Miracle-dz/UniFAR-FTUs huggingface dataset:
Involvement of miltefosine‐mediated ERK activation in glioma cell apoptosis through Fas regulation

The anti‐neoplastic property of alkyl phospholipids has been tested for the treatment of several malignancies. In this study, we evaluated the efficacy of miltefosine (Hexadecylphosphocholine – an alkyl phospholipids analogue) on glioblastoma multiforme. In this study, we demonstrate that miltefosine‐induced apoptosis is accompanied by elevated Fas, Fas‐associated death domain (FADD) expression, caspase‐8 activity and the increased distribution of Fas and FADD towards lipid raft microdomain to form death inducing signaling complex. Treatment with miltefosine resulted in increase in Ras, extracellular signal‐regulated kinase (ERK) and p38MAPK activity. Expression of dominant‐negative Ras (Ras N17) attenuated miltefosine‐mediated apoptosis. Although inhibition of both ERK and p38MAPK decreased the pro‐apoptotic effects of miltefosine, it was the inhibition of ERK and not p38MAPK activation that decreased Fas and FADD expression. An ERK‐dependent increase in the expression of γH2AX‐involved in response to DNA double‐stranded breaks was also observed. Taken together, our findings suggest the involvement of ERK activation in miltefosine‐induced glioma cell apoptosis.
The safety of non-stimulant agents for the treatment of attention-deficit hyperactivity disorder

Due to their well-established efficacy and safety, stimulants are the drugs of first choice if medication for attention-deficit hyperactivity disorder (ADHD) is required. Nevertheless, for some individuals other, non-stimulant treatments are needed for several reasons. If so, atomoxetine is recommended as a second-line treatment. In addition, several tricyclic antidepressants, such as desipramine or imipramine, as well as α-2 agonists, especially clonidine or bupropion, might be efficient in treating ADHD, in particular in specific co-morbid conditions. Despite the fact that non-stimulant treatments in ADHD are usually well-tolerated with side effects being mostly moderate and transient, special safety aspects and precautions, specific for each drug, have to be considered whenever a non-stimulant treatment is chosen. This review focuses on the tolerability, occurrence of adverse events, precautions required to prevent severe adverse events, and essential pharmacological interaction in the treatment of ADHD symptoms by non-stimulants.
Sulfonamides and Sulfonamide Combinations *

Due to low cost and relative efficacy against many common bacterial infections, sulfonamides and sulfonamide combinations with diaminopyrimidines are some of the most common antibacterial agents utilized in veterinary medicine. The sulfonamides are derived from sulfanilamide. These chemicals are structural analogues of ρ-aminobenzoic acid (PABA). All sulfonamides are characterized by the same chemical nucleus. Functional groups are added to the amino group or substitutions made on the amino group to facilitate varying chemical, physical and pharmacologic properties and antibacterial spectra. Most sulfonamides are too alkaline for routine parenteral use. Therefore the drug is most commonly administered orally except in life threatening systemic infections. However, sulfonamide preparations can be administered orally, intramuscularly, intravenously, intraperitoneally, intrauterally and topically.
Work related and non-work related stress in relation to low leisure time physical activity in a Swedish population

Physical activity is regarded as an important component of a healthy lifestyle. Several social and environmental factors have systematically emerged as barriers to low leisure time physical activity (LTPA), for example, lack of money, low social support due to lack of supportive family or friends, and living in high crime rate areas. Low LTPA has been found to be strongly associated with low socioeconomic status groups where psychosocial stressors have been suggested to play a mediating part.1,2 The overall aim of this study was to investigate the association between work and non-work related stressors, respectively, in relation to low LTPA in a general population sample. Our main hypothesis was that psychosocial stressors would act as barriers to physical activity thus generating sedentary behaviour as measured by LTPA. The Scania health survey was conducted during the period of November 1999 through April 2000. After excluding refusals, non-contacts, and other non-responding groups, the final sample consisted of 13 715 persons, making the response rate 59% of the sample size. A self administered questionnaire provided information regarding health related behaviours, sociodemographic characteristic, and psychosocial factors. Our analysis was restricted to currently employed people (52% of the sample population) yielding a study population of 7169 subjects (3877 men and 3292 women). Odds ratios for low LTPA in relation to psychosocial variables were calculated using two logistic regression models, model one with adjustment for age, …
Statistical analysis of amplified fragment length polymorphism data: a toolbox for molecular ecologists and evolutionists

