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Osteoarthritis (OA) treatment is limited by the lack of effective nonsurgical interventions to slow disease progression. Here, we examined the contributions of the subchondral bone properties to OA development. We used parathyroid hormone (PTH) to modulate bone mass before OA initiation and alendronate (ALN) to inhibit bone remodeling during OA progression. We examined the spatiotemporal progression of joint damage by combining histopathological and transcriptomic analyses across joint tissues. The additive effect of PTH pretreatment before OA initiation and ALN treatment during OA progression most effectively attenuated load-induced OA pathology. Individually, PTH directly improved cartilage health and slowed the development of cartilage damage, whereas ALN primarily attenuated subchondral bone changes associated with OA progression. Joint damage reflected early transcriptomic changes. With both treatments, the structural changes were associated with early modulation of immunoregulation and immunoresponse pathways that may contribute to disease mechanisms. Overall, our results demonstrate the potential of subchondral bone-modifying therapies to slow the progression of OA.
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Cartilagem Articular , Osteoartrite , Hormônio Paratireóideo , Animais , Camundongos , Alendronato/farmacologia , Alendronato/uso terapêutico , Osso e Ossos , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Osteoartrite/patologia , Hormônio Paratireóideo/farmacologia , Hormônio Paratireóideo/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Suporte de CargaRESUMO
BACKGROUND: Food insecurity and metabolic diseases both disproportionately affect Hispanic children. Cross-sectional studies have linked food insecurity with adverse cardiometabolic markers, including elevated plasma triglycerides and glucose concentrations. However, the association between changes in food insecurity and changes in cardiometabolic markers in children remains to be explored. Furthermore, few studies have assessed the impact of school-based nutrition interventions on household food insecurity. OBJECTIVE: The objectives of this study are to assess the effect of the TX Sprouts intervention on household food insecurity and to examine the association between changes in household food insecurity and changes in cardiometabolic markers over 1 academic year. METHODS: This secondary analysis used data from TX Sprouts, a cluster-randomized school-based gardening, cooking, and nutrition trial. The study enrolled 3rd-5th-grade students from 16 schools that served primarily (>50%) Hispanic families with low income in Austin, TX. Participants (n = 619) provided household food insecurity data and fasting lipid panels at both baseline and postintervention, â¼9 mo following. RESULTS: There was no intervention effect on household food insecurity. Independent of the intervention, a 1-point increase in food insecurity, indicative of becoming more food insecure, was associated with a 2.61 mg/dL increase in triglycerides (P = 0.001; 95% CI: 1.04, 4.19) at follow-up. Children who were food insecure at baseline and became food secure at follow-up had a mean 5.05 mg/dL decrease in triglycerides compared with a 7.50 mg/dL increase in triglycerides in children who remained food insecure throughout (95% CI: -23.40, -1.71, P = 0.023). There were no other associations between changes in food insecurity and cardiometabolic markers. CONCLUSION: Although the intervention did not improve food insecurity, reductions in food insecurity over 9 mo were associated with improved cardiometabolic markers in high-risk children, emphasizing the need for interventions targeting food insecurity. The study is registered at clinicaltrials.gov under NCT02668744 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT02668744).
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Doenças Cardiovasculares , Abastecimento de Alimentos , Criança , Humanos , Estudos Transversais , Insegurança Alimentar , Hispânico ou LatinoRESUMO
BACKGROUND/OBJECTIVES: Obesity and other predictors of type 2 diabetes disproportionally affect Hispanic and Black children in the US compared to non-Hispanic White (NHW) children. Yet, the prevalence of prediabetes in children remains unestablished, and guidelines for screening young children are lacking. This study examined the relationships between demographic factors and prediabetes in vulnerable youth in central Texas. SUBJECTS/METHODS: This is a cross-sectional analysis of baseline data from 976 3rd-5th graders (7-12 years) who participated in TX Sprouts, a school-based gardening, nutrition, and cooking trial in 16 elementary schools serving mainly children from minority backgrounds and lower-income households. Measures collected included age, sex, ethnicity, free/reduced-priced school lunch (FRL) status, parent educational attainment (questionnaires), BMI from height (stadiometer) and weight (TANITA scale), and prediabetes status from fasting plasma glucose (FPG) and HbA1c. Regressions examined cross-sectional associations between demographics and FPG, HbA1c, and prediabetes. RESULTS: Children were 47% male, 67% Hispanic, and 10% Black, with a mean age of 9.3 years; 71% received FRL, 50% had overweight/obesity, and 26% had prediabetes. Prediabetes rates were 2.8 and 4.8 times higher in Hispanic and Black children compared to NHW children, respectively (p ≤ 0.001), and 1.5 times higher in children with obesity versus normal BMI (p = 0.02). Children of parents with only an 8th-grade education, some high school education, or a high school degree had 3.1, 2.7, and 2.2 times higher odds of having prediabetes compared to children of college graduates, respectively (p ≤ 0.004). Analyses with FPG and HbA1c yielded similar results. CONCLUSION: These findings suggest a potential need for earlier screening, more comprehensive testing guidelines, and prevention programs tailored toward minority children, children with obesity, and children of parents with low educational attainment. Future research should explore this finding in a larger, nationally representative sample.
