Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vitro Model Simulating Gastro-Intestinal Digestion in the Pediatric Population (Neonates and Young Infants)

The focus on drug delivery for the pediatric population has been steadily increasing in the last decades. In terms of developing in vitro models simulating characteristics of the targeted pediatric population, with the purpose of predicting drug product performance after oral administration, it is important to simulate the gastro-intestinal conditions and processes the drug will encounter upon oral administration. When a drug is administered in the fed state, which is commonly the case for neonates, as they are typically fed every 3 h, the digestion of the milk will affect the composition of the fluid available for drug dissolution/solubilization. Therefore, in order to predict the solubilized amount of drug available for absorption, an in vitro model simulating digestion in the gastro-intestinal tract should be utilized. In order to simulate the digestion process and the drug solubilization taking place in vivo, the following aspects should be considered; physiologically relevant media, media volume, use of physiological enzymes in proper amounts, as well as correct pH and addition of relevant co-factors, e.g., bile salts and co-enzymes. Furthermore, physiological transit times and appropriate mixing should be considered and mimicked as close as possible. This paper presents a literature review on physiological factors relevant for digestion and drug solubilization in neonates. Based on the available literature data, a novel in vitro digestion model simulating digestion and drug solubilization in the neonate and young infant pediatric population (2 months old and younger) was designed.
Low-dose naproxen interferes with the antiplatelet effects of aspirin in healthy subjects: recommendations to minimize the functional consequences.

OBJECTIVE To investigate whether low-dose naproxen sodium (220 mg twice a day) interferes with aspirin's antiplatelet effect in healthy subjects. METHODS We performed a crossover, open-label study in 9 healthy volunteers. They received for 6 days 3 different treatments separated by 14 days of washout: 1) naproxen 2 hours before aspirin, 2) aspirin 2 hours before naproxen, and 3) aspirin alone. The primary end point was the assessment of serum thromboxane B(2) (TXB(2)) 24 hours after the administration of naproxen 2 hours before aspirin on day 6 of treatment. In 5 volunteers, the rate of recovery of TXB(2) generation (up to 72 hours after drug discontinuation) was assessed in serum and in platelet-rich plasma stimulated with arachidonic acid (AA) or collagen. RESULTS Twenty-four hours after the last dosing on day 6 in volunteers receiving aspirin alone or aspirin before naproxen, serum TXB(2) was almost completely inhibited (median [range] 99.1% [97.4-99.4%] and 99.1% [98.0-99.7%], respectively). Naproxen given before aspirin caused a slightly lower inhibition of serum TXB(2) (median [range] 98.0% [90.6-99.4%]) than aspirin alone (P = 0.0007) or aspirin before naproxen (P = 0.0045). All treatments produced a maximal inhibition of AA-induced platelet aggregation. At 24 hours, compared with baseline, collagen-induced platelet aggregation was still inhibited by aspirin alone (P = 0.0003), but not by aspirin given 2 hours before or after naproxen. Compared with administration of aspirin alone, the sequential administration of naproxen and aspirin caused a significant parallel upward shift of the regression lines describing the recovery of platelet TXB(2). CONCLUSION Sequential administration of 220 mg naproxen twice a day and low-dose aspirin interferes with the irreversible inhibition of platelet cyclooxygenase 1 afforded by aspirin. The interaction was smaller when giving naproxen 2 hours after aspirin. The clinical consequences of these 2 schedules of administration of aspirin with naproxen remain to be studied in randomized clinical trials.
Prognostic influence of macrophages in patients with diffuse large B-cell lymphoma: a correlative study from a Nordic phase II trial

