Homelessness and Hepatitis C: risk factors and treatment

Hepatitis C is a public health crisis in both developing and developed countries. Direct acting antiviral therapies have revolutionized the fight against Hepatitis C, making the worldwide eradication of the disease feasible. However, screening and access to care for vulnerable patients – especially for patients experiencing homelessness – are lacking. Homelessness exacerbates the effects of Hepatitis C, leading to poor health outcomes for individual patients and high costs for health providers and taxpayers. One potential solution is investing in affordable housing and the housing first model that provide the stability needed to address both acute and chronic health conditions, including Hepatitis C. Partnerships between patients and providers facilitated by supportive housing can benefit individual outcomes and decrease the financial and social costs to communities

Differential chemosensitivity to antifolate drugs between RAS and BRAF melanoma cells.

BACKGROUND: The importance of the genetic background of cancer cells for the individual susceptibility to cancer treatments is increasingly apparent. In melanoma, the existence of a BRAF mutation is a main predictor for successful BRAF-targeted therapy. However, despite initial successes with these therapies, patients relapse within a year and have to move on to other therapies. Moreover, patients harbouring a wild type BRAF gene (including 25% with NRAS mutations) still require alternative treatment such as chemotherapy. Multiple genetic parameters have been associated with response to chemotherapy, but despite their high frequency in melanoma nothing is known about the impact of BRAF or NRAS mutations on the response to chemotherapeutic agents. METHODS: Using cell proliferation and DNA methylation assays, FACS analysis and quantitative-RT-PCR we have characterised the response of a panel of NRAS and BRAF mutant melanoma cell lines to various chemotherapy drugs, amongst them dacarbazine (DTIC) and temozolomide (TMZ) and DNA synthesis inhibitors. RESULTS: Although both, DTIC and TMZ act as alkylating agents through the same intermediate, NRAS and BRAF mutant cells responded differentially only to DTIC. Further analysis revealed that the growth-inhibitory effects mediated by DTIC were rather due to interference with nucleotide salvaging, and that NRAS mutant melanoma cells exhibit higher activity of the nucleotide synthesis enzymes IMPDH and TK1. Importantly, the enhanced ability of RAS mutant cells to use nucleotide salvaging resulted in resistance to DHFR inhibitors. CONCLUSION: In summary, our data suggest that the genetic background in melanoma cells influences the response to inhibitors blocking de novo DNA synthesis, and that defining the RAS mutation status could be used to stratify patients for the use of antifolate drugs

OH emission from warm and dense gas in the Orion Bar PDR

As part of a far-infrared (FIR) spectral scan with Herschel/PACS, we present the first detection of the hydroxyl radical (OH) towards the Orion Bar photodissociation region (PDR). Five OH rotational Lambda-doublets involving energy levels out to E_u/k~511 K have been detected (at ~65, ~79, ~84, ~119 and ~163um). The total intensity of the OH lines is I(OH)~5x10^-4 erg s^-1 cm^-2 sr^-1. The observed emission of rotationally excited OH lines is extended and correlates well with the high-J CO and CH^+ J=3-2 line emission (but apparently not with water vapour), pointing towards a common origin. Nonlocal, non-LTE radiative transfer models including excitation by the ambient FIR radiation field suggest that OH arises in a small filling factor component of warm (Tk~160-220 K) and dense (n_H~10^{6-7} cm^-3) gas with source-averaged OH column densities of ~10^15 cm^-2. High density and temperature photochemical models predict such enhanced OH columns at low depths (A_V<1) and small spatial scales (~10^15 cm), where OH formation is driven by gas-phase endothermic reactions of atomic oxygen with molecular hydrogen. We interpret the extended OH emission as coming from unresolved structures exposed to far-ultraviolet (FUV) radiation near the Bar edge (photoevaporating clumps or filaments) and not from the lower density "interclump" medium. Photodissociation leads to OH/H2O abundance ratios (>1) much higher than those expected in equally warm regions without enhanced FUV radiation fields.Comment: Accepted for publication in A&A Letters. Figure B.2. is bitmapped to lower resolutio

Observational evidence of the formation of cyanopolyynes in CRL618 through the polimerization of HCN

