Investigation of protein quaternary structure via stoichiometry and symmetry information.

The Protein Data Bank (PDB) is the single worldwide archive of experimentally-determined three-dimensional (3D) structures of proteins and nucleic acids. As of January 2017, the PDB housed more than 125,000 structures and was growing by more than 11,000 structures annually. Since the 3D structure of a protein is vital to understand the mechanisms of biological processes, diseases, and drug design, correct oligomeric assembly information is of critical importance. Unfortunately, the biologically relevant oligomeric form of a 3D structure is not directly obtainable by X-ray crystallography, whilst in solution methods (NMR or single particle EM) it is known from the experiment. Instead, this information may be provided by the PDB Depositor as metadata coming from additional experiments, be inferred by sequence-sequence comparisons with similar proteins of known oligomeric state, or predicted using software, such as PISA (Proteins, Interfaces, Structures and Assemblies) or EPPIC (Evolutionary Protein Protein Interface Classifier). Despite significant efforts by professional PDB Biocurators during data deposition, there remain a number of structures in the archive with incorrect quaternary structure descriptions (or annotations). Further investigation is, therefore, needed to evaluate the correctness of quaternary structure annotations. In this study, we aim to identify the most probable oligomeric states for proteins represented in the PDB. Our approach evaluated the performance of four independent prediction methods, including text mining of primary publications, inference from homologous protein structures, and two computational methods (PISA and EPPIC). Aggregating predictions to give consensus results outperformed all four of the independent prediction methods, yielding 83% correct, 9% wrong, and 8% inconclusive predictions, when tested with a well-curated benchmark dataset. We have developed a freely-available web-based tool to make this approach accessible to researchers and PDB Biocurators (http://quatstruct.rcsb.org/).

Fracture resistance of tooth fragment reattachment: effects of different preparation techniques and adhesive materials.

The purpose of this study was to evaluate and compare the bond strengths of experimentally fractured human tooth fragments reattached with different adhesive materials and retentive techniques in vitro. Uncomplicated crown fractures were obtained on intact human mandibular permanent incisors by applying perpendicular load to the buccal aspect of tooth crowns. Fractured teeth were randomly assigned into one of three reattachment protocols: (i) Simple reattachment, (ii) Overcontour preparation, and (iii) Internal dentin groove. The first and second groups were divided into 10 subgroups, and the third group into five subgroups (n = 10 per group) with respect to five different adhesive systems (Prime&Bond NT, Adper Single Bond II, Adper Prompt L-Pop, Clearfil S(3) Bond, G Bond) used with or without a hybrid resin composite (Z250). Restored teeth were subjected to thermal cycling, and subsequently to the same loading protocol used for fracturing intact teeth. Fracture strength after reattachment procedures was recorded as a percentage of the original fracture strength. Both type of adhesive material and placement of an intermediate layer of resin composite affected the fracture resistance (P < 0.05). The highest fracture strength recovery was obtained using the internal dentin groove technique (54 +/- 0.58%, P < 0.05), followed by the overcontour and simple reattachment protocols (49 +/- 0.58% and 32 +/- 0.82%, respectively, P < 0.05). Ultramorphological evaluation of bonded specimens revealed voids and microcracks along the adhesive interface, which might contribute to postadhesive failure.

Hip fractures in a developing country: osteoporosis frequency, predisposing factors and treatment costs.

Hip fractures are a burden to both society and the individual. The aim of this study was to describe the frequency of osteoporosis and the in-hospital treatment costs of patients with hip fractures admitted to Hacettepe University Faculty of Medicine Hospital. Patients with a hip fracture who were admitted to the Orthopedics and Traumatology wards between April 2003 and December 2006 were interviewed and 50 of them were enrolled prospectively in the study protocol. Patient characteristics, predisposing factors for fractures and hospital costs were recorded as well as laboratory test results and bone mineral density measurements. The mean age was 74.2 years and 72% of the patients were women. Sixty-four percent of them presented with an intertrochanteric fracture. The patient population was significantly debilitated with a high prevalence of vitamin D insufficiency and secondary hyperparathyroidism. No association was shown with T scores and dietary habits and lifestyle characteristics of patients. In 34% of patients in whom measurements were available, no osteoporosis could be documented. The mean hospital expenditure was $5983. Factors affecting the total cost were age and functional status of the patient and the duration of hospital stay, independent of the type of fracture and surgical procedure used.

Measurement of depth of Intacs implanted via femtosecond laser using Pentacam.

PURPOSE: To measure the depth of intracorneal ring segments (Intacs, Addition Technology Inc) implanted via femtosecond laser by Pentacam rotating Scheimpflug camera (Oculus Optikgeräte GmbH) and to determine the change in depth at 1-year follow-up. METHODS: Thirty-two eyes of 23 keratoconic patients receiving Intacs intrastromal corneal ring segments implanted by femtosecond laser were included in the study. The depth of intracorneal channel and Intacs segments were measured for 7 predetermined points at 1 week and 1 year postoperatively using Scheimpflug images. RESULTS: Mean achieved intrastromal channel depth exceeded the intended parameter by 6.5 microm to 69.0 microm. The standard deviation varied between +/- 13.5 microm and +/- 44.2 microm. The segment depth decreased at the end of the first postoperative year in all measured points, and the change was statistically significant at the superior, inferior, and temporal sides of the Intacs. The degree of change was not correlated with size of the Intacs, preoperative central corneal thickness, and mean keratometric values. CONCLUSIONS: Pentacam provided imaging of the Intacs segments and measurement of their depth, enabling evaluation of the changes in depth at 1-year follow-up. The Intacs segments tended to shallow over time, which may be a factor for depth-related complications.

