MedicaidJS: a FAIR approach to real-time drug analytics.

Motivation: As prescription drug prices have drastically risen over the past decade, so has the need for real-time drug tracking resources. In spite of increased public availability to raw data sources, individual drug metrics remain concealed behind intricate nomenclature and complex data models. Some web applications, such as GoodRX, provide insight into real-time drug prices but offer limited interoperability. To overcome both obstacles we pursued the direct programmatic operation of the stateless Application Programming interfaces (HTTP REST APIs) maintained by the Food and Drug Administration (FDA), Medicaid, and National Library of Medicine. These data-intensive resources represent an opportunity to develop Software Development Kits (SDK) to streamline drug metrics without downloads or installations, in a manner that addresses the FAIR principles for stewardship in scientific data-Findability, Accessibility, Interoperability, and Reusability. These principles provide a guideline for continual stewardship of scientific data. Results: MedicaidJS SDK was developed to orchestrate API calls to three complementary data resources: Medicaid (data.medicaid.gov), Food and Drug Administration (open.fda.gov), and the National Library of Medicine RxNorm (lhncbc.nlm.nih.gov/RxNav). MedicaidJS synthesizes response data from each platform into a zero-footprint JavaScript modular library that provides data wrangling, analysis, and generation of embeddable interactive visualizations. The SDK is served on github with live examples on observableHQ notebooks. It is freely available and can be embedded into web applications as modules returning structured JSON data with standardized identifiers. Availability and implementation: Open source code publicly available at https://github.com/episphere/medicaid, live at episphere.github.io/medicaid, supplementary interactive Observable Notebooks at observablehq.com/@medicaidsdk/medicaidsdk.

PRScalc, a privacy-preserving calculation of raw polygenic risk scores from direct-to-consumer genomics data.

Motivation: Currently, the Polygenic Score (PGS) Catalog curates over 400 publications on over 500 traits corresponding to over 3000 polygenic risk scores (PRSs). To assess the feasibility of privately calculating the underlying multivariate relative risk for individuals with consumer genomics data, we developed an in-browserPRS calculator for genomic data that does not circulate any data or engage in any computation outside of the user's personal device. Results: A prototype personal risk score calculator, created for research purposes, was developed to demonstrate how the PGS Catalog can be privately and readily applied to readily available direct-to-consumer genetic testing services, such as 23andMe. No software download, installation, or configuration is needed. The PRS web calculator matches individual PGS catalog entries with an individual's 23andMe genome data composed of 600k to 1.4 M single-nucleotide polymorphisms (SNPs). Beta coefficients provide researchers with a convenient assessment of risk associated with matched SNPs. This in-browser application was tested in a variety of personal devices, including smartphones, establishing the feasibility of privately calculating personal risk scores with up to a few thousand reference genetic variations and from the full 23andMe SNP data file (compressed or not). Availability and implementation: The PRScalc web application is developed in JavaScript, HTML, and CSS and is available at GitHub repository (https://episphere.github.io/prs) under an MIT license. The datasets were derived from sources in the public domain: [PGS Catalog, Personal Genome Project].

GWAS Explorer: an open-source tool to explore, visualize, and access GWAS summary statistics in the PLCO Atlas.

The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a prospective cohort study of nearly 155,000 U.S. volunteers aged 55-74 at enrollment in 1993-2001. We developed the PLCO Atlas Project, a large resource for multi-trait genome-wide association studies (GWAS), by genotyping participants with available DNA and genomic consent. Genotyping on high-density arrays and imputation was performed, and GWAS were conducted using a custom semi-automated pipeline. Association summary statistics were generated from a total of 110,562 participants of European, African and Asian ancestry. Application programming interfaces (APIs) and open-source software development kits (SKDs) enable exploring, visualizing and open data access through the PLCO Atlas GWAS Explorer website, promoting Findable, Accessible, Interoperable, and Re-usable (FAIR) principles. Currently the GWAS Explorer hosts association data for 90 traits and >78,000,000 genomic markers, focusing on cancer and cancer-related phenotypes. New traits will be posted as association data becomes available. The PLCO Atlas is a FAIR resource of high-quality genetic and phenotypic data with many potential reuse opportunities for cancer research and genetic epidemiology.

