A study of KIT activating mutations in acute myeloid leukemia M0 subtype in north India

Acute Myeloid Leukemia (AML)-M0 is a cancer of blood-forming cells in the bone marrow. KIT gene is a receptor tyrosine kinase class III that is expressed on by early hematopoietic progenitor cells and plays an important role in hematopoietic stem cell proliferation, differentiation and survival. Mutations of KIT receptor tyrosine kinase are involved in the constitutive activation and development of human hematologic malignancies. We have designed this study aiming to identify and determine the frequency and prevalence of mutations in North Indian patients suffering from AML-M0. To perceive the KIT gene mutations, we have carried out PCR–SSCP followed by direct DNA sequencing in 50 AML-M0 cases. We have found eight cases (24.2%) with t(8;21) having 12 point mutations whereas three cases (17.6%) with inv(16) having four point mutations. The point mutation detected at exon 9 in five cases is Asp496Val. Eight different point mutations were identified at exon 11 in seven AML-M0 cases that include Lys550Asn, Tyr568Ser, Ile571Leu, Tyr578Pro, Trp582Ser and Arg588Met. Point mutations at codons Ile571Leu and Trp582Ser was found in two independent cases. Three point mutations were found in exon 17 (Leu813Pro, Lys818Arg, Val825Ala) in three AML-M0 cases. The results underline that the KIT gene appears to be most frequently mutated target in AML-M0 cases. These observations suggest that mutations in exon 11 of the KIT gene might be useful molecular genetic markers in AML-M0 and these mutations might be related to progression and clinical pathogenesis.Keywords: PCR; SSCP–PAGE; KIT; Malignant; AML-M0; Mutation

Non-stationary dynamo & magnetospheric accretion processes of the classical T Tauri star V2129 Oph

We report here the first results of a multi-wavelength campaign focussing on magnetospheric accretion processes of the classical TTauri star (cTTS) V2129Oph. In this paper, we present spectropolarimetric observations collected in 2009 July with ESPaDOnS at the Canada-France-Hawaii Telescope (CFHT). Circularly polarised Zeeman signatures are clearly detected, both in photospheric absorption and accretion-powered emission lines, from time-series of which we reconstruct new maps of the magnetic field, photospheric brightness and accretion-powered emission at the surface of V2129Oph using our newest tomographic imaging tool - to be compared with those derived from our old 2005 June data set, reanalyzed in the exact same way. We find that in 2009 July, V2129Oph hosts octupolar & dipolar field components of about 2.1 & 0.9kG respectively, both tilted by about 20deg with respect to the rotation axis; we conclude that the large-scale magnetic topology changed significantly since 2005 June (when the octupole and dipole components were about 1.5 and 3 times weaker respectively), demonstrating that the field of V2129Oph is generated by a non-stationary dynamo. We also show that V2129Oph features a dark photospheric spot and a localised area of accretion-powered emission, both close to the main surface magnetic region (hosting fields of up to about 4kG in 2009 July). We finally obtain that the surface shear of V2129Oph is about half as strong as solar. From the fluxes of accretion-powered emission lines, we estimate that the observed average logarithmic accretion rate (in Msun/yr) at the surface of V2129Oph is -9.2+-0.3 at both epochs, peaking at -9.0 at magnetic maximum. It implies in particular that the radius at which the magnetic field of V2129Oph truncates the inner accretion disc is 0.93x and 0.50x the corotation radius in 2009 July and 2005 June respectively.Comment: MNRAS in press - 16 pages, 9 figure

Clinical assessment of a low-cost, hand-held, smartphone-attached intraoral imaging probe for ALA PDT monitoring and guidance

India has one of the highest rates of oral squamous cell carcinoma (OSCC) in the world, with an incidence of 15 per 100,000 and more than 70,000 deaths per year. The problem is exacerbated by lack of medical infrastructure and routine screening, especially in rural areas. This collaboration recently developed, and clinically validated, a low-cost, portable and easy-to-use platform for intraoral photodynamic therapy (PDT) specifically engineered for use in global health settings. Here, we explore the implementation of our low-cost PDT system in conjunction with a small, handheld smartphone-coupled, multichannel fluorescence and white-light oral cancer imaging probe, which was also developed for global health settings. Our study aimed to use this mobile intraoral imaging device for treatment guidance and monitoring PDT using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PS; PpIX) fluorescence. A total of 12 patients with 14 lesions having moderately/well-differentiated micro-invasive OSCC lesions (<2 cm diameter, depth <5 mm) were systemically administered with three doses of 20mg/kg ALA (total 60mg/kg). Lesion site PpIX and auto fluorescence was analyzed before/after ALA administration, and again after light delivery (fractionated, total 100 J/cm^{2} of 630nm red LED light). Quantification of relative PpIX fluorescence enables lesion area segmentation to improve guidance of light delivery and reports extent of photobleaching. These results indicate the utility of this approach for image-guided PDT and treatment monitoring while also laying groundwork for an integrated approach, combining cancer screening and treatment with the same hardware

