Search

The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study of autopsy findings in subjects 15 to 34 years of age developed a risk score using coronary heart disease risk factors (gender, age, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia) to estimate the probability of advanced atherosclerotic lesions in the coronary arteries. The Cardiovascular Risk in Young Finns Study measured coronary heart disease risk factors in a population-based cohort in 1986 and 2001 and measured carotid artery intima-media thickness (IMT) with ultrasonography in 2001. We computed the PDAY risk score from risk factors measured in 1,279 subjects who were 12 to 24 years of age in 1986 and 27 to 39 years of age in 2001. The PDAY risk score early in life (i.e., 1986) and the change in risk score in the following 15 years (i.e., 1986 through 2001) were independent predictors of carotid artery intima-media thickness; the multiplicative effect of 1 point in the 1986 risk score was 1.008 (95% confidence interval 1.005 to 1.012) and the multiplicative effect of a 1-point increase between the 1986 and 2001 risk scores was 1.003 (95% confidence interval 1.001 to 1.006; multiplicative effect of 0.997 for a 1-point decrease). In conclusion, the change in risk score over time (decrease or increase) during adolescence and young adulthood, as well as the risk score early in life, are important predictors of atherosclerosis. [ABSTRACT FROM AUTHOR]

Context: Atherosclerosis, the underlying cause of coronary heart disease, has been shown to be present even in young adults.Objective: To document the extent and severity of atherosclerosis in adolescents and young adults in the United States.Design and Setting: The Pathobiological Determinants of Atherosclerosis in Youth Study, a multi-institutional autopsy study conducted in US medical centers. Subjects A total of 2876 study subjects, between 15 and 34 years old, black and white, men and women, who died of external causes and underwent autopsy between June 1, 1987, and August 31, 1994.Main Outcome Measures: Extent, prevalence, and topography of atherosclerotic lesions.Results: Intimal lesions appeared in all the aortas and more than half of the right coronary arteries of the youngest age group (15-19 years) and increased in prevalence and extent with age through the oldest age group (30-34 years). Fatty streaks were more extensive in black subjects than in white subjects, but raised lesions did not differ between blacks and whites. Raised lesions in the aortas of women and men were similar, but raised lesions in the right coronary arteries of women were less than those of men. The prevalence of total lesions was lower in the right coronary artery than in the aorta, but the proportion of raised lesions among total lesions was higher in the right coronary artery than in the aorta.Conclusions: Atherosclerosis begins in youth. Fatty streaks and clinically significant raised lesions increase rapidly in prevalence and extent during the 15- to 34-year age span. Primary prevention of atherosclerosis, as contrasted with primary prevention of clinically manifest atherosclerotic disease, must begin in childhood or adolescence. [ABSTRACT FROM AUTHOR]

Background/aims: The effect of pregnancy on gastric emptying has not been established, although the predominant clinical assumption is that gastric emptying is delayed during pregnancy. We hypothesized that the rate of emptying of nutrients during pregnancy is not delayed, but is actually more rapid when compared to the non-pregnant state. The rate of gastric emptying is a major determinant of postprandial glucose elevations., Materials and Methods: 24 female and 4 male Spague-Dawley rats were used. Female rats were randomly divided into two groups: eight rats for the control group and sixteen rats for the pregnant group. Using physiologic, non-traumatic nuclear medicine scintigraphy imaging methodology, the authors studied gastric emptying of a liquid mixed meal in pregnant rats and non-pregnant controls. Body weights, daily food ingestion, and the rate of nutrient gastric emptying were recorded in both groups at pre-pregnancy, early pregnancy, and late pregnancy., Results: The authors found that pregnancy in this rat model is associated with a 37-43% increased rate of nutrient gastric emptying from the stomach in late pregnancy as compared to non-pregnant control rats and pre-pregnancy rats., Conclusion: These findings contradict the current clinical assumption that gastric emptying is delayed in pregnancy. If further studies confirm a more rapid gastric emptying rate during human pregnancy, new therapies aimed at slowing the rate of nutrient absorption should be considered for the prevention and treatment of pregnancy-associated nausea, gestational diabetes, and other insulin-resistant pregnancy-associated states such as pre-eclampsia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To evaluate zirconium implant artifact production in cone beam computed tomography images obtained with different protocols., Study Design: One zirconium implant was inserted in an edentulous mandible. Twenty scans were acquired with a ProMax 3D unit (Planmeca Oy, Helsinki, Finland), with acquisition settings ranging from 70 to 90 peak kilovoltage (kVp) and voxel sizes of 0.32 and 0.16 mm. A metal artifact reduction (MAR) tool was activated in half of the scans. An axial slice through the middle region of the implant was selected for each dataset. Gray values (mean ± standard deviation) were measured in two regions of interest, one close to and the other distant from the implant (control area). The contrast-to-noise ratio was also calculated., Results: Standard deviation decreased with greater kVp and when the MAR tool was used. The contrast-to-noise ratio was significantly higher when the MAR tool was turned off, except for low resolution with kVp values above 80. Selection of the MAR tool and greater kVp resulted in an overall reduction of artifacts in images acquired with low resolution., Conclusions: Although zirconium implants do produce image artifacts in cone-bean computed tomography scans, the setting that best controlled artifact generation by zirconium implants was 90 kVp at low resolution and with the MAR tool turned on., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Hepatocellular carcinoma is increasingly important in the United States as the incidence rate rose over the last 30 years. C3HeB/FeJ mice serve as a unique model to study hepatocellular carcinoma tumorigenesis because they mimic human hepatocellular carcinoma with delayed onset, male gender bias, approximately 50% incidence, and susceptibility to tumorigenesis is mediated through multiple genetic loci. Because a human O(6)-methylguanine-DNA methyltransferase (hMGMT) transgene reduces spontaneous tumorigenesis in this model, we hypothesized that hMGMT would also protect from methylation-induced hepatocarcinogenesis. To test this hypothesis, wild-type and hMGMT transgenic C3HeB/FeJ male mice were treated with two monofunctional alkylating agents: diethylnitrosamine (DEN; 0.025 μmol/g body weight) on day 12 of life with evaluation for glucose-6-phosphatase-deficient (G6PD) foci at 16, 24, and 32 weeks or N-methyl-N-nitrosurea (MNU; 25 mg MNU/kg body weight) once monthly for 7 months starting at 3 months of age with evaluation for liver tumors at 12 to 15 months of age. No difference in abundance or size of G6PD foci was measured with DEN treatment. In contrast, it was unexpectedly found that MNU reduces liver tumor prevalence in wild-type and hMGMT transgenic mice despite increased tumor prevalence in other tissues. hMGMT and MNU protections were additive, suggesting that MNU protects through a different mechanism, perhaps through the cytotoxic N7-alkylguanine and N3-alkyladenine lesions which have low mutagenic potential compared with O(6)-alkylguanine lesions. Together, these results suggest that targeting the repair of cytotoxic lesions may be a good preventative for patients at high risk of developing hepatocellular carcinoma., (©2015 American Association for Cancer Research.)

