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1.
Proc Natl Acad Sci U S A ; 120(43): e2313374120, 2023 Oct 24.
Article in English | MEDLINE | ID: mdl-37844220

ABSTRACT

Large increases in the number of low earth orbit satellites are projected in the coming decades [L. Schulz, K.-H. Glassmeier, Adv. Space Res. 67, 1002-1025 (2021)] with perhaps 50,000 additional satellites in orbit by 2030 [GAO, Large constellations of satellites: Mitigating environmental and other effects (2022)]. When spent rocket bodies and defunct satellites reenter the atmosphere, they produce metal vapors that condense into aerosol particles that descend into the stratosphere. So far, models of spacecraft reentry have focused on understanding the hazard presented by objects that survive to the surface rather than on the fate of the metals that vaporize. Here, we show that metals that vaporized during spacecraft reentries can be clearly measured in stratospheric sulfuric acid particles. Over 20 elements from reentry were detected and were present in ratios consistent with alloys used in spacecraft. The mass of lithium, aluminum, copper, and lead from the reentry of spacecraft was found to exceed the cosmic dust influx of those metals. About 10% of stratospheric sulfuric acid particles larger than 120 nm in diameter contain aluminum and other elements from spacecraft reentry. Planned increases in the number of low earth orbit satellites within the next few decades could cause up to half of stratospheric sulfuric acid particles to contain metals from reentry. The influence of this level of metallic content on the properties of stratospheric aerosol is unknown.

2.
Eur J Nutr ; 61(7): 3741-3753, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35708759

ABSTRACT

PURPOSE: Emerging evidence from rodent studies suggests that high-fat-diet (HFD)-induced obesity is characterized by increased oxidative damage in sperm and testis. However, interventions using micronutrient supplementation to mitigate oxidative damage in obesity have not been extensively studied. This study aimed to investigate the effect of an antioxidant-based micronutrient supplement (added folate, vitamin B6, choline, betaine, and zinc) on sperm and testicular oxidative damage in HFD-fed male Sprague Dawley rats. METHODS: Rats (3-weeks-old, 12/group) were weaned onto control (C) or HFD (H) or these diets with micronutrient supplement (CS; HS); sperm and testis were harvested at 30.5 weeks. To assess oxidative stress and antioxidant capacity in testis, levels of malondialdehyde (MDA), glutathione (GSH), folate and susceptibility index (SI) of pro-oxidative damage, mRNA expression of Nrf2, NFκB-p65, IL-6, IL-10 and TNF-α, in addition to superoxide-dismutase (SOD), catalase and glutathione-peroxidase (GPx) activities were measured. 8-hydroxy-2-deoxyguanosine (8-OHdG) were assessed in both sperm and testis. RESULTS: HFD-fed rats had significantly increased 8-OHdG content in sperm and testis, increased testicular SI, decreased testicular weight, SOD and GPx activity compared to control. Strikingly, supplementation of HFD appeared to significantly reduce 8-OHdG in sperm and testis (22% and 24.3%, respectively), reduce testicular SI and MDA content (28% and 40%, respectively), increase testicular weight (24%), SOD and GPX activity (30% and 70%, respectively) and GSH content (19%). Moreover, supplementation had significant impact to increase testicular folate content regardless of diet. Furthermore, an overall effect of supplementation to increase testicular mRNA expression of Nrf2 was observed across groups. Interestingly, testicular SI was positively correlated with sperm and testicular 8-OHdG and MDA content, suggesting a critical role of testicular antioxidant activity to combat oxidative damage in sperm and testis. CONCLUSION: Our findings suggest that antioxidant-based micronutrient supplement has the potential to interrupt HFD-induced sperm and testicular oxidative damage by improving testicular antioxidant capacity.


