The immunological response to syphilis differs by HIV status; a prospective observational cohort study

BACKGROUND: It is not known if there is a difference in the immune response to syphilis between HIV-infected and uninfected individuals. METHODS: We prospectively recruited all patients with a new diagnosis of syphilis and tested their plasma for IFNα, IFNγ, IL-1β, IL-12p40, IL-12p70, IP-10, MCP-1, MIP-1α, MIP-1β, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10 and IL-17A at baseline pre-treatment and 6 months following therapy. RESULTS: A total of 79 HIV-infected [44 primary/secondary syphilis (PSS) and 35 latent syphilis (LS)] and 12 HIV-uninfected (10 PSS and 2 LS) cases of syphilis and 30 HIV-infected controls were included in the study. At the baseline visit, compared to the control group, concentrations of IL-10 were significantly elevated in the HIV-infected and uninfected groups. The level of IL-10 was significantly higher in the HIV-infected compared to the HIV-uninfected PSS group (25.3 pg/mL (IQR, 4.56-41.76) vs 2.73 pg/mL (IQR, 1.55-9.02), P = 0.0192). In the HIV-infected PSS group (but not the HIV-infected LS or HIV-uninfected PSS groups) the IP-10, MIP-1b, IL-6 and IL-8 were raised compared to the controls. IL-10 levels decreased but did not return to control baseline values by 6 months in HIV infected PSS and LS and HIV uninfected PSS. CONCLUSION: PSS and LS in HIV-infected individuals is characterized by an increase in inflammatory and anti-inflammatory cytokines such as IL-10. The increase of IL-10 is greater in HIV-infected than uninfected individuals. Further work is required to ascertain if this is part of an immunological profile that correlates with adverse outcomes such as serofast syphilis and neurosyphilis, in HIV-infected individuals

Schistosoma haematobium infection and Buruli ulcer

No abstract available

Pre-incubation of cell-free HIV-1 group M isolates with non-nucleoside reverse transcriptase inhibitors blocks subsequent viral replication in co-cultures of dendritic cells and T cells.

In order to study the inhibitory effect of various reverse transcriptase inhibitors (RTIs) on cell-free HIV, we adapted a recently described in vitro system, based on co-cultures of dendritic cells and resting CD4 T cells, modelling early target cells during sexual transmission. The compounds tested included the second-generation non-nucleoside RTI (NNRTI) TMC-120 (R147681, dapivirine) and TMC-125 (R165335, travertine), as well as the reference nucleoside RTI AZT (zidovudine), the nucleotide RTI PMPA (tenofovir) and the NNRTI UC-781. The virus strains included the reference strain HIV-1Ba-L and six primary isolates, representative of the HIV-1 group M pandemic. They all display the non-syncytium-inducing and CCR5 receptor-using (NSI/R5) phenotype, important in transmission. Cell-free virus was immobilized on a poly-L-lysine (PLL)-treated microwell plate and incubated with compound for 1 h. Afterwards, the compound was thoroughly washed away; target cells were added and cultured for 2 weeks, followed by an extended culture with highly susceptible mitogen-activated T cells. Viral production in the cultures was measured on supernatant with HIV antigen ELISA. Negative results were confirmed by showing absence of proviral DNA in the cells. TMC-120 and TMC-125 inhibited replication of HIV-1Ba-L with average EC50 values of 38 nM and 117 nM, respectively, whereas the EC50 of UC-781 was 517 nM. Complete suppression of virus and provirus was observed at compound concentrations of 100, 300 and 1000 nM, respectively. Inhibition of all primary isolates followed the same pattern as HIV-1Ba-L. In contrast, pre-treating the virus with the nucleotide RTI PMPA and AZT failed to inhibit infection even at a concentration of 100000 nM. These data clearly suggest that NNRTIs inactivate RT enzymatic activity of different viral clades (predominant in the epidemic) and might be proposed for further testing as a sterilizing microbicide worldwide