Aim: The objective of the study was to compare (i) esthetic, (ii) clinical and (iii) patient-centered outcomes following immediate (Type 1) and early implant placement (Type 2)., Material and Methods: Thirty-eight subjects needing a single extraction (premolar to premolar) were randomly allocated to Type 1 or Type 2 implant placement. Three months following permanent crown insertion, evaluation of (i) esthetic outcomes using soft tissue positions, and the pink and white esthetic scores (PES/WES), (ii) clinical performance using probing pocket depth (PPD), modified plaque index (mPI) and modified sulcus bleeding index (mSBI) around each implant and (iii) patient satisfaction by means of a questionnaire using a visual analogue scale (VAS) was performed., Results: Thirty-two patients completed the 3-month follow-up examination (Type 1, n = 17; Type 2, n = 15) with a 100% implant survival rate. Type 1 implants lost 0.54 ± 0.18 mm of mid-facial soft tissue height, while Type 2 implants lost 0.47 ± 0.31 mm (P > 0.05). The papillae height on the mesial and distal was reduced about 1 mm following both procedures. The PES/WES following Type 1 implant placement amounted to 13.7 ± 0.6 and 12.5 ± 0.7 in the Type 2 group (P > 0.05). PPD, mPI and mSBI were low in both groups (P > 0.05). Patient-centered outcomes failed to demonstrate any statistical difference between the two cohorts., Conclusion: Three months following final crown delivery, there were no significant differences in esthetic, clinical and patient-centered outcomes following Type 1 and Type 2 implant placement. On the short term, one may achieve good optimal esthetic and clinical results irrespective of these two placement protocols. These results need to be confirmed on the long term., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: We explored whether, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary and abdominal risk scores measured at 18 to 30 years of age and changes in these scores would more strongly predict coronary artery calcium (CAC) and abdominal aortic calcium (AAC) assessed 25 years later, than scores measured 25 years later., Methods and Results: In the Coronary Artery Risk Development in Young Adults (CARDIA) study, 3008 participants had measurements of risk score components at 5-year intervals beginning at 18 to 30 years of age. CAC and AAC were assessed at 43 to 55 years of age. Odds ratios (ORs) for the presence and extent of CAC/AAC per/point higher score and c-statistics for predicting CAC/AAC were calculated. The prevalence of CAC was 28% and AAC was 53%. For each 1 point higher PDAY score, the odds of CAC were higher using baseline scores than year 25 scores (OR, 1.29; 95% confidence interval [CI], 1.25-1.33 versus OR, 1.12; 95% CI, 1.11-1.14). For AAC, ORs at years 0 and 25 were similar (OR, 1.29; 95% CI, 1.24-1.34 versus OR, 1.22; 95% CI, 1.19-1.26). C-statistic for CAC prediction was higher at year 0 than year 25 (0.731 versus 0.705) but similar at years 0 and 25 for AAC (0.665 versus 0.670). ORs for CAC were highest at baseline, and, for AAC, ORs were highest at year 10. Including change in PDAY scores with baseline scores improved prediction., Conclusions: Atherosclerosis risk and change in risk assessed in young adulthood years before subclinical atherosclerosis imaging provide strong prediction of future subclinical atherosclerosis. CAC and AAC reflect chronic risk exposure in addition to risk measured at the time of study., (© 2015 American Heart Association, Inc.)

Increased paternal age is associated with a greater risk of producing children with genetic disorders originating from de novo germline mutations. Mice mimic the human condition by displaying an age-associated increase in spontaneous mutant frequency in spermatogenic cells. The observed increase in mutant frequency appears to be associated with a decrease in the DNA repair protein, AP endonuclease 1 (APEX1) and Apex1 heterozygous mice display an accelerated paternal age effect as young adults. In this study, we directly tested if APEX1 over-expression in cell lines and transgenic mice could prevent increases in mutagenesis. Cell lines with ectopic expression of APEX1 had increased APEX1 activity and lower spontaneous and induced mutations in the lacI reporter gene relative to the control. Spermatogenic cells obtained from mice transgenic for human APEX1 displayed increased APEX1 activity, were protected from the age-dependent increase in spontaneous germline mutagenesis, and exhibited increased apoptosis in the spermatogonial cell population. These results directly indicate that increases in APEX1 level confer protection against the murine paternal age effect, thus highlighting the role of APEX1 in preserving reproductive health with increasing age and in protection against genotoxin-induced mutagenesis in somatic cells., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to evaluate and compare the efficacy of cone-beam computed tomography (CBCT) and digital intraoral radiography in diagnosing simulated small external root resorption cavities., Materials and Methods: Cavities were drilled in 159 roots using a small spherical bur at different root levels and on all surfaces. The teeth were imaged both with intraoral digital radiography using image plates and with CBCT. Two sets of intraoral images were acquired per tooth: orthogonal (PA) which was the conventional periapical radiograph and mesioangulated (SET). Four readers were asked to rate their confidence level in detecting and locating the lesions. Receiver operating characteristic (ROC) analysis was performed to assess the accuracy of each modality in detecting the presence of lesions, the affected surface, and the affected level. Analysis of variation was used to compare the results and kappa analysis was used to evaluate interobserver agreement., Results: A significant difference in the area under the ROC curves was found among the three modalities (P=0.0002), with CBCT (0.81) having a significantly higher value than PA (0.71) or SET (0.71). PA was slightly more accurate than SET, but the difference was not statistically significant. CBCT was also superior in locating the affected surface and level., Conclusion: CBCT has already proven its superiority in detecting multiple dental conditions, and this study shows it to likewise be superior in detecting and locating incipient external root resorption.

