A double cryptic chromosome imbalance is an important factor to explain phenotypic variability in Wolf-Hirschhorn syndrome

A total of five Wolf-Hirschhorn syndrome (WHS) patient with a 4p16.3 de novo microdeletion was referred because of genotype-phenotype inconsistencies, first explained as phenotypic variability of the WHS. The actual deletion size was found to be about 12 Mb in three patients, 5 Mb in another one and 20 Mb in the last one, leading us to hypothesize the presence of an extrachromosome segment on the deleted 4p. A der(4)(4qter --> p16.1::8p23 --> pter) chromosome, resulting from an unbalanced de novo translocation was, in fact, detected in four patients and a der(4)(4qter --> q32::4p15.3 --> qter) in the last. Unbalanced t(4;8) translocations were maternal in origin, the rec(4p;4q) was paternal. With the purpose of verifying frequency and specificity of this phenomenon, we investigated yet another group of 20 WHS patients with de novo large deletions (n = 13) or microdeletions (n = 7) and with apparently straightforward genotype-phenotype correlations. The rearrangement was paternal in origin, and occurred as a single anomaly in 19 out of 20 patients. In the remaining patient, the deleted chromosome 4 was maternally derived and consisted of a der(4)(4qter --> 4p16.3::8p23 --> 8pter). In conclusions, we observed that 20% (5/25) of de novo WHS-associated rearrangements were maternal in origin and 80% (20/25) were paternal. All the maternally derived rearrangements were de novo unbalanced t(4;8) translocations and showed specific clinical phenotypes. Paternally derived rearrangements were usually isolated deletions. It can be inferred that a double, cryptic chromosome imbalance is an important factor for phenotypic variability in WHS. It acts either by masking the actual deletion size or by doubling a quantitative change of the genome.     

Alexithymia and Pathological Gambling

ABSTRACT

The purpose of this study was to study the relationship between alexithymia and gambling in a community sample of pathological gamblers. Pathological, problem and non-problem gamblers were recruited from the community via advertisements and completed an assessment of their gambling behavior and the Toronto Alexithymia Scale. Alexithymia was higher among male pathological gamblers who identified slot machines, cards, and lotteries as their primary gambling problem. High alexithymics scored higher on Diagnostic and Statistical Manual symptoms related to poor self-regulation, communication, and problem-solving skills. Although a correlational study, the evidence suggests that further investigation of the clinical significance of alexithymia in individuals with severe gambling pathology is indicated.     

Reconstruction of a complex pelvic perineal defect with pedicled anterolateral thigh flap combined with bilateral lotus petal flap: A case report

Reconstructing extensive perineal defects represents a challenge, and reconstructive choice requires a careful physical assessment of previous radiotherapy, pre‐existing scars, the presence of stomas, and the availability of donor sites. We report a case of a patient affected by an anal carcinoma who underwent a pelvic exenteration and bilateral inguinal iliac obturator lymph node dissection. We performed a pedicled anterolateral thigh flap (ALT) combined with bilateral lotus petal flaps (LPF) to reconstruct the pelvic–perineal area. The result was good, and no major post‐operative complications were reported. Bilateral LPF, combined with a pedicled ALT, may represent a valid option in pelvic–perineal reconstruction following a wide oncological resection. © 2014 Wiley Periodicals, Inc. Microsurgery 35:154–157, 2015.     

Simultaneous colorectal and parenchymal-sparing liver resection for advanced colorectal carcinoma with synchronous liver metastases: Between conventional and mini-invasive approaches

The optimal timing of surgery in case of synchronous presentation of colorectal cancer and liver metastases is still under debate. Staged approach, with initial colorectal resection followed by liver resection (LR), or even the reverse, liver-first approach in specific situations, is traditionally preferred. Simultaneous resections, however, represent an appealing strategy, because may have perioperative risks comparable to staged resections in appropriately selected patients, while avoiding a second surgical procedure. In patients with larger or multiple synchronous presentation of colorectal cancer and liver metastases, simultaneous major hepatectomies may determine worse perioperative outcomes, so that parenchymal-sparing LR should represent the most appropriate option whenever feasible. Mini-invasive colorectal surgery has experienced rapid spread in the last decades, while laparoscopic LR has progressed much slower, and is usually reserved for limited tumours in favourable locations. Moreover, mini-invasive parenchymal-sparing LR is more complex, especially for larger or multiple tumours in difficult locations. It remains to be established if simultaneous resections are presently feasible with mini-invasive approaches or if we need further technological advances and surgical expertise, at least for more complex procedures. This review aims to critically analyze the current status and future perspectives of simultaneous resections, and the present role of the available mini-invasive techniques.     

Recurrent glioblastoma: which treatment? A real-world study from the Neuro-oncology Unit “Regina Elena” National Cancer Institute

Neurological Sciences - The majority of patients with glioblastoma (GBM) experience disease progression. At recurrence, treatment options have limited efficacy. Many studies report a limited and...     

A Critical Role for Thioredoxin-Interacting Protein in Diabetes-Related Impairment of Angiogenesis

Impaired angiogenesis in ischemic tissue is a hallmark of diabetes. Thioredoxin-interacting protein (TXNIP) is an exquisitely glucose-sensitive gene that is overexpressed in diabetes. As TXNIP modulates the activity of the key angiogenic cytokine vascular endothelial growth factor (VEGF), we hypothesized that hyperglycemia-induced dysregulation of TXNIP may play a role in the pathogenesis of impaired angiogenesis in diabetes. In the current study, we report that high glucose–mediated overexpression of TXNIP induces a widespread impairment in endothelial cell (EC) function and survival by reducing VEGF production and sensitivity to VEGF action, findings that are rescued by silencing TXNIP with small interfering RNA. High glucose–induced EC dysfunction was recapitulated in normal glucose conditions by overexpressing either TXNIP or a TXNIP C247S mutant unable to bind thioredoxin, suggesting that TXNIP effects are largely independent of thioredoxin activity. In streptozotocin-induced diabetic mice, TXNIP knockdown to nondiabetic levels rescued diabetes-related impairment of angiogenesis, arteriogenesis, blood flow, and functional recovery in an ischemic hindlimb. These findings were associated with in vivo restoration of VEGF production to nondiabetic levels. These data implicate a critical role for TXNIP in diabetes-related impairment of ischemia-mediated angiogenesis and identify TXNIP as a potential therapeutic target for the vascular complications of diabetes.     

Platelet‐rich plasma counteracts detrimental effect of high‐glucose concentrations on mesenchymal stem cells from Bichat fat pad

Diabetic patients display increased risk of periodontitis and failure in bone augmentation procedures. Mesenchymal stem cells (MSCs) and platelet‐rich plasma (PRP) represent a relevant advantage in tissue repair process and regenerative medicine. We isolated MSCs from Bichat's buccal fat pad (BFP) and measured the effects of glucose and PRP on cell number and osteogenic differentiation potential. Cells were cultured in the presence of 5.5‐mM glucose (low glucose [LG]) or 25‐mM glucose (high glucose [HG]). BFP–MSC number was significantly lower when cells were cultured in HG compared with those in LG. Following osteogenic differentiation procedures, calcium accumulation, alkaline phosphatase activity, and expression of osteogenic markers were significantly lower in HG compared with LG. Exposure of BFP–MSC to PRP significantly increased cell number and osteogenic differentiation potential, reaching comparable levels in LG and in HG. Thus, high‐glucose concentrations impair BFP–MSC growth and osteogenic differentiation. However, these detrimental effects are largely counteracted by PRP.