620 research outputs found
Traditional Chinese Medicine And New Concepts Of Predictive, Preventive And Personalized Medicine In Diagnosis And Treatment Of Suboptimal Health
The premise of disease-related phenotypes is the definition of the counterpart normality in medical sciences. Contrary to clinical practices that can be carefully planned according to clinical needs, heterogeneity and uncontrollability is the essence of humans in carrying out health studies. Full characterization of consistent phenotypes that define the general population is the basis to individual difference normalization in personalized medicine. Self-claimed normal status may not represent health because asymptomatic subjects may carry chronic diseases at their early stage, such as cancer, diabetes mellitus and atherosclerosis. Currently, treatments for non-communicable chronic diseases (NCD) are implemented after disease onset, which is a very much delayed approach from the perspective of predictive, preventive and personalized medicine (PPPM). A NCD pandemic will develop and be accompanied by increased global economic burden for healthcare systems throughout both developed and developing countries. This paper examples the characterization of the suboptimal health status (SHS) which represents a new PPPM challenge in a population with ambiguous health complaints such as general weakness, unexplained medical syndrome (UMS), chronic fatigue syndrome (CFS), myalgic encephalomyelitis (ME), post-viral fatigue syndrome (PVFS) and chronic fatigue immune dysfunction syndrome (CFIDS). Methods: We applied clinical informatic approaches and developed a questionnaire-suboptimal health status questionnaire-25 (SHSQ-25) for measuring SHS. The validity and reliability of this approach were evaluated in a small pilot study and then in a cross-sectional study of 3,405 participants in China. Results: We found a correlation between SHS and systolic blood pressure, diastolic blood pressure, plasma glucose, total cholesterol and high-density lipoprotein (HDL) cholesterol among men, and a correlation between SHS and systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides and HDL cholesterol among women. Conclusions: The SHSQ-25 is a self-rated questionnaire of perceived health complaints, which can be used as a new instrument for PPPM. An ongoing longitudinal SHS cohort survey (China Sub-optimal Health Cohort Study, COACS) consisting of 50,000 participants will provide a powerful health trial to use SHSQ-25 for its application to PPPM through patient stratification and therapy monitoring using innovative technologies of predictive diagnostics and prognosis: an effort of paradigm shift from reactive to predictive medicine
Thickness dependence of unidirectional spin-Hall magnetoresistance in metallic bilayers
A nonlinear magnetoresistance - called unidirectional spin-Hall
magnetoresistance - is recently experimentally discovered in metallic bilayers
consisting of a heavy metal and a ferromagnetic metal. To study the fundamental
mechanism of the USMR, both ferromagnetic and heavy metallic layer thickness
dependence of the USMR are presented in a Pt/Co/AlOx trilayer at room
temperature. To avoid ambiguities, second harmonic Hall measurements are used
for separating spin-Hall and thermal contributions to the non-linear
magnetoresistance. The experimental results are fitted by using a
drift-diffusion theory, with parameters extracted from an analysis of
longitudinal resistivity of the Co layer within the framework of the
Fuchs-Sondheimer model. A good agreement with the theory is found,
demonstrating that the USMR is governed by both the spin-Hall effect in the
heavy metallic layer and the metallic diffusion process in the ferromagnetic
layer
Information gain versus coupling strength in quantum measurements
We investigate the relationship between the information gain and the
interaction strength between the quantum system and the measuring device. A
strategy is proposed to calculate the information gain of the measuring device
as the coupling strength is a variable. For qubit systems, we prove that the
information gain increases monotonically with the coupling strength. It is
obtained that the information gain of the projective measurement along the
x-direction reduces with the increasing of the measurement strength along the
z-direction, and a complementarity of information gain in the measurements
along those two directions is presented.Comment: 7 pages, 1 figure
The correlation timescale of the X-ray flux during the outbursts of soft X-ray transients
Recent studies of black hole and neutron star low mass X-ray binaries (LMXBs)
show a positive correlation between the X-ray flux at which the
low/hard(LH)-to-high/soft(HS) state transition occurs and the peak flux of the
following HS state. By analyzing the data from the All Sky Monitor (ASM)
onboard the Rossi X-ray Timing Explorer (RXTE), we show that the HS state flux
after the source reaches its HS flux peak still correlates with the transition
flux during soft X-ray transient (SXT) outbursts. By studying large outbursts