Recently, the amplified fragment length polymorphism (AFLP) technique has gained a lot of popularity, and is now frequently applied to a wide variety of organisms. Technical specificities of the AFLP procedure have been well documented over the years, but there is on the contrary little or scattered information about the statistical analysis of AFLPs. In this review, we describe the various methods available to handle AFLP data, focusing on four research topics at the population or individual level of analysis: (i) assessment of genetic diversity; (ii) identification of population structure; (iii) identification of hybrid individuals; and (iv) detection of markers associated with phenotypes. Two kinds of analysis methods can be distinguished, depending on whether they are based on the direct study of band presences or absences in AFLP profiles (‘band‐based’ methods), or on allelic frequencies estimated at each locus from these profiles (‘allele frequency‐based’ methods). We investigate the characteristics and limitations of these statistical tools; finally, we appeal for a wider adoption of methodologies borrowed from other research fields, like for example those especially designed to deal with binary data.
Comparison in the immunological properties of Borrelia burgdorferi isolates from Ixodes ricinus derived from three endemic areas in Switzerland

SUMMARY Borrelia burgdorferi isolates were obtained from Ixodes ricinus from three sites in Switzerland. They were examined by SDS-PAGE and immunoblotting. The phenotypes, in respect of three outer surface proteins (Osp), differed between the sites of collection. In site 1, most isolates had an OspA of 31 kDa and an OspB of 34 kDa: in site 2, isolates presenting an OspA of 33 kDa dominated and in site 3, the isolates with an OspA of 32 kDa and an OspB of 35 kDa were most frequent. This distribution differed significantly. About half of the isolates from sites 1 and 3 reacted with anti-OspA monoclonal antibody H5332 compared to 29% from site 2. Site 1 isolates reacted significantly more frequently (81 %) with another anti-OspA monoclonal antibody LA-31 than isolates from site 3 (P < 0·0001). These findings have implications for the epidemiology of Lyme borreliosis, for the further development of serodiagnostic reagents and for the development of a vaccine.
Coronary artery disease and diabetes

Patients with diabetes form a substantial proportion of patients with coronary artery disease.1 In some respects, the assessment, management, and outcome of these patients is different from patients without diabetes. This article outlines these differences in patients with symptomatic coronary disease and then focuses on the problems of managing high risk asymptomatic patients with diabetes. Should we and can we reliably identify these patients? Once identified, are they likely to benefit from intervention? Diabetes is a strong and independent risk factor for the presence of coronary disease increasing the risk, particularly in women, between twofold and fourfold.2 In patients with diabetes, coronary disease is more extensive and severe, and cardiovascular death is three times more common than in non-diabetic patients.3 In patients with non-insulin dependent diabetes, a proportion of the increased risk can be explained by an excess and clustering of established cardiovascular risk factors. The mechanisms accounting for the remaining risk are poorly understood and relate in part to the consequences of hyperglycaemia and abnormalities of the coagulation and fibrinolytic systems. In the settings of acute myocardial infarction and the secondary prevention of coronary disease, the relative benefits of medical treatment have been shown to be similar in patients with and without diabetes. In patients with diabetes and acute myocardial infarction, those with suboptimal blood glucose control have been shown to benefit substantially from insulin treatment.4 In patients with diabetes, most studies of coronary artery surgery have shown that the risks of death, myocardial infarction, and stroke are increased compared with non-diabetic patients.5In those with diabetes and multivessel disease, the long term outcome after coronary angioplasty6 and saphenous vein grafting alone are particularly disappointing compared with the very favourable outcome of diabetic patients after re-vascularisation using internal mammary artery grafting.7 Disappointing …
Evaluation of smoothing in an iterative lp-norm minimization algorithm for surface-based source localization of MEG

The imaging of neural sources of magnetoencephalographic data based on distributed source models requires additional constraints on the source distribution in order to overcome ill-posedness and obtain a plausible solution. The minimum lp norm (0 < p ⩽ 1) constraint is known to be appropriate for reconstructing focal sources distributed in several regions. A well-known recursive method for solving the lp-norm minimization problem, for example, is the focal underdetermined system solver (FOCUSS). However, this iterative algorithm tends to give spurious sources when the noise level is high. In this study, we present an algorithm to incorporate a smoothing technique into the FOCUSS algorithm and test different smoothing kernels in a surface-based cortical source space. Simulations with cortical source patches assumed in auditory areas show that the incorporation of the smoothing procedure improves the performance of the FOCUSS algorithm, and that using the geodesic distance for constructing a smoothing kernel is a better choice than using the Euclidean one, particularly when employing a cortical source space. We also apply these methods to a real data set obtained from an auditory experiment and illustrate their applicability to realistic data by presenting the reconstructed source images localized in the superior temporal gyrus.
Binasal Hemianopia as an Early Stage in Binocular Color Rivalry

Fifty years ago K�llner reported that the initial fleeting sensation in binocular color rivalry is a bipartite color field such that the color presented to the left eye appears to the left of the color presented to the right eye. A method is described for maintaining such quasi hemianopia for long periods of time.
Outsourcing and skill‐specific employment in a small economy: Austria after the fall of the Iron Curtain

