Water Ice and Dust in the Innermost Coma of Comet 103P/Hartley 2

On November 4th, 2010, the Deep Impact eXtended Investigation (DIXI) successfully encountered comet 103P/Hartley 2, when it was at a heliocentric distance of 1.06 AU. Spatially resolved near-IR spectra of comet Hartley 2 were acquired in the 1.05-4.83 micron wavelength range using the HRI-IR spectrometer. We present spectral maps of the inner ~10 kilometers of the coma collected 7 minutes and 23 minutes after closest approach. The extracted reflectance spectra include well-defined absorption bands near 1.5, 2.0, and 3.0 micron consistent in position, bandwidth, and shape with the presence of water ice grains. Using Hapke's radiative transfer model, we characterize the type of mixing (areal vs. intimate), relative abundance, grain size, and spatial distribution of water ice and refractories. Our modeling suggests that the dust, which dominates the innermost coma of Hartley 2 and is at a temperature of 300K, is thermally and physically decoupled from the fine-grained water ice particles, which are on the order of 1 micron in size. The strong correlation between the water ice, dust, and CO2 spatial distribution supports the concept that CO2 gas drags the water ice and dust grains from the nucleus. Once in the coma, the water ice begins subliming while the dust is in a constant outflow. The derived water ice scale-length is compatible with the lifetimes expected for 1-micron pure water ice grains at 1 AU, if velocities are near 0.5 m/s. Such velocities, about three order of magnitudes lower than the expansion velocities expected for isolated 1-micron water ice particles [Hanner, 1981; Whipple, 1951], suggest that the observed water ice grains are likely aggregates.Comment: 51 pages, 12 figures, accepted for publication in Icaru

Constitutive Differential Features of Type 2 Transglutaminase in Cells Derived from Celiac Patients and from Healthy Subjects

Type 2 transglutaminase (TG2) is a ubiquitous enzyme able to modify gliadin peptides introduced into the organism through the diet. By means of its catalytic activity, TG2 seems to have an important pathogenetic role in celiac disease (CD), an inflammatory intestinal disease caused by the ingestion of gluten-containing cereals. A strong autoimmune response to TG2 characterizes CD development. Anti-TG2 antibodies specifically derange the uptake of the α-gliadin peptide 31-43 by control, but not by celiac dermal fibroblasts, underlying some different constitutive features regarding TG2 in healthy and celiac subjects. Our aim was to investigate whether these differences depended on a different TG2 subcellular distribution and whether peptide 31-43 differentially regulated TG2 expression and activity in cells of the two groups of subjects. We found that TG2 was more abundantly associated with membranes of celiac fibroblasts than of control cells, in particular with the early endosomal and autophagic compartments. We also found that peptide 31-43 differentially affected TG2 expression and activity in the two groups of cells, activating TG2 more in control than in celiac cells and inducing TG2 expression in celiac cells, but not in control ones. The different TG2 subcellular localization and the different way the peptide 31-43 modulates TG2 activity and availability into control and CD cells suggested that TG2 is involved in the definition of a constitutive CD cellular phenotype, thus having an important and still undefined role in CD pathogenesis

Couples' decision-making on post-partum family planning and antenatal counselling in Uganda: A qualitative study.

BACKGROUND: Although health workers have been trained to provide post-partum family planning (PPFP), uptake remains low in Uganda. An important reason is that women want the agreement of their partner, who is often absent at the time of delivery. In order to address this, we aimed to understand the views of couples and explore barriers and facilitators to implementation of antenatal couples' counselling on PPFP in Uganda. METHODS: We conducted individual interviews with a purposive sample of 12 postpartum and 3 antenatal couples; and 34 focus groups with a total of 323 participants (68 adolescent women, 83 women aged 20-49, 79 men, 93 health workers) in four contrasting communities (urban and rural) in South-West and Central Uganda. These were recorded, transcribed, translated, and analysed thematically. RESULTS: Although most participants felt that it is important for partners to discuss family planning, half of the couples were unaware of each other's views on contraception. Most had similar views on motivation to use family planning but not on preferred contraceptive methods. Most liked the idea of antenatal couples' counselling on PPFP. The main barrier was the reluctance of men to attend antenatal clinics (ANC) in health facilities. Respondents felt that Village Health Teams (VHTs) could provide initial counselling on PPFP in couples' homes (with telephone support from health workers, if needed) and encourage men to attend ANC. Suggested facilitators for men to attend ANC included health workers being more welcoming, holding ANC clinics at weekends and "outreach" clinics (in rural villages far from health facilities). CONCLUSION: Antenatal couples' counselling has the potential to facilitate agreement PPFP, but some men are reluctant to attend antenatal clinics. Counselling at home by VHTs as well as simple changes to the organisation of antenatal clinics, could make it possible to deliver antenatal couples' counselling on PPFP

Couples' decision-making on post-partum family planning and antenatal counselling in Uganda: A qualitative study.

