Diffuse White Matter Signal Abnormalities on Magnetic Resonance Imaging Are Associated With Human Immunodeficiency Virus Type 1 Viral Escape in the Central Nervous System Among Patients With Neurological Symptoms

Background: Human immunodeficiency virus type 1 (HIV-1) can replicate independently in extravascular compartments such as the central nervous system, resulting in either cerebrospinal fluid (CSF) discordance (viral load [VL] in CSF 0.5 log10 copies HIV-1 RNA greater than plasma VL) or escape (detection of HIV VL >50 copies/mL in CSF in patients with suppressed plasma VL <50 copies/mL). Both discordance and escape may be associated with neurological symptoms. We explored risk factors for CSF discordance and escape in patients presenting with diverse neurological problems. Methods: HIV-infected adult patients undergoing diagnostic lumbar puncture (LP) at a single center between 2011 and 2015 were included in the analysis. Clinical and neuroimaging variables associated with CSF discordance/escape were identified using multivariate logistic regression. Results: One hundred forty-six patients with a median age of 45.3 (interquartile range [IQR], 39.6–51.5) years underwent 163 LPs. Median CD4 count was 430 (IQR, 190–620) cells/µL. Twenty-four (14.7%) LPs in 22 patients showed CSF discordance, of which 10 (6.1%) LPs in 9 patients represented CSF escape. In multivariate analysis, both CSF discordance and escape were associated with diffuse white matter signal abnormalities (DWMSAs) on cranial magnetic resonance imaging (adjusted odds ratio, 10.3 [95% confidence interval {CI}, 2.3–45.0], P = .007 and 56.9 [95% CI, 4.0–882.8], P = .01, respectively). All 7 patients with CSF escape (10 LPs) had been diagnosed with HIV >7 years prior to LP, and 6 of 6 patients with resistance data had documented evidence of drug-resistant virus in plasma. Conclusions: Among patients presenting with diverse neurological problems, CSF discordance or escape was observed in 15%, with treatment-experienced patients dominating the escape group. DWMSAs in HIV-infected individuals presenting with neurological problems should raise suspicion of possible CSF discordance/escape

Extraction of the Volatile Oils of Dictyopteris membranacea Batters 1902 by Focused Microwave-assisted Hydrodistillation and Supercritical Carbon Dioxide: Empirical Kinetic Modelling Approach, Apparent Solubility and Rate Constants

Supercritical carbon dioxide extraction (SCCO2) and focused microwave-assisted hydrodistillation (FMAHD) were used comparatively to isolate the volatile oils of the brown alga Dictyopteris membranacea from the crude ether extract. The volatiles fractions were analysed by GC/MS, the major compounds were: dictyopterene A, 6-butyl-1,4-cycloheptadiene, 1-undecen-3-one, 1,4-undecadien-3-one, (3-oxoundec-4-enyl) sulphur, tetradecanoic acid, hexadecanoic acid, 3-hexyl-4,5-dithiacycloheptanone, and albicanol. A kinetics study of the extraction of the volatile fractions obtained by the two processes was carried out, an external calibration allowed to quantify the content of the main metabolites. Empirical models were applied to adjust the experimental kinetics values but also to determine the values of apparent solubilities for SCCO2 and the rate constants for FMAHD. The results obtained revealed that the SCCO2 process was characterized by the coexistence of three distinct phases. For FMAHD, the extraction mechanism included two steps. This work is licensed under a Creative Commons Attribution 4.0 International License