Subject(s)
Antioxidants , Testis , 8-Hydroxy-2'-Deoxyguanosine , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Diet, High-Fat/adverse effects , Folic Acid/pharmacology , Glutathione/metabolism , Male , Micronutrients , NF-E2-Related Factor 2/metabolism , Obesity/metabolism , Oxidative Stress , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Semen/metabolism , Spermatozoa , Superoxide Dismutase/metabolism
3.
Int J Obes (Lond) ; 46(5): 901-917, 2022 05.
Article in English | MEDLINE | ID: mdl-35022547

ABSTRACT

In the last two decades, evidence from human and animal studies suggests that paternal obesity around the time of conception can have adverse effects on offspring health through developmental programming. This may make significant contributions to the current epidemic of obesity and related metabolic and reproductive complications like diabetes, cardiovascular disease, and subfertility/infertility. To date, changes in seminal fluid composition, sperm DNA methylation, histone composition, small non-coding RNAs, and sperm DNA damage have been proposed as potential underpinning mechanism to program offspring health. In this review, we discuss current human and rodent evidence on the impact of paternal obesity/overnutrition on offspring health, followed by the proposed mechanisms, with a focus on sperm DNA damage underpinning paternal programming. We also summarize the different intervention strategies implemented to minimize effects of paternal obesity. Upon critical review of literature, we find that obesity-induced altered sperm quality in father is linked with compromised offspring health. Paternal exercise intervention before conception has been shown to improve metabolic health. Further work to explore the mechanisms underlying benefits of paternal exercise on offspring are warranted. Conversion to healthy diets and micronutrient supplementation during pre-conception have shown some positive impacts towards minimizing the impact of paternal obesity on offspring. Pharmacological approaches e.g., metformin are also being applied. Thus, interventions in the obese father may ameliorate the potential detrimental impacts of paternal obesity on offspring.


Subject(s)
Fathers , Spermatozoa , Animals , DNA Methylation , Epigenesis, Genetic , Humans , Male , Obesity/metabolism , Social Responsibility
4.
Cells ; 10(7)2021 07 11.
Article in English | MEDLINE | ID: mdl-34359921

ABSTRACT

Obesity increases the risk of metabolic disorders, partly through increased oxidative stress. Here, we examined the effects of a dietary micronutrient supplement (consisting of folate, vitamin B6, choline, betaine, and zinc) with antioxidant and methyl donor activities. Male Sprague Dawley rats (3 weeks old, 17/group) were weaned onto control (C) or high-fat diet (HFD) or same diets with added micronutrient supplement (CS; HS). At 14.5 weeks of age, body composition was measured by magnetic resonance imaging. At 21 weeks of age, respiratory quotient and energy expenditure was measured using Comprehensive Lab Animal Monitoring System. At 22 weeks of age, an oral glucose tolerance test (OGTT) was performed, and using fasting glucose and insulin values, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated as a surrogate measure of insulin resistance. At 30.5 weeks of age, blood and liver tissues were harvested. Liver antioxidant capacity, lipids and expression of genes involved in lipid metabolism (Cd36, Fabp1, Acaca, Fasn, Cpt1a, Srebf1) were measured. HFD increased adiposity (p < 0.001) and body weight (p < 0.001), both of which did not occur in the HS group. The animals fed HFD developed impaired fasting glucose, impaired glucose tolerance, and fasting hyperinsulinemia compared to control fed animals. Interestingly, HS animals demonstrated an improvement in fasting glucose and fasting insulin. Based on insulin release during OGTT and HOMA-IR, the supplement appeared to reduce the insulin resistance developed by HFD feeding. Supplementation increased hepatic glutathione content (p < 0.05) and reduced hepatic triglyceride accumulation (p < 0.001) regardless of diet; this was accompanied by altered gene expression (particularly of CPT-1). Our findings show that dietary micronutrient supplementation can reduce weight gain and adiposity, improve glucose metabolism, and improve hepatic antioxidant capacity and lipid metabolism in response to HFD intake.


Subject(s)
Dietary Supplements , Glucose/metabolism , Lipid Metabolism , Liver/metabolism , Micronutrients , Obesity/metabolism , Animals , Antioxidants/metabolism , Diet, High-Fat , Disease Models, Animal , Gene Expression Regulation , Leptin/blood , Lipid Metabolism/genetics , Lipids/blood , Obesity/genetics , Rats, Sprague-Dawley , Thiobarbituric Acid Reactive Substances/metabolism
5.
Sci Adv ; 7(20)2021 May.
Article in English | MEDLINE | ID: mdl-33990319