BACKGROUND: Although health workers have been trained to provide post-partum family planning (PPFP), uptake remains low in Uganda. An important reason is that women want the agreement of their partner, who is often absent at the time of delivery. In order to address this, we aimed to understand the views of couples and explore barriers and facilitators to implementation of antenatal couples' counselling on PPFP in Uganda. METHODS: We conducted individual interviews with a purposive sample of 12 postpartum and 3 antenatal couples; and 34 focus groups with a total of 323 participants (68 adolescent women, 83 women aged 20-49, 79 men, 93 health workers) in four contrasting communities (urban and rural) in South-West and Central Uganda. These were recorded, transcribed, translated, and analysed thematically. RESULTS: Although most participants felt that it is important for partners to discuss family planning, half of the couples were unaware of each other's views on contraception. Most had similar views on motivation to use family planning but not on preferred contraceptive methods. Most liked the idea of antenatal couples' counselling on PPFP. The main barrier was the reluctance of men to attend antenatal clinics (ANC) in health facilities. Respondents felt that Village Health Teams (VHTs) could provide initial counselling on PPFP in couples' homes (with telephone support from health workers, if needed) and encourage men to attend ANC. Suggested facilitators for men to attend ANC included health workers being more welcoming, holding ANC clinics at weekends and "outreach" clinics (in rural villages far from health facilities). CONCLUSION: Antenatal couples' counselling has the potential to facilitate agreement PPFP, but some men are reluctant to attend antenatal clinics. Counselling at home by VHTs as well as simple changes to the organisation of antenatal clinics, could make it possible to deliver antenatal couples' counselling on PPFP

Gliadin-Mediated Proliferation and Innate Immune Activation in Celiac Disease Are Due to Alterations in Vesicular Trafficking

Background and Objectives: Damage to intestinal mucosa in celiac disease (CD) is mediated both by inflammation due to adaptive and innate immune responses, with IL-15 as a major mediator of the innate immune response, and by proliferation of crypt enterocytes as an early alteration of CD mucosa causing crypts hyperplasia. We have previously shown that gliadin peptide P31-43 induces proliferation of cell lines and celiac enterocytes by delaying degradation of the active epidermal growth factor receptor (EGFR) due to delayed maturation of endocytic vesicles. IL-15 is increased in the intestine of patients affected by CD and has pleiotropic activity that ultimately results in immunoregulatory cross-talk between cells belonging to the innate and adaptive branches of the immune response. Aims of this study were to investigate the role of P31-43 in the induction of cellular proliferation and innate immune activation. Methods/Principal Findings: Cell proliferation was evaluated by bromodeoxyuridine (BrdU) incorporation both in CaCo-2 cells and in biopsies from active CD cases and controls. We used real-time PCR to evaluate IL-15 mRNA levels and FACS as well as ELISA and Western Blot (WB) analysis to measure protein levels and distribution in CaCo-2 cells. Gliadin and P31-43 induce a proliferation of both CaCo-2 cells and CD crypt enterocytes that is dependent on both EGFR and IL-15 activity. In CaCo-2 cells, P31-43 increased IL-15 levels on the cell surface by altering intracellular trafficking. The increased IL-15 protein was bound to IL15 receptor (IL-15R) alpha, did not require new protein synthesis and functioned as a growth factor. Conclusion: In this study, we have shown that P31-43 induces both increase of the trans-presented IL-15/IL5R alpha complex on cell surfaces by altering the trafficking of the vesicular compartments as well as proliferation of crypt enterocytes with consequent remodelling of CD mucosa due to a cooperation of IL-15 and EGFR

Phase I Safety and Immunogenicity Evaluation of MVA-CMDR, a Multigenic, Recombinant Modified Vaccinia Ankara-HIV-1 Vaccine Candidate

