Peak-agnostic high-resolution cis-regulatory circuitry mapping using single cell multiome data.

Single same cell RNAseq/ATACseq multiome data provide unparalleled potential to develop high resolution maps of the cell-type specific transcriptional regulatory circuitry underlying gene expression. We present CREMA, a framework that recovers the full cis-regulatory circuitry by modeling gene expression and chromatin activity in individual cells without peak-calling or cell type labeling constraints. We demonstrate that CREMA overcomes the limitations of existing methods that fail to identify about half of functional regulatory elements which are outside the called chromatin 'peaks'. These circuit sites outside called peaks are shown to be important cell type specific functional regulatory loci, sufficient to distinguish individual cell types. Analysis of mouse pituitary data identifies a Gata2-circuit for the gonadotrope-enriched disease-associated Pcsk1 gene, which is experimentally validated by reduced gonadotrope expression in a gonadotrope conditional Gata2-knockout model. We present a web accessible human immune cell regulatory circuit resource, and provide CREMA as an R package.

Coupling MoSe2 with Non-Stoichiometry Ni0.85 Se in Carbon Hollow Nanoflowers for Efficient Electrocatalytic Synergistic Effect on Li-O2 Batteries.

Li-O2 batteries could deliver ultra-high theoretical energy density compared to current Li-ion batteries counterpart. The slow cathode reaction kinetics in Li-O2 batteries, however, limits their electrocatalytic performance. To this end, MoSe2 and Ni0.85 Se nanoflakes were decorated in carbon hollow nanoflowers, which were served as the cathode catalysts for Li-O2 batteries. The hexagonal Ni0.85 Se and MoSe2 show good structural compatibility with the same space group, resulting in a stable heterogeneous structure. The synergistic interaction of the unsaturated atoms and the built-in electric fields on the heterogeneous structure exposes abundant catalytically active sites, accelerating ion and charge transport and imparting superior electrochemical activity, including high specific capacities and stable cycling performance. More importantly, the lattice distances of the Ni0.85 Se (101) plane and MoSe2 (100) plane at the heterogeneous interfaces are highly matched to that of Li2 O2 (100) plane, facilitating epitaxial growth of Li2 O2 , as well as the formation and decomposition of discharge products during the cycles. This strategy of employing nonstoichiometric compounds to build heterojunctions and improve Li-O2 battery performance is expected to be applied to other energy storage or conversion systems.

Observation of Free-Boundary-Induced Chiral Anomaly Bulk States in Elastic Twisted Kagome Metamaterials.

Chiral anomaly bulk states (CABSs) can be realized by choosing appropriate boundary conditions in a finite-size waveguide composed of two-dimensional Dirac semimetals, which have unidirectional and robust transport similar to that of valley edge states. CABSs use almost all available guiding space, which greatly improves the utilization of metamaterials. Here, free-boundary-induced CABSs in elastic twisted kagome metamaterials with C_{3v} symmetry are experimentally confirmed. The robust valley-locked transport and complete valley state conversion are experimentally observed. Importantly, the sign of the group velocity near the K and K^{'} points can be reversed by suspending masses at the boundary to manipulate the onsite potential. Moreover, CABSs are demonstrated in nanoelectromechanical phononic crystals by constructing an impedance-mismatched hard boundary. These results open new possibilities for designing more compact, space-efficient, and robust elastic wave macro- and microfunctional devices.

Fibrosis, biomarkers and liver biopsy in AAT deficiency and relation to liver Z protein polymer accumulation.