ABSTRACT

Many climate intervention (CI) methods have been proposed to offset greenhouse gas-induced global warming, but the practicalities regarding implementation have not received sufficient attention. Stratospheric aerosol injection (SAI) involves introducing large amounts of CI material well within the stratosphere to enhance the aerosol loading, thereby increasing reflection of solar radiation. We explore a delivery method termed solar-powered lofting (SPL) that uses solar energy to loft CI material injected at lower altitudes accessible by conventional aircraft. Particles that absorb solar radiation are dispersed with the CI material and heat the surrounding air. The heated air rises, carrying the CI material to the stratosphere. Global model simulations show that black carbon aerosol (10 microgram per cubic meter) is sufficient to quickly loft CI material well into the stratosphere. SPL could make SAI viable at present, is also more energy efficient, and disperses CI material faster than direct stratospheric injection.

6.
Hosp Pediatr ; 9(12): 949-957, 2019 12.
Article in English | MEDLINE | ID: mdl-31694831

ABSTRACT

BACKGROUND AND OBJECTIVES: The translation of research findings into routine care remains slow and challenging. We previously reported successful implementation of an asthma evidence-based care process model (EB-CPM) at 8 (1 tertiary care and 7 community) hospitals, leading to a high health care provider (HCP) adherence with the EB-CPM and improved outcomes. In this study, we explore contextual factors perceived by HCPs to facilitate successful EB-CPM implementation. METHODS: Structured and open-ended questions were used to survey HCPs (n = 260) including physicians, nurses, and respiratory therapists, about contextual factors perceived to facilitate EB-CPM implementation. Quantitative analysis was used to identify significant factors (correlation coefficient ≥0.5; P ≤ .05) and qualitative analysis to assess additional facilitators. RESULTS: Factors perceived by HCPs to facilitate EB-CPM implementation were related to (1) inner setting (leadership support, adequate resources, communication and/or collaboration, culture, and previous experience with guideline implementation), (2) intervention characteristics (relevant and applicable to the HCP's practice), (3) individuals (HCPs) targeted (agreement with the EB-CPM and knowledge of supporting evidence), and (4) implementation process (participation of HCPs in implementation activities, teamwork, implementation team with a mix of expertise and professional's input, and data feedback). Additional facilitators included (1) having appropriate preparation and (2) providing education and training. CONCLUSIONS: Multiple factors were associated with successful EB-CPM implementation and may be used by others as a guide to facilitate implementation and dissemination of evidence-based interventions for pediatric asthma and other chronic diseases in the hospital setting.


Subject(s)
Asthma/therapy , Evidence-Based Medicine/methods , Health Personnel , Hospitalization , Pediatrics/methods , Cross-Sectional Studies , Humans , Idaho , Surveys and Questionnaires , Utah
7.
Pediatrics ; 143(6)2019 06.
Article in English | MEDLINE | ID: mdl-31097465

ABSTRACT

BACKGROUND AND OBJECTIVES: Pediatric ambulatory asthma control is suboptimal, reducing quality of life (QoL) and causing emergency department (ED) and hospital admissions. We assessed the impact of the electronic-AsthmaTracker (e-AT), a self-monitoring application for children with asthma. METHODS: Prospective cohort study with matched controls. Participants were enrolled January 2014 to December 2015 in 11 pediatric clinics for weekly e-AT use for 1 year. Analyses included: (1) longitudinal changes for the child (QoL, asthma control, and interrupted and missed school days) and parents (interrupted and missed work days and satisfaction), (2) comparing ED and hospital admissions and oral corticosteroid (OCS) use pre- and postintervention, and (3) comparing ED and hospital admissions and OCS use between e-AT users and matched controls. RESULTS: A total of 327 children and parents enrolled; e-AT adherence at 12 months was 65%. Compared with baseline, participants had significantly (P < .001) increased QoL, asthma control, and reduced interrupted and missed school and work days at all assessment times. Compared with 1 year preintervention, they had reduced ED and hospital admissions (rate ratio [RR]: 0.68; 95% confidence interval [CI]: 0.49-0.95) and OCS use (RR: 0.74; 95% CI: 0.61-0.91). Parent satisfaction remained high. Compared with matched controls, participants had reduced ED and hospital admissions (RR: 0.41; 95% CI: 0.22-0.75) and OCS use (RR: 0.65; 95% CI: 0.46-0.93). CONCLUSIONS: e-AT use led to high and sustained participation in self-monitoring and improved asthma outcomes. Dissemination of this care model has potential to broadly improve pediatric ambulatory asthma care.


