Providing doula support to publicly insured women in central Texas: A financial cost-benefit analysis.

BACKGROUND: Disparities in birth outcomes continue to exist in the United States, particularly for low-income, publicly insured women. Doula support has been shown to be a cost-effective intervention in predominantly middle-to-upper income White populations, and across all publicly insured women at the state level. This analysis extends previous studies by providing an estimate of benefits that incorporates variations in averted outcomes by race and ethnicity in the context of one region in Texas. The objectives of this study were to determine (1) whether the financial value of benefits provided by doula support exceeds the costs of delivering it; (2) whether the cost-benefit ratio differs by race and ethnicity; and (3) how different doula reimbursement levels affect the cost-benefit results with respect to pregnant people covered by Medicaid in central Texas. METHODS: We conducted a forward-looking cost-benefit analysis using secondary data carried out over a short-term time horizon taking a public payer perspective. We focused on a narrow set of health outcomes (preterm delivery and cesarean delivery) that was relatively straightforward to monetize. The current, usual care state was used as the comparison condition. RESULTS: Providing pregnant people covered by Texas Medicaid with access to doulas during their pregnancies was cost-beneficial (benefit-to-cost ratio: 1.15) in the base model, and 65.7% of the time in probabilistic sensitivity analyses covering a feasible range of parameters. The intervention is most cost-beneficial for Black women. Reimbursing doulas at $869 per client or more yielded costs that were greater than benefits, holding other parameters constant. CONCLUSIONS: Expanding Medicaid pregnancy-related coverage to include doula services would be cost-beneficial and improve health equity in Texas.

Analysis of the Actions of RARγ Agonists on Growing Osteochondromas in a Mouse Model.

The actions of the retinoic acid nuclear receptor gamma (RARγ) agonist, palovarotene, on pre-existing osteochondromas were investigated using a mouse multiple osteochondroma model. This approach was based on the knowledge that patients often present to the clinic after realizing the existence of osteochondroma masses, and the findings from preclinical investigations are the effects of drugs on the initial formation of osteochondromas. Systemic administration of palovarotene, with increased doses (from 1.76 to 4.0 mg/kg) over time, fully inhibited tumor growth, keeping the tumor size (0.31 ± 0.049 mm3) similar to the initial size (0.27 ± 0.031 mm3, p = 0.66) while the control group tumor grew (1.03 ± 0.23 mm3, p = 0.023 to the drug-treated group). Nanoparticle (NP)-based local delivery of the RARγ agonist also inhibited the growth of osteochondromas at an early stage (Control: 0.52 ± 0.11 mm3; NP: 0.26 ± 0.10, p = 0.008). Transcriptome analysis revealed that the osteoarthritis pathway was activated in cultured chondrocytes treated with palovarotene (Z-score = 2.29), with the upregulation of matrix catabolic genes and the downregulation of matrix anabolic genes, consistent with the histology of palovarotene-treated osteochondromas. A reporter assay performed in cultured chondrocytes demonstrated that the Stat3 pathway, but not the Stat1/2 pathway, was stimulated by RARγ agonists. The activation of Stat3 by palovarotene was confirmed using immunoblotting and immunohistochemistry. These findings suggest that palovarotene treatment is effective against pre-existing osteochondromas and that the Stat3 pathway is involved in the antitumor actions of palovarotene.

Influences of the Home Language and Literacy Environment on Spanish and English Vocabulary Growth among Dual Language Learners.

Little is known regarding the extent to which aspects of the home language and literacy environment (HLE) promote growth in language skills among dual language learners (DLLs). Therefore, the purpose of this study was to evaluate which aspects of the HLE significantly predict growth in English and Spanish vocabulary among Spanish-speaking DLLs. 944 Spanish-speaking DLLs (51.6% female; mean age = 53.77 months) completed assessments of English and Spanish vocabulary at four time points across two academic years. Parents completed a survey of the HLE that included information on language exposure, reading exposure, and family reading habits. Results indicated that specific literacy-related practices, including availability of books in the home, language read to the child, and parental reading skills were significant predictors of growth in children's Spanish and English vocabulary knowledge, even after controlling children's initial level of language skills and family socioeconomic status.

Cost-effectiveness of a comprehensive immunization program serving high-risk, uninsured adults.

