Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics, efficacy, and safety of mycophenolate mofetil in combination with standard‐dose or reduced‐dose tacrolimus in liver transplant recipients

The pharmacokinetics of mycophenolate mofetil (MMF) in liver transplant recipients may change because of pharmacokinetic interactions with coadministered immunosuppressants or because changes in the enterohepatic anatomy may affect biotransformation of MMF to mycophenolic acid (MPA) and enterohepatic recirculation of MPA through the hydrolysis of mycophenolate acid glucuronide to MPA in the gut. In the latter case, the choice of formulation (oral versus intravenous) could have important clinical implications. We randomized liver transplant patients (n = 60) to standard (10–15 ng/mL) or reduced (5–8 ng/mL) trough levels of tacrolimus plus intravenous MMF followed by oral MMF (1 g twice daily) with corticosteroids. Pharmacokinetic sampling was performed after the last intravenous MMF dose, after the first oral MMF dose, and at selected times over 52 weeks. The efficacy and safety of the 2 regimens were also assessed. Twenty‐eight and 27 patients in the tacrolimus standard‐dose and reduced‐dose groups, respectively, were evaluated. No significant differences between the tacrolimus standard‐dose and reduced‐dose groups were seen in dose‐normalized MPA values of the time to the maximum plasma concentration (1.25 versus 1.28 hours), the maximum plasma concentration (15.5 ± 7.93 versus 13.6 ± 7.03 μg/mL), or the area under the concentration‐time curve from 0 to 12 hours (AUC0–12; 53.0 ± 20.6 versus 43.8 ± 15.5 μg h/mL) at week 26 or at any other time point. No relationship was observed between the tacrolimus trough or AUC0–12 and MPA AUC0–12. Exposure to MPA after oral and intravenous administration was similar. Safety and efficacy were similar in the two treatment groups. In conclusion, exposure to MPA is not a function of exposure to tacrolimus. The similar safety and efficacy seen with MMF plus standard or reduced doses of tacrolimus suggest that MMF could be combined with reduced doses of tacrolimus. Liver Transpl 15:136–147, 2009. © 2009 AASLD.
Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients.

BACKGROUND & AIMS Drugs that inhibit gastric acid might increase the risk of hip fracture. However, little long-term exposure data exist and no large studies have been conducted in the United States. METHODS We conducted a case-control study using data from an integrated health services organization. We evaluated 33,752 patients with incident diagnoses of hip/femur fractures (cases), 130,471 matched members without fractures (controls), prescription data for use of proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) (up to 10 years' cumulative duration), and confounders. RESULTS Patients with hip fractures were more likely than controls to have previously received a > or =2-year supply of PPIs (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.21-1.39) or H2RAs (OR, 1.18; 95% CI, 1.08-1.29). The risk was reduced after discontinuation of medication (OR of 1.30 [95% CI, 1.21-1.41] for current PPI users vs OR of 1.09 [95% CI, 0.64-1.85] for patients who received their last prescription 2-2.9 years ago). Higher dosages (but not increasing cumulative durations) were associated with increased risk (eg, > or =1.5 pills/day: OR, 1.41 [95% CI, 1.21-1.64]; <0.74 pills/day: OR, 1.12 [95% CI, 0.94-1.33]). Excess fracture risk for PPI use was only present among persons with at least one other fracture risk factor. CONCLUSIONS Use of drugs that inhibit gastric acid is associated with an increased risk of hip fracture; however, this association was only found among persons with at least one other risk factor for hip fracture. Acid inhibition might therefore be associated with fracture risk in persons already at risk for osteoporosis, although other confounding cannot be excluded.
Streptomycin causes misreading of natural messenger by interacting with ribosomes after initiation.