PLCOjs, a FAIR GWAS web SDK for the NCI Prostate, Lung, Colorectal and Ovarian Cancer Genetic Atlas project.

MOTIVATION: The Division of Cancer Epidemiology and Genetics (DCEG) and the Division of Cancer Prevention (DCP) at the National Cancer Institute (NCI) have recently generated genome-wide association study (GWAS) data for multiple traits in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Genomic Atlas project. The GWAS included 110 000 participants. The dissemination of the genetic association data through a data portal called GWAS Explorer, in a manner that addresses the modern expectations of FAIR reusability by data scientists and engineers, is the main motivation for the development of the open-source JavaScript software development kit (SDK) reported here. RESULTS: The PLCO GWAS Explorer resource relies on a public stateless HTTP application programming interface (API) deployed as the sole backend service for both the landing page's web application and third-party analytical workflows. The core PLCOjs SDK is mapped to each of the API methods, and also to each of the reference graphic visualizations in the GWAS Explorer. A few additional visualization methods extend it. As is the norm with web SDKs, no download or installation is needed and modularization supports targeted code injection for web applications, reactive notebooks (Observable) and node-based web services. AVAILABILITY AND IMPLEMENTATION: code at https://github.com/episphere/plco; project page at https://episphere.github.io/plco.

Filled hydrogel particles as a delivery system for n-3 long chain PUFA in low-fat frankfurters: Consequences for product characteristics with special reference to lipid oxidation.

This article examines the suitability of filled hydrogel particles for use as a delivery system for n-3 long chain PUFAs in low-fat frankfurters. Their effects on product characteristics over chilled storage were compared with those of frankfurters containing all-pork fat (control) or a comparable amount of fish oil (n-3 LCPUFA) incorporated in liquid form or in an oil-in-water emulsion. In modified samples n-3 fatty acids ranged between 801.34 to 996.37 mg/100g as opposed to 66 mg/100g in all-pork fat product. As compared with the control, hardness and chewiness values were similar (P>0.05) in filled hydrogel frankfurter. The presence of fish oil favoured lipid oxidation to varying degrees depending on delivery system, in descending order: direct oil addition>oil-in-water emulsion>hydrogels. Sensory evaluation demonstrated the advantages, from a sensory point of view, of hydrogel filled particles as n-3 delivery systems in frankfurters.

Oxidative stability of n-3 fatty acids encapsulated in filled hydrogel particles and of pork meat systems containing them.

The effect of storage time (2°C, 19 days) and heating (70°C, 30 min) on physical characteristics and oxidative stability of fish oil encapsulated in filled hydrogel particles was determined and compared with a conventional oil-in-water (O/W) emulsion with the same oil content (8.5%). Subsequently they were used to enrich meat systems with n-3 LCPUFAs, and their lipid oxidation was evaluated and compared with two other meat systems: one containing all animal fat and another with fish oil added directly. Filled hydrogel particles were more effective in lowering the oxidation rate than O/W emulsion, even when thermal treatment was applied. Oxidative stability over the storage time was best in the n-3 LCPUFA-enriched meat system containing filled hydrogel particles, in which TBARS levels were up to 62% lower than other systems containing fish oil. Hydrogel particles offer a promising means of controlling lipid oxidation in n-3 LCPUFA-enriched meat products.

Konjac-based oil bulking system for development of improved-lipid pork patties: technological, microbiological and sensory assessment.

Improved-lipid pork patties were manufactured following two different reformulation strategies: fat reduction by replacement of pork backfat with konjac gel (KG), and fat reduction/lipid improvement by replacement of pork backfat with an improved oil combination (olive, linseed and fish oils) bulking system based on konjac gel (O-KG). Technological, microbiological and sensory properties were analyzed as affected by the type of formulation and by chilled storage (9days, 2°C). Fat was reduced by between 30 and 86%. In the cases where O-KG was incorporated, 12 and 41% of total fat in patties came from the oil combination. There was no observable effect on color parameters in samples with O-K. Higher KG levels produced harder cooked patties. Animal fat replacement in patties promoted an increase in lipid oxidation, which was more pronounced in samples with an oil combination. In general, during chilled storage no major changes were observed in the studied properties as a result of the different treatments.