With the increasing use of digital radiography, the display parameters of the devices used to view radiographs have become important factors in caries detection. Interest in the use of tablet devices for this application has increased due to their availability, portability, and ease of use. However, to be effective in clinical situations, these portable devices must have displays that perform well under multiple lighting conditions and at different angles. The purpose of this study was to assess the utility of the iPad with Retina Display for the detection of Class II caries under common overhead lighting conditions. The device was used in both standing and angled positions by 5 reviewers, and their diagnoses of caries were compared to the diagnoses the same reviewers made using a thin-film transistor flat-panel display (TFT-FPD) in dim lighting conditions. Histological analysis was used as the gold standard to confirm the presence or absence of caries. In a standing position, the tablet device performed as well as the TFT-FPD. When used in the angled position, the tablet performed slightly worse than the TFT-FPD. The findings suggest that if the user can compensate for overhead glare, the tablet device may perform as well as a calibrated, upright display in a dimly lit room.

Creating a learning environment that fosters student acquisition of self-assessment behaviors and skills is critically important in the education and training of health professionals. Self-assessment is a vital component of competent practice and lifelong learning. This article proposes applying a version of confidence scoring of multiple-choice questions as one avenue to address this crucial educational objective for students to be able to recognize and admit what they do not know. The confidence scoring algorithm assigns one point for a correct answer, deducts fractional points for an incorrect answer, but rewards students fractional points for leaving the question unanswered in admission that they are unsure of the correct answer. The magnitude of the reward relative to the deduction is selected such that the expected gain due to random guessing, even after elimination of all but one distractor, is never greater than the reward. Curricular implementation of this confidence scoring algorithm should motivate health professions students to develop self-assessment behaviors and enable them to acquire the skills necessary to critically evaluate the extent of their current knowledge throughout their professional careers. This is a professional development competency that is emphasized in the educational standards of the Commission on Dental Accreditation (CODA).

Background: The authors conducted a prospective cohort study to determine whether poor glycemic control is a contraindication to implant therapy in patients with type 2 diabetes., Methods: The study sample consisted of 117 edentulous patients, each of whom received two mandibular implants, for a total of 234 implants. Implant-retained mandibular overdentures were loaded after a four-month healing period and followed up for an additional one year. The authors assessed implant survival and stability (by means of resonance frequency analysis) relative to glycated hemoglobin A1c (HbA1c) levels, with baseline levels up to 11.1 percent and levels as high as 13.3 percent over one year., Results: Implant survival rates for 110 of 117 patients who were followed up for one year after loading were 99.0 percent, 98.9 percent and 100 percent, respectively, for patients who did not have diabetes (n = 47), those with well-controlled diabetes (n = 44) and those with poorly controlled diabetes (n = 19). The authors considered the seven patients lost to follow-up as having had failed implants; consequently, their conservative estimates of survival rates in the three groups were 93.0 percent, 92.6 percent and 95.0 percent (P = .6510). Two implants failed at four weeks, one in the nondiabetes group and the other in the well-controlled diabetes group. Delays in implant stabilization were related directly to poor glycemic control., Conclusions: The results of this study indicate that elevated HbA1c levels in patients with type 2 diabetes were not associated with altered implant survival one year after loading. However, alterations in early bone healing and implant stability were associated with hyperglycemia.

Children are vulnerable to environmental mutagens, and the developing germline could also be affected. However, little is known about whether exposure to environmental mutagens in childhood will result in increased germline mutations in subsequent adult life. In the present study, male transgenic lacI mice at different ages (7, 25 and 60 days old) were treated with a known environmental mutagen (benzo[a]pyrene, B[a]P) at different doses (0, 50, 200 or 300 mg/kg body weight). Mutant frequency was then determined in a meiotic cell type (pachytene spermatocyte), a post-meiotic cell type (round spermatid) and epididymal spermatozoa after at least one cycle of spermatogenesis. Our results show that 1) mice treated with B[a]P at 7 or 25 days old, both being pre-adult ages, had significantly increased mutant frequencies in all spermatogenic cell types tested when they were 60 days old; 2) spermatogenic cells from mice treated before puberty were more susceptible to B[a]P-associated mutagenesis compared to adult mice; and 3) unexpectedly, epididymal spermatozoa had the highest mutant frequency among the spermatogenic cell types tested. These data show that pre-adult exposure to B[a]P increases the male germline mutant frequency in young adulthood. The data demonstrate that exposure to environmental genotoxins at different life phases (e.g., pre-adult and adult) can have differential effects on reproductive health.

How many incorrect response options (known as distractors) to use in multiple-choice questions has been the source of considerable debate in the assessment literature, especially relative to influence on the likelihood of students' guessing the correct answer. This study compared distractor use by second-year dental students in three successive oral and maxillofacial pathology classes that had three different examination question formats and scoring resulting in different levels of academic performance. One class was given all multiple-choice questions; the two other were given half multiple-choice questions, with and without formula scoring, and half un-cued short-answer questions. Use by at least 1 percent of the students was found to better identify functioning distractors than higher cutoffs. The average number of functioning distractors differed among the three classes and did not always correspond to differences in class scores. Increased numbers of functioning distractors were associated with higher question discrimination and greater question difficulty. Fewer functioning distractors fostered more effective student guessing and overestimation of academic achievement. Appropriate identification of functioning distractors is essential for improving examination quality and better estimating actual student knowledge through retrospective use of formula scoring, where the amount subtracted for incorrect answers is based on the harmonic mean number of functioning distractors.