BACKGROUND AND AIMS: The course of adults with ZZ alpha-1-antitrypsin deficiency (AATD) liver disease is unpredictable. The utility of markers, including liver biopsy, is undefined. METHODS: A prospective cohort, including protocol liver biopsies, was enrolled to address these questions. RESULTS: We enrolled 96 homozygous ZZ AATD adults prospectively at three US sites with standardized clinical evaluations, and protocol liver biopsies. Fibrosis was scored using Ishak (stages 0-6). Also, 51% of the 96 subjects had Ishak score >1 fibrosis (49% Ishak 0-1, 36% Ishak 2-3 and 15% ≥4). Elevated aspartate aminotransferase (AST) more than alanine aminotransferase (ALT), high body mass index (BMI), obesity, AST platelet ratio index and elevated serum Z alpha 1 antitrypsin (AAT) polymer levels were associated with increased fibrosis. Steatosis did not correlate to fibrosis. Increased fibrosis was associated with increased mutant Z polymer globular inclusions (p = .002) and increased diffuse cytoplasmic Z polymer on biopsy (p = .0029) in a direct relationship. Increased globule Z polymer was associated with increased serum AST (p = .007) and increased periportal inflammation on histopathology (p = .004), but there was no relationship of Z polymer hepatocellular accumulation with ALT, gamma glutamine transferase, inflammation in other parts of the lobule, necrosis or steatosis. Serum Z polymer levels were directly correlated to hepatic Z protein polymer content. Lung function, smoking and alcohol consumption patterns were not associated with fibrosis. CONCLUSION: In AATD high BMI, obesity and elevated AST are associated with increased fibrosis. Liver biopsy features are correlated to some serum tests. Serum Z AAT polymer levels could be a future biomarker to detect fibrosis early and is directly correlated to liver Z content.

Emergency department visits in Parkinson's disease: The impact of comorbid conditions.

INTRODUCTION: Older adults have complex, often overlapping, medical conditions requiring careful management that may lead to increased emergency department usage compared to younger adults. Parkinson's disease (PD), a progressive neurodegenerative disorder characterized by distinct motor and nonmotor features, frequently occurs with additional comorbid disease. Classifying comorbid conditions into clinical subgroups allows for further understanding of the heterogeneity in outcomes in patients with PD. The current study examines the reasons for emergency department (ED) visits in a cohort of patients with PD and identifies comorbidities that are potential risk factors for specific ED presenting conditions. METHODS: Using data from Optum's de-identified Integrated Claims-Clinical dataset years 2010-2018, patients with PD were identified based on ICD-9/10 diagnosis codes. We identified all ED visits occurring after the first observed diagnosis code for PD. Comorbid conditions were classified using the AHRQ Clinical Classification Software (CCS). We classified patients using Latent Class Analysis (LCA) and conducted multiple logistic regression models with the outcome of reason-for-visit to examine the associations with comorbidity-profile class, patient demographics, and socio-economic characteristics. RESULTS: The most common reasons for ED admission were injuries such as fractures and contusions, diseases of the circulatory system, and general signs and symptoms, including abdominal pain, malaise, and fatigue. Comorbid medical conditions often observed in this patient population include depression, diabetes mellitus, and chronic pulmonary disease. Patients in the "Poorest Health" classification of the LCA had greater odds for ED admission for diseases related to the gastrointestinal system, musculoskeletal system, and injury/poisoning categories and reduced odds for admission for diseases of the circulatory system. DISCUSSION: Patients with PD who present to the emergency department with injuries are more likely to be in poor health overall with a high comorbidity burden. Clarifying the complex medical needs of patients with PD is the first step to further individualize care, which may reduce ED visits in this population, improve quality of life, and lessen the footprint on the healthcare system.

Anxiety in Parkinson's Patients: What's Timing Got to Do with It?

Background: Parkinson's Disease (PD) affects over 10 million people worldwide. Many PD patients experience comorbid anxiety disorders, which have been correlated with reduced quality of life and can manifest at any time during the course of PD, including prior to motor symptom onset. Purpose: Prior work has demonstrated that patients diagnosed with depression following a PD diagnosis are less likely to receive depression treatment, but no such study has been conducted for anxiety. Research Design: A cross-sectional analysis of secondary electronhic health record data was conducted. Study Sample: Data was obtained through Optum® de-identified Electronic Health Record dataset, using ICD-9 and ICD-10 diagnosis codes to determine PD status and comparing index date of anxiety and PD diagnoses to classify patients by relative time of diagnosis. Data Analysis: Multivariate logistic regression was performed to assess factors associated with receipt of mental health treatment. Results: Of PD patients with anxiety, 52% documented a diagnosis of anxiety prior to PD. Overall, 69% documented some treatment, with 79% of those diagnosed with anxiety prior to PD receiving some treatment compared to 59% of those diagnosed with anxiety on or after PD (P < 0.001). Conclusion: Patients with PD and subsequent anxiety diagnoses are less likely to receive treatment. Further study could explore reasons for variations in mental health care within the context of an existing PD diagnosis.

