Miracle-dz/UniFAR-FTUs huggingface dataset:
Alterations in atrial electrophysiology associated with chronic atrial fibrillation in man.

BACKGROUND The purpose of this study was to determine the changes in atrial electrophysiology associated with chronic persistent atrial fibrillation in man. METHODS AND RESULTS Atrial monophasic action potential duration at 90% repolarization and the effective refractory period were measured in 13 patients with chronic persistent atrial fibrillation after low-energy endocardial cardioversion, and compared to eight controls without a history of atrial fibrillation. Measurements were made at the right atrial appendage and midlateral right atrial wall at basic, 600 ms and 400 ms drive cycle lengths. In control patients, the effective refractory periods were significantly longer at the atrial appendage than the lateral wall at 600 ms (right atrial appendage 265 ms, midlateral right atrial wall 228 ms, P<0.05), and 400 ms cycle lengths (right atrial appendage 270 ms, midlateral right atrial wall 218 ms, P<0.05), but this was not evident in patients with atrial fibrillation. The monophasic action potentials and effective refractory periods at both atrial sites were shorter in the atrial fibrillation patients compared to controls; however, only the effective refractory periods at atrial appendage at 600 ms (atrial fibrillation 210 ms, controls 265 ms, P<0.001), and 400 ms cycle lengths (atrial fibrillation 200 ms, controls 270 ms, P>0.001) reached statistical significance. Effective refractory period dispersion was significantly greater in controls than in patients with atrial fibrillation (cycle length 600 ms: controls 36, atrial fibrillation 13, P=0.01; cycle length 400 ms: controls 54, atrial fibrillation 18, P<0.01). CONCLUSIONS In patients without a history of atrial fibrillation, the refractory period at the right atrial appendage is significantly longer than at the midlateral right atrial wall. This 'normal' pattern of atrial refractory dispersion is lost in patients with chronic persistent atrial fibrillation, with marked shortening of the effective refractory period at the right atrial appendage. This may explain the high risk of recurrence of atrial fibrillation following successful electrical cardioversion.
Prospective Trial of High-Dose Chemotherapy Followed by Infusions of Peripheral Blood Stem Cells and Dose-Escalated Donor Lymphocytes for Relapsed Leukemia after Allogeneic Stem Cell Transplantation

To determine whether induction of graft-versus-host disease (GVHD) improves the outcome of acute relapsed leukemia after stem cell transplantation (SCT), we used high-dose cytarabine (ara-C) followed by infusions of donor-derived buffy coats containing peripheral blood stem cells to treat 12 patients with relapsed leukemia. Donor lymphocyte infusion (DLI) was repeated at least twice over a 5-week interval for patients in whom grade II to IV acute GVHD did not develop after the first DLI. Grade II to IV acute GVHD developed in 4 (33%) of the patients. Chronic GVHD developed in 3 patients, 2 of whom had not experienced acute GVHD. Four (67%) of the 6 patients who developed grade II to IV acute and/or chronic GVHD after DLI responded, but none of the other 6 patients responded. Four (33%) of the patients (2 with acute myelogenous leukemia [AML]and 2 with acute lymphoblastic leukemia [ALL]) achieved complete remission lasting longer than 4 months after the first DLI, but 3 of them had relapses in bone sites. Of these 4 patients, 1 patient with AML and 2 with ALL were alive 8 to 27 months after DLI. These findings indicate that high-dose ara-C combined with megadose DLI may produce durable remission of acute leukemia that has relapsed after SCT when GVHD is induced. The low induction rate of GVHD and extramedullary relapse after remission is achieved with DLI are problems yet to be solved.
Exploring the Effect of Family Control on the Characteristics of SMEs in Northern Italy

We studied the effect of family control on the characteristics of small- and medium-sized enterprises located in the Northern Italian province of Bergamo. The analysis included aspects such as demographic characteristics, cost and productivity of labour, financial ratios, and the performance of 745 SMEs. Family-controlled firms emerged as a predominant organizational type in almost all the industries and a number of relevant differences were found between family-controlled and non-family firms. In sum, family-controlled firms in our sample outperformed their non-family counterparts in terms of return on sales, return on equity and return on assets.
Pharmacophore modeling for COX-1 and -2 inhibitors with LigandScout in comparison to Discovery Studio.

