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The objective of this study was to evaluate the clinical utility of a routine pre-discharge white blood cell count (RPD-WBC) for predicting post-discharge organ space infection (OSI) in children with complicated appendicitis.This was a multicenter study using NSQIP-Pediatric data from 14 hospitals augmented with RPD-WBC data obtained through supplemental chart review. Children with fever or surgical site infection diagnosed during the index admission were excluded. Positive predictive value (PPV) for post-discharge OSI was calculated for RPD-WBC values of persistent leukocytosis (≥9.0x103 cells per microliter), increasing leukocytosis (RPD-WBCpreoperative WBC), quartiles of absolute RPD-WBC, and quartiles of relative proportional change from preoperative WBC. Logistic regression was used to calculate predictive values adjusted for patient age, appendicitis severity, and use of post-discharge antibiotics.1264 children were included, of which 348 (27.5%) had a RPD-WBC obtained (hospital range: 0.8-100%, P0.01). Median RPD-WBC was similar between children who did and did not develop a post-discharge OSI (9.0 vs. 8.9; p=0.57), and leukocytosis was absent in 50% of children who developed a post-discharge OSI. The PPV of RPD-WBC was poor for both persistent and increasing leukocytosis (3.9% and 9.8%, respectively), and for thresholds based on the quartiles of highest RPD-WBC values (11.1, PPV: 6.4%) and greatest proportional change (32% decrease from preoperative WBC; PPV: 7.8%).Routine pre-discharge WBC data have poor predictive value for identifying children at risk for post-discharge OSI following appendectomy for complicated appendicitis.

IMPORTANCE: The clinical significance of gangrenous, suppurative, or exudative (GSE) findings is poorly characterized in children with nonperforated appendicitis. OBJECTIVE: To evaluate whether GSE findings in children with nonperforated appendicitis are associated with increased risk of surgical site infections and resource utilization. DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study used data from the Appendectomy Targeted Database of the American College of Surgeons Pediatric National Surgical Quality Improvement Program, which were augmented with operative report data obtained by supplemental medical record review. Data were obtained from 15 hospitals participating in the Eastern Pediatric Surgery Network (EPSN) research consortium. The study cohort comprised children (aged ≤18 years) with nonperforated appendicitis who underwent appendectomy from July 1, 2015, to June 30, 2020. EXPOSURES: The presence of GSE findings was established through standardized, keyword-based audits of operative reports by EPSN surgeons. Interrater agreement for the presence or absence of GSE findings was evaluated in a random sample of 900 operative reports. MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day postoperative surgical site infections (incisional and organ space infections). Secondary outcomes included rates of hospital revisits, postoperative abdominal imaging, and postoperative length of stay. Multivariable mixed-effects regression was used to adjust measures of association for patient characteristics and clustering within hospitals. RESULTS: Among 6133 children with nonperforated appendicitis, 867 (14.1%) had GSE findings identified from operative report review (hospital range, 4.2%-30.2%; P

Background/Purpose We sought to analyze the use of angioembolization (AE) after pediatric splenic injuries at adult and pediatric trauma centers (ATCs/PTCs). Methods The National Trauma Data Bank (2010–2015) was queried for patients ( Results 14,027 encounters met inclusion criteria. 514 (3.7%) patients underwent AE. When compared to PTCs, patients were older, had a higher ISS, and more often presented in shock at ATCs (p Conclusions AE was associated with improved splenic salvage at ATCs in select patients but appeared overutilized when compared to outcomes at PTCs. PTCs accomplished a higher splenic salvage rate with a lower AE utilization. Level of evidence III – Retrospective cohort study.