Expression of vascular endothelial growth factor-A, matrix metalloproteinase-9, and extravascular matrix patterns and their correlations with clinicopathologic parameters in posterior uveal melanomas.

PURPOSE: To assess extravascular matrix patterns (EMP) and expression of vascular endothelial growth factor-A (VEGF-A) and matrix metalloproteinase-9 (MMP-9) in posterior uveal melanomas and their correlations with histopathologic parameters and metastasis. METHODS: This study was conducted on 100 consecutive eyes enucleated for posterior uveal melanomas. All tumors were examined by immunohistochemical techniques for VEGF-A and MMP-9 expression, and the presence of EMPs was assessed on routine paraffin sections stained with reticulin. Cell type, tumor localization, degree of pigmentation, necrosis, mitotic index, lymphocytic infiltration, and scleral and optic nerve invasion were analyzed by using light microscopy. No eyes had received prior treatment such as radiotherapy or transpupillary thermotherapy. RESULTS: Identified histopathologically, cell types were spindle cells in 60% of the cases, mixed cells in 14%, and epithelioid cells in 26% of tumors. Positive reaction for VEGF-A and MMP-9 was present in 84% and 72% of the tumors, respectively. Microvascular loops and/or networks were seen in 34% of the tumors, with the remaining 16% of the tumors displaying an arc pattern, 21% displaying a parallel pattern, and 29% displaying the normal pattern. The relationships between VEGF-A and MMP-9 expression and necrosis, the degree of lymphocyte infiltration, mitotic rate, and the formation of loop and network patterns were found to be statistically significant (P < 0.05). Metastatic disease developed in 14 patients during follow up. CONCLUSIONS: The incidence of metastatic melanoma increased with the increasing expression of VEGF-A and MMP-9. Our data suggest that increasing VEGF-A and MMP-9 expression and the EMP can be used as independent prognostic factors in the management of posterior uveal melanoma following enucleation.

Demographic, socioeconomic and educational aspects of obesity in an adult population.

Obesity as a disease is a yet-unidentified sum of genetic and environmental factors. Risky eating behavior and lifestyle may bring the disease. The aim of the study was to find out risk factors for obesity factors influencing definition of obesity. Participants (n = 1500) who filled out a questionnaire about eating habits are grouped according to their body mass indices as normal weight, overweight and obese (n = 500 in each group). According to our results, the prevalence of having obese first-degree relatives is significantly higher in obese individuals (p < 0.001). Sixty-two of normal weighing subjects were university graduates, whereas this ratio was only 31% in the obese group (p < 0.001). Incidence of obesity was higher in married participants when compared to the single or divorced/widowed persons (p < 0.001). Multinomial logistic regression analysis gave the following results: risk of obesity was 57% less in participants lacking a family history of obesity when compared to the ones with a positive family history (p = 0.005). Being married increases the risk of obesity 2.5 times; being a primary school graduate increases the risk about 1.5 times. Lower educational level, unemployment and lack of counseling seem to be risk factors associated with obesity. Diverging patterns of sociodemographic features, lifestyles and perception were evident even between overweight and obese populations.

Is elevated level of soluble endothelial protein C receptor a new risk factor for retinal vein occlusion?

BACKGROUND: To evaluate the systemic and thrombophilic risk factors for retinal vein occlusion (RVO) and to determine whether the elevated level of soluble endothelial protein C receptor (sEPCR) is a risk factor for thrombosis. METHODS: In this case-control study, 56 patients with central RVO (CRVO), 26 patients with branch RVO (BRVO) and 78 healthy sex- and age-matched subjects were enrolled. Following ophthalmological examination, venous blood was analysed for glucose, lipid profile, lipoprotein (a), homocysteine, activated partial thromboplastin time, fibrinogen, factor VIII, protein C activity, protein S activity, activated protein C resistance, antithrombin III activity, lupus anticoagulant, anti-cardiolipin antibody, anti-phospholipid antibody, sEPCR, factor V Leiden mutation and prothrombin G20210A mutation. RESULTS: Apart from hypertension, glaucoma, lipoprotein (a), homocysteine and factor VIII, elevated levels of sEPCR were found to be a risk factor for CRVO (odds ratio, 1.02; 95% confidence interval, 1.007-1.028; P = 0.001). Patients with CRVO had significantly higher levels of sEPCR than those with BRVO and controls (respectively, 160.1 +/- 83.8, 116.8 +/- 65.2 and 111.3 +/- 60.5; P = 0.005). Moreover, 39% of patients with CRVO had levels of sEPCR more than 200 ng/mL, and only 5% of controls and 11% of patients with BRVO had similar high levels. CONCLUSIONS: Besides known classical risk factors, elevated levels of sEPCR seem to be an important candidate risk factor for especially CRVO.

