Bone morphogenetic protein (BMP)9 in cancer development: mechanistic, diagnostic, and therapeutic approaches?

Bone morphogenetic protein (BMP)-9 is considered a member of the transforming growth factor (TGF)ß superfamily. It was first found as an inducer of bone and cartilage formation and then discovered that this factor mediates several physiologic functions and hemostasis. Besides physiological conditions, BMP9 has also been elucidated that it is involved in several pathological situations, especially cancer. In various cancers, dysregulation of BMP9 has raised the issue that BMP9 might play a conflicting role in tumour development. BMP9 binding to its receptors (BMPRs), including ALKs and BMPRII, induces canonical SMAD-dependent and non-canonical PI3K/AKT and MAPK signalling pathways in tumour cells. BMP9, via inducing apoptosis, inhibiting tumour-promoting cell signalling pathways, suppressing epithelial-mesenchymal transition (EMT) process, blocking angiogenesis, and preventing cross-talk in the tumour microenvironment, mainly exerts tumour-suppressive functions. In contrast, BMP9 triggers tumour-supportive signalling pathways, promotes EMT, and enhances angiogenesis, suggesting that BMP9 is also involved in tumour development. It has been demonstrated that modulating BMP9 expression and functions might be a promising approach to cancer treatment. It has also been indicated that evaluating BMP9 expression in cancers might be a biomarker for predicting cancer prognosis. Overall, BMP9 would provide a promising target in cancer management.

Additional Imaging is of Limited Value in Traumatic Hip Fractures With a History of Distant Malignancy and No Suspicious Lesion on Plain Radiographs.

OBJECTIVE: To determine the value of obtaining additional preoperative imaging in patients with a traumatic hip fracture and a history of malignancy in whom plain radiographs show no lesion suspicious for metastases. DESIGN: Retrospective review. SETTING: Teaching NHS Trust in the United Kingdom, over an 8-year period treating 4421 hip fractures. PATIENTS/PARTICIPANTS: Three hundred sixty-seven patients with hip fracture and a history of malignancy at a site distant to the hip. Three hundred thirty patients had a history of trauma and no lesion on the plain radiograph suspicious for metastases. MAIN OUTCOMES MEASUREMENTS: Whether obtaining additional imaging preoperatively (MRI, CT, and bone scan) identified metastases or affected management. RESULTS: 32/330 patients had further preoperative imaging, none of which demonstrated a pathological fracture secondary to malignancy. On follow-up, 3/330 (0.9%) cases were found to have occult metastasis at the hip fracture site. All 3 had only plain radiographs before surgery. In 2, this was identified on histological examination of intraoperative samples, and in 1, radiologically as a metastatic metaphyseal lesion 18 months after a hemiarthroplasty. Only in the latter case, preoperative identification of hip metastasis could have altered surgical management. Patients undergoing further preoperative imaging waited significantly longer for surgery (35 ± 26 vs. 51 ± 26 hours, P = 0.0011). CONCLUSIONS: In the absence of a suspicious metastatic lesion on initial plain radiographs, further preoperative imaging is unlikely to identify a lesion that will affect management and confers significant delays to surgery. Sending intraoperative histological samples may help guide postoperative oncological management, but further work is needed to prove its utility. LEVEL OF EVIDENCE: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Prevalence of xerostomia in patients attending Shorish dental speciality in Sulaimani city.

OBJECTIVES: The aim of this study was to investigate the prevalence of xerostomia among dental patients and explore the possible risk factors and symptoms associated with this condition. PATIENT AND METHODS: The prevalence of xerostomia and its associations were investigated among patients (n=1132) who were visiting the department of oral medicine at shorish dental speciality in sulaimani city. The age range was between 10-79 years. 512 (45.2%) of participants were males and 620 (54.8%) were females. The data collected were age, sex, systemic diseases, medications and habit of smoking. Logistic regression models to estimate odds ratios and 95% confidence intervals were used to investigate the association of xerostomia with age, systemic diseases and medications and Chi Square test was also used to analyze the data. RESULTS: Prevalence of xerostomia was 16.07%. Prevalence of xerostomia was significantly higher among females (19.51%) than males (11.91%) (P=0.001). The most common diseases with the highest prevalence of xerostomia were psychological disorders (57.14%) followed by diabetes mellitus (53.84%), neurological disorders (40%), thyroid disorders (37.5%) and hypertension (36.48%). The most common medication with the highest prevalence of xerostomia was antihistamine (66.66%) followed by psychotherapeutic medications (60%), pain medications (55.88%), endocrinologic agents (51.21%), antidyslipidic agents (50%) and antihypertensive medication (38.98%). Xerostomia was significantly associated with ageing (OR: 1.02, P=0.000), systemic diseases (OR: 2.80, P=0.000) and medications (OR: 5.17, P=0.000). There was a high prevalence of reported symptoms of xerostomia and these symptoms were more prevalent among females, Prevalence of xerostomia was higher in heavy smoker patients (19.48%) than non smoker patients but not significantly (16.14%) (p= 0.44). CONCLUSIONS: There was a high prevalence of xerostomia among dental patients; xerostomia was significantly more prevalent among females and significantly associated with age, systemic diseases and medications; xerostomia adversely affects oral functions; dentist must be familial with sign and symptoms of xerostomia and can have an active role in the management of xerostomia and preventing or treating complications. Key words:Ageing, medications, xerostomia, prevalence.