Objectives: The objective of this study was to compare the accuracy of root fracture detection in endodontically treated teeth using scans acquired with a 180° rotation motion compared with a 360° after which the patient exposure and number of basis images are doubled., Methods: Sixty-six roots were collected and decoronated. All were treated endodontically. One-half of the roots were fractured, resulting in 2 root fragments which were then glued together. The roots were placed randomly in 8 prepared beef rib fragments. Five reviewers independently reviewed the scans twice, at different times., Results: The specificity of the 360° scan was significantly higher than the 180° scan; doubling the basis images leads to a significant decrease in false-positive rates. Accuracy and sensitivity were not significantly different., Conclusions: Only the specificity is improved by the increased rotation and doubling of images. The accuracy and sensitivity are not improved., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The prevalence of hepatocellular carcinoma (HCC) was diminished from 60% to 18% at 15 months of age in C3HeB/FeJ male transgenic mice expressing hMGMT in our previous studies. To directly test if the methyltransferase activity is required for diminished tumor prevalence, two separate lines of transgenic mice bearing an enzymatically inactive form of hMGMT were used. In these lines, cysteine 145 was substituted with alanine (C145A). Expression of the hMGMT C145A transgene in liver was demonstrated by Northern blots and Western blots. Immunohistochemistry revealed predominantly nuclear localization of the hMGMT C145A protein. hMGMT C145A transgenic mice were crossed with lacI transgenic mice to assess mutant frequencies in the presence of the mutant protein. Mutant frequencies were similar among livers of lacI × hMGMT C145A bi-transgenic mice and lacI × wild-type (WT) mice. DNA sequence analysis of recovered lacI mutants revealed similar mutation spectra for hMGMT C145A and WT mice. The prevalence of HCC was also similar for the two tested lines of hMGMT C145A mice, 45% and 48% prevalence with median tumor sizes of 11 and 8 mm, and WT mice, 40% prevalence and median tumor size of 10 mm. These results provide evidence that residue C145 in hMGMT is required to reduce the prevalence of HCC in C3HeB/FeJ mice transgenic for hMGMT., (Copyright © 2011 Wiley Periodicals, Inc.)

Genetically based diseases constitute a major human health burden, and de novo germline mutations represent a source of heritable genetic alterations that can cause such disorders in offspring. The availability of transgenic rodent systems with recoverable, mutation reporter genes has been used to assess the occurrence of spontaneous point mutations in germline cells. Previous studies using the lacI mutation reporter transgenic mouse system showed that the frequency of spontaneous mutations is significantly lower in advanced male germ cells than in somatic cell types from the same individuals. Here we used this same mutation reporter transgene system to show that female germ cells also display a mutation frequency that is lower than that in corresponding somatic cells and similar to that seen in male germ cells, indicating this is a common feature of germ cells in both sexes. In addition, we showed that statistically significant differences in mutation frequencies are evident between germ cells and somatic cells in both sexes as early as mid-fetal stages in the mouse. Finally, a comparison of the mutation frequency in a general population of early type A spermatogonia with that in a population enriched for Thy-1-positive spermatogonia suggests there is heterogeneity among the early spermatogonial population such that a subset of these cells are predestined to form true spermatogonial stem cells. Taken together, these results support the disposable soma theory, which posits that genetic integrity is normally maintained more stringently in the germ line than in the soma and suggests that this is achieved by minimizing the initial occurrence of mutations in early germline cells and their subsequent gametogenic progeny relative to that in somatic cells.

Objectives: Two-dimensional intraoral radiography is the most common tool for diagnosing root fractures (RFs). Cone beam CT (CBCT) is widely used to depict RFs in endodontically treated teeth. Beam hardening and other artefacts caused by gutta percha may result in an incorrect diagnosis when using CBCT only. A comparison of two CBCT machines with photostimulated phosphor (PSP) plate images enhanced with the equalization tool was carried out to detect RFs in endodontically treated teeth., Methods: 66 roots were collected, decoronated and treated endodontically using the same technique with gutta percha. 33 of these roots were randomly selected and fractured; the 2 root fragments were glued together with 1 layer of methyl methacrylate and placed randomly in 8 prepared beef rib fragments. Large fields of view (FOVs) were acquired with one CBCT unit and small FOVs with the second CBCT unit. Periapical radiographs (using intraoral PSP plates) were also acquired. A contrast enhancement tool was used when evaluating the PSP plate images., Results: Small FOV images had significantly higher accuracy (area under the receiver operating characteristic curve) and sensitivity in detecting RFs than PSP plates and large FOV images. The specificity of the enhanced PSP images was higher than, although not significantly higher than, the small FOV images and was significantly higher than the large FOV images., Conclusions: CBCT small FOVs should be acquired for depicting RFs of endodontically treated teeth. Images obtained using PSP plates had the lowest rate of false-positive results and their use can save the patient a radiation dose.