Diurnal variation of intraocular pressure and its correlation with retinal nerve fiber analysis in Turkish patients with exfoliation syndrome.

PURPOSE: The purpose was to evaluate the diurnal variation (DV) of intraocular pressure (IOP) in patients with exfoliation syndrome (XS), to measure retinal nerve fiber layer (RNFL) thickness by using scanning laser polarimetry, and to compare these measurements with those of normal subjects. METHODS: Forty-five subjects with XS and 40 healthy, age/sex matched subjects were recruited into the study. A detailed ophthalmologic examination was performed. IOP measurements were obtained at 08:00 am, 12:00 pm, 03:00 pm, and 06:00 pm. The XS group was further divided into DV > or = 5 mmHg and DV < 5 mmHg groups and also according to the existence of IOP fluctuation. The IOP measurements and RNFL thickness measurements were compared between the groups. RESULTS: The mean IOP value was found to be highest in the morning both in the XS and control groups. IOP showed a gradual decrease from 8.00 am to 6.00 pm in the control group, whereas a second peak at 03:00 pm was observed in the XS group. There was a fluctuation in 53.3% of the XS group, while none of the healthy subjects showed fluctuation. Superior and inferior ratios were statistically lower in XS patients than those in control subjects (p<0.05). Moreover, in patients with XS showing a DV > or = 5 mmHg and/or a fluctuation, the superior ratio, inferior ratio, the number, superior average and superior integral were significantly different (all p values <0.05) from those of control subjects. CONCLUSIONS: As the XS patients with high diurnal IOP variation and fluctuating pattern of IOP had lower RNFL thickness measurements, it is crucial to follow up these patients by performing scanning laser polarimetry in order to discover any possible glaucomatous damage at an earlier stage than with the use of conventional visual field analysis.

Relationship between physical, environmental and sociodemographic factors and school performance in primary schoolchildren.

Poor primary school performance is a risk factor for low high-school and university graduation, as well as poverty in later life. In this case-control study, the relation between a variety of physical, environmental and sociodemographic factors, and primary school performance was investigated. Grade one students with good and poor school achievement, from different socioeconomic levels were studied. A questionnaire about the sociodemographic characteristics and child's medical history, together with a Child Behavior Checklist, was filled out by parents. Physical examination, visual and hearing screening were performed. Blood count and blood lead levels were determined. Wechsler Intelligence Scale for Children-Revised (WISC-R) was performed to determine the IQ. A total of 177 students participated in the study. Stepwise logistic regression revealed an independent positive relation between duration of study (OR, 2.69; Cl, 1.19-6.05; p=0.016), maternal education (OR, 1.47; Cl, 1.14-1.87; p=0.002), full scale score of WISC-R (OR, 1.08; Cl, 1.03-1.3; p=0.002) and school performance. Multinomial logistic regression revealed that the risk of having a below average full scale WISC-R score was higher among children having a hearing loss, uncorrected vision loss, heating house with stove, cigarette smoking of both parents, and low paternal education (less than 8 years). The chance of having an above average full scale WISC-R score was lower among children whose either parent smoked cigarettes, height-for-age percentile was below 10, and maternal education was less than 8 years. Policies for increasing male and female education, growth monitoring, appropriate feeding (breastfeeding and weaning), well-baby and child followup and clean environment (indoor and outdoor) will not only promote the physical health but also promote the cognitive development of the new generations.

Evaluation of kidney damage in patients with acute lymphoblastic leukemia in long-term follow-up: value of renal scan.

In order to evaluate potential long-term kidney damage of childhood leukemia and risk factors affecting renal damage, we studied 116 children treated for acute lymphoblastic leukemia (ALL) using the St. Jude Total XI and XIII protocols in 1991-1998. The median follow-up period after the completion of treatment was 35 months. The following parameters were examined: urinalysis, urinary creatinine (Cr), calcium (Ca), phosphorus, beta2-microglobulin, glomerular filtration rate (GFR), tubular phosphorus reabsorption (TPR), and renal function tests. Radiological evaluation included renal ultrasonography (US), and renal scans with DMSA or MAG-3 were performed. Blood chemistry and renal US patients were normal in all patients except two. GFR, TPR, urinary Ca/Cr, beta2-microglobulin, and renal scan were abnormal in 19.0%, 16.4%, 13.8%, 6.0%, and 40.5% of patients, respectively. The abnormality rate in GFR was significantly higher in patients <2 years of age. TPR abnormality was found to be significantly higher in patients who did not have G-CSF. An abnormal renal scan was associated with Hb < 10 g/dL, kidney infiltration, or hypertension at presentation and also occurred patients who underwent methotrexate treatment with frequent intervals during the follow-up period. Patients should be followed-up after cessation of therapy with the conventional tests mentioned above. In case of any abnormality, further detailed tests should be performed; renal scan seems to be more predictive for renal damage.