BACKGROUND Pharmacophore modeling has become an integrated tool in drug discovery. However, no prospective study compares the performance of the available software. METHODS The two widely used pharmacophore modeling and screening software programs Discovery Studio and LigandScout were used to generate, validate, and prospectively apply COX-1 and -2 models. Selected virtual hits were tested in cell-free enzymatic assays. The correct retrieval of active compounds was compared. RESULTS In the enzymatic testing, 10.5% of the tested hits for COX-2 and 6.6% of the predicted compounds for COX-1 were active. To directly compare the two models, both based on the same PDB entry, were selected for virtual screening. The two programs yielded vastly different hit lists, but both predicted active compounds. CONCLUSION To obtain a comprehensive selection of active compounds, more than one program should be used for modeling.
First trimester serum PAPP‐A and NGAL in the prediction of late‐onset pre‐eclampsia

Pre-eclampsia (PE) is a syndrome that complicates 3 to 5% of all pregnancies and is responsible for a high rate of maternal and fetal morbidity and mortality (Sibai et al., 2005). Placental inadequacy is considered central to the pathogenesis of the early onset (beginning at <34 weeks’ gestation) type of this syndrome (Khong et al., 1986), whereas in late-onset PE, which occurs after 34 weeks’ gestation, the placenta is usually normal with normal fetal growth (Egbor et al., 2006). Pregnancy outcome is usually better in late-onset than in early onset PE. Endothelial damage occurs in both, and it is responsible for the signs of the syndrome: hypertension and proteinuria. Early detection or prediction of PE with highly sensitive and specific markers is desirable. We have evaluated two molecules in the first trimester: neutrophil gelatinase-associated lipocalin (NGAL) and pregnancy-associated plasma protein-A (PAPP-A) that may be considered as markers of endothelium (Anwaar et al., 1998) and placental damage (Poon et al., 2009), respectively. NGAL is a 25-kDa glycoprotein initially found in granules of human neutrophils (Kjeldsen et al., 1994). Our group has recently demonstrated that second trimester serum NGAL is a reliable marker of PE in both early and late-onset forms, confirming that elevated concentrations of NGAL may be a consequence of endothelium damage (D’Anna et al., 2008). PAPP-A is produced by syncitiotrophoblast and it has been identified as a protease for insulin-like growth factor binding protein (IGFBP)-4, which plays a key role in regulating fetal growth (Constancia et al., 2002). Recent reports have demonstrated that first trimester low maternal serum levels of PAPP-A are associated with PE, particularly the early onset type (Poon et al., 2009). In this study, we have evaluated whether NGAL and PAPP-A may be useful first trimester markers in predicting PE. From a cohort of 2432 pregnant outpatients, who participated in a 2-year screening program for Down syndrome (9–11 weeks’ gestation) and who delivered in the
Treatment of low risk gestational trophoblastic disease.

Introduction Today, most patients diagnosed with gestational trophoblastic disease (GTD) will be cured. Approximately 80% of patients diagnosed with complete moles and 95% of patients diagnosed with partial moles will have been cured of their disease after evacuation without any further treatment. A small fraction of patients treated for a molar pregnancy will ultimately develop persistence of their disease and require further therapy. Until the mid 1950s, the prognosis for these patients was extraordinarily poor. Fortunately, with the identification that fetal tissue requires large amounts of folic acid to grow combined with the identification of an anti-folic acid compound, Li and associates in 1956 reported the first successful treatment of a patient diagnosed with metastatic gestational trophoblastic disease (GTD) by using methotrexate. By 1961, Hertz & Lewis reported the first series documenting the clinical utility of both methotrexate and dactinomycin in the treatment of GTD. Since that initial report, there have been extensive investigations identifying clinical factors that contribute to the likelihood of persistent disease and response to treatment. The purpose of this chapter will be to clarify the identification of patients who are considered to be at low risk and therefore eligible for less extensive therapeutic regimens. We will review the various treatment options and chemotherapeutic regimens and their respective likelihood of success.
Efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes mellitus: a meta-analysis.

