OBJECTIVETo investigate the association between plasma neurofilament light chain (pNfL) levels and the risk of developing sustained disability worsening.
METHODSConcentrations of pNfL were determined ...in 4,385 persons with multiple sclerosis (MS) and 1,026 randomly selected population-based sex- and age-matched controls using the highly sensitive Single Molecule Array (SimoaTM) NF-Light Advantage Kit. We assessed the impact of age-stratified pNfL levels above the 80th, 95th, and 99th percentiles among controls on the risk of Expanded Disability Status Scale (EDSS) worsening within the following year and reaching sustained EDSS scores of 3.0, 4.0, and 6.0 and conversion to secondary progressive multiple sclerosis (SPMS).
RESULTSThe median (interquartile range IQR) pNfL was 7.5 (4.1) pg/mL in controls and 11.4 (9.6) pg/mL in MS (p < 0.001). The median (IQR) duration of follow-up was 5 (5.1) years. High pNfL was associated with increased adjusted rates of EDSS worsening ranging between 1.4 (95% confidence intervals CIs1.1–1.8) and 1.7 (95% CI1.4–2.3). High pNfL was also associated with the risk of reaching a sustained EDSS score of 3.0, with adjusted rates ranging between 1.5 (95% CI1.2–1.8) and 1.55 (95% CI1.3–1.8) over all percentile cutoffs (all p < 0.001). Similar increases were observed for the risk of sustained EDSS score 4.0. In contrast, the risk of reaching sustained EDSS score 6.0 and conversion to SPMS was not consistently significant.
CONCLUSIONSElevated pNfL levels at early stages of MS are associated with an increased risk of reaching sustained disability worsening. Hence, pNfL may serve as a prognostic tool to assess the risk of developing permanent disability in MS.
Abstract
Background
The emergence of resistance to artemisinin derivatives in Southeast Asia constitutes a serious threat for other malaria endemic areas, particularly in Côte d’Ivoire. To delay this ...resistance, the application of the control measures recommended by the National Malaria Control Programme (NMCP) for a correct management, in the private pharmacies, is a necessity. The purpose of this study was, therefore, to assess the level of knowledge and practices of private pharmacy auxiliary in Abidjan about the management of malaria.
Methods
A descriptive cross-sectional study was conducted from April to November 2015. It included auxiliaries of private pharmacies in Abidjan. Data collection material was a structured an open pretested questionnaire. Data analysis was carried out using Package for Social Science (SPSS) software version 21.1. Chi square test was used to compare proportions for a significance threshold of 0.05 for the p value.
Results
A total, 447 auxiliaries from 163 private pharmacies were interviewed. It was noted that the auxiliaries had a good knowledge of clinical signs of uncomplicated malaria (99.1%), biological examinations (54.6% for the thick film and 40.7% for rapid diagnostic tests (RDTs) and anti-malarial drugs (99.3% for artemether + lumefantrine, AL). The strategies of vector control (long-lasting insecticide-treated mosquito nets (LLITNs, Repellent ointments, cleaning gutters, elimination of larvae breeding site and intermittent preventive treatment with sulfadoxine–pyrimethamine (IPTp-SP) in pregnant women were also known by the auxiliaries, respectively 99.8% and 77.4%. However, the malaria pathogen (25.1%) and the NMCP recommendations (e.g. use of AL or AS + AQ as first-line treatment for uncomplicated malaria and IPTp-SP in pregnant women) were not well known by the auxiliaries (28.2% and 26.9% for uncomplicated and severe malaria). Concerning the practices of the auxiliaries, 91.1% offered anti-malarial drugs to patients without a prescription and 47.3% mentioned incorrect dosages. The combination artemether + lumefantrine was the most recommended (91.3%). The delivery of anti-malarial drugs was rarely accompanied by advice on malaria prevention, neither was it carried out on the result of an RDT.
Conclusion
The epidemiology and the NMCP recommendations for the diagnostic and therapeutic management of malaria, are not well known to auxiliaries, which may have implications for their practices. These results show the need to sensitize and train private pharmacy auxiliaries, and also to involve them in NMCP activities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Malaria is a major public health problem, particularly in the tropical regions of America, Africa and Asia. Plasmodium falciparum is not only the most widespread but also the most deadly species. The ...share of Plasmodium infections caused by the other species (Plasmodium ovale and Plasmodium malariae) is clearly underestimated. The objective of the study was to determine the molecular epidemiology of plasmodial infection due to P. malariae and P. ovale in Côte d'Ivoire.
The study was cross-sectional. The study participants were recruited from Abengourou, San Pedro and Grand-Bassam. Sample collection took place from May 2015 to April 2016. Questionnaires were administered and filter paper blood samples were collected for parasite DNA extraction. The molecular analysis was carried out from February to March 2021. A nested PCR was used for species diagnosis. The data was presented in frequencies and proportions.
