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Calcium oxalate (CaOx) kidney stones are common and recurrent, lacking pharmacological prevention. Randall's plaques (RPs), calcium deposits in renal papillae, serve as niduses for some CaOx stones. This study explores the role of osteogenic-like cells in RP formation resembling ossification. CaP crystals deposit around renal tubules, interstitium, and blood vessels in RP tissues. Human renal interstitial fibroblasts (hRIFs) exhibit the highest osteogenic-like differentiation potential compared to chloride voltage-gated channel Ka positive tubular epithelial cells, aquaporin 2 positive collecting duct cells, and vascular endothelial cells, echoing the upregulated osteogenic markers primarily in hRIFs within RP tissues. Utilizing RNA-seq, osteomodulin (OMD) is found to be upregulated in hRIFs within RP tissues and hRIFs following osteogenic induction. Furthermore, OMD colocalizes with CaP crystals and calcium vesicles within RP tissues. OMD can enhance osteogenic-like differentiation of hRIFs in vitro and in vivo. Additionally, crystal deposits are attenuated in mice with Omd deletion in renal interstitial fibroblasts following CaOx nephrocalcinosis induction. Mechanically, a positive feedback loop of OMD/BMP2/BMPR1A/RUNX2/OMD drives hRIFs to adopt osteogenic-like fates, by which OMD induces osteogenic-like microenvironment of renal interstitium to participate in RP formation. We identify OMD upregulation as a pathological feature of RP, paving the way for preventing CaOx stones.
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BACKGROUND: Previous studies have linked kidney stone disease (KSD) with depression, but there are no reports on the relationship between anxiety and KSD, and the mechanism underlying the potential relationship remains unclear. METHODS: Associations of anxiety and incident KSD were assessed in the National Health and Nutrition Examination Survey (NHENES) using multivariate logistic regression. Two-sample bidirectional Mendelian randomization studies and a two-step two-sample MR was used to estimate the mediating factors that influence KSD risk. RESULTS: Examinations of NHANES data revealed that a rise in the frequency and intensity of anxiety were independently associated with incident KSD. In MR analysis, anxiety (uk-a-51 and uk-b-6519) were from the UK Biobank, with sample sizes of 328,717 and 450,765 respectively. KSD data were from the FinnGen, including 8597 cases and 333,128 controls. In the IVW analysis, genetically predicted anxieties (ukb-a-51 and ukb-b-6519) were found to be causally associated with a higher risk of KSD, with odds ratios of 6.18 (95 % CI 2.54-15.04) and 3.44 (95 % CI 1.67-7.08), respectively. There were no reverse causal effects. Further mediation analysis indicated that anxiety increases the risk of KSD by raising eGFR, through which 11.8 % of the effect of anxiety on KSD risk was mediated. LIMITATIONS: The research was confined to individuals of European heritage, and there could be specific genetic variances among diverse ethnicities. CONCLUSION: The current study suggests anxiety as an independent causal risk factor for KSD and unveils a new pathogenic mechanism, showing that anxiety raises eGFR, thereby increasing the risk of KSD.
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Ansiedad , Receptores ErbB , Cálculos Renales , Análisis de la Aleatorización Mendeliana , Humanos , Cálculos Renales/genética , Cálculos Renales/epidemiología , Masculino , Femenino , Ansiedad/epidemiología , Persona de Mediana Edad , Receptores ErbB/genética , Adulto , Factores de Riesgo , Encuestas Nutricionales , AncianoRESUMEN
Genetic manipulation of animal models is a fundamental research tool in biology and medicine but is challenging in large animals. In rodents, models can be readily developed by knocking out genes in embryonic stem cells or by knocking down genes through in vivo delivery of nucleic acids. Swine are a preferred animal model for studying the cardiovascular and immune systems, but there are limited strategies for genetic manipulation. Lipid nanoparticles (LNPs) efficiently deliver small interfering RNA (siRNA) to knock down circulating proteins, but swine are sensitive to LNP-induced complement activation-related pseudoallergy (CARPA). We hypothesized that appropriately administering optimized siRNA-LNPs could knock down circulating levels of plasminogen, a blood protein synthesized in the liver. siRNA-LNPs against plasminogen (siPLG) reduced plasma plasminogen protein and hepatic plasminogen mRNA levels to below 5% of baseline values. Functional assays showed that reducing plasminogen levels modulated systemic blood coagulation. Clinical signs of CARPA were not observed, and occasional mild and transient hepatotoxicity was present in siPLG-treated animals at 5 h post-infusion, which returned to baseline by 7 days. These findings advance siRNA-LNPs in swine models, enabling genetic engineering of blood and hepatic proteins, which can likely expand to proteins in other tissues in the future.
