Aven‐mediated checkpoint kinase control regulates proliferation and resistance to chemotherapy in conventional osteosarcoma

Conventional high‐grade osteosarcoma is the most common primary bone sarcoma, with relatively high incidence in young people. In this study we found that expression of Aven correlates inversely with metastasis‐free survival in osteosarcoma patients and is increased in metastases compared to primary tumours. Aven is an adaptor protein that has been implicated in anti‐apoptotic signalling and serves as an oncoprotein in acute lymphoblastic leukaemia. In osteosarcoma cells, silencing Aven triggered G₂ cell‐cycle arrest; Chk1 protein levels were attenuated and ATR–Chk1 DNA damage response signalling in response to chemotherapy was abolished in Aven‐depleted osteosarcoma cells, while ATM, Chk2 and p53 activation remained intact. Osteosarcoma is notoriously difficult to treat with standard chemotherapy, and we examined whether pharmacological inhibition of the Aven‐controlled ATR–Chk1 response could sensitize osteosarcoma cells to genotoxic compounds. Indeed, pharmacological inhibitors targeting Chk1/Chk2 or those selective for Chk1 synergized with standard chemotherapy in 2D cultures. Likewise, in 3D extracellular matrix‐embedded cultures, Chk1 inhibition led to effective sensitization to chemotherapy. Together, these findings implicate Aven in ATR–Chk1 signalling and point towards Chk1 inhibition as a strategy to sensitize human osteosarcomas to chemotherapy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Four cancer cases after esophageal atresia repair: Time to start screening the upper gastrointestinal tract

Esophageal atresia(EA) is one of the most common congenital digestive malformations and requires surgical correction early in life. Dedicated centers have reported survival rates up to 95%. The most frequent comorbidities after EA repair are dysphagia(72%) and gastroesophageal reflux(GER)(67%). Chronic GER after EA repair might lead to mucosal damage, esophageal stricturing, Barrett's esophagus and eventually esophageal adenocarcinoma. Several long-term follow-up studies found an increased risk of Barrett's esophagus and esophageal carcinoma in EA patients, both at a relatively young age. Given these findings, the recent ESPGHAN-NASPGHAN guideline recommends routine endoscopy in adults born with EA. We report a series of four EA patients who developed a carcinoma of the gastrointestinal tract: three esophageal carcinoma and one colorectal carcinoma in a colonic interposition. These cases emphasize the importance of lifelong screening of the upper gastrointestinal tract in EA patients.     

Effects of Erxian decoction, a Chinese medicinal formulation, on serum lipid profile in a rat model of menopause

Background

Infantile colic is a common painful clinical condition associated with signs of distended intestines and an increase in colon peristalsis. However, clinical documentation of observed gastrointestinal functions in the condition is still lacking. Even though the ailment is common, no clear treatment guidelines exist. While acupuncture with minimal stimulation has been shown to be effective in reducing crying behaviour of infants suffering from colic, the documented effect of acupuncture on gastrointestinal function in children with infantile colic is scarce. This case series study aims to document the symptoms of routinely rated gastrointestinal function and the changes in these symptoms after minimal acupuncture in a larger group of children with infantile colic.

Methods

This study included 913 infants with normal weights, and lengths at birth. The infants' mean age was 5.4 weeks when the observations started, and had colic symptoms since two weeks after birth. Light needling stimulation of the acupuncture point LI4 was performed for 10-20 seconds bilaterally on a daily basis for a mean of 6.2 consecutive days. A questionnaire with verbal rating scales for the parents' evaluation was used before and after the treatment period.

Results

Before treatment the infants were assessed by the parents in terms of 'often have inflated stomachs' (99%) and 'seldom drool' (76%), 'regurgitate' (53%) and 'belch' (62%). Moreover, the reported frequency of defecation was 5-8 times per day (64%), with a yellowish-green colour (61%) and with a water-thin consistency (74%). After treatment, the variables of inflated stomachs, drooling and regurgitating were systematically changed, and rated by the parents as occurring 'sometimes' while belching was rated as occurring 'often' and the frequency of defecation was reduced to 1-4 times/day with a mustard yellow colour and a gruel-like consistency. The parents also rated their impression of the infants' general colic symptoms including crying behaviour as much ameliorated in 76% of the cases.