The prognostic impact of the tumor microenvironment in diffuse large B-cell lymphoma has not been systematically assessed. We analyzed mRNA and antigen expression of monocytes, macrophages, lymphocytes, dendritic and natural killer cells in pretreatment tumor samples of patients with high-risk diffuse large B-cell lymphoma using gene expression microarray and immunohistochemistry. The patients were treated in a Nordic phase II study with dose-dense chemoimmunotherapy and central nervous system prophylaxis. Of the studied markers for non-malignant inflammatory cells, CD68 expression and CD68+ macrophage counts correlated with favorable outcome. Five-year progression-free survival rates were 83% and 43% for the patients with high and low CD68 mRNA levels, respectively (P=0.007), while overall survival rates were 83% and 64%, respectively (P=ns). The patients with high CD68+ macrophage counts had better 5-year progression-free survival (74% versus 40%; P=0.003) and overall survival (90% versus 60%; P=0.009) than the patients with low macrophage counts. Low CD68+ macrophage count retained its prognostic impact on overall survival with age-adjusted International Prognostic Index [RR=5.0 (95% CI 1.024–19.088); P=0.017]. The findings were validated in three independent cohorts of patients treated with chemoimmunotherapy. In contrast, in patients treated with chemotherapy, high CD68+ macrophage count was associated with poor progression-free survival (40% versus 72%; P=0.021) and overall survival (39% versus 72%; P=0.015). Together, the data suggest that macrophages exhibit a dual, treatment-specific role in diffuse large B-cell lymphoma. For the patients treated with chemoimmunotherapy, high pretreatment CD68 mRNA levels and CD68+ macrophage numbers predict a favorable outcome.
Discovery of Complex Mixtures of Novel Long‐Chain Quorum Sensing Signals in Free‐Living and Host‐Associated Marine Alphaproteobacteria

More than 100 bacterial isolates from various marine habitats were screened for AHL production by using gfp reporter constructs based on the lasR system of Pseudomonas aeruginosa and the luxR system of Vibrio fischeri. Of the 67 Alphaproteobacteria tested, most of which belonged into the so‐called Roseobacter clade, 39 induced fluorescence in either one or both sensor strains up to 103‐fold compared to controls. Acylated homoserine lactones were identified by GC‐MS analysis and shown to have chain lengths of C8, C10, C13–C16, and C18. One or two double bonds were often present, while a keto or hydroxyl group occurred only rarely in the side chain. Most strains produced several different AHLs. C18‐en‐HSL and C18‐dien‐HSL were produced by Dinoroseobacter shibae, an aerobic anoxygenic phototrophic bacterium isolated from dinoflagellates, and are among the longest AHLs found to date. Z7‐C14‐en‐HSL, which has previously been detected in Rhodobacter sphaeroides, was produced by Roseovarius tolerans and Jannaschia helgolandensis. This signal molecule was synthesised and shown to induce a similar response to the culture supernatant in the respective sensor strain. The widespread occurrence of quorum‐sensing compounds in marine Alphaproteobacteria, both free‐living strains and those associated to eukaryotic algae, points to a great importance of this signalling mechanism for the adaptation of the organisms to their widely different ecological niches.
Antibodies to platelet factor 4-heparin complex and outcome in hemodialysis patients with diabetes.

BACKGROUND AND OBJECTIVES Hemodialysis patients with type 2 diabetes exhibit an excessive cardiovascular risk and regularly receive heparin. We tested whether antibodies to the platelet factor 4-heparin complex (PF4-H-AB) contribute to outcome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In 1255 hemodialysis patients with type 2 diabetes, the German Diabetes Dialysis Study evaluated the effect of atorvastatin (20 mg/d) versus placebo. In a post hoc analysis, the association among PF4-H-ABs, biochemistry, and prespecified, centrally adjudicated end points (combined cardiovascular end point [CVE], all-cause mortality, sudden death, myocardial infarction, stroke) was investigated. RESULTS During 4 years, 460 patients reached the CVE; 605 died, 159 of sudden death. Myocardial infarction and stroke occurred in 199 and 97 patients, respectively. Positive PF4-H-AB status was found in 231 (18.7%) of 1236 tested patients and was associated with lower albumin, higher C-reactive protein, and arrhythmia. In a multivariate model adjusted for demographics, comorbidities, and biochemistry, PF4-H-ABs were associated with sudden death. No significant association between PF4-H-ABs and all-cause mortality, myocardial infarction, stroke, or the CVE was observed. Detecting an interaction between acetylsalicylic acid and PF4-H-ABs regarding sudden death and mortality, we found that the association between PF4-H-ABs and outcomes was restricted to patients with acetylsalicylic acid use, most likely because of indication bias. CONCLUSIONS In hemodialysis patients who have type 2 diabetes and are treated with acetylsalicylic acid, PF4-H-ABs are associated with sudden and all-cause death. Further studies are needed to elucidate this association.
A longitudinal study of psychiatric outcome: developmental variables vs. psychiatric symptoms.