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BACKGROUND: Proton pump inhibitors (PPIs) are widely used throughout the world as an effective gastrointestinal drug. Nevertheless, according to the existing literature, PPIs can reduce the excretion of magnesium, calcium and other components in urine, which may promote the formation of kidney stones. We used the National Health and Nutrition Examination Survey (NHANES) database to further investigate the association between the use of PPIs and the prevalence of kidney stones. METHODS: We performed a cross-sectional analysis using data from 2007 to 2018 NHANES. PPIs use information of 29,910 participants was obtained by using prescription medications in the preceding month, and kidney stones were presented by a standard questionnaire. Multiple regression analysis and stratified analysis were used to estimate the association between PPIs use and kidney stones after an adjustment for potential confounders. RESULTS: The multiple logistic regression indicated that the PPIs exposure group (P1) had a significantly higher risk of nephrolithiasis than the PPIs non-exposure group (P0) in Model 3 (OR 1.24, 95% CI 1.10-1.39, P < 0.001). The stratified analyses indicated there were significant statistical differences between PPIs use and kidney stones among females (OR 1.36, 95% CI 1.15-1.62, P < 0.001), non-Hispanic whites (OR 1.27, 95% CI 1.09-1.48, P = 0.002), individuals with an education level than 11th grade (OR 1.41, 95% CI 1.13-1.76, P = 0.002) and individuals with an annual family income of $0 to $19,999 (OR 1.32, 95% CI 1.06-1.65, P = 0.014) and $20,000 to $44,999 (OR 1.25, 95% CI 1.02-1.54, P = 0.033) in Model 3. CONCLUSIONS: Our study revealed that PPIs use is associated with a higher prevalence of kidney stones for the US population, primarily among women, non-Hispanic whites, individuals with low education levels and individuals with low household income levels. Further studies are required to confirm our findings.
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Cálculos Renales , Encuestas Nutricionales , Inhibidores de la Bomba de Protones , Humanos , Inhibidores de la Bomba de Protones/efectos adversos , Femenino , Masculino , Estudios Transversales , Cálculos Renales/epidemiología , Cálculos Renales/inducido químicamente , Persona de Mediana Edad , Prevalencia , Adulto , Estados Unidos/epidemiología , Anciano , Factores de Riesgo , Adulto JovenRESUMEN
INTRODUCTION: Hemorrhage is responsible for 91% of preventable prehospital deaths in combat. Bleeding from anatomic junctions such as the groin, neck, and axillae make up 19% of these deaths, and reports estimate that effective control of junctional hemorrhage could have prevented 5% of fatalities in Afghanistan. Hemostatic dressings are effective but are time-consuming to apply and are limited when proper packing and manual pressure are not feasible, such as during care under fire. CounterFlow-Gauze is a hemostatic dressing that is effective without compression and delivers thrombin and tranexamic acid into wounds. Here, an advanced prototype of CounterFlow-Gauze, containing a range of low thrombin doses, was tested in a lethal swine model of junctional hemorrhage. Outcomes were compared with those of Combat Gauze, the current dressing recommended by Tactical Combat Casualty Care. MATERIALS AND METHODS: CounterFlow-Gauze containing thrombin doses of 0, 20, 200, and 500 IU was prepared. Swine received femoral arteriotomies, and CounterFlow-Gauze was packed into wounds without additional manual compression. In a separate study using a similar model of junctional hemorrhage without additional compression, CounterFlow-Gauze containing 500 IU thrombin was tested and compared with Combat Gauze. In both studies, the primary outcomes were survival to 3 h and volume of blood loss. RESULTS: CounterFlow-Gauze with 200 and 500 IU had the highest 3-h survival, achieving 70 and 75% survival, respectively. CounterFlow-Gauze resulted in mean peak plasma tranexamic acid concentrations of 9.6 ± 1.0 µg/mL (mean ± SEM) within 3 h. In a separate study with smaller injury, CounterFlow-Gauze with 500 IU achieved 100% survival to 3 h compared with 92% in Combat Gauze animals. CONCLUSIONS: An advanced preclinical prototype of CounterFlow-Gauze formulated with a minimized thrombin dose is highly effective at managing junctional hemorrhage without compression. These results demonstrate that CounterFlow-Gauze could be developed into a feasible alternative to Combat Gauze for hemorrhage control on the battlefield.
