Relative effect of urinary calcium and oxalate on saturation of calcium oxalate Rapid Communication

Relative effect of urinary calcium and oxalate on saturation of calcium oxalate.BackgroundThe study compared the effect of urinary calcium with that of oxalate on urinary saturation [relative saturation ratio (RSR)] of calcium oxalate.MethodsA retrospective data analysis was conducted on urinary stone risk analysis from 667 patients with predominantly calcium oxalate stones. Urinary RSR of calcium oxalate was individually calculated using Equil 2. A “theoretical” curve of the relationship between urinary RSR of calcium oxalate and concentration of calcium or oxalate was obtained at two stability constants for calcium oxalate complex, while varying calcium or oxalate and using group mean values for urinary constituents.ResultsAt the stability constant of 7.07 × 103, the increase in RSR of calcium oxalate was less marked with calcium than with oxalate. However, at the stability constant of 2.746 × 103 from the Equil 2 that is considered the “gold standard,” calcium and oxalate were equally effective in increasing RSR of calcium oxalate. The above theoretical curves (relating RSR with calcium or oxalate) were closely approximated by the actual curves constructed with data from individual urine samples. Urinary saturation of calcium oxalate was equally dependent on urinary concentrations of calcium and oxalate (r = 0.75 unadjusted and 0.57 adjusted for variables, and P < 0.0001 for calcium; r = 0.73 unadjusted and 0.60 adjusted, P <0.0001 for oxalate).ConclusionAmong calcium oxalate stone-formers, urinary calcium is equally effective as urinary oxalate in increasing RSR of calcium oxalate

Weaning of Moderately Preterm Infants from the Incubator to the Crib: A Randomized Clinical Trial

OBJECTIVE: To assess whether length of hospital stay is decreased among moderately preterm infants weaned from incubator to crib at a lower vs higher weight. STUDY DESIGN: This trial was conducted in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants with gestational ages 29-33 weeks, birthweight <1600 g, and in an incubator were randomly assigned to a weaning weight of 1600 or 1800 g. Within 60 to 100 g of weaning weight, the incubator temperature was decreased by 1.0°C to 1.5°C every 24 hours until 28.0°C. The infants were weaned to the crib following stable temperature at 36.5°C to 37.4°C for 8 to 12 hours. Clothing and bedcoverings were standardized. The primary outcome was length of hospital stay from birth to discharge; secondary outcomes included length of stay and growth velocity from weaning to discharge. Adverse events were monitored. RESULTS: Of 1565 infants screened, 885 were eligible, and 366 enrolled-187 to the 1600-g and 179 to the 1800-g group. Maternal and neonatal characteristics did not differ among weight groups. Length of hospital stay was a median of 43 days in the lower and 41 days in the higher weight group (P = .12). Growth velocity from completion of weaning to discharge was higher in the lower weight group, 13.7 g/kg/day vs 12.8 g/kg/day (P = .005). Groups did not differ in adverse events. CONCLUSIONS: Among moderately preterm neonates, weaning from incubator to crib at a lower weight did not decrease length of stay, but was safe and was accompanied by higher weight gain after weaning

Effect of Depth and Duration of Cooling on Death or Disability at Age 18 Months Among Neonates With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial

Importance Hypothermia for 72 hours at 33.5°C for neonatal hypoxic-ischemic encephalopathy reduces death or disability, but rates continue to be high. Objective To determine if cooling for 120 hours or to a temperature of 32.0°C reduces death or disability at age 18 months in infants with hypoxic-ischemic encephalopathy. Design, Setting, and Participants Randomized 2 × 2 factorial clinical trial in neonates (≥36 weeks’ gestation) with hypoxic-ischemic encephalopathy at 18 US centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network between October 2010 and January 2016. Interventions A total of 364 neonates were randomly assigned to 4 hypothermia groups: 33.5°C for 72 hours (n = 95), 32.0°C for 72 hours (n = 90), 33.5°C for 120 hours (n = 96), or 32.0°C for 120 hours (n = 83). Main Outcomes and Measures The primary outcome was death or moderate or severe disability at 18 to 22 months of age adjusted for center and level of encephalopathy. Severe disability included any of Bayley Scales of Infant Development III cognitive score less than 70, Gross Motor Function Classification System (GMFCS) level of 3 to 5, or blindness or hearing loss despite amplification. Moderate disability was defined as a cognitive score of 70 to 84 and either GMFCS level 2, active seizures, or hearing with amplification. Results The trial was stopped for safety and futility in November 2013 after 364 of the planned 726 infants were enrolled. Among 347 infants (95%) with primary outcome data (mean age at follow-up, 20.7 [SD, 3.5] months; 42% female), death or disability occurred in 56 of 176 (31.8%) cooled for 72 hours and 54 of 171 (31.6%) cooled for 120 hours (adjusted risk ratio, 0.92 [95% CI, 0.68-1.25]; adjusted absolute risk difference, −1.0% [95% CI, −10.2% to 8.1%]) and in 59 of 185 (31.9%) cooled to 33.5°C and 51 of 162 (31.5%) cooled to 32.0°C (adjusted risk ratio, 0.92 [95% CI, 0.68-1.26]; adjusted absolute risk difference, −3.1% [95% CI, −12.3% to 6.1%]). A significant interaction between longer and deeper cooling was observed (P = .048), with primary outcome rates of 29.3% at 33.5°C for 72 hours, 34.5% at 32.0°C for 72 hours, 34.4% at 33.5°C for 120 hours, and 28.2% at 32.0°C for 120 hours. Conclusions and Relevance Among term neonates with moderate or severe hypoxic-ischemic encephalopathy, cooling for longer than 72 hours, cooling to lower than 33.5°C, or both did not reduce death or moderate or severe disability at 18 months of age. However, the trial may be underpowered, and an interaction was found between longer and deeper cooling. These results support the current regimen of cooling for 72 hours at 33.5°C

Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants

Background: Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia. Methods: We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity. Results: A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively. Conclusions: In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity

The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data

The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs

sci_corr3

Organic iodides have been shown to induce thyroid hypertrophy and increase alterations in colloid in rats, although the mechanism involved in this toxicity is unclear. To evaluate the effect that free iodide has on thyroid toxicity, we exposed rats for 2 weeks by daily gavage to sodium iodide (NaI). To compare the effects of compounds with alternative mechanisms (increased thyroid hormone metabolism and decreased thyroid hormone synthesis, respectively), we also examined phenobarbital (PB) and propylthiouracil (PTU) as model thyroid toxicants. Follicular cell hypertrophy and pale-staining colloid were present in thyroid glands from PB-treated rats, and more severe hypertrophy/colloid changes along with diffuse hyperplasia were present in thyroid glands from PTU-treated rats. In PBand PTU-treated rats, thyroid-stimulating hormone (TSH) levels were significantly elevated, and both thyroxine and triiodothyronine hormone levels were significantly decreased. PB induced hepatic uridine diphosphate-glucuronyltransferase (UDPGT) activity almost 2-fold, whereas PTU reduced hepatic 5´-deiodinase I (5´-DI) activity to &lt; 10% of control in support of previous reports regarding the mechanism of action of each chemical. NaI also significantly altered liver weights and UDPGT activity but did not affect thyroid hormone levels or thyroid pathology. Thyroid gene expression analyses using Affymetrix U34A GeneChips, a regularized t-test, and Gene Map Annotator and Pathway Profiler demonstrated significant changes in rhodopsin-like G-protein-coupled receptor transcripts from all chemicals tested. NaI demonstrated dose-dependent changes in multiple oxidative stress-related genes, as also determined by principal component and linear regression analyses. Differential transcript profiles, possibly relevant to rodent follicular cell tumor outcomes, were observed in rats exposed to PB and PTU, including genes involved in Wnt signaling and ribosomal protein expression. could be obtained that correlate with clinical and pathological end points in rats, and determine whether profiles are predictive of the carcinogenic potential of each chemical in rats. Materials and Methods In Vivo Studies Adult male Crl:CD (SD)IGS BR rats, approximately 8 weeks of age, were treated with NaI, PB, and PTU for 14 consecutive days. NaI, PB, and PTU were purchased from Sigma Chemical Company (St. Louis, MO). Rats (n = 20/group) were dosed by oral gavage with vehicle (water or 0.25% methylcellulose), NaI (0.1, 1, 10, or 100 mg/kg/day), PB (100 mg/kg/day), or PTU (10 mg/kg/day) at a dose volume of 5 mL/kg. NaI was dissolved in water, whereas PB and PTU were dissolved in methylcellulose. On day 15, all rats were euthanized by carbon dioxide anesthesia and exsanguination. Blood samples were collected from the inferior vena cava of each animal at necropsy to measure serum levels of TSH, T 4 , T 3 , and reverse T 3 (rT 3 ). Terminal body, thyroid gland, and liver weights were recorded for the first 10 animals of each dose group. The thyroid gland and surrounding tissue from the first 10 animals of each dose group were processed for histopathological evaluation. A liver sample from the first five animals of each dose group was processed to measure 5´-deiodinase I (5´-DI) and uridine diphosphateglucuronyltransferase (UDPGT) activity. Thyroid glands from the last 10 animals (five from methylcellulose group) from each dose group were removed and placed in RNALater (Ambion, Austin, TX) overnight at 4°C. The next day, thyroids were removed from the RNALater and stored at -80°C until processed for total RNA. The research described in this publication was conducted in a laboratory accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care International, and the investigators complied with the regulations and standards of the Animal Welfare Act and adhered to the principles of the Guide for the Care and Use of Laboratory Animals (National Research Council 1996). Pathological Evaluations After euthanization the thyroid glands and surrounding tissue from the first 10 animals from each group were removed and placed into formalin fixative for at least 48 hr before trimming and weighing. After fixation, one individual performed a final dissection under a dissecting microscope. This