Proteomics on human cerebral cavernous malformations reveals novel biomarkers in neurovascular dysfunction for the disease pathology.

Background: Cerebral cavernous malformation (CCM) is a disease associated with an elevated risk of focal neurological deficits, seizures, and hemorrhagic stroke. The disease has an inflammatory profile and improved knowledge of CCM pathology mechanisms and exploration of candidate biomarkers will enable new non-invasive treatments.

Methods: We analyzed protein signatures in human CCM tissue samples by using a highly specific and sensitive multiplexing technique, proximity extension assay.

Circulating biomarkers in familial cerebral cavernous malformation.

Background: Cerebral Cavernous Malformation (CCM) is a rare cerebrovascular disease, characterized by the presence of multiple vascular malformations that may result in intracerebral hemorrhages (ICHs), seizure(s), or focal neurological deficits (FND). Familial CCM (fCCM) is due to loss of function mutations in one of the three independent genes KRIT1 (CCM1), Malcavernin (CCM2), or Programmed Cell death 10 (PDCD10/CCM3). The aim of this study was to identify plasma protein biomarkers of fCCM to assess the severity of the disease and predict its progression.

Single-Cell RNA Sequencing for the Detection of Clonotypic V(D)J Rearrangements in Multiple Myeloma.

Multiple myeloma (MM) has a highly heterogeneous genetic background, which complicates its molecular tracking over time. Nevertheless, each MM patient's malignant plasma cells (PCs) share unique V(D)J rearranged sequences at immunoglobulin loci, which represent ideal disease biomarkers. Because the tumor-specific V(D)J sequence is highly expressed in bulk RNA in MM patients, we wondered whether it can be identified by single-cell RNA sequencing (scRNA-seq).

Mapping endothelial-cell diversity in cerebral cavernous malformations at single-cell resolution.

Cerebral cavernous malformation (CCM) is a rare neurovascular disease that is characterized by enlarged and irregular blood vessels that often lead to cerebral hemorrhage. Loss-of-function mutations to any of three genes results in CCM lesion formation; namely, , , and . Here, we report for the first time in-depth single-cell RNA sequencing, combined with spatial transcriptomics and immunohistochemistry, to comprehensively characterize subclasses of brain endothelial cells (ECs) under both normal conditions and after deletion of ( in a mouse model of CCM.

NOTCH1 gene amplification promotes expansion of Cancer Associated Fibroblast populations in human skin.

Cancer associated fibroblasts (CAFs) are a key component of the tumor microenvironment. Genomic alterations in these cells remain a point of contention. We report that CAFs from skin squamous cell carcinomas (SCCs) display chromosomal alterations, with heterogeneous NOTCH1 gene amplification and overexpression that also occur, to a lesser extent, in dermal fibroblasts of apparently unaffected skin.

Intronless WNT10B-short variant underlies new recurrent allele-specific rearrangement in acute myeloid leukaemia.

Defects in the control of Wnt signaling have emerged as a recurrent mechanism involved in cancer pathogenesis and acute myeloid leukaemia (AML), including the hematopoietic regeneration-associated WNT10B in AC133 leukaemia cells, although the existence of a specific mechanism remains unproven. We have obtained evidences for a recurrent rearrangement, which involved the WNT10B locus (WNT10B) within intron 1 (IVS1) and flanked at the 5' by non-human sequences whose origin remains to be elucidated; it also expressed a transcript variant (WNT10B) which was mainly detected in a cohort of patients with intermediate/unfavorable risk AML. We also identified in two separate cases, affected by AML and breast cancer respectively, a genomic transposable short form of human WNT10B (ht-WNT10B).

Identification of kit(M541L) somatic mutation in chronic eosinophilic leukemia, not otherwise specified and its implication in low-dose imatinib response.

Activating mutations of KIT receptor tyrosine kinase have been reported in different neoplasms. The M541L KIT substitution (KIT(M541L)) has been described to be associated with pediatric mastocytosis, to enhance growth rate of the affected cells and to confer higher sensitivity to imatinib therapy. We investigated the presence of KIT(M541L) in five males with chronic eosinophilic leukemia, not otherwise specified (CEL, NOS), all negative for Platelet-derived growth factor-alpha (PDGFR) or PDGFRbeta abnormalities, which responded to imatinib therapy.

