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Background. White matter lesions (WMLs) may contribute to cognitive deficits in patients with mild cognitive impairment (MCI), but their pathogenesis is complex. Fluctuations of blood pressure (BP) over 24 hours and genetic predisposition to develop vascular damage have been implicated. Methods. In 63 MCI patients 65 years old or older, BP was measured both clinically and with ambulatory BP monitoring. Patients were classified in two groups: no/very mild (n = 34) and mild to severe (n = 29) WMLs, based on a visual scale on magnetic resonance (mean age 71.8 +/- 4.7 vs 74.6 +/- 5.1, and female gender 53% vs 66%, respectively). The volume of WMLs was measured by a semi-automatic method, separately for periventricular caps and rim, periventricular confluent, subcortical punctate, and subcortical confluent. Polymorphisms of cystatin C (CST3) and cholesterol 24-hydroxylase (CYP46) genes, putative risk factors for cerebrovascular disease, were determined. Results. The prevalence of cerebrovascular risk factors was similar in the two MCI groups of different WML severity, as well as clinic and ambulatory BP. In patients with mild to severe, but not in those with no/very mild WMLs, the volume of periventricular confluent WMLs increased with increasing daytime systolic BP (regression coefficient.47, 95% confidence interval [CI],.13 to.71 vs.02, 95% CI, -.32 to.36, p =.003 for the difference between slopes). The volume of other WML subtypes was not associated with ambulatory BP. Participants carrying both CST3*B and CYP46*T alleles were overrepresented in the MCI group with mild to severe WMLs (43% vs 17%, p.03). Conclusions. BP and gene putative risk factors for cerebrovascular disease are differentially associated with WMLs in two MCI groups of different WML severity. WMLs might develop for the convergence of innate with acquired factors. [ABSTRACT FROM AUTHOR]

In vitro co-culture models between tumor cells and peripheral blood mononuclear cells (PBMCs) allow studying the interplay between these cell populations, potentially gaining insight into the in vivo response of the immune system to the presence of the tumor, as well as to possible other agents as radiation used for therapeutic purposes. However, great care is needed in the experimental optimization of models and choice of conditions, as some setups might offer a limited possibility to capture subtle immune perturbations. A co-culture model of PBMCs from healthy donors and colorectal adenocarcinoma Caco-2 cells was successfully adopted in a previous work to measure effects on Caco-2 and modulation of signaling when these latter are irradiated. We here tested if the same experimental setting allows to measure perturbations to the main PBMC subsets: we performed immunophenotyping by means of flow cytometry and quantified helper and cytotoxic T cells, NK cells, and B cells, when PBMCs are cultured alone (control), in presence of non-irradiated Caco-2 cells or when these latter are exposed to a 10 Gy X-ray dose from a conventional radiotherapy accelerator. To measure a baseline response in all experimental conditions, PBMCs were not further stimulated, but only followed in their time-evolution up to 72 h post-irradiation of Caco-2 and assembly of the co-culture. In this time interval PBMCs maintain a high viability (measured via the MTT assay). Caco-2 viability (MTT) is slightly affected by the presence of PBMCs and by the high radiation dose, confirming their radioresistance. Immunophenotyping results indicate a large inter-individual variability for different population subsets already at the control level. We analyzed relative population changes and we detected only a small but significant perturbation to cytotoxic T cells. We conclude that this model, as it is, is not adequate for the measurements of subtler immune perturbations (if any, not washed-out by inter-individual differences). For this purpose, the model needs to be modified and further optimized e.g., including a pre-treatment strategy for PBMCs. We also performed a pooled analysis of all experimental observations with principal component analysis, suggesting the potential of this tool to identify subpopulations of similarly-responding donors., (Copyright © 2020 Borsci, Barbieri, Guardamagna, Lonati, Ottolenghi, Ivaldi, Liotta, Tabarelli de Fatis, Baiocco and Savio.)

Although medicinal mushroom extracts have been proposed as promising anti-cancer agents, their precise impacts on metastatic breast cancer are still to be clarified. For this purpose, the present study exploited the effect of a novel medicinal mushroom blend, namely Micotherapy U-care, in a 4T1 triple-negative mouse breast cancer model. Mice were orally administered with Micotherapy U-care , consisting of a mixture of Agaricus blazei , Ophiocordyceps sinensis , Ganoderma lucidum, Grifola frondosa , and Lentinula edodes . The syngeneic tumor-bearing mice were generated by injecting 4T1 cells in both supplemented and non-supplemented mice. After sacrifice 25 days later, specific endpoints and pathological outcomes of the murine pulmonary tissue were evaluated. (i) Histopathological and ultrastructural analysis and (ii) immunohistochemical assessment of TGF-ß1, IL-6 and NOS2, COX2, SOD1 as markers of inflammation and oxidative stress were performed. The QoL was comparatively evaluated. Micotherapy U-care supplementation, starting before 4T1 injection and lasting until the end of the experiment, dramatically reduced the pulmonary metastases density, also triggering a decrease of fibrotic response, and reducing IL-6, NOS, and COX2 expression. SOD1 and TGF-ß1 results were also discussed. These findings support the valuable potential of Micotherapy U-care as adjuvant therapy in the critical management of triple-negative breast cancer., Competing Interests: The authors declare no conflict of interest.