was done in order to reduce the variability of the dissection procedure, thereby reducing the variability of the thyroid gland weights. Organ weights were calculated relative to body weight. The formalin-fixed thyroid glands were examined microscopically. Hormonal Measurements Blood was collected at the time of euthanization from all animals. Serum was prepared and stored between -65°C and -85°C until analyzed for serum hormone concentrations. Serum TSH (Amersham Biosciences Corp., Piscataway, NJ), T 3 and T 4 (Diagnostic Products Corp., Los Angeles, CA), and rT 3 (Polymedco Corp., Cortlandt Manor, NY) concentrations were measured using commercially available RIA kits. Microsomal Preparations At necropsy, a section of the liver from the first five animals from each group was removed, and hepatic microsomes were prepared for biochemical evaluation. A portion of the liver was homogenized (1 g tissue/8 mL buffer) in buffer containing 50 mM Tris-HCl, 0.25 M sucrose, and 5.4 mM EDTA, pH 7.4. The homogenates were centrifuged at 15,000 × g for 15 min at 4°C. The resulting supernatants were removed and centrifuged at 100,000 × g for 70 min at 4°C; these pellets contained the microsomal fractions. The microsomal pellets were resuspended in the homogenization buffer at a protein concentration of 10-20 mg/mL, aliquoted, and stored between -65°C and -85°C until analyzed for UDPGT and 5´-DI. The protein content of the microsomes was measured before and after analyses by the BioRad method 5´-Deiodenase I Measurements Microsomal 5´-DI activity was determined using modifications of the methods of PazosMoura et al. (1991) and UDPGT Measurements Microsomal UDPGT activity was determined spectrophotometrically using a modification of the method of Microarray Analysis RNA preparation and analysis was done according to the Affymetrix-recommended protocol (Affymetrix 2002). Briefly, total RNA from four animals from each dose group was prepared individually using the TRIzol procedure (Invitrogen, Carlsbad, CA) and cleaned using the Qiagen RNeasy mini RNA cleanup protocol (Qiagen, Valencia, CA). The integrity of each RNA sample was determined using an Agilent 2100 Bioanalyzer (Agilent, Foster City, CA). After this, double-stranded cDNA from three of the four samples was prepared from 16 µg of total RNA using Superscript II reverse transcriptase (Invitrogen) and a T7 primer (Genset, Boulder, CO) for first-strand synthesis, and DNA polymerase and ligase (Invitrogen) for second-strand synthesis. Subsequently, labeled cRNA was synthesized from the cDNA using the Enzo RNA transcript labeling kit (Affymetrix, Santa Clara, CA) according to the manufacturer&apos;s instructions. Approximately 20 µg of biotin-labeled cRNA was then fragmented in a solution of 40 mM Tris-acetate, pH 8.1, 100 mM KOAc, and 30 mM MgOAc at 94°C for 35 min. Labeled cRNA was hybridized to the Affymetrix GeneChip Test2 Array (Affymetrix) to verify the quality of labeled cRNA. After this, cRNA was hybridized to the Affymetrix Rat Genome U34A GeneChip Probe Array (RG-U34A; Affymetrix). The cRNA in hybridization Gene expression profiles of rat thyroid toxicity Environmental Health Perspectives • VOLUME 113 | NUMBER 10 | October 2005 1355 cocktail was incubated overnight at 45°C while rotating in a hybridization oven. After approximately 16 hr of hybridization, the cocktail was removed and the arrays were washed and stained in a Fluidics Station 400 (Affymetrix) according to the Affymetrixrecommended protocol (Affymetrix 2002). Briefly, several cycles of washes were done initially with a nonstringent buffer (1 M NaCl, 67 mM NaH 2 PO 4 , 6.7 mM EDTA, 0.01% Tween 20) at 25°C and then with stringent buffer [100 mM MES, 0.1 M Na + , 0.01% Tween 20] at 50°C. The arrays were then stained in streptavidin phycoerythrin (SAPE) solution (10 µg/mL SAPE, 2 mg/mL acetylated BSA, 100 mM MES, 1 M Na + , 0.05% Tween 20) at 25°C, washed in nonstringent buffer, stained in antibody solution (2 mg/mL acetylated BSA, 100 mM MES, 1 M [Na + ], 0.05% Tween 20, 0.1 mg/mL normal goat IgG, 3 µg/mL anti-streptavidin biotinylated antibody) at 25°C, stained again in SAPE solution at 25°C, and then washed again in nonstringent buffer at 30°C. Arrays were then scanned on a GeneArray scanner (Agilent). Image analysis, quantification of raw gene expression values, mismatched probe background subtraction, and present/absent calls were performed using the Microarray Suite software (version 5.0; Affymetrix). Data Analysis Differential gene expression was determined by the regularized t-test, which uses a Bayesian procedure (Baldi and Long 2001). Briefly, the expression level of each gene is assumed to be from a normal distribution with µ and σ 2 . Using a conjugate prior, the