Objectives: The objectives were to determine whether the images obtained from different cone-beam computerized tomography (CBCT) field of view (FOV) sizes with varying scan time and kilovolt peak using the Picasso Master 3D machine (Vatech, Hwasung, South Korea) differ in contrast-to-noise ratio (CNR)., Study Design: A phantom was used. Scans were acquired using the same voxel size, 2 scan times (15 and 24 seconds) for 3 different FOV sizes and 5 different kilovolt peaks. The contrast and CNR were calculated for each FOV., Results: The CNRs were similar for the 2 scan times for all 3 FOV sizes. The CNR was lower in the 20 × 19 cm FOV compared with the other 2 FOVs for both scan times., Conclusions: The CNR does not vary significantly with increasing scan times for all FOV sizes. Smaller FOVs result in enhanced CNR and contrast., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Each of three cone beam computed tomography (CBCT) machines offer a small field of view (FOV); Promax, Accuitomo 3D, and Kodak 9000. The objectives were to determine, when using a small FOV, the difference in contrast-to-noise ratios (CNR) of images obtained from different machines and different scan settings within each machine. A phantom made of a dry mandible with an epoxy resin based substitute (ERBS) block was used. The ERBS block was fixed to the lingual cortex in the posterior left mandible. Water was used to simulate soft tissue. Twenty scans were acquired. CNR was calculated as the difference in density of the ERBS block and a control area divided by the standard deviation of the difference. The CNR obtained from images acquired with the Promax machine (voxel size of 0.2 mm) was higher than the other machines (voxel sizes 0.076, 0.08, or 0.125 mm) when using a small FOV. The Accuitomo 360° scan had higher CNR than the Accuitomo 180° scan due to the doubling of the number of basis images acquired. Smaller voxel size does not necessarily lead to enhanced CNR. Increasing the number of basis images did increase the CNR.

Objectives: An algorithm and software to reduce metal artefact has been developed recently and is available in the Picasso Master 3D® (VATECH, Hwaseong, Republic of Korea), which under visual assessment produces better quality images than were obtainable previously. The objective of this in vitro study was to investigate whether the metal artefact reduction (MAR) algorithm of the Picasso Master 3D machine reduced the incidence of metal artefacts and increased the contrast-to-noise ratio (CNR) while maintaining the same gray value when there was no metallic body present within the scanned volume., Methods: 20 scans with a range of 50-90 kVp were acquired, of which 10 had a metallic bead inserted within a phantom. The images obtained were analysed using public domain software (ImageJ; NIH Image, Bethesda, MD). Area histograms were used to evaluate the mean gray level variation of the epoxy resin-based substitute (ERBS) block and a control area. The CNR was calculated., Results: The MAR algorithm increased the CNR when the metallic bead was present; it enhanced the ERBS gray level independently of the presence of the metallic bead. The image quality also improved as peak tube potential was increased., Conclusion: Improved quality of images and regaining of the control gray values of a phantom were achieved when the MAR algorithm was used in the presence of a metallic bead.

Spontaneous mutant frequency in the male germline increases with age, thereby increasing the risk of siring offspring with genetic disorders. In the present study we investigated the effect of age on ionizing radiation-induced male germline mutagenesis. lacI transgenic mice were treated with ionizing radiation at 4-, 15- and 26-month-old, and mutant frequencies were determined for pachytene spermatocytes and round spermatids at 15 days or 49 days after ionizing radiation treatment. Cells collected 15 days after treatment were derivatives of irradiated differentiating spermatogenic cells while cells collected 49 days later were derivatives of spermatogonial stem cells. The results showed that (1) spontaneous mutant frequency increased in spermatogenic cells recovered from nonirradiated old mice (26-months-old), particularly in the round spermatids; (2) mutant frequencies were significantly increased in round spermatids obtained from middle-aged mice (15-months-old) and old age mice (26-months-old) at 15 and 49 days after irradiation compared to the sham-treated old mice; and (3) pachytene spermatocytes obtained from 15- or 26-month-old mice displayed a significantly increased mutant frequency at 15 days post irradiation. This study indicates that age modulates the mutagenic response to ionizing radiation in the male germline., (Published by Elsevier B.V.)

Background: Metal in a patient's mouth has been shown to cause artefacts that can interfere with the diagnostic quality of cone beam CT. Recently, a manufacturer has made an algorithm and software available which reduces metal streak artefact (Picasso Master 3D® machine; Vatech, Hwaseong, Republic of Korea)., Objectives: The purpose of this investigation was to determine whether or not the metal artefact reduction algorithm was effective and enhanced the contrast-to-noise ratio., Methods: A phantom was constructed incorporating three metallic beads and three epoxy resin-based bone substitutes to simulate bone next to metal. The phantom was placed in the centre of the field of view and at the periphery. 10 data sets were acquired at 50-90 kVp. The images obtained were analysed using a public domain software ImageJ (NIH Image, Bethesda, MD). Profile lines were used to evaluate grey level changes and area histograms were used to evaluate contrast. The contrast-to-noise ratio was calculated., Results: The metal artefact reduction option reduced grey value variation and increased the contrast-to-noise ratio. The grey value varied least when the phantom was in the middle of the volume and the metal artefact reduction was activated. The image quality improved as the peak kilovoltage increased., Conclusion: Better images of a phantom were obtained when the metal artefact reduction algorithm was used.

The prevalence of spontaneous mutations increases with age in the male germline; consequently, older men have an increased risk of siring children with genetic disease due to de novo mutations. The lacI transgenic mouse can be used to study paternal age effects, and in this system, the prevalence of de novo mutations increases in the male germline at old ages. Mutagenesis is linked with DNA repair capacity, and base excision repair (BER), which can ameliorate spontaneous DNA damage, decreases in nuclear extracts of spermatogenic cells from old mice. Mice heterozygous for a null allele of the Apex1 gene, which encodes apurinic/apyrimidinic endonuclease I (APEN), an essential BER enzyme, display an accelerated increase in spontaneous germline mutagenesis early in life. Here, the consequences of lifelong reduction of APEN on genetic instability in the male germline were examined, for the first time, at middle and old ages. Mutant frequency increased earlier in spermatogenic cells from Apex1(+/-) mice (by 6 months of age). Nuclear DNA damage increased with age in the spermatogenic lineage for both wild-type and Apex1(+/-) mice. By old age, mutant frequencies were similar for wild-type and APEN-deficient mice. Mitochondrial genome repair also depends on APEN, and novel analysis of mitochondrial DNA (mtDNA) damage revealed an increase in the Apex1(+/-) spermatogenic cells by middle age. Thus, Apex1 heterozygosity results in accelerated damage to mtDNA and spontaneous mutagenesis, consistent with an essential role for APEN in maintaining nuclear and mtDNA integrity in spermatogenic cells throughout life., (Published 2011 Wiley Periodicals, Inc. This article is a U.S. Government work and is in the public domain in the USA.)