Magnetic properties of silicon steel after plastic deformation

The energy efficiency of electric machines can be improved by optimizing their manufacturing process. During the manufacturing of ferromagnetic cores, silicon steel sheets are cut and stacked. This process introduces large stresses near cutting edges. The steel near cutting edges is in a plastically deformed stress state without external mechanical load. The magnetic properties of the steel in this stress state are investigated using a custom magnetomechanical measurement setup, stress strain measurements, electrical resistance measurements, and transmission electron microscopic (TEM) measurements. Analysis of the core energy losses is done by means of the loss separation technique. The silicon steel used in this paper is non-grain oriented (NGO) steel grade M270-35A. Three differently cut sets of M270-35A are investigated, which differ in the direction they are cut with respect to the rolling direction. The effect of sample deformation was measured—both before and after mechanical load release—on the magnetization curve and total core energy losses. It is known that the magnetic properties dramatically degrade with increasing sample deformation under mechanical load. In this paper, it was found that when the mechanical load is released, the magnetic properties degrade even further. Loss separation analysis has shown that the hysteresis loss is the main contributor to the additional core losses due to sample deformation. Releasing the mechanical load increased the hysteresis loss up to 270% at 10.4% pre-release strain. At this level of strain, the relative magnetic permeability decreased up to 45% after mechanical load release. Manufacturing processes that introduce plastic deformation are detrimental to the local magnetic material properties

Is vitamin D deficiency involved in the immune reconstitution inflammatory syndrome?

<p>Abstract</p> <p>Background</p> <p>About 20–30% of persons with HIV infection, especially those living in countries with limited resources, experience an immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral treatment. The active form of vitamin D, 1,25-dihydroxyvitamin D, is a key player in the clearance of pathogens and influences the level of inflammation and macrophage activation.</p> <p>Presentation of the hypothesis</p> <p>We hypothesize that low availability of 1,25-dihydroxyvitamin D, either due to vitamin D deficiency or due to polymorphisms in the vitamin D receptor or in its activating/inactivating enzymes, contributes to the appearance of IRIS. Furthermore, drug interactions with the enzymatic pathways of vitamin D could favour the development of IRIS.</p> <p>Testing the hypothesis</p> <p>Our hypothesis could be explored by a case-control study to assess the prevalence of vitamin D deficiency in HIV-infected patients on antiretroviral treatment who develop and do not develop IRIS.</p> <p>Implications of the hypothesis</p> <p>If the role of vitamin D in IRIS is confirmed, we would be able to screen patients at risk for IRIS by screening for vitamin D deficiency. After confirmation by means of a clinical trial, vitamin D supplementation could be a cheap and safe way to reduce the incidence of IRIS.</p

Innovation through Wearable Sensors to Collect Real-Life Data among Pediatric Patients with Cardiometabolic Risk Factors

Background. While increasing evidence links environments to health behavior, clinicians lack information about patients’ physical activity levels and lifestyle environments. We present mobile health tools to collect and use spatio-behavioural lifestyle data for personalized physical activity plans in clinical settings. Methods. The Dyn@mo lifestyle intervention was developed at the Sainte-Justine University Hospital Center to promote physical activity and reduce sedentary time among children with cardiometabolic risk factors. Mobility, physical activity, and heart rate were measured in free-living environments during seven days. Algorithms processed data to generate spatio-behavioural indicators that fed a web-based interactive mapping application for personalised counseling. Proof of concept and tools are presented using data collected among the first 37 participants recruited in 2011. Results. Valid accelerometer data was available for 5.6 (SD=1.62) days in average, heart rate data for 6.5 days, and GPS data was available for 6.1 (2.1) days. Spatio-behavioural indicators were shared between patients, parents, and practitioners to support counseling. Conclusion. Use of wearable sensors along with data treatment algorithms and visualisation tools allow to better measure and describe real-life environments, mobility, physical activity, and physiological responses. Increased specificity in lifestyle interventions opens new avenues for remote patient monitoring and intervention