The abundance ratio of consecutive members of the cyanopolyynes family has been explored in CRL618 using data acquired in a complete line survey covering the frequency range 81-356 GHz. The Jup range explored for the different molecules is the following: 1 to 4 for HCN and HNC, 9 to 39 for HC3N, 31 to 133 for HC5N, and 72 to 85 for HC7N (not detected beyond Jup=85). The lowest vibrationally excited state of HC7N (nu_15 at 62 cm^-1) has been tentatively detected. Data analysis has been performed by extending our previous geometrical and radiative transfer model of the slowly expanding envelope (SEE) surrounding the compact central continuum source of CRL 618, that was established from the study of rotational lines in several vibrationally excited states of HC_3N. The new lines analyzed here require to model the high velocity wind (HVW) component and the colder circumstellar gas, remnant of the AGB phase of CRL618. The derived HC3N/HC5N and HC5N/HC7N abundance ratios from this set of uniformly calibrated lines are between 3 and 6 in the different regions, similar to standard values in the CSM and ISM, and consistent with previous estimates obtained from ISO observations and chemical models. However, the abundance ratios of HC3N, HC5N and HC7N with respect to HCN are at least two orders of magnitude larger than those typical for AGB C-rich stars, such as IRC+10216. This fact indicates that, in the short transition toward the Planetary Nebula phase, HCN is quickly reprocessed into longer cyanopolyyne chains. A similar behavior was previously found in this object for the polyacetylenic chains (C(2n)H2).Comment: 8 figures, accepted in ApJ main journa

Animal models in the study and treatment of orofacial pain

Pain is one of the first causes of medical consultation in the world and by extension of dental consultation too. Orofacial pain comprehends the oral and facial regions including teeth, oral mucosa, gingiva, tongue and lips, but also the muscles of the jaw and neck, the temporomandibular joint, face, head and neck. Despite its highly estimated prevalence, it appears controversial and hard to quantify given the lack of common criteria to select the population under study and the difficulties to classify the different types of pain. Although for many patients the problem eventually fades after tissue healing, certain sub-chronic and chronic pain conditions remain notoriously undertreated. In this respect, animal models can be of great help. A systematic search was conducted in PubMed-Medline with appropriate keywords: orofacial pain, prevalence and dentist. Seven groups were generated and a second search based on each of these groups and on animal models was made. Search was restricted to English and Spanish, but no time restriction was applied. There are as yet few experimental models of orofacial pain: there hardly exists no other than trigeminal nerve injury for neuropathic pain, a bunch of oral squamous cell carcinoma models (mainly referred to the tongue) for cancer pain and none for the painful swelling of salivary glands. Similarly occurs for the burning mouth syndrome. A few more exist for inflammatory odontalgiae, aphthae, joint, myofascial and muscle inflammatory pains, although scarcely diverse as regards the nature of the noxious stimulus. Given the relevance of envisaging the mechanistic of the various types of orofacial pain, new experimental models are needed on the basis of the dentist?s perspective for their correct management

Spectral line survey of the ultracompact HII region Mon R2

Ultracompact (UC) HII regions constitute one of the earliest phases in the formation of a massive star and are characterized by extreme physical conditions (Go>10^5 Habing field and n>10^6 cm^-3). The UC HII Mon R2 is the closest one and therefore an excellent target to study the chemistry in these complex regions. We carried out a 3mm and 1mm spectral survey using the IRAM 30-m telescope towards three positions that represent different physical environments in Mon R2: (i) the ionization front (IF) at (0",0"); two peaks in the molecular cloud (ii) MP1 at the offset (+15",-15") and (iii) MP2 at the farther offset (0",40"). In addition, we carried out extensive modeling to explain the chemical differences between the three observed regions. We detected more than thirty different species. We detected SO+ and C4H suggesting that UV radiation plays an important role in the molecular chemistry of this region. We detected the typical PDR molecules CN, HCN, HCO, C2H, and c-C3H2. While the IF and the MP1 have a chemistry similar to that found in high UV field and dense PDRs like the Orion Bar, the MP2 is more similar to lower UV/density PDRs like the Horsehead nebula. We also detected complex molecules that are not usually found in PDRs (CH3CN, H2CO, HC3N, CH3OH and CH3C2H). Sulfur compounds CS, HCS+, C2S, H2CS, SO and SO2 and the deuterated species DCN and C2D were also identified. [DCN]/[HCN]=0.03 and [C2D]/[C2H]=0.05, are among the highest in warm regions. Our results show that the high UV/dense PDRs present a different chemistry from that of the low UV case. Abundance ratios like [CO+]/[HCO+] or [HCO]/[HCO+] are good diagnostics to differentiate between them. In Mon R2 we have the two classes of PDRs, a high UV PDR towards the IF and the adjacent molecular bar and a low-UV PDR which extends towards the north-west following the border of the cloud.Comment: 31 page

