Activation of mutated TRPA1 ion channel by resveratrol in human prostate cancer associated fibroblasts (CAF)

Previous studies showed the effects of resveratrol (RES) on several cancer cells, including prostate cancer (PCa) cell apoptosis without taking into consideration the impact of the tumor microenvironment (TME). The TME is composed of cancer cells, endothelial cells, blood cells and cancer-associated fibroblasts (CAF), the main source of growth factors. The latter cells might modify in the TME the impact of RES on tumor cells via secreted factors. Recent data clearly show the impact of CAF on cancer cells apoptosis resistance via secreted factors. However, the effects of RES on PCa CAF have not been studied so far. We have investigated here for the first time the effects of RES on the physiology of PCa CAF in the context of TME. Using a prostate cancer CAF cell line and primary cultures of CAF from prostate cancers, we show that RES activates the N-terminal mutated Transient Receptor Potential Ankyrin 1 (TRPA1) channel leading to an increase in intracellular calcium concentration and the expression and secretion of growth factors (HGF and VEGF) without inducing apoptosis in these cells. Interestingly, in the present work, we also show that when the prostate cancer cells were co-cultured with CAF, the RES-induced cancer cell apoptosis was reduced by 40%, an apoptosis reduction canceled in the presence of the TRPA1 channel inhibitors. The present work highlights CAF TRPA1 ion channels as a target for RES and the importance of the channel in the epithelial-stromal crosstalk in the TME leading to resistance to the RES-induced apoptosis

Micronutrient fortification to improve growth and health of maternally HIV-unexposed and exposed Zambian infants: a randomised controlled trial

Background: The period of complementary feeding, starting around 6 months of age, is a time of high risk for growth faltering and morbidity. Low micronutrient density of locally available foods is a common problem in low income countries. Children of HIV-infected women are especially vulnerable. Although antiretroviral prophylaxis can reduce breast milk HIV transmission in early infancy, there are no clear feeding guidelines for after 6 months. There is a need for acceptable, feasible, affordable, sustainable and safe (AFASS by WHO terminology) foods for both HIV-exposed and unexposed children after 6 months of age. Methods and Findings: We conducted in Lusaka, Zambia, a randomised double-blind trial of two locally made infant foods: porridges made of flour composed of maize, beans, bambaranuts and groundnuts. One flour contained a basal and the other a rich level of micronutrient fortification. Infants (n = 743) aged 6 months were randomised to receive either regime for 12 months. The primary outcome was stunting (length-for-age Z < -2) at age 18 months. No significant differences were seen between trial arms overall in proportion stunted at 18 months (adjusted odds ratio 0.87; 95% CI 0.50, 1.53; P = 0.63), mean length-for-age Z score, or rate of hospital referral or death. Among children of HIV-infected mothers who breastfed <6 months (53% of HIV-infected mothers), the richly-fortified porridge increased length-for-age and reduced stunting (adjusted odds ratio 0.17; 95% CI 0.04, 0.84; P = 0.03). Rich fortification improved iron status at 18 months as measured by hemoglobin, ferritin and serum transferrin receptors. Conclusions: In the whole study population, the rich micronutrient fortification did not reduce stunting or hospital referral but did improve iron status and reduce anemia. Importantly, in the infants of HIV-infected mothers who stopped breastfeeding before 6 months, the rich fortification improved linear growth. Provision of such fortified foods may benefit health of these high risk infants

Temporal trends of population viral suppression in the context of Universal Test and Treat: the ANRS 12249 TasP trial in rural South Africa

Introduction: The universal test-and-treat (UTT) strategy aims to maximize population viral suppression (PVS), that is, the proportion of all people living with HIV (PLHIV) on antiretroviral treatment (ART) and virally suppressed, with the goal of reducing HIV transmission at the population level. This article explores the extent to which temporal changes in PVS explain the observed lack of association between universal treatment and cumulative HIV incidence seen in the ANRS 12249 TasP trial conducted in rural South Africa. Methods: The TasP cluster-randomized trial (2012 to 2016) implemented six-monthly repeat home-based HIV counselling and testing (RHBCT) and referral of PLHIV to local HIV clinics in 2 9 11 clusters opened sequentially. ART was initiated according to national guidelines in control clusters and regardless of CD4 count in intervention clusters. We measured residency status, HIV status, and HIV care status for each participant on a daily basis. PVS was computed per cluster among all resident PLHIV (≥16, including those not in care) at cluster opening and daily thereafter. We used a mixed linear model to explore time patterns in PVS, adjusting for sociodemographic changes at the cluster level. Results: 8563 PLHIV were followed. During the course of the trial, PVS increased significantly in both arms (23.5% to 46.2% in intervention, +22.8, p < 0.001; 26.0% to 44.6% in control, +18.6, p < 0.001). That increase was similar in both arms (p = 0.514). In the final adjusted model, PVS increase was most associated with increased RHBCT and the implementation of local trial clinics (measured by time since cluster opening). Contextual changes (measured by calendar time) also contributed slightly. The effect of universal ART (trial arm) was positive but limited. Conclusions: PVS was improved significantly but similarly in both trial arms, explaining partly the null effect observed in terms of cumulative HIV incidence between arms. The PVS gains due to changes in ART-initiation guidelines alone are relatively small compared to gains obtained by strategies to maximize testing and linkage to care. The achievement of the 90-90-90 targets will not be met if the operational and implementational challenges limiting access to care and treatment, often context-specific, are not properly addressed. Clinical trial number: NCT01509508 (clinicalTrials.gov)/DOH-27-0512-3974 (South African National Clinical Trials Register)

