Miracle-dz/UniFAR-FTUs huggingface dataset:
Interaction of Morphine, Fentanyl, Sufentanil, Alfentanil, and Loperamide with the Efflux Drug Transporter P-glycoprotein

Background The efflux transporter P-glycoprotein, a member of the adenosine triphosphate–binding cassette superfamily, is a major determinant of the pharmacokinetics and pharmacodynamics of the opioid loperamide, a well-recognized antidiarrheal agent. Animal studies indicate that P-glycoprotein limits morphine entry into the brain. In this study, the authors examined whether other opioids of importance to anesthesiologists such as fentanyl, sufentanil, and alfentanil, and also morphine-6-glucuronide and morphine-3-glucuronide, are P-glycoprotein substrates and whether, in turn, these opioids act also as P-glycoprotein inhibitors. Methods The transcellular movement of the various opioids, including loperamide and morphine, was assessed in L-MDR1 (expressing P-glycoprotein) and LLC-PK1 cell monolayers (P-glycoprotein expression absent). A preferential basal-to-apical versus apical-to-basal transport in the L-MDR cells but not the LLC-PK1 cells is seen for P-glycoprotein substrates. In addition, the effect of the various opioids on the transcellular movement of the prototypical P-glycoprotein substrate digoxin was examined in Caco-2 cell monolayers. IC50 values were calculated according to the Hill equation. Results Loperamide was a substrate showing high dependence on P-glycoprotein in that basal–apical transport was nearly 10-fold greater than in the apical–basal direction in L-MDRI cells. Morphine also showed a basal-to-apical gradient in the L-MDR1 cell monolayer, indicating that it too is a P-glycoprotein substrate, but with less dependence than loperamide in that only 1.5-fold greater basal–apical directional transport was observed. Fentanyl, sufentanil, and alfentanil did not behave as P-glycoprotein substrates, whereas the morphine glucuronides did not cross the cell monolayers at all, whether P-glycoprotein was present or not. Loperamide, sufentanil, fentanyl, and alfentanil inhibited P-glycoprotein–mediated digoxin transport in Caco-2 cells with IC50 values of 2.5, 4.5, 6.5, and 112 &mgr;m, respectively. Morphine and its glucuronides (20 &mgr;m) did not inhibit digoxin (5 &mgr;m) transport in Caco-2 cells, and therefore IC50 values were not determined. Conclusions Opioids have a wide spectrum of P-glycoprotein activity, acting as both substrates and inhibitors, which might contribute to their varying central nervous system–related effects.
A distinct phenotype of distal myopathy in a large Finnish family

Objectives: The authors carried out clinical, histopathologic, immunocytochemical, electrophysiologic, and imaging investigations and molecular genetic analysis in seven patients with distal myopathy belonging to a Finnish family. Results: The disease showed autosomal dominant inheritance. Age at onset ranged from 32 to 45 years. The first symptoms for referral were clumsiness with the hands and frequent stumbling from a steppage gait. Muscle weakness was characterized by early involvement of the small muscles of the hands, gluteus medium, and both anterior and posterior muscle compartments of the legs. The disease progressed to involve other intrinsic muscles of the hands, as well as the forearm muscles, triceps and infraspinatus, and proximal lower limbs. Asymmetry of muscle involvement was common. EMG showed myopathic features, serum CK was normal or slightly elevated, and muscle biopsy showed many rimmed vacuoles and dystrophic changes. There was no evidence of linkage to Welander distal myopathy or tibial muscular dystrophy loci. Conclusion: These patients may have a distinct distal myopathy. Genome-wide scan is undertaken in order to identify the disease locus.
Lactogenesis After Early Postpartum Use of the Contraceptive Implant: A Randomized Controlled Trial