Kinematics of the ionized-to-neutral interfaces in Monoceros R2

Context. Monoceros R2 (Mon R2), at a distance of 830 pc, is the only ultra-compact H ii region (UC H ii) where its associated photon-dominated region (PDR) can be resolved with the Herschel Space Observatory. Aims. Our aim is to investigate observationally the kinematical patterns in the interface regions (i.e., the transition from atomic to molecular gas) associated with Mon R2. Methods. We used the HIFI instrument onboard Herschel to observe the line profiles of the reactive ions CH+, OH+ and H2O+ toward different positions in Mon R2. We derive the column density of these molecules and compare them with gas-phase chemistry models. Results. The reactive ion CH+ is detected both in emission (at central and red-shifted velocities) and in absorption (at blue-shifted velocities). OH+ is detected in absorption at both blue- and red-shifted velocities, with similar column densities. H2O+ is not detected at any of the positions, down to a rms of 40 mK toward the molecular peak. At this position, we find that the OH+ absorption originates in a mainly atomic medium, and therefore is associated with the most exposed layers of the PDR. These results are consistent with the predictions from photo-chemical models. The line profiles are consistent with the atomic gas being entrained in the ionized gas flow along the walls of the cavity of the H ii region. Based on this evidence, we are able to propose a new geometrical model for this region. Conclusions. The kinematical patterns of the OH+ and CH+ absorption indicate the existence of a layer of mainly atomic gas for which we have derived, for the first time, some physical parameters and its dynamics.Comment: 6 pages, 5 figures. Accepted for publication in A&

First detection of [N II] 205 micrometer absorption in interstellar gas

We present high resolution [NII] 205 micrometer ^3P_1-^3P_0 spectra obtained with Herschel-HIFI towards a small sample of far-infrared bright star forming regions in the Galactic plane: W31C (G10.6-0.4), W49N (G43.2-0.1), W51 (G49.5-0.4), and G34.3+0.1. All sources display an emission line profile associated directly with the HII regions themselves. For the first time we also detect absorption of the [NII] 205 micrometer line by extended low-density foreground material towards W31C and W49N over a wide range of velocities. We attribute this absorption to the warm ionised medium (WIM) and find N(N^+)\approx 1.5x10^17 cm^-2 towards both sources. This is in agreement with recent Herschel-HIFI observations of [CII] 158 micrometer, also observed in absorption in the same sight-lines, if \approx7-10 % of all C^+ ions exist in the WIM on average. Using an abundance ratio of [N]/[H] = 6.76x10^-5 in the gas phase we find that the mean electron and proton volume densities are ~0.1-0.3 cm^-3 assuming a WIM volume filling fraction of 0.1-0.4 with a corresponding line-of-sight filling fraction of 0.46-0.74. A low density and a high WIM filling fraction are also supported by RADEX modelling of the [NII] 205 micrometer absorption and emission together with visible emission lines attributed mainly to the WIM. The detection of the 205 micrometer line in absorption emphasises the importance of a high spectral resolution, and also offers a new tool for investigation of the WIM.Comment: 7 pages, 4 figures, accepted for publication in Astronomy & Astrophysics, 11 June 201

Star Formation Near Photodissociation Regions: Detection of a Peculiar Protostar Near Ced 201

We present the detection and characterization of a peculiar low-mass protostar (IRAS 22129+7000) located ~0.4 pc from Ced 201 Photodissociation Region (PDR) and ~0.2 pc from the HH450 jet. The cold circumstellar envelope surrounding the object has been mapped through its 1.2 mm dust continuum emission with IRAM-30m/MAMBO. The deeply embedded protostar is clearly detected with Spitzer/MIPS (70 um), IRS (20-35 um) and IRAC (4.5, 5.8, and 8 um) but also in the K_s band (2.15 um). Given the large "near- and mid-IR excess" in its spectral energy distribution, but large submillimeter-to-bolometric luminosity ratio (~2%), IRAS 22129+7000 must be a transition Class 0/I source and/or a multiple stellar system. Targeted observations of several molecular lines from CO, 13CO, C18O, HCO+ and DCO+ have been obtained. The presence of a collimated molecular outflow mapped with the CSO telescope in the CO J=3-2 line suggests that the protostar/disk system is still accreting material from its natal envelope. Indeed, optically thick line profiles from high density tracers such as HCO+ J=1-0 show a red-shifted-absorption asymmetry reminiscent of inward motions. We construct a preliminary physical model of the circumstellar envelope (including radial density and temperature gradients, velocity field and turbulence) that reproduces the observed line profiles and estimates the ionization fraction. The presence of both mechanical and (non-ionizing) FUV-radiative input makes the region an interesting case to study triggered star formation