We present a model, in which a small industrialised economy outsources part of its production into a small foreign country which is well endowed with low-skilled labour. We analyse under which conditions sinking trade costs stimulate outsourcing activities, thereby increasing the wage dispersion and, if labour markets are unionised, also the employment of high-skilled relative to low-skilled labour. For a panel of Austrian industries, we find first that decreasing trade barriers, which can be associated with the fall of the Iron Curtain, indeed stimulate outsourcing to Eastern Europe and the former Soviet Union, and second, that outsourcing to these countries significantly shifts relative employment in favour of high- skilled labour.
Molecular comparison of retroviruses associated with human and simian AIDS

Infectious retrovirus(es) associated with the human (LAV, HTLV‐III, ARV) and simian (SAIDS‐1) acquired immune deficiency syndrome were compared by electron microscopy, immunofluorescence and immunoblotting techniques and by restriction endonuclease mapping of the viral genomes. The extracellular virus particles had similar type D morphology, but intracytoplasmic type A nucleoids were found only in SAIDS virus infected cells. Although the antigens of the three prototype AIDS viruses were similar, no cross‐reactivity with the SAIDS virus was detected. Molecular hybridization and restriction enzyme analysis also revealed that the SAIDS and AIDS viruses were genetically unrelated. However, only minor differences, consistent with strain polymorphism, were found between the three AIDS virus isolates. Thus, the retroviruses associated with AIDS in macaques and humans are unique to each species.
BK channels blockage inhibits hypoxia‐induced migration and chemoresistance to cisplatin in human glioblastoma cells

Glioblastoma (GBM) cells express large‐conductance, calcium‐activated potassium (BK) channels, whose activity is important for several critical aspects of the tumor, such as migration/invasion and cell death. GBMs are also characterized by a heavy hypoxic microenvironment that exacerbates tumor aggressiveness. Since hypoxia modulates the activity of BK channels in many tissues, we hypothesized that a hypoxia‐induced modulation of these channels may contribute to the hypoxia‐induced GBM aggressiveness. In U87‐MG cells, hypoxia induced a functional upregulation of BK channel activity, without interfering with their plasma membrane expression. Wound healing and transwell migration assays showed that hypoxia increased the migratory ability of U87‐MG cells, an effect that could be prevented by BK channel inhibition. Toxicological experiments showed that hypoxia was able to induce chemoresistance to cisplatin in U87‐MG cells and that the inhibition of BK channels prevented the hypoxia‐induced chemoresistance. Clonogenic assays showed that BK channels are also used to increase the clonogenic ability of U87‐MG GBM cells in presence, but not in absence, of cisplatin. BK channels were also found to be essential for the hypoxia‐induced de‐differentiation of GBM cells. Finally, using immunohistochemical analysis, we highlighted the presence of BK channels in hypoxic areas of human GBM tissues, suggesting that our findings may have physiopathological relevance in vivo. In conclusion, our data show that BK channels promote several aspects of the aggressive potential of GBM cells induced by hypoxia, such as migration and chemoresistance to cisplatin, suggesting it as a potential therapeutic target in the treatment of GBM.
Atomic Force Imaging of Ocular Tissues : morphological study of healthy and cataract lenses

A. Antunes, F. V. Gozzo, M. I. Borella, M. Nakamura, A. M. V. Safatle, P. S. M. Barros, H. E. Toma Departamento de Cirurgia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP, Brazil Instituto de Física, Universidade de São Paulo, São Paulo, SP, Brazil Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil
Analysis of macroeconomic time series by the HP filter

This paper analyzes the transmission characteristics of the Hodrick-Prescott (HP) filter and frequency characteristics of exponential series, defines 3dB bandwidths of both the HP filter and exponential time series. Formulas of the 3dB bandwidths of the HP filter and exponential time series are derived. Thus, a method to determine the smoothing parameters of the HP filter by the series length is proposed. The examples showed the proposed method can effectively control the magnitude of fluctuation components, provides a way for the HP filter to deal with different macroeconomic time series by selecting a suitable smoothing parameter.
Development and pilot testing of the collaborative practice assessment tool

Collaborative practice is receiving increased attention as a model of healthcare delivery that positively influences the effectiveness and efficiency of patient care while improving the work environment of healthcare providers. The collaborative practice assessment tool (CPAT) was developed from the literature to enable interprofessional teams to assess their collaborative practice. The CPAT survey included 56 items across nine domains including: mission and goals; relationships; leadership; role responsibilities and autonomy; communication; decision-making and conflict management; community linkages and coordination; perceived effectiveness and patient involvement; in addition to three open-ended questions. The tool was developed for use in a variety of settings involving a diversity of healthcare providers with the aim of helping teams to identify professional development needs and corresponding educational interventions. The results of two pilot tests indicated that the CPAT is a valid and reliable tool for assessing levels of collaborative practice within teams. This article describes the development of the tool, the pilot testing and validation process, as well as limitations of the tool.
Towards an ethics for telehealth