BACKGROUND Obesity is closely related to type 2 diabetes mellitus, and weight reduction is an important part of the care delivered to obese persons with diabetes. The objective of this review was to assess the efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes. METHODS A systematic review of the literature was performed, and studies were included if pharmacotherapy was used as the primary strategy for weight loss among adults with type 2 diabetes. Published and unpublished studies with any design were included. A random effects model was used to combine outcomes from randomized controlled trials. RESULTS Sufficient data for the meta-analysis were available for fluoxetine, orlistat, and sibutramine. Fourteen randomized, placebo-controlled trials were included in the review, with a total of 2231 patients. Pharmacotherapy produced modest reductions in weight for fluoxetine (3.4 kg [95% confidence interval (CI), 1.7-5.2 kg] at 8-16 weeks of follow-up; 5.1 kg [95% CI, 3.3-6.9 kg] at 24-30 weeks; and 5.8 kg [ 95% CI, 0.8-10.8 kg] at 52 weeks); orlistat (2.6 kg [95% CI, 2.1-3.2 kg] [2.6% loss] at 52 weeks); and sibutramine (4.5 kg [95% CI, 1.8-7.2 kg] [3.3% loss] at up to 26 weeks). Glycated hemoglobin was also modestly reduced: fluoxetine (1.0% [95% CI, 0.4%-1.5%] at 8-16 weeks; 1.0% [95% 0.6%-1.4%] at 24-30 weeks; and 1.8% [95% CI, -0.2%-3.8%] at 52 weeks); orlistat (0.4% [95% CI, 0.3%-0.5%]); and sibutramine (0.7% [95% CI, -0.5%-1.9%]). Gastrointestinal adverse effects were common with orlistat; tremor, somnolence, and sweating with fluoxetine; and palpitations with sibutramine. CONCLUSIONS Fluoxetine, orlistat, and sibutramine can achieve statistically significant weight loss over 26 to 52 weeks. However, the magnitude of weight loss was modest, and the long-term health benefits and safety remain unclear. Interventions that combine pharmacologic therapy with intensive behavioral interventions may be more effective but need additional research.
Distinct Roles of Chromatin Insulator Proteins in Control of the Drosophila Bithorax Complex

Chromatin insulators are remarkable regulatory elements that can bring distant genomic sites together and block unscheduled enhancer–promoter communications. Insulators act via associated insulator proteins of two classes: sequence-specific DNA binding factors and “bridging” proteins. The latter are required to mediate interactions between distant insulator elements. Chromatin insulators are critical for correct expression of complex loci; however, their mode of action is poorly understood. Here, we use the Drosophila bithorax complex as a model to investigate the roles of the bridging proteins Cp190 and Mod(mdg4). The bithorax complex consists of three evolutionarily conserved homeotic genes Ubx, abd-A, and Abd-B, which specify anterior–posterior identity of the last thoracic and all abdominal segments of the fly. Looking at effects of CTCF, mod(mdg4), and Cp190 mutations on expression of the bithorax complex genes, we provide the first functional evidence that Mod(mdg4) acts in concert with the DNA binding insulator protein CTCF. We find that Mod(mdg4) and Cp190 are not redundant and may have distinct functional properties. We, for the first time, demonstrate that Cp190 is critical for correct regulation of the bithorax complex and show that Cp190 is required at an exceptionally strong Fub insulator to partition the bithorax complex into two topological domains.
ROLE MODELS, ROLE CONCEPTIONS, AND ROLE DEPRIVATION

If a profession is to direct its progress realistically, it must do so with a full knowledge of the threads of the past which it wishes to perpetuate and of those values which, while appropriate at another time or place, are ill-suited to nursing in modern society(1). A study of role conception changes and role deprivation of collegiate nurses from three California State College nursing programs following graduation and initial employment was made over a period of approximately six months. Three Likert-type scales were used to measure the respondents' loyalty to the ideals and values implied in the concepts of service, professional, and bureaucratic roles and their felt role deprivation. Findings suggested that: 1) the bureaucratic orientation of neophyte nurses increases with length of employment, 2) this increase in bureaucratic value orientation is related to a shift from a school—or professionally-centered model to a work-centered model, and 3) role deprivation is greater for subjects retaining instructor role models than for those who shift to work-centered models.
Identification of the viral sequence required for the generation of recovered avian sarcoma viruses and characterization of a series of replication-defective recovered avian sarcoma viruses