To evaluate whether redosing antibiotics within an hour of incision is associated with a reduction in incisional surgical site infection (iSSI) in children with appendicitis.Existing data remain conflicting as to whether children with appendicitis receiving antibiotics at diagnosis benefit from antibiotic redosing prior to incision.This was a multicenter retrospective cohort study using data from the Pediatric National Surgical Quality Improvement Program augmented with antibiotic utilization and operative report data obtained though supplemental chart review. Children undergoing appendectomy at 14 hospitals participating in the Eastern Pediatric Surgery Network from 7/2016-6/2020 who received antibiotics upon diagnosis of appendicitis between 1-6 hours prior to incision were included. Multivariable logistic regression was used to compare odds of iSSI in those who were and were not redosed with antibiotics within one hour of incision, adjusting for patient demographics, disease severity, antibiotic agents, and hospital-level clustering of events.3,533 children from 14 hospitals were included. Overall, 46.5% were redosed (hospital range: 1.8%-94.4%, P0.001) and iSSI rates were similar between groups (redosed: 1.2% vs. non-redosed: 1.3%; OR 0.84, [95%CI 0.39-1.83]). In subgroup analyses, redosing was associated with lower iSSI rates when cefoxitin was used as the initial antibiotic (redosed: 1.0% vs. non-redosed: 2.5%; OR 0.38, [95%CI 0.17-0.84]), but no benefit was found with other antibiotic regimens, longer periods between initial antibiotic administration and incision, or with increased disease severity.Redosing of antibiotics within one hour of incision in children who received their initial dose within 6 hours of incision was not associated with reduction in risk of incisional site infection unless cefoxitin was used as the initial antibiotic.

Although physiologic differences exist between younger and older children, pediatric trauma analyses are weighted toward older patients. Trauma-induced coagulopathy, determined by rapid thrombelastography (rTEG), is a predictor of outcome in trauma patients, but the significance of rTEG values among very young trauma patients remains unknown. Our objective was to identify the prehospital or physiologic factors, including rTEG values, that were associated with mortality in trauma patients younger than 5 y old.Patients younger than 5 y old that met the highest-level trauma activation criteria at an academic children's hospital from 2010-2016 were included. Data regarding demographics, pre-hospital management, laboratory values, injury severity, and outcome were queried. Univariate and multivariate analyses were performed comparing survivors and non-survivors.A total of 356 patients were included. 60% were male, and the median age was 3 y (IQR 1-4). Overall mortality was 13% (n = 45); brain injury (91%) and hemorrhage (9%) were the causes of death. Compared to survivors, rTEG values in nonsurvivors showed longer activated clotting time and slower speed of clot formation. Clot strength was also decreased in nonsurvivors. On stepwise regression modeling, rTEG values were not significant predictors of mortality. Admission base deficit, arrival temperature, and head injury severity were identified as independent predictors of mortality.While rTEG identified coagulopathy in trauma patients5 y old, it was not an independent predictor of mortality. Our findings suggest that trauma providers should pay close attention to admission base deficit, arrival temperature, and head injury severity when managing the youngest trauma patients.

Recent work has questioned the accuracy of the Injury Severity Score (ISS) and the Abbreviated Injury Scale (AIS) in the pediatric population. We sought to determine mortality rates in pediatric trauma patients at ISSs considered "severe" in adults and whether mortality would vary substantially between adults and children sustaining injuries with the same AIS.Univariate logistic regression was used to generate mortality rates associated with ISS scores, for children (16 years of age) and adults, using the 2016 National Trauma Data Bank. Mortality rates at an ISS of 15 were calculated in both groups. We similarly calculated ISS scores associated with mortality rates of 10%, 25%, and 50%. Receiver operating characteristic curves were constructed to compare the discriminative ability of ISS to predict mortality after blunt and penetrating injuries in adults and children. Mortality rates associated with 1 or more AIS 3 injuries per body region were defined.There were 855,454 cases, 86,414 (10.1%) of which were children. The ISS associated with 10%, 25%, and 50% mortality were 35, 44, and 53, respectively, in children; they were 27, 38, and 48 in adults. At an ISS of 15, pediatric mortality was 1.0%; in adults, it was 3.1%. A 3.1% mortality rate was not observed in children until an ISS of 25. On receiver operating characteristic analysis, the ISS performed better in children compared with adults (area under the curve, 0.965 vs 0.860 [P0.001]). Adults consistently suffered from higher mortality rates than did children with the same number of severe injuries to a body region, and mortality varied widely between specific selected AIS 3 injuries.Although the ISS predicts mortality well, children have lower mortality than do adults for the same ISS, and therefore, the accepted definition of severe injury is not equivalent between these 2 cohorts. Mortality risk is highly dependent on the specific nature of the injury, with large variability in outcomes despite identical AIS scores.