Despite the numerous social and economic benefits of vaccination, adult immunization rates fall far short of recommended levels costing the United States $9 billion annually in health care expenditures and reduced productivity. While it is well recognized that childhood immunization is highly cost-effective, the economic impact of adult immunization programs varies by disease and is influenced by population demographics. This study aimed to assess the cost-effectiveness of a comprehensive adult immunization program serving high-need populations delivered by a local health department (LHD) in partnership with community organizations. We modeled incremental cost-effectiveness taking the payer perspective of each vaccine separately in simulated cohorts of 100,000 over a 20-year horizon using data provided by the LHD and data from the published literature. We adjusted the results to align with actual program delivery and used them to estimate an incremental cost-effectiveness ratio (ICER) for the entire program. We assessed the effects of varying our base model parameters in univariate sensitivity analyses. We discounted benefits and life years saved (LYS) at 3% and adjusted results to 2016 US$. Four of seven disease models were cost-effective (using a $100,000 CE threshold) with ICERS ranging from $14,260 to $79,022/LYS. Sensitivity analyses did not substantially impact the results. The ICER for program as a whole was $67,940/LYS. A community-delivered comprehensive immunization program serving uninsured, low income, high-risk adults is a cost-effective investment even when most do not receive the full regimen of some vaccines.

Household costs of breast cancer morbidity: An empirical assessment from Pakistan.

PURPOSE: Health care costs attributable to breast cancer are substantial. In countries with high poverty, lack of public health infrastructure and low availability of health insurance, the economic burden of disease does not accrue solely to health care, but also on patients and their families. This study was conducted to explore the cost burden (i.e. direct medical costs, direct non-medical costs and indirect non-medical costs) incurred by breast cancer patients and their families over diagnosis and treatment. METHODS: Data was collected from 200 breast cancer patients at two hospitals in Lahore, provincial capital of Punjab, Pakistan, by employing purposive sampling technique. Costs were aggregated into three categories and compared with each other as per their weightage. RESULTS: The study found that direct medical care (US$ 1262.18/ Local currency (PKR) 129,717) is the largest expense, followed by direct non-medical (US$ 310.88 / PKR 31,950) and indirect non-medical costs (US$ 273.38 / PKR 28,096). CONCLUSIONS: The results of this study provide rich insight into the financial burden borne by households of breast cancer patients and suggest policy implications.

Asthma, allergy, and obesity: Examining the relationship among Nevada children.

OBJECTIVE: The majority of pediatric asthma is atopic, but whether pediatric obese asthma is atopic is indeterminate in the literature. In Nevada, children become sensitized to aeroallergens, a risk factor for asthma, at young ages. Additionally, Nevada children have high rates of obesity. Our objective is to determine whether elevated body mass index (BMI) is associated with asthma severity, allergen sensitization, and polysensitization. METHODS: Medical records from a pediatric allergy clinic provided BMI percentile, physician-diagnosed asthma severity, skin prick test data, and sociodemographics such as age, race, sex, and insurance status from asthmatic patients. Descriptive statistics and binary and multinomial logistic regression were conducted. RESULTS: In this population (N = 125) aged 1-16, 61% were male, 65% were white, and 74% had private health insurance. Sixty-five percent of children were under/healthy weight and 29% were overweight/obese. Asthma symptoms were moderate in 66% of the population, and severe in 18%. Nearly 85% of this population was atopic, and 82% were polysensitized. Sensitization and polysensitization occurred in all weight categories. Asthma severity and elevated BMI were not associated significantly. Overweight/obese children (≥85th percentile) had lower odds of allergen sensitization (adjusted odds ratio 0.26, 95% CI = 0.85-0.78, p = 0.016) and polysensitization (adjusted odds ratio 0.30, 95% CI = 0.11-0.85, p = 0.023) than healthy weight children (<85th percentile). CONCLUSION: Although overweight children did show allergen sensitization, those who were overweight had lower odds of allergen sensitization and lower odds of polysensitization, as compared to normal weight asthmatic children. Elevated BMI was not a significant predictor of asthma severity.

Cost-effectiveness of a community-based weight control intervention targeting a low-socioeconomic-status Mexican-origin population.

