Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 7 de 7
Filter
1.
Ann Clin Transl Neurol ; 9(4): 564-569, 2022 04.
Article in English | MEDLINE | ID: mdl-35243826

ABSTRACT

Both retinal atrophy measured through optical coherence tomography and plasma neurofilament light chain (NfL) levels are markers of neurodegeneration, but their relationship is unknown. Therefore, we assessed their determinants and association in 4369 participants of a population-based study. Both plasma NfL levels and inner retinal atrophy increased exponentially with age. In the presence of risk factors for neurodegeneration (including age, smoking, and a history of neurological disorders), plasma NfL levels were associated with inner retinal atrophy and outer retinal thickening. Our findings indicate that inner retinal atrophy can reflect neuroaxonal damage as mirrored by rising plasma NfL levels.


Subject(s)
Intermediate Filaments , Atrophy , Biomarkers , Humans
2.
Preprint in English | medRxiv | ID: ppmedrxiv-21263019

ABSTRACT

ObjectiveTo assess whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with changes in plasma levels of neurofilament light chain (NfL), an extremely sensitive marker of neuroaxonal damage, in community-dwelling individuals. SettingThis study was embedded within the Rhineland Study, an ongoing community-based cohort study in Bonn, Germany DesignCross-sectional nested case-control study. ParticipantsParticipants were selected based on results from a previously conducted seroprevalence survey within the framework of the Rhineland Study. Cases were defined as those individuals who had had two positive confirmatory test results, including a recombinant spike-based immunofluorescence assay and a plaque reduction neutralization test (N=21). As controls, a random sample of individuals with a negative ELISA test result (Controls I, N=1117), and those with a borderline or positive ELISA test result who failed confirmatory testing (Controls II, N=68), were selected. Outcome measuresPlasma levels of NfL at the time of measurement, as well as change in plasma NfL levels compared to previously measured pre-pandemic levels ResultsAfter adjustment for age, sex and batch effects, serologically confirmed SARS-CoV-2 infection was neither associated with cross-sectional NfL levels, nor with the magnitude of change from pre-pandemic levels, compared to either of the two control groups. Similarly, after adjustment for age, sex and batch effects, self-reported neurological symptoms - including altered sense of smell or taste, headache, myalgia and fever - were not associated with changes in NfL levels in participants with a serologically confirmed SARS-CoV-2 infection (all p [≥] 0.56). ConclusionsOur findings indicate that mild-to-moderate coronavirus disease-19 is unlikely to be associated with a clinically relevant degree of neuroaxonal damage, even in those cases associated with neurological symptoms.

3.
Front Cell Infect Microbiol ; 11: 631333, 2021.
Article in English | MEDLINE | ID: mdl-33791239

ABSTRACT

Severe thrombocytopenia can be a determinant factor in the morbidity of Plasmodium vivax, the most widespread human malaria parasite. Although immune mechanisms may drive P. vivax-induced severe thrombocytopenia (PvST), the current data on the cytokine landscape in PvST is scarce and often conflicting. Here, we hypothesized that the analysis of the bidirectional circuit of inflammatory mediators and their regulatory miRNAs would lead to a better understanding of the mechanisms underlying PvST. For that, we combined Luminex proteomics, NanoString miRNA quantification, and machine learning to evaluate an extensive array of plasma mediators in uncomplicated P. vivax patients with different degrees of thrombocytopenia. Unsupervised clustering analysis identified a set of PvST-linked inflammatory (CXCL10, CCL4, and IL-18) and regulatory (IL-10, IL-1Ra, HGF) mediators. Among the mediators associated with PvST, IL-6 and IL-8 were critical to discriminate P. vivax subgroups, while CCL2 and IFN-γ from healthy controls. Supervised machine learning spotlighted IL-10 in P. vivax-mediated thrombocytopenia and provided evidence for a potential signaling route involving IL-8 and HGF. Finally, we identified a set of miRNAs capable of modulating these signaling pathways. In conclusion, the results place IL-10 and IL-8/HGF in the center of PvST and propose investigating these signaling pathways across the spectrum of malaria infections.