BACKGROUND Pediatric firearm injury is a leading cause of death for U.S. children. We sought to further characterize children who die from these injuries using a validated national database. METHODS The National Trauma Data Bank 2010 to 2016 was queried for patients aged 0 to 19 years old. International Classification of Diseases external cause of injury codes were used to classify patients by intent. Differences between groups were analyzed using χ or Mann-Whitney U tests. Patterns over time were analyzed using nonparametric tests for trend. Multivariable logistic regression was used to investigate associations between the above factors and mortality. RESULTS There were a total of 45,288 children with firearm injuries, 12.0% (n = 5,412) of whom died. Those who died were younger and more often white than survivors. Mortality was associated with increased injury severity, shock on presentation, and polytrauma (p < 0.001 for all). There was an increasing trend in the proportion of self-inflicted injuries over the study period (p < 0.001), and mortality from these self-inflicted injuries increased concordantly (35.3% in 2010 to 47.8% in 2016, p = 0.001). Location of severe injuries had significant different mortality rates, ranging from 51.3% of head injuries to 3.9% in the extremities. In the multivariable model, treatment at a pediatric trauma center was protective against mortality, with odds ratios of 2.10 (confidence interval, 1.64-2.68) and 1.80 (confidence interval, 1.39-2.32) for death at adult and dual-designated trauma centers, respectively. This finding was confirmed in age-stratified cohorts. CONCLUSION Proportions of self-inflicted pediatric firearm injury in the National Trauma Data Bank increased from 2010 to 2016, as did mortality from self-inflicted injury. Because mortality is highest in this subpopulation, prevention and treatment efforts should be prioritized in this group of firearm-injured children. LEVEL OF EVIDENCE Epidemiological study, level V.

The significance and management of pediatric pneumatosis intestinalis (PI) remains poorly defined. We sought to add clarity in children beyond the neonatal period. Pediatric patients 3 months–18 years admitted to a quaternary children’s hospital with a diagnosis of PI were included in this retrospective study. Pathologic PI was defined as irreversible, transmural intestinal ischemia. 167 children were identified with PI. Of these children, 155 (92.8%) had benign PI and 12 (7.2%) developed pathologic PI. The most common underlying diagnosis for pathologic PI was global developmental delay (75%), although we identified a spectrum of underlying diagnoses at risk for PI. Physical exam notable for abdominal distension (p = 0.023) or guarding (p = 0.028), and imaging with portal venous gas (p

We sought to analyze the use of angioembolization (AE) after pediatric splenic injuries at adult and pediatric trauma centers (ATCs/PTCs).The National Trauma Data Bank (2010-2015) was queried for patients (18 years) who experienced blunt splenic trauma. Multivariate logistic regression was used to determine the association of AE with splenectomy. Propensity score matching was used to explore the relationship between trauma center designation and AE utilization.14,027 encounters met inclusion criteria. 514 (3.7%) patients underwent AE. When compared to PTCs, patients were older, had a higher ISS, and more often presented in shock at ATCs (p0.001 for all). Regression models demonstrated no difference in mortality between cohorts. Odds of splenectomy were lower for patients undergoing AE (OR 0.16 [CI: 0.08-0.31]), however this effect was mostly driven by utilization at ATCs. Using a 1:1 propensity score matching model, patients treated at ATCs were 4 times more likely to undergo AE and 7 times more likely to require a splenectomy compared to PTCs (p0.001). Over 6 years, PTCs performed only 27 splenectomies and 23 AEs (1.1% and 0.9%, respectively).AE was associated with improved splenic salvage at ATCs in select patients but appeared overutilized when compared to outcomes at PTCs. PTCs accomplished a higher splenic salvage rate with a lower AE utilization.III - Retrospective cohort study.

