Effects of quercetin on exercise performance, physical activity and blood supply in a novel model of sustained hind-limb ischaemia

Background: There are currently few effective drugs to treat the leg symptoms of peripheral arterial disease (PAD). Previous studies have suggested that the nutraceutical, quercetin, can improve exercise performance and reduce pain sensitivity in healthy mice and improve blood supply in a rodent model of acute hind-limb ischaemia. These models may not be relevant to people with PAD. The aim of this study was to examine the effect of quercetin on exercise performance, physical activity and blood supply in a novel mouse model of sustained hind-limb ischaemia. Methods: Hind-limb ischaemia was induced in 6-month-old male apolipoprotein E-deficient mice using a novel two-stage surgical procedure. Five days after induction of ischaemia, mice were allocated to commence dietary quercetin or a control diet for 4 weeks. The primary outcome was exercise performance evaluated using a treadmill test. Other outcomes included physical activity, estimated by an open field test, and hind-limb blood supply, assessed by laser Doppler monitoring. Results: A sustained reduction in relative limb blood supply (P < 0.001) was achieved consistently in all 48 mice before allocation to a control (n = 24) or quercetin (n = 24) diet. Quercetin did not improve exercise performance (P = 0.785), physical activity (P = 0.151) or relative limb blood supply (P = 0.954) over the 4-week assessment period. Conclusion: These data suggest that quercetin does not improve exercise performance, physical activity or limb blood supply in mice with sustained hind-limb ischaemia, and therefore is unlikely be an effective treatment for PAD

Comparative study of syndromic and etiological diagnosis of reproductive tract infections/sexually transmitted infections in women in Delhi

SummaryBackgroundThe adequacy of the World Health Organization's syndromic approach for the diagnosis and management of sexually transmitted diseases (STDs), especially at primary health centers (PHCs) and at other levels, is still debatable in different settings in India and requires validation.ObjectivesA cross-sectional study was carried out in women attending the peripheral government clinics of Delhi in order to (1) enumerate their self-reported reproductive tract infection (RTI)/sexually transmitted infection (STI) symptoms; (2) assess their clinical status; (3) determine the syndromic diagnosis of RTI/STI in symptomatic women and etiological diagnosis in both symptomatic and asymptomatic women; and (4) compare the level of agreement between self-reporting of morbidity and syndromic and etiological diagnosis.Materials and methodsThe study was conducted over 26 months in 4090 women attending peripheral government healthcare centers, both rural and urban, in four zones of Delhi. They were recruited into four different study groups: group I, non-pregnant, reporting with symptoms of RTI/STI; group II, with a bad obstetric history or infertility; group III, pregnant women in any trimester attending the antenatal clinic; and group IV, the control group. Gynecological examination, followed by the collection of genital specimens and blood, were performed after informed and written consent was obtained. Every symptomatic patient was managed on the basis of algorithms of the syndromic approach as recommended by the National AIDS Control Organisation (NACO), India. All specimens were transported to the STD Reference Laboratory, Safdarjung Hospital, New Delhi and processed by standard methods to diagnose the various STDs. Laboratory reports were sent to the clinicians and appropriate treatment was instituted. Data were analyzed by applying statistical methods.ResultsOverall, self-reporting of morbidity was 65.0%. However, the percentage of women with some STD-related syndrome was 71.4%. The rural women were observed to have significantly more STD syndromes than their urban counterparts. The etiological diagnosis could be established in only 32.2% of cases.ConclusionsThis study highlights the wide variation between self-reporting of morbidity and syndromic- and etiology-based diagnosis in women from both rural and urban settings. This has implications for the syndromic approach to STI case management. These observations call for a review of the diagnostic policy for RTIs/STIs by national authorities in order to avoid the overuse of antimicrobials. The study also highlights the need for the introduction and/or strengthening of facilities for simple diagnostic tests for RTIs/STIs, especially at the peripheral healthcare level

Kondo Effect of Quantum Dots in the Quantum Hall Regime

Quantum dots in the quantum Hall regime can have pairs of single Slater determinant states that are degenerate in energy. We argue that these pairs of many body states may give rise to a Kondo effect which can be mapped into an ordinary Kondo effect in a fictitious magnetic field. We report on several properties of this Kondo effect using scaling and numerical renormalization group analysis. We suggest an experiment to investigate this Kondo effect.Comment: To appear in Phys. Rev. B (5 pages, 4 figures); references added; several changes in tex