Subject(s)
Ambulatory Care/methods , Asthma/therapy , Disease Management , Parents , Self-Management/methods , Adolescent , Ambulatory Care/psychology , Ambulatory Care Facilities , Asthma/psychology , Child , Child, Preschool , Cohort Studies , Female , Humans , Male , Parents/psychology , Prospective Studies , Self-Management/psychology
8.
Geophys Res Lett ; 46(2): 1061-1069, 2019 Jan 28.
Article in English | MEDLINE | ID: mdl-34219825

ABSTRACT

Convective systems dominate the vertical transport of aerosols and trace gases. The most recent in situ aerosol measurements presented here show that the concentrations of primary aerosols including sea salt and black carbon drop by factors of 10 to 10,000 from the surface to the upper troposphere. In this study we show that the default convective transport scheme in the National Science Foundation/Department of Energy Community Earth System Model results in a high bias of 10-1,000 times the measured aerosol mass for black carbon and sea salt in the middle and upper troposphere. A modified transport scheme, which considers aerosol activation from entrained air above the cloud base and aerosol-cloud interaction associated with convection, dramatically improves model agreement with in situ measurements suggesting that deep convection can efficiently remove primary aerosols. We suggest that models that fail to consider secondary activation may overestimate black carbon's radiative forcing by a factor of 2.

9.
J Psychiatr Res ; 109: 96-106, 2019 02.
Article in English | MEDLINE | ID: mdl-30513490

ABSTRACT

People living with mental illness often experience poor sleep quality compared to the general population. Poor sleep quality exacerbates symptoms of mental illness and contributes to increased physical comorbidities. Exercise has been shown to be an effective non-pharmacological treatment for managing poor sleep in the general population. Little is known regarding the efficacy of targeted exercise interventions for improving sleep quality amongst individuals with a mental illness. We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) examining the impact of exercise on sleep quality in people with mental illness. Major electronic databases were searched from inception until June 2018 for exercise-based RCTs that included either subjective and/or objective measures of sleep quality in people with severe mental illness (SMI). Eight RCT's were included in the meta-analysis, involving use of a range of exercise modalities in people with SMI diagnoses. Overall, exercise had a large statistically significant effect on sleep quality (hedges g = 0.73, 95% CI; (0.18, 1.28), p-value = 0.01; N = 8, n = 1,329, I2 = 91.15%). The beneficial effect of exercise on sleep quality outlined in this study highlights the important role exercise has in improving health outcomes for people living with mental illness. Further research is required to determine the efficacy of exercise on sleep in people experiencing a psychiatric illness and to explore the effects of exercise intervention elements such as modality, frequency, intensity and delivery settings.


Subject(s)
Exercise Therapy/statistics & numerical data , Exercise , Mental Disorders/therapy , Sleep Wake Disorders/therapy , Sleep , Humans
11.
Hosp Pediatr ; 2018 Jan 09.
Article in English | MEDLINE | ID: mdl-29317461

ABSTRACT

OBJECTIVES: Collecting social determinants data is challenging. We assigned patients a neighborhood-level social determinant measure, the area of deprivation index (ADI), by using census data. We then assessed the association between neighborhood deprivation and asthma hospitalization outcomes and tested the influence of insurance coverage. METHODS: A retrospective cohort study of children 2 to 17 years old admitted for asthma at 8 hospitals. An administrative database was used to collect patient data, including hospitalization outcomes and neighborhood deprivation status (ADI scores), which were grouped into quintiles (ADI 1, the least deprived neighborhoods; ADI 5, the most deprived neighborhoods). We used multivariable models, adjusting for covariates, to assess the associations and added a neighborhood deprivation status and insurance coverage interaction term. RESULTS: A total of 2270 children (median age 5 years; 40.6% girls) were admitted for asthma. We noted that higher ADI quintiles were associated with greater length of stay, higher cost, and more asthma readmissions (P < .05 for most quintiles). Having public insurance was independently associated with greater length of stay (ß: 1.171; 95% confidence interval [CI]: 1.117-1.228; P < .001), higher cost (ß: 1.147; 95% CI: 1.093-1.203; P < .001), and higher readmission odds (odds ratio: 1.81; 95% CI: 1.46-2.24; P < .001). There was a significant deprivation-insurance effect modification, with public insurance associated with worse outcomes and private insurance with better outcomes across ADI quintiles (P < .05 for most combinations). CONCLUSIONS: Neighborhood-level ADI measure is associated with asthma hospitalization outcomes. However, insurance coverage modifies this relationship and needs to be considered when using the ADI to identify and address health care disparities.

