Journal of Developmental Origins of Health and Disease最新文献

{"title":"Programming fetal cardiometabolic pathways: the double-edged role of glucocorticoids in heart development.","authors":"Reza Amanollahi, Melanie Bertossa, Kent Thornburg, Michael Wiese, Mitchell Lock, Janna Morrison","doi":"10.1017/S2040174425100330","DOIUrl":"https://doi.org/10.1017/S2040174425100330","url":null,"abstract":"<p><p>In a normal pregnancy, glucocorticoids (GC), such as cortisol, play an essential role in early heart development. GC concentrations surge in late gestation to facilitate the maturation of fetal systems in preparation for birth. However, pregnancy complications related to stress, lifestyle factors, disease, and commonly used antenatal care treatments (GC therapy and artificial reproductive technology) can lead to prematurely increased GC concentrations that are detrimental to the heart before it is mature enough to benefit. These findings underpin the hypothesis that GC play a double-edged role that benefits normal heart development but is potentially harmful when dysregulated. However, the mechanisms by which both physiological and pathological elevations in GC concentrations influence the fetal cardiometabolic pathways that lead to detrimental long-term cardiovascular outcomes remain unclear. This review will, firstly, describe how cortisol regulates different aspects of cardiac development and, secondly, compare findings from different animal models that have provided mechanistic insight into how excess cortisol/GC during pregnancy impacts cardiac health across the life course.</p>","PeriodicalId":49167,"journal":{"name":"Journal of Developmental Origins of Health and Disease","volume":"16 ","pages":"e50"},"PeriodicalIF":1.5,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental polychlorinated biphenyl mixture exposure promotes selective neural alterations: An immunohistochemical study in adult rat offspring.","authors":"Nazneen Rustom, James Reynolds","doi":"10.1017/S2040174425100329","DOIUrl":"https://doi.org/10.1017/S2040174425100329","url":null,"abstract":"<p><p>The fetus and neonate are especially vulnerable to toxic effects of polychlorinated biphenyls (PCBs), that have been shown to perturb behavioral and neuropsychological development. This study aimed to examine the long-term effects of developmental exposure to PCBs. Doses selected were environmentally relevant to those found in epidemiological studies, on the central nervous system (CNS) of adult rat offspring. Pregnant Sprague Dawley rats were fed cookies that contained a mixture of fourteen PCBs or vehicle (corn oil) daily. PCB doses were 0.011 mg/kg maternal body weight/day (\"low\") or 1.10 mg/kg maternal body weight/day (\"high\"), for 42 days throughout gestation and lactation. Adult offspring were euthanized on postnatal day 450. A battery of immunohistochemical markers of brain structure and function were selected to assess possible effects of developmental PCB exposure. Using a 3×2 factorial design (treatment and sex), two-way analysis of variance revealed significant effects of treatment through the CNS, with no main effect of sex or interaction effects. In comparison with controls, both low and high dose developmental PCB exposure significantly (<i>p</i> < 0.05) increased inhibitory enzyme glutamic acid decarboxylase (GAD67) immunoreactivity in the cerebellar vermis, and decreased lipofuscin autofluorescence in the locus coeruleus (LC). Low dose developmental PCB exposure significantly decreased the perimeter of endothelial cells in the periaqueductal gray, ventral orbitofrontal cortex; and decreased lipofuscin in the dorsal striatum, compared to controls. Findings support the Developmental Origins of Health and Disease concept, which broadly posits that early-life perturbations may influence health trajectories over the lifespan.