To determine the incidence and outcomes of firearm injuries in adolescents and the effect of trauma center (TC) designation on their mortality.The National Trauma Data Bank (2010-2016) was queried for all encounters involving adolescents aged 13-16 years with firearm injuries. Multivariable logistic regression was employed to determine the association of covariates with mortality (α = .05). Propensity score matching was also used to explore the relationship between TC designation and mortality.A total of 9,029 adolescents met inclusion criteria. Patients aged 15 and 16 years compromised 77.8% of the cohort and were more often male (87.9% vs. 80.6%, p.001), black (63.8% vs. 56.1%, p.001), injured in the abdomen (25.4% vs. 22.4%, p = .007) or extremities (62.3% vs. 56.7%, p.001), and incurred severe injuries (54.5% vs. 50.9%, p = .004) versus 13- and 14-year-old patients. Younger patients were more often injured in the head/neck (23.8% vs. 20.5%, p = .001). Multivariable logistic regression demonstrated no difference in mortality between age groups. Poor neurologic presentation, severe injury, abdominal, chest, and head injuries were all associated with an increased odds of death. Odds of mortality were 2.88 times higher at adult TCs compared to pediatric TCs (CI: 1.55-5.36, p = .001). However, using a 1:1 propensity score matching model, no difference in mortality was found between TC types (p = NS).Variability exists in outcomes for adolescents after firearm injuries. Understanding and identifying the potential differences between pediatric and adult TCs managing adolescent firearm victims may improve survival in all treatment venues, but these data support patients being treated at the closest available TC.

Chest x-ray (CXR) has been shown to be an effective detection tool for clinically significant trauma. We evaluated differences in findings between CXR and computed tomography of the chest (CCT), their impact on clinical management and the performance of the CXR.This retrospective study examined children (less than 18 years) who received a CXR and CCT between 2009 and 2015. We compared characteristics of children by conducting univariate analysis, reporting the proportion of additional diagnoses captured by CCT, and using it to evaluate the sensitivity and specificity of the CXR. Outcome variables were diagnoses made by CCT as well as the ensuing changes in the clinical management attributable to the diagnoses reported by the CCT and not observed by the CXR.In 1235 children, CCT was associated with diagnosing higher proportions of contusion or atelectasis (60% vs 31%; p .0001), pneumothorax (23% vs 9%; p .0001), rib fracture (18% vs 7%; p .0001), other fracture (20% vs 10%; p .0001), diaphragm rupture (0.2% vs 0.1%; p = .002), and incidental findings (7% vs 2%; p .0001) as compared to CXR. CCT findings changed the management of 107 children (8.7%) with 32 (2.6%) of the changes being surgical procedures. The overall sensitivity and specificity of the CXR were 57.9% (95% CI: 54.5-61.2) and 90.2% (95% CI: 86.8-93.1), respectively. The positive predictive value and negative predictive value were 93.1% and 48.6%, respectively.CXR is a useful initial screening tool to evaluate pediatric trauma patients along with clinical presentation in the Emergency Department in children.Level III, diagnostic test.

Necrotizing fasciitis in the pediatric population is a particularly difficult diagnostic and management challenge. Options for soft tissue reconstruction of wounds following surgical debridement have been historically limited, yet recent advancements in bioengineered tissue and matrices have introduced alternative methods of treatment for these patients. We present a case of neonatal necrotizing fasciitis of the scalp requiring full-thickness surgical debridement, which was successfully reconstructed using Epicel cultured epidermal autograft (CEA). A 4-day-old female neonate (gestational age 40 weeks) presented with scalp erythema, blistering, and sepsis following peripartum fetal scalp electrode monitoring. She underwent surgical excision of the scalp to healthy bleeding tissue resulting in a defect of approximately 97% of the scalp, measuring 18 × 19 cm including 4 × 3.5 cm of exposed bone at the occiput. Initial provisional coverage of the defect was obtained with Integra collagen matrix bilayer dressing to stimulate granulation over exposed bone. Concurrently, a 2 × 4-cm excisional biopsy of the left groin skin was obtained for CEA in vitro expansion over 21 days. Then, autograft sheets were applied to achieve total scalp coverage. Clinical assessments at 1 week, 1 month, and 2 months postoperatively exhibited, approximately, 60% take, 80% take, and 90% take, respectively. Scalp involvement in neonatal necrotizing infections is a notably rare presentation as surmised by our review of the literature, and to our knowledge, this is the first report on the use of Integra and CEA for near-total neonatal scalp coverage.