OBJECTIVE: To evaluate lactogenesis after early postpartum insertion of the etonogestrel contraceptive implant. METHODS: Healthy peripartum women with healthy, term newborns who desired the etonogestrel implant for contraception were randomly assigned to early (1–3 days) or standard (4–8 weeks) postpartum insertion. The primary outcomes, time to lactogenesis stage II and lactation failure, were documented by a validated measure. The noninferiority margin for the mean difference in time to lactogenesis stage II was defined as 8 additional hours. Secondary data (device continuation and contraceptive use, breast milk analysis, supplementation rates, side effects, and bleeding patterns) were collected at periodic intervals for 6 months. RESULTS: Sixty-nine women were enrolled. Thirty-five were randomly assigned to early insertion and 34 to standard insertion. There were no statistically significant differences between the groups in age, race, parity, mode of delivery, use of anesthesia, or prior breastfeeding experience. Early insertion was demonstrated to be noninferior to standard insertion in time to lactogenesis stage II (early: [mean±standard deviation] 64.3±19.6 hours; standard: 65.2±18.5 hours, mean difference, −1.4 hours, 95% confidence interval [CI] −10.6 to 7.7 hours). Early insertion was also demonstrated to be noninferior to standard insertion in incidence of lactation failure (1/34 [3%] in the early insertion group, 0/35 [0%] in the standard insertion group [risk difference, 0.03, 95% CI −0.02 to 0.08]). Use of formula supplementation was not significantly different between the groups. Milk composition at 6 weeks was not significantly different between the groups. CONCLUSION: Breastfeeding outcomes were similar in women who underwent early compared with standard postpartum insertion of the etonogestrel implant. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials. gov, NCT00847587. LEVEL OF EVIDENCE: I
The cytostome–cytopharynx complex of Trypanosoma cruzi epimastigotes disassembles during cell division

ABSTRACT The cytostome–cytopharynx complex is the main site for endocytosis in epimastigotes of Trypanosoma cruzi. It consists of an opening at the plasma membrane surface – the cytostome – followed by a membrane invagination – the cytopharynx. In G1/S cells, this structure is associated with two specific sets of microtubules, a quartet and a triplet. Here, we used electron microscopy and electron tomography to build 3D models of the complex at different stages of the cell cycle. The cytostome–cytopharynx is absent in late G2 and M phase cells, whereas early G2 cells have either a short cytopharynx or no visible complex, with numerous vesicles aligned to the cytostome–cytopharynx microtubules. The microtubule quartet remains visible throughout cell division (albeit in a shorter form), and is duplicated during G2/M. In contrast, the microtubule triplet is absent during late G2/M. Cells in cytokinesis have an invagination of the flagellar pocket membrane likely to represent early stages in cytostome–cytopharynx assembly. Cells in late cytokinesis have two fully developed cytostome–cytopharynx complexes. Our data suggest that the microtubule quartet serves as a guide for new cytostome–cytopharynx assembly. Summary: As shown by focused ion beam scanning electron microscopy, the cytostome–cytopharynx complex of T. cruzi epimastigotes disassembles in mitosis, to assemble again in each daughter cell at the end of cell division.
What do returns to acquiring firms tell us? Evidence from firms that make many acquisitions

We study shareholder returns for firms that acquired five or more public, private, and/or subsidiary targets within a short time period. Since the same bidder chooses different types of targets and methods of payment, any variation in returns must be due to the characteristics of the target and the bid. Results indicate bidder shareholders gain when buying a private firm or subsidiary but lose when purchasing a public firm. Further, the return is greater the larger the target and if the bidder offers stock. These results are consistent with a liquidity discount, and tax and control effects in this market.
Effect of Chronic Blockade of the Kallikrein-Kinin System on the Development of Hypertension in Rats