12.
Sci Rep ; 7: 45753, 2017 03 31.
Article in English | MEDLINE | ID: mdl-28362001

ABSTRACT

Unhealthy diets, and ensuing weight gain, predispose individuals to the development of esophageal adenocarcinoma. We examined the effect of chronic high fat diet (HFD) on the esophageal microbiota of Sprague Dawley rats using Illumina MiSeq amplicon sequencing (V4, 515 F/806 R) and on esophageal expression of IL18, PTGS2, PPARA, FFAR3, and CRAT. The relationships among metabolic parameters, esophageal microbiota, and host gene expression were determined. We observed a significant difference between the upper and lower esophageal microbiota in control fed rats, emphasized by enrichment of Lactobacillus species in the lower esophagus. Rats on HFD gained significantly more fat and had reduced insulin sensitivity. Diet type significantly affected the esophageal microbiota, with Clostridium sensu stricto being enriched in both upper and lower segments of HFD fed rats. Of interest, bacterial pathways related to carotenoid biosynthesis were significantly decreased in the lower esophagus of HFD fed rats. We observed strong correlations between metabolic parameters, the esophageal microbial profiles, and host esophageal gene expression. In particular, Fusobacterium, Rothia, and Granulicatella showed consistent correlations across a range of metabolic and gene markers. Our data indicates that unhealthy diets can significantly alter the esophageal microbiota, and enrich for bacterial species previously associated with chronic gastrointestinal diseases.


Subject(s)
Diet, High-Fat , Esophagus/metabolism , Esophagus/microbiology , Gastrointestinal Microbiome , Gene Expression , Animals , Insulin Resistance , Male , Rats, Sprague-Dawley
13.
BMJ Open Qual ; 6(2): e000116, 2017.
Article in English | MEDLINE | ID: mdl-29450284

ABSTRACT

Functional constipation (FC) is a common medical problem in children, with minimal risk of long-term complications. We determined that a large number of children were being admitted to our children's hospital for FC in which there was no neurological or anatomical cause. Our hospital experienced a patient complication in which a patient died after inpatient treatment of FC. Subsequently, we developed a standardised approach to determine when paediatric patients needed hospitalisation for FC, as well as to develop a regimented outpatient therapeutic approach for such children to prevent hospitalisation. Our quality improvement initiative resulted in a large decrease in the number of children with FC admitted into the hospital as well as a decrease in the number of children needing faecal disimpaction in the operating room. Our quality improvement process can be used to decrease hospitalisations, decrease healthcare costs and improve patient care for paediatric FC.

14.
Am J Physiol Endocrinol Metab ; 312(2): E117-E125, 2017 02 01.
Article in English | MEDLINE | ID: mdl-27965204

ABSTRACT

Emerging evidence suggests that paternal obesity plays an important role in offspring health. Our previous work using a rodent model of diet-induced paternal obesity showed that female offspring from high-fat diet (HFD)-fed fathers develop glucose intolerance due to impairment of pancreatic insulin secretion. Here, we focused on the health outcomes of male offspring from HFD-fed fathers. Male Sprague-Dawley rats (3 wk old) were fed control (CD-F0) or HFD (HFD-F0) for 12 wk before mating with control-fed females. Male offspring were fed control diets for up to 8 wk or 6 mo. Although male offspring from HFD-F0 did not develop any obvious glucose metabolism defects in this study, surprisingly, a growth deficit phenotype was observed from birth to 6 mo of age. Male offspring from HFD-F0 had reduced birth weight compared with CD-F0, followed by reduced postweaning growth from 9 wk of age. This resulted in 10% reduction in body weight at 6 mo with significantly smaller fat pads and skeletal muscles. Reduced circulating levels of growth hormone (GH) and IGF-I were detected at 8 wk and 6 mo, respectively. Expression of adipogenesis markers was decreased in adipose tissue of HFD-F0 offspring at 8 wk and 6 mo, and expression of growth markers was decreased in muscle of HFD-F0 offspring at 8 wk. We propose that the reduced GH secretion at 8 wk of age altered the growth of male offspring from HFD-F0, resulting in smaller animals from 9 wk to 6 mo of age. Furthermore, increased muscle triglyceride content and expression of lipogenic genes were observed in HFD-F0 offspring, potentially increasing their metabolic risk.


