Elimination of 15N-thymidine after oral administration in human infants.

BACKGROUND: We have developed a new clinical research approach for the quantification of cellular proliferation in human infants to address unanswered questions about tissue renewal and regeneration. The approach consists of oral 15N-thymidine administration to label cells in S-phase, followed by Multi-isotope Imaging Mass Spectrometry for detection of the incorporated label in cell nuclei. To establish the approach, we performed an observational study to examine uptake and elimination of 15N-thymidine. We compared at-home label administration with in-hospital administration in infants with tetralogy of Fallot, a form of congenital heart disease, and infants with heart failure. METHODS: We examined urine samples from 18 infants who received 15N-thymidine (50 mg/kg body weight) by mouth for five consecutive days. We used Isotope Ratio Mass Spectrometry to determine enrichment of 15N relative to 14N (%) in urine. RESULTS/FINDINGS: 15N-thymidine dose administration produced periodic rises of 15N enrichment in urine. Infants with tetralogy of Fallot had a 3.2-fold increase and infants with heart failure had a 4.3-fold increase in mean peak 15N enrichment over baseline. The mean 15N enrichment was not statistically different between the two patient populations (p = 0.103). The time to peak 15N enrichment in tetralogy of Fallot infants was 6.3 ± 1 hr and in infants with heart failure 7.5 ± 2 hr (mean ± SEM). The duration of significant 15N enrichment after a dose was 18.5 ± 1.7 hr in tetralogy of Fallot and in heart failure 18.2 ± 1.8 hr (mean ± SEM). The time to peak enrichment and duration of enrichment were also not statistically different (p = 0.617 and p = 0.887). CONCLUSIONS: The presented results support two conclusions of significance for future applications: (1) Demonstration that 15N-thymidine label administration at home is equivalent to in-hospital administration. (2) Two different types of heart disease show no differences in 15N-thymidine absorption and elimination. This enables the comparative analysis of cellular proliferation between different types of heart disease.

The Need for Responsive Workforce Development During the Pandemic and Beyond: A Case Study of the Regional Public Health Training Centers.

CONTEXT: The COVID-19 pandemic underscored the importance of a strong public health infrastructure for protecting and supporting the health of communities. This includes ensuring an adaptive workforce capable of leading through rapidly changing circumstances, communicating effectively, and applying systems thinking to leverage cross-sector partnerships that help promote health equity. The 10 Regional Public Health Training Centers (PHTCs) advance the capacity of the current and future public health workforce through skill development and technical assistance in these and other strategic areas. PROGRAM: This study examines activities through which the Regional PHTCs and their partners supported the public health workforce during the pandemic. Representatives of the 10 Regional PHTCs completed a survey in the spring of 2022. The survey included (1) pulling trends in training usage from 2018-2021 annual performance reports and (2) questions assessing the type, content, and reach of training needs assessments, training and technical assistance, student placements, and PHTC Network collaborative activities that occurred from January 1, 2020, to December 31, 2021. Respondents also reflected on trends in use, challenges, lessons learned, stories of impact, and future PHTC practice. EVALUATION: During the pandemic, the Regional PHTCs engaged in numerous efforts to assess needs, provide training and technical assistance to the practice community, facilitate projects that built student competency to support public health agency efforts, and collaborate as the PHTC Network on national-level initiatives. Across these activities, the Regional PHTCs adjusted their approaches and learned from each other in order to meet regional needs. DISCUSSION: The Regional PHTCs provided student and professional development in foundational public health knowledge and skills within their regions and nationally while being flexible and responsive to the changing needs of the field during the pandemic. Our study highlights opportunities for collaboration and adaptive approaches to public health workforce development in a postpandemic environment.

Control of cytokinesis by ß-adrenergic receptors indicates an approach for regulating cardiomyocyte endowment.

One million patients with congenital heart disease (CHD) live in the United States. They have a lifelong risk of developing heart failure. Current concepts do not sufficiently address mechanisms of heart failure development specifically for these patients. Here, analysis of heart tissue from an infant with tetralogy of Fallot with pulmonary stenosis (ToF/PS) labeled with isotope-tagged thymidine demonstrated that cardiomyocyte cytokinesis failure is increased in this common form of CHD. We used single-cell transcriptional profiling to discover that the underlying mechanism of cytokinesis failure is repression of the cytokinesis gene ECT2, downstream of ß-adrenergic receptors (ß-ARs). Inactivation of the ß-AR genes and administration of the ß-blocker propranolol increased cardiomyocyte division in neonatal mice, which increased the number of cardiomyocytes (endowment) and conferred benefit after myocardial infarction in adults. Propranolol enabled the division of ToF/PS cardiomyocytes in vitro. These results suggest that ß-blockers could be evaluated for increasing cardiomyocyte division in patients with ToF/PS and other types of CHD.