</p>","PeriodicalId":49167,"journal":{"name":"Journal of Developmental Origins of Health and Disease","volume":"16 ","pages":"e49"},"PeriodicalIF":1.5,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parental birth weight as a predictor of neonatal and childhood outcomes in children: a systematic review and meta-analysis.","authors":"Deep Dutta, Lakshmi Nagendra, Saptarshi Bhattacharya, A B M Kamrul-Hasan, Chittaranjan Sakerlal Yajnik","doi":"10.1017/S2040174425100366","DOIUrl":"10.1017/S2040174425100366","url":null,"abstract":"<p><p>Several studies have been published studying association between parental low birth weight (BW) and neonatal outcomes of their children. To date no systematic review and meta-analysis (SRM) has been published to quantify the impact of maternal and paternal BW on outcomes in the next generation. The aim of this SRM was to analyse the association between parental BW and anthropometric and metabolic outcomes in their children.Electronic databases were searched for studies documenting BW of parents and children with neonatal outcomes. Primary outcome was to evaluate impact of parental BW on occurrence of LBW in children. Secondary outcomes were to assess impact of parental BW on occurrence of macrosomia, small for gestational age (SGA), preterm labour/delivery, and burden of non-communicable disease in later life.We screened 54,961 articles, data from 14 studies (320,515 parent-child pairs), which fulfilled all criteria, were analysed. Maternal LBW was associated with higher chances of neonatal LBW [odds ratio (OR)1.95 (95% CI:1.56-2.46); <i>P</i> < 0.01; <i>I</i>² = 91%], neonatal SGA [OR 2.29(95% CI:1.72-3.05); <i>P</i> < 0.01; <i>I</i>² = 37%], lower chances of neonatal macrosomia [OR 0.50 (95% CI:0.39-0.65); <i>P</i> < 0.01; <i>I</i>² = 35%] and had no impact on preterm labour/delivery [OR1.20(95% CI:0.67-2.16); <i>P</i> = 0.53; <i>I</i>² = 88%]. Maternal macrosomia was associated with higher neonatal macrosomia [OR 2.66 (95% CI:2.44-3.16); <i>P</i> < 0.01; <i>I</i>² = 48%], lower SGA [OR 0.40(95% CI:0.29-0.53); <i>P</i> < 0.01; <i>I</i>² = 0%] and preterm labour/delivery [OR 0.77 (95% CI:0.63-0.94); <i>P</i> < 0.01; <i>I</i>² = 4%]. Paternal but not maternal LBW was predictor of metabolic syndrome and diabetes in adulthood.Maternal LBW is an important predictor of LBW and SGA in neonates. Maternal macrosomia is an important predictor of neonatal macrosomia; is protective against SGA and preterm labour/childbirth. Neonatal size of parents is reflected in neonatal size of their children.</p>","PeriodicalId":49167,"journal":{"name":"Journal of Developmental Origins of Health and Disease","volume":"17 ","pages":"e1"},"PeriodicalIF":1.5,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early life trajectories of head circumference predict executive function and fluid cognitive skills at age 4 in Kenya.","authors":"Michael T Willoughby, Amanda J Wylie, Hemstone Mugala, Rachel Kamau, Brent Collett, Emily Begnel, Ednah Ojee, Judith Adhiambo, Eliza Mabele, Soren Gantt, Sarah Benki-Nugent, Cheryl Day, Jennifer Slyker, John Kinuthia, Dalton Wamalwa","doi":"10.1017/S2040174425100275","DOIUrl":"10.1017/S2040174425100275","url":null,"abstract":"<p><p>Head circumference (HC) is a low-cost proxy for early brain development, yet few studies have examined its predictive value for specific neurocognitive outcomes in low- and middle-income countries. This study investigated whether trajectories of HC growth from 1 to 24 months predict executive function and fluid cognitive skills at age 4 in a Kenyan cohort (<i>N</i> = 182). Using latent growth curve modeling, we found that greater HC growth was significantly associated with better EF and fluid cognitive skills, independent of initial HC and sociodemographic factors. These associations were robust across subgroups defined by prenatal exposure to HIV and atypical physical growth (i.e., extreme values for weight-for-length, underweight, or HC). Moreover, the predictive association between early HC and later neurocognition was evident within the first 15 months of life. This study highlights the value of monitoring changes in HC as one aspect of early child health and wellbeing. Infants who do not exhibit normative increases in HC in infancy may benefit from early neurocognitive assessments and/or the receipt of early intervention services.