Interactions between genes and environment play a critical role in the pathogenesis of type 2 diabetes. Low birth weight, due to genetic and environmental variables affecting fetal growth, is associated with increased susceptibility to the development of type 2 diabetes and metabolic disorders in adulthood. Clinical studies have shown that polymorphisms in the Insulin-like growth factor 1 (IGF-1) gene or heterozygous mutations in IGF-1 and IGF-1 receptor (IGF-1R) genes, resulting in reduced IGF-1 action, are associated with low birth weight and post-natal growth. Mice lacking one of the IGF-1R alleles (Igf1r(+/-)) exhibit a 10% reduction in post-natal growth, and develop glucose intolerance (males) and insulin resistance (males and females) as they age. To investigate whether adverse environmental factors could accelerate the onset of the metabolic syndrome, we conducted a short duration intervention of high fat diet (HFD) feeding in male and female Igf1r(+/-) and wild-type (WT) control mice. The HFD resulted in insulin resistance, hyperglycemia, and impaired glucose tolerance in males of both genotypes whereas in females exacerbated diabetes was observed only in the Igf1r(+/-) genotype, thus suggesting a sexual dimorphism in the influence of obesity on the genetic predisposition to diabetes caused by reduced IGF-1 action., (Copyright © 2011 Elsevier Inc. All rights reserved.)

During the first wave of spermatogenesis, and in response to ionizing radiation, elevated mutant frequencies are reduced to a low level by unidentified mechanisms. Apoptosis is occurring in the same time frame that the mutant frequency declines. We examined the role of apoptosis in regulating mutant frequency during spermatogenesis. Apoptosis and mutant frequencies were determined in spermatogenic cells obtained from Bax-null or Trp53-null mice. The results showed that spermatogenic lineage apoptosis was markedly decreased in Bax-null mice and was accompanied by a significantly increased spontaneous mutant frequency in seminiferous tubule cells compared to that of wild-type mice. Apoptosis profiles in the seminiferous tubules for Trp53-null were similar to control mice. Spontaneous mutant frequencies in pachytene spermatocytes and in round spermatids from Trp53-null mice were not significantly different from those of wild-type mice. However, epididymal spermatozoa from Trp53-null mice displayed a greater spontaneous mutant frequency compared to that from wild-type mice. A greater proportion of spontaneous transversions and a greater proportion of insertions/deletions 15 days after ionizing radiation were observed in Trp53-null mice compared to wild-type mice. Base excision repair activity in mixed germ cell nuclear extracts prepared from Trp53-null mice was significantly lower than that for wild-type controls. These data indicate that BAX-mediated apoptosis plays a significant role in regulating spontaneous mutagenesis in seminiferous tubule cells obtained from neonatal mice, whereas tumor suppressor TRP53 plays a significant role in regulating spontaneous mutagenesis between postmeiotic round spermatid and epididymal spermatozoon stages of spermiogenesis.

Diabetes mellitus is considered a relative contra-indication for implant therapy. However, the effect of glycemic level on implant integration in persons with diabetes remains poorly understood. The hypothesis of this research was that poor glycemic control is directly related to short-term-impairment implant stabilization. This prospective clinical study evaluated 10 non-diabetic individuals (12 implants) and 20 persons with type 2 diabetes (30 implants). Glycated hemoglobin (HbA1c) levels ranged from 4.7-12.6%. Implant stability was assessed by resonance frequency analysis over 4 months following placement. Minimum stability levels were observed 2-6 weeks following placement for all 42 implants. Persons with HbA1c > or = 8.1% had a greater maximum decrease in stability from baseline and required a longer time for healing, as indicated by return of stability level to baseline. This study demonstrates alterations in implant stability consistent with impaired implant integration for persons with type 2 diabetes mellitus in direct relation to hyperglycemic conditions.

Objective: To examine the associations of the coronary heart disease (CHD) risk factors with lipid composition of arterial tissue in 397 autopsied subjects 15-34 years of age from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study., Methods and Results: We measured esterified cholesterol, free cholesterol, and phospholipid in the left circumflex coronary artery and two segments of the abdominal aorta, one of which is more susceptible to advanced atherosclerosis than the other, and also measured the major CHD risk factors. Non-HDL cholesterol concentration was positively associated, and HDL cholesterol concentration was negatively associated, with tissue lipids in the left circumflex coronary artery and the abdominal aorta. Hypertension was positively associated with tissue lipids in both arteries. Hyperglycemia was associated with tissue lipids in the left circumflex coronary artery and smoking with lipids in the abdominal aorta. PDAY risk scores summarize the effects of the CHD risk factors on advanced atherosclerosis. These risk scores, computed from the mutable risk factors, were associated with tissue lipids in the left circumflex coronary artery and both segments of the abdominal aorta., Conclusions: The CHD risk factors are associated with lipids in arterial tissue just as they are associated with gross and microscopic lesions. These results support the proposal that early control of risk factors is likely to prevent or delay progression of atherosclerosis and prevent or delay the onset of CHD.