Depression After Parkinson's Disease: Treated Differently or Not At All?

Depression is a common, potentially debilitating non-motor symptom of Parkinson's disease which may manifest at any time and can respond to treatment. Although depression is a known primary mediator of health-related quality of life, it is currently unknown whether the timing of depression diagnosis relative to PD diagnosis affects receipt of depression treatment. Electronic health record data were examined to explore differences in depression treatment among patients diagnosed with depression before or after PD diagnosis. Compared to PD patients diagnosed with depression prior to PD, those diagnosed with depression following PD are less likely to receive any treatment, either pharmacologic or non-pharmacologic, indicating a temporal association between the time of PD diagnosis and receipt of depression treatment. This highlights a potentially substantial treatment gap, despite the existence of efficacious treatment. Diagnosis with PD appears to alter depression treatment and further research is warranted to determine potential causes and effective interventions.

Single-cell analysis of progenitor cell dynamics and lineage specification in the human fetal kidney.

The mammalian kidney develops through reciprocal interactions between the ureteric bud and the metanephric mesenchyme to give rise to the entire collecting system and the nephrons. Most of our knowledge of the developmental regulators driving this process arises from the study of gene expression and functional genetics in mice and other animal models. In order to shed light on human kidney development, we have used single-cell transcriptomics to characterize gene expression in different cell populations, and to study individual cell dynamics and lineage trajectories during development. Single-cell transcriptome analyses of 6414 cells from five individual specimens identified 11 initial clusters of specific renal cell types as defined by their gene expression profile. Further subclustering identifies progenitors, and mature and intermediate stages of differentiation for several renal lineages. Other lineages identified include mesangium, stroma, endothelial and immune cells. Novel markers for these cell types were revealed in the analysis, as were components of key signaling pathways driving renal development in animal models. Altogether, we provide a comprehensive and dynamic gene expression profile of the developing human kidney at the single-cell level.

Provider specialty and odds of a new codeine, hydrocodone, oxycodone and tramadol prescription before and after the CDC opioid prescribing guideline publication.

The CDC Guideline for Prescribing Opioids for Chronic Pain cautioned against high dose prescribing but did not provide guidance on type of opioid for new pain episodes. We determined if new prescriptions for Schedule II opioids vs. tramadol decreased in the 18 months after vs. before the CDC guideline and if this decrease was associated with physician specialty. New opioid prescriptions, provider type and covariates were measured using a nationally distributed, Optum® de-identified Electronic Health Record (EHR) data base. Eligible patients were free of cancer and HIV and started a new prescription for Schedule II opioids (i.e. codeine, hydrocodone, oxycodone) or Schedule IV (tramadol) in the 18 months before (n = 141,219) or 18 months after (n = 138,216) guideline publication. Fully adjusted multilevel multinomial models estimated the association between provider type (anesthesiology/pain medicine, surgical specialty, emergency, hospital, primary care, other specialty and unknown) before and after adjusting for covariates. New oxycodone prescriptions were most common among surgical and anesthesia/pain management, and new tramadol prescriptions were most common in primary care. The greatest decreases in odds of a Schedule II opioid vs. tramadol were observed in emergency care (oxycodone vs. tramadol OR = 0.82; 95%CI:0.76-0.88) and primary care (hydrocodone vs. tramadol OR = 0.85; 95%CI:0.81-0.89). Surgical specialists were least likely to start opioid therapy with tramadol. In the 18 months after vs. before the CDC guideline, emergency care and primary care providers increased tramadol prescribing. Guidelines tailored to specialists that frequently begin opioid therapy with oxycodone may enhance safe opioid prescribing.

[Optimization of polysaccharide extraction from Hippocampus by deep neural network and Box-Behnken design-response surface methodology].

In this paper, the extraction rate of crude polysaccharides and the yield of polysaccharides from Hippocampus served as test indicators. The comprehensive evaluation indicators were assigned by the R language combined with the entropy weight method. The Box-Behnken design-response surface methodology(BBD-RSM) and the deep neural network(DNN) were employed to screen the optimal parameters for the polysaccharide extraction from Hippocampus. These two modeling methods were compared and verified experimentally for the process optimization. This study provides a reference for the industrialization of effective component extraction from Chinese medicinals and achieves the effective combination of modern technology and traditional Chinese medicine.

