Aberrant p16 methylation, a possible epigenetic risk factor in familial esophageal squamous cell carcinoma

Aim. Detection of methylation in the p16 gene, an inhibitor of cyclin D-dependent protein kinase, as a new tumor marker for early detection of esophageal squamous cell carcinoma (ESCC) in DNA derived from blood and serum. Method. A large family with clustering of ESCC was assessed in Khorasan province in northeastern Iran. The family had three histologically proven cases of ESCC in two consecutive generations and several other deceased cases with histories of ESCC. DNA from blood of 28 living family members in three consecutive generations, 30 sporadic ESCC cases (from serum, blood, and tumor tissues), and 30 healthy volunteers (from blood) were examined for the methylation status of p16 promoter using methylation-specific PCR (MSP). Results. Aberrant p16 promoter methylation was found in 64.3% (n=28) of ESCC family members and none (n=30) of our normal volunteers. Five of the 28 family members with esophageal cancer symptoms had negative endoscopy results for ESCC, while four of these members had p16 hypermethylation in their blood. The family members with negative endoscopy and positive p16 promoter methylation are being monitored closely for signs of ESCC development through regular check-ups and chromoendoscopies. In sporadic ESCC in northeastern Iran, 73.3% (n=30) of tumor tissue samples had p16 hypermethylation. Serum and blood samples from the same patients showed p16 hypermethylation in 26.6% and 43.3% of the samples, respectively. Conclusion. Aberrant p16 methylation may be a valuable diagnostic tool as a tumor marker for the early identification of individuals in high risk ESCC families.     

Liver transplantation as a definitive treatment for familial hypercholesterolemia: A series of 36 cases

FH is a genetic disorder characterized by an increase in serum LDL and total cholesterol values. The afflicted patients are at increased risk of premature atherosclerosis and myocardial infarction. Different treatment modalities are present, including pharmacological agents and surgical procedures. The most effective method of therapy in refractive cases is liver transplantation. Herein, we report our experience on 36 cases of patients with FH undergoing liver transplantation in our center, the main referral center of liver transplantation in Iran. The clinical findings, hospital courses, post‐operative complications, and patient follow‐up are also described.     

The tyrosine kinase regulator Cbl enhances the ubiquitination and degradation of the platelet-derived growth factor receptor α

The Cbl protooncogene product has emerged as a negative regulator of receptor and nonreceptor tyrosine kinases. We recently demonstrated that oncogenic Cbl mutants upregulate the endogenous tyrosine kinase signaling machinery when expressed in the NIH 3T3 cells, and identified the platelet-derived growth factor receptor-α (PDGFRα) as one of the tyrosine kinases targeted by these oncogenes. These findings suggested a role for the normal Cbl protein in negative regulation of the PDGFRα. However, the mechanism of such negative regulation remained to be determined. Here we show that overexpression of the wild-type Cbl enhances the ligand-induced ubiquitination of the PDGFRα. Concomitantly, the PDGFRα in Cbl-overexpressing cells undergoes a faster ligand-induced degradation compared with that in the control cells. These results identify a role for Cbl in the regulation of ligand-induced ubiquitination and degradation of receptor tyrosine kinases and suggest one potential mechanism for evolutionarily conserved negative regulatory influence of Cbl on tyrosine kinases.     

Persistent Truncus Arteriosus With Intact Ventricular Septum: Clinical,Hemodynamic and Short-term Surgical Outcome

Introduction:

Truncus arteriosus with intact ventricular septum is a rare and unique variant of persistent truncus arteriosus (PTA) which usually presents with central cyanosis and congestive heart failure in neonate and early infancy. Associated cardiac and non-cardiac anomalies may affect morbidity and mortality of these patients.

Case Presentation:

We describe clinical presentation, echocardiography and angiographic features of a 7-month old boy with PTA and intact ventricular septum who underwent surgical repair of the anomaly at our institution. Operative findings, surgical procedure and short-term outcome are reported.

Conclusions:

While our patient had systemic pulmonary arterial pressure at the time of complete surgical repair, it was improved after surgery.     