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Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Adolescente , Humanos , Criança , Masculino , Pré-Escolar , Feminino , Etnicidade , Estado Pré-Diabético/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Transversais , Hemoglobinas Glicadas , Escolaridade , Obesidade/epidemiologiaRESUMO
BACKGROUND: School-based gardening and nutrition education interventions report improvements in dietary intake, notably through fruit and vegetables. However, gardening, cooking, and nutrition randomized controlled trials are limited in evaluating dietary quality, and none have examined processed food consumption to date. OBJECTIVES: The study examined the effects of Texas Sprouts (TX Sprouts), a gardening, cooking, and nutrition education intervention, compared with control on unprocessed and ultra-processed food (UPF) consumption in predominately low-income Hispanic children. METHODS: TX Sprouts was a school-based cluster randomized controlled trial that consisted of 16 elementary schools randomly assigned to either the TX Sprouts intervention (n = 8 schools) or control (delayed intervention; n = 8 schools) over 3 y (2016-2019). TX Sprouts schools received an outdoor teaching garden and 18 1-h lessons taught by trained educators throughout the school year. Dietary intake data via 2 24-h dietary recalls were collected on a random subsample (n = 468) at baseline and postintervention. All foods and beverages were categorized using the NOVA food classification system (e.g., unprocessed, processed, ultra-processed). Generalized linear mixed effects modeling tested changes in percent calories and grams of NOVA groups between the intervention and control estimates with schools as random clusters. RESULTS: Of the sample, 63% participated in the free and reduced-price lunch program, and 57% were Hispanic, followed by non-Hispanic White (21%) and non-Hispanic Black (12%). The intervention, compared to the control, resulted in an increase in consumption of unprocessed foods (2.3% compared with -1.8% g; P < 0.01) and a decrease in UPF (-2.4% compared with 1.4% g; P = 0.04). In addition, Hispanic children in the intervention group had an increase in unprocessed food consumption and a decrease in UPF consumption compared to non-Hispanic children (-3.4% compared with 1.5% g; P < 0.05). CONCLUSIONS: Study results suggest that school-based gardening, cooking, and nutrition education interventions can improve dietary intake, specifically increasing unprocessed food consumption and decreasing UPF consumption. This trial was registered at clinicaltrials.gov as NCT02668744.
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Jardinagem , Promoção da Saúde , Criança , Humanos , Culinária/métodos , Dieta , Alimento Processado , Jardinagem/educação , Jardinagem/métodos , Promoção da Saúde/métodos , VerdurasRESUMO
Importance: Although school-based gardening programs for children have consistently been shown to improve dietary behaviors, no cluster randomized clinical trial (RCT) has evaluated the effects of a school-based gardening intervention on metabolic outcomes. Objective: To evaluate the effects of a school-based gardening, nutrition, and cooking intervention (Texas Sprouts) on changes in metabolic outcomes in elementary schoolchildren. Design, Setting, and Participants: This study was a secondary analysis of a cluster RCT, conducted over 3 years from 2016 to 2019, at low-income elementary schools with majority Hispanic students in the greater Austin, Texas, area. Data were analyzed from January to August 2022. Interventions: Texas Sprouts was 1 school year long (9 months) and consisted of (1) Garden Leadership Committee formation; (2) a 0.25-acre outdoor teaching garden; (3) 18 student gardening, nutrition, and cooking lessons taught by trained educators throughout the school year; and (4) 9 monthly parent lessons. The delayed intervention was implemented the following academic year and received an identical intervention. Main Outcomes and Measures: The following measures were obtained at baseline and postintervention (9 months): demographics via survey; measured height, weight, and body mass index parameters; and glucose, insulin, homeostatic model assessment of insulin resistance, and a lipid panel via an optional fasting blood draw. Results: Sixteen elementary schools were randomly assigned to either Texas Sprouts intervention (8 schools) or to delayed intervention (control, 8 schools). A total of 3302 children (aged 7-12 years) were enrolled in Texas Sprouts, and fasting blood samples were obtained from 1104 children (or 33% of those enrolled) at baseline. The final analytic sample included 695 children (307 boys [44.17%]; mean [SE] age, 9.28 [0.04] years; 480 Hispanic children [69.02%]; 452 [65.03%] eligible for free or reduced lunch) with complete demographic data and baseline and postintervention (9-month) fasting blood draws. Compared with control schools, children from Texas Sprouts schools had a 0.02% reduction in mean hemoglobin A1c (95% CI, 0.03%-0.14%; P = .005) and a 6.40 mg/dL reduction in mean low-density lipoprotein cholesterol (95% CI, 3.82-8.97 mg/dL; P = .048). There were no intervention effects on glucose, insulin, homeostatic model assessment of insulin resistance, or other lipid parameters. Conclusions and Relevance: In this cluster RCT, Texas Sprouts improved glucose control and reduced low-density lipoprotein cholesterol in high-risk youth. These findings suggest that elementary schools should incorporate garden-based interventions as a way to improve metabolic parameters in children. Trial Registration: ClinicalTrials.gov Identifier: NCT02668744.