Prevalence of recurrent aphthous ulceration experience in patients attending Piramird dental speciality in Sulaimani City.

OBJECTIVE: The aim of this study is to report the prevalence and risk factors of recurrent aphthous ulceration (RAU) in patients attending Piramird dental speciality for seeking dental treatment. STUDY DESIGN: A cross-sectional survey was carried out among patients (n=1100) who were visiting the department of oral medicine at Piramird dental speciality center in Sulaimani from December 2011-February 2012. The age range of the patients were between 10-79 years, with mean age of (34.27±14.14). 446 (44.6%) of participants were males and 554 (55.4%) were females, with male/female ratios of 0.80:1. All individuals had to answer specific questions including personal data (age, sex), level of education, occupation and smoking habit; etc. Additional questions were related to the risk factors that might be related to the condition. Chi Square test was used to analyze the data. RESULT: The life time prevalence of RAU experience was 28.2% (n=282). It was highly significantly more common among females (31.76%) (p<0.004). The most commonly affected age group was 20-29 years (36.28%). The highest prevalence of RAU experience was seen among mere students (36.8%); Among non smokers there were highly significantly more patients with RAU experience (30%) than in heavy smoker patients (12.22%), (p=0.000). 34.4% of patients had family history of RAU. Lips and buccal mucosae were the commonest sites of ulcerations (73.10%), and the major risk factor was stress (43.3%). CONCLUSION: This study has provided information about the epidemiologic aspects of recurrent aphthous ulceration, Based on the finding of this study, RAU is a common, recurrent painful oral ulceration. This study point to the importance of a thorough history taking to identify the patient's main risk factors to get preventive measures, therefore treatment will be tailored for each patient accordingly. And the author concluded that stress was the major risk factor, thus, stress-management interventions suggested to be beneficial in reducing RAU recurrence episodes. Key words:Recurrent aphthous ulceration, prevalence, stress.

Impact of the characteristics of patients and their clinical management on outcomes in children with homozygous familial hypercholesterolemia.

OBJECTIVE: To relate clinical factors to the development of cardiovascular atherosclerosis for patients with homozygous familial hypercholesterolemia. BACKGROUND: Homozygous familial hypercholesterolemia is associated with extreme elevations in levels of cholesterol causing aggressive atherosclerosis. METHODS: We reviewed 10 children, 8 of whom were male, assessed at a single institution. We found that individual characteristics, levels of lipid, cardiovascular investigations, and management were related to the activity of low density lipoprotein receptors. RESULTS: Activity of low density lipoprotein receptors was defined as absent, being less than 2% of normal, in 4 patients who presented at the ages of 0.3, 1.4, 1.8, and 4.5 years, respectively. The activity was minimal, representing 5%-30% of normal, in another 4 patients presenting at the ages of 6.1, 9.6, 9.9, and 12 years, and was undetermined in 2 patients who presented at the ages of 3.5, and 12.1 years. Levels of low density lipoprotein cholesterol at presentation ranged from 12.2 to 24 millimoles per litre. Plasmapheresis was performed bi-weekly in 9 patients. Patients with absence of receptor activity were less likely to have a serial decrease in the levels of low density lipoprotein cholesterol prior to plasmapheresis, and one of these patients was increased to weekly plasmapheresis. In addition, they had more aggressive cardiovascular involvement of the coronary arteries, aortic valve and aorta, requiring surgical intervention at the age of 8 and 12 years in 2 patients, with sudden death at the age of 3.1 years in one patient. In contrast, 1 patient with minimal receptor activity had surgical intervention at the age of 16.6 years and another patient died suddenly at the age of 33.6 years. CONCLUSION: Complete cardiac assessment is recommended at presentation. The frequency of plasmapheresis should be adjusted according to the activity of low density lipoprotein receptors and the individual response of the patient.