Facial movement before and after masseteric-facial nerves anastomosis: A three-dimensional optoelectronic pilot study

To quantify the effects of facial palsy reanimation, 14 patients aged 17–66 years were analysed. All patients had unilateral facial paralysis, and were candidates for surgical masseteric to facial nerve anastomosis. Two patient groups were measured: seven patients were waiting for surgery, the other seven patients had already been submitted to surgery, and had regained facial mimicry. Each patient performed three facial animations: brow raise; free smile; lip purse. These were recorded using an optoelectronic motion analyser.The three-dimensional coordinates of facial landmarks were obtained, their movements were computed, and asymmetry indices calculated (differential movements between the two hemi-faces: healthy and paretic/rehabilitated). Before surgery, mobility was larger in the healthy than in the paretic side; after surgery, the differences were reduced (brow raise and lip purse), or even reversed (smile). Before surgery, lip purse was performed with significant labial asymmetry (p = 0.042; larger healthy side movement). After surgery, asymmetry indices reduced. Total labial asymmetry during smiling was significantly different from 0 before surgery (p = 0.018, larger healthy side movement). After surgery, all asymmetry indices became non-significant. Before surgery the lateral displacements of all labial landmarks were towards the healthy side, while they normalized after surgery.     

Loss of heterozygosity in 7q myeloid disorders: clinical associations and genomic pathogenesis

Loss of heterozygosity affecting chromosome 7q is common in acute myeloid leukemia and myelodysplastic syndromes, pointing toward the essential role of this region in disease phenotype and clonal evolution. The higher resolution offered by recently developed genomic platforms may be used to establish more precise clinical correlations and identify specific target genes. We analyzed a series of patients with myeloid disorders using recent genomic technologies (1458 by single-nucleotide polymorphism arrays [SNP-A], 226 by next-generation sequencing, and 183 by expression microarrays). Using SNP-A, we identified chromosome 7q loss of heterozygosity segments in 161 of 1458 patients (11%); 26% of chronic myelomonocytic leukemia patients harbored 7q uniparental disomy, of which 41% had a homozygous EZH2 mutation. In addition, we describe an SNP-A-isolated deletion 7 hypocellular myelodysplastic syndrome subset, with a high rate of progression. Using direct and parallel sequencing, we found no recurrent mutations in typically large deletion 7q and monosomy 7 patients. In contrast, we detected a markedly decreased expression of genes included in our SNP-A defined minimally deleted regions. Although a 2-hit model is present in most patients with 7q uniparental disomy and a myeloproliferative phenotype, haplodeficient expression of defined regions of 7q may underlie pathogenesis in patients with deletions and predominant dysplastic features.     

A focused update on emerging prognostic determinants in distal left main percutaneous coronary intervention

A distal location of the atherosclerotic plaque is one of the most powerful predictors of adverse events after left main angioplasty. However, bifurcations are not alike and may differ with regards to a number of variables, including the angle of the bifurcation, the presence of a ramus, the burden of downstream coronary artery disease, the involvement of stemming arteries and their mismatch. For these reasons, research is seeking to identify new specific predictors that are relevant to this patient population. Simple variables, including stenting strategy, SYNTAX (SYNergy between percutaneous coronary interventions with TAXus and cardiac surgery) score, angles and plaque distribution carry a prognostic value and may be useful to drive decisions in distal left main disease. We reviewed the evidences to date that specifically address the treatment of left main bifurcations, with emphasis on emerging prognostic determinants in this challenging scenario.     

Physical contact with endothelial cells through β1- and β2- integrins rescues chronic lymphocytic leukemia cells from spontaneous and drug-induced apoptosis and induces a peculiar gene expression profile in leukemic cells

Background

Chronic lymphocytic leukemia B cells display prolonged survival in vivo, but when cultured in vitro rapidly undergo spontaneous apoptosis. We hypothesize that interactions with endothelial cells in infiltrated tissues and during recirculation may have a pathogenic role in chronic lymphocytic leukemia.

Design and Methods

We evaluated apoptosis of leukemic cells after co-culture on a monolayer of human umbilical vein endothelial cells with addition of fludarabine and antibodies that block adhesion. Then, we compared microarray-based gene expression profiles between leukemic cells at baseline and after co-culture.