Subject(s)
Adiposity , Fathers , Growth and Development , Obesity , Prenatal Exposure Delayed Effects , Animals , Female , Male , Pregnancy , Prenatal Exposure Delayed Effects/metabolism , Prenatal Exposure Delayed Effects/physiopathology , Rats , Rats, Sprague-Dawley
15.
Hosp Pediatr ; 6(12): 707-713, 2016 12.
Article in English | MEDLINE | ID: mdl-27879283

ABSTRACT

OBJECTIVES: Tube feedings are commonly prescribed to infants with swallowing abnormalities detected by videofluoroscopic swallow study (VFSS), but there are no studies demonstrating efficacy of these interventions to reduce risk of acute respiratory illness (ARI). We sought to measure the association between swallowing interventions and future ARI, among VFSS-tested infants. METHODS: Retrospective cohort of all infants (<12 months) tested with VFSS at a children's hospital between January 1, 2010, and January 1, 2012. Hospital ARI encounters (emergency, observation, or inpatient status) in a 22-hospital integrated health care delivery system, between the first VFSS and age 3 years, were measured. VFSS results were grouped by normal, intermediate, and oropharyngeal aspiration (OPA), with OPA further subdivided by silent versus cough and thin versus thick liquid OPA. Cox regression modeled the association between swallowing interventions (thickened or nasal tube feedings) and ARI, accounting for changes in swallowing and interventions over time. RESULTS: 576 infants were tested with a VFSS in their first year of life, receiving a total of 1051 VFSSs in their first 3 years of life. More than 60% of infants received a measured feeding intervention. With the exception of infants with silent OPA who received thickened feedings, neither thickening nor nasal tube feedings, compared with no intervention, were associated with a decreased risk of subsequent ARI. CONCLUSIONS: Swallowing interventions and repeated testing are common among VFSS-tested infants. However, the importance of diagnosing and intervening on VFSS-detected swallowing abnormalities for the majority of tested infants remains unclear.


Subject(s)
Deglutition Disorders , Diagnostic Techniques, Digestive System , Respiratory Aspiration , Respiratory Insufficiency/prevention & control , Deglutition/physiology , Deglutition Disorders/complications , Deglutition Disorders/diagnosis , Deglutition Disorders/physiopathology , Deglutition Disorders/therapy , Enteral Nutrition/methods , Female , Fluoroscopy/methods , Humans , Infant , Male , Outcome and Process Assessment, Health Care , Reproducibility of Results , Respiratory Aspiration/complications , Respiratory Aspiration/diagnosis , Respiratory Aspiration/physiopathology , Respiratory Aspiration/therapy , Respiratory Insufficiency/etiology , Retrospective Studies , Utah , Videotape Recording/methods
16.
Hosp Pediatr ; 6(10): 569-577, 2016 10.
Article in English | MEDLINE | ID: mdl-27655424

ABSTRACT

OBJECTIVES: To delineate the drivers of cost associated with the most-costly inpatients in a tertiary pediatric hospital. METHODS: We identified the 10% most-costly inpatients treated at a large regional children's hospital in 2010. From this group we randomly selected, within representative specialties, 2 groups of 50 inpatients for detailed chart review. By using daily cost data and clinical records, 2 independent reviewers examined the clinical course of each patient to identify events that drove cost beyond that expected for standard of care. By using an iterative process, these events were grouped into themes or "cost drivers." Linear regression was used to measure the association of number of cost drivers and total 2010 inpatient cost. RESULTS: We identified 7 cost drivers: medical complications (49%), futile treatment (6%), failure to identify family care preferences (9%), system errors (65%), preventable admissions (21%), complex family dynamics (11%), and expensive diagnosis with no other cost driver (15%). Cost drivers were associated with increased total costs. CONCLUSIONS: We developed a novel method for understanding high-cost inpatients. This method allowed a more detailed understanding of cost drivers than could be achieved with administrative data alone. Many of these cost drivers were related to problems with communication.