</p>","PeriodicalId":49167,"journal":{"name":"Journal of Developmental Origins of Health and Disease","volume":"16 ","pages":"e45"},"PeriodicalIF":1.6,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12926735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145769781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the relationships between food insecurity, maternal stress, and maternal-infant health outcomes during the COVID-19 pandemic.","authors":"Landry Kalembo, Shannon Bainbridge, Bénédicte Fontaine-Bisson","doi":"10.1017/S2040174425100317","DOIUrl":"https://doi.org/10.1017/S2040174425100317","url":null,"abstract":"<p><p>The COVID-19 pandemic intensified food insecurity (FI) and stress for many pregnant individuals, which may have contributed to adverse fetal developmental programming. This study aimed to identify key social determinants of health associated with pandemic-related FI and stress, and their association with gestational weight gain (GWG) and newborn birth weight in a Canadian pregnant cohort. Data were collected retrospectively from 273 pregnant individuals who delivered infants in Canada during the pandemic (March 2020-March 2023). Validated questionnaires were used to assess FI and pandemic-related stress, and GWG and infant birth weight were self-reported. FI was experienced by 55.7% of the participants, while 33.7% and 19.7% reported heightened stress related to COVID-19 infection and pregnancy preparedness, respectively. Participants from food-secure and food-insecure households differed significantly in parental structure, age, sexual orientation, housing status, household income, number of children in the household and pregnancy planning (all <i>p</i> values < 0.01). Heightened stress for both pregnancy preparedness and COVID-19 infection was also significantly associated with these same factors (all <i>p</i> values < 0.05) but not for age and housing status. FI and heightened stress were not associated with GWG outside the recommended range. However, significantly higher likelihood of birth weight extremes was observed with heightened COVID-19 infection-related stress (OR, 95% CI 1.50, 1.05-2.12, <i>p</i> = 0.02) and pregnancy preparedness-related stress (1.60, 1.10-2.31, <i>p</i> = 0.01), but not with FI. These findings underscore the influence of psychosocial factors on FI and stress during pregnancy, which may negatively impact infant health outcomes during the pandemic.</p>","PeriodicalId":49167,"journal":{"name":"Journal of Developmental Origins of Health and Disease","volume":"16 ","pages":"e47"},"PeriodicalIF":1.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small for gestational age by grandmaternal smoking during pregnancy: Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.","authors":"Mustakim, Mami Ishikuro, Chikana Kawaguchi, Genki Shinoda, Aoi Noda, Masatsugu Orui, Keiko Murakami, Hirohito Metoki, Taku Obara, Shinichi Kuriyama","doi":"10.1017/S2040174425100305","DOIUrl":"https://doi.org/10.1017/S2040174425100305","url":null,"abstract":"<p><p>Small-for-gestational age (SGA) is an important global public health issue because of its increasing prevalence and long-term effects. Maternal smoking is a known risk factor for SGA; however, the effect of grandmaternal smoking on the risk of SGA in grandchildren SGA remains unclear. In this study, we examined whether grandmaternal smoking during pregnancy was associated with small birth weight, length, and head circumference for gestational age. Data were obtained from 23,730 pregnant women and their offspring from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Studies. A total of 1,130 grandmaternal-maternal-child triads were identified. Grandmaternal smoking during pregnancy was defined by the Maternal and Child Health Handbook owned by the mothers at birth mothers when they were born. Birth outcomes of grandchildren were obtained from medical records and converted to SGA using the 10^th percentile for weight, length, and head circumference. A multivariate logistic regression and propensity scores were used for the analysis. Prevalence of <10th percentile for birth weight, length, and head circumference in grandmaternal smokers were 10.2%, 2.0%, and 10.2%, respectively. Grandmaternal smoking during pregnancy was associated with the lower grandchild's birth weight (odds ratio (OR) [95% (CI)]: 2.86 [1.05-7.82]) and remained consistent when adjusted by propensity score (OR [95% CI]: 2.87 [1.04-7.92]). Grandmaternal smoking should not be ignored when assessing the SGA risk. Future work should consider the complex mediating relationship between smoking and growth restriction across generations.