Surface Optical Waves at Air/Metal Interfaces: Surface Plasmon Polaritons

The surface plasmon resonance (SPR) phenomenon has been known for nearly five decades now; since then this method has made great advances in terms of instrumentation development and applications, and it still attracts researchers because of certain subtle issues that could benefit from it mainly detection and analysis of chemical and biochemical substances in different areas including medicine, environmental monitoring, biotechnology and drug and food monitoring. Our interest is focused on the use of this technique for studying thin coating and some application in nanophotonics. In this paper, we discuss the configuration of surface plasmons at air/metal interface by Atenuated total reflection (ATR) technique in the Kretchman configuration, and we present preliminary experimental results on surface plasmons at a Ag/air interface that we obtained in our laboratory.The surface plasmon resonance (SPR) phenomenon has been known for nearly five decades now; since then this method has made great advances in terms of instrumentation development and applications, and it still attracts researchers because of certain subtle issues that could benefit from it mainly detection and analysis of chemical and biochemical substances in different areas including medicine, environmental monitoring, biotechnology and drug and food monitoring. Our interest is focused on the use of this technique for studying thin coating and some application in nanophotonics. In this paper, we discuss the configuration of surface plasmons at air/metal interface by Atenuated total reflection (ATR) technique in the Kretchman configuration, and we present preliminary experimental results on surface plasmons at a Ag/air interface that we obtained in our laboratory

NOD2 Gene Status in Pediatric and Adult Crohn Disease Patients in Algerian Population

Background: Chronic Inflammatory Bowel Diseases (IBD), including Crohn disease (CD) and ulcerative colitis (UC) are gastrointestinal disorders under the influence of a complex genetic basis. One hundred sixty-three predisposition loci were identified by genome-wide association (GWAS) studies, refocusing the pathogenesis of IBD on immunity genes. The NOD2 gene has been widely implicated in the pathogenesis of IBD in different geographical populations. Three most common mutations within NOD2 gene were selected, namely SNP8, C/T (R702W variant), SNP12, G/C (G908R variant) and SNP13, (1007fsinsC variant). We investigated these three SNP in a pediatric Algerian cohort for the first time, since no previous association studies between pediatric IBD and the NOD2 gene were available for the Algerian population. Methods: A case-control study was performed in the pediatric IBD population. PCR-RFLP was used to detect the three NOD2 gene mutations in 46 CD patients and 100 healthy control subjects. All samples were genotyped for the NOD2 gene Polymorphisms by the PCR-RFLP method. Statistical study was performed by the Fisher exact test or Chi-2 using the GraphPad Prism 7.0 software. Then data from the pediatric cohort were compared to our precedent published data from a case-control study performed on a cohort including 132 IBD patients and 114 healthy control subjects. Results: In the pediatric cohort, there is no statistically differences in allelic frequencies between cases and controls respectively R702W (6.36% vs. 6.38%; p=1), G908R (2.72% vs. 1.06%; p=0.6) and 1007fsinsC mutation was found neither in the CD patients nor in control. In the adult cohort, the R702W allelic variant showed the highest frequency in CD patients (8%) (p = 0.09, OR = 3.67, 95%CI: 0.48-4.87) but its frequency was also high in controls (5%) (p = 0.4; OR = 1.4; 95%CI: 0.65-3.31). Likewise, G908R and 1007fsinsC mutations showed similar frequency in CD patients and in controls (3% vs. 2%; p= 0.5; OR=1.67; 95%CI: 0.44-6.34; 2% vs.1%; p=0.4, OR=2.69; 95%CI: 0.48-14.87, respectively). The total frequency of the mutated NOD2 chromosomes was higher in adult CD patients (13%) than in pediatric CD patients (9%). In our precedent study on the adult cohort, we have confirmed that the NOD2 gene is significantly associated with a specific clinical sub-phenotype in CD, indicating that the NOD2 gene is involved in IBD susceptibility across Algerian adult population. However, we failed to show any association between the three variants of the NOD2 gene across Algerian pediatric CD patients. Conclusion: In our precedent study, we have confirmed that the NOD2 gene is significantly associated with a specific clinical sub-phenotype in adult CD patients. Here, our results show no association of NOD2 gene variants with pediatric MC. The low penetrance of the at-risk genotypes we observed indicates that the NOD2 gene does not delineate a subgroup of simple Mendelian diseases

Baseline PI susceptibility by HIV-1 Gag-protease phenotyping and subsequent virological suppression with PI-based second-line ART in Nigeria

