Actin and myosin contribute to mammalian mitochondrial DNA maintenance.

Mitochondrial DNA maintenance and segregation are dependent on the actin cytoskeleton in budding yeast. We found two cytoskeletal proteins among six proteins tightly associated with rat liver mitochondrial DNA: non-muscle myosin heavy chain IIA and ß-actin. In human cells, transient gene silencing of MYH9 (encoding non-muscle myosin heavy chain IIA), or the closely related MYH10 gene (encoding non-muscle myosin heavy chain IIB), altered the topology and increased the copy number of mitochondrial DNA; and the latter effect was enhanced when both genes were targeted simultaneously. In contrast, genetic ablation of non-muscle myosin IIB was associated with a 60% decrease in mitochondrial DNA copy number in mouse embryonic fibroblasts, compared to control cells. Gene silencing of ß-actin also affected mitochondrial DNA copy number and organization. Protease-protection experiments and iodixanol gradient analysis suggest some ß-actin and non-muscle myosin heavy chain IIA reside within human mitochondria and confirm that they are associated with mitochondrial DNA. Collectively, these results strongly implicate the actomyosin cytoskeleton in mammalian mitochondrial DNA maintenance.

The accessory subunit of mitochondrial DNA polymerase gamma determines the DNA content of mitochondrial nucleoids in human cultured cells.

The accessory subunit of mitochondrial DNA polymerase gamma, POLGbeta, functions as a processivity factor in vitro. Here we show POLGbeta has additional roles in mitochondrial DNA metabolism. Mitochondrial DNA is arranged in nucleoprotein complexes, or nucleoids, which often contain multiple copies of the mitochondrial genome. Gene-silencing of POLGbeta increased nucleoid numbers, whereas over-expression of POLGbeta reduced the number and increased the size of mitochondrial nucleoids. Both increased and decreased expression of POLGbeta altered nucleoid structure and precipitated a marked decrease in 7S DNA molecules, which form short displacement-loops on mitochondrial DNA. Recombinant POLGbeta preferentially bound to plasmids with a short displacement-loop, in contrast to POLGalpha. These findings support the view that the mitochondrial D-loop acts as a protein recruitment centre, and suggest POLGbeta is a key factor in the organization of mitochondrial DNA in multigenomic nucleoprotein complexes.

Quality of life research: is there a difference in output between the major cancer types?

As a result of more people living with or surviving cancer, outputs for quality of life research may have increased over time to reflect the needs of the growing number of people affected by cancer. To determine if this is the case, the authors sought to examine the number and proportion of publications concerned with cancer patients' quality of life for four major cancer sites (breast, lung, prostate, colorectal) over five equal time periods (1985, 1990, 1995, 2000, 2005). A computer-based literature search using Medline and PsycINFO databases was undertaken. A comparison search with cancer-related biomedical terms was conducted. The results showed that the number of quality of life publications was substantially lower compared with biomedical publications over time, although the average annual relative increase in publications was greatest for quality of life. The total number of quality of life publications was greatest for breast cancer and lowest for colorectal cancer at all five time points. The relative increase over time of quality of life publications was greatest for prostate cancer and lowest for breast cancer. More research is needed regarding quality of life for cancer patients. Breast cancer has dominated quality of life research outputs despite a lower relative increase in publications over time compared with other cancer sites. There is need for debate among funding agencies and researchers to ensure research efforts are shared among cancer types.

Quality of life research: types of publication output over time for cancer patients, a systematic review.

To examine the type of published research regarding quality of life for cancer patients over two 24-month periods: 1995-1996 and 2005-2006. A computer-based literature search was conducted using Medline. Two random samples of 120 publications identified in 1995-1996 and in 2005-2006 were coded as data-based research, reviews or programme descriptions. Data-based publications were further coded as measurement, descriptive or intervention research. Intervention publications were coded as psychosocial- or biomedical-based. Psychosocial intervention papers were coded using Cochrane Review criteria. In 1995-1996, 419 publications were identified and 1271 publications in 2005-2006. The majority of publications were data-based. The proportion of types of publications (data-based, reviews or programme description/case report categories) did not change significantly over time. Descriptive research dominated data-based publication outputs in 1995-1996 and 2005-2006. The current approach to quality of life research for cancer patients may be less than optimal for providing successful development of knowledge, improving healthcare delivery and lessening the burden of suffering.

Long-term stability of surgical open-bite correction by Le Fort I osteotomy.

