Low-cost electrochemical detection of arsenic in the groundwater of Guanajuato state, central Mexico using an open-source potentiostat

Arsenic is a carcinogenic groundwater contaminant that is toxic even at the parts-per-billion (ppb) level and its on-site determination remains challenging. Colorimetric test strips, though cheap and widely used, often fail to give reliable quantitative data. On the other hand, electrochemical detection is sensitive and accurate but considerably more expensive at the onset. Here, we present a study on arsenic detection in groundwater using a low-cost, open-source potentiostat based on Arduino technology. We tested different types of gold electrodes (screen-printed and microwire) with anodic stripping voltammetry (ASV), achieving low detection limits (0.7 μg L(-1)). In a study of arsenic contaminated groundwaters in Mexico, the microwire technique provides greater accuracy than test strips (reducing the median error from -50% to +2.9%) and greater precision (reducing uncertainties from ±25% to ±4.9%). Most importantly, the rate of false negatives versus the World Health Organisation’s 10 μg L(-1) limit was reduced from 50% to 0% (N = 13 samples). Arsenic determination using open-source potentiostats may offer a low-cost option for research groups and NGOs wishing to perform arsenic analysis in-house, yielding superior quantitative data than the more widely used colorimetric test strips

In vivo expansion of naive and activated CD4+CD25+FOXP3+ regulatory T cell populations in interleukin-2-treated HIV patients.

International audienceHIV-1 infection is characterized by a progressive decline in CD4(+) T cells leading to a state of profound immunodeficiency. IL-2 therapy has been shown to improve CD4(+) counts beyond that observed with antiretroviral therapy. Recent phase III trials revealed that despite a sustained increase in CD4(+) counts, IL-2-treated patients did not experience a better clinical outcome [Abrams D, et al. (2009) N Engl J Med 361(16):1548-1559]. To explain these disappointing results, we have studied phenotypic, functional, and molecular characteristics of CD4(+) T cell populations in IL-2-treated patients. We found that the principal effect of long-term IL-2 therapy was the expansion of two distinct CD4(+)CD25(+) T cell populations (CD4(+)CD25(lo)CD127(lo)FOXP3(+) and CD4(+)CD25(hi)CD127(lo)FOXP3(hi)) that shared phenotypic markers of Treg but could be distinguished by the levels of CD25 and FOXP3 expression. IL-2-expanded CD4(+)CD25(+) T cells suppressed proliferation of effector cells in vitro and had gene expression profiles similar to those of natural regulatory CD4(+)CD25(hi)FOXP3(+) T cells (Treg) from healthy donors, an immunosuppressive T cell subset critically important for the maintenance of self-tolerance. We propose that the sustained increase of the peripheral Treg pool in IL-2-treated HIV patients may account for the unexpected clinical observation that patients with the greatest expansion of CD4(+) T cells had a higher relative risk of clinical progression to AIDS

Hydrogeological and hydrogeophysical insights into karst aquifer unsaturated zone. Challenges and limits

International audienc

Voltammetric determination of inorganic arsenic in mildly acidified (pH 4.7) groundwaters from Mexico and India.