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Hemostáticos , Ácido Tranexámico , Animales , Porcinos , Trombina/uso terapéutico , Ácido Tranexámico/farmacología , Ácido Tranexámico/uso terapéutico , Técnicas Hemostáticas , Modelos Animales de Enfermedad , Hemorragia/tratamiento farmacológico , Hemostáticos/farmacología , Hemostáticos/uso terapéutico , Vendajes , CegueraRESUMEN
Low femoral neck bone mineral density (BMD) was associated with the increased risk of kidney stones. Low dietary magnesium intake and increased serum alkaline phosphatase were associated with the increased risk of low femoral neck BMD in kidney stone formers. PURPOSE: To evaluate whether low femoral neck bone mineral density (BMD) was associated with a higher risk of kidney stones, and identify risk factors for the comorbidity of osteoporosis/osteopenia and kidney stones. METHODS: We analyzed individuals aged ≥ 20 years from National Health and Nutrition Examination Survey 2007-2020 data. Osteoporosis/osteopenia is defined as any T-score < -1.0 of femoral neck, total femoral, and mean lumbar spine (L1-L4) BMD. Dietary intakes (sodium, potassium, magnesium, calcium, phosphorus, calcium/phosphorus, vitamin D (25OHD2+25OHD3)) and serum parameters (sodium, potassium, calcium, phosphorus, bicarbonate, vitamin D, alkaline phosphatase (ALP)) were screened for identifying risk factors for the comorbidity. RESULTS: The prevalence of comorbidity of osteoporosis/osteopenia and kidney stones was 4.82%. Femoral neck BMD T-score was negatively associated with the prevalence of kidney stones (n=11,864). Dietary magnesium intake, serum phosphorus, and bicarbonate were negatively associated with the comorbidity prevalence, and serum ALP was positively associated with the comorbidity prevalence (n=6978). Additionally, there remain significant associations of dietary magnesium intake, serum ALP, and bicarbonate with not only femoral neck BMD T-score (n=11331), but also the prevalence of kidney stones (n=23,111) in general population. Furthermore, dietary magnesium intake was positively correlated to femoral neck BMD T-score in stone formers (SFs), while serum ALP was negatively correlated to femoral neck BMD T-score in SFs (n=1163). CONCLUSION: Low femoral neck BMD was closely associated with an increased risk of kidney stones. Low magnesium intake and increased serum ALP were associated with the increased risk of the comorbidity, as well as indicative of low femoral neck BMD T-score in SFs, which offered a clue to further clarify the mechanism leading to paradoxical calcification of bone resorption and kidney stones, and had the potential to perform personalized diagnostic workup for low BMD in SFs.
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Enfermedades Óseas Metabólicas , Cálculos Renales , Osteoporosis , Humanos , Densidad Ósea , Estudios Transversales , Calcio , Fosfatasa Alcalina , Magnesio , Encuestas Nutricionales , Bicarbonatos , Osteoporosis/complicaciones , Enfermedades Óseas Metabólicas/etiología , Vitamina D , Factores de Riesgo , Cálculos Renales/epidemiología , Cálculos Renales/complicaciones , Vértebras Lumbares , Comorbilidad , Fósforo , Potasio , SodioRESUMEN
Background and objective: The early identification of modifiable risk factors is important for preventing kidney stones but determining causal associations can be difficult with epidemiological data. We aimed to genetically assess the causality between modifiable factors (lifestyle factors, serum parameters, and metabolic comorbidities) and the risk of kidney stones. Additionally, we aimed to explore the causal impact of education on kidney stones and its potential mediating pathways. Methods: We conducted a two-sample Mendelian randomization (MR) study to explore the causal association between 44 modifiable risk factors and kidney stones. The FinnGen dataset initially explored the causal relationship of risk factors with kidney stones and the UK Biobank dataset was used as the validation set. Then, a meta-analysis was conducted by combining discovery and validation datasets. We used two-step MR to assess potential mediators and their mediation proportions between education and kidney stones. Results: The combined results indicated that previous exposures may increase the risk of kidney stones, including sedentary behavior, urinary sodium, the urinary sodium/potassium ratio, the urinary sodium/creatinine ratio, serum calcium, 25-hydroxyvitamin D (25OHD), the estimated creatinine-based glomerular filtration rate (eGFRcrea), GFR estimated by serum cystatin C (eGFRcys), body mass index (BMI), waist circumference, type 2 diabetes mellitus (T2DM), fasting insulin, glycated hemoglobin, and hypertension. Coffee intake, plasma caffeine levels, educational attainment, and the urinary potassium/creatinine ratio may decrease the risk of kidney stones. Ranked by mediation proportion, the effect of education on the risk of kidney stones was mediated by five modifiable risk factors, including sedentary behavior (mediation proportion, 25.7%), smoking initiation (10.2%), BMI (8.2%), T2DM (5.8%), and waist circumference (3.2%). Conclusion: This study provides MR evidence supporting causal associations of many modifiable risk factors with kidney stones. Sedentary lifestyles, obesity, smoking, and T2DM are mediating factors in the causal relationship between educational attainment and kidney stones. Our results suggest more attention should be paid to these modifiable factors to prevent kidney stones.
