Association between a genetic variant of type-1 cannabinoid receptor and inflammatory neurodegeneration in multiple sclerosis

Genetic ablation of type-1 cannabinoid receptors (CB1Rs) exacerbates the neurodegenerative damage of experimental autoimmune encephalomyelitis, the rodent model of multiple sclerosis (MS). To address the role on CB1Rs in the pathophysiology of human MS, we first investigated the impact of AAT trinucleotide short tandem repeat polymorphism of CNR1 gene on CB1R cell expression, and secondly on the inflammatory neurodegeneration process responsible for irreversible disability in MS patients. We found that MS patients with long AAT repeats within the CNR1 gene (≥12 in both alleles) had more pronounced neuronal degeneration in response to inflammatory white matter damage both in the optic nerve and in the cortex. Optical Coherence Tomography (OCT), in fact, showed more severe alterations of the retinal nerve fiber layer (RNFL) thickness and of the macular volume (MV) after an episode of optic neuritis in MS patients carrying the long AAT genotype of CNR1. MS patients with long AAT repeats also had magnetic resonance imaging (MRI) evidence of increased gray matter damage in response to inflammatory lesions of the white matter, especially in areas with a major role in cognition. In parallel, visual abilities evaluated at the low contrast acuity test, and cognitive performances were negatively influenced by the long AAT CNR1 genotype in our sample of MS patients. Our results demonstrate the biological relevance of the (AAT)n CNR1 repeats in the inflammatory neurodegenerative damage of MS

Clinical study in phase- contrast mammography: image-quality analysis

The first clinical study of phase-contrast mammography (PCM) with synchrotron radiation was carried out at the Synchrotron Radiation for Medical Physics beamline of the Elettra synchrotron radiation facility in Trieste (Italy) in 2006–2009. The study involved 71 patients with unresolved breast abnormalities after conventional digital mammography and ultrasonography exams carried out at the Radiology Department of Trieste University Hospital. These cases were referred for mammography at the synchrotron radiation facility, with images acquired using a propagation-based phase-contrast imaging technique. To investigate the contribution of phase-contrast effects to the image quality, two experienced radiologists specialized in mammography assessed the visibility of breast abnormalities and of breast glandular structures. The images acquired at the hospital and at the synchrotron radiation facility were compared and graded according to a relative seven-grade visual scoring system. The statistical analysis highlighted that PCM with synchrotron radiation depicts normal structures and abnormal findings with higher image quality with respect to conventional digital mammography

The role of immune suppression in COVID-19 hospitalization: clinical and epidemiological trends over three years of SARS-CoV-2 epidemic

Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients >17 years that were hospitalized for COVID-19 at the “Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico” in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8–20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p < 0.001) and be vaccinated (37% vs. 12.7%, p < 0.001). We evaluated the contribution of immune suppression to hospitalization during the various stages of the epidemic and investigated whether immune suppression contributed to severe outcomes and death, also considering the vaccination status of the patients. The proportion of immune suppressed patients among all hospitalizations (initially stable at <20%) started to increase around December 2021, and remained high (30–50%). This change coincided with an increase in the proportions of older patients and patients with co-morbidities and with a decrease in the proportion of patients with severe outcomes. Vaccinated patients showed a lower proportion of severe outcomes; among non-vaccinated patients, severe outcomes were more common in immune suppressed individuals. Immune suppression was a significant predictor of severe outcomes, after adjusting for age, sex, co-morbidities, period of hospitalization, and vaccination status (OR: 1.64; 95% CI: 1.23–2.19), while vaccination was a protective factor (OR: 0.31; 95% IC: 0.20–0.47). However, after November 2021, differences in disease outcomes between vaccinated and non-vaccinated groups (for both immune suppressed and immune competent subjects) disappeared. Since December 2021, the spread of the less virulent Omicron variant and an overall higher level of induced and/or natural immunity likely contributed to the observed shift in hospitalized patient characteristics. Nonetheless, vaccination against SARS-CoV-2, likely in combination with naturally acquired immunity, effectively reduced severe outcomes in both immune competent (73.9% vs. 48.2%, p < 0.001) and immune suppressed (66.4% vs. 35.2%, p < 0.001) patients, confirming previous observations about the value of the vaccine in preventing serious disease

Clinical study in phase- contrast mammography: image-quality analysis

The first clinical study of phase-contrast mammography (PCM) with synchrotron radiation was carried out at the Synchrotron Radiation for Medical Physics beamline of the Elettra synchrotron radiation facility in Trieste (Italy) in 2006–2009. The study involved 71 patients with unresolved breast abnormalities after conventional digital mammography and ultrasonography exams carried out at the Radiology Department of Trieste University Hospital. These cases were referred for mammography at the synchrotron radiation facility, with images acquired using a propagation-based phase-contrast imaging technique. To investigate the contribution of phase-contrast effects to the image quality, two experienced radiologists specialized in mammography assessed the visibility of breast abnormalities and of breast glandular structures. The images acquired at the hospital and at the synchrotron radiation facility were compared and graded according to a relative seven-grade visual scoring system. The statistical analysis highlighted that PCM with synchrotron radiation depicts normal structures and abnormal findings with higher image quality with respect to conventional digital mammography

CB₁R protein expression in MS lymphocytes.

<p>A. Calibration curve of the ELISA test with different concentrations of CHO-CB₁ cell extracts. Specific binding (SB) of anti-CB₁ antibody to CHO-CB₁ cell extracts followed the equation y = 0.01133×+0.01951 (R² = 0.9775). B. Dispersion graphs of CB₁ protein content in human lymphocytes from short AAT group (white circles and bar) and long AAT group (black circles and bar) of patients. C. Histogram of cumulative data shown in panel B. *p = 0.0335.</p

Demographic and clinical characteristics of MS subjects.

<p>ns, not significant; M, male; F, female; EDSS, Expanded Disability Status Scale.</p

Interaction between the <i>CNR1</i> genotype and T2-weighted lesion loads on regional GM volumes.

<p>In yellow, there are shown those areas (i.e., left frontal and cingulate cortex, and right temporal cortex) in which an inverse correlation exists between T2-lesion load and local grey matter volumes in individuals with long AAT repeats, but that is absent in those with short AAT repeats. The plot on the top right shows this effect of interaction in the left frontal and cingulate area. This same effect is also confirmed, on a subject by subject basis, by the sctatterplot on the bottom right. Statistical threshold: p values FWE-corrected <0.05. Spatial coordinates (x,y,z) in the figure are in MNI space. Abbreviations: LL = T2-weighted lesion load; GM = grey matter.</p