Etude et optimisation des performances de l'instrument MXT, télescope X à micro-canaux, embarqué à bord de la mission spatiale d'astronomie SVOM

SVOM is a Sino-French space mission to be launched at the end of 2021. Its objective is the study of gamma-ray bursts (GRBs) and other transient high energy sources. These GRBs are very powerful cosmic explosions that can be detected at extreme distances. They appear randomly on all the sky and emit radiation in a wide wavelength range, from the infrared emission to gamma rays. SVOM space mission will shed new light on the physical phenomena associated to GRBs by detecting and observing them in real time over a wide energy range. The satellite, which will be injected on a low Earth orbit, will carry four instruments sensitive from the visible to the gamma-ray domain. Ground based telescopes will complement the space borne ones and will allow for follow-up observations from the visible to the infrared band. The MXT instrument, whose optics are based on the “lobster eyes” principle, will observe GRBs soft X-rays counterparts (afterglows) between 0.2 and 10 keV. This optics will be used for the first time for an X-ray telescope which means to characterize this optics. MXT will play a key role in the localization of these astrophysical sources that will be transmitted, in real time, to ground based instruments allowing for fast and precise observations. During my thesis, I developed an MXT observation simulator in order to predict the performances of the instrument during the mission. I also developed localization algorithms to be implemented on board the SVOM satellite and made use of the state of the art knowledge about X-ray afterglows in order to predict the localization capabilities of MXT. I demonstrated thaht 50% of these afterglows will be localized with a better precision than the arc-minute. I finally applied my simulation tools in the case of gravitational wave sources and, in particular, to assess the capabilities of MXT to observe bright X-ray counterparts of binary neutron star mergers.SVOM est une mission spatiale franco-chinoise qui sera lancée à la fin de l’année 2021. Son objectif est d’étudier les sursauts gamma et autres sources transitoires du ciel X et gamma. Les sursauts gamma sont des explosions cosmiques brèves et très énergétiques permettant leurs détections à des distances extrêmes. Ils apparaissent de manière aléatoire sur tout le ciel et émettent de la radiation dans une large gamme de longueurs d’ondes, allant de l’émission en infrarouge jusqu’aux rayons gamma. SVOM, qui évoluera en orbite basse autour de la Terre, sera composé de quatre instruments, sensibles du domaine visible aux rayons gamma, et sera couplé à des télescopes situés sur Terre qui effectueront des observations complémentaires dans les longueurs d’ondes allant du visible à de l’infrarouge. Le travail que je présente dans cette thèse est basé sur l’étude des performances du télescope MXT, dont l’optique est inspirée du principe de fonctionnement des “yeux des langoustes”. Elle sera mise en place pour la première fois dans le cadre de télescopes X, nécessitant donc de comprendre la réponse de cette optique. MXT est chargé d’observer, la contrepartie qui suit les sursauts gamma, dite émission rémanente, dans la gamme des rayons X entre 0,2 et 10 keV. Il joue un rôle clé dans la localisation précise de ces sources astrophysiques afin de transmettre, en temps réel, leurs positions aux télescopes situés au sol, qui observeront à leur tour, rapidement et précisément, le phénomène. Au cours de mon travail de thèse, j’ai mis en place un simulateur d’observation de MXT qui m’a permis d’estimer et d’étudier les performances attendues de l’instrument au cours de la mission. J’ai également développé des algorithmes de localisation qui seront implémentés à bord du satellite. Ceux-ci m’ont ensuite permis de tester les capacités de localisation de MXT à partir d’une base de données des rémanences de sursauts gamma et de montrer que 50% de ces rémanences seront localisées plus précisément que la minute d’arc. J’ai enfin appliqué une partie de mes modélisations numériques dans le cas de sources d’ondes gravitationnelles afin d’évaluer la détection des contreparties X d’étoiles à neutrons binaires

