Altered interplay between gut mucosa and microbiota during treated HIV infection may possibly contribute to increased bacterial translocation and chronic immune activation, both of which are ...predictors of morbidity and mortality. Although a dysbiotic gut microbiota has recently been reported in HIV+ individuals, the metagenome gene pool associated with HIV infection remains unknown. The aim of this study is to characterize the functional gene content of gut microbiota in HIV+ patients and to define the metabolic pathways of this bacterial community, which is potentially associated with immune dysfunction. We determined systemic markers of innate and adaptive immunity in a cohort of HIV-infected individuals on successful antiretroviral therapy without comorbidities and in healthy non-HIV-infected subjects. Metagenome sequencing revealed an altered functional profile, with enrichment of the genes involved in various pathogenic processes, lipopolysaccharide biosynthesis, bacterial translocation, and other inflammatory pathways. In contrast, we observed depletion of genes involved in amino acid metabolism and energy processes. Bayesian networks showed significant interactions between the bacterial community, their altered metabolic pathways, and systemic markers of immune dysfunction. This study reveals altered metabolic activity of microbiota and provides novel insight into the potential host-microbiota interactions driving the sustained inflammatory state in successfully treated HIV-infected patients.
Altered interactions between the gut mucosa and bacteria during HIV infection seem to contribute to chronic immune dysfunction. A deeper understanding of how nutritional interventions could ...ameliorate gut dysbiosis is needed. Forty-four subjects, including 12 HIV
viremic untreated (VU) patients, 23 antiretroviral therapy-treated (ART
) virally suppressed patients (15 immunological responders and 8 non-responders) and 9 HIV
controls (HIV
), were blindly randomized to receive either prebiotics (scGOS/lcFOS/glutamine) or placebo (34/10) over 6 weeks in this pilot study. We assessed fecal microbiota composition using deep 16S rRNA gene sequencing and several immunological and genetic markers involved in HIV immunopathogenesis. The short dietary supplementation attenuated HIV-associated dysbiosis, which was most apparent in VU individuals but less so in ART
subjects, whose gut microbiota was found more resilient. This compositional shift was not observed in the placebo arm. Significantly, declines in indirect markers of bacterial translocation and T-cell activation, improvement of thymic output, and changes in butyrate production were observed. Increases in the abundance of Faecalibacterium and Lachnospira strongly correlated with moderate but significant increases of butyrate production and amelioration of the inflammatory biomarkers soluble CD14 and high-sensitivity C-reactive protein, especially among VU. Hence, the bacterial butyrate synthesis pathway holds promise as a viable target for interventions.
Convalescent plasma, widely utilized in viral infections that induce neutralizing antibodies, has been proposed for COVID-19, and preliminary evidence shows that it might have beneficial effect. Our ...objective was to determine the risk factors for 28-days mortality in patients who received convalescent plasma for COVID-19 compared to those who did not, who were admitted to hospitals in Buenos Aires Province, Argentina, throughout the pandemic.
This is a multicenter, retrospective cohort study of 2-month duration beginning on June 1, 2020, including unselected, consecutive adult patients with diagnosed COVID-19, admitted to 215 hospitals with pneumonia. Epidemiological and clinical variables were registered in the Provincial Hospital Bed Management System. Convalescent plasma was supplied as part of a centralized, expanded access program.
We analyzed 3,529 patients with pneumonia, predominantly male, aged 62±17, with arterial hypertension and diabetes as main comorbidities; 51.4% were admitted to the ward, 27.1% to the Intensive Care Unit (ICU), and 21.7% to the ICU with mechanical ventilation requirement (ICU-MV). 28-day mortality was 34.9%; and was 26.3%, 30.1% and 61.4% for ward, ICU and ICU-MV patients. Convalescent plasma was administered to 868 patients (24.6%); their 28-day mortality was significantly lower (25.5% vs. 38.0%, p<0.001). No major adverse effects occurred. Logistic regression analysis identified age, ICU admission with and without MV requirement, diabetes, and preexistent cardiovascular disease as independent predictors of 28-day mortality, whereas convalescent plasma administration acted as a protective factor.