Cloning by somatic cell nuclear transfer (SCNT) circumvents processes that normally function during gametogenesis to prepare the gamete genomes to support development of new progeny following fertilization. One such process is enhanced maintenance of genetic integrity in germ cells, such that germ cells typically carry fewer spontaneously acquired mutations than somatic cells in the same individual. Thus, embryos produced from somatic cells by SCNT could directly inherit more mutations than naturally conceived embryos. Alternatively, they could inherit epigenetic programming that predisposes more rapid accumulation of de novo mutations during development. We used a transgenic mouse system to test these possibilities by producing cloned midgestation mouse fetuses from three different donor somatic cell types carrying significantly different initial frequencies of spontaneous mutations. We found that on an individual locus basis, mutations acquired spontaneously in a population of donor somatic cells are not likely to be propagated to cloned embryos by SCNT. In addition, we found that the rate of accumulation of spontaneous mutations was similar in fetuses produced by either natural conception or cloning, indicating that cloned fetuses do not acquire mutations more rapidly than naturally conceived fetuses. These results represent the first direct demonstration that the process of cloning by SCNT does not lead to an increase in the frequency of point mutations. These results also demonstrate that epigenetic mechanisms normally contribute to the regulation of genetic integrity in a tissue-specific manner, and that these mechanisms are subject to reprogramming during cloning.

Atherosclerosis begins in childhood with fatty streaks, which progress seamlessly to fibrous plaques in adulthood. These plaques, in turn, might rupture and cause thrombotic arterial occlusion and ischemic damage to vital organs. The earliest stages and progression of atherosclerosis in youth are influenced by the same major established risk factors for this condition in adults-dyslipidemia, hypertension, smoking, obesity, and diabetes mellitus. Controlling these risk factors at any age is beneficial, but the earlier primary prevention begins, the better the result. As recommended by the American Academy of Pediatrics, pediatricians should support both control and prevention of these risk factors in children via lifestyle modification. Drug treatment can be used to supplement lifestyle modification in the few cases of children with genetic dyslipidemias who do not respond to diet changes. Ultimately, however, effective prevention of adult disease requires a massive cultural change.

Gametes carry the DNA that will direct the development of the next generation. By compromising genetic integrity, DNA damage and mutagenesis threaten the ability of gametes to fulfill their biological function. DNA repair pathways function in germ cells and serve to ameliorate much DNA damage and prevent mutagenesis. High base excision repair (BER) activity is documented for spermatogenic cells. DNA polymerase-beta (POLB) is required for the short-patch BER pathway. Because mice homozygous null for the Polb gene die soon after birth, mice heterozygous for Polb were used to examine the extent to which POLB contributes to maintaining spermatogenic genomic integrity in vivo. POLB protein levels were reduced only in mixed spermatogenic cells. In vitro short-patch BER activity assays revealed that spermatogenic cell nuclear extracts obtained from Polb heterozygous mice had one third the BER activity of age-matched control mice. Polb heterozygosity had no effect on the BER activities of somatic tissues tested. The Polb heterozygous mouse line was crossed with the lacI transgenic Big Blue mouse line to assess mutant frequency. The spontaneous mutant frequency for mixed spermatogenic cells prepared from Polb heterozygous mice was 2-fold greater than that of wild-type controls, but no significant effect was found among the somatic tissues tested. These results demonstrate that normal POLB abundance is necessary for normal BER activity, which is critical in maintaining a low germline mutant frequency. Notably, spermatogenic cells respond differently than somatic cells to Polb haploinsufficiency.

Genetic instability has been implicated as a causal factor in cancer and aging. Caloric restriction (CR) and suppression of the somatotroph axis significantly increase life span in the mouse and reduce multiple symptoms of aging, including cancer. To test if in vivo spontaneous mutation frequency is reduced by such mechanisms, we crossed long-lived Ames dwarf mice with a C57BL/6J line harboring multiple copies of the lacZ mutation reporter gene as part of a plasmid that can be recovered from tissues and organs into Escherichia coli to measure mutant frequencies. Four cohorts were studied: (1) ad lib wild-type; (2) CR wild-type; (3) ad lib dwarf; and (4) CR dwarf. While both CR wild-type and ad lib dwarf mice lived significantly longer than the ad lib wild-type mice, under CR conditions dwarf mice did not live any longer than ad lib wild-type mice. While this may be due to an as yet unknown adverse effect of the C57BL/6J background, it did not prevent an effect on spontaneous mutation frequencies at the lacZ locus, which were assessed in liver, kidney and small intestine of 7- and 15-month-old mice of all four cohorts. A lower mutant frequency in the ad lib dwarf background was observed in liver and kidney at 7 and 15 months of age and in small intestine at 15 months of age as compared to the ad lib wild-type. CR also significantly reduced spontaneous mutant frequency in kidney and small intestine, but not in liver. In a separate cohort of lacZ-C57BL/6J mice CR was also found to significantly reduce spontaneous mutant frequency in liver and small intestine, across three age levels. These results indicate that two major pro-longevity interventions in the mouse are associated with a reduced mutation frequency. This could be responsible, at least in part, for the enhanced longevity associated with Ames dwarfism and CR.

This study determined the biodistribution of rhenium-186 ((186)Re) encapsulated in biotin-liposomes containing patent blue dye, injected intraperitoneally (IP) with avidin in an OVCAR-3 ovarian cancer xenograft model and evaluated tumor response of this therapy with fluorine-18-fluorodeoxyglucose ((18)F-FDG) microPET imaging. Treated rats (n = 8) received an IP injection of (186)Re-blue-biotin-liposomes (1000 MBq/kg) 30 min before an IP injection of avidin (5 mg), whereas control rats (n = 4) received a sham IP injection of saline. Scintigraphic images showed that (186)Re-blue-biotin liposomes/avidin were retained in the peritoneal cavity with 18% of the original activity remaining after 5 days. From 1 to 4 weeks post-treatment, peritoneal (18)F-FDG standard uptake values decreased 30% in treatment group, yet increased 44% in control group. Total number of cells in ascites was significantly higher in control versus treatment group. Omental fat in control rats had numerous tumor cells compared with treated rats. Results show the potential for (186)Re-blue-biotin-liposome/avidin system in treating advanced ovarian cancer involving peritoneal carcinomatosis.

