Myron Allukian

An in vivo study on enamel fluoride in children living in a fluoridated and in a non-fluoridated area

Fluoride was determined in intact surface enamel from three tooth types in 9–11 yr old continuous residents of the communities of Salem (water F: 1 ppm) and Hyannis (water F < 0.1 ppm) in Massachusetts. The mean F concentrations of central incisors at the approximate depth of 0.5 μm were 3000 ppm and 2100 ppm in Salem and Hyannis, respectively. The concentrations decreased by about 1000 ppm over the subsequent 1.5 μm depth interval. Comparisons between the two populations on the basis of lateral incisors and of first molars yielded similar results. The findings also indicated that differences within a mouth between various tooth types were fairly small. There was a marked individual variation within each population. In Salem, the F levels of enamel in males were significantly higher than in females. A similar trend was found in Hyannis. No elevation of enamel F shortly after the use of an F dentifrice could be shown.

Dysregulation of collagen production in diabetes following recurrent skin injury: Contribution to the development of a chronic wound

Recurrent injury has been implicated in the development of chronic diabetic wounds. We have developed a chronic diabetic wound model based upon recurrent injury in diabetic mice. We hypothesized that dysregulation of collagen production at both the mRNA and microRNA levels contributes to the development of chronic diabetic wounds. To test this, both diabetic and nondiabetic mice were made to undergo recurrent injury. Real‐time PCR for TGF‐β1, SMAD‐3, Col1α1, Col3α1, microRNA‐25, and microRNA‐29a and Western blot for collagen I and III were performed 7 days following each injury. Diabetic wounds displayed decreased collagen at all time points. This was associated with dysregulated collagen production at both the gene and microRNA levels at all time points. Following the final injury, however, diabetic collagen production significantly improved. This appeared to be due to a substantial decrease in both microRNAs as well as an increase in the expression of collagen pathway genes. That dysregulated collagen production progressed throughout the course of wounding suggests that this is one factor contributing to the development of chronic diabetic wounds. Future studies using this model will allow for the determination of other factors that may also contribute to the development and/or persistence of chronic diabetic wounds.

Reduction of diaryl alkenes by hypophosphorous acid-iodine in acetic acid

Abstract A mixture of 50% aqueous H 3 PO 2 and I 2 (in catalytic amount) in HOAc efficiently reduces aryl alkenes to the corresponding alkanes in high yield. Addition of acetic anhydride to the medium results in ring-acetylation (or N -acetylation in the case of amines). H 3 PO 2 costs only one-fifth as much as hydriodic acid on a mole basis and one mole of H 3 PO 2 produces four moles of HI, resulting in a 20-fold cost advantage for H 3 PO 2 /I 2 over aqueous HI as a source of HI.

Mammalian Fetal Cardiac Regeneration After Myocardial Infarction Is Associated With Differential Gene Expression Compared With the Adult

BACKGROUND In adults, myocardial infarction (MI) results in a brisk inflammatory response, myocardium loss, and scar formation. We have recently reported the first mammalian large-animal model of cardiac regeneration after MI in fetal sheep. We hypothesize that the ability of the fetus to regenerate functional myocardium after MI is owing to differential gene expression regulating the response to MI in the fetus compared with the adult. METHODS Myocardial infarction was created in adult (n=4) or early gestation fetal (n=4) sheep. Tissue was harvested after 3 or 30 days, and RNA was extracted for microarray, followed by principal component analysis and global gene expression analysis for the following gene ontology terms: response to wounding, inflammatory response, extracellular matrix, cell cycle, cell migration, cell proliferation, and apoptosis. RESULTS Principal component analysis demonstrated that the global gene expression pattern in adult infarcts was distinctly different from the uninfarcted region at 3 days and remained different at 30 days after MI. In contrast, gene expression in the fetal infarct was different from the uninfarcted region at 3 days, but by 30 days it returned to a baseline expression pattern similar to the uninfarcted region. Three days after MI there was an increase in the expression of genes related to all gene ontology terms in fetal and adult infarcts, but this increase was much more pronounced in adults. By 30 days, the fetal gene expression returned to baseline, whereas in the adult it remained significantly elevated. CONCLUSIONS These data demonstrate that the global gene expression pattern is dramatically different in the fetal regenerative response to MI compared with the adult response and may partly be responsible for the regeneration.