Skeletal changes greater than those observed in untreated adults have been noted beyond 1 year post-surgery in adult patients who had surgical correction of a long face deformity. The stability of skeletal landmarks and dental relationships from 1 to >3 years post-surgery was examined in 28 patients who had undergone surgery of the maxilla only, and in 26 patients who had undergone 2-jaw surgery to correct >2 mm anterior open bite. Although the average changes in almost all landmark positions and skeletal dimensions were less than 1 mm, point B moved down >2 mm and face height increased >2 mm in one-third of the maxilla-only group and in 40% of the 2-jaw group (>4 mm in 10% and 22% respectively). Overbite decreased 2-4 mm in only 7% of the maxilla-only and 12% of the 2 groups, with no changes >4 mm, because in three-fourths of the patients with an increase in anterior face height, further eruption of the incisors maintained the overbite relationship. In the maxilla-only group, mandibular length (Co-Pg) showed >2 mm long-term change in 45% of the patients, two-thirds of whom showed an increase rather than a decrease in length. In the 2-jaw group, no patients showed a decrease in Co-Pg length and one-third had an increase. For both groups, changes in overjet were smaller and less frequent than changes in mandibular length.

Assessment of patients for orthognathic surgery.

Rapid advances in orthognathic surgery now allow the clinician to treat severe dentofacial deformities that were once only manageable by orthodontic camouflage. These cases were often compromised with unacceptable facial esthetics and unstable occlusal results. Over the past 25 years, there have been numerous improvements in technology and the surgical management of dentofacial deformities. These progressions now allow more predictable surgical outcomes, which ensure patient satisfaction. Not all patients are candidates for surgical treatment; therefore, patient assessment and selection remains paramount in the process of diagnosing and treatment planning for this type of irreversible treatment. The inclusion of patients in the decision-making process increases their awareness and acceptance of the final result. The past three decades indicate an increased usage of orthodontic treatment by both children and adults. Patient demographic profiles for severe occlusal and facial characteristics are presented in an effort to understand the epidemiological factors of malocclusion and predict the population's need for this service.

Accuracy of measurements of mandibular anatomy and prediction of asymmetry in panoramic radiographic images.

OBJECTIVES: Measurements of ideally positioned and systematically mis-positioned skulls were used to evaluate errors in linear measurements and symmetry ratios made with panoramic X-ray images. METHODS: Digital panoramic images of 30 skulls placed in ideal, shifted and rotated positions, were assessed by measuring distances between anatomic points and fiducial references. Differences between photographic measurements (control) and radiographic measurements were compared. Horizontal measurements included a 20 mm wire and the distance from gonion to mental foramen (G-MF). Vertical distances measured included a 40 mm wire, condyle to sigmoid notch length, and condyle to gonion (posterior mandibular height or PMH). A relative symmetry ratio comparing the difference between right and left PMH was also calculated. Distances measured in panoramic images were corrected using the left vertical wire distance or the panoramic unit's stated magnification factor (1.25x). RESULTS: Greatest differences were noted for horizontal measurements and shifted skull positions. Use of an arbitrary magnification correction was consistently less accurate than use of an internal calibration and resulted in general underestimation of actual dimensions. Measures of PMH varied significantly from expected values for each of the three skull positions (P<0.005). Panoramic accuracy for detecting asymmetry was 67% for ideal, 70% for rotated, and 47% for shifted skull positions when an internal reference was used. CONCLUSIONS: Panoramic radiographs should be used with caution in making absolute measurements or relative comparisons. Even when internal fiducial calibration for image distortion of anatomy is used, measurements such as those assessing posterior mandibular facial symmetry may be unreliable.

Superimposition of 3D cone-beam CT models of orthognathic surgery patients.

OBJECTIVES: To evaluate the registration of 3D models from cone-beam CT (CBCT) images taken before and after orthognathic surgery for the assessment of mandibular anatomy and position. METHODS: CBCT scans were taken before and after orthognathic surgery for ten patients with various malocclusions undergoing maxillary surgery only. 3D models were constructed from the CBCT images utilizing semi-automatic segmentation and manual editing. The cranial base was used to register 3D models of pre- and post-surgery scans (1 week). After registration, a novel tool allowed the visual and quantitative assessment of post-operative changes via 2D overlays of superimposed models and 3D coloured displacement maps. RESULTS: 3D changes in mandibular rami position after surgical procedures were clearly illustrated by the 3D colour-coded maps. The average displacement of all surfaces was 0.77 mm (SD=0.17 mm), at the posterior border 0.78 mm (SD=0.25 mm), and at the condyle 0.70 mm (SD=0.07 mm). These displacements were close to the image spatial resolution of 0.60 mm. The average interobserver differences were negligible. The range of the interobserver errors for the average of all mandibular rami surface distances was 0.02 mm (SD=0.01 mm). CONCLUSION: Our results suggest this method provides a valid and reproducible assessment of craniofacial structures for patients undergoing orthognathic surgery. This technique may be used to identify different patterns of ramus and condylar remodelling following orthognathic surgery.