Humans are exposed to ionizing radiation (IR) under various circumstances, e.g. cosmic radiation, diagnostic X-rays and radiotherapy for cancer. It has been shown that IR can impair spermatogenesis and can cause mutations in germ cells. However, the mutagenic responses of germ cells exposed to IR at different stages of testicular maturation have not been examined by directly assessing the mutant frequency in defined spermatogenic cell types. This study was performed to address whether preadult exposure to IR can increase mutations in adult germ cells that could in turn have a major impact on adult reproductive function and the health of ensuing offspring. Male Lac I transgenic mice were irradiated with a single dose of 2.5 Gy of gamma-ray at different ages before adulthood, reflecting different stages of testicular maturation, and then mutant frequency (MF) was determined directly in spermatogenic cell types emanating from the irradiated precursor cells. The results showed that (1) preadult exposure to IR did not significantly increase MF in adult epididymal spermatozoa; (2) spermatogenic stages immediately following the irradiated stage(s) displayed an elevated mutant frequency; but (3) the mutant frequency was restored to unirradiated levels in later stages of spermatogenesis. These findings provide evidence that there is a mechanism(s) to prevent spermatogenic cells with elevated mutant frequencies from progressing through spermatogenesis.

Atherosclerosis begins in childhood or adolescence and progresses during the young adult years to cause clinical coronary heart disease (CHD) in middle-aged and older individuals. This article reviews evidence regarding the association of the major established CHD risk factors with atherosclerosis in adolescents and young adults, with emphasis on the findings of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. Age, non-high-density lipoprotein cholesterol concentration, smoking, hypertension, obesity, and hyperglycemia are positively associated with atherosclerotic lesions, whereas female gender and high-density lipoprotein cholesterol concentration are negatively associated with lesions. The PDAY study developed a risk score that provides a weighted summary of the risk factor effects on advanced atherosclerosis. Although developed to predict advanced atherosclerotic lesions, the risk score is also associated with all stages of lesion severity, including the transition from normal tissue to the earliest anatomically detectable lesion. Application of the PDAY risk score to data from longitudinal studies of risk factors in young adults shows that early measurement of risk factors predicts atherosclerosis assessed noninvasively up to 15 years later, and that subsequent change in risk score during the 15-year interval also predicts atherosclerosis. These findings provide strong support for maintaining a low lifetime risk and for focusing on preventing atherosclerosis as the most effective way to prevent CHD. Risk-factor control beginning in the late teenage years will retard development of the earliest stage of atherosclerosis and its progression, and will reduce or delay occurrence of CHD.

Background: Disease is sometimes best studied by examination of tissue obtained from autopsied individuals. Results derived from autopsied persons are considered biased because many factors influence the decision to perform an autopsy, and variables measured postmortem may be affected by changes immediately prior to death and emergency medical treatment., Methods: The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study measured coronary heart disease risk factors postmortem in autopsied young adults 23-34 years of age dying from external causes (accidents, homicides, suicides). The Coronary Artery Risk Development in Young Adults (CARDIA) study measured risk factors in living subjects of similar ages., Results: Within sex, race, and age groups, the differences in body mass index between PDAY and CARDIA were significant but small. The prevalences of hyperglycemia/diabetes within sex, race, and age groups were similar in PDAY and CARDIA; overall, blacks in PDAY, but not in CARDIA, had a higher prevalence than whites. Serum lipoprotein concentrations were slightly and significantly higher and significantly more variable in PDAY subjects than in CARDIA subjects; the greater variability was interpreted as due primarily to emergency medical treatment. Prevalences of smoking and hypertension were substantially higher in PDAY subjects., Conclusions: Although there were statistically significant differences, the overall similarity of the risk factors in the two studies supports the validity of investigating associations of risk factors measured postmortem with anatomically determined arterial lesions in autopsied young adults dying from external causes. The greater variability in postmortem serum measurements attenuates but does not obscure associations.

Assisted reproductive technologies (ARTs) have now contributed to the birth of >3 million babies worldwide, but concerns remain regarding the safety of these methods. We have used a transgenic mouse model to examine the effects of ARTs on the frequency and spectrum of point mutations in midgestation mouse fetuses produced by either natural reproduction or various methods of ART, including preimplantation culture, embryo transfer, in vitro fertilization, intracytoplasmic sperm injection, and round spermatid injection. Our results show that there is no significant difference in the frequency or spectrum of de novo point mutations found in naturally conceived fetuses and fetuses produced by in vitro fertilization, intracytoplasmic sperm injection, or round spermatid injection. These results, based on analyses of a transgenic mouse system, indicate that with respect to maintenance of genetic integrity, ARTs appear to be safe.

The basic tenet of several theories on aging is increasing genomic instability resulting from interactions with the environment. Chromosomal aberrations have been used as classic examples of increasing genomic instability since they demonstrate an increase in numerical and structural abnormalities with age in many species including humans. This accumulating damage may augment many aging processes and initiate age-related diseases, such as neoplasias. Calorie restriction (CR) is one of the most robust interventions for reducing the frequency of age-related diseases and for extending life span in many short-lived organisms. However, the mechanisms for the anti-aging effects of CR are not yet well understood. A study of rhesus monkeys was begun in 1987 to determine if CR is also effective in reducing the frequency of age-related diseases and retarding aging in a long-lived mammal. Male monkeys were begun on the diet in 1987, and females were added in 1992 to examine a possible difference in response to CR by sex. The CR monkeys have been maintained for over 10 years on a low-fat nutritional diet that provides a 30% calorie reduction compared to a control (CON) group. Because of the greater similarity of nonhuman primates to humans in life span and environmental responses to diet compared with those of rodents, the rhesus monkey provides an excellent model for the effects of CR in humans. This study examined the effects of CR on chromosomal instability with aging. Significant age effects were found in both CR and CON groups for the number of cells with aneuploidy: old animals had a higher loss and a higher gain than young animals. However, there was no effect of age on chromosomal breakage or structural aberrations in either diet group. Diet had only one significant effect: the CR group had a higher frequency of chromatid gaps than did the CON group. CR, implemented in adult rhesus monkeys, does not have a major effect on the reduction of numerical or structural aberrations related to aging.