Stellar Coronal and Wind Models: Impact on Exoplanets

Surface magnetism is believed to be the main driver of coronal heating and stellar wind acceleration. Coronae are believed to be formed by plasma confined in closed magnetic coronal loops of the stars, with winds mainly originating in open magnetic field line regions. In this Chapter, we review some basic properties of stellar coronae and winds and present some existing models. In the last part of this Chapter, we discuss the effects of coronal winds on exoplanets.Comment: Chapter published in the "Handbook of Exoplanets", Editors in Chief: Juan Antonio Belmonte and Hans Deeg, Section Editor: Nuccio Lanza. Springer Reference Work

Merkel cell carcinoma: a population-based study on mortality and the association with other cancers

Few population-based epidemiological data are available on Merkel cell carcinoma (MCC), a rare lethal non-melanoma skin cancer. We analysed multiple-cause-of-death records to describe MCC mortality and trends and the association with other primary cancers. We reviewed all 6,713,059 death certificates in Italy (1995-2006) to identify those mentioning MCC. We evaluated the association with other primary cancers by calculating the ratio of observed to expected deaths, using a standardized mortality ratio (SMR)-like analysis. We also evaluated the geographic distribution of deaths. We identified 351 death certificates with the mention of MCC. The age-adjusted mortality was 0.031/100,000, with a significant trend of increase and a slight north-south gradient. There was a significant deficit for solid cancers (SMR = 0.15) and a non-significant excess for lymphohematopoietic malignancies (SMR = 1.62). There were significant excesses for chronic lymphocytic leukemia (SMR = 4.07) and Waldenstrom's macroglobulinemia (SMR = 27.2) and a non-significant excess for chronic myeloid leukemia (SMR = 5.12). The increase in MCC mortality reflects the incidence trend in the literature. The association with chronic lymphocytic leukemia confirms the importance of immunologic factors in MCC. Regarding Waldenstrom's macroglobulinemia, an association with MCC has never been reported

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

A review of wearable motion tracking systems used in rehabilitation following hip and knee replacement

Clinical teams are under increasing pressure to facilitate early hospital discharge for total hip replacement and total knee replacement patients following surgery. A wide variety of wearable devices are being marketed to assist with rehabilitation following surgery. A review of wearable devices was undertaken to assess the evidence supporting their efficacy in assisting rehabilitation following total hip replacement and total knee replacement. A search was conducted using the electronic databases including Medline, CINAHL, Cochrane, PsycARTICLES, and PubMed of studies from January 2000 to October 2017. Five studies met the eligibility criteria, and all used an accelerometer and a gyroscope for their technology. A review of the studies found very little evidence to support the efficacy of the technology, although they show that the use of the technology is feasible. Future work should establish which wearable technology is most valuable to patients, which ones improve patient outcomes, and the most economical model for deploying the technolog

HIV-1 Efficient Entry in Inner Foreskin Is Mediated by Elevated CCL5/RANTES that Recruits T Cells and Fuels Conjugate Formation with Langerhans Cells

Male circumcision reduces acquisition of HIV-1 by 60%. Hence, the foreskin is an HIV-1 entry portal during sexual transmission. We recently reported that efficient HIV-1 transmission occurs following 1 h of polarized exposure of the inner, but not outer, foreskin to HIV-1-infected cells, but not to cell-free virus. At this early time point, Langerhans cells (LCs) and T-cells within the inner foreskin epidermis are the first cells targeted by the virus. To gain in-depth insight into the molecular mechanisms governing inner foreskin HIV-1 entry, foreskin explants were inoculated with HIV-1-infeceted cells for 4 h. The chemokine/cytokine milieu secreted by the foreskin tissue, and resulting modifications in density and spatial distribution of T-cells and LCs, were then investigated. Our studies show that in the inner foreskin, inoculation with HIV-1-infected cells induces increased CCL5/RANTES (1.63-fold) and decreased CCL20/MIP-3-alpha (0.62-fold) secretion. Elevated CCL5/RANTES mediates recruitment of T-cells from the dermis into the epidermis, which is blocked by a neutralizing CCL5/RANTES Ab. In parallel, HIV-1-infected cells mediate a bi-phasic modification in the spatial distribution of epidermal LCs: attraction to the apical surface at 1 h, followed by migration back towards the basement membrane later on at 4 h, in correlation with reduced CCL20/MIP-3-alpha at this time point. T-cell recruitment fuels the continuous formation of LC-T-cell conjugates, permitting the transfer of HIV-1 captured by LCs. Together, these results reveal that HIV-1 induces a dynamic process of immune cells relocation in the inner foreskin that is associated with specific chemokines secretion, which favors efficient HIV-1 entry at this site