Cancer screening and early detection: managing malpractice risk.

PURPOSE: The purpose of this report is to educate healthcare professionals about the legal risks of conducting cancer screening examinations and necessary risk reduction practices. OVERVIEW: The authors describe the elements of a medical malpractice claim, the healthcare professionals' legal standard of care, theories of malpractice liability, common factors related to missed or delayed diagnoses, malpractice defenses, and risk reduction practices. CLINICAL IMPLICATIONS: Healthcare professionals, including physicians, physician assistants, advanced practice nurses, and social workers, have been shown to be clinically effective in cancer screening, and early detection of many cancers leads to improved long-term survival rates. Healthcare professionals who conduct cancer early detection examinations and counsel patients in cancer screening programs need to be aware of the common legal theories under which lawsuits are brought related to cancer detection examinations. Important steps in reducing the risk of malpractice include developing creative strategies to address the theories of liability in the area of cancer screening and early detection; keeping abreast of changes in national and international cancer screening recommendations; monitoring the literature for approaches to decrease liability; and scrupulously maintaining documentation of all findings and interactions among providers and between providers and patients.

Effects of carbon monoxide and hypoxia on cleft lip in A/J mice.

Epidemiologic evidence indicates an increase in cleft lip with or without cleft palate [CL(P)] in infants of mothers who smoke cigarettes. It appears that the principle mechanism is through carbon monoxide (CO) decreasing the oxygen (O2) available to the embryo. Previous studies have shown that maternal respiratory hypoxia can increase the incidence of CL(P) in mice. The present investigation was designed to analyze the effects of altered levels of CO and O2 in respiratory gases on the incidence of CL(P) in genetically susceptible A/J mice. Results from blood gas analysis, after a 24-hour exposure of pregnant mice during the time of primary palate development, showed that CO levels of 180 ppm in air decrease oxyhemoglobin (%O2Hb) and increased carboxyhemoglobin (%COHb) to slightly above the high end of the range found in human studies of cigarette smokers. Interestingly, the control COHb levels were higher in our CL(P) sensitive mouse strain compared with those of the range of increases found in human smokers, versus nonsmoker studies, and that the increase for treated mice (3x) was at the low end of the range for smokers. Decreasing O2 levels to 10% from 21% (normal percentage in air) more severely decreased %O2Hb and moderately decreased %COHb. At 24 hours of exposure, the incidence of CL(P) and resorption was approximately the same for both the CO and the control groups, but there were significant increases in the incidence of resorptions in the hypoxia group and of CL(P) in relation to the CO group.(ABSTRACT TRUNCATED AT 250 WORDS)

Level of agreement in clinicians' perceptions of Class II malocclusions.

To evaluate the extent to which surgeons and orthodontists agree on the nature and severity of dentofacial problems requiring orthognathic surgery, three clinicians active in a specialized clinic for treatment of dentofacial deformities scored the pretreatment records of 37 adult class II patients. Each clinician first indicated whether a skeletal/dental problem existed in the maxilla and mandible and then rated the severity of the problem on a visual analog scale. The level of agreement among the three clinicians was highest for dental problems and lowest for skeletal anteroposterior measures. There was a significant difference among the clinicians in the percentage of patients identified as having a retrusive midface and excessive facial thirds. The agreement on the severity of the problem was generally low even for those patients for whom the clinicians agreed on the type of problem. The data suggest that personal experience and clinical background play a major role in diagnosis and treatment planning. Joint treatment planning conferences between the surgeon and orthodontist offer an opportunity for different plans to be discussed, with the preferred treatment option selected for an individual patient.

Relative growth rates of maxillary mesenchyme in the chick embryo.