The kallikrein-kininogen-kinin system is an important vasodilator and vasodepressor component of the cardiovascular system. Acting mainly through B2 receptors, kinins may counterbalance the pressor effect of angiotensin II, salt, and mineralocorticoids plus salt. Using rats lacking the bradykinin precursors low- and high-molecular-weight kininogen or a B2 kinin receptor antagonist (icatibant), we investigated whether absence or blockade of the kallikrein-kinin system alters blood pressure (BP) in rats given (1) chronic infusion of Ang II, (2) a normal or high salt diet, or (3) chronic administration of deoxycorticosterone acetate (DOCA) plus salt. We confirmed the genotype and phenotype of Brown Norway Katholiek rats (BNK) and found that they had a G-to-A point mutation on the kininogen gene compared with Brown Norway (BN) and Sprague-Dawley (SD) rats, very low levels of high-molecular-weight kininogen (17±3 ng/mL) compared with BN and SD (1814±253 and 2397±302 ng/mL, respectively;P <0.01), and plasma low-molecular-weight kininogen concentrations below detectable limits compared with 1773±74 and 1781±140 ng/mL for BN and SD, respectively. Basal BP was the same in BNK and BN. Chronic infusion of icatibant did not alter BP in BN or Wistar rats. At doses that blocked the acute effect of bradykinin, icatibant did not potentiate the pressor effect of a chronic subpressor or pressor dose of angiotensin II in male and female Wistar rats nor that of a high salt diet (2%) plus unilateral nephrectomy in male Wistar rats. Moreover, blockade of the kallikrein-kininogen-kinin system in either BN rats given a very high dose of icatibant or kinin-deficient rats (BNK) did not potentiate the pressor effect of angiotensin II (nonpressor dose) or a high salt (3% NaCl) diet given for 2 weeks. Established DOCA-salt hypertension was not exaggerated in rats treated with icatibant but was partially attenuated by ramipril (1.5 mg · kg−1 · d−1 for 7 days;P <0.002). This antihypertensive effect was abolished by icatibant (P <0.002, ramipril versus ramipril plus icatibant). These results suggest that endogenous kinins do not participate in the maintenance of normal blood pressure or antagonize the development of hypertension induced by chronic infusion of angiotensin II, a high salt diet, or DOCA-salt. However, kinins appear to play an important role in the antihypertensive effect of angiotensin-converting enzyme inhibitors in DOCA-salt hypertension.
Access to Quality Health Services for All South Africans through the National Health Insurance Scheme: Lessons from Singapore

The South African health system both in the public and private sectors is fraught with many challenges which render the system unsustainable, costly, hospi-centric, and destructive. In order to curb this loop hole in the health sector, South Africa introduced the National Health Insurance (NHI) that is aimed at providing universal coverage of health care. The objectives of NHI is to provide improved access to quality health services for all South Africans irrespective of whether they are employed or not; to pool risks and funds so that equity and social solidarity will be achieved through the creation of a single fund, to procure services on behalf of the entire population and efficiently mobilize and control key financial resources and to strengthen the under-resourced and strained public sector so as to improve health systems performance. This paper evaluates the Reconstruction and Development Programme (RDP), Growth, Employment and Redistribution (GER), New Growth Path (NGP) and National Development Plan (NDP) policies to determine the challenges and positive aspects of these policies that can be used for the successful implementation of the NHI. The paper further draws lessons from Singapore that has already implemented the NHI and argues that South Africa can learn a lot from these countries experiences. It is concluded that each of the countries provide inspiring positive lessons and also show areas of challenges from which South Africa can draw some lessons. DOI: 10.5901/mjss.2014. v5n23p2722
Deconstructing the Tower of London: Alternative moves and conflict resolution as predictors of task performance

Despite widespread use the cognitive demands of the five-disc Tower of London (TOL) are unknown. Research suggests that conflict moves (those that are essential to the solution but do not place a disc in its final position) are a key aspect of performance. These were examined in three studies via a verification paradigm, in which normal participants were asked to decide whether a demonstrated move was correct. Experiment 1 showed that individual move latencies increase with the number of intermediate moves until the disc is placed in its goal position (resolution). Post hoc tests suggested that the number of alternative moves and moves to resolve a disc were independent predictors of performance. Experiment 2 successfully manipulated these factors in an experimental design. Experiment 3 showed that they remain determinants of performance as familiarity increased. Overall, errors on the task were significantly correlated with spatial memory. The implications of these findings for the use of the TOL in cognitive psychology and as an assessment tool are discussed.
Female voice communications in high levels of aircraft cockpit noises--Part I: spectra, levels, and microphones.