Preparation and Application of CO2-Triggered Switchable Solvents in Separation of Toluene/n-Heptane.

Extraction is a common approach to separating aromatics and alkanes, but solvent recovery remains an issue. The polarity, hydrophobic/hydrophilic balance, and other properties of switchable solvents can be reversibly changed in the presence of various triggers, and taking advantage of this property can greatly simplify the process of solvent recovery. In this work, quaternation and anion exchange were used to prepare several switchable solvents by introducing OH- ions to derivatives of the amidine compound 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The resulting compounds exhibited reversible switching in response to exposure to CO2. Using toluene/n-heptane as a model hydrocarbon mixture, a reversible phase change extraction process was established. Among the four switchable solvents prepared, [C2DBU]OH showed the highest selectivity value and so was used to investigate the effect of various parameters on hydrocarbon separation. The extraction process was found to rapidly reach equilibrium when a two-phase system was generated by bubbling CO2 through the extraction mixture. Increasing the proportion of the solvent increased the selectivity for toluene, while a 1:1 ratio between the solvent and the toluene/n-heptane mixture enhanced the extraction. Increasing the initial toluene concentration reduced the selectivity for toluene, with a value of 5.97 at a toluene concentration of 20%. The switchable solvent recovered its initial state when heated at 60 °C for 1 h. Upon being reused after removal of CO2, the solvent exhibited poor separation characteristics, although the selectivity coefficient remained constant at approximately 3.1 during 10 regenerations. Finally, the mechanism of the switchable solvent effect and modeling of experimental data were investigated.

Impacts of center and clinical factors in antihypertensive medication use after kidney transplantation.

Hypertension guidelines recommend calcium channel blockers (CCBs), thiazide diuretics, and angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) as first-line agents to treat hypertension. Hypertension is common among kidney transplant (KTx) recipients, but data are limited regarding patterns of antihypertensive medication (AHM) use in this population. We examined a novel database that links national registry data for adult KTx recipients (age > 18 years) with AHM fill records from a pharmaceutical claims warehouse (2007-2016) to describe use and correlates of AHM use during months 7-12 post-transplant. For patients filling AHMs, individual agents used included: dihydropyridine (DHP) CCBs, 55.6%; beta-blockers (BBs), 52.8%; diuretics, 30.0%; ACEi/ARBs, 21.1%; non-DHP CCBs, 3.0%; and others, 20.1%. Both BB and ACEi/ARB use were significantly lower in the time period following the 2014 Eighth Joint National Committee (JNC-8) guidelines (2014-2016), compared with an earlier period (2007-2013). The median odds ratios generated from case-factor adjusted models supported variation in use of ACEi/ARBs (1.51) and BBs (1.55) across transplant centers. Contrary to hypertension guidelines for the general population, KTx recipients are prescribed relatively more BBs and fewer ACEi/ARBs. The clinical impact of this AHM prescribing pattern warrants further study.

Variation in use of procurement biopsies and its implications for discard of deceased donor kidneys recovered for transplantation.

The use of procurement biopsies in deceased donor kidney acceptance is controversial. We analyzed Scientific Registry of Transplant Recipients data (n = 59 328 allografts, 2014-2018) to describe biopsy practices across US organ procurement organizations (OPOs) and examine relationships with discards, using hierarchical modeling to account for OPO and donor factors. Median odds ratios (MORs) provide the median of the odds that allografts with identical reported traits would be biopsied or discarded from 2 randomly drawn OPOs. Biopsies were obtained for 52.7% of kidneys. Biopsy use rose in a graded manner with kidney donor profile index (KDPI). Biopsy rates differed significantly among OPOs (22.8% to 77.5%), even after adjustment for KDPI and other donor factors. Discard rates also varied from 6.6% to 32.1% across OPOs. After adjustment for donor factors and OPO, biopsy was associated with more than 3 times the likelihood of discard (adjusted odds ratio [95%LCL aOR95%UCL ], 3.29 3.513.76 ). This association was most pronounced for low-risk (KDPI <20) kidneys (aOR, 5.45 6.477.69 ), with minimal impact at KDPI >85 (aOR, 0.88 1.151.51 ). Adjusted MORs for kidney discard and biopsy were greatest for low-risk kidneys. Reducing the rate of unnecessary biopsy and improving the accuracy of histologic assessments in higher KDPI organs may help reduce graft discard rates.

