Tooth agenesis and craniofacial morphology in an orthodontic population.

Previous reports have produced conflicting conclusions regarding the relationship among tooth agenesis, the congenital absence of teeth, and variations in craniofacial morphology. Traditional cephalometric assessment and computer-assisted morphometric analysis of jaw size were used to reexamine this relationship in a white orthodontic population. A positive diagnosis of tooth agenesis (including third molar determination) was made in 89 subjects of mixed age and sex who previously had orthodontic treatment but who were not determined to have a recognized syndrome or a craniofacial anomaly. Cephalograms for these subjects were compared with control data from subjects reported in Bolton Standards of Dentofacial Developmental Growth. Missing teeth and their locations were correlated with changes in selected linear and angular measurements of the Bolton cephalometric analysis. Area measurements of the jaw size of the subjects grouped by age were compared with Bolton cephalometric templates. Relatively little correlation was found between missing teeth and changes in cephalometric measurements. Where identified, a decreased maxillary jaw size and maxillary tooth agenesis were generally associated. Two-dimensional area measurements showed that most age groups had significant decreases in maxillary jaw size associated with tooth agenesis. Relatively few groups had significant changes in mandibular size associated with tooth agenesis.     

HOXA methylation in normal endometrium from premenopausal women is associated with the presence of ovarian cancer: A proof of principle study

DNA methylation of polycomb group target (PCGT) genes is an early step in carcinogenesis and could potentially be assayed to determine cancer risk prediction. To assess whether methylation changes in PCGT genes in normal tissue is able to predict the presence of cancer, we studied HOXA gene methylation in normal endometrium from premenopausal ovarian cancer patients and age‐matched healthy controls without ovarian cancer. DNA methylation of HOXA9 and HOXA11 genes in normal endometrium was associated with ovarian cancer in an initial test set and this was subsequently confirmed in independent validation sample sets. The overall risk of ovarian cancer was increased 12.3‐fold by high HOXA9 methylation for all stages, and 14.8‐fold for early stage ovarian cancers, independent of age, phase of the menstrual cycle and histology of the cancer. The results of this proof of principle study demonstrate the potential to detect ovarian cancer via analysis of normal endometrial cells and provide insight into the possible contribution of this novel approach in ovarian cancer risk prediction and prevention. © 2009 UICC     

Outcome of thyroglossal duct cyst excision is independent of presenting age or symptomatology

BACKGROUND: Thyroglossal duct cysts (TGDCs) are the most common form of congenital neck cyst, accounting for up to 70% of such lesions. There has been no consensus on which factors predict outcome of thyroglossal duct cyst excision. The objective of the current study is to evaluate the relevance of symptomatology and age at presentation with outcome of TGDCs. METHODS: Retrospective review of patients with TGDC at a tertiary care children's hospital. Data collected included patient's age, gender, clinical presentation, presence or absence of preoperative infection, imaging modality, type of procedure performed, size and location of the lesion, postoperative infection, complications, and recurrence of disease. RESULTS: Twenty-nine patients were identified (59% female, 41% male). Age of presentation was bimodal and ranged from 18 months to 14 years. The most common presenting symptom was the presence of an asymptomatic midline neck mass (76%). A history of preoperative TGDC infection was present in 22% of patients /=5 years of age. Recurrence rate after the Sistrunk procedure was 3.4%. CONCLUSIONS: The finding of a midline neck mass is the most common presentation of TGDCs in toddlers, whereas infection is the most common presenting symptoms in school-aged children. The incidence of preoperative infection was 41% in our series, much higher than previously reported. Independent of presenting age and symptomatology, recurrence of TGDC remains low when the Sistrunk procedure is employed.     

Educational inequalities in mortality of patients with atrial fibrillation in Norway

Objectives: We explored the educational gradient in mortality in atrial fibrillation (AF) patients.

Design: We prospectively followed patients hospitalized with AF as primary discharge diagnosis in the Cardiovascular Disease in Norway 2008-2012 project. The average length of follow-up was 2.4 years. Mortality by educational level was assessed by Cox proportional hazard models. Population attributable fractions (PAF) were calculated. Analyses stratified by age (≤75 and >75 years of age), and adjusted for age, gender, medical intervention, and Charlson Comorbidity Index.

Results: Of 42,138 AF patients, 16% died by end of 2012. Among younger patients, those with low education (≤10 years) had a HR of 2.3 (95% confidence interval 2.0, 2.6) for all-cause mortality relative to those with any college or university education. Similar results were observed for cardiovascular mortality. Disparities in mortality were greater among younger than older patients. A PAF of 35.9% (95% confidence interval 27.9, 43.1) was observed for an educational level of high school/vocational school or less versus higher education in younger patients.

