Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics and Pharmacodynamics of Combined use of Lopinavir/Ritonavir and Rosuvastatin in HIV-Infected Patients

Background Lopinavir/ritonavir-containing antiretro-viral therapy can cause hyperlipidaemia. However, most statins are contraindicated due to drug-drug interactions. Rosuvastatin undergoes minimal metabolism by CYP450, so no CYP450-based interaction with lopinavir/ritonavir is expected. This study explored the lipid-lowering effect of rosuvastatin and assessed the effect of lopinavir/ritonavir on the pharmacokinetics of rosuvastatin and vice versa. Methods HIV-infected patients on lopinavir/ritonavir (viral load <400 copies/ml) with total cholesterol (TC) >6.2 mmol/l were treated with rosuvastatin for 12 weeks, starting on 10 mg once daily. If fasting target values (TC<5.0 mmol/l, high-density lipoprotein-cholesterol >1.0 mmol/l, low-density lipoprotein-cholesterol [LDL-c] <2.6 mmol/l and triglycerides <2.0 mmol/l) were not reached, rosuvastatin was escalated to 20 mg or 40 mg at week 4 and 8, respectively. Plasma lopinavir/ritonavir trough levels (Cmin) were determined at week 0, 4, 8 and 12 and rosuvastatin Cmin, at week 4, 8 and 12. Results Twenty-two patients completed the study. Mean reductions in TC and LDL-c from baseline to week 4 (on rosuvastatin 10 mg once a day) were 27.6% and 31.8%, respectively. Lopinavir/ritonavir concentrations were not influenced by rosuvastatin (P=0.44 and 0.26, repeated-measures analysis). Median (interquartile range) rosuvastatin Cmin for 10 mg, 20 mg and 40 mg once daily were 0.97 (0.70–1.5), 2.5 (1.3–3.3) and 5.5 (3.3–8.8) ng/ml, respectively. Conclusions Rosuvastatin appeared to be an effective statin in hyperlipidaemic HIV-infected patients. Lopinavir/ritonavir levels were not affected by rosuvastatin, but rosuvastatin levels unexpectedly appeared to be increased 1.6-fold compared with data from healthy volunteers. Until safety and efficacy have been confirmed in larger studies, the combination of rosuvastatin and lopinavir/ritonavir should be used with caution.
Leakage characteristics of substrate integrated waveguide with parallel metallic plates

The leakage characteristics of the substrate integrated waveguide are presented. The numerical method based on the hybrid generalized scattering matrix (GSM) is successfully validated by using the published measured data of the SIW designs in Ku- and Ka-bands. The new structural parameters of the SIW, including the thickness of the periodical metal wall, and the width of the extended parallel metallic plates are reported. The theoretical extractions show that the thickness of the metal wall seriously affects the cutoff frequency of the SIW. The additional metallic plate can induce additional leakage when the SIW is in the fast-wave region.
Dr. Wouter Basson, Americans, and Wild Beasts: Men's Conspiracy Theories of HIV/AIDS in the South African Lowveld

ABSTRACT This article investigates HIV/AIDS as a cosmological problem among Northern Sotho and Tsonga-speakers in the South African lowveld. Based on in-depth interviews with 70 informants (35 men and 35 women) I show how the attribution of blame for HIV/AIDS articulates gendered concerns. I suggest that women blamed men and envious nurses for spreading the virus and that these discourses expressed women's ideological association with the domestic domain. By contrast, men invoked conspiracy theories, blaming translocal agents—such as Dr. Wouter Basson, Americans, soldiers, and governments—for the pandemic. I suggest that these theories are informed by men's humiliating experiences of job losses and deindustrialization in the global labour market. My discussion highlights the need for HIV/AIDS interventions in order to address not only women's oppression but also men's gendered concerns.
ALPHA AND BETA ADRENERGIC RECEPTOR MECHANISMS IN THE SYSTEMIC VENOUS BED.