Using multiple regression techniques, this study investigated the prognostic significance of childhood school behavior, home environment, adult premorbid social competence, and psychiatric symptoms at first admission in 141 psychiatric patients. The analyses focused on known psychiatric outcome, deliberately disregarding diagnoses. The presence of hallucination s at initial hospitalization was the surest indicator of poor prognosis. Withdrawal in men and perplexity or confusion in women were about equally dependable predictors. Length of hospitalization was easily foretold for both sexes by level of social competence attained before breakdown. Childhood developmental variables implicating individual personality traits and family disruption were at least as discriminating as adult psychiatric symptoms in predicting long-term outcome: ten of the significant predictors concerned childhood school behavior or the home environment, as compared with five psychiatric symptoms. Prediction equations based on the multiple regression analyses accurately classified the outcome of more than half of the patients. These results underline the importance of taking a robust longitudinal perspective in prognostic formulations, rather than a narrowly time-limited diagnostic perspective.
Effects of ammonia load on glucose metabolism by isolated ovine duodenal mucosa.

To determine the effects of ammonia load on glucose metabolism in ruminant small intestinal tissues, duodenal mucosal cells (DMC) were isolated from growing female sheep (n = 10; 46. 0 +/- 0. 8 kg of BW) fed diets differing in CP content: high (19. 4%) vs. low (13. 1%). Ammonia concentration in the duodenal digesta fluid was greater for sheep fed a high CP diet compared with those fed a low CP diet (16. 4 +/- 1. 0 vs. 9. 1 +/- 1. 8 mM). The isolated primary mucosal cells were incubated for 90 min with [2-(13)C] glucose (3 mM) and ammonium chloride (0, 0. 1, 1, 5, 10, 20, or 50 mM) in Krebs-Ringer HEPES buffer. It was hypothesized that DMC would increase glucose carbon utilization for the synthesis of nonessential AA when the ammonia concentration in the incubation media increased. However, utilization of glucose carbon for alanine synthesis decreased linearly (P = 0. 03) as the ammonia concentration in the incubation media increased. Furthermore, glucose disappearance and utilization of glucose carbon for aspartate synthesis were not affected (P > 0. 47) by the ammonia concentration. Contrarily, in vitro glucose disappearance was greater (P = 0. 03) for DMC isolated from sheep fed a low CP diet vs. a high CP diet [14. 6 +/- 1. 6 vs. 8. 6 +/- 1. 3 nmol. (10(6) cells)(-1). (90 min) (-1)], and hexokinase activity was greater (P = 0. 01) in the mucosa of sheep fed a low CP diet compared with a high CP diet (1. 22 +/- 0. 05 vs. 1. 04 +/- 0. 02 mUnit/mg of protein). These observations indicate that ammonia load does not affect the extent of glucose utilization by DMC, and that glucose carbon may not play a significant role for the synthesis of alanine, aspartate, or glutamate when DMC are exposed to increased concentrations of ammonia.
CONTEXTUALIZED ASSESSMENT WITH BATTERED WOMEN: STRATEGIC SAFETY PLANNING TO COPE WITH MULTIPLE HARMS

Given the prevalence of domestic violence and the likelihood that many victims will not receive services from specialized domestic violence providers, this article provides a framework for contextualized assessment that can be used by generalist practitioners. Drawing from stress and coping theory, the authors discuss the relevance of assessing appraisals and emotional responses within the context of environmental and individual risk and protective factors. Through an illustrative case assessment, the authors describe the contextualized assessment process and its ramifications for strategic safety planning.
Biomechanical and Histologic Observations of Vocal Fold Fibrous Proteins