Our study suggests that the administration of convalescent plasma in COVID-19 pneumonia admitted to the hospital might be associated with improved outcomes.
The ultrahigh‐pressure pyrope whiteschists from the Brossasco‐Isasca Unit of the Southern Dora‐Maira Massif represent metasomatic rocks originated at the expense of post‐Variscan granitoids by the ...influx of fluids along shear zones. In this study, geochemical, petrological and fluid‐inclusion data, correlated with different generations of pyrope‐rich garnet (from medium, to very‐coarse‐grained in size) allow constraints to be placed on the relative timing of metasomatism and sources of the metasomatic fluid. Geochemical investigations reveal that whiteschists are strongly enriched in Mg and depleted in Na, K, Ca and LILE (Cs, Pb, Rb, Sr, Ba) with respect to the metagranite. Three generations of pyrope, with different composition and mineral inclusions, have been distinguished: (i) the prograde Prp I, which constitutes the large core of megablasts and the small core of porphyroblasts; (ii) the peak Prp II, which constitutes the inner rim of megablasts and porphyroblasts and the core of small neoblasts; and (iii) the early retrograde Prp III, which locally constitutes an outer rim. Two generations of fluid inclusions have been recognized: (i) primary fluid inclusions in prograde kyanite that represent a NaCl‐MgCl2‐rich brine (6–28 wt% NaCleq with Si and Al as other dissolved cations) trapped during growth of Prp I (type‐I fluid); (ii) primary multiphase‐solid inclusions in Prp II that are remnants of an alumino‐silicate aqueous solution, containing Mg, Fe, alkalies, Ca and subordinate P, Cl, S, CO32‐, LILE (Pb, Cs, Sr, Rb, K, LREE, Ba), U and Th (type‐II fluid), at the peak pressure stage. We propose a model that illustrates the prograde metasomatic and metamorphic evolution of the whiteschists and that could also explain the genesis of other Mg‐rich, alkali‐poor schists of the Alps. During Alpine metamorphism, the post‐Variscan metagranite of the Brossasco‐Isasca Unit experienced a prograde metamorphism at HP conditions (stage A: ∼1.6 GPa and ≤ 600 °C), as indicated by the growth of an almandine‐rich garnet in some xenoliths. At stage B (1.7–2.1 GPa and 560–590 °C), the influx of external fluids, originated from antigorite breakdown in subducting oceanic serpentinites, promoted the increase in Mg and the decrease of alkalies and Ca in the orthogneiss toward a whiteschist composition. During stage C (2.1 < P < 2.8 GPa and 590 < T < 650 °C), the metasomatic fluid influx coupled with internal dehydration reactions involving Mg‐chlorite promoted the growth of Prp I in the presence of the type‐I MgCl2‐brine. At the metamorphic peak (stage D: 4.0–4.3 GPa and 730 °C), Prp II growth occurred in the presence of a type–II alumino‐silicate aqueous solution, mostly generated by internal dehydration reactions involving phlogopite and talc. The contribution of metasomatic external brines at the metamorphic climax appears negligible. This fluid, showing enrichment in LILE and depletion in HFSE, could represent a metasomatic agent for the supra‐subduction mantle wedge.
In this study, tin-bronze analogues of archaeological objects were investigated in the presence of an aerobic
Pseudomonas fluorescens
strain in a solution, containing chlorides, sulfates, carbonates ...and nitrates according to a previous archaeological characterization. Classical fixation protocols were employed in order to verify the attachment capacity of such bacteria. In addition, classical metallurgical analytical techniques were used to detect the effect of bacteria on the formation of uncommon corrosion products in such an environment. Results indicate quite a good attachment capacity of the bacteria to the metallic surface and the formation of the uncommon corrosion products sulfates and sulfides is probably connected to the bacterial metabolism.