The effects of isoproterenol, phenylephrine, and norepinephrine were studied in an experimental canine preparation in which cardio-pulmonary bypass permitted exclusion of the heart and lungs, and allowed continuous measurement of alterations of intravascular blood volume. In all experiments the beta adrenergic receptor stimulator, isoproterenol, resulted in a decrease in systemic vascular blood volume, similar to that observed with the alpha receptor stimulating agents, phenylephrine and norepinephrine. By the use of appropriate adrenergic blocking agents, it was demonstrated that the systemic venous bed contains both beta and alpha adrenergic receptors. Thus, in contrast to the opposing actions of these receptors in the arterial bed, stimulation of either alpha or beta receptors produces venoconstriction.
Morphological Evolution and Systematics of Synthyris and Besseya (Veronicaceae): A Phylogenetic Analysis

Abstract Phylogenetic analyses are used to examine the morphological diversity and systematics of Synthyris and Besseya. The placement of Synthyris and Besseya in Veronicaceae is strongly supported in parsimony analyses of nuclear ribosomal ITS DNA sequences. Parsimony and maximum likelihood (ML) criteria provide consistent hypotheses of clades of Synthyris and Besseya based on the ITS data. The combination of morphological characters and ITS data resolve additional clades of Synthyris and Besseya. The results show that Synthyris is paraphyletic to Besseya. In the monophyletic Synthyris clade, Besseya forms part of a Northwest clade that also includes the alpine S. canbyi, S. dissecta, and S. lanuginosa and mesic forest S. cordata, S. reniformis, S. platycarpa, and S. schizantha. The Northwest clade is the sister of S. borealis. An Intermountain clade, comprising S. ranunculina, S. laciniata, S. pinnatifida, and S. missurica, is the sister to the rest of the Synthyris clade. Constraint topologies are used to test prior hypotheses of relationships and morphological similarities. Parametric bootstrapping is used to compare the likelihood values of the best trees obtained in searches under constraints to that of the best tree found without constraints. These results indicate that topologies in which a monophyletic Synthyris is the sister of Besseya are significantly worse than the best ML tree in which Synthyris is paraphyletic to Besseya. Similarly, forcing either the monophyly of all taxa that have deeply incised leaf margins or those that have reniform laminas and broadly rounded apices results in trees that are significantly worse than the best ML tree, in which leaf margin incision and reniform laminas are homoplastic. We propose a new classification for Synthyris that emphasizes monophyletic groups. The new combination Synthyris oblongifolia is proposed.
Society and housing form: home-centredness in England vs. family-centredness in Japan.

This paper demonstrates some of the ways in which culture affects house form by considering the premise that increased privatised living leads to increased demarcation of private living space. Historical data from England and Japan make it evident that Japanese privatised living was family-centred as compared with English home-centredness, and was reflected in observable differences in the evolution of house forms. While supporting the premise that cultural values influence house forms, the paper concludes that the original framework is too simple, but can be developed to accommodate data from different cultures.
Population and economic impact of the 2013 ACC/AHA guidelines compared with European guidelines to prevent cardiovascular disease.

Recently, the American College of Cardiology (ACC) and the American Heart Association (AHA) issued new guidelines on management of cardiovascular (CV) risk in primary prevention.1 They developed a new CV risk calculator [new pooled cohort atherosclerotic CV disease (CVD) risk equation] targeting individuals between 40 and 75 years and based on four American population-based cohorts.2,3 Statin treatment is recommended for individuals with an estimated 10-year risk of CVD ≥7.5%, including stroke. Conversely, the guidelines of the European Society of Cardiology (ESC) advocate the use of the SCORE equation for individuals aged between 40 and 65 years, and initiation of a statin treatment is recommended if the estimated 10-year risk of death from CVD is ≥5%. 4 Whether applying the ACC/AHA guidelines has similar public health consequences as applying the ESC guidelines …
Thalamic sensitization transforms localized pain into widespread allodynia

Focal somatic pain can evolve into widespread hypersensitivity to nonpainful and painful skin stimuli (allodynia and hyperalgesia, respectively). We hypothesized that transformation of headache into whole‐body allodynia/hyperalgesia during a migraine attack is mediated by sensitization of thalamic neurons that process converging sensory impulses from the cranial meninges and extracephalic skin.
Salient features of Haemophilus vaginalis

A total of 78 strains of Haemophilus vaginalis were examined for 104 features. All strains fermented dextrin, maltose, and starch. Additionally, more than 90% of the strains fermented galactose, glucose, and ribose. Arbutin, cellobiose, melibiose, rhamnose, and salicin were not fermented by any of these strains. None of the strains acidified any of 14 alcohols or alkalinized any of 25 organic salts and amides. More than 90% of the strains hemolyzed human blood agar and hydrolyzed hippurate. No strain hemolyzed sheep blood agar. A recommendation is included for those minimal features that best differentiate H. vaginalis from other oxidase- and catalase-negative, gram-negative organisms.
Human lung macrophage-derived histamine-releasing activity is due to IgE-dependent factors.