Prescription opioid use before and after heart transplant: Associations with posttransplant outcomes.

Impacts of the prescription opioid epidemic have not yet been examined in the context of heart transplantation. We examined a novel database in which national U.S. transplant registry records were linked to a large pharmaceutical claims warehouse (2007-2016) to characterize prescription opioid use before and after heart transplant, and associations (adjusted hazard ratio, 95%LCL aHR95%UCL ) with death and graft loss. Among 13 958 eligible patients, 40% filled opioids in the year before transplant. Use was more common among recipients who were female, white, or unemployed, or who underwent transplant in more recent years. Of those with the highest level of pretransplant opioid use, 71% continued opioid use posttransplant. Pretransplant use had graded associations with 1-year posttransplant outcomes; compared with no use, the highest-level use (>1000 mg morphine equivalents) predicted 33% increased risk of death (aHR 1.10 1.331.61 ) in the year after transplant. Risk relationships with opioid use in the first year posttransplant were stronger, with highest level use predicting 70% higher mortality (aHR 1.46 1.701.98 ) over the subsequent 4 years (from >1 to 5 years posttransplant). While associations may, in part, reflect underlying conditions or behaviors, opioid use history is relevant in assessing and providing care to transplant candidates and recipients.

Associations of obesity with antidiabetic medication use after living kidney donation: An analysis of linked national registry and pharmacy fill records.

We examined a novel linkage of national US donor registry data with records from a pharmacy claims warehouse (2007-2016) to examine associations (adjusted hazard ratio, LCL aHRUCL ) of post-donation fills of antidiabetic medications (ADM, insulin or non-insulin agents) with body mass index (BMI) at donation and other demographic and clinical factors. In 28 515 living kidney donors (LKDs), incidence of ADM use at 9 years rose in a graded manner with higher baseline BMI: underweight, 0.9%; normal weight, 2.1%; overweight, 3.5%; obese, 8.5%. Obesity was associated with higher risk of ADM use compared with normal BMI (aHR, 3.36 4.596.27 ). Metformin was the most commonly used ADM and was filled more often by obese than by normal weight donors (9-year incidence, 6.87% vs 1.85%, aHR, 3.55 5.007.04 ). Insulin use was uncommon and did not differ significantly by BMI. Among a subgroup with BMI data at the 1-year post-donation anniversary (n = 19 528), compared with stable BMI, BMI increase >0.5 kg/m2 by year 1 was associated with increased risk of subsequent ADM use (aHR, 1.03 1.482.14, P = .04). While this study did not assess the impact of donation on the development of obesity, these data support that among LKD, obesity is a strong correlate of ADM use.

Transplant recipients are vulnerable to coverage denial under Medicare Part D.

Transplant immunosuppressants are often used off-label because of insufficient randomized prospective trial data to achieve organ-specific US Food and Drug Administration (FDA) approval. Transplant recipients who rely on Medicare Part D for immunosuppressant drug coverage are vulnerable to coverage denial for off-label prescriptions, unless use is supported by Centers for Medicare & Medicaid Services (CMS)-approved compendia. An integrated dataset including national transplant registry data and 3 years of dispensed pharmacy records was used to identify the prevalence of immunosuppression use that is both off-label and not supported by CMS-approved compendia. Numbers of potentially vulnerable transplant recipients were identified. Off-label and off-compendia immunosuppression regimens are frequently prescribed (3-year mean: lung 66.5%, intestine 34.2%, pancreas 33.4%, heart 21.8%, liver 16.5%, kidney 0%). The annual retail cost of these at-risk medications exceeds $30 million. This population-based study of transplant immunosuppressants vulnerable to claim denials under Medicare Part D coverage demonstrates a substantial gap between clinical practice, current FDA approval processes, and policy mandates for pharmaceutical coverage. This coverage barrier reduces access to life-saving medications for patients without alternative resources and may increase the risk of graft loss and death from medication nonadherence.

Center practice drives variation in choice of US kidney transplant induction therapy: a retrospective analysis of contemporary practice.