Scalability of an Evidence-Based Adolescent Pregnancy Prevention Program: New Evidence From 5 Cluster-Randomized Evaluations of the Teen Outreach Program.

OBJECTIVES: To determine if the Teen Outreach Program (TOP), a youth development and service learning program, can reduce sexual risk-taking behaviors compared with a business as usual or benign counterfactual. METHODS: We synthesized results of 5 independent studies conducted in 5 geographically and ethnically diverse locations between 2011 and 2015 with 17 194 middle and high school students. Each study cluster-randomized classes, teachers, or schools to treatment or control groups and included the students enrolled in those clusters at baseline in an intent-to-treat analysis. Multilevel models tested impacts on recent sexual activity, recent unprotected sexual activity, and sexual initiation among the sexually inexperienced at baseline at approximately 1 and 2 years after baseline. RESULTS: Precision-weighted average effect sizes showed nonsignificant reductions of 1 percentage point or less in recent sexual activity (5 studies: -0.6; P = .32), recent unprotected sex (5 studies: -0.2; P = .76), and sexual initiation (4 studies: -1.1; P = .10) after 1 year. CONCLUSIONS: There was little evidence of the effectiveness of TOP in reducing sexual risk-taking behaviors. Results underscored the importance of continually evaluating evidence-based programs that have previously been shown to be effective.

What is the prevalence of senior-athlete rotator cuff injuries and are they associated with pain and dysfunction?

BACKGROUND: Older individuals with rotator cuff injuries may have difficulties not only with activities of daily living, but also with sports activities. QUESTIONS/PURPOSES: (1) How frequent and severe are rotator cuff abnormalities, as identified by ultrasound, in senior athletes? (2) To what degree does the severity of ultrasound-identified rotator cuff pathology correlate with pain and shoulder dysfunction? METHODS: We assessed pain and shoulder function in 141 elite athletes older than 60 years of age (median age, 70 years; range 60-84) at the Senior Olympics who volunteered to participate. An ultrasound evaluation of the rotator cuff of the dominant shoulder was performed by an experienced musculoskeletal radiologist in all of these elite athletes. We then determined the relationship between ultrasound findings and shoulder pain and shoulder function as assessed with the Disabilities of the Arm, Shoulder and Hand (DASH) and American Shoulder and Elbow Surgeons (ASES) scores. RESULTS: There were 20 shoulders with a normal cuff (14.2% [20 of 141], of which 5% [one of 20] were painful), 23 with tendinosis (16.3% [23 of 141], of which 30% [six of 20] were painful), 68 with a partial-thickness rotator cuff tear (48.2% [68 of 141], of which 32% [20 of 63] were painful), and 30 with a full-thickness rotator cuff tear (21.3% [30 of 141], of which 25% [seven of 28] were painful). Only 5% of athletes (one of 20) with a normal cuff on ultrasound evaluation reported shoulder pain, whereas 30% of athletes (33 of 111) with any degree of rotator cuff damage on ultrasound evaluation reported shoulder pain, This resulted in an odds ratio of 8.0 (95% confidence interval, 1.0-62.5). The proportion of patients who had pain was not different in those with different severities of rotator cuff pathology. Neither the ASES nor the DASH was different in those with different severities. CONCLUSIONS: The frequency of full-thickness rotator cuff tears in senior athletes was 21.3% (30 of 141). Pain was a predictor of rotator cuff injury but not of its severity. The odds of having shoulder pain was eight times greater in those athletes with any rotator cuff damage as compared with those without any rotator cuff damage. Those with pain had poorer shoulder function but the ASES and DASH were poor predictors of the severity of rotator cuff pathology. Rotator cuff tears in older individuals are often not painful and may not need to be repaired for successful participation in athletics. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Do patients with juvenile idiopathic arthritis in clinical remission have evidence of persistent inflammation on 3T magnetic resonance imaging?

