Design and Rationale of Penn Medicine Healthy Heart, a Randomized Trial of Effectiveness of a Centrally Organized Approach to Blood Pressure and Cholesterol Improvement Among Patients at Elevated Risk of Atherosclerotic Cardiovascular Disease.

RATIONALES: Atherosclerotic Cardiovascular Disease (ASCVD) is the leading cause of morbidity and mortality in the United States. Suboptimal control of hypertension and hyperlipidemia are common factors contributing to ASCVD risk. The Penn Medicine Healthy Heart (PMHH) Study is a randomized clinical trial testing the effectiveness of a system designed to offload work from primary care clinicians and improve patient follow-through with risk reduction strategies by using a centralized team of non-clinical navigators and advanced practice providers, remote monitoring, and bi-directional text messaging, augmented by behavioral science engagement strategies. The intervention builds on prior non-randomized evaluations of these design elements that demonstrated significant improvement in patients' systolic blood pressure and LDL Cholesterol (LDL-C). PRIMARY HYPOTHESIS: Penn Medicine Healthy Heart will significantly improve systolic blood pressure and LDL-C compared to usual care over the 6 months of this intervention. DESIGN: Randomized clinical trial of Penn Medicine Healthy Heart in patients aged 35-80 years at elevated risk of ASCVD whose systolic blood pressure and LDL-C are not well controlled. The intervention consists of four modules that address blood pressure management, lipid management, nutrition, and smoking cessation, offered in a phased approach to give the participant time to learn about each topic, adopt any recommendations, and build a relationship with the care team. SITES: University of Pennsylvania Health System at primary care practices located in inner-city urban and rural/semi-rural areas PRIMARY OUTCOMES: Improvement in systolic blood pressure and LDL-C SECONDARY OUTCOMES: Cost-effectiveness analyses are planned to evaluate the health care costs and health outcomes of the intervention approach. An implementation evaluation is planned to understand factors influencing success of the intervention. ESTIMATED ENROLLMENT: 2,420 active patients of Penn Medicine primary care practices who have clinical ASCVD, or who are at elevated risk for ASCVD, and who are (a) not on statins or have LDL-C > 100 despite being on statins and (b) had systolic blood pressure>140 at two recent ambulatory visits. ENROLLMENT DATES: March 2024-March 2025. The intervention will last 6 months with a 12-month follow-up to determine whether its effects persist. CURRENT STATUS: Enrolling (1,240 enrolled as of August 15, 2024) CLINICAL TRIAL REGISTRATION: NCT06062394.

DNA synthesis in cartilage cells is stimulated by oscillating electric fields.

External oscillating electric fields (1166 volts per centimeter, 5 hertz) enhanced the incorporation of [3H] thymidine into the DNA of chondrocytes isolated from the proliferative layer of embryonic (16 days) chick epiphysis. Verapamil or tetrodotoxin at 10(-6)M concentrations completely blocked the electric field effect. Tetracaine reduced the incorporation of [3H] thymidine in both control and electrically stimulated cells. The findings support the hypothesis that Na and Ca2 fluxes generated by the electrical perturbation trigger DNA synthesis in these cells.

Calcium incorporation in cultured chondroblasts perturbed by an electromagnetic field.

We tested the hypothesis that electric perturbation influences 45Ca incorporation in extracellular matrix (ECM) of cartilage in vitro. Hypertrophic chondroblasts of tibial epiphyses (HC), sternum (SC), and skin fibroblasts (F) were cultured from chick embryos. HC, SC, and F cells were micromass seeded three times per week and maintained at 37.5 degrees C with 5% CO2 for two weeks. Cultures were randomly designated control (C) or exposed (E) to a pulsed electromagnetic field (PEMF). A time course experiment of calcium incorporation for all cultured groups showed that 24 h of exposure produced the largest biological response in chondroblasts. Calcium incorporation required supplemental phosphate. Autoradiography data indicated that the calcium incorporation into macromolecules largely occurred in the ECM. 45Ca steady-state perturbation was enhanced by Streptomyces hyaluronidase (SH) but not by testicular hyaluronidase (TH). 45Ca incorporation experiments tested the effects of phosphate, SH, TH, and PEMF alone and in various combinations on these cultures. Only PEMF or SH plus PEMF with phosphate enhanced 45Ca incorporation. Other experiments examined the effect of rotenone or freeze-thawing on cells exposed to PEMF. PEMF plus freeze-thaw enhanced calcium incorporation in HC only. PEMF appeared to cause disruption of the ECM, enhancing the probability of matrix calcification.

