Analysis of mutational status, SNP rs16754, and expression levels of Wilms tumor 1 (WT1) gene in acute promyelocytic leukemia

Overexpression, polymorphisms, and mutations of the WT1 gene have been reported in several human tumors including acute myeloid leukemia (AML) and variably correlated with prognosis. Acute promyelocytic leukemia (APL) represents the AML subset disclosing higher WT1 expression levels; however, no WT1 studies specifically focused on APL have been conducted. We screened for the presence of mutations, SNP rs16754, and expression levels of WT1 gene in 103 adult patients with newly diagnosed APL. Fms-like tyrosine kinase (FLT3) mutations were analyzed as well. WT1 mutations were identified in four (4?%) patients. At least one copy of the minor SNP rs16754 allele (WT1 ^AG or WT1 ^GG) was detected in 30 (29?%) patients. Six patients (6?%) were homozygous for the minor allele (WT1 ^GG ) and this genotype was associated with higher WT1 mRNA copies (p?=?0.018). FLT3 mutations were found in 37?% of patients and correlated with high WT1 mRNA expression (p?=?0.004). Patients heterozygous or homozygous for the minor allele and patients homozygous for major (WT1 ^AA) allele did not differ in terms of presenting features. In adult APL, WT1 gene mutational and polymorphic profile shows similarities with pediatric AML rather than with adult AML.     

Negative correlation between D-dimer and plasminogen activator inhibitor-1 levels is absent in obese women

Obesity is characterized by alterations in haemostatic processes that lead to a prothrombotic state. D-dimer (D-Di) is the last product of the fibrinolysis and may reflect the haemostatic balance. As the plasminogen activator inhibitor (PAI)-1 is the main inhibitor of fibrinolysis and it is elevated in obese, we hypothesize that negative correlation exists between PAI-1 and D-Di. In addition, we evaluated if plasma levels of PAI-1 and D-Di may be correlated with clinical parameters of adiposity [waist circumference and waist-to-hip ratio (WHR)]. We measured plasma PAI-1 and D-Di concentrations using ELISA in 60 women: 21 lean women without comorbidities and 39 obese women. We found higher levels of D-Di and PAI-1 in obese groups compared to control group (P < 0.05). No differences were observed between obese and obese untreated hypertensives. PAI-1 levels, but not of D-Di, are positively correlated with BMI (control, r = 0.44) and WHR (all obese, r = 0.40). Negative correlation was found between PAI-1 and D-Di in control (r = -0.56), no association was observed in obese, signalizing to a particular attention regarding the clinical use of D-Di. Our results indicate the magnitude of central obesity as a risk factor for development of disorders related to prothrombotic states.     

Role of chemotherapy in the management of vulvar carcinoma

The aim of this review is to evaluate the use of chemotherapy (CT) in the treatment of squamous vulvar cancer. Since the 90s there was a continuous evolution in the therapeutic approach to this tumour. Although primary surgery is now considered the most effective approach, there are advanced diseases in which surgery may compromise anatomical structures causing severe mutilation. These are the reasons why CHT, with or without concomitant radiotherapy RT, started to be strongly recommended as neoadjuvant strategy. Chemotherapeutic agents have also been used alone as adjuvant treatment or in association with RT, by exploiting the radiosensitizing effect of these drugs. There are few data about the use of CHT as palliative treatment but recent studies point to the use of target therapy. In conclusion, clinical data and the evidence of chemo-sensitivity in vulvar squamous cell carcinoma open new possibilities to future research in this field.     

Prevalence of upper aerodigestive symptoms in patients who underwent thyroidectomy with and without the use of intraoperative laryngeal nerve monitoring

Background: Upper aerodigestive symptoms (UADS) have been reported by patients who have had thyroidectomies. This study evaluated the long-term prevalence of UADS after thyroidectomy in patients who did and who did not have intraoperative neuromonitoring (IONM). Methods: This was a cross-sectional study of patients with normal vocal fold mobility who had a thyroidectomy. It included patients who did and did not have this surgery with IONM. All patients answered a questionnaire regarding UADS occurring one or more years after thyroidectomy. The questionnaire dealt with UADS relating to voice and swallowing symptoms and sought to quantify their severity. The 208 patients who underwent thyroidectomy without IONM were designated the control group (CG). The 100 patients who underwent thyroidectomy with IONM were designated the neuromonitored group (NMG). Results: The proportion of patients in the CG who reported UADS was 45%; 25.9% of these patients reported voice symptoms, and 33.6% reported swallowing symptoms. The proportion of patients in the NMG who reported UADS was 39%; 27% of these patients reported voice symptoms, and 22% reported swallowing symptoms. Thus, patients in the CG had more swallowing symptoms and a greater severity of UADS-related symptoms than patients in the NMG. Conclusions: In this study, IONM had a favorable effect in terms of decreasing the prevalence and severity of UADS occurring one year or more after thyroidectomy.     

Session II: Mechanisms of age-related cognitive change and targets for intervention: neural circuits, networks, and plasticity

Age-related changes in neural circuits, neural networks, and their plasticity are central to our understanding of age changes in cognition and brain structure and function. This paper summarizes selected findings on these topics presented at the Cognitive Aging Summit II. Specific areas discussed were synaptic vulnerability and plasticity, including the role of different types of synaptic spines, and hormonal effects in the dorsolateral prefrontal cortex of nonhuman primates, the impact of both compensatory processes and dedifferentiation on demand-dependent differences in prefrontal activation in relation to age and performance, the role of vascular disease, indexed by white matter signal abnormalities, on prefrontal activation during a functional magnetic resonance imaging-based cognitive control paradigm, and the influence of amyloid-β neuropathology on memory performance in older adults and the networks of brain activity underlying variability in performance. A greater understanding of age-related changes in brain plasticity and neural networks in healthy aging and in the presence of underlying vascular disease or amyloid pathology will be essential to identify new targets for intervention. Moreover, this understanding will assist in promoting the utilization of existing interventions, such as lifestyle and therapeutic modifiers of vascular disease.     

Trends in HIV Diagnoses and Testing Among U.S. Adolescents and Young Adults

The Centers for Disease Control and Prevention recommends routine HIV screening in health care settings. Using national surveillance data, we assessed trends in HIV diagnoses and testing frequency in youth aged 13–24 diagnosed with HIV in 2005–2008. Diagnosis rates increased among black (17.0% per year), Hispanic (13.5%), and white males (8.8%), with increases driven by men who have sex with men (MSM). A higher percentage of white males and MSM had previously been tested than their counterparts. No increases in diagnoses or differences in testing were observed among females. Intensified interventions are needed to reduce HIV infections and racial/ethnic disparities.