Routine monitoring of inorganic arsenic in groundwater using sensitive, reliable, easy-to-use and affordable analytical methods is integral to identifying sources, and delivering appropriate remediation solutions, to the widespread global issue of arsenic pollution. Voltammetry has many advantages over other analytical techniques, but the low electroactivity of arsenic(V) requires the use of either reducing agents or relatively strong acidic conditions, which both complicate the analytical procedures, and require more complex material handling by skilled operators. Here, we present the voltammetric determination of total inorganic arsenic in conditions of near-neutral pH using a new commercially available 25 μm diameter gold microwire (called the Gold Wirebond), which is described here for the first time. The method is based on the addition of low concentrations of permanganate (10 μM MnO4-) which fulfils two roles: (1) to ensure that all inorganic arsenic is present as arsenate by chemically oxidising arsenite to arsenate and, (2) to provide a source of manganese allowing the sensitive detection of arsenate by anodic stripping voltammetry at a gold electrode. Tests were carried out in synthetic solutions of various pH (ranging from 4.7 to 9) in presence/absence of chloride. The best response was obtained in 0.25 M chloride-containing acetate buffer resulting in analytical parameters (limit of detection of 0.28 μg L-1 for 10 s deposition time, linear range up to 20 μg L-1 and a sensitivity of 63.5 nA ppb-1. s-1) better than those obtained in acidic conditions. We used this new method to measure arsenic concentrations in contrasting groundwaters: the reducing, arsenite-rich groundwaters of India (West Bengal and Bihar regions) and the oxidising, arsenate-rich groundwaters of Mexico (Guanajuato region). Very good agreement was obtained in all groundwaters with arsenic concentrations measured by inductively coupled plasma-mass spectrometry (slope = +1.029, R2 = 0.99). The voltammetric method is sensitive, faster than other voltammetric techniques for detection of arsenic (typically 10 min per sample including triplicate measurements and 2 standard additions), easier to implement than previous methods (no acidic conditions, no chemical reduction required, reproducible sensor, can be used by non-voltammetric experts) and could enable cheaper groundwater surveying campaigns with in-the-field analysis for quick data reporting, even in remote communities

A French survey on the lockdown consequences of COVID-19 pandemic in Parkinson's disease. The ERCOPARK study

International audienceBackground: In 2020 the coronavirus disease 19 (COVID-19) pandemic imposed a total and sudden lockdown. We aimed to investigate the consequences of the first COVID-19 lockdown (mid-March - mid-April 2020) on motor and non-motor symptoms (NMS) in a cohort of French people with Parkinson's disease (PwP).Methods: PwP were enrolled either by an on-line survey sent from the national France Parkinson association (FP) to reach the French community of PwP or as part of outpatients' telemedicine visits followed by an hospital-based Parkinson Expert Center (PEC). All patients were evaluated using the same standardized questionnaire assessing motor and NMS (including a list of most disabling, new or worsened symptoms and Patient's Global Impression-Improvement scales [PGI-I]) psycho-social queries and quality of life.Results: 2653 PwP were included: 441 (16.6%) in the PEC group and 2122 (83.4%) in the community-based group. Physiotherapy was interrupted among 88.6% of the patients. 40.9% referred a clinical modification of their symptoms. Based on the questionnaire, pain (9.3%), rigidity (9.1%) and tremor (8.5%) were the three most frequently new or worsened reported symptoms. Based on the PGI-I, the motor symptoms were the most affected domain, followed by pain and psychic state. PwP in community-based group tended to have more frequent worsening for motor symptoms, motor complications, pain and confusion than those of the PEC group.Conclusions: The first COVID-19 lockdown had a negative impact on motor and NMS of PwP. Efforts should be allocated to avoid interruption of care, including physiotherapy and physical activities and implement telemedicine

High levels of A2AR and endogenous cAMP in CD4+ T cells from HIV infected patients and lack of IL-2 production

<p>. (A) CD45RA+ and CD45RA− CD4+ T cells were purified from the blood of ART-naive HIV-infected patients (n = 5) and healthy controls (n = 5). A2AR mRNA expression was assessed using qPCR. Horizontal lines correspond to the mean for each data set. (B) CD4+ T cells were purified from the blood of ART-naive HIV-infected patients (n = 6) and healthy controls (n = 8). Intra-cellular cAMP is measured using the cAMP direct enzyme immunoassay from GE healthcare Biosciences. (C) Purified naive CD4+ T cells form HIV+ART- patients and healthy controls were stimulated with high doses of anti-CD3/CD28 mAbs (5 µg/ml) during 6H and IL-2 mRNA levels were quantified by RT-PCR. (D) The epigenetic changes on methylation of the unique essential CpG site of <i>il-2</i> gene promoter in naïve CD4+ T cells from HIV+ART- patients <i>vs.</i> healthy controls following anti-CD3/CD28 mAbs activation. To reach the technical limitation due to the low frequency of naïve CD4+ T cells in HIV+ART- patients, the Clonal analysis was performed on a pool of the extracted DNA from naïve CD4 T cells of HIV+ patients and healthy controls before and after CD3/CD28 mAbs activation. *P<0.05, **P<0.01.</p

Regulatory T cells differentially modulate the maturation and apoptosis of human CD8+ T-cell subsets.