Human lung macrophages obtained from surgical specimens spontaneously secreted a factor(s) (which we term macrophage factor) during 24-hr culture that induced calcium-dependent histamine release from human basophils and lung mast cells. Macrophage factor induced noncytotoxic histamine release from purified (85%) basophils. The kinetics of release were relatively slow and similar to that of anti-IgE. We performed a series of experiments to test the IgE dependence of macrophage factor-induced release. Preincubation of basophils with anti-IgE in calcium-free medium resulted in complete desensitization to macrophage factor-induced histamine release (i.e., when calcium and macrophage factor were added to the basophils, no histamine release occurred), and preincubation with macrophage factor in calcium-free medium resulted in partial desensitization to anti-IgE-induced histamine release. Pretreatment of basophils with pH 3.9 lactic acid buffer, which dissociates basophil IgE from its receptors, markedly reduced the capacity of basophils to release histamine in response to macrophage factor. Basophils that were incubated with IgE myeloma (but not with IgG) after lactic acid treatment partially or completely regained their capacity to release histamine in response to macrophage factor. Fluid-phase IgE myeloma (15 micrograms/ml) (but not IgG) inhibited basophil histamine release induced by two macrophage-derived supernatants, whereas IgE myeloma (200 micrograms/ml) did not inhibit release due to other supernatants. IgE-affinity columns removed the histamine-releasing activity of five macrophage-derived supernatants, and IgG-affinity columns had similar effects. However, neither affinity column removed the histamine-releasing activity of three other macrophage-derived supernatants. On Sephadex G-75 chromatography, nearly all of the histamine-releasing activity migrated as single peak with an apparent m.w. of 18,000. These results suggest that, although macrophage factor are heterogeneous, they are related, as they are a IgE-dependent factors that induce histamine release by interacting with cell surface IgE. These macrophage factors may be responsible for stimulation of basophil/mast cell mediator release in chronic allergic reactions.
Hong Kong Hospital Authority resource efficiency evaluation: Via a novel DEA-Malmquist model and Tobit regression model

The Hospital Authority (HA) is a statutory body managing all the public hospitals and institutes in Hong Kong (HK). In recent decades, Hong Kong Hospital Authority (HKHA) has been making efforts to improve the healthcare services, but there still exist some problems like unfair resource allocation and poor management, as reported by the Hong Kong medical legislative committee. One critical consequence of these problems is low healthcare efficiency of hospitals, leading to low satisfaction among patients. Moreover, HKHA also suffers from the conflict between limited resource and growing demand. An effective evaluation of HA is important for resource planning and healthcare decision making. In this paper, we propose a two-phase method to evaluate HA efficiency for reducing healthcare expenditure and improving healthcare service. Specifically, in Phase I, we measure the HKHA efficiency changes from 2000 to 2013 by applying a novel DEA-Malmquist index with undesirable factors. In Phase II, we further explore the impact of some exogenous factors (e.g., population density) on HKHA efficiency by Tobit regression model. Empirical results show that there are significant differences between the efficiencies of different hospitals and clusters. In particular, it is found that the public hospital serving in a richer district has a relatively lower efficiency. To a certain extent, this reflects the socioeconomic reality in HK that people with better economic condition prefers receiving higher quality service from the private hospitals.
Database for exchangeable gene trap clones: Pathway and gene ontology analysis of exchangeable gene trap clone mouse lines