Background In contrast to adults, the fetal response to myocardial infarction (MI) is regenerative, requiring the recruitment of cardiac progenitor cells to replace infarcted myocardium. Macrophage contribution to tissue repair depends on their phenotype: M1 are proinflammatory and initiate angiogenesis; M2a are profibrotic and contribute to blood vessels maturation; and M2c are proremodeling and proangiogenesis. The goal of the present study was to expand on this work by examining cardiac progenitor cells recruitment, and the role of macrophages in promoting angiogenesis and cardiac regeneration in the fetal heart after MI. Methods Fetal and adult sheep underwent MI and were sacrificed 3 or 30 days after MI. Some fetal hearts received stromal cell-derived factor-1α-inhibitor treatment. The microvasculature was evaluated by micro–computed tomography, gene expression was evaluated by real-time polymerase chain reaction, and vessels counts were evaluated by immunohistochemistry. Results Micro–computed tomography analysis showed restoration of microvasculature in fetal hearts after MI. Vascular endothelial growth factor-α increased, and the expression of tissue markers associated with the M1, M2a, and M2c macrophage phenotypes were elevated at day 3 after MI, but returned to baseline by 30 days after MI. In contrast, adult hearts after MI exhibited low vascular endothelial growth factor-α and persistent upregulation of all macrophage markers, consistent with prolonged inflammation, fibrosis, and remodeling. Inhibition of stromal cell-derived factor-1α in fetal infarcts prevented angiogenesis, decreased vascular endothelial growth factor-α, and was associated with a sustained increase in M1, M2a, and M2c markers after MI. Conclusions Changes in angiogenesis and macrophage phenotype-related gene expression after MI are important for the fetal regenerative response to MI and are mediated at least in part by cardiac progenitor cells recruitment.

Background Global extracellular matrix (ECM)-related gene expression is decreased after myocardial infarction (MI) in fetal sheep when compared with adult sheep. Transforming growth factor (TGF)-β1 is a key regulator of ECM; therefore we hypothesize that TGF-β1 is differentially expressed in adult and fetal infarcts after MI. Methods Adult and fetal sheep underwent MI via ligation of the left anterior descending coronary artery. Expression of TGF-β1 and ECM-related genes was evaluated by ovine-specific microarray and quantitative polymerase chain reaction. Fibroblasts from the left ventricle of adult and fetal hearts were treated with TGF-β1 or a TGF-β1 receptor inhibitor (LY36497) to evaluate the effect of TGF-β1 on ECM-related genes. Results Col1a1, col3a1, and MMP9 expression were increased in adult infarcts 3 and 30 days after MI but were upregulated in fetal infarcts only 3 days after MI. Three days after MI elastin expression was increased in adult infarcts. Despite upregulation in adult infarcts both 3 and 30 days after MI, TGF-β1 was not upregulated in fetal infarcts at any time point. Inhibition of the TGF-β1 receptor in adult cardiac fibroblasts decreased expression of col1a1, col3a1, MMP9, elastin, and TIMP1, whereas treatment of fetal cardiac fibroblasts with TGF-β1 increased expression of these genes. Conclusions TGF-β1 is increased in adult infarcts compared with regenerative, fetal infarcts after MI. Although treatment of fetal cardiac fibroblasts with TGF-β1 conveys an adult phenotype, inhibition of TGF-β1 conveys a fetal phenotype to adult cardiac fibroblasts. Decreasing TGF-β1 after MI may facilitate myocardial regeneration by "fetalizing" the otherwise fibrotic, adult response to MI.

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.

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.

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.