The ability of transformation-defective deletion mutants of Schmidt-Ruppin Rous sarcoma virus to induce tumors and generate recovered sarcoma viruses (rASVs) was correlated with the partial src sequences retained in the transformation-defective viral genomes. Since all the transformation-defective viruses that were capable of generating rASVs retained a portion of the 3' src sequence, regardless of the extent of the 5' src deletion, and those lacking the 3' src were unable to generate rASVs, it appears that the 3', but most likely not the 5', src sequence retained in the transformation-defective viral genome is essential for rASV formation. However, rASVs derived from a particular mutant, td109, which retained a portion of the 3' src sequence, but lacked most (if not all) of the 5' src sequence, were all found to be defective in replication. Analyses of the genomic sequences of 13 isolates of td109-derived rASVs revealed that they contained various deletions in viral envelope (env), polymerase (pol), and structural protein (gag) genes. Ten isolates of rASVs contained env deletions. One isolate (rASV3812) contained a deletion of env and the 3' half of pol, and one isolate (rASV398) contained a deletion of env and pol. The one with the most extensive deletion (rASV374) had a deletion from the p12-coding sequence through pol and env. In addition, the 5' src region of td109-derived rASVs were heterogeneous. Among the 7 isolates analyzed in detail, one isolate of rASV had a small deletion of the 5' src sequence, whereas three other isolates contained extra new sequences upstream from src. Both env- and env- pol- rASVs were capable of directing the synthesis of precursor and mature gag proteins in the infected nonproducer cells. We attribute the deletions in the replication-defective rASVs to the possibility that the 5' recombination site between the td109 and c-src sequence, involved regions of only partial homology due to lack of sufficient 5' src sequence in the td109 genome for homologous recombination. A model of recombination between the viral genome and the c-src sequence is proposed to account for the requirement of the 3' src sequence and the basis for the generation of deletions in td109-derived rASVs.
Channel-Dependent Permeation of Water and Glycerol in Mouse Morulae1

Abstract The cryosensitivity of mammalian embryos depends on the stage of development. Because permeability to water and cryoprotectants plays an important role in cryopreservation, it is plausible that the permeability is involved in the difference in the tolerance to cryopreservation among embryos at different developmental stages. In this study, we examined the permeability to water and glycerol of mouse oocytes and embryos, and tried to deduce the pathway for the movement of water and glycerol. The water permeability (LP, μm min−1 atm−1) of oocytes and four-cell embryos at 25°C was low (0.63–0.70) and its Arrhenius activation energy (Ea, kcal/mol) was high (11.6–12.3), which implies that the water permeates through the plasma membrane by simple diffusion. On the other hand, the Lp of morulae and blastocysts was quite high (3.6–4.5) and its Ea was quite low (5.1–6.3), which implies that the water moves through water channels. Aquaporin inhibitors, phloretin and p-(chloromercuri) benzene-sulfonate, reduced the Lp of morulae significantly but not that of oocytes. By immunocytochemical analysis, aquaporin 3, which transports not only water but also glycerol, was detected in the morulae but not in the oocytes. Accordingly, the glycerol permeability (PGLY, × 10−3 cm/min) of oocytes was also low (0.01) and its Ea was remarkably high (41.6), whereas PGLY of morulae was quite high (4.63) and its Ea was low (10.0). Aquaporin inhibitors reduced the PGLY of morulae significantly. In conclusion, water and glycerol appear to move across the plasma membrane mainly by simple diffusion in oocytes but by facilitated diffusion through water channel(s) including aquaporin 3 in morulae.
Comparison of media and culture techniques for detection of Streptococcus pneumoniae in respiratory secretions