Conclusions: Increasing educational level associated with better prognosis suggesting underlying education-related behavioral and medical determinants of mortality. A considerable proportion of mortality within 5 years following hospital discharge could be prevented.     

Identification of a small molecule inhibitor of the aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib] using mixture-based combinatorial libraries

The aminoglycoside, 6′-N-acetyltransferase type Ib [AAC(6')-Ib] is the most widely distributed enzyme among AAC(6')-I-producing Gram-negative pathogens and confers resistance to clinically relevant aminoglycosides, including amikacin. This enzyme is therefore an ideal target for enzymatic inhibitors that could overcome resistance to aminoglycosides. The search for inhibitors was carried out using mixture-based combinatorial libraries, the scaffold ranking approach, and the positional scanning strategy. A library with high inhibitory activity had pyrrolidine pentamine scaffold and was selected for further analysis. This library contained 738,192 compounds with functionalities derived from 26 different amino acids (R1, R2 and R3) and 42 different carboxylic acids (R4) in four R–group functionalities. The most active compounds all contained S-phenyl (R1 and R3) and S-hydromethyl (R2) functionalities at three locations and differed at the R4 position. The compound containing 3-phenylbutyl at R4 (compound 206) was a robust enzymatic inhibitor in vitro, in combination with amikacin it potentiated the inhibition of growth of three resistant bacteria in culture, and it improved survival when used as treatment of Galleria mellonella infected with aac(6')-Ib-harboring Klebsiella pneumoniae and Acinetobacter baumannii strains.     

Investigation of DNA damage response and apoptotic gene methylation pattern in sporadic breast tumors using high throughput quantitative DNA methylation analysis technology

Background-  

Sporadic breast cancer like many other cancers is proposed to be a manifestation of abnormal genetic and epigenetic changes. For the past decade our laboratory has identified genes involved in DNA damage response (DDR), apoptosis and immunesurvelliance pathways to influence sporadic breast cancer risk in north Indian population. Further to enhance our knowledge at the epigenetic level, we performed DNA methylation study involving 17 gene promoter regions belonging to DNA damage response (DDR) and death receptor apoptotic pathway in 162 paired normal and cancerous breast tissues from 81 sporadic breast cancer patients, using a high throughput quantitative DNA methylation analysis technology.     

Diagnostic Performance of Serum Human Epididymis Protein 4 (HE4) for Prediction of Malignancy in Ovarian Masses

Background: Early diagnosis of ovarian cancer is essential for long term disease control and mortality reduction.This has been achieved using tumor markers like cancer antigen 125 (CA-125) which is elevated in malignant as wellas non-malignant conditions. This dilemma led to efforts towards development of newer markers like serum humanepididymis secretory protein E4 (HE4). Present study aimed to evaluate role of HE4 in diagnosing ovarian cancersand comparing it with CA-125. Methods: Serum samples from 67 patients with ovarian cancer, 42 with benignovarian masses and 26 healthy controls were collected preoperatively and tested for serum HE4 levels and CA-125levels. Diagnostic performance of both tumor markers (HE4/CA-125) to diagnose malignancy in ovarian masses wascalculated and compared to each other. Results: Mean CA-125 and HE4 levels were significantly higher in patientswith ovarian cancer than in those with benign disease (p<0.001) or healthy controls (p< 0.001). Serum HE4 levelssignificantly increased in epithelial ovarian cancers when compared to non-epithelial ovarian cancers (p<0.01). Usingbenign control as comparison, receiver operating characteristic curve (ROC) was generated to predict a cut-off valuefor diagnosing malignancy for serum HE4 and CA-125. Compared to CA-125, HE4 had a similar sensitivity (83.6%vs. 85.10%) and higher specificity (100% vs. 90.48%); combination of serum HE4 and CA-125 improved the sensitivityto detect ovarian cancer to 92.54%. Sensitivity of HE4 to detect early stage ovarian cancer was superior to CA-125(92.61% vs. 63.41%). Conclusion: Serum HE4, a novel tumor marker, discriminated epithelial ovarian cancer frombenign ovarian masses. HE4 levels were related to the stage and histological types with the lowest levels in mucinousepithelial ovarian cancer and non-epithelial malignancy. Measuring serum HE4 levels alongwith CA-125 may providehigher accuracy for detecting epithelial ovarian cancer particularly in the early stages.