INTRODUCTION: The objective of our study was to evaluate the cost-effectiveness of a community-based intervention designed to improve physical activity levels and dietary intake and to reduce diabetes risk in a largely Hispanic population residing along the U.S.-Mexico border. METHOD: We forecasted disease outcomes, quality-adjusted life-years (QALYs) gained, and lifetime costs associated with actual and projected attainment of 2% and 5% weight loss taking a societal cost perspective. We extrapolated changes in beverage calorie consumption between baseline and 6-month follow-up to attain projected weight loss measures. Outcomes were projected 5, 10, and 20 years into the future and discounted at a 3.0% rate. RESULTS: The incremental cost-effectiveness ratio was $57,430 and $61,893, respectively, per QALY gained when compared with usual care for the 2% and 5% weight loss scenarios. The intervention was particularly cost-effective for morbidly obese participants. Cost-effectiveness improves when using 3-year weight loss projections based on changes in sugar-sweetened beverage caloric consumption to $49,478 and $24,092 for the 2% and 5% weight loss scenarios. CONCLUSIONS: This analysis demonstrates that a culturally sensitive community-based weight loss and maintenance intervention can be cost-effective even when healthy weight individuals participate.

Oxandrolone for the treatment of bone marrow failure in Fanconi anemia.

BACKGROUND: A majority of Fanconi anemia (FA) patients will experience bone marrow failure (BMF) and androgen therapy (most often oxymetholone) may be utilized as a treatment to improve BMF-related cytopenias. However, oxymetholone is associated with toxicities making identification of other agents of interest. In this study we aimed to evaluate the toxicity profile and hematologic response in patients with FA who are treated with low-dose oxandrolone, a synthetic non-fluorinated anabolic steroid, similar to oxymetholone, with known dosing thresholds for virilization. PROCEDURE: A single arm, Phase I/II study was designed to treat patients on low-dose oxandrolone. If no toxicity or hematologic response was noted at 16 weeks, a single dose escalation was offered. Subjects were regularly assessed for toxicity, including determinations of virilization, behavioral changes, and liver and kidney function. At 32 weeks, those who demonstrated hematologic response were allowed to continue study treatment, and those without improvement were deemed non-responsive. RESULTS: Nine subjects completed the study and were followed for a median of 99 weeks (46-136 weeks). Three (33.3%) subjects developed mild sub-clinical virilization and continued treatment with a dose reduction. None (0%) had adverse behavioral changes. Two (22.2%) developed elevated liver function tests at 42 and 105 weeks. Seven (77.8%) subjects had a hematologic response. CONCLUSION: Oxandrolone appears to be well-tolerated, has limited toxicities at the administered doses in FA with patients, and may be an alternative androgen for the treatment of BMF in FA.

Stereospecific gating of functional motions in Pin1.

Pin1 is a modular enzyme that accelerates the cis-trans isomerization of phosphorylated-Ser/Thr-Pro (pS/T-P) motifs found in numerous signaling proteins regulating cell growth and neuronal survival. We have used NMR to investigate the interaction of Pin1 with three related ligands that include a pS-P substrate peptide, and two pS-P substrate analogue inhibitors locked in the cis and trans conformations. Specifically, we compared the ligand binding modes and binding-induced changes in Pin1 side-chain flexibility. The cis and trans binding modes differ, and produce different mobility in Pin1. The cis-locked inhibitor and substrate produced a loss of side-chain flexibility along an internal conduit of conserved hydrophobic residues, connecting the domain interface with the isomerase active site. The trans-locked inhibitor produces a weaker conduit response. Thus, the conduit response is stereoselective. We further show interactions between the peptidyl-prolyl isomerase and Trp-Trp (WW) domains amplify the conduit response, and alter binding properties at the remote peptidyl-prolyl isomerase active site. These results suggest that specific input conformations can gate dynamic changes that support intraprotein communication. Such gating may help control the propagation of chemical signals by Pin1, and other modular signaling proteins.

Interdomain interactions support interdomain communication in human Pin1.

Pin1 is an essential mitotic regulator consisting of a peptidyl-prolyl isomerase (PPIase) domain flexibly tethered to a smaller Trp-Trp (WW) binding domain. Communication between these domains is important for Pin1 in vivo activity; however, the atomic basis for this communication has remained elusive. Our previous nuclear magnetic resonance (NMR) studies of Pin1 functional dynamics suggested that weak interdomain contacts within Pin1 enable allosteric communication between the domain interface and the distal active site of the PPIase domain.1,2 A necessary condition for this hypothesis is that the intrinsic properties of the PPIase domain should be sensitive to interdomain contact. Here, we test this sensitivity by generating a Pin1 mutant, I28A, which weakens the wild-type interdomain contact while maintaining the overall folds of the two domains. Using NMR, we show that I28A leads to altered substrate binding affinity and isomerase activity. Moreover, I28A causes long-range perturbations to conformational flexibility in both domains, for both the apo and substrate-complexed states of the protein. These results show that the distribution of conformations sampled by the PPIase domain is sensitive to interdomain contact and strengthen the hypothesis that such contact supports interdomain allosteric communication in Pin1. Other modular systems may exploit interdomain interactions in a similar manner.

Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis.

BACKGROUND: Neurosurgical resection is the standard treatment for subependymal giant-cell astrocytomas in patients with the tuberous sclerosis complex. An alternative may be the use of everolimus, which inhibits the mammalian target of rapamycin, a protein regulated by gene products involved in the tuberous sclerosis complex. METHODS: Patients 3 years of age or older with serial growth of subependymal giant-cell astrocytomas were eligible for this open-label study. The primary efficacy end point was the change in volume of subependymal giant-cell astrocytomas between baseline and 6 months. We gave everolimus orally, at a dose of 3.0 mg per square meter of body-surface area, to achieve a trough concentration of 5 to 15 ng per milliliter. RESULTS: We enrolled 28 patients. Everolimus therapy was associated with a clinically meaningful reduction in volume of the primary subependymal giant-cell astrocytoma, as assessed on independent central review (P<0.001 for baseline vs. 6 months), with a reduction of at least 30% in 21 patients (75%) and at least 50% in 9 patients (32%). Marked reductions were seen within 3 months and were sustained. There were no new lesions, worsening hydrocephalus, evidence of increased intracranial pressure, or necessity for surgical resection or other therapy for subependymal giant-cell astrocytoma. Of the 16 patients for whom 24-hour video electroencephalography data were available, seizure frequency for the 6-month study period (vs. the previous 6-month period) decreased in 9, did not change in 6, and increased in 1 (median change, -1 seizure; P=0.02). The mean (±SD) score on the validated Quality-of-Life in Childhood Epilepsy questionnaire (on which scores can range from 0 to 100, with higher scores indicating a better quality of life) was improved at 3 months (63.4±12.4) and 6 months (62.1±14.2) over the baseline score (57.8±14.0). Single cases of grade 3 treatment-related sinusitis, pneumonia, viral bronchitis, tooth infection, stomatitis, and leukopenia were reported. CONCLUSIONS: Everolimus therapy was associated with marked reduction in the volume of subependymal giant-cell astrocytomas and seizure frequency and may be a potential alternative to neurosurgical resection in some cases, though long-term studies are needed. (Funded by Novartis; ClinicalTrials.gov number, NCT00411619.).

Innovative use of a flipped-classroom approach to teach fundamental nursing skills.

Prelicensure nursing students are required to master fundamental nursing skills. The COVID-19 pandemic created challenges in maintaining excellence while teaching skill acquisition. The purpose of this study was to evaluate skill validation scores and student satisfaction and self-confidence using a flipped classroom approach and a low-fidelity simulation model to innovatively teach skill acquisition. Researchers used a quasi-experimental method to compare skill validation scores of a control group and intervention group using independent samples t-test. Researchers also evaluated whether prelicensure nursing students had satisfaction and self-confidence with this teaching strategy. Findings suggested that skills validations scores were no different using a flipped-classroom approach than in-person instruction. Prelicensure nursing students were satisfied and self-confident following the implementation of this teaching strategy. This teaching strategy has the potential to decrease in-person clinical practice time, provide alternative opportunities for clinical make-up and remediation, and decrease cost.

The power of feedback: Implementing a comprehensive hand hygiene observer program.

BACKGROUND: Hand hygiene (HH) is a fundamental component of infection prevention within all healthcare settings. We implemented a hospital-wide program built on overt HH observation, real-time feedback, and thematic analysis of HH misses. METHODS: A robust observer training program was established to include foundational training in the WHO's My Five Moments of HH. Observational data from 2011 to 2019 were analyzed by unit, provider type, and thematic analyses of misses. RESULTS: During the study period, we conducted 160,917 hospital-wide observations on 29 units (monthly average of 1,490 observations). Institutional compliance remained above 95% from 2013 to 2019. Thematic analysis revealed "touching self" and "touching phone" as common, institution-wide reasons for HH misses. DISCUSSION: Overt observations facilitated communication between HH program and healthcare staff to better understand workflow and educate staff on HH opportunities. This program is an integral part of the Infection Prevention team and has been deployed to collect supplemental data during clusters and outbreaks investigations. CONCLUSIONS: In addition to having rich HH data, successes of this program, include increased awareness of IPC practices, enhanced communication about patient safety, enriched dialog and feedback around HH misses, and relationship building among program observers, unit staff and leaders.