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Diabetes Mellitus Tipo 2 , Cálculos Renales , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etiología , Creatinina , Análisis de la Aleatorización Mendeliana , Cálculos Renales/etiología , Cálculos Renales/genética , Potasio , SodioRESUMEN
Background: Gut microbiota, particularly Oxalobacter formigenes, has been previously reported to be associated with kidney stones. However, the conflicting results from both observational and intervention studies have created substantial uncertainty regarding the contribution of Oxalobacter formigenes to the formation of kidney stone. Methods: We employed a two-sample MR analysis to investigate the causal relationship between gut microbiota and kidney stones using GWASs summary statistics obtained from the MiBioGen and FinnGen consortia. Moreover, we conducted a reserve MR analysis to assess the direction of the causal associations between gut microbiota and kidney stones. The inverse variance weighted (IVW) approach represents the primary method of Mendelian Randomization (MR) analysis. Results: Our analyses do not yield supportive evidence for a causal link between the genus Oxalobacter (OR = 0.99, 95% CI: 0.90-1.09, p = 0.811) and the formation of kidney stones. The order Actinomycetales (OR = 0.79, 95% CI: 0.65-0.96, p = 0.020), family Actinomycetaceae (OR = 0.79, 95% CI: 0.65-0.96, p = 0.019), family Clostridiaceae 1 (OR = 0.80, 95% CI: 0.67-0.96, p = 0.015), genus Clostridiumsensustricto 1 (OR = 0.81, 95% CI: 0.67-0.98, p = 0.030) and genus Hungatella (OR = 0.86, 95% CI: 0.74-0.99, p = 0.040) had protective effects on kidney stones, and the genus Haemophilus (OR = 1.16, 95% CI: 1.01-1.33, p = 0.032), genus Ruminococcaceae (UCG010) (OR = 1.38, 95% CI: 1.04-1.84, p = 0.028), genus Subdoligranulum (OR = 1.27, 95% CI: 1.06-1.52, p = 0.009) were risk factors for kidney stones. Differential abundance analysis provide no evidence of a association between Oxalobacter formigenes and kidney stones, and showed genus Subdoligranulum were risk factors for kidney stones. Reverse MR analysis did not indicate any causal association of kidney stones on gut microbiota. No considerable heterogeneity of instrumental variables or horizontal pleiotropy was observed. Conclusion: Our two-sample MR study did not find any causal relationship between genus Oxalobacter and kidney stones. The association between gut microbiota and kidney stones does not solely depend on the presence of genus Oxalobacter/Oxalobacter formigenes. A more integrated approach using multiple omics platforms is needed to better understand the pathogenesis of kidney stones in the context of complex gene-environment interactions over time.
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BACKGROUND: Parents play an important role in shaping youth's lifestyle behaviors. This study aimed to investigate physical activity parenting practices (PAPP) for Chinese early adolescents and compare reporting discrepancies between parents and adolescent boys and girls. METHODS: Fifty-five adolescent-parent dyads participated in 16 paired focus group interviews, and an additional 122 dyads completed questionnaire surveys with open-ended questions. Participants were recruited from 3 public middle schools in Suzhou, China. Qualitative data were analyzed inductively using an open-coding scheme. Frequencies of codes were compared by parent-child role and adolescent gender using chi-square tests. RESULTS: Eighteen types of PAPP were identified and grouped into 6 categories: goals/control, structure, parental physical activity participation, communication, support, and discipline. These PAPP were viewed as promotive, preventive, or ineffective. Participants had mixed opinions on the effects of 11 PAPP and identified parental, adolescent, and environmental barriers for parents to promote youth physical activity. Compared with parents, adolescents were more likely to value the effects of setting expectation, scheduling, and coparticipation as well as dislike pressuring, restriction, and punishment. Girls were more likely to favor coparticipation and were more sensitive about negative communication than boys. Parents paid more attention to environmental barriers, whereas adolescents, especially girls, focused more on personal issues. CONCLUSIONS: Future studies need to address both positive and negative PAPP as well as perception discrepancies by child-parent role and adolescent gender to generate more evidence to promote parents as favorable socialization agents of youth physical activity.
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Ejercicio Físico , Responsabilidad Parental , Masculino , Femenino , Humanos , Adolescente , Pueblos del Este de Asia , Padres , Relaciones Padres-HijoRESUMEN
Research indicates that sleep problem is a behavioral risk factor of obesity. However, few research have applied a multi-dimensional approach to investigate the relationship between sleep health and adiposity. Therefore, the current study aimed to examine the associations of sleep characteristics (duration, quality) and chronotype with overweight/obesity as measured by body mass index. Data were obtained from 2014 college students from the Dali University in the Yunnan province of China in the year 2021. Sleep characteristics and chronotype were measured using self-reported questionnaires. The presence of overweight/obesity was assessed by anthropometric measurements. Multiple logistic regression models and restricted cubic spline hazard models were established to examine associations between sleep characteristics, chronotype and adiposity. After adjusting for demographic characteristics and other obesity-related behavioral risk factors, evening type was positively associated with overweight/obesity, and an L-shaped dose-effect relationship was observed between chronotype scores and the presence of overweight/obesity. However, sleep duration and quality were not associated with the presence of overweight/obesity in the logistic regression models and restrictive cubic splines models. This study indicated that Chinese college students who had the evening chronotype were more likely to be affected by overweight/obesity. Chronotype as an important dimension of sleep health should be incorporated in obesity intervention programs.