This article discusses the molecular composition of the vocal fold and the relationship of fibrous molecules to the biomechanical and physiological performance of the tissue. The components of the extracellular matrix may be divided into fibrous proteins and interstitial proteins. The fibrous proteins, consisting of collagens and elastins, are the focus of this report. Elastin concentration varies by tissue depth in the vocal folds. Variation of elastin by age is reported, but some controversy exists. The biomechanical terms of stress and strain (and stress-strain curves of human vocal folds) are related to the fibrous proteins of the vocal folds. The fibrous proteins, their role in stress, and their effect on the dynamic range of vocal pitch are presented.
Inhibition of Fibrocyte Differentiation by Serum Amyloid P 1

Wound healing and the dysregulated events leading to fibrosis both involve the proliferation and differentiation of fibroblasts and the deposition of extracellular matrix. Whether these fibroblasts are locally derived or from a circulating precursor population is unclear. Fibrocytes are a distinct population of fibroblast-like cells derived from peripheral blood monocytes that enter sites of tissue injury to promote angiogenesis and wound healing. We have found that CD14+ peripheral blood monocytes cultured in the absence of serum or plasma differentiate into fibrocytes within 72 h. We purified the factor in serum and plasma that prevents the rapid appearance of fibrocytes, and identified it as serum amyloid P (SAP). Purified SAP inhibits fibrocyte differentiation at levels similar to those found in plasma, while depleting SAP reduces the ability of plasma to inhibit fibrocyte differentiation. Compared with sera from healthy individuals and patients with rheumatoid arthritis, sera from patients with scleroderma and mixed connective tissue disease, two systemic fibrotic diseases, were less able to inhibit fibrocyte differentiation in vitro and had correspondingly lower serum levels of SAP. These results suggest that low levels of SAP may thus augment pathological processes leading to fibrosis. These data also suggest mechanisms to inhibit fibrosis in chronic inflammatory conditions, or conversely to promote wound healing.
[Monthly distribution of intestinal parasites detected in a part of western Turkey between May 2009-April 2010-results of acid fast and modified trichrome staining methods].

OBJECTIVE In this study, 5073 fecal specimens and cellophane tapes from patients were examined during the period of May 1, 2009-April 30, 2010 in the parasitology laboratory of the Ege University Medical School. METHODS Sticky tape test and ethyl acetate sedimentation methods, saline, iodine, modified kinyoun's acid-fast, Trichrome, modified Trichrome and giemsa staining procedures have been applied to the stool samples. RESULTS After the macroscopic and microscopic examinations, 1138 (22.43%) intestinal parasites were determined. Cryptosporidium spp. (n=381; 33.47%), Blastocystis hominis (n=368; 32.33%) and Cyclospora spp. (n=187; 16.43%) were the three most common parasites obtained during the examination. The most commonly determined helminth was Enterobius vermicularis (n=33; 2.89%). CONCLUSION Detection of Microsporidium spores in immununosuppressed patients showed also the importance of specific staining methods. Intestinal parasites are causing serious public health problems in our region.
Hajdu–Cheney syndrome with severe dural ectasia

Hajdu–Cheney syndrome (HCS) is an autosomal dominant condition comprising osteolysis of the terminal phalanges, characteristic craniofacial abnormalities, dental anomalies, and proportionate short stature. The clinical and radiological findings develop and progress with age. Here, we report on a HCS patient with severe scoliosis and exceptionally massive dural ectasia. Congenital scoliosis and dural ectasia have not been reported previously in HCS. © 2011 Wiley‐Liss, Inc.
Antiarrhythmic properties of tedisamil (KC8857), a putative transient outward K+ current blocker

