lipids and endotoxin biosynthesis (notably from Proteobacteria), hepatic inflammation and dysregulation of aromatic and branched-chain amino acid metabolism. We demonstrated that fecal microbiota transplants and chronic treatment with phenylacetic acid, a microbial product of aromatic amino acid metabolism, successfully trigger steatosis and branched-chain amino acid metabolism. Molecular phenomic signatures were predictive (area under the curve = 87%) and consistent with the gut microbiome having an effect on the steatosis phenome (>75% shared variation) and, therefore, actionable via microbiome-based therapies. Metabolic activity of specific human gut microorganisms contributes to liver steatosis in obese women.

Dietary lipids can affect metabolic health through gut microbiota-mediated mechanisms, but the influence of lipid-microbiota interaction on liver steatosis is largely unknown. We investigate the impact of dietary lipids on human gut microbiota composition and the effects of microbiota-lipid interactions on steatosis in male mice. In humans, low intake of saturated fatty acids (SFA) is associated with increased microbial diversity independent of fiber intake. In mice, poorly absorbed dietary long-chain SFA, particularly stearic acid, induce a shift in bile acid profile and improved metabolism and steatosis. These benefits are dependent on the gut microbiota, as they are transmitted by microbial transfer. Diets enriched in polyunsaturated fatty acids are protective against steatosis but have minor influence on the microbiota. In summary, we find that diets enriched in poorly absorbed long-chain SFA modulate gut microbiota profiles independent of fiber intake, and this interaction is relevant to improve metabolism and decrease liver steatosis.

The measures adopted to control the spread of the COVID-19 pandemic in several countries included mobility and social restrictions that produced an immediate impact on the lifestyle of their inhabitants. We assessed the association between the consequences of these measures and depressive symptomatology using a population-based sample of 692 individuals aged 18 or over from an ongoing study in the province of Girona (Catalonia, Spain). Participants responded to a telephone-based survey that included questions related to the consequences of confinement and the Patient Health Questionnaire-9 (PHQ-9) was used to assess depressive symptomatology. Multivariate logistic and linear regressions were used to identify which changes in lifestyle resulting from confinement were independently associated with a possible depression episode and depressive symptomatology. The prevalence of a possible depressive episode during the confinement was 12.7% (95% CI = 10.3–15.4). An adverse work situation, expected economic distress, self-reported worsening of the mental health and of the dietary pattern, and worries about a relative's potential infection were variables related to an increased risk of having a possible depressive episode. The changes in lifestyle accounted for 32% of the variance of the PHQ-9 score. The findings indicate an association of the job situation, the expected negative economic consequences, the perceived worsening of health and habits, and the worries about COVID-19 infection with depressive symptomatology during the confinement. •The prevalence of depressive episode during the confinement among individuals aged 18 years or over was 12.7%.•Work status, expected economic distress, health worsening, and reduction of activities were related to depressive symptoms.•Affective symptoms were related to the length of confinement and somatic symptoms with physical activity restrictions.

BackgroundObesity-related alterations in the gut microbiota have been linked to cognitive decline, yet their relationship with attention remains poorly understood.ObjectiveTo evaluate the possible relationships among gut metagenomics, plasma metabolomics and attention.DesignWe conducted faecal shotgun metagenomics and targeted plasma tryptophan metabolomics across three independent cohorts (n=156, n=124, n=804) with functional validations in preclinical models, including three faecal microbiota transplantation (FMT) experiments in mice and Drosophila melanogaster.ResultsObesity was consistently associated with reduced attention. Metagenomics analyses identified Proteobacteria species and microbial functions related to tryptophan biosynthesis from anthranilic acid (AA) as negatively associated with attention in obesity. Plasma tryptophan metabolic profiling and machine learning revealed that 3-hydroxyanthranilic acid (3-HAA) was positively associated with attention, particularly in obesity, while AA showed a negative association. Bariatric surgery improved attention and enriched microbial species linked to attention. In mice, diet-induced obesity (DIO) and microbiota depletion reduced 3-HAA and 5-hydroxy-indole acetic acid (5-HIAA) concentrations in the prefrontal cortex (PFC), which were restored by FMT. Global metabolic profiling (>600 metabolites) of PFC from the FMT group identified 3-HAA and the tryptophan and tyrosine pathways among the most significant in mice receiving microbiota from high-attention donors. A second FMT experiment also revealed a consistent enrichment of the tryptophan and tyrosine metabolism at the transcriptional level in the PFC, with Haao (3-hydroxyantrhanilic acid dioxygenase) and Aox4 (aldehyde oxidase 4), key in 3-HAA and 5-HIAA degradation, among the significantly regulated genes. In a third FMT study, attentional traits were transmitted from humans to mice alongside modulation of serotonergic and dopaminergic pathways. In Drosophila, mono-colonisation with Enterobacter cloacae and DIO induced attention deficit-like behaviours, which were mitigated by 3-HAA supplementation.ConclusionsWe have identified the microbiota and 3-HAA as potential therapeutic targets to improve attention, especially in obesity.