The induction of misreading by streptomycin in vitro, previously observed with synthetic messengers, is now demonstrated with natural (endogenous or viral) messenger by the use of extracts of temperature sensitive mutants lacking Glu--tRNA or Val--tRNA synthetase. With chain-elongating but noninitiating ribosomes (i.e., purified polysomes) deprived of an aminoacyl--tRNA, streptomycin and other aminoglycosides, over a wide range of concentrations, stimulate incorporation. With ribosomes initiating in the presence of streptomycin stimulation is also observed but it is restricted, just like phenotypic suppression in cells, to very low streptomycin concentrattions which evidently allow some ribosomes to initiate and later encounter them in the course of chain elongation. The stimulation is accompanied by an increase in the size of the products; hence, it is evidently due to substitution of an incorrect aminoacyl--tRNA for a missing one. The test introduced here also has revealed a misreading effect of streptomycin on resistant ribosomes. In addition, significant intrinsic misreading was observed without streptomycin, indicating that under optimal conditions for in vitro protein synthesis an empty codon is frequently read by an incorrect aminoacyl--tRNA.
A LONG‐TERM STUDY ON SEASONAL CHANGES OF GAMETIC DISEQUILIBRIUM BETWEEN ALLOZYMES AND INVERSIONS IN DROSOPHILA SUBOBSCURA

Abstract Seasonal variation (spring, early summer, late summer, and autumn) of gametic disequilibrium between gene arrangements (OST and O3+4) of the O chromosome and Lap, Pept‐1, and Acph allozyme loci, located inside these inversions, has been recorded in a natural population of Drosophila subobscura during seven years over a 15‐year period. The length of the study allowed us to investigate the temporal variation of the allozyme‐inversion associations by statistical methods of time series analysis. Cyclic seasonal changes of allozyme‐inversion associations for both Lap and Pept‐1 are detected in the natural population. In both cases, the patterns of seasonal change are due to the seasonal change of frequency of Lap and Pept‐1 allozymes occurring exclusively within the OST gene arrangement. In contrast, the allozyme frequencies at these loci within the O3+4 gene arrangement are stable along seasons. The patterns of temporal variation of allozyme‐inversion associations for Lap and Pept‐1 in the natural population are contrasted with those previously published that correspond to gene arrangements of the O chromosome and nucleotide polymorphism at the rp49 region located inside these inversions, suggesting that natural selection is operating on these allozyme‐inversion associations.
Cholecystokinin stimulation leads to increased oxytocin secretion in women.

OBJECTIVE To find out if cholecystokinin (CCK) stimulates the secretion of oxytocin in humans, and if there are any differences in secretion between healthy women and those with normal-transit constipation. DESIGN Prospective open study. SETTING Teaching hospital, Sweden. SUBJECTS 8 healthy female volunteers and 6 women with chronic refractory normal-transit constipation. INTERVENTIONS Subjects were fasted before experiments. On one day they were given emulsified corn oil and another an intravenous injection of 1 Ivy dog unit (IDU) CCK/kg body weight. Blood samples were taken before each experiment at 10 minutes and at the time the experiments started. Blood samples were also taken after each experiment at 10, 20, 30, 45, 60, 90 and 120 minutes. MAIN OUTCOME MEASURES Concentrations of CCK and oxytocin. RESULTS Ingestion of corn oil significantly increased the plasma concentration of CCK in both groups (healthy women p = 0.03 and constipated women p = 0.008). Injection of CCK also led as expected to hypercholecystokininaemia in both groups (p = 0.008 and p = 0.03, respectively). The corn oil increased oxytocin secretion in both groups (p = 0.02 and 0.03, respectively) and exogenous CCK increased the secretion still further (p = 0.008 and 0.03, respectively). CONCLUSIONS Both corn oil and injection of CCK led to an increased CCK concentration in plasma. Oxytocin was secreted in response to endogenous as well as exogenous CCK stimulation. There was no difference between healthy and constipated women in either parameter analysed.
Decellularization does not eliminate thrombogenicity and inflammatory stimulation in tissue-engineered porcine heart valves.