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Cronotipo , Sobrepeso , Humanos , Índice de Masa Corporal , Universidades , Ritmo Circadiano , China/epidemiología , Sueño , Obesidad/epidemiología , Obesidad/etiología , Encuestas y CuestionariosRESUMEN
Community-based programs may contribute to Latino pediatric obesity prevention; however, attendance remains low. This study aimed to identify factors associated with Latino father/male caregiver attendance in family-based adolescent obesity prevention programs conducted as part of a randomized controlled trial. The study used cross-sectional data from 137 fathers in the program, involving eight weekly sessions to improve their children's energy balance-related behaviors. Evaluation data were collected at baseline and post-intervention. Fathers in a waitlisted control group attended sessions after post-intervention data collection. Attendance patterns were identified using cluster analysis: consistently high attendance (50% of fathers), declining attendance (19%), and non-attendance (31%) clusters. Multinomial logistic regression was used to examine associations between attendance patterns and variables. Compared to consistently high attendance, fathers in the non-attendance cluster were more likely to have been assigned to the control group (odds ratio [OR] = 7.86, p < 0.001), tended to have lower household income (OR = 2.50, p = 0.098), and attended the program at a site where the program occurred weekdays (OR = 0.35, p = 0.094). Maintaining contact during waiting periods and providing sessions online or during weekends could reduce non-attendance by enhancing convenience for low-income fathers working multiple jobs.
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BACKGROUND: Randall's plaques (RP) are identified as anchored sites for kidney calcium oxalate stones, but the mechanism remains unclear. Given the importance of osteogenic-like cells in RP formation and OCT4 in reprogramming differentiated cells to osteoblasts, the current study explored the potential role of OCT4 in RP formation. METHODS: OCT4 and biomineralization were evaluated in RP, and immunofluorescence co-staining was performed to identify these cells with alteration of OCT4 and osteogenic markers. Based on the analysis of tissue, we further investigated the mechanism of OCT4 in regulating osteogenic-like differentiation of primary human renal interstitial fibroblasts (hRIFs) in vitro and vivo. RESULTS: We identified the upregulated OCT4 in RP, with a positive correlation to osteogenic markers. Interestingly, fibroblast marker Vimentin was partially co-localized with upregulated OCT4 and osteogenic markers in RP. Further investigations revealed that OCT4 significantly enhanced the osteogenic-like phenotype of hRIFs in vitro and in vivo. Mechanically, OCT4 directly bound to BMP2 promoter and facilitated its CpG island demethylation to transcriptionally promote BMP2 expression. Furthermore, combination of RIP and RNA profiling uncovered that lncRNA OLMALINC physically interacted with OCT4 to promote its stabilization via disrupting the ubiquitination. Additionally, OLMALINC was upregulated in fibroblasts in RP visualized by FISH, and a positive correlation was revealed between OLMALINC and OCT4 in RP. CONCLUSIONS: The upregulation of OCT4 in hRIFs was a pathological feature of RP formation, and OLMALINC/OCT4/BMP2 axis facilitated hRIFs to acquire osteogenic-like phenotype under osteogenic conditions, through which the pathway might participate in RP formation. Our findings opened up a new avenue to better understand RP formation in which osteogenic-like process was partially triggered by lncRNAs and pluripotency maintenance related genes.
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Proteína Morfogenética Ósea 2 , Cálculos Renales , Factor 3 de Transcripción de Unión a Octámeros , ARN Largo no Codificante , Humanos , Proteína Morfogenética Ósea 2/genética , Oxalato de Calcio/metabolismo , Fibroblastos/metabolismo , Riñón/metabolismo , Cálculos Renales/metabolismo , Médula Renal/patología , Fenotipo , ARN Largo no Codificante/genética , Factor 3 de Transcripción de Unión a Octámeros/genéticaRESUMEN
Parenting practices have been associated with adolescent lifestyle behaviors and weight status. Evidence is limited regarding the efficacy of interventions to address father influences on adolescent lifestyle behaviors through availability and modeling practices. Therefore, the purpose of this study was to evaluate changes in father parenting practices after Latino families with adolescents participated in the Padres Preparados Jóvenes Saludables (Padres) program. Time-1 (baseline) and Time-2 (post-intervention) data were used from Latino father/adolescent (10-14 years) dyads enrolled in the Padres two-arm (intervention vs. delayed-treatment control group) randomized controlled trial in four community locations. The program had eight weekly, 2.5-h experiential learning sessions on food preparation, parenting practices, nutrition, and physical activity. Two types of parenting practices (role modeling and home food availability) were assessed by father report via questionnaire for each of 7 lifestyle behaviors, for a total of 14 parenting practices. Linear regression mixed models were used to evaluate the intervention effects. A total of 94 father/adolescent dyads completed both Time-1 and Time-2 evaluations. Significant positive intervention effects were found for frequencies of fruit modeling (p = 0.002) and screen time modeling (p = 0.039). Non-significant results were found for the other 12 father parenting practices.