To assess factors that influence the choice of induction regimen in contemporary kidney transplantation, we examined center-identified, national transplant registry data for 166 776 US recipients (2005-2014). Bilevel hierarchical models were constructed, wherein use of each regimen was compared pairwise with use of interleukin-2 receptor blocking antibodies (IL2rAb). Overall, 82% of patients received induction, including thymoglobulin (TMG, 46%), IL2rAb (22%), alemtuzumab (ALEM, 13%), and other agents (1%). However, proportions of patients receiving induction varied widely across centers (0-100%). Recipients of living donor transplants and self-pay patients were less likely to receive induction treatment. Clinical factors associated with use of TMG or ALEM (vs. IL2rAb) included age, black race, sensitization, retransplant status, nonstandard deceased donor, and delayed graft function. However, these characteristics explained only 10-33% of observed variation. Based on intraclass correlation analysis, "center effect" explained most of the variation in TMG (58%), ALEM (66%), other (51%), and no induction (58%) use. Median odds ratios generated from case-factor adjusted models (7.66-11.19) also supported large differences in the likelihood of induction choices between centers. The wide variation in induction therapy choice across US transplant centers is not dominantly explained by differences in patient or donor characteristics; rather, it reflects center choice and practice.

Antidepressant medication use before and after kidney transplant: implications for outcomes - a retrospective study.

We examined a novel database wherein national US transplant registry identifiers were linked to records from a large pharmaceutical claims warehouse (2008-2015) to characterize antidepressant use before and after kidney transplantation, and associations [adjusted hazard ratio (aHR) 95% CI] with death and graft failure. Among 72 054 recipients, 12.6% filled antidepressant medications in the year before transplant, and use was more common among women and patients who were white, unemployed, and had limited functional status. Pre-transplant antidepressant use was associated with 39% higher 1-year mortality (aHR 1.39, 95% CI 1.18-1.64) and 15% higher all-cause graft loss risk (aHR 1.15, 95% CI 1.02-1.30). More than 50% of patients who filled antidepressants pre-transplant continued fill post-transplant. Antidepressant use in the first year after transplant was associated with twofold higher risk of death (aHR 1.94, 95% CI 1.60-2.35), 38% higher risk of death-censored graft failure, and 61% higher risk of all-cause graft failure in the subsequent year. Pre-listing antidepressant use was also associated with increased mortality, but transplantation conferred a survival benefit regardless of prelisting antidepressant use status. While associations may in part reflect underlying behaviors or comorbidities, kidney transplant candidates and recipients treated with antidepressant medications should be monitored and supported to reduce the risk of adverse outcomes.

The cost of a pediatric neurocritical care program for traumatic brain injury: a retrospective cohort study.

BACKGROUND: Inpatient care for children with severe traumatic brain injury (sTBI) is expensive, with inpatient charges averaging over $70,000 per case (Hospital Inpatient, Children Only, National Statistics. Diagnoses- clinical classification software (CCS) principal diagnosis category 85 coma, stupor, and brain damage, and 233 intracranial injury. Diagnoses by Aggregate charges [ https://hcupnet.ahrq.gov/#setup ]). This ranks sTBI in the top quartile of pediatric conditions with the greatest inpatient costs (Hospital Inpatient, Children Only, National Statistics. Diagnoses- clinical classification software (CCS) principal diagnosis category 85 coma, stupor, and brain damage, and 233 intracranial injury. Diagnoses by Aggregate charges [ https://hcupnet.ahrq.gov/#setup ]). The Brain Trauma Foundation developed sTBI intensive care guidelines in 2003, with revisions in 2012 (Kochanek, Carney, et. al. PCCM 3:S1-S2, 2012). These guidelines have been widely disseminated, and are associated with improved health outcomes (Pineda, Leonard. et. al. LN 12:45-52, 2013), yet research on the cost of associated hospital care is limited. The objective of this study was to assess the costs of providing hospital care to sTBI patients through a guideline-based Pediatric Neurocritical Care Program (PNCP) implemented at St. Louis Children's Hospital, a pediatric academic medical center in the Midwest United States. METHODS: This is a retrospective cohort study. We used multi-level regression to estimate pre-/post-implementation effects of the PNCP program on inflation adjusted total cost of in-hospital sTBI care. The study population included 58 pediatric patient discharges in the pre-PNCP implementation group (July 15, 1999 - September 17, 2005), and 59 post-implementation patient discharges (September 18, 2005 - January 15, 2012). RESULTS: Implementation of the PNCP was associated with a non-significant difference in the cost of care between the pre- and post-implementation periods (eß = 1.028, p = 0.687). CONCLUSIONS: Implementation of the PNCP to support delivery of guideline-based care for children with sTBI did not change the total per-patient cost of in-hospital care. A key strength of this study was its use of hospital cost data rather than charges. Future research should consider the longitudinal post-hospitalization costs of this approach to sTBI care.