1 Rats were used to evaluate the antiarrhythmic properties of tedisamil, a novel agent with the electrophysiological properties of a Class III antiarrhythmic drug. Tedisamil was tested against coronary artery occlusion‐induced arrhythmias in conscious animals. 2 The actions of tedisamil on the ECG, as well as responses to electrical stimulation, were compared with those on the configuration of epicardial intracellular action potentials recorded in vivo. 3 Tedisamil (1–4 mg kg−1, i.v.) caused bradycardia, elevated blood pressure and dose‐dependently reduced ventricular fibrillation (VF) induced by occlusion of the left anterior descending coronary artery. Other ischaemia‐associated arrhythmias were not so well suppressed. Antiarrhythmic activity was greatest when the tedisamil‐induced bradycardia was prevented by electrically‐pacing the left ventricle. 4 Tedisamil dose‐dependently lengthened the effective refractory period and prevented electrically‐induced VF. In vivo, tedisamil (0.5–4 mg kg−1, i.v.) prolonged the duration of epicardial intracellular action potentials by up to 400%. 5 Results showed that tedisamil possessed antifibrillatory actions in rats that were related to Class III electrophysiological actions as revealed by electrical stimulation and electrophysiological analyses.
AURORAL RADIO EMISSION FROM LATE L AND T DWARFS: A NEW CONSTRAINT ON DYNAMO THEORY IN THE SUBSTELLAR REGIME

We have observed six late L and T dwarfs with the Karl G. Jansky Very Large Array (VLA) to investigate the presence of highly circularly polarized radio emission, associated with large-scale auroral currents. Previous surveys encompassing ∼60 L6 or later targets have yielded only one detection. Our sample includes the previously detected T6.5 dwarf 2MASS 10475385+2124234, as well as five new targets selected for the presence of Hα emission and/or optical infrared photometric variability, which are possible manifestations of auroral activity. We detect 2MASS 10475385+2124234, as well as four of the five targets in our biased sample, including the strong IR-variable source SIMP J01365662+0933473 and bright Hα emitter 2MASS 12373919+6526148, reinforcing the possibility that activity at these disparate wavelengths is related. The radio emission frequency corresponds to a precise determination of the lower-bound magnetic field strength near the surface of each dwarf, and this new sample provides robust constraints on dynamo theory in the low-mass brown dwarf regime. Magnetic fields ≳ 2.5 ? > kG are confirmed for five of six targets. Our results provide tentative evidence that the dynamo operating in this mass regime may be inconsistent with predicted values from a recently proposed model. Further observations at higher radio frequencies are essential for verifying this assertion.
The Impact of Automation of Systems on Medical Errors: Evidence from Field Research

We use panel data from multiple wards from two hospitals spanning a three-year period to investigate the impact of automation of the core error prevention functions in hospitals on medical error rates. Although there are studies based on anecdotal evidence and self-reported data on how automation impacts medical errors, no systematic studies exist that are based on actual error rates from hospitals. Further, there is no systematic evidence on how incremental automation over time and across multiple wards impacts the rate of medical errors. The primary objective of our study is to fill this gap in the literature by empirically examining how the automation of core error prevention functions affects two types of medical errors. We draw on the medical informatics literature and principal-agency theory and use a unique panel data set of actual documented medical errors from two major hospitals to analyze the interplay between automation and medical errors. We hypothesize that the automation of the sensing function (recording and observing agent actions) will have the greatest impact on reducing error rates. We show that there are significant complementarities between quality management training imparted to hospital staff and the automation of control systems in reducing interpretative medical errors. We also offer insights to practitioners and theoreticians alike on how the automation of error prevention functions can be combined with training in quality management to yield better outcomes. Our results suggest an optimal implementation path for the automation of error prevention functions in hospitals.
Lignicolous fungi from northern Serbia as natural sources of antioxidants

As a result of an interest in natural derived metabolites, lignicolous fungi have taken on great importance in biochemical investigations. In the present study, antioxidative screening analyses have included in vitro testing of different extracts (aqueous, methanol, chloroform) of four fungal species using three different assays: Fe2+/ascorbate-induced lipid peroxidation by TBA assay, the neutralisation of OH· radicals and the radical scavenging capacity with the DPPHk]assay. TLC analysis confirmed the existance of phenolics in the extracts, but also indicates the presence of some other compounds. The obtained results indicate that MeOH extracts manifested a degree of activity higher than that of CHCl3 extracts. With respect to antioxidative activity, the extracts can be ranged in the following declining order: G. lucidum, G. applanatum, M. giganteus and F. velutipes. These results suggest that analyzed fungi are of potential interest as sources of strong natural antioxidants that could be used in the food industries and nutrition.