Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Risk Score in Young Adults Predicts Coronary Artery and Abdominal Aorta Calcium in Middle Age: The CARDIA Study.

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.

DNA Alkylating Agent Protects Against Spontaneous Hepatocellular Carcinoma Regardless of O6-Methylguanine-DNA Methyltransferase Status.

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.

Esthetic, clinical and patient-centered outcomes of immediately placed implants (Type 1) and early placed implants (Type 2): preliminary 3-month results of an ongoing randomized controlled clinical trial.

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.

Increased human AP endonuclease 1 level confers protection against the paternal age effect in mice.

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.

Fostering dental student self-assessment of knowledge by confidence scoring of multiple-choice examinations.

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).

The effects of elevated hemoglobin A(1c) in patients with type 2 diabetes mellitus on dental implants: Survival and stability at one year.

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.

Early-life exposure to benzo[a]pyrene increases mutant frequency in spermatogenic cells in adulthood.

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.

Improving multiple-choice questions to better assess dental student knowledge: distractor utilization in oral and maxillofacial pathology course examinations.

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.

Number of basis images effect on detection of root fractures in endodontically treated teeth using a cone beam computed tomography machine: an in vitro study.

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.

Enhanced genetic integrity in mouse germ cells.

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.

Human O6 -methylguanine-DNA methyltransferase containing C145A does not prevent hepatocellular carcinoma in C3HeB/FeJ transgenic mice.

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.

Contrast-to-noise ratio with different large volumes in a cone-beam computerized tomography machine: an in vitro study.

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.

Short-answer questions and formula scoring separately enhance dental student academic performance.

In this study, numerical course scores of second-year dental students in four successive classes in an oral and maxillofacial pathology course were compared. While the course content and teaching methods were essentially unchanged throughout the four years, two modest departures from the sole use of multiple-choice format questions were made in the assessment of student achievements. The modifications consisted of creating a more challenging examination procedure through the inclusion of un-cued short-answer format questions and the institution of correction-for-guessing scoring on multiple-choice examinations. Academically, the students in the four classes were comparable, as indicated by their respective numerical course score distributions in a prerequisite general pathology course in which the course content was unchanged, and all multiple-choice format questions were used to assess student academic achievements. This four-year study demonstrated that two qualitative changes in the educational environment-utilization of un-cued short-answer questions and correction for guessing scoring of multiple-choice questions-separately resulted in significant improvements in student course scores. Our results support the notion that, without any changes in curricular content or emphasis, combinations of qualitative changes in the assessment procedures alter student behavior and, as a consequence, appreciably improve their academic achievements.

Ionizing radiation-induced mutant frequencies increase transiently in male germ cells of older mice.

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.

Age-related instability in spermatogenic cell nuclear and mitochondrial DNA obtained from Apex1 heterozygous mice.

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.

High fat diet induced insulin resistance and glucose intolerance are gender-specific in IGF-1R heterozygous mice.

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.

BAX and tumor suppressor TRP53 are important in regulating mutagenesis in spermatogenic cells in mice.

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.

Short-answer examinations improve student performance in an oral and maxillofacial pathology course.

The effect of examination question format on student performance was assessed by investigating three academically comparable second-year dental school classes in an oral and maxillofacial pathology course. One class was given examinations with all multiple-choice questions, one class was given examinations with all short-answer questions, and one class was given examinations with half multiple-choice questions and half short-answer questions. The class given examinations with half short-answer questions along with half multiple-choice questions had a significantly higher average score and grade category distribution (80-100 percent, 70-79 percent, <70 percent) than the class given examinations with all multiple-choice questions. When students in these two classes were divided into three academic ability groups based on the student's score in a prerequisite general pathology course, the class given examinations with half short-answer questions and half multiple-choice questions in the oral and maxillofacial pathology course had significantly higher scores and grade category distributions in all three ability groups. The average score and grade category distribution in the class given examinations with all short-answer questions in the oral and maxillofacial pathology course were not significantly different from the average score and grade category distribution in the class given examinations with half short-answer and half multiple-choice questions. Our interpretation of these results is that the utilization of examinations containing short-answer questions created a more challenging learning environment that motivated students to adopt more effective study regimens.

Epigenetic regulation of genetic integrity is reprogrammed during cloning.

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.

Are pediatricians responsible for prevention of adult cardiovascular disease?

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.