Gene trapping in embryonic stem (ES) cells is a proven method for large‐scale random insertional mutagenesis in the mouse genome. We have established an exchangeable gene trap system, in which a reporter gene can be exchanged for any other DNA of interest through Cre/mutant lox‐mediated recombination. We isolated trap clones, analyzed trapped genes, and constructed the database for Exchangeable Gene Trap Clones (EGTC) [http://egtc.jp]. The number of registered ES cell lines was 1162 on 31 August 2013. We also established 454 mouse lines from trap ES clones and deposited them in the mouse embryo bank at the Center for Animal Resources and Development, Kumamoto University, Japan. The EGTC database is the most extensive academic resource for gene‐trap mouse lines. Because we used a promoter‐trap strategy, all trapped genes were expressed in ES cells. To understand the general characteristics of the trapped genes in the EGTC library, we used Kyoto Encyclopedia of Genes and Genomes (KEGG) for pathway analysis and found that the EGTC ES clones covered a broad range of pathways. We also used Gene Ontology (GO) classification data provided by Mouse Genome Informatics (MGI) to compare the functional distribution of genes in each GO term between trapped genes in the EGTC mouse lines and total genes annotated in MGI. We found the functional distributions for the trapped genes in the EGTC mouse lines and for the RefSeq genes for the whole mouse genome were similar, indicating that the EGTC mouse lines had trapped a wide range of mouse genes.
European Comparison of Costs and Quality in the Treatment of Acute Back Pain

Study Design. Retrospective multicenter observational study. Objectives. To compare the outpatient quality and costs of treating acute back pain in England, Germany, the Netherlands, and Switzerland. Summary of Background Data. No study has yet attempted to compare the quality, costs, and resource utilization of acute back pain treatment in Europe. Methods. A total of 130 randomly selected physician practices assessed services for 1 hypothetical average patient during the first 4 weeks of treatment (cost evaluation) and 127 practices reported retrospective data on 1 real patient (quality evaluation) in 2001. Reimbursement fees served as unit costs for Germany and Switzerland. Average reimbursement fees were used to measure resource utilization in all countries. Quality of care was assessed in terms of the following unnecessary treatments and diagnoses: bed rest for more than 2 days; exercise therapy; scheduling of a radiograph or other imaging tests; and referral to another provider. Responses were weighted with the level of scientific evidence for overuse. Results. Weighted-average overuse ranged from 18% in the Netherlands to 31% in Germany. In England, Germany, and Switzerland, at least a third of the resources used to treat back pain were wasted. Conclusions. There was considerable waste in treating acute back pain. The Netherlands had highest quality and lowest resource utilization in providing treatment for acute back pain.
In vivo metabolism of apolipoproteins A-IV and A-I associated with high density lipoprotein in normolipidemic subjects.

The kinetics of apolipoprotein A-IV associated with high density lipoproteins (HDL) of plasma from fasting human subjects was followed for 15 days in five healthy normolipidemic volunteers. Purified apoA-IV and apoA-I were radioiodinated, respectively, with 125I and 131I, incubated in vitro with normal HDL, isolated at density 1.250 g/ml, and finally reinjected intravenously as HDL-125I-labeled apoA-IV and HDL-131I-labeled apoA-I. Blood samples were withdrawn at regular intervals for 15 days, and 24-h urine samples were collected. More than 93% (93.5 +/- 0.9%) of apoA-IV was recovered in apoA-I-containing lipoprotein particles after affinity chromatography on an anti-apoA-I column and 69.7 +/- 4.8% was bound to apoA-II in apoA-I:A-II particles separated on an anti-apoA-II column. 125I-labeled apoA-IV showed a much faster decay than 131I-labeled apoA-I for the first 5 days and thereafter the curves became parallel. Urinary/plasma ratios (U/P) for the 125I-labeled parallel. Urinary/plasma ratios (U/P) for the 125I-labeled apoA-IV were much higher than those for 131I-labeled apoA-I for the first days, but the U/P curves became parallel for the last 7 days, suggesting heterogeneity of apoA-IV metabolism. A heterogeneous multicompartmental model was constructed to describe the metabolism of lipoprotein particles containing apoA-IV and apoA-I and to calculate the kinetic parameters, fitting simultaneously all plasma and urine data for both tracers. (ABSTRACT TRUNCATED AT 250 WORDS)
Resumption of estrogen-induced gonadotropin surges in postpartum monkeys.