OBJECTIVE: Up to 90% of adults with rheumatoid arthritis (RA) in clinical remission have persistent synovitis and/or bone marrow lesions (BMLs) on magnetic resonance imaging (MRI). MRI findings in patients with juvenile idiopathic arthritis (JIA) in clinical remission have not been described. We utilized 3T MRI with contrast enhancement to examine JIA patients with hand and/or wrist involvement who were in clinical remission and compared them with a cohort of adult RA patients. METHODS: In total, 11 JIA patients and 10 RA patients with arthritis involving the hands and/or wrists were identified by their primary rheumatologist as being in physician-defined clinical remission, having no signs or symptoms of active arthritis and no medication changes for at least 6 months. A study rheumatologist performed a joint evaluation for tenderness, swelling, and limitation of motion, and study participants self-reported tender joint counts. The participants underwent MRI with intravenous contrast enhancement of 1 hand and wrist with a history of prior symptoms. A pediatric musculoskeletal radiologist blinded to the clinical data scored the MRIs for synovitis, tenosynovitis, and/or BMLs. RESULTS: Sixty-three percent of the JIA cohort and 70% of the RA cohort had MRI findings of synovitis, BMLs, and/or tenosynovitis. All pediatric patients with MRI abnormalities had normal physician tender and swollen joint counts. The patients' self-report of painful joint counts did not predict MRI abnormalities. CONCLUSION: Over one-half of the patients in clinical remission had MRI evidence of persistent inflammation, defined as the presence of synovitis, tenosynovitis, or BMLs. A substantial portion of patients with JIA may have subclinical disease despite clinical remission.

Participation in high-impact sports predicts bone mineral density in senior olympic athletes.

BACKGROUND: Loss of bone mineral density (BMD) and resultant fractures increase with age in both sexes. Participation in resistance or high-impact sports is a known contributor to bone health in young athletes; however, little is known about the effect of participation in impact sports on bone density as people age. HYPOTHESIS: To test the hypothesis that high-impact sport participation will predict BMD in senior athletes, this study evaluated 560 athletes during the 2005 National Senior Games (the Senior Olympics). STUDY DESIGN: Cross-sectional methods. The athletes completed a detailed health history questionnaire and underwent calcaneal quantitative ultrasound to measure BMD. Athletes were classified as participating in high impact sports (basketball, road race [running], track and field, triathalon, and volleyball) or non-high-impact sports. Stepwise linear regression was used to determine the influence of high-impact sports on BMD. RESULTS: On average, participants were 65.9 years old (range, 50 to 93). There were 298 women (53.2%) and 289 men (51.6%) who participated in high-impact sports. Average body mass index was 25.6 ± 3.9. The quantitative ultrasound-generated T scores, a quantitative measure of BMD, averaged 0.4 ± 1.3 and -0.1 ± 1.4 for the high-impact and non-high-impact groups, respectively. After age, sex, obesity, and use of osteoporosis medication were controlled, participation in high-impact sports was a significant predictor of BMD (R(2) change 3.2%, P < .001). CONCLUSIONS: This study represents the largest sample of BMD data in senior athletes to date. Senior participation in high-impact sports positively influenced bone health, even in the oldest athletes. CLINICAL RELEVANCE: These data imply that high-impact exercise is a vital tool to maintain healthy BMD with active aging.

Behavioral health in multiracial adolescents: the role of Hispanic/Latino ethnicity.

OBJECTIVES: The purpose of the present study was twofold: (1) to determine whether adolescents who self-identify as multiracial have more adverse health behaviors than their monoracial counterparts, and (2) to examine whether the health behaviors of adolescents who are multiracial and Hispanic are more similar to those who identify as monoracial Hispanic or those who are multiracial and non-Hispanic. METHODS: Secondary analyses of data in a subsample from the Youth Risk Behavior Survey of 3,704 (27.2%) adolescents who identified as Hispanic/Latino only, multiracial Hispanic, or multiracial non-Hispanic were conducted. Regression analyses were conducted using SUDAAN for the complex sampling to test for differences in health behaviors (i.e., smoking, exercise, substance abuse, and suicide risk) among the three ethnicity/race groups. RESULTS: Each health behavior scale yielded significant between-group differences according to ethnic/racial identity: Hispanic/Latino adolescents scored significantly lower than both multiracial groups on the measure of cigarette smoking, lower than multiracial Hispanic adolescents on the substance abuse scale, and lower than multiracial non-Hispanic adolescents on the measure of exercise. The multiracial Hispanic group was also at marginally increased risk for suicide compared to the Hispanic/Latino group. CONCLUSIONS: The results support the hypothesis that multiracial Hispanic adolescents have more behavioral health problems than monoracial Hispanic adolescents. The second hypothesis--that multiracial Hispanic adolescents are more similar to multiracial non-Hispanic adolescents--was also supported. The implications of these findings for the classification of Hispanic adolescents in terms of ethnicity and race in relation to health behaviors are discussed.

Hamstring anterior cruciate ligament reconstruction: a comparison of bioabsorbable interference screw and endobutton-post fixation.