BACKGROUND AND AIM OF THE STUDY In tissue engineering of heart valves using decellularized xenogenic valves, it has been suggested that cell elimination would result in a biologically inert matrix. The aim of this in-vitro investigation was to evaluate different decellularization methods in regard to the completeness of cell removal, inflammatory response, and thrombocyte activation. METHODS Decellularized porcine Synergraft valves were compared with porcine pulmonary conduits decellularized with Triton X-100, sodium deoxycholate, Igepal CA-630 and ribonuclease. Completeness of decellularization was evaluated with staining for nuclei and alpha-Gal epitope. Decellularized heart valves with and without seeding with endothelial cells (ECs) were incubated with human platelet-rich plasma and stained for CD41 and PAC-1 to evaluate thrombocyte activation. Samples were processed for laser scanning microscopy (LSM) and scanning electron microscopy (SEM). Migration of human monocytic cells towards extracted valve proteins was tested. RESULTS In contrast to the Synergraft, complete cell removal and elimination of the alpha-gal epitope was achieved with the new decellularization method. Numerous adherent and activated platelets were found on the decellularized matrix. This was inhibited by seeding with ECs. Even in completely cell-free valve tissue extracellular matrix proteins attracted human monocytic cells as in early inflammation, depending on whether porcine or human tissue was used. CONCLUSION Important differences were found in the decellularization efficacy of treatment methods. However, even complete elimination of cells and their remnants did not result in a biologically inert matrix. The decellularized porcine heart valve matrix has the potential to attract inflammatory cells and to induce platelet activation. These findings suggest that it will be important to control the different inflammation-stimulating factors if porcine tissues are to be used successfully in tissue engineering.
Mutual emotion regulation and the stability of conduct problems between preschool and early school age

Mutual regulation of anger plays a role in both healthy adjustment and mental health problems. This study of 85 preschooler boys and girls examined mother–preschooler anger regulation during a frustration in relation to the child's preschool and school age problem status. Less mutual positive emotion, more mutual anger, and more emotional mismatches than other dyads characterized dyads with a stable conduct problem child. Maternal emotion predicted school age conduct problems, particularly for boys. Maternal emotion also predicted stability versus improvement of symptoms. The emotional dynamics of mother–preschooler angry exchanges may redirect girls' conduct problems and may contribute to the stability of boys' conduct problems.
Cellular expression of growth hormone and prolactin receptors in human breast disorders

Growth hormone (GH) and prolactin (PRL) exert their regulatory functions in the mammary gland by acting on specific receptors. Using isotopic in situ hybridization and immunohistochemistry, we have localized the expression of hGH receptor (hGHR) and hPRL receptor (hPRLR) in a panel of human breast disorders. Surgical specimens from adult females included normal breast, inflamatory lesions (mastitis) benign proliferative breast disease (fibroadenoma, papilloma, adenosis, epitheliosis), intraductal carcinoma or lobular carcinoma in situ, and invasive ductal, lobular or medullary carcinoma. Cases of male breast enlargement (gynecomastia) were also studied. In situhybridization analysis demonstrated the co‐expression of hGHR and hPRLR mRNA in all samples tested. Epithelial cells of both normal and tumor tissues were labelled. Quantitative estimation of receptor mRNA levels was regionally measured in areas corresponding to tumor cells and adipose cells from the same section. It demonstrated large individual variation and no correlation emerged according to the histological type of lesion. Receptor immunoreactivity was detected both in the cytoplasm and nuclei or in the cytoplasm alone. Scattered stromal cells were found positive in some cases, but the labeling intensity was always weaker than for neoplastic epithelial cells. Our results demonstrate the expression of the hGHR and hPRLR genes and their translation in epithelial cells of normal, proliferative and neoplastic lesions of the breast. They also demonstrate that stromal components express GHR and PRLR genes. Thus the putative role of hGH or hPRL in the progression of proliferative mammary disorders is not due to grossly altered levels of receptor expression. Int. J. Cancer (Pred. Oncol.) 79:202–211, 1998. © 1998 Wiley‐Liss, Inc.
Megakaryocyte and platelet abnormalities in a patient with a W33C mutation in the conserved SH3-like domain of myosin heavy chain IIA