[Correlation of reproductive hormone levels and seminal plasma oxidative stress with semen quality in obese males].

OBJECTIVE: To investigate the correlation of the levels of reproductive hormones and oxidative stress in the seminal plasma with semen parameters in obese males. METHODS: Based on the body mass index (BMI), we divided 138 infertile men into three groups: normal (BMI <24 kg/m2, n = 48), overweight (24 kg/m2≤BMI<28 kg/m2, n = 47), and obesity (BMI ≥28 kg/m2, n = 43). We determined the concentrations of follicle-stimulating hormone (FSH), luteotropic hormone (LH), prolactin (PRL), testosterone (T) and estradiol (E2) in the serum by electrochemiluminescence and measured the levels of superoxide dismutase (SOD), glutathione-S-transferases (GSTs), reactive oxygen species (ROS) and malondialdehyde (MDA) in the seminal plasma by ELISA, compared the above indexes among the three groups, and analyzed their correlation with the semen volume, sperm concentration, total sperm count, and percentage of progressively motile sperm (PMS). RESULTS: The semen volume was significantly lower in the obesity than in the normal group (ï¼»2.63 ± 0.74ï¼½ vs ï¼»3.37 ± 1.00ï¼½ ml, P < 0.05), and so was the percentage of PMS in the overweight and even lower in the obesity than in the normal group (ï¼»47.91 ± 12.89ï¼½ and ï¼»41.27 ± 15.77ï¼½ vs ï¼»54.04 ± 13.29ï¼½%, P < 0.05). Compared with the normal group, both the overweight and obesity groups showed markedly decreased levels of serum T (ï¼»4.83 ± 1.42ï¼½ vs ï¼»3.71 ± 1.22ï¼½ and ï¼»3.49 ± 1.12ï¼½ ng/ml, P<0.05), T/LH ratio (1.53 ± 0.57 vs 1.19 ± 0.54 and 0.97 ± 0.51, P<0.05), SOD (ï¼»112.05 ± 10.54ï¼½ vs ï¼»105.85 ± 6.93ï¼½ and ï¼»99.33 ± 8.39ï¼½ U/ml, P<0.05), and GSTs (ï¼»31.75±6.03ï¼½ vs ï¼»29.54±5.78ï¼½ and ï¼»29.02±4.52ï¼½ U/L, P<0.05), but remarkably increased seminal plasma ROS (ï¼»549.93±82.41ï¼½ vs ï¼»620.61±96.13ï¼½ and ï¼»701.47±110.60ï¼½ IU/ml, P<0.05) and MDA (ï¼»7.46 ± 2.13ï¼½ vs ï¼»8.72 ± 1.89ï¼½ and ï¼»10.47 ± 2.10ï¼½ nmol/L, P<0.05). BMI was correlated positively with ROS and MDA, but negatively with the semen volume, PMS, T, T/LH, SOD and GSTs (P<0.05); LH negatively with sperm concentration, total sperm count and GSTs (P<0.05); PRL negatively GSTs (P<0.05); E2 positively with SOD (P<0.05); T positively with SOD (P<0.05) but negatively with MDA (P<0.05); T/LH positively with PMS and SOD (P<0.05) but negatively with ROS and MDA (P<0.05); SOD positively with semen volume, PMS and GSTs (P<0.05) but negatively with ROS and MDA (P<0.05); GSTs negatively with sperm concentration; total sperm count and MDA (P<0.05); ROS positively with MDA (P<0.01) but negatively with PMS (P<0.05); and MDA negatively with semen volume (P<0.05). Multivariate logistic regression analysis showed that the independent factors influencing the semen volume were BMI and GSTs, those influencing the total sperm count were BMI and T, and those influencing PMS were BMI and MDA. CONCLUSIONS: Increased BMI induces changes in the levels of male reproductive hormones and seminal plasma oxidative stress and affects semen quality, which may be associated with male infertility.