Community water fluoridation (CWF) and its effect in reducing the burden of dental caries (tooth decay) is considered one of the 10 public health achievements in the 20th century. In the U.S., three-quarters (74.4%) of people on community water supplies have optimally fluoridated water, and each year approximately 90 communities actively consider starting or discontinuing CWF. CWF exists within the policy environment and includes actions taken by local community councils, health and water boards, and groups; state legislatures and health departments; national regulatory and science agencies; independent science entities; and professional and nonprofit organizations. Epidemiologists have been in the forefront of CWF. Experience with the past 70 years reveals that the coming decades will bring additional questions, recommendations, and challenges for CWF. The continued involvement of epidemiologists as part of multidisciplinary teams is needed in research, surveillance, peer review of studies, assessment of systematic review findings, and in the translation and communication of science findings to audiences with limited science/health literacy. This chapter's purpose is to 1) examine how epidemiologic evidence regarding CWF has been translated into practice and policy, 2) examine how recommendations for and challenges to CWF have affected epidemiologic research and community decision-making, and 3) identify lessons learned for epidemiologists.

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.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.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 (p0.001) and a significant decrease in the number of nkx2.5+ cells repopulating the infarct (p0.001).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.

Fetal wounds have been found to have increased levels of high-molecular-weight hyaluronan (HMW-HA) compared with those of adults. The primary enzyme responsible for producing HMW-HA is hyaluronic acid synthase-1 (HAS-1). We hypothesized that over-expression of HAS-1 in adult dermal wounds would decrease inflammation and promote regenerative healing. To test this hypothesis, the flanks of adult C57Bl/6 mice were treated with a lentiviral construct containing either HAS-1-GFP or GFP transgenes. After 48 h, a 4-mm excisional wound was made at the site of treatment. Wounds were harvested at days 3, 7, or 28 after wounding. Wound phenotype was assessed by histology to examine tissue architecture and immunohistochemistry for CD45. At 7 and 28 days, lenti-HAS-1-treated wounds demonstrated the restoration of the normal dermal elements and organized collagen fiber orientation. In contrast, the lenti-GFP-treated wounds lacked normal dermal architecture and demonstrated a disorganized collagen scar. At 3 and 7 days, wounds treated with lenti-HAS-1 exhibited a significant decrease in the number of inflammatory cells when compared with wounds treated with lenti-GFP. Thus, HAS-1 over-expression promotes dermal regeneration, in part by decreasing the inflammatory response and by recapitulation of fetal extracellular matrix HMW-HA content.

Objectives:Theadult response to myocardialinfarctionresults in inflammation, scarformation,left ventriculardilatation, andloss of regional and global function. Regenerative scarless healing has been demonstrated in foetal dermis and tendon and is associated with diminished inflammation. We hypothesised that following foetal myocardial infarction, there would be minimal inflammation, regenerative healing, and preservation of function. Methods: Anteroapical myocardial infarction encompassing 20% of the left ventricle was created in adult or early gestation foetal sheep. Myocardial function was serially assessed using quantitative echocardiography. Infarct architecture was examined histologically for evidence of scar formation. Cellular inflammation, cellular proliferation, and apoptosis were assessed using immunohistochemistry. Results: In the adult sheep 4 weeks following myocardial infarction, there was a significant decline in ejection fraction (EF) (41 � 7.4% to 26 � 7.4%, p < 0.05), and the akinetic myocardial segment increased in size (6.9 � 0.8 cm to 7.9 � 1.1 cm, p < 0.05). By contrast, there was no decline in the foetal EF (53 � 8.1% to 55 � 8.8%) and no akinetic foetal myocardial segment 4 weeks post-infarction. The foetal infarcts lacked an inflammatory cell infiltrate and healed with minimal fibrosis, compared with the adults. Foetal infarcts also demonstrated 5-bromo-20deoxyuridine (BrdU)+ proliferating cells, including cardiomyocytes, within the infarct. Conclusions: These data demonstrate that the foetal response to myocardial infarction is dramatically different from the adult and is characterised by minimal inflammation, lack of fibrosis, myocardial proliferation and restoration of cardiac function. Diminished inflammation is associated with foetal regenerative cardiac healing following injury. Understanding the mechanisms involved in foetal myocardial regeneration may lead to applications to alter the adult response following myocardial infarction. # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Reduction of substituted benzophenones, benzhydrols, diaryl alkenes, and benzylideneacetophenones with D3PO2 in DOAc in the presence of a small amount of iodine results in reduction to the corresponding alkanes efficiently, relatively inexpensively, and with regioselective incorporation of deuterium. Isotopic exchange results in incorporation of more than the expected amount of deuterium with the last two classes of compound.