Modulation of the inflammatory response by increasing fetal wound size or interleukin‐10 overexpression determines wound phenotype and scar formation

Wound size impacts the threshold between scarless regeneration and reparative healing in the fetus with increased inflammation showed in fetal scar formation. We hypothesized that increased fetal wound size increases pro‐inflammatory and fibrotic genes with resultant inflammation and fibroplasia and that transition to scar formation could be reversed by overexpression of interleukin‐10 (IL‐10). To test this hypothesis, 2‐mm and 8‐mm dermal wounds were created in mid‐gestation fetal sheep. A subset of 8‐mm wounds were injected with a lentiviral vector containing the IL‐10 transgene (n = 4) or vehicle (n = 4). Wounds were harvested at 3 or 30 days for histology, immunohistochemistry, analysis of gene expression by microarray, and validation with real‐time polymerase chain reaction. In contrast to the scarless 2‐mm wounds, 8‐mm wounds showed scar formation with a differential gene expression profile, increased inflammatory cytokines, decreased CD45+ cells, and subsequent inflammation. Lentiviral‐mediated overexpression of the IL‐10 gene resulted in conversion to a regenerative phenotype with decreased inflammatory cytokines and regeneration of dermal architecture. In conclusion, increased fetal wounds size leads to a unique gene expression profile that promotes inflammation and leads to scar formation and furthermore, these results show the significance of attenuated inflammation and IL‐10 in the transition from fibroplasia to fetal regenerative healing.

Mammalian cardiac regeneration after fetal myocardial infarction requires cardiac progenitor cell recruitment.

BACKGROUND In contrast to the adult, fetal sheep consistently regenerate functional myocardium after myocardial infarction. We hypothesize that this regeneration is due to the recruitment of cardiac progenitor cells to the infarct by stromal-derived factor-1α (SDF-1α) and that its competitive inhibition will block the regenerative fetal response. METHODS A 20% apical infarct was created in adult and fetal sheep by selective permanent coronary artery ligation. Lentiviral overexpression of mutant SDF-1α competitively inhibited SDF-1α in fetal infarcts. Echocardiography was performed to assess left ventricular function and infarct size. Cardiac progenitor cell recruitment and proliferation was assessed in fetal infarcts at 1 month by immunohistochemistry for nkx2.5 and 5-bromo-2-deoxyuridine. RESULTS Competitive inhibition of SDF-1α converted the regenerative fetal response into a reparative response, similar to the adult. SDF-inhibited fetal infarcts demonstrated significant infarct expansion by echocardiography (p < 0.001) and a significant decrease in the number of nkx2.5+ cells repopulating the infarct (p < 0.001). CONCLUSIONS The fetal regenerative response to myocardial infarction requires the recruitment of cardiac progenitor cells and is dependent on SDF1α. This novel model of mammalian cardiac regeneration after myocardial infarction provides a powerful tool to better understand cardiac progenitor cell biology and to develop strategies to cardiac regeneration in the adult.

The Practice and Infrastructure of Dental Public Health in the United States

Dental public health is a unique and challenging American Dental Association-recognized specialty because the patient is the entire community or population, such as a school, neighborhood, city, state, or the nation, with a focus on vulnerable populations. Limited resources are maximized through prevention, policies, programs, and organized community efforts to respond to great unmet needs. Although dental public health professionals are few in number, millions of people every day have better oral health because of these professionals, who work on the local, state, and national level.