Background The gut microbiome and iron status are known to play a role in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), although their complex interaction remains unclear. Results Here, we applied an integrative systems medicine approach (faecal metagenomics, plasma and urine metabolomics, hepatic transcriptomics) in 2 well-characterised human cohorts of subjects with obesity (discovery n = 49 and validation n = 628) and an independent cohort formed by both individuals with and without obesity ( n = 130), combined with in vitro and animal models. Serum ferritin levels, as a markers of liver iron stores, were positively associated with liver fat accumulation in parallel with lower gut microbial gene richness, composition and functionality. Specifically, ferritin had strong negative associations with the Pasteurellaceae , Leuconostocaceae and Micrococcaea families. It also had consistent negative associations with several Veillonella , Bifidobacterium and Lactobacillus species, but positive associations with Bacteroides and Prevotella spp. Notably, the ferritin-associated bacterial families had a strong correlation with iron-related liver genes. In addition, several bacterial functions related to iron metabolism (transport, chelation, heme and siderophore biosynthesis) and NAFLD (fatty acid and glutathione biosynthesis) were also associated with the host serum ferritin levels. This iron-related microbiome signature was linked to a transcriptomic and metabolomic signature associated to the degree of liver fat accumulation through hepatic glucose metabolism. In particular, we found a consistent association among serum ferritin, Pasteurellaceae and Micrococcacea families, bacterial functions involved in histidine transport, the host circulating histidine levels and the liver expression of GYS2 and SEC24B. Serum ferritin was also related to bacterial glycine transporters, the host glycine serum levels and the liver expression of glycine transporters. The transcriptomic findings were replicated in human primary hepatocytes, where iron supplementation also led to triglycerides accumulation and induced the expression of lipid and iron metabolism genes in synergy with palmitic acid. We further explored the direct impact of the microbiome on iron metabolism and liver fact accumulation through transplantation of faecal microbiota into recipient’s mice. In line with the results in humans, transplantation from ‘high ferritin donors’ resulted in alterations in several genes related to iron metabolism and fatty acid accumulation in recipient’s mice. Conclusions Altogether, a significant interplay among the gut microbiome, iron status and liver fat accumulation is revealed, with potential significance for target therapies. 5HRkabMBtxskC5-wBBcq1w Video abstract

Background/Objectives: Magnetic resonance imaging (MRI) and MRI–ultrasound (US) fusion-targeted biopsy have improved prostate cancer diagnosis, particularly for clinically significant disease. However, the added value of combining systematic biopsy with targeted biopsy remains debated. This study aimed to evaluate the diagnostic accuracy of MRI–US fusion-targeted and systematic transperineal biopsies in detecting prostate cancer and explore the correlation between PI-RADS score and histology. Methods: We retrospectively analyzed 356 patients with 452 MRI-detected lesions who underwent both MRI–US fusion-targeted and transperineal systematic biopsies between 2020 and 2023. Clinically significant prostate cancer (csPCa) was defined as International Society of Urological Pathology (ISUP) grade ≥ 2. Diagnostic performance metrics (sensitivity, specificity, and accuracy) were calculated for each technique using the combined result as a reference. Subgroup analysis was performed for patients under active surveillance. Results: Prostate cancer was diagnosed in 323 of 452 lesions (71%) and csPCa in 223 lesions (49%). Targeted biopsy demonstrated higher sensitivity (93.7%) and accuracy (79.9%) than systematic biopsy (85.7% sensitivity and 77.6% accuracy), although systematic biopsy provided slightly higher specificity. Systematic biopsy alone identified 8.2% of PCa cases missed by targeted biopsy and upgraded 9.9% of lesions to csPCa. csPCa detection increased with PI-RADS score (23% in PI-RADS 3 and 73% in PI-RADS 5). In active surveillance patients, csPCa was found in 65% of lesions. Conclusions: MRI–US fusion-targeted biopsy improves csPCa detection, but systematic biopsy remains valuable, especially for identifying additional or higher-grade disease. The combined approach provides an optimal diagnostic yield, supporting its continued use in both initial and repeat biopsy settings.