We conducted a Phase I randomized, dose-escalation, route-comparison trial of MVA-CMDR, a candidate HIV-1 vaccine based on a recombinant modified vaccinia Ankara viral vector expressing HIV-1 genes env/gag/pol. The HIV sequences were derived from circulating recombinant form CRF01_AE, which predominates in Thailand. The objective was to evaluate safety and immunogenicity of MVA-CMDR in human volunteers in the US and Thailand.MVA-CMDR or placebo was administered intra-muscularly (IM; 10(7) or 10(8) pfu) or intradermally (ID; 10(6) or 10(7) pfu) at months 0, 1 and 3, to 48 healthy volunteers at low risk for HIV-1 infection. Twelve volunteers in each dosage group were randomized to receive MVA-CMDR or placebo (10∶2). Volunteers were actively monitored for local and systemic reactogenicity and adverse events post vaccination. Cellular immunogenicity was assessed by a validated IFNγ Elispot assay, an intracellular cytokine staining assay, lymphocyte proliferation and a (51)Cr-release assay. Humoral immunogenicity was assessed by ADCC for gp120 and binding antibody ELISAs for gp120 and p24. MVA-CMDR was safe and well tolerated with no vaccine related serious adverse events. Cell-mediated immune responses were: (i) moderate in magnitude (median IFNγ Elispot of 78 SFC/10(6) PBMC at 10(8) pfu IM), but high in response rate (70% (51)Cr-release positive; 90% Elispot positive; 100% ICS positive, at 10(8) pfu IM); (ii) predominantly HIV Env-specific CD4(+) T cells, with a high proliferative capacity and durable for at least 6 months (100% LPA response rate by the IM route); (iv) dose- and route-dependent with 10(8) pfu IM being the most immunogenic treatment. Binding antibodies against gp120 and p24 were detectable in all vaccination groups with ADCC capacity detectable at the highest dose (40% positive at 10(8) pfu IM).MVA-CMDR delivered both intramuscularly and intradermally was safe, well-tolerated and elicited durable cell-mediated and humoral immune responses.ClinicalTrials.gov NCT00376090

Motor ability and attention span among individuals dependent on illicit psychotropic drugs

Psychoactive substances act on the central nervous system producing mental and behavioral changes leading to clinical manifestations associated with drug abuse. Objective: To evaluate the motor ability and attention span among individuals dependent on psychotropic drugs, who were in treatment in a psychiatric hospital. Method: A single case study, whose unit of analysis was a hospital, assessed the motor skills and attention span of 10 male individuals addicted to illicit psychotropic drugs, with mean age of 31.9 ± 7.07 years and average hospitalization of 23.9 days. The following instruments were used: a structured socio-demographic interview, the Motor Scale for Elderly (EMTI) adapted, and the Trail Making Test (TMT A and B). The average age at first consumption was 15.1 years; and there was a slower performance in the TMT A and B in all age groups. In general motor ability, individuals were classified as follows: two “superior”, two “above average”, five “average”, and one “below average”. Results: Their temporal organization was the variable with the lowest performance. Conclusion: Attention deficits were encountered along with average general motor ability and a strong negative association or correlation between motor performance and attention span.As substâncias psicoativas atuam no sistema nervoso central produzindo alterações mentais e de comportamento levando a manifestações clínicas associadas ao uso abusivo de drogas. Objetivo: Avaliar a aptidão motora e a atenção em indivíduos dependentes de drogas psicotrópicas ilícitas, que se encontravam internados em Hospital Psiquiátrico. Método: Estudo de caso único, cuja unidade de análise foi uma unidade hospitalar, o qual avaliou a aptidão motora e a atenção em 10 indivíduos dependentes de drogas psicotrópicas ilícitas, do sexo masculino, com média de idade de 31,9 ± 7,07 anos e média de internação de 23,9 dias. Utilizados os seguintes instrumentos: entrevista estruturada sócio-demográfica e Escala Motora para Terceira Idade (EMTI) adaptada e Teste de Traços (TMT A e B). A idade média de início do consumo 15,1 anos; maior tempo de execução do TMT A e B em todas as faixas etárias. Resultados: Na aptidão motora geral os indivíduos foram classificados: dois como “superior”, dois “normal alto”, cinco “normal médio” e um “inferior”. A organização temporal foi a variável com desempenho mais baixo. Conclusão: Foi encontrado déficit na atenção, com média da aptidão motora geral normal e forte associação negativa ou correlação entre o desempenho motor e atenção