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.

In the United States, 95 percent of teens and 85 percent of adults use the Internet. Two social media outlets, Facebook and Twitter, reach more than 150 billion users. This study describes anti-fluoridation activity and dominance on the Internet and social media, both of which are community water fluoridation (CWF) information sources.Monthly website traffic to major fluoridation websites was determined from June 2011 to May 2012. Facebook, Twitter, and YouTube fluoridation activity was categorized as "proCWF" or "anti-CWF." Twitter's anti-CWF tweets were further subcategorized by the argument used against CWF.Anti-CWF website traffic was found to exceed proCWF activity five- to sixty-fold. Searching "fluoride" and "fluoridation" on Facebook resulted in 88 to 100 percent anti-CWF groups and pages; "fluoridation" on Twitter and YouTube resulted in 64 percent anti-CWF tweets and 99 percent anti-CWF videos, respectively. "Cancer, " "useless, " and "poisonous" were the three major arguments used against fluoridation.Anti-fluoridation information significantly dominates the Internet and social media. Thousands of people are being misinformed daily about the safety, health, and economic benefits of fluoridation.

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.

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

During the 1980s, national policy promoted military expenditures and downsized domestic programs. These priorities, along with tax reform and deregulation, created a "domestic gulf crisis" with a new wave of vulnerable populations--poor children, the homeless, the elderly, and the uninsured. Our lack of a national health program compounds the problem. The 1990s will be a decade of change and challenge. To forge a healthier and stronger future for our nation, we must implement five public health imperatives: (1) We must have a national health program that is universal, comprehensive, and prevention-oriented, with built-in assurances for quality, efficiency, and a strong public health infrastructure. (2) We must have a comprehensive national health education and promotion program for all schoolchildren. (3) Women must have freedom of choice. (4) Prevention and public health must become one of our country's highest health priorities. (5) The federal government must increase its leadership, commitments, and resources to reach the goals set forth in Healthy Communities 2000 and Healthy People 2000.

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.

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.

The first US surgeon general’s report on oral health will be released soon. Oral diseases have been called a “neglected epidemic,”1–4 because, although they affect virtually the entire population, they have not been made a priority in our country. The surgeon general’s report can help educate and sensitize policy-makers and health leaders about the importance of oral health and the need to make oral health an integral component of all health programs. In the words of former Surgeon General C. Everett Koop, “You’re not healthy without good oral health.” We must seize this unprecedented opportunity to ensure that the mouth becomes reconnected to the rest of the body in health policies and programs. It makes no sense that children, diabetic persons, or senior citizens with an abscess on their leg can receive care through their health insurance or a health program, but if the abscess is in their mouth, they may not be covered. For vulnerable populations and the “have-nots,” the barriers to dental care are even greater. Although we have made much progress in improving oral health since the 1970s as a result of fluoridation, fluorides, new technology, changing attitudes, and increased use of services, oral diseases are still a neglected epidemic. The facts speak for themselves. Seventy-eight percent of 17-year-olds have had tooth decay, with an average of 7 affected tooth surfaces (C. M. Vargas, unpublished estimates, Third National Health and Nutrition Examination Survey, 2000), and 98% of 40- to 44-year-olds have had tooth decay, with an average of 45 affected tooth surfaces (C. M. Vargas, unpublished estimates, Third National Health and Nutrition Examination Survey, 2000). Thirty percent of Americans older than 65 years have no teeth at all.5 Twenty-two percent of 35- to 44-year-olds have destructive periodontal disease.5 Finally, more Americans die from oral and pharyngeal cancer than cervical cancer or melanoma each year.6 Although tooth decay in children has decreased considerably,7 it still affects most children and adults, especially as people live longer and retain more of their teeth. Populations at higher socioeconomic levels are able to pay for dental care; however, dental care is often a luxury for vulnerable and high-risk populations. Jonathan Kozol writes, “Bleeding gums, impacted teeth and rotting teeth are routine matters for the children I have interviewed in the South Bronx. Children get used to feeling constant pain. They go to sleep with it. They go to school with it. … Children live for months with pain that grown-ups would find unendurable.”8(p20,21)

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.