Subject(s)
Malaria, Vivax , MicroRNAs , Thrombocytopenia , Humans , Inflammation Mediators , Plasmodium vivax
4.
Infect Genet Evol ; 40: 162-166, 2016 06.
Article in English | MEDLINE | ID: mdl-26946405

ABSTRACT

Recent reports showed that, in mice, symptomatic Plasmodium infection triggers NLRP3/NLRP12-dependent inflammasome formation and caspase-1 activation in monocytes. In humans, few works demonstrated that inflammasome is activated in malaria. As Plasmodiumvivax is a potent inducer of inflammatory response we hypothesised that inflammasome genetics might affect P. vivax malaria clinical presentation. For this purpose, selected SNPs in inflammasome genes were analysed among patients with symptomatic P. vivax malaria. 157 Brazilian Amazon patients with P. vivax malaria were genotyped for 10 single nucleotide polymorphisms (SNPs) in inflammasome genes NLRP1, NLRP3, AIM2, CARD8, IL1B, IL18 and MEFV. Effect of SNPs on hematologic and clinical parameters was analysed by multivariate analysis. Our data suggested an important role of NLRP1 inflammasome receptor in shaping the clinical presentation of P. vivax malaria, in term of presence of fever, anaemia and thrombocytopenia. Moreover IL1B rs1143634 resulted significantly associated to patients' parasitaemia, while IL18 rs5744256 plays a protective role against the development of anaemia. Polymorphisms in inflammasome genes could affect one or other aspects of malaria pathogenesis. Moreover, these data reveal novel aspects of P.vivax/host interaction that involved NLRP1-inflammasome.


Subject(s)
Genetic Predisposition to Disease , Inflammasomes/genetics , Malaria, Vivax/genetics , Malaria, Vivax/parasitology , Plasmodium vivax , Adaptor Proteins, Signal Transducing/genetics , Adult , Aged , Aged, 80 and over , Alleles , Apoptosis Regulatory Proteins/genetics , Female , Gene Frequency , Genotype , Humans , Inflammasomes/metabolism , Interleukin-18/genetics , Interleukin-1beta/genetics , Linkage Disequilibrium , Malaria, Vivax/diagnosis , Malaria, Vivax/metabolism , Male , Middle Aged , NLR Proteins , Phenotype , Polymorphism, Single Nucleotide , Selection, Genetic
5.
Int J Obes (Lond) ; 39(1): 61-8, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25189178

ABSTRACT

BACKGROUND: Maternal vitamin D status during fetal development may influence offspring growth and risk of obesity; however, evidence in humans is limited. OBJECTIVE: To investigate whether maternal circulating 25-hydroxyvitamin D3 (25(OH)D3) concentration in pregnancy is associated with offspring prenatal and postnatal growth and overweight. METHODS: Plasma 25(OH)D3 concentration was measured in pregnant women (median weeks of gestation 14.0, range 13.0-15.0) from the INMA (INfancia y Medio Ambiente) cohort (Spain, 2003-2008) (n = 2358). Offspring femur length (FL), biparietal diameter (BPD), abdominal circumference (AC) and estimated fetal weight (EFW) were evaluated at 12, 20 and 34 weeks of gestation by ultrasound examinations. Fetal overweight was defined either as AC or as EFW ⩾ 90th percentile. Child's anthropometry was recorded at ages 1 and 4 years. Rapid growth was defined as a weight gain z-score of >0.67 from birth to ages 6 months and 1 year. Age- and sex-specific z-scores for body mass index (BMI) were calculated at ages 1 and 4 years (World Health Organization referent); infant's overweight was defined as a BMI z-score ⩾ 85th percentile. RESULTS: We found no association of maternal 25(OH)D3 concentration with FL and a weak inverse association with BPD at 34 weeks. Maternal deficit of 25(OH)D3 (<20 ng ml(-1)) was associated with increased risk of fetal overweight defined as AC ⩾ 90th percentile (odds ratio (OR) = 1.50, 95% confidence interval (CI): 1.01-2.21; P = 0.041) or either as EFW ⩾ 90th percentile (OR = 1.47, 95% CI: 1.00-2.16; P = 0.046). No significant associations were found with rapid growth. Deficit of 25(OH)D3 in pregnancy was associated with an increased risk of overweight in offspring at age 1 year (OR = 1.42, 95% CI: 1.02-1.97; P = 0.039); however, the association was attenuated at age 4 years (OR = 1.19, 95% CI: 0.83-1.72; P = 0.341). CONCLUSIONS: Vitamin D deficiency in pregnancy may increase the risk of prenatal and early postnatal overweight in offspring. Clinical trials are warranted to determine the role of vitamin D in the early origins of obesity.