Pulsed electromagnetic fields alter phenotypic expression in chondroblasts in tissue culture.

We hypothesize that pulsed electromagnetic fields (PEMF) alter phenotypic expression of chondroblasts by promoting the production of alkaline phosphatase (AP) and altering the structure of proteoglycans. Chondroblasts from the hypertrophic zone of tibial epiphyses (HC), sternum (SC), and skin fibroblasts (F) were cultured from 16 day chick embryos. Cultures were randomly designated control (C) or experimental (E). E received PEMF for 24 h in a 6 h on, 6 h rest sequence. The controls were in the same incubator shielded by Mu metal. Assays for AP activity were performed and normalized to protein content. Proteoglycan synthesis assay involved labeling with 35S fractionating in a 5% to 20% surcrose gradient determining total protein and chondroitin sulfate content. PEMF showed no change of AP activity on F. A high AP basal activity was found in HC, but was not increased above the control. PEMF increased AP in the SC samples (E/C ratio). The sucrose gradient data showed a shift in peaks for SC only altering the ratio of carbohydrate to protein for the SC. Analysis of carbohydrate and protein indicated that the effect was decreased synthesis or degradation of protein. We conclude that PEMF alters the phenotypic expression of sternal chondroblasts in our in vitro system.

Attachment of epiphyseal cartilage cells and 17/28 rat osteosarcoma osteoblasts using mussel adhesive protein.

These experiments show that mussel adhesive protein (MAP) enhances the attachment of osteoblasts and epiphyseal cartilage cells to plastic culture dishes and Vitallium. When MAP was applied to culture plate surfaces, there were two- to fivefold increases in the numbers of cells attaching compared to control surfaces (no MAP). Results were confirmed using two different cell attachment assay techniques. Osteoblast replication and culture on MAP is possible, suggesting that MAP is not toxic to cells. MAP also holds applied cells to surfaces as initially attached.

A device for the application of known simulated orthodontic forces to human cells in vitro.

Connective tissues are responsive to mechanical forces. In orthodontic tooth movement it appears that the periodontal ligament (PDL) is the source of a pleuropotential cell population and extracellular matrix structure which translates mechanical perturbation information into a host of cellular events. These include proliferation, repair, differentiation, and shape change. We have designed, built, and tested a simple, adaptable machine which enables us to examine molecular changes or events in the cell nucleus, cell membrane, and the cytoskeleton of any eukasytic cell that will adhere to a membrane. These responses to clinically simulated forces applied to an in vitro system can be measured.

Electrical stimulation of osteogenesis in pathological osseous defects.

Although the literature on bioelectric phenomena is extensive, there is a paucity of research on its application in the field of dentistry. This study was designed to evaluate the effect of bioelectrical stimulation on pathological osseous defects in the periodontium of Beagle dogs. Galvanic and thermocouple generators were designed to deliver a current in the nanoampere range. The galvanic unit produced a constant direct current. The thermocouple unit was designed to deliver an oscillating dc current. The generators were implanted in the area of periodontal osseous defects in five dogs. These sites were randomly designated as experimental, active controls, and passive controls. The experimental and control units were implanted submucoperiosteally with the negative electrodes extending into osseous defects. The bone was labeled with Procion Red H-8BS at 1 week. Clinical and radiographic evaluation revealed no significant changes in the depth of the defects. The animals were sacrificed at 45 days and block sections were prepared for histological measurement. From the results of this study it was concluded: 1. Induced constant or oscillating negative dc current levels in the nanoampere range were unsucessful in causing regeneration of periodontal osseous defects either clinically or radiographically in the Beagle dog over a 45-day period of application. 2. Constant or oscillating negative dc current levels in the nanoampere range did not stimulate a significant amount of periosteal osseous apposition. 3. Oscillating negative nanoampere dc currents produced an increase in endosteal osseous apposition as compared to controls. 4. Constant negative dc current in the nanoampere range produced an increase in endosteal osseous apposition as compared to controls. 5. The histological density of the bone in the area of pathological periodontal defects was increased in all experimental sites as compared to controls. 6. Devices of comparable size and construction to both the galvanic and thermocouple electronic units used in this study are acceptable for future investigation of the effect of bioelectrical stimulation on osteogenesis in alveolar bone.