Re-evaluation of the value of ascitic fluid pH lactate dehydrogenase and total proteins in the diagnosis of spontaneous bacterial peritonitis (SBP)

In view of high mortality, variable clinical presentation, and late results of bacterial culture, early diagnosis of SBP and treatment are based on indirect parameters of infection. Forty-two patients with ascites and liver cirrhosis were studied. Ascitic fluid (AF) was examined for total protein content, pH, lactate dehydrogenase, amylase, absolute polymorphonuclear cell count (PMN) and for presence of bacteria by examining a fresh smear of the deposit and culture of the fluid under aerobic and anaerobic conditions. AF/serum gradient of total proteins and LDH was calculated. One patient proved to have a malignant ascites and was excluded. The remaining 41 patients fell into two groups: Group I PMN less than 250 cell mm-3, culture negative, sterile ascites, 36 patients. Group II PMN greater than 250 cell mm-3. (a) Culture positive neutrophilic ascites (SBP), three patients. (b) Culture negative neutrophilic ascites (CNNA), two patients. In both CNNA and SBP:AF/serum total LDH gradient greater than 0.75 In the sterile group: AF/serum total LDH gradient less than 0.58 There was no correlation between presence of infection and ascitic fluid pH, protein content and AF/serum total protein gradient. Therefore AF PMN greater than 250 mm and AF/serum total LDH gradient greater than 0.6 should be considered reliable, indirect parameters of infection, and CNNA a variant of SBP with a small bacterial inoculum size.     

A serine cluster prevents recycling of the V2 vasopressin receptor

Receptor recycling plays a critical role in the regulation of cellular responsiveness to environmental stimuli. Agonist-promoted phosphorylation of G protein-coupled receptors has been related to their desensitization, internalization, and sequestration. Dephosphorylation of internalized G protein-coupled receptors by cytoplasmic phosphatases has been shown to be pH-dependent, and it has been postulated to be necessary for receptors to recycle to the cell surface. The internalized V2 vasopressin receptor (V2R) expressed in HEK 293 cells is an exception to this hypothesis because it does not recycle to the plasma membrane for hours after removal of the ligand. Because this receptor is phosphorylated only by G protein-coupled receptor kinases (GRKs), the relationship between recycling and GRK-mediated phosphorylation was examined. A nonphosphorylated V2R, truncated upstream of the GRK phosphorylation sites, rapidly returned to the cell surface after removal of vasopressin. Less-drastic truncations of V2R revealed the presence of multiple phosphorylation sites and suggested a key role for a serine cluster present at the C terminus. Replacement of any one of Ser-362, Ser-363, or Ser-364 with Ala allowed quantitative recycling of full-length V2R without affecting the extent of internalization. Examination of the stability of phosphate groups incorporated into the recycling S363A mutant V2Rs revealed that the recycling receptor was dephosphorylated after hormone withdrawal, whereas the wild-type V2R was not, providing molecular evidence for the hypothesis that GRK sites must be dephosphorylated prior to receptor recycling. These experiments uncovered a role for GRK phosphorylation in intracellular sorting and revealed a GRK-dependent anchoring domain that blocks V2R recycling.     

A virtual pointer to support the adoption of professional vision in laparoscopic training

Purpose

To assess a virtual pointer in supporting surgical trainees’ development of professional vision in laparoscopic surgery.

Methods

We developed a virtual pointing and telestration system utilizing the Microsoft Kinect movement sensor as an overlay for any imagine system. Training with the application was compared to a standard condition, i.e., verbal instruction with un-mediated gestures, in a laparoscopic training environment. Seven trainees performed four simulated laparoscopic tasks guided by an experienced surgeon as the trainer. Trainee performance was subjectively assessed by the trainee and trainer, and objectively measured by number of errors, time to task completion, and economy of movement.

Results

No significant differences in errors and time to task completion were obtained between virtual pointer and standard conditions. Economy of movement in the non-dominant hand was significantly improved when using virtual pointer (\(p = 0.012\)). The trainers perceived a significant improvement in trainee performance in virtual pointer condition (\(p < 0.001\)), while the trainees perceived no difference. The trainers’ perception of economy of movement was similar between the two conditions in the initial three runs and became significantly improved in virtual pointer condition in the fourth run (\(p = 0.017\)).

Conclusions

Results show that the virtual pointer system improves the trainer’s perception of trainee’s performance and this is reflected in the objective performance measures in the third and fourth training runs. The benefit of a virtual pointing and telestration system may be perceived by the trainers early on in training, but this is not evident in objective trainee performance until further mastery has been attained. In addition, the performance improvement of economy of motion specifically shows that the virtual pointer improves the adoption of professional vision— improved ability to see and use laparoscopic video results in more direct instrument movement.

     

Walking and talking activities as nursing therapy for improving quality of life among older adults

Objective

The most prominent problem resulting from decreased body function in older adults is declining quality of life. Walking and talking among older adults in peer group may become a nursing therapy to improve their quality of life. The objective of this study was to identify the impact of walking and talking intervention of quality of life among community dwelling older adults in Depok, Indonesia.

The association between stereotyping and interprofessional collaborative practice

Objective

This study aimed to identify the association between stereotyping and professional intercollaborative practice.