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Padre , Responsabilidad Parental , Niño , Adolescente , Masculino , Humanos , Crianza del Niño , Hispánicos o Latinos , Tiempo de PantallaRESUMEN
BACKGROUND: Childhood obesity is associated with adult major depressive disorder (MDD), but their causality is not clear. METHODS: We performed a two-sample Mendelian randomization (MR) analysis to explore the causality of childhood body mass index (BMI) and childhood obesity on MDD, followed by a multivariable MR (MVMR) analysis to investigate the potential role of adult BMI in mediating such effect. We accessed genome-wide association summary statistics of childhood BMI, childhood obesity, adult BMI and adult MDD from the Early Growth Genetics consortium (nBMI = 47 541, nobesity = 24 160), the Genetic Investigation of Anthropometric Traits consortium (nadult_BMI = â¼700 000) and the Psychiatric Genomics consortium (nMDD = 500 199), respectively. The MR-PRESSO test was performed to remove SNPs with potential pleiotropic effect. The MR analysis was performed by inverse-variance weighted test. Further sensitivity analyses, including the MR-Egger intercept test and leave-one-out analysis, were performed to evaluate the reliability of the results. RESULTS: Our study found that childhood obesity might increase the odds of developing MDD in adults (OR = 1.03, 95% CI: 1.01-1.06, p = 2.6 × 10-3 ). Children with higher BMI were more likely to develop MDD in adulthood, with an OR of 1.12 per standard deviation score (SDS) increase in BMI (95% CI: 1.07-1.17, p = 4.4 × 10-7 ). Sensitivity analyses verified the reliability of the causality between childhood BMI/obesity and MDD. Further MVMR results revealed that the impact of childhood BMI on MDD risk was predominantly mediated by adult BMI. CONCLUSION: Our findings provided evidence of a causal relationship between childhood BMI/obesity and adult MDD, thus providing new insights into the prevention of MDD.
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Trastorno Depresivo Mayor , Obesidad Infantil , Adulto , Niño , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Obesidad Infantil/epidemiología , Obesidad Infantil/genética , Obesidad Infantil/complicaciones , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/complicaciones , Estudio de Asociación del Genoma Completo , Reproducibilidad de los Resultados , Índice de Masa Corporal , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUNDS: Many literature reviews summarized relationships between screen time and child health, but they only included a few studies conducted in Chinese children and adolescents. The potential influence of screen time may vary by social context. The current systematic review and meta-analysis aimed to evaluate relationships between screen time and health issues among Chinese school-aged children and adolescents. METHODS: Peer-reviewed articles written in Chinese and English were retrieved from CNKI, Wanfang, PubMed, Embase, and Web of Science from inception to June 2020. The Downs & Black checklist was applied to assess study quality. Meta analyses used random effect models and mixed effects model to calculate pooled adjusted odds ratios and 95% confidence intervals. Heterogeneity, sensitivity, and publication bias were assessed using Q and I2 statistics, "one-study removed" analysis, the funnel plot, trim and fill analysis, and classical fail-safe N, respectively. RESULTS: In total, we identified 252 articles reporting 268 studies with unique samples. These studies investigated relationships between screen time and health issues of adiposity, myopia, psycho-behavioral problems, poor academic performance, cardiometabolic disease risks, sleep disorder, poor physical fitness, musculoskeletal injury, sub-health, and miscellaneous issues of height and pubertal growth, injury, sick leave, and respiratory symptoms. Proportions of studies reporting positive relationships with screen time were lowest in adiposity (50.6%) and higher in myopia (59.2%) and psycho-behavioral problems (81.8%). Other health issues were examined in 10 or less studies, all of which had more than half showing positive relationships. The pooled odds ratio from 19 studies comparing health risks with the screen time cutoff of 2 hours per day was 1.40 (95% CI: 1.31 to 1.50, I2 = 85.9%). The pooled effect size was 1.29 (95% CI: 1.20 to 1.39) after trimming 7 studies for publication bias adjustments. CONCLUSIONS: Findings exclusively generated from Chinese school-aged children and adolescents resonate those mainly from western countries. Evidence suggests that higher levels of screen time are related with greater risks of various health issues, although the relationships appear to be weak and intertwined with other confounding factors. Future studies need to investigate health-specific dose effects and mechanisms of screen time.