At active volcanoes, petrological studies have been proven to be a reliable approach in defining the depth conditions of magma transport and storage in both the mantle and the crust. Based on fluid ...inclusion and mineral geothermobarometry in mantle xenoliths, we propose a model for the magma plumbing system of the Island of El Hierro (Canary Islands). The peridotites studied here were entrained in a lava flow exposed in the El Yulan Valley. These lavas are part of the rift volcanism that occurred on El Hierro at approximately 40–30 ka. The peridotites are spinel lherzolites, harzburgites, and dunites which equilibrated in the shallow mantle at pressures between 1.5 and 2 GPa and at temperatures between 800 and 950 °C (low-temperature peridotites; LT), as well as at higher equilibration temperatures of 900 to 1100 °C (high-temperature peridotites; HT). Microthermometry and Raman analyses of fluid inclusions reveal trapping of two distinct fluid phases: early type I metasomatic CO
2
-N
2
fluids (
X
N2
= 0.01–0.18; fluid density (d) = 1.19 g/cm
3
), coexisting with silicate-carbonate melts in LT peridotites, and late type II pure CO
2
fluids in both LT
(d
= 1.11–1.00 and 0.75–0.65 g/cm
3
) and HT (
d
= 1.04–1.11 and 0.75–0.65 g/cm
3
) peridotites. While type I fluids represent metasomatic phases in the deep oceanic lithosphere (at depths of 60–65 km) before the onset of magmatic activity, type II CO
2
fluids testify to two fluid trapping episodes during the ascent of xenoliths in their host mafic magmas. Identification of magma accumulation zones through interpretation of type II CO
2
fluid inclusions and mineral geothermobarometry indicate the presence of a vertically stacked system of interconnected small magma reservoirs in the shallow lithospheric mantle between a depth of 22 and 36 km (or 0.67 to 1 GPa). This magma accumulation region fed a short-lived magma storage region located in the lower oceanic crust at a depth of 10–12 km (or 0.26–0.34 GPa). Following our model, the 40–30-ka-old volcanic activity of El Hierro is related to this mantle-based magma system, a system that we propose fed the recent 2011–2012 eruption.
Primary multiphase solid (MS) inclusions without preserved fluid are found within peak minerals in kyanite quartzite
±
topaz and kyanite–phengite–epidote eclogite from Donghai area (Su-Lu terrane). ...Typical mineral association in inclusions is: paragonite
+
muscovite
+
anhydrite
±
corundum
±
“alunite-type” sulphate
±
zircon
±
calcite
±
chlorite
±
SiO
2
±
barite
±
pyrite
±
apatite in quartzites, and paragonite
+
rutile
+
apatite
±
amphibole
±
Zn-staurolite
±
magnetite
±
plagioclase
±
zircon
±
pyrite
±
“alunite-type” sulphate
±
Zn–Mg–Fe–Al–Ti spinel in eclogites.
On the basis of the fluid inclusion textures and of the daughter-phase assemblage, calculated fluid composition is as follows: in quartzites 24 wt.% SiO
2, 30 wt.% Al
2O
3, 9 wt.% CaO, 5 wt.% K
2O, 3 wt.% Na
2O, 11 wt.% SO
3, 18 wt.% H
2O, with traces of TiO
2, Fe
2O
3, FeO, MgO, BaO, P
2O
5, Cl
−, F, and (CO
3)
2−, and in eclogites 26 wt.% SiO
2, 21 wt.% TiO
2, 20 wt.% Al
2O
3, 2 wt.% MgO, 4 wt.% FeO, 6 wt.% Fe
2O
3, 7 wt.% CaO, 3 wt.% Na
2O, 3 wt.% P
2O
5, 7 wt.% H
2O, 1 wt.% Cl, and traces of ZnO, MnO, K
2O, SO
3, and F. Originally trapped chloride-poor aqueous fluids contained very high amounts – in the order of tens of wt.% – of Si
4+, Al
3+, and Ti
4+. Solute species reflect the chemical composition of the host rocks: Mg
2+, Fe
2+, Ti
4+, P
5+, and Na
+, are abundant in the fluids present in eclogites, while fluids are enriched in Al
3+, K
+, Na
+, (SO
4)
2−, (CO
3)
2− in quartzites.