PURPOSE: The purpose of this study was to evaluate hamstring anterior cruciate ligament (ACL) reconstruction using aperture fixation with bioabsorbable interference screw (BIS) and distant fixation using EndoButton (Smith & Nephew, Andover, MA) and screw-post (ENDO). TYPE OF STUDY: Prospective nonrandomized clinical outcome study. METHODS: Two groups of 15 patients who underwent autogenous hamstring ACL reconstruction with a minimum of 2 years' follow-up evaluation (mean 35 months) were included in the study. The BIS group underwent poly-L-lactic acid interference screw fixation at both femoral and tibial tunnels and the ENDO group underwent EndoButton fixation on the femoral side and screw-post fixation on the tibial side. Clinical evaluation included International Knee Documentation Committee (IKDC) and arthrometer measurements. Tunnel enlargement, screw integrity, graft integrity, and graft-tunnel interface were evaluated using radiographs and magnetic resonance imaging. Statistical analyses were performed using the Student t test, with significance set at 0.05. RESULTS: All patients in both groups had functionally normal or near-normal IKDC scores. The average IKDC subjective knee form scores were 85 +/- 11 versus 81 +/- 17 (BIS v ENDO) and side-to-side KT differences were 3.2 +/- 2.6 mm versus 2.4 +/- 1.8 mm (P >.05). For both groups, tunnel enlargement was present on radiographs at both femoral and tibial sides (36% to 77%). Tunnel enlargement was more significant at the femoral tunnels (53% to 77%) than the tibial tunnels (36% to 42%). In the BIS group, magnetic resonance imaging revealed 9 partially degraded screws and 2 intact screws on the femoral side. On the tibial side, 4 partially degraded and 10 intact screws were seen. For both groups, the grafts have partial or complete incorporation at all tunnels. Tunnel enlargement measured on radiographs correlate well with measurements on magnetic resonance images. CONCLUSIONS: Our results showed that rigid aperture fixation using BIS did not lead to significant differences in clinical outcome when compared with distant fixation using ENDO at 24 to 40 months follow-up evaluation. Significant tunnel enlargement was present in both groups, more pronounced on the femoral side. Magnetic resonance imaging findings showed that BIS were not degraded even at 2 to 4 years after surgery. LEVEL OF EVIDENCE: Level II.

Surgical management of knee dislocations.

BACKGROUND: The evaluation and management of knee dislocations remain variable and controversial. The purpose of this study was to describe our method of surgical treatment of knee dislocations with use of a standardized protocol and to report the clinical results. METHODS: Forty-seven consecutive patients presented with an occult (reduced) or grossly dislocated knee. Fourteen of these patients were not included in this series because of confounding variables: four had an open knee dislocation, five had vascular injury requiring repair, three were treated with external fixation, and two had associated injury. The remaining thirty-three patients underwent surgical treatment for the knee dislocation with our standard approach. Anatomical repair and/or replacement was performed with fresh-frozen allograft tissue. Thirty-one of the thirty-three patients returned for subjective and objective evaluation with use of four different knee rating scales at a minimum of twenty-four months after the operation. RESULTS: Nineteen of the thirty-one patients were treated acutely (less than three weeks after the injury) and twelve, chronically. The mean Lysholm score was 91 points for the acutely reconstructed knees and 80 points for the chronically reconstructed knees. The Knee Outcome Survey Activities of Daily Living scores averaged 91 points for the acutely reconstructed knees and 84 points for the chronically reconstructed knees. The Knee Outcome Survey Sports Activity scores averaged 89 points for the acutely reconstructed knees and 69 points for the chronically reconstructed knees. According to the Meyers ratings, twenty-three patients had an excellent or good score and eight had a fair or poor score. Sixteen of the nineteen acutely reconstructed knees and seven of the twelve chronically reconstructed knees were given an excellent or a good Meyers score. The average loss of extension was 1 degrees, and the average loss of flexion was 12 degrees. There was no difference in the range of motion between the acutely and chronically treated patients. Four acutely reconstructed knees required manipulation because of loss of flexion. Laxity tests demonstrated consistently improved stability in all patients, with more predictable results in the acutely treated patients. CONCLUSIONS: Surgical treatment of the knee dislocations in our series provided satisfactory subjective and objective outcomes at two to six years postoperatively. The patients who were treated acutely had higher subjective scores and better objective restoration of knee stability than did patients treated three weeks or more after the injury. Nearly all patients were able to perform daily activities with few problems. However, the ability of patients to return to high-demand sports and strenuous manual labor was less predictable.