Effect of cooking method on the fatty acid content of reduced-fat and PUFA-enriched pork patties formulated with a konjac-based oil bulking system.

The effect of cooking methods (electric grilling and pan-frying in olive oil) on the composition of reduced-fat and reduced-fat/PUFA enriched pork patties was studied. Fat reduction was performed by replacing pork backfat (38% and 100%) with konjac gel and PUFA-enrichment by replacing pork backfat (49%) with a konjac-based oil bulking system stabilizing a healthier oil combination (olive, linseed and fish oils). Cooking losses (13%-27%) were affected (p<0.05) by formulation and cooking procedure. Compared with raw products, cooked samples had higher (p<0.05) concentrations of MUFAs and PUFAs (both n-3 and n-6); the difference was greater (p<0.05) in the pan-fried patties. Fatty acid retention was generally better in pan-fried than in grilled samples. When cooked, the PUFA levels in the medium-fat/improved sample containing the oil bulking system ranged between 1.4 and 1.6g/100g (0.47-0.51 from n-3 PUFAs), with EPA+DHA concentrations of around 75mg/100g. Konjac materials were successfully used to produce pork patties with a better lipid composition.

Antioxidant activity of hydroxytyrosol in frankfurters enriched with n-3 polyunsaturated fatty acids.

The capacity of hydroxytyrosol (HXT) to inhibit lipid oxidation in cooked pork meat batter, oil-in-water emulsions and potential functional frankfurters formulated with a healthier oil combination (as animal fat replacer) was studied during chilling storage, and its effect compared with those produced by synthetic antioxidants (BHA/BHT). Although efficiency varied, HXT was an effective antioxidant during chilling storage in the three food matrices studied. In general the order of inhibition capacity of HXT against lipid oxidation (thiobarbituric acid-reactive substances-TBARS) was cooked meat batter>oil-in-water emulsion>frankfurters, whereas in the case of BHA/BHT (with lower inhibitory activity than HXT) it was cooked meat batter>oil-in-water emulsion, and there was no antioxidative effect in frankfurters. Whereas significant correlations were established between lipid oxidation (TBARS) and antioxidative capacity measured by photochemiluminescence (PCL) in frankfurters supplemented with HXT and BHA/BHT, no significant correlations were found between ferric reducing/antioxidant power assay (FRAP) and TBARS and PCL.

Is a leaky gut involved in the pathogenesis of intrahepatic cholestasis of pregnancy?

Increased gastrointestinal permeability has been demonstrated in several liver diseases. It may facilitate the absorption of gut-derived endotoxin-stimulating Kupffer cells to release proinflammatory cytokines or other potentially hepatotoxic compounds. We examined gastrointestinal permeability, plasma levels of anti-lipopolysacharides (anti-LPS), and four proinflammatory cytokines in 20 patients with intrahepatic cholestasis of pregnancy (ICP) compared with 22 normal pregnant and 29 non-pregnant women. Urinary excretion of sucrose and the urinary lactulose/mannitol (L/M) ratio after a standard oral load were used to assess gastrointestinal permeability. Anti-LPS (IgA, IgM, and IgG) were measured in peripheral blood by Human EndoCAb test kit; TNF-alpha, IL-1beta, IL-6, and IL-10 by Quantikine HS human immunoassays. Sucrose urinary excretion was similar in the three groups, indicating normal gastric permeability. The urinary L/M ratio was significantly higher in ICP than in the other groups [median (interquartile range): 0.018% (0.011-0.023) in ICP, 0.012% (0.009-0.016) in normal pregnancies, and 0.009% (0.008-0.012) in non-pregnant women, P < .01]. No significant differences were found in anti-LPS or cytokines plasma levels except slightly higher levels of IL-6 in ICP patients than in non-pregnant women (P < .05). Four of five women with abnormal urinary L/M ratio during ICP continued to show abnormalities in tests up to 2 years after delivery. In conclusion, an increased intestinal permeability was detected in ICP patients during and after pregnancy. A "leaky gut" may participate in the pathogenesis of ICP by enhancing the absorption of bacterial endotoxin and the enterohepatic circulation of cholestatic metabolites of sex hormones and bile salts.

Ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy. A 12-year experience.

OBJECTIVE: To assess the efficacy of ursodeoxycholic acid (UDCA) in patients with intrahepatic cholestasis of pregnancy (ICP) and in the outcome of pregnancy. METHODS: Retrospective analysis of our 12-year experience treating ICP patients with UDCA. Thirty-two patients with pruritus starting before week 34 of pregnancy and with increased serum bile salts (BS) and alanine aminotransferase (ALT) received UDCA (15 mg/kg/day) for at least 3 weeks before delivery. They were compared with 16 historical controls who did not receive UDCA. All patients were followed up until delivery and in puerperium. Newborns were followed up during 3 months. RESULTS: UDCA treatment attenuated pruritus (P < 0.05), serum bilirubin and ALT decreased (P < 0.05) and BS declined. Delivery at term (> or = 37 weeks) occurred in 65.7% of UDCA-treated patients compared with only 12.5% in controls (P < 0.01). Infants born to mothers treated with UDCA weighed a mean of 500 g more than the controls (2882+/-582 vs 2385+/-582; P < 0.01). At 3 months, all infants developed normally. Twenty-six children whose mothers received UDCA were re-examined after 1-12 years and they and their mothers were healthy. CONCLUSIONS: UDCA improved pruritus and biochemical cholestasis, and facilitated deliveries at term in ICP patients, with a higher birthweight compared with historical controls. The drug was well tolerated and no adverse effects were detected in their infants.

Estudio clínico de la eclampsia / Clinical study of eclampsia

En un estudio retrospectivo de tres años (julio de 1983 a junio de 1986), se analizan todos los casos de eclampsia ocurridos en el Hospital Paula Jaraquemada, de la ciudad de Santiago de Chile. En un total de 32.729 partos, hubo 29 eclampsias, con una incidencia de 0,89%, es decir, una eclampsia cada 1.128 partos. 62% de nuestras pacientes eran nulíparas;37%, menores de 19 años;55% eran solteras, y 28 de las enfermas tuvieron asistencia prenatal. 62% presentó la crisis convulsiva en el preparto, y con respecto a la edad de gestación, 55% eran de pretérmino. En 11 de las pacientes la crisis se presentó fuera del recinto hospitalario. Todas las pacientes fueron tratadas con terapia anticonvulsiva con sulfato de magnesio, y en algunas se agregó Diazepam endovenoso. Se usó hidralazina como droga hipotensora. La resolución del parto fue mediante cesárea en 86,2%, y la anestesia general se dió en un 55%. La interrupción del embarazo fue dentro de las 12 primeras horas después de iniciadas las crisis convulsivas. La morbalidad materna fue de 31%; desprendimiento prematuro de placenta ocurrió en cuatro casos. Se consignan, además, dos casos de insuficiencia renal aguda, uno de neumonía aspirativa y dos de edema cerebral. No hubo mortalidad materna. Con respecto a los neonatos, cabe considerar que hubo un embarazo gemelar, por lo cual los recién nacidos fueron 30. Hubo una alta incidencia de recién nacidos de pretérmino (43,3%);recién nacidos de bajo peso (36,6%), pequeños para la edad de gestación (26,6%). Asimismo, hubo una alta morbilidad perinatal (53,3%), lo cual se atribuye a la prematuridad, retardo de crecimiento intrauterino, sufrimiento fetal agudo. Sólo un recién nacido falleció. La mortalidad perinatal fue de 33%. Estos resultados, tanto de mortalidad materna como perinatal, son los mejores publicados en nuestro país