We propose that multiphase solid inclusions represent remnants of high-density supercritical silicate-rich aqueous fluids that were in equilibrium with peak minerals at UHP conditions. These fluids show characters which are transitional between aqueous fluids and silicate melts, and were probably produced by dehydration reactions of the host rocks during the latest stages of subduction.
Abstract
Objectives
To analyse the frequency and causes of treatment discontinuation in patients who were treated with an integrase strand transfer inhibitor (INSTI), with a focus on neuropsychiatric ...adverse events (NPAEs).
Methods
Patients in 18 HIV reference centres in France were prospectively included in the Dat’AIDS cohort. Data were collected from all patients starting an INSTI-containing regimen between 1 January 2006 and 31 December 2016. All causes of INSTI-containing regimen discontinuations were analysed, and patients’ characteristics related to discontinuation due to NPAEs were sought.
Results
INSTIs were prescribed to 21315 patients: 6274 received dolutegravir, 3421 received elvitegravir boosted by cobicistat, and 11620 received raltegravir. Discontinuation was observed in 12.5%, 20.2% and 50.9% of the dolutegravir-, elvitegravir- and raltegravir-treated patients, respectively (P < 0.001). Discontinuation for NPAEs occurred in 2.7%, 1.3% and 1.7% of the dolutegravir-, elvitegravir-, and raltegravir-treated patients, respectively (P < 0.001). In the multivariate analysis, discontinuation for NPAEs was related to dolutegravir versus elvitegravir (HR = 2.27; 95% CI 1.63–3.17; P < 0.0001) and versus raltegravir (HR = 2.46; 95% CI 2.00–3.40; P < 0.0001), but neither gender (HR for women = 1.19; 95% CI 0.97–1.46; P = 0.09) nor age (P = 0.12) was related. The association with abacavir was not retained in the final model.
Conclusions
Although discontinuation for side effects was less frequent with dolutegravir than with boosted elvitegravir, discontinuation for NPAEs, although rare (2.7%), was more frequent with dolutegravir. No patient characteristic was found to be associated with these side effects in this very large population.
Chronic and systemic inflammatory alterations occur in HIV-infected patients and elderly uninfected subjects and in both scenarios these alterations are associated with the development of chronic ...morbidities and mortality. However, whether the levels of inflammatory alterations in untreated HIV-infected patients and elderly individuals are similar is unknown. Moreover, whether long-term antiretroviral therapy normalizes inflammatory alterations compared with HIV-uninfected persons of different age is not known.
We analysed soluble inflammatory levels high-sensitivity C-reactive protein, interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8 and IL-17 in a cohort of viraemic HIV-infected patients compared with (i) age-matched, (ii) elderly and (iii) non-survivor elderly, uninfected healthy controls. We longitudinally analysed the effect of long-term 48 and 96 week suppressive combined antiretroviral therapy (cART) on the soluble inflammatory levels compared with those found in control subjects.
Baseline IL-6 and IL-8 levels were at similar or lower concentrations in untreated patients compared with healthy elderly individuals. However, TNF-α and IFN-γ levels broadly exceeded those found in survivors and non-survivor elderly individuals. Long-term suppressive cART normalized most of the inflammatory markers, with the exception of TNF-α levels, which persisted as high as those in elderly non-survivor controls.
Chronic inflammatory alterations associated with HIV infection are maintained at a different level from those of ageing. The persistent alteration of TNF-α levels in HIV-infected patients might cause tissue damage and have implications for developing non-AIDS-defining illnesses, even when HIV replication is long-term controlled by cART.
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