Subject(s)
Diagnosis-Related Groups/economics , Hospital Costs/statistics & numerical data , Hospitals, Pediatric , Medical Errors/economics , Medical Futility , Adolescent , Child , Child, Preschool , Costs and Cost Analysis/methods , Data Collection , Female , Hospitalization/economics , Hospitals, Pediatric/organization & administration , Hospitals, Pediatric/statistics & numerical data , Humans , Infant , Infant, Newborn , Inpatients/statistics & numerical data , Male , Professional-Family Relations , Random Allocation , Tertiary Care Centers/organization & administration , Tertiary Care Centers/statistics & numerical data , Utah
17.
Nutrients ; 8(9)2016 Aug 23.
Article in English | MEDLINE | ID: mdl-27563922

ABSTRACT

Along with diabetes and obesity, chronic kidney disease (CKD) is increasing across the globe. Although some data support an effect of maternal obesity on offspring kidney, the impact of paternal obesity is unknown; thus, we have studied the effect of paternal obesity prior to conception. Male Sprague Dawley rats were fed chow diet or high fat diet (HFD) for 13-14 weeks before mating with chow-fed females. Male offspring were weaned onto chow and killed at 27 weeks for renal gene expression and histology. Fathers on HFD were 30% heavier than Controls at mating. At 27 weeks of age offspring of obese fathers weighed 10% less; kidney triglyceride content was significantly increased (5.35 ± 0.84 vs. 2.99 ± 0.47 µg/mg, p < 0.05, n = 8 litters per group. Histological analysis of the kidney demonstrated signs of tubule damage, with significantly greater loss of brush border, and increased cell sloughing in offspring of obese compared to Control fathers. Acat1, involved in entry of fatty acid for beta-oxidation, was significantly upregulated, possibly to counteract increased triglyceride storage. However other genes involved in lipid metabolism, inflammation and kidney injury showed no changes. Paternal obesity was associated with renal triglyceride accumulation and histological changes in tubules, suggesting a mild renal insult in offspring, who may be at risk of developing CKD.


Subject(s)
Dietary Fats/administration & dosage , Kidney Tubules/drug effects , Lipid Metabolism , Paternal Inheritance/genetics , Renal Insufficiency, Chronic/genetics , Animals , Creatinine/blood , Electrolytes/blood , Fatty Acids, Nonesterified/blood , Female , Kidney Tubules/pathology , Lipid Metabolism/genetics , Lipids/administration & dosage , Lipids/blood , Male , Obesity/genetics , Rats , Rats, Sprague-Dawley , Serum Albumin
18.
Asian J Androl ; 18(6): 930-936, 2016.
Article in English | MEDLINE | ID: mdl-26608942

ABSTRACT

There is now strong evidence that the paternal contribution to offspring phenotype at fertilisation is more than just DNA. However, the identity and mechanisms of this nongenetic inheritance are poorly understood. One of the more important questions in this research area is: do changes in sperm DNA methylation have phenotypic consequences for offspring? We have previously reported that offspring of obese male rats have altered glucose metabolism compared with controls and that this effect was inherited through nongenetic means. Here, we describe investigations into sperm DNA methylation in a new cohort using the same protocol. Male rats on a high-fat diet were 30% heavier than control-fed males at the time of mating (16-19 weeks old, n = 14/14). A small (0.25%) increase in total 5-methyl-2Ͳ-deoxycytidine was detected in obese rat spermatozoa by liquid chromatography tandem mass spectrometry. Examination of the repetitive fraction of the genome with methyl-CpG binding domain protein-enriched genome sequencing (MBD-Seq) and pyrosequencing revealed that retrotransposon DNA methylation states in spermatozoa were not affected by obesity, but methylation at satellite repeats throughout the genome was increased. However, examination of muscle, liver, and spermatozoa from male 27-week-old offspring from obese and control fathers (both groups from n = 8 fathers) revealed that normal DNA methylation levels were restored during offspring development. Furthermore, no changes were found in three genomic imprints in obese rat spermatozoa. Our findings have implications for transgenerational epigenetic reprogramming. They suggest that postfertilization mechanisms exist for normalising some environmentally-induced DNA methylation changes in sperm cells.