or flares of GX 339-4, Aql X-1 and 4U 1705-44, we have found that the
correlation holds up to 250, 40, and 50 d after the LH-to-HS state transition,
respectively. These time scales correspond to the viscous time scale in a
standard accretion disk around a stellar mass black hole or a neutron star at a
radius of ~104-5 Rg, indicating that the mass accretion rates in the accretion
flow either correlate over a large range of radii at a given time or correlate
over a long period of time at a given radius. If the accretion geometry is a
two-flow geometry composed of a sub-Keplerian inflow or outflow and a disk flow
in the LH state, the disk flow with a radius up to ~105 Rg would have
contributed to the nearly instantaneous non-thermal radiation directly or
indirectly, and therefore affects the time when the state transition occurs.Comment: 7 pages, 3 figure
Revisiting the SAR of the antischistosomal aryl hydantoin (Ro 13-3978)
The aryl hydantoin 1 (Ro 13-3978) was identified in the early 1980s as a promising antischistosomal lead compound. However, this series of aryl hydantoins produced antiandrogenic side effects in the host, a not unexpected outcome given their close structural similarity to the antiandrogenic drug nilutamide. Building on the known SAR of this compound series, we now describe a number of analogs of 1 designed to maximize structural diversity guided by incorporation of substructures and functional groups known to diminish ligand-androgen receptor interactions. These analogs had calculated polar surface area (PSA), measured LogD7.4, aqueous kinetic solubility, and estimated plasma protein binding values in ranges predictive of good ADME profiles. The principal SAR insight was that the hydantoin core of 1 is required for high antischistosomal activity. We identified several compounds with high antischistosomal efficacy that were less antiandrogenic than 1. These data provide direction for the ongoing optimization of antischistosomal hydantoins
Peroxide Antimalarial Drugs Target Redox Homeostasis in Plasmodium Falciparum Infected Red Blood Cells
Plasmodium falciparum causes the most lethal form of malaria. Peroxide antimalarials based on artemisinin underpin the frontline treatments for malaria, but artemisinin resistance is rapidly spreading. Synthetic peroxide antimalarials, known as ozonides, are in clinical development and offer a potential alternative. Here, we used chemoproteomics to investigate the protein alkylation targets of artemisinin and ozonide probes, including an analogue of the ozonide clinical candidate, artefenomel. We greatly expanded the list of proteins alkylated by peroxide antimalarials and identified significant enrichment of redox-related proteins for both artemisinins and ozonides. Disrupted redox homeostasis was confirmed by dynamic live imaging of the glutathione redox potential using a genetically encoded redox-sensitive fluorescence-based biosensor. Targeted liquid chromatography-mass spectrometry (LC-MS)-based thiol metabolomics also confirmed changes in cellular thiol levels. This work shows that peroxide antimalarials disproportionately alkylate proteins involved in redox homeostasis and that disrupted redox processes are involved in the mechanism of action of these important antimalarials
Consensus on treatment goals in hereditary angioedema : a global Delphi initiative
Background: Hereditary angioedema (HAE) is a rare, life-threatening genetic disorder characterized by recurrent episodes of subcutaneous or submucosal angioedema. The ultimate goals of treatment for HAE remain ill-defined. Objectives: The aim of this Delphi process was to define the goals of HAE treatment and to examine which factors should be considered when assessing disease control and normalization of the patient's life. Methods: The Delphi panel comprised 23 participants who were selected based on involvement with scientific research on HAE or coauthorship of the most recent update and revision of the World Allergy Organization/European Academy of Allergy and Clinical Immunology guideline on HAE. The process comprised 3 rounds of voting. The final round aimed to aggregate the opinions of the expert panel and to achieve consensus. Results: Two direct consensus questions were posed in round 2, based on the responses received in round 1, and the panel agreed that the goals of treatment are to achieve total control of the disease and to normalize the patient's life. For the third round of voting, 21 statements were considered, with the participants reaching consensus on 18. It is clear from the wide-ranging consensus statements that the burdens of disease and treatment should be considered when assessing disease control and normalization of patients’ lives. Conclusions: The ultimate goal for HAE treatment is to achieve no angioedema attacks. The availability of improved treatments and disease management over the last decade now makes complete control of HAE a realistic possibility for most patients
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