We compared the relative efficacy of three methods for the isolation of Streptococcus pneumoniae in lower respiratory secretions. Based on results from 294 clinical specimens, we found that S. pneumoniae was isolated at a frequency of 65% with 5% sheep blood agar or 5% sheep blood agar containing 5 micrograms of gentamicin per ml, both incubated in 5% CO2. Anaerobic incubation of 5% sheep blood agar enhanced the recovery rate of S. pneumoniae to 93%. The improved efficacy with anaerobic incubation is due to the greater ease of recognition of the larger and more mucoid colonies of S. pneumoniae, and to the suppression of the growth of other oral bacteria present in the respiratory sections.
Airway Management in Patients With Isolated Pierre Robin Sequence During the First Year of Life

Managing the airway of patients with Pierre Robin sequence is diagnostically and therapeutically challenging. Like many other pathologies, Pierre Robin sequence is best managed with a multidisciplinary team. Providing a comprehensive evaluation is important to detect patients who may have silent events during activities of early life. Children with airway obstruction should have a complete assessment to anatomically define the site of airway obstruction. Therefore, management options can be targeted to the specific deficiency. The present article outlines a treatment protocol for patients who present with isolated Pierre Robin sequence. The authors propose that initial diagnostic and therapeutic interventions remain relatively noninvasive. Using this protocol, more than 80% of patients with isolated Pierre Robin sequence who the authors have examined for airway obstruction in the neonatal period have been effectively treated with positioning or tongue–lip adhesion. While more aggressive and successful techniques have been reported, the authors have not found them necessary for the majority of patients with isolated Pierre Robin sequence. The following review details their approach to patients with Pierre Robin sequence.
Neuropsychological evidence for a convergent route model for action

We present a detailed analysis of the relations between acting, naming, and recognising objects from vision, touch, and verbal labels, in a series of three cases. We demonstrate that: (1) there can be better “use” than gesturing of objects even in a patient with impaired semantic information for the objects; (2) this is contingent on direct proprioceptive feedback in action; and (3) there are impaired gestures to “non-action” parts of objects even when the patients can gesture to names and can identify the objects. These results are consistent with a “convergent route” model of action, which holds that direct, modality-specific associations between objects and actions constrain the retrieval of actions from semantic representations.
Prevalence of childhood asthma in Taipei, Taiwan, and other Asian Pacific countries.

UNLABELLED Two epidemiological surveys of the prevalence of bronchial asthma in schoolchildren in Taipei, Taiwan, were conducted in 1974 and 1985. The same questionnaire and school, and schoolchildren of the same age (7-15 years), were studied in these two surveys. Bronchial asthma was defined as at least three paroxysmal, recurrent attacks of wheezing and dyspnea in the previous 12 months. A total of 23,678 children were studied in 1974 and 147,373 children in 1985. Data from other Asian Pacific countries were also reviewed. THE RESULTS 1) The questionnaire was able to differentiate asthmatics from nonasthmatics on the basis of differences in methacholine challenge, intracutaneous skin testing, total eosinophil count, total serum IgE, and RAST between the two groups. 2) The prevalence of childhood asthma increased from 1.30% in 1974 to 5.07% in 1985, with boys dominating in both studies. 3) The increase in asthma prevalence could not be explained by air pollution or exposure to new allergens. 4) The prevalence of childhood asthma in the Asian Pacific countries are generally comparable to those of Western countries, and the present study and studies from Japan and New Guinea showed an increasing tendency. Thus childhood asthma is a major problem in the Asian Pacific countries as well as in Western countries.
The Effect of Innate Immunity on Autoimmune Diabetes and the Expression of Toll-Like Receptors on Pancreatic Islets1

Viral infections have previously been implicated as a trigger of autoimmune diabetes. In this study, we compared a viral mimic with other microbial components derived from bacteria in triggering diabetes development in C57BL/6-rat insulin promoter-B7.1 mice that do not normally develop diabetes. It is striking that only the viral mimic induced the development of diabetes in our model system. Further mechanistic studies suggest that diabetes is induced, in part, by the combination of direct recognition of this virus-like stimulus by pancreatic islets through the expression of the innate immune receptor, Toll-like receptor 3. In addition, the functions of APCs are up-regulated, and this could stimulate islet Ag-reactive T cells that will attack β cells leading to autoimmune diabetes.