International audienceThe balanced manifestation of effector functions and the generation of long-living memory cells is a hallmark of efficient CD8(+) T-cell response. Accumulating data pinpoint CD4(+) CD25(high) regulatory T (Treg) cells as a key factor for the inefficiency of CD8(+) T-cell responses in viral persistence. Little is known about the effects of Treg cells on the homeostasis of healthy donor CD8(+) T cells. The present study demonstrates that Treg cells exert differential effects on CD8(+) T-cell subsets. Treg cells inhibited mostly the polyclonal proliferation of CD27(-) effector cells compared with CD27(+) memory CD8(+) T cells. Moreover, they inhibited the polyclonal and antigen-driven differentiation of memory cells into functional effectors as defined by IFN-gamma secretion and induction of CD160 expression. Finally, Treg cells reduced the apoptosis of memory but not of effector and terminal effector cell populations. These effects were at least in part mediated by a decreased expression of PD-L1, but not of programmed death 1 (PD-1), on CD8(+) T cells after activation. Thus, in the setting of a healthy immune system, Treg cells fine-tune the memory/effector cell balance and promote the accumulation of long-living memory cells in case of strong stimulation

CD39/Adenosine Pathway Is Involved in AIDS Progression.

International audienceHIV-1 infection is characterized by a chronic activation of the immune system and suppressed function of T lymphocytes. Regulatory CD4+ CD25(high) FoxP3+CD127(low) T cells (Treg) play a key role in both conditions. Here, we show that HIV-1 positive patients have a significant increase of Treg-associated expression of CD39/ENTPD1, an ectoenzyme which in concert with CD73 generates adenosine. We show in vitro that the CD39/adenosine axis is involved in Treg suppression in HIV infection. Treg inhibitory effects are relieved by CD39 down modulation and are reproduced by an adenosine-agonist in accordance with a higher expression of the adenosine A2A receptor on patients' T cells. Notably, the expansion of the Treg CD39+ correlates with the level of immune activation and lower CD4+ counts in HIV-1 infected patients. Finally, in a genetic association study performed in three different cohorts, we identified a CD39 gene polymorphism that was associated with down-modulated CD39 expression and a slower progression to AIDS

Amantadine use in the French prospective NS-Park cohort

International audienceObjective: To assess amantadine use and associated factors in the patients with Parkinson's disease (PD).Background: Immediate-release amantadine is approved for the treatment of PD and is largely used in clinical practice to treat "levodopa-induced dyskinesia (LIDs). Its use varies according to countries and PD stages. The prospective NS-Park cohort collects features of PD patients followed by 26 French PD Expert Centres.Methods: Variables used for the analyses included demographics, motor and non-motor PD symptoms and motor complications [motor fluctuations (MFs), LIDs)], antiparkinsonian pharmacological classes and levodopa equivalent daily dose (LEDD). We evaluated: (i) prevalence of amantadine use and compared clinical features of amantadine users vs. non-users (cross-sectional analysis); (ii) factors associated with amantadine initiation (longitudinal analysis); (iii) amantadine effect on LIDs, MFs, apathy, impulse control disorders and freezing of gait (Fog) (longitudinal analysis).Results: Amantadine use prevalence was 12.6% (1,585/12,542, median dose = 200 mg). Amantadine users were significantly younger, with longer and more severe PD symptoms, greater LEDD and more frequent use of device-aided/surgical treatment. Factors independently associated with amantadine initiation were younger age, longer PD duration, more frequent LIDs, MFs and FoG, higher LEDD and better cognitive function. 9 of the 658 patients on amantadine had stopped it at the following visit, after 12-18 months (1.3%). New users of amantadine presented a higher improvement in LIDs and MF compared to amantadine never users.Conclusions: About 12% of PD patients within the French NS-Park cohort used amantadine, mostly those with younger age and more severe PD. Amantadine initiation was associated with a subsequent reduction in LIDs and MFs