To evaluate the functional integrity of the hypothalamic-pituitary (H-P) system in postgestational monkeys, peripheral serum concentrations of LH and FSH were determined in postpartum (nursing and nonnursing) and postabortion (midpregnancy) females challenged with estradiol benzoate (EB) at a dose known to be effective in eliciting gonadotropin surges in cycling monkeys. In a longitudinal study of nursing and nonnursing postpartum mothers and postabortion females, EB was administered serially during weeks 1, 3, 5, 7, 9, and 11 post delivery. Some nursing monkeys were challenged with EB up to 6 months post partum. In a cross-sectional study of nursing mothers, this response to EB was evaluated during weeks 1, 3, 5, 7, and 9 postpartum. H-P responsivity to EB was impaired in nursing monkeys through 180 days post partum, in that FSH or LH surges were not induced by estrogen therapy. In contrast, nonnursing postpartum mothers and postabortion females regained their sensitivity to this positive feedback action.
Ravenstein and the “ laws of migration ”

E. G. Ravenstein’s three articles on migration, the tirst published one hundred years ago, form the basis for most modern research on migration; if the three articles are collated, his “laws” or perhaps more accurately, hypotheses, total eleven. This article considers, briefly, Ravenstein’s career, the sources on which his “laws” were based and some of the difficulties of interpreting the British Census place of birth data. The bulk of the article reviews subsequent work on his eleven hypotheses with reference to nineteenth-century British internal migration. Subsequent work has confirmed that migration was mainly short distance and that there was relatively little increase in the average distance travelled by migrants until after 1850. His step-by-step hypothesis remains untested, but his belief that most migration was from the countryside to the towns is contirmed as is his identification of counter currents. His ideas on sex and age differentials have been borne out. However, his assumptions about the relative importance of natural increase and migration in the growth of cities and the relative importance of “push” and “pull” factors in causing migration merit further research. His original hypotheses have for the most part been confirmed. However, the defects of the published data suggest that nineteenth-century migration will not be properly understood until the enumerators’ schedules for the century have been analysed.
Apoptosis and leukaemia

Defects in the intrinsic ability of haematopoietic progenitor cells to undergo apoptosis may allow the cell to acquire further mutations, survive inappropriately and eventually become malignant. Additionally, this defect could account for the resistance to cell death, observed in leukaemic cells, following treatment with chemotherapy. This review discusses some of the molecules known to influence apoptosis in leukaemic cells, particularly the novel fusion proteins produced as a result of leukaemia‐associated chromosomal translocations. The ultimate aim of understanding how apoptosis is altered in leukaemia cells is so that the process can be modulated to overcome resistance to chemotherapy and improve clinical outcomes. The relationship of leukaemia‐related fusion proteins such as PML‐RARα, BCR‐ABL, E2A‐HLF, AML1‐ETO and the various MLL fusions to the biochemical pathways involved in apoptosis are discussed as well as the consequences for therapeutic applications.
Minocycline and Other Tetracycline Derivatives: A Neuroprotective Strategy in Parkinson's Disease and Huntington's Disease

Remarkable progress has been made during the past decade in our understanding of mechanisms of cell death in neurodegenerative disorders such as Parkinson’s disease (PD), Huntington’s disease (HD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS). These findings provide evidence that cell death in neurodegenerative diseases involves complex mechanisms leading to abnormal processing and accumulation of mutant or damaged proteins. Dysfunction of the ubiquitin–proteasomal pathway, coupled with increased oxidative stress, mitochondrial dysfunction, excitotoxicity, and inflammation, has been suggested to lead to protein aggregation and formation of inclusions, eventually resulting in cell death via apoptosis or necrosis (1–4). Several neuroprotective treatments aimed at reducing oxidative stress (antioxidants) have been tried without much success for patients with PD and HD. Therapies targeted against the inflammatory and apoptotic mechanisms may prove to be more effective in slowing the neurodegenerative process. Tetracycline and its derivatives, especially minocycline (MC), are a group of semisynthetic antibiotic agents that, in addition to their antiinflammatory and antimicrobial properties, interfere with activation of enzymes in the apoptotic pathway. We review here the current evidence from laboratory studies and pilot clinical trials supporting the hypothesis that tetracycline derivatives could exert a neuroprotective effect for patients with PD and HD.