Subject(s)
Femur/diagnostic imaging , Mothers , Pediatric Obesity/etiology , Pregnancy Complications/metabolism , Ultrasonography, Prenatal , Vitamin D Deficiency/complications , Age of Onset , Body Mass Index , Child Development , Child, Preschool , Female , Humans , Infant , Male , Odds Ratio , Pediatric Obesity/epidemiology , Pediatric Obesity/metabolism , Predictive Value of Tests , Pregnancy , Prospective Studies , Spain/epidemiology , Vitamin D Deficiency/epidemiology , Weight Gain
6.
Am J Trop Med Hyg ; 88(2): 325-8, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23249684

ABSTRACT

Understanding the pathogenesis of Plasmodium vivax malaria is challenging. We hypothesized that susceptibility to P. vivax-induced thrombocytopenia could be associated with polymorphisms on relevant platelet membrane integrins: integrin α2 (C807T), and integrin ß3 (T1565C). Although ß3 polymorphism was not related with P. vivax malaria, α2 807T carriers, which show high levels of integrin α2ß1, had a higher probability for severe thrombocytopenia than wild-type carriers. This evidence of the association of integrin polymorphism and P. vivax morbidity was further demonstrated by a moderate but significant correlation between clinical disease and surface levels of the integrin α2ß1.


Subject(s)
Integrin alpha2beta1/genetics , Malaria, Vivax/genetics , Plasmodium vivax/pathogenicity , Polymorphism, Genetic , Thrombocytopenia/parasitology , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Genotype , Humans , Integrin alpha2/genetics , Integrin alpha2/metabolism , Integrin alpha2beta1/metabolism , Integrin beta3/genetics , Integrin beta3/metabolism , Malaria, Vivax/parasitology , Male , Middle Aged , Young Adult
7.
PLoS One ; 6(5): e19842, 2011.
Article in English | MEDLINE | ID: mdl-21611202

ABSTRACT

BACKGROUND: Given the increasing evidence of Plasmodium vivax infections associated with severe and fatal disease, the identification of sensitive and reliable markers for vivax severity is crucial to improve patient care. Circulating nucleic acids (CNAs) have been increasingly recognized as powerful diagnostic and prognostic tools for various inflammatory diseases and tumors as their plasma concentrations increase according to malignancy. Given the marked inflammatory status of P. vivax infection, we investigated here the usefulness of CNAs as biomarkers for malaria morbidity. METHODS AND FINDINGS: CNAs levels in plasma from twenty-one acute P. vivax malaria patients from the Brazilian Amazon and 14 malaria non-exposed healthy donors were quantified by two different methodologies: amplification of the human telomerase reverse transcriptase (hTERT) genomic sequence by quantitative real time PCR (qPCR), and the fluorometric dsDNA quantification by Pico Green. CNAs levels were significantly increased in plasma from P. vivax patients as compared to healthy donors (p<0.0001). Importantly, plasma CNAs levels were strongly associated with vivax morbidity (p<0.0001), including a drop in platelet counts (p = 0.0021). These findings were further sustained when we assessed CNAS levels in plasma samples from 14 additional P. vivax patients of a different endemic area in Brazil, in which CNAS levels strongly correlated with thrombocytopenia (p = 0.0072). We further show that plasma CNAs levels decrease and reach physiological levels after antimalarial treatment. Although we found both host and parasite specific genomic sequences circulating in plasma, only host CNAs clearly reflected the clinical spectrum of P. vivax malaria. CONCLUSIONS: Here, we provide the first evidence of increased plasma CNAs levels in malaria patients and reveal their potential as sensitive biomarkers for vivax malaria morbidity.


Subject(s)
Malaria, Vivax/blood , Malaria, Vivax/epidemiology , Nucleic Acids/blood , Adult , Aged , Antimalarials/pharmacology , Antimalarials/therapeutic use , Base Sequence , Brazil/epidemiology , Female , Genome/genetics , Humans , Malaria, Vivax/complications , Malaria, Vivax/drug therapy , Male , Middle Aged , Plasmodium vivax/drug effects , Plasmodium vivax/genetics , Thrombocytopenia/blood , Thrombocytopenia/complications , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL
...