Results

We found that the endothelial layer protected leukemic cells from apoptosis inducing a 2-fold mean decrement in apoptotic cells after 2 days of co-culture. Moreover, the endothelial layer decreased the sensitivity of chronic lymphocytic leukemia B cells to fludarabine-induced apoptosis. Physical contact with endothelium mediated by both β₁- and β₂- integrins is essential for the survival advantage of leukemic cells. In particular, blocking CD106 on endothelial cells or CD18 on leukemic B cells led to the almost complete abrogation of the survival advantage (>70% inhibition of viability). However, a reduction of apoptosis was also measured in leukemic cells cultured in conditioned medium collected after 2 days of co-culture, implying that survival is partially mediated by soluble factors. Overall, the contact with endothelial cells modulated 1,944 genes in chronic lymphocytic leukemia B cells, establishing a peculiar gene expression profile: up-regulation of angiogenesis-related genes, an increase of genes involved in TGFβ and Wnt signaling pathways, secretion of cytokines recruiting stromal cells and macrophages and up-regulation of anti-apoptotic molecules such as Bcl2 and Survivin.

Conclusions

Our study supports the notion that endothelial cells are major players in the chronic lymphocytic leukemia microenvironment. Adhesion to endothelium strongly supports survival, protects from drug-induced apoptosis and extensively modifies the gene expression profile of leukemic cells.     

Limitations of blood pressure target in non-dialysis chronic kidney disease: a question of method?

International guidelines recommend to reduce blood pressure (BP) levels below 130/80 mmHg in non-dialysis chronic kidney disease (CKD) patients. However, this BP target has not been validated by randomized controlled trials and is mainly driven by data obtained in observational and post-hoc analyses suggesting that it improves the renal and, to some extent, cardiovascular prognosis. The inconclusive results on the prognostic role of the BP target in patients with CKD might also relate to the limited ability of office BP readings to adequately stratify the global risk of this population. In fact, alterations of the pressure profile (such as white-coat hypertension) and nighttime hypertension are common in CKD patients. Recent studies have demonstrated that ambulatory blood pressure monitoring (ABPM) is superior to clinic BP measurements in predicting renal death and cardiovascular events. Therefore, while waiting for the results from the ongoing randomized Systolic Blood Pressure Intervention Trial (SPRINT) comparing the effect on cardiorenal prognosis of two BP target levels, the more widespread use of ABPM is desirable in CKD patients.     

Male–female differences in left-handedness in Sardinia,Italy

Males were consistently found to be more likely than females to report left-hand preference in single-hand tasks, but the literature reports negative results too. Using data from a large sample in Sardinia, we aimed at testing the links of left-handedness with sex, age, residence, and seasonality of birth. A total of 4239 participants (males = 1589; females = 2650) were recruited in public places such as high schools, university classes, or gyms in one of the major islands of Italy. Hand preference was established with the question: Which hand do you normally use to write legibly? The monthly distribution of births was studied with the Rayleigh test. In the sample, 270 female participants reported left-hand preference in writing (10.2%) versus 161 male participants (10.1%). Left-hand preference in writing was negatively related to age, with increasing left-hand preference in the younger generations. Left-hand preference in writing was not more common in urban than in suburban or rural settings. The month of birth was found to have a seasonal effect on the left-handed (p=.031) but not on the right-handed (p=.80) participants, and this seasonal effect was more evident in males (p=.04) than in females (p =.26). In our sample males were not more likely to report left-hand preference in writing than females. On the other hand, left-hand preference does vary by age and, in all likelihood, this is an effect of the reduced cultural pressure to write with the right hand in the younger generations.     

The p.A382T TARDBP gene mutation in Sardinian patients affected by Parkinson's disease and other degenerative parkinsonisms

Based on our previous finding of the p.A382T founder mutation in ALS patients with concomitant parkinsonism in the Sardinian population, we hypothesized that the same variant may underlie Parkinson's disease (PD) and/or other forms of degenerative parkinsonism on this Mediterranean island. We screened a cohort of 611 patients with PD (544 cases) and other forms of degenerative parkinsonism (67 cases) and 604 unrelated controls for the c.1144G > A (p.A382T) missense mutation of the TARDBP gene. The p.A382T mutation was identified in nine patients with parkinsonism. Of these, five (0.9 % of PD patients) presented a typical PD (two with familiar forms), while four patients (6.0 % of all other forms of parkinsonism) presented a peculiar clinical presentation quite different from classical atypical parkinsonism with an overlap of extrapyramidal–pyramidal–cognitive clinical signs. The mutation was found in eight Sardinian controls (1.3 %) consistent with a founder mutation in the island population. Our findings suggest that the clinical presentation of the p.A382T TARDBP gene mutation may include forms of parkinsonism in which the extrapyramidal signs are the crucial core of the disease at onset. These forms can present PSP or CBD-like clinical signs, with bulbar and/or extrabulbar pyramidal signs and cognitive impairment. No evidence of association has been found between TARDBP gene mutation and typical PD.