</p>","PeriodicalId":49167,"journal":{"name":"Journal of Developmental Origins of Health and Disease","volume":"16 ","pages":"e46"},"PeriodicalIF":1.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fetal renal growth and hemodynamics in pregnancies complicated by maternal diabetes: a comparative study.","authors":"Fırat Ersan, Verda Alpay, Barış Boza","doi":"10.1017/S2040174425100342","DOIUrl":"https://doi.org/10.1017/S2040174425100342","url":null,"abstract":"<p><p>Maternal diabetes during pregnancy, including pre-gestational and gestational diabetes mellitus (DM), can significantly affect fetal development, particularly in the kidneys. This study aimed to investigate the effects of maternal diabetes on fetal kidney size, parenchymal thickness, and renal artery hemodynamics using ultrasonography. A total of 128 pregnant women were enrolled and classified into pre-gestational DM (<i>n</i> = 28), gestational DM (<i>n</i> = 36), and control (<i>n</i> = 64) groups. Fetal kidney measurements, including anteroposterior, mediolateral, and longitudinal diameters as well as renal parenchymal thickness (RPT) and renal artery pulsatility index (PI), were assessed between 28 and 38 weeks of gestation. Fetal kidney volumes and their ratios to estimated fetal weight (EFW) and abdominal circumference (AC) were significantly lower in both the pre-gestational and gestational DM groups than in the controls (<i>p</i> < 0.05). However, no significant differences were observed in the RPT/AC ratios or renal artery PI among the groups. Furthermore, no significant correlations were found between maternal hemoglobin A1c (HbA1c) levels and fetal kidney or blood flow parameters. These findings suggest that maternal diabetes alters fetal kidney growth patterns relative to the overall fetal size, potentially reflecting developmental programming that may affect nephron endowment and long-term renal health. The lack of significant differences in RPT/AC ratios and renal artery PI may be attributed to effective diabetes management or limitations in detecting subtle changes using the current ultrasound methodologies. Further longitudinal studies with larger cohorts and postnatal follow-up are warranted to clarify long-term renal outcomes and explore the precise mechanisms underlying these developmental changes.</p>","PeriodicalId":49167,"journal":{"name":"Journal of Developmental Origins of Health and Disease","volume":"16 ","pages":"e48"},"PeriodicalIF":1.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-dose cyantraniliprole alters hepatorenal parameters in pubertal and adult male Wistar rats exposed during pregnancy and lactation.","authors":"Lucas Marcelo Meira Silva, Isadora Chagas Vercellone, Ana Camila Ferreira de Menezes, João Vinicius Honório Silva, Pedro Rocha Tenório, Mariana Marques Bertozzi, Matheus Deroco Veloso Silva, Waldiceu Aparecido Verri, Glaura Scantamburlo Alves Fernandes, Fábio Goulart de Andrade","doi":"10.1017/S2040174425100263","DOIUrl":"https://doi.org/10.1017/S2040174425100263","url":null,"abstract":"<p><p>Cyantraniliprole is a widely used insecticide that disrupts calcium homeostasis by binding to ryanodine receptors (RyRs) in the sarcoplasmic reticulum. Insects have a type of RyR with a 47% sequence homology to mammalian RyRs. Due to the high homology and strong affinity of cyantraniliprole for insect RyRs, concerns have been raised about potential adverse effects in mammals. This study aimed to evaluate the effects of cyantraniliprole on the liver and kidneys of male Wistar rat offspring exposed to a dose of 10 mg/kg during gestation and lactation. Thirty-three 80-day-old pregnant Wistar rats were randomly assigned to either a control group or a cyantraniliprole group (10 mg/kg). The treatment period lasted from the 5th gestational day to the 21st lactational day. The offspring were euthanized on postnatal day 55 (puberty) or 90 (adulthood). Blood samples were collected for biochemical assays, and liver and kidney samples were collected