Background Mechanical ventilation to alter and improve respiratory gases is a fundamental feature of critical care and intraoperative anesthesia management. The range of inspired O 2 and expired CO 2 during patient management can significantly deviate from values in the healthy awake state. It has long been appreciated that hyperoxia can have deleterious effects on organs, especially the lung and retina. Recent work shows intraoperative end-tidal (ET) CO 2 management influences the incidence of perioperative neurocognitive disorder (POND). The interaction of O 2 and CO 2 on cerebral blood flow (CBF) and oxygenation with alterations common in the critical care and operating room environments has not been well studied. Methods We examine the effects of controlled alterations in both ET O 2 and CO 2 on cerebral blood flow (CBF) in awake adults using blood oxygenation level-dependent (BOLD) and pseudo-continuous arterial spin labeling (pCASL) MRI. Twelve healthy adults had BOLD and CBF responses measured to alterations in ET CO 2 and O 2 in various combinations commonly observed during anesthesia. Results Dynamic alterations in regional BOLD and CBF were seen in all subjects with expected and inverse brain voxel responses to both stimuli. These effects were incremental and rapid (within seconds). The most dramatic effects were seen with combined hyperoxia and hypocapnia. Inverse responses increased with age suggesting greater risk. Conclusions Human CBF responds dramatically to alterations in ET gas tensions commonly seen during anesthesia and in critical care. Such alterations may contribute to delirium following surgery and under certain circumstances in the critical care environment. Trial registration ClincialTrials.gov NCT02126215 for some components of the study. First registered April 29, 2014.

Intravoxel incoherent motion (IVIM) is an MRI technique with potential applications in measuring brain tumor perfusion, but its clinical impact remains to be determined. We assessed the usefulness of IVIM-metrics in predicting survival in newly diagnosed glioblastoma. Fifteen patients with glioblastoma underwent MRI including spin-echo echo-planar DWI using 13 b-values ranging from 0 to 1000 s/mm2. Parametric maps for diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were generated for contrast-enhancing regions (CER) and non-enhancing regions (NCER). Regions of interest were manually drawn in regions of maximum f and on the corresponding dynamic susceptibility contrast images. Prognostic factors were evaluated by Kaplan-Meier survival and Cox proportional hazards analyses. We found that fCER and D*CER correlated with rCBFCER. The best cutoffs for 6-month survival were fCER>9.86% and D*CER>21.712 x10-3mm2/s (100% sensitivity, 71.4% specificity, 100% and 80% positive predictive values, and 80% and 100% negative predictive values; AUC:0.893 and 0.857, respectively). Treatment yielded the highest hazard ratio (5.484; 95% CI: 1.162-25.88; AUC: 0.723; P = 0.031); fCER combined with treatment predicted survival with 100% accuracy. The IVIM-metrics fCER and D*CER are promising biomarkers of 6-month survival in newly diagnosed glioblastoma.

BackgroundMedium vessel occlusion (MVO) mechanical thrombectomy (MT) has shown promising outcomes and safety profiles, comparable to those of large vessel occlusion thrombectomy.ObjectiveTo assess the efficacy and safety of the CatchView Mini (CVM) stent retriever (Balt, Montmorency, France) in patients with acute stroke with proximal and distal MVO (pMVO vs dMVO), respectively.MethodsWe analyzed retrospective data of consecutive patients with MVO who underwent MT with the CVM stent retriever. We categorized occlusions into pMVO group (segments A1, M2, and P1) versus dMVO group (segments A2, A3, M3, P2, and P3). Demographic, clinical, angiographic, and clinical outcome data (National Institute of Health Stroke Scale score at 24 hours and modified Rankin Scale (mRS) score at 3 months) were compared. The first pass effect (FPE) was defined as that which achieved modified Thrombolysis in Cerebral Infarction (mTICI) 2c–3 after a single device pass.ResultsA total of 196 patients were included (44.3% female, median (IQR) age 74 (67–84) years), of whom 151 (77%) had pMVO and 45 (23%) dMVO. FPE was achieved in 108 (55.1%) patients, and final successful reperfusion (mTICI 2c–3) was attained in 156 (79.6%) cases, with up to two passes in 78% of patients. Rescue MT was performed in 24 (12.2%) patients. The dMVO group had a higher FPE rate (84.4% vs 46.3%; P<0.001), fewer number of passes, and lower symptomatic hemorrhage rate (0% vs 0.6%; P=0.009) than the pMVO group. Around 75% of patients in both groups achieved similar favorable outcomes (mRS score 0–2) at 3 months.ConclusionsThe CVM device appears effective and safe for pMVO and dMVO thrombectomy.