A methodical study of shape changes in human oral cells perturbed by a simulated orthodontic strain in vitro.

Cells are known to alter their shape as a response to physical and chemical changes. Mechanical loads applied to teeth produced cellular perturbations resulting in orthodontic movement. An in vitro model was developed to simulate the in vivo strain of orthodontic movement. Calibrated forces were applied to human periodontal ligament cells and buccal mucosal fibroblasts (controls). A biaxial strain-producing device was used to stretch vital cells growth on flexible polytetrafluorethylene membranes. In addition, a new cell adhesive, Cell Tak, was employed to examine the effect of an adhesive substrate on the cellular response to two known loads. The shape changes of unstrained (control) and strained cells were evaluated by time-lapse telemicroscopy, and plots of time-dependent alterations in area and shape were recorded. The fusiform cells became more rounded over a given time of up to 1400 s. The responses appeared to be independent of cell type, the strain employed, and the presence of cell adhesive. Scanning electron microscopy demonstrated, irrespective of cell type, that the surface of stressed cells produced a striking number of microvilli as compared with the relatively smooth-surfaced controls.

Self-induced trauma to the nails.

Both frequent and rare deformities of the nails have been reported that are due to self-inflicted damage. Some of these disorders may be confused with common diseases such as psoriasis, lichen planus, onychomycosis, or industrial injury. Awareness of the common patterns, inspection of the periungual tissues, observation of the patient's attitude toward his or her nail disorder, and inclusion of self-trauma in the differential diagnosis will lower the incidence of ineffective treatments and unnecessary laboratory tests.

Orthodontic tooth movement response in Ehlers-Danlos syndrome: report of case.

The clinical manifestations of Ehlers-Danlos syndrome have been discussed. These include oral symptoms and problems with the integument, joints, and vasculature. An outline of the variations in the types of Ehlers-Danlos syndrome was given. The expected tissue response to tooth movement was discussed. Finally, a report of the orthodontic treatment of a patient with Ehlers-Danlos syndrome with its special clinical considerations was provided.

The effect of aging cellular mechanisms on tooth movement.

In summary, there appears to be indirect evidence that the dentoalveolar system undergoes a number of changes with age. These changes have the potential of affecting the biologic response of these tissues to the forces of tooth movement. They should not, however, create a barrier toward the successful completion of orthodontic therapy in most cases.

Periodontal considerations in orthodontic treatment.

Orthodontic treatment of a patient with periodontal problems is within the realm of a knowledgeable general practitioner. After a diagnosis is made, one must establish a problem list, a solution list, a logical sequential treatment plan, a mechanics plan, a retention plan, and a means of evaluating whether treatment objectives have been reached. Unfortunately, orthodontic treatment occasionally poses some hazards to the detention and its supporting structure. Recognition of these pitfalls and care during treatment will help avoid many problems. Dental scientists throughout the world are trying to understand the nature of these hazards. Their goal is to provide the practicing dentist with a means of preventing unwanted side effects and possible tissue destruction.

Specific mechanics for abutment uprighting.

General practitioners can use adjunctive orthodontics in preparation for complex comprehensive dental restorative procedures. Two orthodontic educators from opposite sides of the world explain and illustrate the biomechanics of controlled abutment uprighting. Solutions to the common mechanical and clinical problems are discussed.

Problems + Solutions.

Readers are invited to submit questions relating to problem cases. Inquiries will be answered by qualified consultants and replies forwarded by mail promptly. Selected problems and solutions are published every month in this section.

Bioelectric perturbations of bone. Research directions and clinical applications.

Bioelectric perturbation of living hard tissue produces clinically useful effects. It is being used effectively in the treatment of intractable orthopedic problems such as nonunion and avascular necrosis. Dental applications of this phenomenon are still in the early stages of research and development. Barring untoward circumstances, this form of local growth control may be used as an adjunct to localized bone induction therapy such as in the treatment of periodontal diseases, bone grafting or implantation of biocompatible products. It also appears to show promise in enhancing the rate of tooth movement or the stability of anchor teeth. The mechanism for these perturbation-induced changes in cells has not been explained. This is an active area of research with many implications for helping the clinician understand the molecular biology of hard-tissue cell proliferation, migration and differentiation.