Summary Heterozygous mutations in MYH9, which encodes non-muscle myosin heavy chain IIA (MHC-IIA),result in autosomal dominant inherited MYH9-related disorders characterised by macrothrombocytopenia, granulocyte inclusions, variable sensorineural deafness, cataracts and nephritis. MHC-IIA is assembled into a complex consisting of two pairs of light chains and two heavy chains, where the latter contain a neck region, SH3-like, motor and rod domains. We describe a patient with a Trp33Cys missense mutation in the SH3-like domain of MHC-IIA. Abnormal platelet function was observed using platelet aggregometry with the agonists epinephrine and adenosine diphosphate (ADP). Patient granulocytes and megakaryocytes, but not platelets, contained abnormal MHC-IIA inclusions visualised by confocal immunofluorescence or electron microscopy. Megakaryocytes grown in culture were smaller and contained hypolobulated nuclei compared to controls. Bone marrow-derived megakaryocytes revealed a preponderance of immature forms, the presence of structurally diverse inclusion bodies, and frequent emperipolesis as assessed by electron microscopy. Platelets and leukocytes contained indistinguishable amounts of total MHCIIA determined by immunoblotting. Molecular modelling studies indicated that mutation of Trp33 destabilises the interface between the SH3-like and motor domain of MHC-IIA, which is close to previously described motor domain mutations, implying an important structural and/or functional role for this region in MHC-IIA.
Multicell Three-Phase AC–DC Driver for HB-LED Lighting Applications

High-brightness light-emitting diodes (HB-LEDs) are becoming omnipresent across all aspects of illumination products, due to their incredible characteristics such as efficiency, reliability, long lifetime, controllability, etc. This paper proposes power conversion topologies to drive medium to high power HB-LEDs in three-phase power grids when these connections are available. For that reason, an evaluation of several drivers for medium to high power HB-LEDs in three-phase power grids is done. Moreover, a new topology is proposed, which complies with IEC 1000-3-2 Class C requirements, achieves high power factor, low total harmonic distortion, and the capability to have a flicker free behavior while disposing of the bulk capacitor and having galvanic isolation. The HB-LED driver is based on a modular approach with several cells working together with their inputs connected to the three-phase network and their outputs connected in parallel generating a dc output. Each one of these cells is a dc–dc converter operating as a loss free resistor. In order to validate the concept, a prototype has been built by the use of flyback converters operating in discontinuous conduction mode. Furthermore, it operates in the full range of the European three-phase line voltage, which varies between 380 and 420 V, and it supplies an output voltage of 48 V with maximum power of 90 W.
Ever vs never smoking among an urban, multiethnic sample of Haitian-, Caribbean-, and U.S.-born blacks.

BACKGROUND Despite the high rate of current smoking among blacks in the United States, to date there have been no studies comparing smoking rates or predictors of smoking among adults from different black ethnic groups living in the United States. If cancer control programs are to successfully reduce the risk of smoking-related cancers within black communities, more extensive data on demographics, knowledge, attitudes, beliefs, and practices within ethnic groups are needed. METHODS We conducted a structured telephone interview to assess smoking status, alcohol use, cancer-related attitudes and beliefs, and demographic information among Haitian-born (N = 165), Caribbean-born (N = 354), and U.S.-born (N = 402) blacks living in New York City in 1992. RESULTS Relative to U.S.-born participants, both Caribbean- and Haitian-born participants were significantly less likely to have ever smoked. Although both groups of foreign-born men were much more likely to have ever smoked relative to their female counterparts, U.S.-born men and women were equally likely to have ever smoked. Alcohol use was consistently related to smoking across ethnic and gender groups, and this association was enhanced among older drinkers. The belief that smoking is not related to cancer was associated with an almost twofold increase of ever smoking. CONCLUSIONS The rate of ever smoking among urban, foreign-born blacks is considerably lower than among U.S.-born blacks; among the foreign-born participants, ever smoking was lower among women relative to men. Alcohol use is an important predictor of smoking status, particularly among older drinkers.
Non-destructive photoacoustic detecting method for high-speed rail surface defects

The rail defect detection is vital to the rapid development of high-speed rail. A new, easily available nondestructive testing method which applies the photoacoustic detection technology is proposed here for the rail defect detection. Based on the ultrasonic sensor, a real-time photoacoustic imaging system for the rail non-destructive testing is established. The model of the system and its numerical solution are built first, and then the corresponding experiments and analysis are conducted. The photoacoustic image with damage characteristics can be reconstructed through the photoacoustic signals which excited by pulsed laser and then reflected back from the rail surface. According to the reconstructed image, the damage information such as the appearance, extension trend, and the depth of the rail defect can be effectively identified. It has been proved that the established photoacoustic detecting method for high-speed rail surface detection is an effective and non-destructive detecting technology.
Evaluating affective usability experiences of an exergaming platform for seniors

