Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study

Journal of Neurology - To identify baseline factors associated with disease activity in patients with relapsing–remitting multiple sclerosis (RRMS) under teriflunomide treatment. This was an...     

A 1 Mb de novo deletion within 11q13.1q13.2 in a boy with mild intellectual disability and minor dysmorphic features

We report a 11 year old male patient ascertained for mild intellectual disability and minor dysmorphic features, carrying a 1 Mb de novo deletion on chromosome 11q13.1q13.2 detected by aCGH. This is the first report of a deletion in this region in a patient presenting with intellectual impairment and mild dysmorphic traits. The 1 Mb deleted area encompasses 47 RefSeq genes, including Cornichon homologue 2 (CNIH2), Cofilin-1 (CFL1) and neuronal PAS domain-containing protein 4 (NPAS4), which are highly expressed in the central nervous system. Knockout of the CNIH2 and CFL1 orthologues in animals results in migration disturbances, while low or no expression of Npas4 in mice results in impairment of memory and learning. These three genes have previously been suggested as candidate genes for neurological disorders.     

Genetically driven CD39 expression shapes human tumor-infiltrating CD8+ T-cell functions

In our study, we investigated the role of CD39 on tumor-infiltrating CD8⁺ T lymphocytes (CD8⁺ TILs) in colorectal, head and neck and pancreatic cancers. Partially confirming recent observations correlating the CD39 expression with T-cell exhaustion, we demonstrated a divergent functional activity in CD39⁺CD8⁺ TILs. On the one hand, CD39⁺CD8⁺ TILs (as compared to their CD39⁻ counterparts) produced significantly lower IFN-γ and IL-2 amounts, expressed higher PD-1, and inversely correlated with perforin and granzyme B expression. On the other, they displayed a significantly higher proliferative capacity ex vivo that was inversely correlated with the PD-1 expression. Therefore, CD39⁺CD8⁺ TILs, including those co-expressing the CD103 (a marker of T resident memory [TRM] cells), were defined as partially dysfunctional T cells that correlate with tumor patients with initial progression stages. Interestingly, our results identified for the first time a single nucleotide polymorphism (SNP rs10748643 A>G), as a genetic factor associated with CD39 expression in CD8⁺ TILs. Finally, we demonstrated that compounds inhibiting CD39-related ATPases improved CD39⁺CD8⁺ T-cell effector function ex vivo, and that CD39⁺CD8⁺ TILs displayed effective suppression function in vitro. Overall these data suggest that the SNP analysis may represent a suitable predictor of CD39⁺CD8⁺ T-cell expression in cancer patients, and propose the modulation of CD39 as a new strategy to restore partially exhausted CD8⁺ TILs.     

Higher levels of neuroticism in older adults predict lower executive functioning across time: the mediating role of perceived stress

Neuroticism has been associated with individual differences across multiple cognitive functions. Yet, the literature on its specific association with executive functions (EF) in older adults is scarce, especially using longitudinal designs. To disentangle the specific influence of neuroticism on EF and on coarse cognitive functioning in old adulthood, respectively, we examined the relationship between neuroticism, the Trail Making Test (TMT) and the Mini-Mental State Examination (MMSE) in a 6-year longitudinal study using Bayesian analyses. Data of 768 older adults (M_age?=?73.51 years at Wave 1) were included in a cross-lagged analysis. Results showed no cross-sectional link between neuroticism and TMT performance at Wave 1 and no longitudinal link between neuroticism at Wave 1 and MMSE at Wave 2. However, neuroticism at Wave 1 predicted TMT performance at Wave 2, indicating that the more neurotic participants were, the lower they performed on the TMT six years later. Additional analyses showed that this relation was fully mediated by participants’ perceived stress. Our results suggest that the more neurotic older adults are the more stress they may perceive six years later, which in turn negatively relates to their EF. In sum, this study demonstrates that neuroticism may lead to lower EF in older age across six years. It further suggests older adults’ perceived stress as mediator, thereby providing novel insights into the mechanisms underlying this relation. Possible intervention approaches to counter these effects are discussed.

     

Patient’s point of view on the use of telemedicine in multiple sclerosis: a web-based survey

Neurological Sciences - Restrictions in the access to healthcare facilities during COVID-19 pandemic have raised the need for remote monitoring of chronic medical conditions, including multiple...     

Postmortem CT pulmonary findings in SARS-CoV-2-positive cases: correlation with lung histopathological findings and autopsy results

International Journal of Legal Medicine - Postmortem computed tomography (PMCT) is a valuable tool for analyzing the death of patients with SARS-CoV-2 infection. The purpose of this study was to...     

Cutaneous vascular patterns in psoriasis

Microvascular abnormalities are a characteristic feature of psoriasis and play a crucial role in its pathogenesis. Investigational studies have shown that activated keratinocytes in lesional skin undergo an accelerated epidermal cell turnover and are a major source of pro‐angiogenic cytokines, like as VEGF, ESAF, PDECGE/TP, TNF‐α, TGF‐α and PDGF, suggesting that the epidermis is capable of inducing vascular proliferation. On the other hand, microvascular alterations are essential for the development and persistence of the psoriatic lesions as they provide cellular and tissue nutrition to hyperplastic keratinocytes and promote inflammatory cell migration. Also, dilated and slightly tortuous blood vessels within dermal papillae represent one of the earliest detectable histological changes for all stages of lesional development. Videodermatoscopy is a new non invasive imaging technique able to identify modifications of microvascular architecture in vivo and such evaluation will be useful for the dermatologist both for diagnostic and prognostic evaluation, as well as for post‐therapeutic follow‐up. In this review, the role of microvascular abnormalities in the pathogenesis of psoriasis as well as the mechanisms underlying vascular changes and their primary therapeutic implications will be reviewed and discussed.