Nutrient-regulated dynamics of chondroprogenitors in the postnatal murine growth plate.

Longitudinal bone growth relies on endochondral ossification in the cartilaginous growth plate, where chondrocytes accumulate and synthesize the matrix scaffold that is replaced by bone. The chondroprogenitors in the resting zone maintain the continuous turnover of chondrocytes in the growth plate. Malnutrition is a leading cause of growth retardation in children; however, after recovery from nutrient deprivation, bone growth is accelerated beyond the normal rate, a phenomenon termed catch-up growth. Although nutritional status is a known regulator of long bone growth, it is largely unknown whether and how chondroprogenitor cells respond to deviations in nutrient availability. Here, using fate-mapping analysis in Axin2CreERT2 mice, we showed that dietary restriction increased the number of Axin2+ chondroprogenitors in the resting zone and simultaneously inhibited their differentiation. Once nutrient deficiency was resolved, the accumulated chondroprogenitor cells immediately restarted differentiation and formed chondrocyte columns, contributing to accelerated growth. Furthermore, we showed that nutrient deprivation reduced the level of phosphorylated Akt in the resting zone and that exogenous IGF-1 restored the phosphorylated Akt level and stimulated differentiation of the pooled chondroprogenitors, decreasing their numbers. Our study of Axin2CreERT2 revealed that nutrient availability regulates the balance between accumulation and differentiation of chondroprogenitors in the growth plate and further demonstrated that IGF-1 partially mediates this regulation by promoting the committed differentiation of chondroprogenitor cells.

Nutrient-regulated dynamics of chondroprogenitors in the postnatal murine growth plate.

Longitudinal bone growth relies on endochondral ossification in the cartilaginous growth plate where chondrocytes accumulate and synthesize the matrix scaffold that is replaced by bone. The chondroprogenitors in the resting zone maintain the continuous turnover of chondrocytes in the growth plate. Malnutrition is a leading cause of growth retardation in children; however, after recovery from nutrient deprivation, bone growth is accelerated beyond the normal rate, a phenomenon termed catch-up growth. Though nutritional status is a known regulator of long bone growth, it is largely unknown if and how chondroprogenitor cells respond to deviations in nutrient availability. Here, using fate-mapping analysis in Axin2Cre ERT2 mice, we showed that dietary restriction increased the number of Axin2+ chondroprogenitors in the resting zone and simultaneously inhibited their differentiation. Once nutrient deficiency was resolved, the accumulated chondroprogenitor cells immediately restarted differentiation and formed chondrocyte columns, contributing to accelerated growth. Furthermore, we showed that nutrient deprivation reduced the level of phosphorylated Akt in the resting zone, and that exogenous IGF-1 canceled this reduction and stimulated differentiation of the pooled chondroprogenitors, decreasing their numbers. Our study of Axin2Cre ERT2 revealed that nutrient availability regulates the balance between accumulation and differentiation of chondroprogenitors in the growth plate, and further demonstrated that IGF-1 partially mediates this regulation by promoting the committed differentiation of the chondroprogenitor cells.

Cost-effectiveness analysis of a community health worker intervention for low-income Hispanic adults with diabetes.

INTRODUCTION: The objective of our study was to estimate the long-term cost-effectiveness of a lifestyle modification program led by community health workers (CHWs) for low-income Hispanic adults with type 2 diabetes. METHODS: We forecasted disease outcomes, quality-adjusted life years (QALYs) gained, and lifetime costs associated with attaining different hemoglobin A1c (A1c) levels. Outcomes were projected 20 years into the future and discounted at a 3.0% rate. Sensitivity analyses were conducted to assess the extent to which our results were dependent on assumptions related to program effectiveness, projected years, discount rates, and costs. RESULTS: The incremental cost-effectiveness ratio of the intervention ranged from $10,995 to $33,319 per QALY gained when compared with usual care. The intervention was particularly cost-effective for adults with high glycemic levels (A1c > 9%). The results are robust to changes in multiple parameters. CONCLUSION: The CHW program was cost-effective. This study adds to the evidence that culturally sensitive lifestyle modification programs to control diabetes can be a cost-effective way to improve health among Hispanics with diabetes, particularly among those with high A1c levels.

Dodging the bundle-Persistent healthcare-associated rhinovirus infection throughout the pandemic.