Antiretroviral Treatment-Associated Tuberculosis in a Prospective Cohort of HIV-Infected Patients Starting ART

Commencement of antiretroviral treatment (ART) in severely immunosuppressed HIV-infected persons is associated with unmasking of subclinical disease. The subset of patients that are diagnosed with tuberculosis (TB) disease while on ART have been classified as ART-associated TB. Few studies have reported the incidence of ART-associated TB and unmasking TB-IRIS according to the International Network for the Study of HIV-Associated IRIS (INSHI) consensus definition. To determine the incidence and predictors of ART-associated TB, we screened 219 patients commencing ART at the Infectious Diseases Clinic in Kampala, Uganda for TB by symptoms, sputum microscopy, and chest X-rays and followed them for one year. Fourteen (6.4%) patients were diagnosed with TB during followup. Eight (3.8%) patients had ART-associated TB (incidence rate of 4.3 per 100 person years); of these, three patients fulfilled INSHI criteria for unmasking TB-associated IRIS (incidence rate of 1.6 per 100 person years). A body mass index of less than 18.5 kg/m2 BMI (HR 5.85 95% CI 1.24–27.46, P = .025) and a C-reactive protein greater than 5 mg/L (HR 8.23 95% CI 1.36–38.33, P = .020) were risk factors for ART-associated TB at multivariate analysis. In conclusion, with systematic TB screening (including culture and chest X-ray), the incidence of ART-associated TB is relatively low in settings with high HIV and TB prevalence

Human immunodeficiency virus (HIV)-infected patients accept finger stick blood collection for point-of-care CD4 testing

INTRODUCTION HIV-infected patients require antiretroviral treatment for life. To improve access to care, CD4 enumeration and viral load tests have been redesigned to be used as point-of-care techniques using finger-stick blood. Accurate CD4 counting in capillary blood requires a free flowing blood drop that is achieved by blade incision. The aim of this study was to assess the attitude of the patients toward blade-based finger-stick blood donation. METHODS Four hundred and ninety-nine patients were included (299 patients from South Africa and 200 from Belgium). They completed a questionnaire to express their preference for finger stick or venipuncture, after undergoing both. The South African patient cohort was divided in two groups, receiving either single or multiple finger stick for CD4 and other HIV-related tests. The Belgian patients received a single finger stick for CD4 testing, and were asked to respond directly and again after two days. RESULTS The majority of the patients preferred the finger stick to the venipuncture. The perceived pain using the blade was superior to a small needle, but similar to a large needle. They preferred up to three finger sticks over one venipuncture. Up to 30% of the patients changed their mind over two days. The main reason for choosing a finger stick was continued bleeding after venipuncture. The most cited objection to finger stick was pain/soreness. CONCLUSION Patient perceptions support the implementation of donating capillary blood with bladebased finger stick during CD4 point-of-care testing.S1 File. Questionnaire for group 1 in South Africa. Patients with single finger stick. (PDF)S2 File. Questionnaire for group 2 in South Africa. Patients with multiple finger stick. (PDF)S3 File. First questionnaire in Antwerp (English). For preference immediately after finger stick. (PDF)S4 File. First questionnaire in Antwerp (Dutch). For preference immediately after finger stick. (PDF)S5 File. First questionnaire in Antwerp (French). For preference immediately after finger stick. (PDF)S6 File. Second questionnaire in Antwerp (English). For preference two days after finger stick. (PDF)S7 File. Second questionnaire in Antwerp (Dutch). For preference two days after finger stick. (PDF)S8 File. Second questionnaire in Antwerp (French). For preference two days after finger stick. (PDF)The study in South Africa was funded by Grand Challenges Canada [Grant number 0007-02-01-01, url http://www.grandchallenges.ca]http://www.plosone.orghttp://www.grandchallenges.caam2016Haematolog