Study and optimization of the MXT instrument, microchannel X-ray telescope onboard the SVOM space mission

SVOM est une mission spatiale franco-chinoise qui sera lancée à la fin de l’année 2021. Son objectif est d’étudier les sursauts gamma et autres sources transitoires du ciel X et gamma. Les sursauts gamma sont des explosions cosmiques brèves et très énergétiques permettant leurs détections à des distances extrêmes. Ils apparaissent de manière aléatoire sur tout le ciel et émettent de la radiation dans une large gamme de longueurs d’ondes, allant de l’émission en infrarouge jusqu’aux rayons gamma. SVOM, qui évoluera en orbite basse autour de la Terre, sera composé de quatre instruments, sensibles du domaine visible aux rayons gamma, et sera couplé à des télescopes situés sur Terre qui effectueront des observations complémentaires dans les longueurs d’ondes allant du visible à de l’infrarouge. Le travail que je présente dans cette thèse est basé sur l’étude des performances du télescope MXT, dont l’optique est inspirée du principe de fonctionnement des “yeux des langoustes”. Elle sera mise en place pour la première fois dans le cadre de télescopes X, nécessitant donc de comprendre la réponse de cette optique. MXT est chargé d’observer, la contrepartie qui suit les sursauts gamma, dite émission rémanente, dans la gamme des rayons X entre 0,2 et 10 keV. Il joue un rôle clé dans la localisation précise de ces sources astrophysiques afin de transmettre, en temps réel, leurs positions aux télescopes situés au sol, qui observeront à leur tour, rapidement et précisément, le phénomène. Au cours de mon travail de thèse, j’ai mis en place un simulateur d’observation de MXT qui m’a permis d’estimer et d’étudier les performances attendues de l’instrument au cours de la mission. J’ai également développé des algorithmes de localisation qui seront implémentés à bord du satellite. Ceux-ci m’ont ensuite permis de tester les capacités de localisation de MXT à partir d’une base de données des rémanences de sursauts gamma et de montrer que 50% de ces rémanences seront localisées plus précisément que la minute d’arc. J’ai enfin appliqué une partie de mes modélisations numériques dans le cas de sources d’ondes gravitationnelles afin d’évaluer la détection des contreparties X d’étoiles à neutrons binaires.SVOM is a Sino-French space mission to be launched at the end of 2021. Its objective is the study of gamma-ray bursts (GRBs) and other transient high energy sources. These GRBs are very powerful cosmic explosions that can be detected at extreme distances. They appear randomly on all the sky and emit radiation in a wide wavelength range, from the infrared emission to gamma rays. SVOM space mission will shed new light on the physical phenomena associated to GRBs by detecting and observing them in real time over a wide energy range. The satellite, which will be injected on a low Earth orbit, will carry four instruments sensitive from the visible to the gamma-ray domain. Ground based telescopes will complement the space borne ones and will allow for follow-up observations from the visible to the infrared band. The MXT instrument, whose optics are based on the “lobster eyes” principle, will observe GRBs soft X-rays counterparts (afterglows) between 0.2 and 10 keV. This optics will be used for the first time for an X-ray telescope which means to characterize this optics. MXT will play a key role in the localization of these astrophysical sources that will be transmitted, in real time, to ground based instruments allowing for fast and precise observations. During my thesis, I developed an MXT observation simulator in order to predict the performances of the instrument during the mission. I also developed localization algorithms to be implemented on board the SVOM satellite and made use of the state of the art knowledge about X-ray afterglows in order to predict the localization capabilities of MXT. I demonstrated thaht 50% of these afterglows will be localized with a better precision than the arc-minute. I finally applied my simulation tools in the case of gravitational wave sources and, in particular, to assess the capabilities of MXT to observe bright X-ray counterparts of binary neutron star mergers

The effects of micronutrient-fortified complementary/replacement food on intestinal permeability and systemic markers of inflammation among maternally HIV-exposed and unexposed Zambian infants.