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Miopía , Tiempo de Pantalla , Adolescente , Niño , China/epidemiología , Humanos , Aptitud FísicaRESUMEN
Parental perception of children's weight may influence parents' feeding practices, and in turn, child dietary intake and weight status; however, there is limited evidence generated for preschoolers. The aim of this cross-sectional study was to investigate associations between Chinese parents' perceptions of child weight, feeding practices and preschoolers' dietary patterns. Participants (1616 parent-child pairs) were recruited from six kindergartens in Hunan, China. Parents' misperception, concern, and dissatisfaction on child weight were collected through a self-administered caregiver questionnaire. Parental feeding practices and children's dietary intake were, respectively, assessed using the Child Feeding Questionnaire and a Food Frequency Questionnaire. Linear regression models were applied to analyze associations between parental weight perceptions, feeding practices, and preschooler's dietary patterns. Associations between parents' weight perceptions and dietary patterns were significant only among underweight children. Regardless of child weight status, parental weight underestimation and preference for a heavier child were positively associated with pressure-to-eat. Parental weight concern was positively associated with restriction in normal weight child, but this was not found in other weight groups. In conclusion, Parents' misperception, concern, and dissatisfaction about child weight are associated with parents' feeding practices and may influence preschoolers' dietary quality, but the relationships vary by children's actual weight status.
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Ingestión de Alimentos/psicología , Conducta Alimentaria/psicología , Responsabilidad Parental/psicología , Padres/psicología , Percepción del Peso , Adulto , Pueblo Asiatico/psicología , Peso Corporal , Preescolar , China , Estudios Transversales , Dieta/psicología , Femenino , Humanos , Modelos Lineales , Masculino , Relaciones Padres-Hijo , Encuestas y Cuestionarios , Delgadez/psicologíaRESUMEN
Inflammatory arthritis (IA) is a common disease that affects millions of individuals worldwide. Proinflammatory events during IA pathogenesis are well studied; however, loss of protective immunity remains underexplored. Earlier, we reported that 14-3-3zeta (ζ) has a role in T-cell polarization and interleukin (IL)-17A signal transduction. Here, we demonstrate that 14-3-3ζ knockout (KO) rats develop early-onset severe arthritis in two independent models of IA, pristane-induced arthritis and collagen-induced arthritis. Arthritic 14-3-3ζ KO animals showed an increase in bone loss and immune cell infiltration in synovial joints. Induction of arthritis coincided with the loss of anti-14-3-3ζ antibodies; however, rescue experiments to supplement the 14-3-3ζ antibody by passive immunization did not suppress arthritis. Instead, 14-3-3ζ immunization during the presymptomatic phase resulted in significant suppression of arthritis in both wild-type and 14-3-3ζ KO animals. Mechanistically, 14-3-3ζ KO rats exhibited elevated inflammatory gene signatures at the messenger RNA and protein levels, particularly for IL-1ß. Furthermore, the immunization with recombinant 14-3-3ζ protein suppressed IL-1ß levels, significantly increased anti-14-3-3ζ antibody levels and collagen production, and preserved bone quality. The 14-3-3ζ protein increased collagen expression in primary rat mesenchymal cells. Together, our findings indicate that 14-3-3ζ causes immune suppression and extracellular remodeling, which lead to a previously unrecognized IA-suppressive function.
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Proteínas 14-3-3/metabolismo , Proteínas 14-3-3/farmacología , Artritis/inducido químicamente , Inflamación/tratamiento farmacológico , Proteínas 14-3-3/genética , Proteínas 14-3-3/inmunología , Animales , Anticuerpos , Artritis/genética , Artritis/metabolismo , Densidad Ósea , Enfermedades Óseas/metabolismo , Enfermedades Óseas/prevención & control , Colágeno/metabolismo , Colágeno/toxicidad , Femenino , Adyuvante de Freund/farmacología , Eliminación de Gen , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/inmunología , Inmunización Pasiva , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Terpenos/toxicidadRESUMEN
Encouraging greater consumption of vegetarian foods could be a strategy to improve plant-based food intake among non-vegetarians. Prior research on vegetarianism has focused mostly on people's motivations to be a vegetarian. However, the factors that motivate non-vegetarians to consume vegetarian meals remain largely unknown. The current research tested associations between attitudes, self-identity, and vegetarian meal consumption among 746 U.S. college students and 484 Chinese college students. Two types of attitudes were assessed: attitudes towards vegetarian food (ATF), which represents the personal benefits (including healthiness, tastiness, and enjoyableness) and attitudes towards people who are vegetarians (ATP), which represents the social benefits (perceived as being environmentally friendly, nice, and good-looking). Results showed that U.S. college students were more likely to be either vegetarians or non-vegetarians, while more Chinese college students tended to report being semi-vegetarians. In both samples, ATF and ATP were positively associated with self-identity and vegetarian meal consumption. Moderation analyses suggested that associations between attitudes and consumption were significant only among people who do not hold a definite self-identity as a vegetarian. In addition, ATP was significantly associated with vegetarian meal consumption among U.S. non- and semi-vegetarians alike, but among Chinese non-vegetarians only. These findings suggest that self-identity and cross-cultural differences are important to consider in promoting consumption of vegetarian meals through improving the public's attitudes towards vegetarian food and vegetarians.