mean of the posterior (MP) estimate of µ is the sample mean. The MP estimate of σ 2 is where n is the sample size, s 2 is the sample variance, v 0 is the degrees of freedom of the prior (a value of 10 is used in the analysis), and σ 0 2 is the mean of sample variances of genes in the neighborhood of the gene under consideration. The neighborhood is the 50 genes with sample means immediately above and below the sample mean of the gene under consideration; that is, the neighborhood consists of the 101 genes centered on the gene. After the MP estimates of µ and σ 2 are obtained, the t-test of unequal variances is used to calculate a p-value of differential expression. Multiple linear regressions are used to determine dose-dependent expression after NaI treatments of 0.1, 1, 10, or 100 mg/kg/day. Some genes respond to NaI linearly, but for other genes, the induction or repression of expression may become saturated after some dose levels. Therefore, two types of multiple linear regressions were performed. The first type was the linear regression of the gene expression levels and the dose levels, and the other type was the linear regression of the gene expression levels and the logarithms of the dose levels. A principal component analysis was also performed on the data. Three animals were measured within each treatment for each gene. The treatment means were then subjected to principal component analysis. The components were thus determined on a per-treatment basis rather than a per-gene basis, as in Results Liver Weights and Hormone Metabolism After the 2-week exposure period, liver weights were increased in a dose-dependent manner and were significantly higher in rats administered 10 and 100 mg/kg/day NaI (8-13% increase) and 100 mg/kg/day PB (44% increase) compared with control rats that received water alone UDPGT activity was significantly higher (99% increase) in rats administered 100 mg/ kg/day PB compared with controls ( Thyroid Hormone Levels and Histopathology Treatment-related effects on thyroid hormone levels were observed in the 100 mg/kg/day PB and 10 mg/kg/day PTU groups. Compared with controls, T 3 , T 4 , and rT 3 levels were reduced 23, 40, and 28%, respectively, in PBtreated rats and 80, 99, and 56%, respectively, in PTU-treated rats Treatment-related changes in thyroid gland histopathology were observed in the PB and PTU treatment groups gland weights (percent of body weight) were also significantly increased (~3-fold) in the PTU treatment group compared with controls Thyroid Gland Gene Expression Principal component analysis. Thyroid gene expression data were analyzed using principal component analysis, a regularized t-test and multiple linear regressions. Principal component analysis of gene expression data from all 24 samples demonstrated grouping according to treatment. Six principal components were identified To understand these principal components, it is helpful to express each as a linear combination of the means of the six treatments Large negative values (i.e., negative numbers large in absolute value) of this component tend to be associated with down-regulation in one of more NaI treatments. The second component is an indicator for an effect due to PB and PTU. A large value of Pcomp2 (principal component 2) indicates an up-regulation, whereas a large negative value indicates a downregulation. Component 3 is primarily a contrast between the PB and PTU treatments. The fourth principal component is primarily an indicator of effect at low doses of NaI. Based on these principal component analysis findings, further gene ontology work was directed to the first two principal components, namely, genomic profiles associated with NaI exposure or PB and PTU exposure. Multiple linear regressions. Dose-dependent expression, as determined by multiple linear regressions, was observed after NaI treatment. Transcript levels most influenced by dose (p ≤ 0.001), included the NIS [Slc5a5; GenBank accession no. U60282; (http:// www.ncbi.nlm.gov)] and antioxidant enzymes such as glutathione peroxidase 2 (Gpx2), thioredoxin reductase (Txnrd1), and glutathione S-transferase pi (GST-pi; Gstp2) ( Regularized t-test (Bayesian procedure). In a separate analysis using the regularized t-test, 872, 948, and 1552 gene transcripts (of 8,740 transcripts present in all samples) were significantly (p &lt; 0.01) changed by 100 mg/kg/day NaI, 100 mg/kg/day PB, and 10 mg/kg/day PTU administration compared with controls, respectively. To further characterize these genomic changes according to biological function and identify molecular pathways involved in the mode of action of each chemical, these gene lists were uploaded into GenMAPP (Gene Map Annotator and Pathway Profiler, version 1.0