The present randomised trial investigated the effects of feeding Zambian infants from 6 to 18 months old either a richly or basal micronutrient-fortified complementary/replacement food on gut integrity and systemic inflammation. Blood samples were obtained from all infants (n 743) at 6 and 18 months for the assessment of serum C-reactive protein (CRP) and α1-acid glycoprotein (AGP). A subsample of 502 infants, selected from the main cohort to include a larger proportion of infants with HIV-positive mothers, was assigned to lactulose/mannitol gut permeability tests. Lactulose:mannitol (L:M) ratio analyses were adjusted for baseline urinary L:M ratio, socio-economic status, mother's education, season of birth and baseline stunting, and stratified by maternal antenatal HIV status, child's sex, concurrent breast-feeding status and anaemia at baseline. There was no significant difference in geometric mean L:M ratio between the richly fortified and basal-fortified porridge arms at 12 months (0·47 (95 % CI 0·41, 0·55) v. 0·41 (95 % CI 0·34, 0·49); P = 0·16 adjusted). At 18 months, the richly fortified porridge group had a significantly higher geometric mean L:M ratio than the basal-fortified group (0·23 (95 % CI 0·19, 0·28) v. 0·15 (95 % CI 0·12, 0·19); P = 0·02 adjusted). This effect was evident for all stratifications, significantly among boys (P = 0·04), among the infants of HIV-negative mothers (P = 0·01), among the infants of HIV-negative mothers not concurrently breast-fed (P = 0·01) and among those who were not anaemic at baseline (P = 0·03). CRP, but not AGP, was positively associated with L:M ratio, but there were no significant effects of the diet on either CRP or AGP. In conclusion, a richly fortified complementary/replacement food did not benefit and may have worsened intestinal permeability

Anti-p200 pemphigoid responding to dapsone

Anti-p200 pemphigoid is a rare autoimmune subepidermal blistering disease. Clinical presentation is similar to standard bullous pemphigoid (BP) but mucous membranes and cephalic lesions are more frequent. Histology and direct immunofluorescence (IF) are identical to BP but indirect IF discloses linear deposits of immunoglobulin G (IgG) on the dermal side of artificial salt-split skin. Specific diagnosis is based on western immunoblotting that shows circulating IgG recognizing a 200-kDa protein localized on the dermal extract. The 200-kDa antigen was recently identified as laminin γ1. Anti-p200 pemphigoid should be considered before all atypical or topical steroid-resistant bullous disease, as well as mucous membranes pemphigoid or epidermolysis bullosa acquisita. Dapsone appears to be the most effective treatment and should be used as the first option in combination with topical steroids. In this report, we describe the case of a patient with a typical clinical and immunopathological anti-p200 pemphigoid, responding to a combination of topical steroids and dapsone

UBC Food Systems Project: Moving UBC Food Outlets Beyond Climate Neutral

Disclaimer: “UBC SEEDS provides students with the opportunity to share the findings of their studies, as well as their opinions, conclusions and recommendations with the UBC community. The reader should bear in mind that this is a student project/report and is not an official document of UBC. Furthermore readers should bear in mind that these reports may not reflect the current status of activities at UBC. We urge you to contact the research persons mentioned in a report or the SEEDS Coordinator about the current status of the subject matter of a project/report.”Land and Food Systems, Faculty ofUnreviewedUndergraduat

Cost-effectiveness of adding a birth dose of hepatitis B vaccine in the Dafra district of the Hauts-Bassins Region in Burkina Faso (NéoVac Study)

International audienceBackground: The World Health Organization (WHO) recommends a first hepatitis B vaccine dose within 24 h of birth (HepB-BD) to prevent mother-to-child transmission. Evidence for this strategy's economic value in Africa is limited. We assessed the costs and cost-effectiveness of adding HepB-BD to the current three-dose pentavalent schedule (HepB3) in the Dafra district of the Hauts-Bassins Region in Burkina Faso.Methods: Using a decision tree combined with a Markov model, we estimated the expected number of life-years (LY) and disability-adjusted life-years (DALYs) saved, incremental costs, and incremental cost-effectiveness ratios (ICER) of HepB-BD + HepB3 versus HepB3 alone in Dafra's 2017 birth cohort (n = 11,462). Institutional delivery rates, vaccine coverage, and vaccination costs from a health system perspective were estimated from field-collected data. We estimated the effectiveness of HepB-BD, age-specific transition probabilities, and horizontal transmission risks using data from previous African studies. Costs and health outcomes were discounted at an annual rate of 3%. We conducted one-way and probabilistic sensitivity analyses to assess uncertainty.Results: In the base-case analysis without discounting, HepB-BD + HepB3 yielded a net cost saving of US$18,979 and saved 163 DALYs compared with HepB3 alone. With discounting, HepB-BD + HepB3 compared with HepB3 resulted in an incremental cost of US$554 and 31 DALYs averted, translating into an ICER of US$18/DALY averted. In one-way sensitivity analyses, HepB-BD + HepB3 remained cost-effective (at the cost-effectiveness threshold of US$671 i.e. the Burkina Faso per-capita gross domestic product) for all parameter changes. However, results were very sensitive to variations in HepB-BD unit cost per vaccinated neonate and perinatal transmission risk in mothers carrying the hepatitis B e antigen. The probabilities of HepB-BD + HepB3 being cost-effective were 71.7% and 86.7%, at the cost-effectiveness thresholds of US$335 and US$671, respectively.Conclusion: Introducing HepB-BD in Burkina Faso is likely to be cost-effective