Pinacol reduction-cum-rearrangement. A re-examination of the reduction of aryl alkyl ketones by zinc-aluminum chloride

Reduction of alkyl phenyl ketones by zinc and aluminum chloride in acetonitrile results in pinacol condensation followed by rearrangement. The phenyl group migrates in every instance.

APHA PRESIDENTS SUPPORT DENTAL THERAPISTS

As past presidents of the American Public Health Association, we were quite surprised to read the commentary coauthored by Dr. Sekiguchi,1 a past president of the American Dental Association (ADA), and ADA staff in the May 2005 American Journal of Public Health opposing the use of dental therapists in rural Alaska.1 This commentary, which was published without an Op-Ed piece, would be comparable to the Journal publishing a commentary from only the American Medical Association in the 1960s stating that there is no need for pilot programs for nurse practitioners, physician assistants, or nurse-midwives, even in high-need areas, and that only physicians should provide health care. I am sure our readers would be quite upset. New Zealand has successfully trained dental therapists for more than 80 years, and many other countries also use them.2 The Alaskan dental therapists are receiving state-of-the-art training, and they are being monitored and evaluated from A to Z.3 Although the ADA has a good track record of supporting preventive measures, such as community water fluoridation and most public health programs, they have a long record of preventing anyone except dentists from providing treatment, even to the underserved. This commentary includes some useful information and correctly documents the array of ongoing efforts of the Indian Health Service and the Tribes to respond to the dental access crisis of Alaskan Natives. However, the authors’ opposition to a pilot program for 6 to 12 dental health therapists without any evidence, data, or studies marginalizes the credibility of the authors and the ADA. Beginning in 1966, the American Public Health Association Governing Council has supported the use of expanded duties at least 3 times.4 This commentary by itself would not normally create much concern; however, because organized dentistry is lobbying state and federal decisionmakers to stop this pilot program, including a full-page ad to the governor in the Juneau Empire newspaper,5 we can not help but think that there was a hidden political agenda for their publication. In these times of dwindling resources, complex access issues, and evidence-based medicine, dentistry, and public health, now is not the time to block innovative programs trying to serve the underserved. Let the Alaskan Natives, a sovereign nation, decide for themselves who can best meet their long-standing, unmet dental needs.

Can We Identify Futility in Kids? An Evaluation of Admission Parameters Predicting 100% Mortality in 1,292 Severely Injured Children

BACKGROUND Objective parameters predicting futility of care in severely injured pediatric patients are lacking. Although futility of care has been investigated in a limited number of studies in trauma patients, none of these studies achieves a 100% success rate in a large cohort of pediatric patients. The purpose of the current study was to identify extreme laboratory values that could be used to predict 100% mortality in severely injured children. STUDY DESIGN We evaluated a registry-based, historical cohort of all severely injured children (Level I trauma, younger than 16 years old) who were not dead on arrival between January 2010 and December 2016 from a single Level I trauma center. Extreme arrival laboratory data were evaluated both alone and in conjunction with traumatic brain injury. RESULTS There were 1,292 patients who met inclusion criteria, of which 1,169 (90.5%) survived and 123 (9.5%) died. Those who died were significantly younger, with higher head Abbreviated Injury Scale scores and overall Injury Severity Scores. Single extreme laboratory values were identified that predicted mortality perfectly (100% positive predictive value): international normalized ratio ≥3.0, pH ≤6.95, base excess ≤ -22, platelet count ≤30,000, hemoglobin ≤5.0 g/dL, rapid thromboelastography ≤30 mm, and rapid thromboelastography lysis at 30 minutes ≥50%. When 2 laboratory values or the presence of traumatic brain injury were added, lower thresholds for futility were noted. CONCLUSIONS Extreme admission laboratory values are capable of predicting 100% mortality and futility of additional care in severely injured children with a high level of accuracy. Validation of these single-center findings is warranted and, if supported, should initiate a discussion within the pediatric trauma community about application and cessation of resuscitation efforts to optimize resource use.