Subject(s)
DNA Methylation/genetics , Epigenesis, Genetic , Obesity/genetics , Spermatozoa/metabolism , Animals , Female , Genome , Male , Obesity/metabolism , Rats
19.
Pediatrics ; 136(6): e1602-10, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26527553

ABSTRACT

BACKGROUND AND OBJECTIVES: Gaps exist in inpatient asthma care. Our aims were to assess the impact of an evidence-based care process model (EB-CPM) 5 years after implementation at Primary Children's Hospital (PCH), a tertiary care facility, and after its dissemination to 7 community hospitals. METHODS: Participants included asthmatics 2 to 17 years admitted at 8 hospitals between 2003 and 2013. The EB-CPM was implemented at PCH between January 2008 and March 2009, then disseminated to 7 community hospitals between January and June 2011. We measured compliance using a composite score (CS) for 8 quality measures. Outcomes were compared between preimplementation and postimplementation periods. Confounding was addressed through multivariable regression analyses. RESULTS: At PCH, the CS increased and remained at >90% for 5 years after implementation. We observed sustained reductions in asthma readmissions (P = .026) and length of stay (P < .001), a trend toward reduced costs (P = .094), and no change in hospital resource use, ICU transfers, or deaths. The CS also increased at the 7 community hospitals, reaching 80% to 90% and persisting >2 years after dissemination, with a slight but not significant readmission reduction (P = .119), a significant reduction in length of stay (P < .001) and cost (P = .053), a slight increase in hospital resource use (P = .032), and no change in ICU transfers or deaths. CONCLUSIONS: Our intervention resulted in sustained, long-term improvement in asthma care and outcomes at the tertiary care hospital and successful dissemination to community hospitals.


Subject(s)
Asthma/therapy , Hospitalization/statistics & numerical data , Hospitals, Community/organization & administration , Hospitals, Pediatric/organization & administration , Quality Improvement/organization & administration , Adolescent , Asthma/economics , Child , Child, Preschool , Female , Hospital Costs/statistics & numerical data , Hospitalization/economics , Hospitals, Community/economics , Hospitals, Community/statistics & numerical data , Hospitals, Pediatric/economics , Hospitals, Pediatric/statistics & numerical data , Humans , Male , Outcome and Process Assessment, Health Care , Program Evaluation , Prospective Studies , Quality Improvement/statistics & numerical data , Quality Indicators, Health Care/statistics & numerical data , Utah
20.
BMC Med Inform Decis Mak ; 15: 84, 2015 Oct 14.
Article in English | MEDLINE | ID: mdl-26467091

ABSTRACT

BACKGROUND: Pediatric asthma affects 7.1 million American children incurring an annual total direct healthcare cost around 9.3 billion dollars. Asthma control in children is suboptimal, leading to frequent asthma exacerbations, excess costs, and decreased quality of life. Successful prediction of risk for asthma control deterioration at the individual patient level would enhance self-management and enable early interventions to reduce asthma exacerbations. We developed and tested the first set of models for predicting a child's asthma control deterioration one week prior to occurrence. METHODS: We previously reported validation of the Asthma Symptom Tracker, a weekly asthma self-monitoring tool. Over a period of two years, we used this tool to collect a total of 2912 weekly assessments of asthma control on 210 children. We combined the asthma control data set with patient attributes and environmental variables to develop machine learning models to predict a child's asthma control deterioration one week ahead. RESULTS: Our best model achieved an accuracy of 71.8 %, a sensitivity of 73.8 %, a specificity of 71.4 %, and an area under the receiver operating characteristic curve of 0.757. We also identified potential improvements to our models to stimulate future research on this topic. CONCLUSIONS: Our best model successfully predicted a child's asthma control level one week ahead. With adequate accuracy, the model could be integrated into electronic asthma self-monitoring systems to provide real-time decision support and personalized early warnings of potential asthma control deteriorations.


Subject(s)
Asthma/diagnosis , Models, Statistical , Adolescent , Child , Child, Preschool , Female , Humans , Machine Learning , Male , Prognosis , Sensitivity and Specificity
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