Chick embryos were injected with [3H]-thymidine at days 3-7 of incubation and were fixed and embedded in plastic. The embryos were divided into three stage groupings of development [Hamburger and Hamilton: J Morphol 88:49-92, 1951], and labeling indices were determined for each of the following delineated regions within the maxillary process at each stage: region 1, subepithelial mesenchyme located at the medial side of the maxillary process adjacent to the roof of the stomodeum; region 2, subepithelial mesenchyme at the ventral tip of the maxillary process (as seen on cross section); region 3, subepithelial mesenchyme at the lateral portion of the maxillary process below the eye; and region 4, interior mesenchyme defined as the central portion of the maxillary process and separated from the epithelium by the three other regions. Results indicated that differences exist among the regions examined and that these differences were stage specific. At stages 19-21 and stages 24-25 1/2, growth rates were higher in subepithelial regions than interiorly. At stages 28-29, however, a statistically significant difference among the regions was not found. These results suggested that there is an association between growth rates in the maxillary process mesenchyme and its proximity to the overlying epithelium and that these effects are related to the stage of development.

Soft tissue changes after superior repositioning of the maxilla with Le Fort I osteotomy: 5-year follow-up.

Long-term changes in soft tissue landmark positions were examined in 49 patients following superior repositioning of the maxilla by Le Fort I osteotomy. From presurgery to 1 year, on average the upper lip moved up one third the distance that the upper incisor and point A did, but there was considerable variability. In 25% of the patients the upper lip moved up more than 2 mm, and in 6% it moved up more than 4 mm. As the mandible rotated upward and forward in response to the maxillary movement, soft tissue movements paralleled the adjacent hard tissue movements almost exactly in the absence of genioplasty. From 1 to 5 years postsurgery, in 25% of the patients the maxilla moved downward more than 2 mm, and the mandible rotated down and back, often without relapse of occlusal relationships. In both jaws, long-term changes in soft tissue landmarks exceeded hard tissue changes, meaning soft tissue points tended to move downward even if hard tissue points were stable and moved down more than the corresponding hard tissue points when skeletal changes occurred.

Surgical Class III treatment: long-term stability and patient perceptions of treatment outcome.

To evaluate long-term changes after surgical correction of skeletal Class III deformity, postoperative cephalometric radiographs at 1 year and 2 or more years postsurgery were digitized for 92 patients who had received either a bilateral sagittal split osteotomy for mandibular setback, Le Fort I maxillary advancement, or a combination of the two procedures. Patients' perceptions of treatment were determined by four self-administered questionnaires: satisfaction, postsurgical perception of occlusion and function, problems with facial sensation, and postsurgical perceptions. From 1 year to longest follow-up, there were almost no mean changes in landmark positions for the maxillary advancement group and minimal mean changes in the mandibular setback and two-jaw groups. In all three groups, more than 90% of the patients showed no clinically significant long-term changes, which suggests that long-term changes are less likely after Class III than Class II treatment. At long-term recall, 89% of the patients expressed satisfaction with their treatment and would recommend it to others, 74% reported improved social interaction, and 63% said their appearance changed as they expected. The predominant problems reported were altered facial sensation for 67% of the patients and surprise at the length of recovery for 52%.

Long-term soft tissue changes after orthognathic surgery.

The assumption is often mode that the soft tissue changes resulting from orthognathic surgery have stabilized by 6 to 12 months, but longer-term changes may differ from the normal aging process observed in nonsurgical patients. Soft tissue changes that occurred between 1 year and 3 to 5 years post-surgery in 79 orthognathic surgery patients who had received either a bilateral sagittal split osteotomy or a Le Fort I osteotomy in conjunction with a bilateral sagittal split osteotomy were compared to those experienced by a group of 36 patients who had received only orthodontic treatment. Although soft tissue changes did occur, there were no significant differences between average annualized soft tissue changes in the three treatment groups.

Stability following superior repositioning of the maxilla by Le Fort I osteotomy: five-year follow-up.

Changes in dental and skeletal relationships were evaluated 5 years postsurgically in 49 patients whose maxilla had been superiorly repositioned by a Le Fort I osteotomy. All of the patients had at least 2 mm of intrusion at the maxillary incisor and molar; none had a mandibular ramus osteotomy or other osteotomy except genioplasty. Only 6.5% had 2 mm or greater of net vertical change in skeletal or dental landmarks at 1 year postsurgery. From 1 to 5 years postsurgery, minimal changes in skeletal and dental landmarks occurred in the majority of the patients, but approximately 25% of the patients showed 2 mm or more of downward movement of the maxilla and/or eruption of maxillary teeth, leading to downward-backward rotation of the mandible. Only one patient had more than 1 mm of open bite on long-term follow-up. An increase in overbite, resulting from incisor eruption, was noted in 14%, and an increase in overjet occurred in 12% as the mandible rotated. It appears that modest long-term skeletal and dental changes occur in some surgically treated long-face patients. The likelihood of long-term change was not related to the age of the patient, stability during the first postsurgical year, or segmentation of the maxilla at surgery.