Over the last two decades, a public rationale for the implementation of telehealth has emerged at the interplay of specialised literature and political orientations. Despite the lack of consistent findings on the magnitude of its benefits, telehealth is nowadays presented as a worthy solution both for patients and healthcare institutions. Far from denying the potential advantages of telehealth, the main objective of this work is to provide a critical assessment on the spread of the remote services as a vector of positive transformation of contemporary health systems. For pursuing this objective, the EU agenda for the promotion of telehealth will be retraced, and the main evidences alleged to sustain the implementation of remote care services will be assessed. Furthermore, it will be evaluated the attempt made by the European Commission to establish an ethical framework for guiding the use of telehealth in daily practice, and a roadmap of the most relevant legal and ethical issues posed by the spread of telehealth will be traced. In the conclusions, it will be argued that the radical transformations induced by this form of technological innovation call on to a new, ad hoc ethics through which critically evaluate benefits and implications of telehealth services, with a view to keep high the standard of healthcare against the economic interests of private stakeholders and ICTs’ vendors.
Determination of channel temperature in AlGaN/GaN HEMTs grown on sapphire and silicon substrates using DC characterization method

Self-heating effects and temperature rise in AlGaN/GaN HEMTs grown on silicon and sapphire substrates are studied, exploiting transistor DC characterization methods. A negative differential output resistance is observed for high dissipated power levels. An analytical formula for a source-drain current drop as a function of parasitic source resistance and threshold voltage changes is proposed to explain this behavior. The transistor source resistance and threshold voltage is determined experimentally at different elevated temperatures to construct channel temperature versus dissipated power transfer characteristic. It is found that the HEMT channel temperature increases rapidly with dissipated power and at 6 W/mm reaches values of /spl sim/320/spl deg/C for sapphire and /spl sim/95/spl deg/C for silicon substrate, respectively.
Impact of Prophylactic Postoperative β-Blockade on Post-Cardiothoracic Surgery Length of Stay and Atrial Fibrillation

BACKGROUND Previous studies have shown that post-cardiothoracic surgery atrial fibrillation (AF) increases the risk of hospital length of stay (LOS), overall mortality, pulmonary edema, and need for a balloon pump. A meta-analysis of 2 previous trials showed a nonsignificant reduction in LOS with postoperative β-blockers but only encompassed 1200 patients, with few valve surgery patients, and neither study used a hospital within the US. OBJECTIVE To evaluate the impact of postoperative β-blockers on LOS and AF. Secondary endpoints of overall mortality, pulmonary edema, and need for an intra-aortic balloon pump (IABP) were also evaluated between groups. METHODS This was a prospective cohort evaluation of all patients undergoing cardiothoracic surgery at our institution between October 1999 and October 2003. Patients receiving prophylactic postoperative β-blockers were matched (1:1) with patients not receiving prophylaxis for age >70 years, valvular surgery, history of AF, gender, and use of preoperative digoxin and β-blockers. RESULTS Patients (n = 1660) receiving postoperative β-blockade had a reduction in LOS (mean ± SD 10.22 ± 11.38 vs 12.40 ± 15.67; p = 0.001) and AF (23.5% vs 28.4%; p = 0.02). Mortality, pulmonary edema, and need for IABP were reduced by >50% (p < 0.001; p = 0.001; p < 0.001, respectively), while myocardial infarction and stroke were not significantly impacted. CONCLUSIONS In this observational cohort study, prophylactic postoperative β-blocker use was associated with shorter hospital LOS by an average of 2.2 days and a 17.3% lower incidence of AF. It may also be associated with reductions in overall mortality, pulmonary edema, and need for an IABP.
The IS10 transposase mRNA is destabilized during antisense RNA control.

RNA stability is an important component of gene expression, and antisense RNAs have been proposed to alter target RNA stability. We show here that the IS10 transposase mRNA, RNA‐IN, is rendered unstable during control by the IS10 antisense RNA, RNA‐OUT. Destabilization requires RNA‐OUT/RNA‐IN pairing and ribonuclease III cleavage. Independent of such cleavage, RNA‐OUT is rendered unstable through disruption of its secondary structure. Pairing has no other obvious effects on RNA‐IN transcription or stability. Nevertheless, RNA‐IN destabilization is not required for antisense control in vivo. In the accompanying paper [Ma,C. and Simons, R.W. (1990) EMBO J., 9, 1267‐1274 we show that pairing blocks ribosome binding to RNA‐IN. Were it not for control at this level, destabilization would play a more prominent role.