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Dieta Vegetariana , Vegetarianos , Actitud , China , Humanos , Comidas , EstudiantesRESUMEN
OBJECTIVE: To investigate the influence of general parenting dimensions on adolescents' energy balance-related behaviours (EBRB) and its interactions with behaviour-specific parenting practices based on Darling and Steinberg's contextual model of parenting style. DESIGN: Multiple linear regression analyses and the Hayes PROCESS procedure to analyse self-reported cross-sectional survey data. SETTING: In-person survey. PARTICIPANTS: Latino early adolescents and their fathers (n 225 dyads) recruited using convenience sampling from metropolitan areas of north-central USA. RESULTS: Both paternal parenting dimensions of warmth and autonomy granting were positively associated with adolescents' fruit intake, vegetable intake and physical activity. Coercive control was positively associated with adolescents' sugary drink intake and sweets/salty snack intake. These associations were predominantly mediated by the parenting practices of setting expectations/allowances, role modelling, and managing availability and accessibility for corresponding EBRB. After adjusting for parenting practices, paternal warmth was inversely associated with adolescents' screen time, paternal autonomy was positively associated with sugary drink intake, and both paternal warmth and autonomy granting were positively associated with adolescents' fast food intake. In addition, positive associations between fathers' parenting practices and adolescents' sugary drink intake were significantly stronger among those who perceived high v. low levels of paternal warmth and autonomy granting. CONCLUSIONS: Paternal warmth and autonomy granting showed mixed effects on adolescents' EBRB, and coercive control showed undesirable relationships with adolescents' dietary intake via interactions with behaviour-specific parenting practices. Lifestyle intervention programmes for Latino adolescents need to consider incorporating paternal parenting education components.
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Padre , Responsabilidad Parental , Adolescente , Estudios Transversales , Hispánicos o Latinos , Humanos , Masculino , Relaciones Padres-Hijo , Tiempo de PantallaRESUMEN
BACKGROUND: Food security status has been assessed as a representative score for households; however, different members in the same household may perceive and report food insecurity differently. A high prevalence of food insecurity has been reported among Latino households, therefore understanding differences in reporting food insecurity by Latino father-mother dyads may improve accuracy of assessment and plans to address food insecurity. This study aimed to 1) determine demographic characteristics and/or food-related factors associated with perceptions of food security status among Latino father-mother dyads, and 2) identify factors associated with discordance in perceptions of food insecurity between dyads. METHODS: Baseline data were used from a community-based, youth obesity prevention program among Latino families (n = 106 father-mother dyads). Food security was assessed with a 2-item food insecurity screen. Logistic regression models were used to evaluate associations between reporting food security status and predictor variables for fathers, mothers, and dyad-discordant responses. RESULTS: Food insecurity was reported by 39% of fathers and 55% of mothers. Adjusted odds of reporting food insecurity were significantly higher for fathers perceiving their neighborhood was unsafe vs. safe (OR: 3.7, p < 0.05) and reporting lower vs. higher household income (OR: 3.2, p < 0.05). Adjusted odds of reporting food insecurity were significantly higher for mothers perceiving their neighborhood was unsafe vs. safe (OR: 4.1, p < 0.01) and reporting lower vs. higher home availability of fruit and vegetable (OR: 5.5, p < 0.01). Dyad discordance in reporting food security status occurred in 24% of the dyads. Adjusted odds of dyad discordant reports of food insecurity status were significantly higher for dyads reporting discordant responses regarding previous nutrition education (OR: 3.4, p < 0.05) and higher home fruit and vegetable accessibility (OR: 3.1, p < 0.05) compared to dyads reporting concordant responses. Among the 28 dyads who reported discordant nutrition education participation, 21 reported that fathers had never participated but mothers had participated more than once. CONCLUSIONS: Differential factors were associated with reporting food security among Latino father-mother dyads. Nutrition education for fathers that improves awareness of home food supplies and a better understanding of how food accessibility influences maternal perceptions may improve dyad discordance in reporting household food security.