HYPOTHESIS Female produced speech, although more intelligible than male speech in some noise spectra, may be more vulnerable to degradation by high levels of some military aircraft cockpit noises. The acoustic features of female speech are higher in frequency, lower in power, and appear more susceptible than male speech to masking by some of these military noises. Current military aircraft voice communication systems were optimized for the male voice and may not adequately accommodate the female voice in these high level noises. METHODS This applied study investigated the intelligibility of female and male speech produced in the noise spectra of four military aircraft cockpits at levels ranging from 95 dB to 115 dB. The experimental subjects used standard flight helmets and headsets, noise-canceling microphones, and military aircraft voice communications systems during the measurements. RESULTS The intelligibility of female speech was lower than that of male speech for all experimental conditions; however, differences were small and insignificant except at the highest levels of the cockpit noises. Intelligibility for both genders varied with aircraft noise spectrum and level. Speech intelligibility of both genders was acceptable during normal cruise noises of all four aircraft, but improvements are required in the higher levels of noise created during aircraft maximum operating conditions. CONCLUSIONS The intelligibility of female speech was unacceptable at the highest measured noise level of 115 dB and may constitute a problem for other military aviators. The intelligibility degradation due to the noise can be neutralized by use of an available, improved noise-canceling microphone, by the application of current active noise reduction technology to the personal communication equipment, and by the development of a voice communications system to accommodate the speech produced by both female and male aviators.
New results on Construction A lattices based on very sparse parity-check matrices

We address the problem of transmission of information over the AWGN channel using lattices. In particular, we will deal with previously introduced LDA lattices which are obtained by Construction A from LDPC codes over the finite field Fp. We will show how to build a particular ensemble of LDA lattices related to bipartite graphs with good expansion properties. We investigate the quality of this family under lattice decoding and show that a random member in it can be reliably decoded for any value of the channel noise variance up to Poltyrev limit. Values of p and the parameters for which optimal performance is guaranteed under lattice decoding are in accordance with the optimal parameters found experimentally under iterative decoding.
3-Hydroxy-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-4-ium chloride dihydrate: (+)-vasicinol hydrochloride dihydrate from Peganum harmala L

The title compound, C11H13N2O+·Cl−·2H2O, the dihydrate of (+)-vasicinol hydrochloride, is a pyrrolidinoquinazoline alkaloid. It was isolated from the ethyl acetate fraction of the leaves of Peganum harmala L. The pyrrolidine ring has an envelope conformation with the C atom at position 2 acting as the flap and the C atom at position 3, carrying the hydroxyl substituent, has an S configuration. The absolute configuration was determined as a result of the anomalous scattering of the Cl atom. In the crystal structure, molecules stack along the a axis, connected to one another via intermolecular O—H⋯Cl and N—H⋯Cl hydrogen bonds, forming approximately triangular-shaped R 2 1(7) rings, and O—H⋯Cl and O—H⋯O hydrogen bonds, forming pentagonal-shaped R 5 4(10) rings. The overall effect is a ribbon-like arrangement running parallel to the a axis.
Quality of Life, Physical Diseases, and Psychological Impairment among Survivors 3 Years after Wenchuan Earthquake: A Population Based Survey

Background Few research studies have addressed the long-term effects caused by catastrophes, and no study has ever explored the life quality, physical diseases, and psychological impairment of earthquake survivors at the same time. This study seeks to reveal survivors' quality of life, physical diseases, and mental health. Methods A cross-sectional survey was conducted through multi-stage sampling approach three years after the Wenchuan earthquake. Results A total of 2525 subjects were interviewed. Symptoms of PTSD were reported by 8.8% of the respondents from the seriously affected areas and 0.5%, the less hit areas. Prevalence of chronic diseases was 39.2% and 22.1% respectively, and two-week prevalence rate, 24.9% and 12.7% respectively. In the multivariate analysis, two-week prevalence, displacement, no regular income, receiving mental health support after the disaster, family members died or missing, injured due to the quake, and person who witnessed someone being killed or injured were independently associated with higher prevalence for symptoms of PTSD. Most subscales of SF-12 negatively correlated with age, chronic diseases, two-week prevalence, injured due to the disaster, home or property loss, and score of the 3-year PTSD symptoms, but positively correlated with higher education and higher household income. Conclusions The rates of physical diseases and symptoms of PTSD were relatively high, and the quality of life was poor among victims in the hard-hit areas 3 years after the earthquake. Physical impairment correlated with symptom of PTSD, and both were negatively associated with quality of life.
Sequence analysis of myostatin promoter in cattle