Patterns of nerve regeneration in dental pulps of monkeys following surgical transection at 1 year.

Previous studies have reported revascularization and reorganization of dental pulp chambers with periodontal tissues of monkeys following complete surgical transection through a portion of the apical roots. This study observed 128 teeth in four adult monkeys. Following surgical transection, the tissues were acquired by perfusion fixation, serially sectioned, and stained for cellular detail with hematoxylin and eosin. Collagen tissues were stained with Preece's trichrome and neural tissues with Rowles' silver cyanate for controlled impregnation. At 1 and 2 weeks the coronal tissues showed tissue disruption, necrosis, and degenerating nerves. The 3- and 4-week tissues that had been completely transected showed replacement healing of the pulp tissue with periodontal ligament connective tissue, but no nerves were present. At 6 weeks, no nerves were present in the coronal chambers of those teeth with complete vital transection. The 24-, 36-, and 52-week pulp chambers with complete transection failed to show nerve fibers in their reorganized connective tissues.

Incisor retraction and profile changes in adult patients.

The aims of this study were to evaluate the changes in the facial profile related to maxillary incisor retraction and to check for correlations between changes in the lip and changes in the positions of the teeth and alveolar bone during orthodontic treatment. Initial and final lateral cephalometric radiographs of 25 nongrowing Brazilian patients were selected for this study. All patients initially presented with Class I or II malocclusions and had their maxillary incisors retracted at least 2 mm during orthodontic treatment. Changes in lip position, length, and width, as well as changes in the positions of the alveolar bones and incisors, were calculated. Statistically significant differences from pretreatment to posttreatment were observed for all measurements except for upper lip length and point A. A high correlation was demonstrated between changes in the lower lip sulcus and point B and between changes in the lower lip sulcus and the mandibular incisor. Changes in the maxillary and mandibular incisors did not show a high correlation to the total lip changes, but high correlation coefficients were obtained when the changes in lip width were excluded from the total lip changes. In other words, changes in lip width tended to mask the changes in lip position caused by retraction of the maxillary incisors.

Long-term cephalometric changes in untreated adults compared to those treated with orthognathic surgery.

A surprisingly large amount of long-term remodeling of facial structures has been noted in the period between 1 and 5 years post-orthognathic surgery. To evaluate whether these changes are greater than in patients with similar morphology who did not have surgery, long-term changes in hard tissue landmarks were examined in 33 untreated adults and compared to long-term changes in skeletal Class II surgery patients who underwent maxillary impaction, mandibular advancement, or both. Although the changes were small in both groups, mean changes were greater in the surgical patients; the surgical patients also showed a higher percentage of significant changes. Horizontal changes were in a forward direction in the untreated group and a backward direction in the surgical groups. We conclude that normal adult growth cannot account for the long-term changes observed following jaw surgery. In some instances, postsurgical changes leading to relapse continue much longer than would have been expected.

Who seeks surgical-orthodontic treatment: a current review.

Records for more than 2,000 individuals seen in the Dentofacial Clinic of the University of North Carolina were examined to evaluate trends in referral patterns for orthognathic surgery and acceptance of surgical treatment The vast majority of patients have been white and female from the beginning, and the female-male ratio remained constant at 2:1 throughout the 1990s. The proportion of nonwhite patients increased significantly after 1995, with the change resulting almost totally from more Hispanic and Asian patients. The proportion of African Americans, who represent 22% of the general population, remained almost constant at 10%. Class III and long-face individuals were more likely to seek evaluation than those with Class II problems, but of those who were offered orthognathic surgery, relatively more of the Class II group accepted it. This may reflect greater severity of a Class II problem before a patient seeks treatment. More than 1 of the Clinic population had some sort of facial asymmetry, but the presence of asymmetry did not seem to influence the decision to have surgical treatment. The dental and skeletal characteristics of those who had surgery were similar to those of patients who did not have surgery, suggesting that the decision to elect a surgical treatment plan was influenced by factors other than clinical characteristics.