A potential overlap between bipolar disorder (BD) and borderline personality disorder (BPD) has been recently proposed. We aimed to assess similarities and differences of brain structural features in BD and BPD. Structural magnetic resonance imaging (MRI) was performed in 26 inpatients with BPD, 14 with BD, and 40 age-and sex-matched healthycontrols (HC). Voxel-based morphometry analysis with Statistical Parametric Mapping (SPM) was used to localize and quantify gray (GM) and white matter (WM) abnormalities in BD and BPD compared to HC and to identify those specifically affected in each patient group. Region of interest (ROI)-based analyses were also performed for confirmation. GM density changes in BD are significantly more diffuse and severe than in BPD, as demonstrated in both SPM- and ROI-based analyses. The topography of GM alterations showed some regions of overlap, but each disorder had specific regions of abnormality (involving both cortical and subcortical structures in BD, confined mainly to fronto-limbic regions in BPD). WM density changes were less pronounced in both conditions and involved completely different regions. Although BPD and BD show a considerable overlap of GM changes, the topography of alterations is more consistent with the separate conditions hypothesis and with the vulnerability of separate neural systems., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To investigate the possible effect of the APOE epsilon4 allele on age-related regional volume loss within the corpus callosum (CC) in healthy epsilon4 allele carriers compared with noncarriers., Materials and Methods: A total of 211 subjects, ages 27 to 83 years, 51 epsilon4 carriers and 160 noncarriers underwent T1-weighted MRI scan. All subjects had normal MRI scan and performed within normal range on a neuropsychological battery of tests. CC was segmented into seven functionally relevant regions using a previously published probabilistic map of the CC connectivity. We measured the volumes of the CC and its subregions. We used a regression model (with volumes as dependent and age as independent variables) and compared the slopes between carriers and noncarriers using an analysis of covariance model. We also carried out voxel-based-morphometry analysis to investigate the possible effect of the APOE epsilon4 gene on the gray matter., Results: We found that the volume of the CC and all subregions decreased with increasing age in both groups. The slope was steeper in the APOE epsilon4 carriers compared withthe noncarriers particularly in the prefrontal region (P = 0.02). No gray matter differences were observed between the two groups., Conclusion: APOE epsilon4 polymorphism is associated with accelerated age-related volume loss in the prefrontal callosal tracts without gray matter loss. This result suggests the role of APOE epsilon4 in the brain aging by primarily affecting white matter structures particularly in the frontal lobe.

Background: Alexithymia relates to difficulty recognizing and describing own feelings. Recent literature shows that specific structures process emotions. Aim of this study was to investigate whether alexithymia is associated with a specific cerebral morphology of candidate structures in healthy adults., Methods: Fifty-four female volunteers were enrolled in the study and the 20-item Toronto Alexithymia Scale (TAS-20) was self-administered. Gray matter (GM) volume was assessed with an optimized voxel-based morphometry (VBM) protocol on high-resolution 3D magnetic resonance images. The following three experiments were carried out: 1) contrast between the 14 volunteers with TAS-20 scores > or = 61 (alexithymic) and the 30 with scores < 51 (non-alexithymic), 2) correlation of TAS-20 scores on the whole sample and 3) contrast between the 14 alexithymic and 14 non-alexithymic matched by age. The significant threshold for VBM comparisons and correlation was set at p<0.005 uncorrected., Results: The alexithymic group showed smaller GM volume in the anterior cingulate cortex (cluster size: 735 voxel no.; z=3.26; stereotaxic coordinates: -12, 22, 30) and middle temporal gyrus (256; 3.21; -60, 2, -20). Of specific biological relevance, smaller clusters were located in the anterior insula, orbitofrontal cortex and superior temporal sulcus. The opposite comparison was negative. The correlation analysis confirmed the pattern of results mainly in the left hemisphere., Conclusions: Our findings suggest that the ability to process emotional aspects of the self correlates with morphology of a specific set of cerebral structures known to be involved in decision making and self awareness and rich in neurons subserving social competence.