INTRODUCTION: Healthcare-associated viral infections (HAVI) are a common cause of patient harm in the pediatric population. We implemented a HAVI prevention bundle in 2015, which included 6 core elements: caregiver screening, symptom-based isolation, personal protective equipment (PPE), hand hygiene, staff illness procedures, and monitoring of environmental cleanliness. Enhanced bundle elements were introduced at the start of the COVID-19 pandemic, which provided an opportunity to observe the effectiveness of the bundle with optimal adherence to prevention practices, and to measure the impact on respiratory HAVI epidemiology. METHODS: Respiratory HAVIs were confirmed through review of medical records and application of the National Health Safety Network (NHSN) surveillance criteria for upper respiratory infections (URIs) with predetermined incubation periods for unit attribution. Descriptive statistics of the study population were examined, and comparative analyses were performed on demographic and process metrics. Data analysis was conducted using R statistical software. RESULTS: We observed an overall decrease in respiratory HAVI of 68%, with prepandemic rates of 0.19 infections per 1,000 patient significantly decreased to a rate of 0.06 per 1,000 patient days in the pandemic period (P < .01). Rhinovirus made up proportionally more of our respiratory HAVI in the pandemic period (64% vs 53%), with respiratory HAVI secondary only to rhinovirus identified during 8 of 16 months in the pandemic period. Compliance with our HAVI prevention bundle significantly improved during pandemic period. CONCLUSIONS: Enhancement of our HAVI bundle during the COVID-19 pandemic contributed toward significant reduction in nosocomial transmission of respiratory HAVI. Even with prevention practices optimized, respiratory HAVIs secondary to rhinovirus continued to be reported, likely due to the capacity of rhinovirus to evade bundle elements in hospital, and infection prevention efforts at large in the community, leaving vulnerable patients at continued risk.

Inhibition of glucose use improves structural recovery of injured Achilles tendon in mice.

Injured tendons do not regain their native structure except at fetal or very young ages. Healing tendons often show mucoid degeneration involving accumulation of sulfated glycosaminoglycans (GAGs), but its etiology and molecular base have not been studied substantially. We hypothesized that quality and quantity of gene expression involving the synthesis of proteoglycans having sulfated GAGs are altered in injured tendons and that a reduction in synthesis of sulfated GAGs improves structural and functional recovery of injured tendons. C57BL6/j mice were subjected to Achilles tendon tenotomy surgery. The injured tendons accumulated sulfate proteoglycans as early as 1-week postsurgery and continued so by 4-week postsurgery. Transcriptome analysis revealed upregulation of a wide range of proteoglycan genes that have sulfated GAGs in the injured tendons 1 and 3 weeks postsurgery. Genes critical for enzymatic reaction of initiation and elongation of chondroitin sulfate GAG chains were also upregulated. After the surgery, mice were treated with the 2-deoxy-d-glucose (2DG) that inhibits conversion of glucose to glucose-6-phosphate, an initial step of glucose metabolism as an energy source and precursors of monosaccharides of GAGs. The 2DG treatment reduced accumulation of sulfated proteoglycans, improved collagen fiber alignment, and reduced the cross-sectional area of the injured tendons. The modulus of the 2DG-treated groups was higher than that in the vehicle group, but not of statistical significance. Our findings suggest that mucoid degeneration in injured tendons may result from the upregulated expression of genes involved the synthesis of sulfate proteoglycans and can be inhibited by reduction of glucose utilization.

Analysis of Association between Morphometric Parameters of Growth Plate and Bone Growth of Tibia in Mice and Humans.

OBJECTIVE: The purposes of this study are to evaluate which growth plate parameters are associated with bone growth in mice and to compare the mouse results with those in humans. DESIGN: The sagittal sections of the proximal growth plate of the mouse tibia from neonate to young adult stages were subjected to histomorphometric and functional analyses. The radiographic images of tibias of human patients until puberty were analyzed to obtain the tibia length and the proximal growth plate height. It was found that a linear correlation best modeled the relationship between the growth plate variables with the tibia growth rate and length. RESULTS: In mice, total height, resting zone height, combined height of the proliferation and prehypertrophic zones, proliferation activity, and the total width of tibia growth plate showed high linear correlation with tibia bone length and bone growth rate, but the hypertrophic zone height and the growth plate area did not. In both mice and humans, the total growth plate width of tibia was found to have the strongest correlation with tibia length and growth rate. CONCLUSIONS: The results validated that growth plate total height, the height of the resting zone and cell proliferation activity are appropriate parameters to evaluate the balance between growth plate activity and bone growth in mice, consistent with previous reports. The study also provided a new growth plate parameter candidate, growth plate width for growth plate activity evaluation in both mouse and human tibia bone.