Conclusion

The results of the present study show that minimal acupuncture at LI4 in infantile colic is an effective and easy treatment procedure that, furthermore, is reported to be without serious side effects.     

Genetics of cardiovascular and renal complications in diabetes

The development of debilitating complications represents a major heathcare burden associated with the treatment of diabetes. Despite advances in new therapies for controlling hyperglycemia, the burden associated with diabetic complications remains high, especially in relation to cardiovascular and renal complications. Furthermore, an increasing proportion of patients develop type 2 diabetes at a younger age, putting them at higher risk of developing complications as a result of the increased exposure to hyperglycemia. Diabetes has become the main contributing cause to end‐stage renal disease in most countries. Although there has been important breakthroughs in our understanding of the genetics of type 1 and type 2 diabetes, bringing important insights towards the pathogenesis of diabetes, there has been comparatively less progress in our understanding of the genetic basis of diabetic complications. Genome‐wide association studies are beginning to expand our understanding of the genetic architecture relating to diabetic complications. Improved understanding of the genetic basis of diabetic cardiorenal complications might provide an opportunity for improved risk prediction, as well as the development of new therapies.     

Acinic cell carcinoma of the lacrimal gland with intracranial extension: a case report.

PURPOSE: To describe a patient with acinic cell carcinoma of the lacrimal gland presenting with atypical manifestations including erosion of the orbital roof and intracranial extension. We compare his clinical manifestations with two previously reported cases. METHODS: Case report. RESULTS: A 51-year-old man presented with a firm, tender, palpable mass in the superior temporal portion of his right orbit. CT scan demonstrated a large homogeneously enhancing mass displacing the globe inferiorly and eroding the roof of the orbit. MRI of the orbit showed intracranial extension of tumor. Biopsy revealed an acinic cell carcinoma of the lacrimal gland. CONCLUSIONS: Acinic cell carcinoma is a rare neoplasm occurring primarily in the major and minor salivary glands.     

Elastic strain energy in the low back muscles during human walking

Summary A simple model of the thorax, pelvis and three columns of the intrinsic lumbar back muscles (=ILBM) was constructed. The model was used to study the length of the ILBM during the different stages of the walking cycle. The length of the right ILBM (especially the lateral column) was largest at right toe off, exactly the stage of the walking cycle in which most force was needed to prevent the torso from falling forwards and laterally.     

Bamboo skewer perforation of the bowel: Computed tomography appearances

A 25-year-old Chinese woman presented with a painful left-lower-quadrant abdominal mass. Computed tomography (CT) demonstrated a dense forked foreign body within an extraluminal mass. A 2.5 cm bamboo skewer surrounded by inflamed omentum was found at laparotomy. Different CT densities of bamboo skewers were obtained when exposed to air, water and 2% Gastrografin in an in vitro experiment. Awareness of the possible variations in appearances of wooden foreign bodies in and around the bowel may aid their CT diagnoses.     

Blepharoptosis repair by fascia lata suspension with direct tarsal and frontalis fixation

Nine patients with blepharoptosis and no levator palpebrae superioris muscle function were treated by fixating irradiated fascia lata to the tarsus and frontalis muscles under direct visualization. No recurrences were noted on follow-up, which ranged from four to 24 months. There were no postoperative infections or granuloma reactions. Cosmetically, the height, contour, and symmetry of the eyelid margin and eyelid crease were predictable and satisfactory. This modified method of frontalis suspension may provide a more predictable and cosmetically pleasing result in the treatment of blepharoptosis when minimal or no levator muscle function is present.     

Three-compartment wrist arthrography: use of a low-iodine-concentration contrast agent to decrease study time

To decrease examination time, the authors used a contrast agent with a low iodine concentration for three-compartment (radiocarpal joint, distal radioulnar joint, midcarpal compartment) wrist arthrography. The material was used in 24 patients. Many patients demonstrated dissipation of contrast material in the radiocarpal joint by 30 minutes after injection. By 45 minutes, all patients demonstrated sufficient dissipation to permit the second injection. The technique produces diagnostic images and reduces the time required for the study.