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Resistência à Insulina , Insulinas , Masculino , Criança , Humanos , Adolescente , Jardinagem/educação , Promoção da Saúde , Culinária , Lipoproteínas LDL , Colesterol , LipídeosRESUMO
As rates of metabolic syndrome rise, children consume too few vegetables and too much added sugar. Because children tend to eat what is available at home, the home environment plays a key role in shaping dietary habits. This secondary analysis evaluated the effects of a school-based gardening, cooking, and nutrition education intervention (TX Sprouts) compared to control on the availability of vegetables, fruit juice, and sugar-sweetened beverages (SSBs) at home. In the TX Sprouts cluster-randomized trial, 16 schools were randomized to TX Sprouts (n = 8 schools) or control (n = 8 schools) for one academic year. All schools served predominately Hispanic families with low incomes. TX Sprouts built school gardens and taught 18 lessons to all 3rd-5th grade students at intervention schools. TX Sprouts also offered monthly caregiver lessons before and/or after school. Caregivers completed questionnaires pre and post, providing demographics and information about home availability of vegetables, fruit juice, and SSBs. Summary statistics were used to describe the sociodemographic characteristics of participants. Linear regression assessed the change in scores (pre to post) for the food/ beverage availability question. The model was adjusted for the caregiver's education, employment status, child's grade, and free or reduced-price lunch eligibility. The analytic sample included 895 participants. Compared to control, the intervention positively changed the home availability of targeted foods and beverages, largely by improving the availability of vegetables and vegetable juice. This study showed that a school gardening, nutrition, and cooking program delivered to elementary children may positively influence the home food environment.
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Human COPA mutations affecting retrograde Golgi-to-endoplasmic reticulum (ER) protein transport cause diffuse alveolar hemorrhage (DAH) and ER stress ("COPA syndrome"). Patients with SLE also can develop DAH. C57BL/6 (B6) mice with pristane-induced lupus develop monocyte-dependent DAH indistinguishable from human DAH, whereas BALB/c mice are resistant. We examined Copa and ER stress in pristane-induced lupus. Copa expression, ER stress, vascular injury, and apoptosis were assessed in mice and COPA was quantified in blood from patients with SLE. Copa mRNA and protein expression were impaired in B6 mice with pristane-induced DAH, but not in pristane-treated BALB/c mice. An ER stress response (increased Hsp5a/BiP, Ddit3/CHOP, Eif2a, and spliced Xbp1) was seen in lungs from pristane-treated B6, but not BALB/c, mice. Resistance of BALB/c mice to DAH was overcome by treating them with low-dose thapsigargin plus pristane. CB6F1 mice did not develop DAH or ER stress, suggesting that susceptibility was recessive. Increased pulmonary expression of von Willebrand factor (Vwf), a marker of endothelial injury, and the chemokine Ccl2 in DAH suggested that pristane promotes lung microvascular injury and monocyte recruitment. Consistent with that possibility, lung endothelial cells and infiltrating bone marrow-derived cells from pristane-treated B6 mice expressed BiP and showed evidence of apoptosis (annexin-V and activated caspase-3 staining). COPA expression also was low in patients with SLE with lung involvement. Pristane-induced DAH may be initiated by endothelial injury, resulting in ER stress, apoptosis of lung endothelial cells, and recruitment of myeloid cells that propagate lung injury. The pathogenesis of DAH in SLE and COPA syndrome may overlap.