Old and new prognostic factors in acute myeloid leukemia with deranged core-binding factor beta.

Acute myeloid leukemia (AML) with deranged core-binding factor beta (CBFβ) is usually associated with a favorable prognosis with 50-70% of patients cured using contemporary treatments. We analyzed the prognostic significance of clinical features on 58 patients with CBFβ-AML aged ≤60 years. Increasing age was the only predictor for survival (P <0.

Regeneration-associated WNT signaling is activated in long-term reconstituting AC133bright acute myeloid leukemia cells.

Acute myeloid leukemia (AML) is a genetically heterogeneous clonal disorder characterized by two molecularly distinct self-renewing leukemic stem cell (LSC) populations most closely related to normal progenitors and organized as a hierarchy. A requirement for WNT/β-catenin signaling in the pathogenesis of AML has recently been suggested by a mouse model. However, its relationship to a specific molecular function promoting retention of self-renewing leukemia-initiating cells (LICs) in human remains elusive.

Tamoxifen retinopathy: does it really exist?

Background: Tamoxifen retinopathy is known to be an adverse effect of high-dose tamoxifen treatment. Evidence of ocular toxicity at lower doses is less convincing: the aim of this study was to assess the prevalence of the above-mentioned retinopathy in a population treated with low-dose tamoxifen.

Methods: One hundred and twenty-nine women treated with low-dose tamoxifen (20 mg/day) were examined.

Factors related to drug consumption during pregnancy.

A survey on drug intake during pregnancy was carried out in a sample of 3268 women who delivered live-born infants in 11 hospitals located throughout Italy. A large questionnaire on drug use and other aspects of maternal life-style was administered within five days of delivery to 3112 women who consented to the interview. An overall mean consumption of 2.

Moderate maternal drinking and outcome of pregnancy.

The adverse effect of light or moderate maternal drinking during pregnancy on the well being of the newborn has been investigated. The study group included 2145 live births in the obstetric units of 11 Italian cities between February 1989 and July 1990. A detailed life style questionnaire was administered to the mothers.

[Paralysis of oculomotor nerves in diabetes mellitus. A retrospective study of 44 cases].

Data from the clinical charts of 44 diabetic patients with oculomotor palsy were studied. The sixth cranial nerve was involved in 55 p. 100 of cases, the third in 39 p.

[Effects of moderate maternal drinking on some neonatal parameters].

A cross-sectional study was conducted on 2415 mother/newborn pairs, in order to evaluate the relationship between maternal alcohol consumption and birth weight. The results of this study are consistent with previous reports, that pointed out the casual relationship between maternal drinking during pregnancy, and reduction in birth weight. This reduction was evident only on the subset of smokers.

Effect of passive smoking during pregnancy on selected perinatal parameters.

A prospective study of 1004 consecutive deliveries was carried out to investigate the effect of passive smoking during pregnancy on a set of perinatal parameters. The data set was a cooperative study involving 11 Italian cities, distributed nationally. The study group was divided in three categories according to the mother's cigarette smoke exposure during pregnancy, ie, not smokers, passive smokers, direct smokers.

Central vision impairment from optic disk drusen in the young.

Reduced visual acuity apparently due to the effects of drusen on the optic nerve is rare. We describe two young patients with central vision impairment from optic disk drusen: a man with a reduction of visual acuity to light perception, a women with a very fast evolution of the drusen, that, not visible at the clinical onset, could be documented in autofluorescence one month later. The appearance of drusen in disks initially diagnosed as pseudopapilledema is supposed to be related to axonal degeneration from abnormal axoplasmic flow.

[Severe neonatal cardiac insufficiency due to arteriovenous fistula of the vein of Galen].

The cerebral arteriovenous fistula is a rare cause of neonatal cardiac failure. We have recently observed three cases of severe cardiac failure associated with an arterio-venous malformation of the vein of Galen. At echocardiography and angiography the right cardiac chambers were seen to be more enlarged than the left ones.