FitForAll (FFA) exergaming platform helps elderly to entertain themselves while they do their workout. Motion sensing devices depict user's movement patterns on a game screen. The work described here, highlights the significance of developing human-computer interaction systems focusing on the needs of end-users. Specific design techniques are adopted in order to provide seniors with content that is easily accessible and comprehensible. Some early results of a first prototype are presented. 14 seniors in total, either healthy or with cognitive decline (either mild cognitive impairment or mild dementia) have provided feedback on several aspects of platform usability. An additional evaluation component of the platform that is thoroughly investigated is the affective evaluation of the FFA platform. An important conclusion that stems from the present research is the highly significant predictive value of affective states on usability evaluation, highlighting the important role of the entertaining exergaming environment regarding its usability. Further investigation on the enhancement of seniors' affective experience during game play is of utmost importance to us, as there is strong evidence that dynamic game content adaptation according to one's affective state would result into better training adherence and seniors' reinforcement of motivation.
Behavioural integration of auditory and antennal stimulation during phonotaxis in the field cricket Gryllus bimaculatus

ABSTRACT Animals need to flexibly respond to stimuli from their environment without compromising behavioural consistency. For example, female crickets orienting toward a conspecific male's calling song in search of a mating partner need to stay responsive to other signals that provide information about obstacles and predators. Here, we investigate how spontaneously walking crickets and crickets engaging in acoustically guided goal-directed navigation, i.e. phonotaxis, respond to mechanosensory stimuli detected by their long antennae. We monitored walking behaviour of female crickets on a trackball during lateral antennal stimulation, which was achieved by moving a wire mesh transiently into reach of one antenna. During antennal stimulation alone, females reduced their walking speed, oriented toward the object and actively explored it with antennal movements. Additionally, some crickets initially turned away from the approaching object. Females responded in a similar way when the antennal stimulus was presented during ongoing phonotaxis: forward velocity was reduced and phonotactic steering was suppressed while the females turned toward and explored the object. Further, rapid steering bouts to individual chirps, typical for female phonotaxis, no longer occurred. Our data reveal that in this experimental situation, antennal stimulation overrides phonotaxis for extended time periods. Phonotaxis in natural environments, which require the integration of multiple sensory cues, may therefore be more variable than phonotaxis measured under ideal laboratory conditions. Combining this new behavioural paradigm with neurophysiological methods will show where the sensory-motor integration of antennal and acoustic stimulation occurs and how this is achieved on a mechanistic level. Summary: Investigation of the effect of antennal mechanosensory stimulation in female crickets walking on a trackball shows that phonotaxis to male calling song is suppressed while the animals explore objects with their antennae.
Helicobacter pylori in peptic ulcer: have Koch's postulates been fulfilled?

This brief review considers whether or not Koch's postulates have been fulfilled for Helicobacter pylori and peptic ulceration. The histological features of peptic ulcer disease in man are active chronic gastritis with antral predominance, duodenal gastric metaplasia and active duodenitis. Other features are hyperpepsinogenaemia, relative postprandial hypergastrinaemia and basal acid hypersecretion. The macroscopic features are duodenal bulb ulceration or lesser curve and antral gastric ulceration. At present, gastric colonization with H. pylori has been produced in small animal species (rats and mice), but the infection is difficult to establish in immunocompetent animals, and histological gastritis is unconvincing. In larger animals the germ-free pig has been the most reliable model but the gastritis tends to be chronic with little activity. The best examples of acute infection are in three 'self-administration' experiments in humans. In these cases acute gastritis with hypochlorhydria developed which, when it converted to active chronic gastritis, tended to be asymptomatic. Either the circumstances were incompatible with ulceration, or the experiments were not continued for the many years necessary to develop peptic ulceration. It is concluded that only one of the many steps required for the development of peptic ulceration has so far been fulfilled, i.e. the ability of H. pylori to produce histological gastritis in a susceptible host.