Objectives: Previous work showed that gag-protease-derived phenotypic susceptibility to PIs differed between HIV-1 subtype CRF02_AG/subtype G-infected patients who went on to successfully suppress viral replication versus those who experienced virological failure of lopinavir/ritonavir monotherapy as first-line treatment in a clinical trial. We analysed the relationship between PI susceptibility and outcome of second-line ART in Nigeria, where subtypes CRF02_AG/G dominate the epidemic. Methods: Individuals who experienced second-line failure with ritonavir-boosted PI-based ART were matched (by subtype, sex, age, viral load, duration of treatment and baseline CD4 count) to those who achieved virological response (‘successes’). Successes were defined by viral load <400 copies of HIV-1 RNA/mL by week 48. Full-length Gag-protease was amplified from patient samples for in vitro phenotypic susceptibility testing, with PI susceptibility expressed as IC50 fold change (FC) relative to a subtype B reference strain. Results: The median (IQR) lopinavir IC50 FC was 4.04 (2.49–7.89) for virological failures and 4.13 (3.14–8.17) for virological successes (P = 0.94). One patient had an FC >10 for lopinavir at baseline and experienced subsequent virological failure with ritonavir-boosted lopinavir as the PI. There was no statistically significant difference in single-round replication efficiency between the two groups (P = 0.93). There was a moderate correlation between single-round replication efficiency and FC for lopinavir (correlation coefficient 0.32). Conclusions: We found no impact of baseline HIV-1 Gag-protease-derived phenotypic susceptibility on outcomes of PI-based second-line ART in Nigeria

The hypoxia-regulated ectonucleotidase CD73 is a host determinant of HIV latency

Deciphering the mechanisms underlying viral persistence is critical to achieving a cure for human immunodeficiency virus (HIV) infection. Here, we implement a systems approach to discover molecular signatures of HIV latently infected CD4+ T cells, identifying the immunosuppressive, adenosine-producing ectonucleotidase CD73 as a key surface marker of latent cells. Hypoxic conditioning, reflecting the lymphoid tissue microenvironment, increases the frequency of CD73+ CD4+ T cells and promotes HIV latency. Transcriptomic profiles of CD73+ CD4+ T cells favor viral quiescence, immune evasion, and cell survival. CD73+ CD4+ T cells are capable of harboring a functional HIV reservoir and reinitiating productive infection ex vivo. CD73 or adenosine receptor blockade facilitates latent HIV reactivation in vitro, mechanistically linking adenosine signaling to viral quiescence. Finally, tissue imaging of lymph nodes from HIV-infected individuals on antiretroviral therapy reveals spatial association between CD73 expression and HIV persistence in vivo. Our findings warrant development of HIV-cure strategies targeting the hypoxia-CD73-adenosine axis

Prise en charge du couple mère enfant de la varicelle pendant la grossesse

La varicelle est une maladie généralement bénigne chez l’enfant, cependant l’atteinte de l’adulte est potentiellement grave et son association à la grossesse expose la mère et le nouveau né à des risques de complications plus redoutables.La prise en charge multidisciplinaire associant obstétricien, biologiste et pédiatre est indispensable pour limiter les effets délétères de l’infection par la varicelle pendant la grossesse.Nous rapportons dans cet article les approches thérapeutiques actuellement proposées pour la prise en charge anté et péripartum du couple mère-enfant en cas d’infection par la varicelle pendant la grossesse et nous proposons des conduites visant à atténuer les complications maternelles

The moonlighting RNA-binding activity of cytosolic serine hydroxymethyltransferase contributes to control compartmentalization of serine metabolism

Enzymes of intermediary metabolism are often reported to have moonlighting functions as RNA-binding proteins and have regulatory roles beyond their primary activities. Human serine hydroxymethyltransferase (SHMT) is essential for the one-carbon metabolism, which sustains growth and proliferation in normal and tumour cells. Here, we characterize the RNA-binding function of cytosolic SHMT (SHMT1) in vitro and using cancer cell models. We show that SHMT1 controls the expression of its mitochondrial counterpart (SHMT2) by binding to the 5'untranslated region of the SHMT2 transcript (UTR2). Importantly, binding to RNA is modulated by metabolites in vitro and the formation of the SHMT1-UTR2 complex inhibits the serine cleavage activity of the SHMT1, without affecting the reverse reaction. Transfection of UTR2 in cancer cells controls SHMT1 activity and reduces cell viability. We propose a novel mechanism of SHMT regulation, which interconnects RNA and metabolites levels to control the cross-talk between cytosolic and mitochondrial compartments of serine metabolism