Myostatin (GDF8) acts as a negative regulator of muscle growth. Mutations in the gene are responsible for the double muscling phenotype in several European cattle breeds. Here we describe the sequence of the upstream 5′ region of the myostatin gene. The sequence analysis was carried out on three animals of nine European cattle breeds, with the aim to search for polymorphisms. A T/A polymorphism at –371 and a G/C polymorphism at –805 (relative to ATG) were found. PCR- RFLP was used to further screen 353 animals of the nine breeds studied and to assess the frequencies of the SNPs. The promoter region of the gene contains several binding sites for transcription factors found also in other myogenic genes. This may play an important role in the regulation of the protein and consequently on muscular development.
Interaction between Staphylococcus aureus and Pseudomonas aeruginosa is beneficial for colonisation and pathogenicity in a mixed biofilm

Debate regarding the co-existence of Staphylococcus aureus and Pseudomonas aeruginosa in wounds remains contentious, with the dominant hypothesis describing a situation akin to niche partitioning, whereby both microorganisms are present but occupy distinct regions of the wound without interacting. In contrast, we hypothesised that these microorganisms do interact during early co-colonisation in a manner beneficial to both bacteria. We assessed competitive interaction between S. aureus and P. aeruginosa in biofilm cultured for 24-72 h and bacterial aggregates analogous to those observed in early (<24 h) biofilm formation, and interaction with human keratinocytes. We observed that S. aureus predominated in biofilm and non-attached bacterial aggregates, acting as a pioneer for the attachment of P. aeruginosa. We report for the first time that S. aureus mediates a significant (P < 0.05) increase in the attachment of P. aeruginosa to human keratinocytes, and that P. aeruginosa promotes an invasive phenotype in S. aureus. We show that co-infected keratinocytes exhibit an intermediate inflammatory response concurrent with impaired wound closure that is in keeping with a sustained proinflammatory response which allows for persistent microbial colonisation. These studies demonstrate that, contrary to the dominant hypothesis, interactions between S. aureus and P. aeruginosa may be an important factor for both colonisation and pathogenicity in the chronic infected wound.
Grass Species and Endophyte Effects on Survival and Development of Fall Armyworm (Lepidoptera: Noctuidae)

Abstract Grass selections including 10 zoysiagrasses, 18 paspalums, 34 Bermuda grasses, tall fescue, creeping red fescue, and perennial ryegrasses with and without endophyte were evaluated for potential resistance to fall armyworm, Spodoptera frugiperda (J. E. Smith), larvae. Laboratory evaluations assessed the degree of antibiosis among >70 grass lines to first-instar fall armyworms. When all parameters measured were considered, the trend in resistance to fall armyworm among endophyte-infected (E+) and endophyte-free (E-) cool season grasses from greatest to least was: ‘Dawson’ E+ > APR 1234 > ‘Dawson’ E- > ‘Rosalin’ E+ > Lp 5425, ‘Rosalin’ E-, ATF 480 > ‘Tulsa’ or: E+ slender creeping red fescue > E+ turf- type perennial ryegrass > E- slender creeping red fescue > E+ forage-type perennial ryegrass > E- forage-type perennial ryegrasses, and E+ tall fescue > E- turf-type tall fescue. Among warm season grasses larval weight gain was reduced on all zoysiagrasses. Larval weight gain also was lower on the Bermuda grasses ‘Tifsport’, ‘Tifgreen’, 97–4, 97–14, 97–22, 97–28, 97–39, 97–40, 97–54, 98–15, 98–30, and 98–45 than when larvae were fed ‘Tulsa’ tall fescue or the diet control. Only APR1234 and ‘Dawson’ creeping red fescue reduced larval survival to the same extent that was observed for zoysiagrasses. Survival on Bermuda grasses was least on 97–8. Seashore paspalums were only rarely less susceptible to fall armyworm than tall fescue, although pupal weights were consistently lower on ‘Temple 1’ and ‘Sea Isle 1’ paspalums than that on ‘Tulsa’ tall fescue. Genetic resistance to key grass pests can reduce insecticide use and simplify management of these cultivars.