for histopathological analysis, oxidative stress biomarkers, and inflammatory profile assessment. The results indicated that exposure to cyantraniliprole caused vacuolation and vascular congestion in the pubertal and adult offspring, as well as significant morphological changes in the liver and kidneys. There was an increase in catalase and glutathione S-transferase activity in response to oxidative stress induced by the insecticide in the liver, with elevated levels of thiobarbituric acid reactive substances in the liver of adult animals and increased myeloperoxidase activity in pubertal animals. These findings suggest that exposure to cyantraniliprole induces significant damage to the organs involved in metabolism and excretion.</p>","PeriodicalId":49167,"journal":{"name":"Journal of Developmental Origins of Health and Disease","volume":"16 ","pages":"e44"},"PeriodicalIF":1.5,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145642099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anthropometry to advanced technologies: evaluation of growth and body composition in neonates.","authors":"Cansu Cakici, Eda Koksal","doi":"10.1017/S2040174425100299","DOIUrl":"https://doi.org/10.1017/S2040174425100299","url":null,"abstract":"<p><p>Neonatal growth assessment during the first 28 days of life is a critical determinant of infant health and survival. Anthropometric measurements provide a simple, inexpensive, and non-invasive means to evaluate neonatal size, nutritional status, and growth, as well as to predict long-term health outcomes. Alongside standard growth curves, methods for assessing neonatal body composition offer additional insights into fat and fat-free mass distribution, which are linked to later risks such as childhood obesity and metabolic complications. This review summarizes the commonly used anthropometric measures and advanced laboratory techniques for assessing neonatal growth and body composition, discusses their advantages and limitations, and highlights the importance of their combined use in clinical and research settings. Understanding these methods is essential for early identification of growth disturbances and for promoting optimal nutrition and health outcomes throughout the life course.</p>","PeriodicalId":49167,"journal":{"name":"Journal of Developmental Origins of Health and Disease","volume":"16 ","pages":"e43"},"PeriodicalIF":1.5,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145607060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of the heat shock response by human milk-derived extracellular vesicles in neonates with perinatal high-fat diet exposure.","authors":"Jasmyne A Storm, Jueqin Lu, Mon Francis Obtial, Sanoji Wijenayake","doi":"10.1017/S2040174425100287","DOIUrl":"https://doi.org/10.1017/S2040174425100287","url":null,"abstract":"<p><p>Maternal consumption of a high-fat diet (mHFD) during perinatal life influences hypothalamic-pituitary-adrenal (HPA) axis activation and impacts the long-term physiological and metabolic health of offspring. Milk-derived extracellular vesicles (MEVs) are lipid-coated nanovesicles that transfer biological materials from mother to infant and can survive intestinal degradation and cross the blood-brain barrier. MEVs provide cytoprotection in peripheral organs; however, their pro-survival functions remain unknown in the neonatal brain. Further, sex differences resulting from MEV treatment require investigation, as male and female neonates display variable responses to early life nutrient stress. We investigated the interaction between MEVs and the heat shock protein response in the liver, hypothalamus, and prefrontal cortex in male and female neonatal rats exposed to perinatal mHFD at postnatal day 11. MEV treatment robustly modulated the HSR in female neonates with the largest response recorded in the prefrontal cortex. These results suggest that MEVs may influence pro-survival outcomes in the prefrontal cortex by activating HSF1-mediated pro-survival in a sex-specific manner.</p>","PeriodicalId":49167,"journal":{"name":"Journal of Developmental Origins of Health and Disease","volume":"16 ","pages":"e42"},"PeriodicalIF":1.5,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}