Magnetotransport through a strongly interacting quantum dot

We study the effect of a magnetic field on the conductance through a strongly interacting quantum dot by using the finite temperature extension of Wilson's numerical renormalization group method to dynamical quantities. The quantum dot has one active level for transport and is modelled by an Anderson impurity attached to left and right electron reservoirs. Detailed predictions are made for the linear conductance and the spin-resolved conductance as a function of gate voltage, temperature and magnetic field strength. A strongly coupled quantum dot in a magnetic field acts as a spin filter which can be tuned by varying the gate voltage. The largest spin-filtering effect is found in the range of gate voltages corresponding to the mixed valence regime of the Anderson impurity model.Comment: Revised version, to appear in PRB, 4 pages, 4 figure

Steady-State Properties of Single-File Systems with Conversion

We have used Monte-Carlo methods and analytical techniques to investigate the influence of the characteristic parameters, such as pipe length, diffusion, adsorption, desorption and reaction rate constants on the steady-state properties of Single-File Systems with a reaction. We looked at cases when all the sites are reactive and when only some of them are reactive. Comparisons between Mean-Field predictions and Monte-Carlo simulations for the occupancy profiles and reactivity are made. Substantial differences between Mean-Field and the simulations are found when rates of diffusion are high. Mean-Field results only include Single-File behavior by changing the diffusion rate constant, but it effectively allows passing of particles. Reactivity converges to a limit value if more reactive sites are added: sites in the middle of the system have little or no effect on the kinetics. Occupancy profiles show approximately exponential behavior from the ends to the middle of the system.Comment: 15 pages, 20 figure

Nonequilibrium Transport through a Kondo Dot in a Magnetic Field: Perturbation Theory

Using nonequilibrium perturbation theory, we investigate the nonlinear transport through a quantum dot in the Kondo regime in the presence of a magnetic field. We calculate the leading logarithmic corrections to the local magnetization and the differential conductance, which are characteristic of the Kondo effect out of equilibrium. By solving a quantum Boltzmann equation, we determine the nonequilibrium magnetization on the dot and show that the application of both a finite bias voltage and a magnetic field induces a novel structure of logarithmic corrections not present in equilibrium. These corrections lead to more pronounced features in the conductance, and their form calls for a modification of the perturbative renormalization group.Comment: 16 pages, 7 figure

Systems consequences of amplicon formation in human breast cancer

Chromosomal structural variations play an important role in determining the transcriptional landscape of human breast cancers. To assess the nature of these structural variations, we analyzed eight breast tumor samples with a focus on regions of gene amplification using mate-pair sequencing of long-insert genomic DNA with matched transcriptome profiling. We found that tandem duplications appear to be early events in tumor evolution, especially in the genesis of amplicons. In a detailed reconstruction of events on chromosome 17, we found large unpaired inversions and deletions connect a tandemly duplicated ERBB2 with neighboring 17q21.3 amplicons while simultaneously deleting the intervening BRCA1 tumor suppressor locus. This series of events appeared to be unusually common when examined in larger genomic data sets of breast cancers albeit using approaches with lesser resolution. Using siRNAs in breast cancer cell lines, we showed that the 17q21.3 amplicon harbored a significant number of weak oncogenes that appeared consistently coamplified in primary tumors. Down-regulation of BRCA1 expression augmented the cell proliferation in ERBB2-transfected human normal mammary epithelial cells. Coamplification of other functionally tested oncogenic elements in other breast tumors examined, such as RIPK2 and MYC on chromosome 8, also parallel these findings. Our analyses suggest that structural variations efficiently orchestrate the gain and loss of cancer gene cassettes that engage many oncogenic pathways simultaneously and that such oncogenic cassettes are favored during the evolution of a cancer.Singapore. Agency for Science, Technology and ResearchNational Science Foundation (U.S.) (East Asia and Pacific Summer Institutes (OISE-1108282)

Epilepsy due to PNPO mutations: genotype, environment and treatment affect presentation and outcome

Mutations in PNPO are a known cause of neonatal onset seizures that are resistant to pyridoxine but responsive to pyridoxal phosphate (PLP). Mills etal. show that PNPO mutations can also cause neonatal onset seizures that respond to pyridoxine but worsen with PLP, as well as PLP-responsive infantile spasm

Multiwavelength studies of MHD waves in the solar chromosphere: An overview of recent results

The chromosphere is a thin layer of the solar atmosphere that bridges the relatively cool photosphere and the intensely heated transition region and corona. Compressible and incompressible waves propagating through the chromosphere can supply significant amounts of energy to the interface region and corona. In recent years an abundance of high-resolution observations from state-of-the-art facilities have provided new and exciting ways of disentangling the characteristics of oscillatory phenomena propagating through the dynamic chromosphere. Coupled with rapid advancements in magnetohydrodynamic wave theory, we are now in an ideal position to thoroughly investigate the role waves play in supplying energy to sustain chromospheric and coronal heating. Here, we review the recent progress made in characterising, categorising and interpreting oscillations manifesting in the solar chromosphere, with an impetus placed on their intrinsic energetics.Comment: 48 pages, 25 figures, accepted into Space Science Review