Atenção à saúde em grupos sob a perspectiva dos idosos

La finalidad fue analizar las actividades en los grupos de ancianos en las unidades de la salud. Portador de enfermedades degenerativas, el adulto mayor pide cuidados continuos y más frecuentes de los servicios de salud, lo que puede facilitarse a través de las acciones en grupos, privilegiando la acción educativa. Se observó gran diversidad de los métodos usados, equipos responsables y composición de los grupos. En cuanto a las personas, se verificó que esta actividad permite una mejor comprensión y aceptación del proceso de salud-enfermedad, así como la toma de papeles sociales y la ocupación del tiempo libre. Para los servicios, los grupos posibilitan la expansión del vínculo, pidiendo, sin embargo, la capacitación y la educación permanente de los profesionales en el sentido de permitir un diálogo significante. La tendencia de aumento de estas acciones en Campinas/SP está acompañando las directivas del proyecto PAIDÉIA de Salud del la Familia, siendo un posible y privilegiado espacio de aplicación del «método de la rueda».Este estudo objetivou descrever e analisar as atividades em grupos de idosos em unidades básicas de saúde. Portador de múltiplos transtornos, o idoso requer cuidados contínuos e freqüentes dos serviços de saúde, o que pode ser facilitado pelas ações em grupos, privilegiando a ação educativa. Observou-se grande diversidade de métodos, equipes responsáveis e composição dos grupos. Em relação aos idosos constatou-se que essa atividade permite a sua melhor compreensão e aceitação do adoecimento, bem como a retomada de papéis sociais e a ocupação do tempo livre. Para os serviços, os grupos possibilitam a ampliação do vínculo, requerendo, entretanto, a capacitação e educação permanente dos profissionais no sentido de possibilitar um diálogo significativo. A tendência de aumento dessas ações em Campinas-SP vem acompanhando as diretrizes do projeto PAIDÉIA de Saúde da Família, sendo o grupo um espaço possível e privilegiado de aplicação do "método da roda".This study aimed to describe and analyze the activities in elderly groups at basic health care units. Suffering from chronic-degenerative diseases, the elderly need continuous and more frequent health care. This can be facilitated by group actions, privileging educational activities. We found great diversity in methods, responsible teams and group composition. As to the patients, this activity allows for a better understanding and acceptance of the illness, as well as for the recovery of social roles and the occupation of leisure time. For services, the groups permit increased bonding. However, this requires training and permanent education for professionals, with a view to a significant dialogue. The increasing tendency of these actions in Campinas/SP is accompanying the guidelines of the Family Health PAIDÉIA project. The group is a possible and privileged space to apply the PAIDÉIA method

Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration

Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In the present study, we analyzed the SQSTM1 coding sequence for mutations in an extended cohort of 1,808 patients with frontotemporal lobar degeneration (FTLD), ascertained within the European Early-Onset Dementia consortium. As control dataset, we sequenced 1,625 European control individuals and analyzed whole-exome sequence data of 2,274 German individuals (total n = 3,899). Association of rare SQSTM1 mutations was calculated in a meta-analysis of 4,332 FTLD and 10,240 control alleles. We identified 25 coding variants in FTLD patients of which 10 have not been described. Fifteen mutations were absent in the control individuals (carrier frequency < 0.00026) whilst the others were rare in both patients and control individuals. When pooling all variants with a minor allele frequency < 0.01, an overall frequency of 3.2 % was calculated in patients. Rare variant association analysis between patients and controls showed no difference over the whole protein, but suggested that rare mutations clustering in the UBA domain of SQSTM1 may influence disease susceptibility by doubling the risk for FTLD (RR = 2.18 [95 % CI 1.24-3.85]; corrected p value = 0.042). Detailed histopathology demonstrated that mutations in SQSTM1 associate with widespread neuronal and glial phospho-TDP-43 pathology. With this study, we provide further evidence for a putative role of rare mutations in SQSTM1 in the genetic etiology of FTLD and showed that, comparable to other FTLD/ALS genes, SQSTM1 mutations are associated with TDP-43 pathology

Thyroid hormone inhibits hepatocellular carcinoma progression via induction of differentiation and metabolic reprogramming

The limited therapeutic options available for hepatocellular carcinoma (HCC) make mandatory to find alternative effective treatments for this tumor. Based on the recent finding that systemic or local hypothyroidism is associated with HCC development in humans and rodents, we investigated whether the thyroid hormone triiodothyronine (T3) could inhibit the progression of hepatocellular carcinomas (HCCs)