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Pneumopatias , Lesão Pulmonar , Lúpus Eritematoso Sistêmico , Vasculite , Humanos , Camundongos , Animais , Alvéolos Pulmonares/patologia , Lesão Pulmonar/patologia , Células Endoteliais/patologia , Camundongos Endogâmicos C57BL , Pulmão/patologia , Pneumopatias/patologia , Hemorragia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Vasculite/patologia , Estresse do Retículo EndoplasmáticoRESUMO
BACKGROUND: The innate immune regulation, especially by the type I IFN signature in the CD14+ monocytes, is known to be critical in the pathogenesis of autoimmune Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE). OBJECTIVE: Since patients with one condition can be overlapped with another, this study is to identify shared differentially expressed genes (DEGs) in SjS and SLE compared to healthy controls (HCs) and refine transcriptomic profiles with the integrated Reactome and gene-drug network analysis for an anti-inflammation therapy. METHODS: CD14+ monocytes were purified from whole blood of SjS and SLE patients (females, ages from 32 to 62) and subject to bulk RNA-sequencing, followed by data analyses for comparison with HC monocytes (females, ages 30 and 33). Functional categorizations, using Gene Ontology (GO) and the Reactome pathway analysis, were performed and DEGs associated with therapeutic drugs were identified from the Drug Repurposing Hub (DHUB) database. RESULTS: The GO analysis revealed that DEGs in the inflammatory response and the cellular response to cytokine were highly enriched in both conditions. A propensity toward M1 macrophage differentiation appears to be prominent in SjS while the Response to Virus was significant in SLE monocytes. Through the Reactome pathway analysis, DEGs in the IFN signaling and the cytokine signaling in immune system were most significantly enriched in both. Upregulation of NGF-induced transcription activity in SjS and the complement cascade activity in SLE were also noted. Multiple anti-inflammatory drugs, such as prostaglandin-endoperoxide synthase and angiotensin-I-converting- enzyme were associated with the DEGs in these conditions. CONCLUSIONS: Taken together, our analysis indicates distinct inflammatory transcriptomic profiles shared in SjS and SLE monocytes. Comprehensive characterizations of the data from these conditions will ultimately allow differential diagnosis of each condition and identification of therapeutic targets.
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Lúpus Eritematoso Sistêmico , Síndrome de Sjogren , Adulto , Angiotensinas , Citocinas , Feminino , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/genética , Pessoa de Meia-Idade , Monócitos/metabolismo , Fator de Crescimento Neural , Prostaglandina-Endoperóxido Sintases , RNA , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/genéticaRESUMO
Selective medical perspectives of pediatric sports medicine are explored in this issue and behavioral perspectives of pediatric sports medicine are discussed in a subsequent journal issue. Concepts are considered now dealing with sports readiness involving the child and adolescent that involve understanding the limits imposed by growth and development at different ages as well as pubertal stages. Specializing in one sport too soon is not recommended. Sports readiness also involves understanding and counseling about proper diet and nutrition for maximum sports activity as well as overall health benefits. As clinicians understand sports readiness they can provide a beneficial pre-participation sports examination and deal with qualifications for sports play. Various medical conditions arise in dealing with pediatric persons involved in sports and these are considered in this discussion. They include the female athlete triad, iron deficiency anemia, sports anemia, musculoskeletal overuse injuries, obesity, sudden cardiac death, return to learning after sports-related concussion, epilepsy, asthma, diabetes mellitus, gastrointestinal disorders, genitourinary disorders and dermatology disorders in sports. Clinicians can be very helpful to these young athletes and work with them to ensure the full benefits of sport activities.
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Anemia , Traumatismos em Atletas , Concussão Encefálica , Transtornos Traumáticos Cumulativos , Medicina Esportiva , Adolescente , Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/terapia , Criança , Feminino , HumanosRESUMO
OBJECTIVE: Missense mutations in HIV-1 reverse transcriptase are frequently selected in response to therapy; we examined whether silent mutations were also selected for by HIV therapy. DESIGN: Retrospective, observational analysis. Biochemical assays. METHODS: A comparison of the reverse transcriptase gene, from antiretroviral- naive (N = 812) and experienced individuals (N = 2212), reveals two silent mutations (K65K and K66K) that are strongly associated with treatment experience. To assess reverse transcription efficiency, steady-state kinetic assays were carried out using recombinant purified HIV-1 reverse transcriptase and a series of synthetic RNA/DNA template/primer substrates. The RNA templates spanned codons 60-77 in the reverse transcriptase and included different combinations of mutations at codons 65, 66, 67, and 70. RESULTS: Silent AAG mutations (or mixtures) at reverse transcriptase codons 65 and/or 66 were observed in 812 samples from 351 patients and 2129 samples from 829 patients, respectively. In clade B samples, there was a very strong relationship between the silent mutations and the thymidine analogue mutations, in particular D67N. Steady-state kinetic experiments demonstrated that HIV-1 reverse transcriptase exhibited a strong tendency to pause and/or dissociate at codons 65 and 66 on RNA templates that contained the D67N and K70R mutations. However, when the K66 or K66 AAA to AAG mutations were added to the background of the 67 and 70 mutational changes, these pausing and/or dissociation events were largely alleviated. CONCLUSION: Silent mutations at codons 65 and/or 66 are strongly coselected with thymidine analogue mutations. These data provide the first evidence for an RNA-level mechanism of direct relevance to drug resistance.