A total of 360 patients were recruited, including 179 men (49,7%) for 181 women (50,3%). The overall Plasmodium positive rate was 72.5% (261/360). The specific index was 77.4% and 1.5% for P. falciparum and P. malariae in mono-infection, respectively. There was also 15% P. falciparum and P. malariae co-infection, 3.4% P. falciparum and P. ovale co-infection and 2.3% P. falciparum, P. malariae and P. ovale triple-infection. Typing of P. ovale subspecies showed a significant predominance of P. ovale curtisi (81.2% of cases).
Plasmodium falciparum remains the most prevalent malaria species in Côte d'Ivoire, but P. malariae and P. ovale are also endemic mostly in co-infection. Malaria elimination requires a better understanding of the specific epidemiological characteristics of P. malariae and P. ovale with a particular emphasis on the identification of asymptomatic carriers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•High injection pressures up to 5000 bar were achieved under different conditions.•Schlieren, Mie-scattering and OH* chemiluminescence techniques were applied.•Injection rates up to ...4000 bar of injection pressure present fast opening needle.•Highest injection pressures create shock waves inside the chamber improving mixing.•Increased mixing and shorter ignition delay times are achieved at higher pressures.
The aim of this work is to investigate a novel very high-pressure diesel injector under different working conditions. Furthermore, the aim of this work is also to analyse the behaviour of the evaporation, mixing and combustion of a diesel spray in a quiescent environment at very high injection pressures. In order to achieve this, the injector was first characterized from 2500 bar to 4000 bar of injection pressure. Then, an experimental matrix was designed to study the high-pressure spray under (i) cold non-evaporating, (ii) evaporating non-reactive and (iii) reactive conditions under different injection pressures up to 5000 bar. The experiments were carried out in a constant volume cell equipped with optical accesses. This allowed the application of the schlieren, mie-scattering and OH* chemiluminescence techniques at high speed to quantify the propagation of the spray through the ambient gases. The injector used was a prototype single-hole axial injector working with reference diesel as the injection fluid. The results showed a strong dependency of the spray tip penetration on the injection pressure. In some conditions creating shock waves inside the chamber that would disrupt the spray flow, causing it to mix better. Although the higher exit velocities made the fuel travel faster, resulting in longer penetrations of both phases, it also caused the fuel to evaporate faster due to slightly better mixing, resulting in similar liquid length values. This increased momentum enhanced mixing, resulting also in shorter ignition delay times. The higher velocities caused the flame base to stabilise further from the nozzle, which led to longer lift-off lengths.
Background and purpose
Serum neurofilaments are markers of axonal injury. We addressed their diagnostic and prognostic role in acute ischemic stroke (AIS) and transient ischemic attack (TIA).
Methods
...Nested within a prospective cohort study, we compared levels of serum neurofilament light chain (sNfL) drawn within 24 h from symptom onset in patients with AIS or TIA. Patients without magnetic resonance imaging on admission were excluded. We assessed whether sNfL was associated with: (i) clinical severity on admission, (ii) diagnosis of AIS vs. TIA, (iii) infarct size on admission magnetic resonance diffusion‐weighted imaging (MR‐DWI) and (iv) functional outcome at 3 months.
Results
We analyzed 504 patients with AIS and 111 patients with TIA. On admission, higher National Institutes of Health Stroke Scale (NIHSS) scores were associated with higher sNfL: NIHSS score < 7, 13.1 pg/mL interquartile range (IQR), 5.3–27.8; NIHSS score 7–15, 16.7 pg/mL (IQR, 7.4–34.9); and NIHSS score > 15, 21.0 pg/mL (IQR, 9.3–40.4) (P = 0.01). Compared with AIS, patients with TIA had lower sNfL levels 9.0 pg/mL (95% confidence interval, 4.0–19.0) vs. 16.0 pg/mL (95% confidence interval, 7.3–34.4), P < 0.001, also after adjusting for age and NIHSS score (P = 0.006). Among patients with AIS, infarct size on admission MR‐DWI was not associated with sNfL, either in univariate analysis (P = 0.15) or after adjusting for age and NIHSS score on admission (P = 0.56). Functional outcome 3 months after stroke was not associated with sNfL after adjusting for established predictors.
Conclusions
In conclusion, among patients admitted within 24 h of AIS or TIA onset, admission sNfL levels were associated with clinical severity on admission and TIA diagnosis, but not with infarct size on MR‐DWI acquired on admission or functional outcome at 3 months.
Neurodegenerative diseases are heterogeneous in their cause and clinical presentation making clinical assessment and disease monitoring challenging. Because of this, there is an urgent need for ...objective tools such as fluid biomarkers able to quantitate different aspects of the disease. In the last decade, technological improvements and awareness of the importance of biorepositories led to the discovery of an evolving number of fluid biomarkers covering the main characteristics of neurodegenerative diseases such as neurodegeneration, protein aggregates and inflammation. The ability to quantitate each aspect of the disease at a high definition enables a more precise stratification of the patients at inclusion in clinical trials, hence reducing the noise that may hamper the detection of therapeutical efficacy and allowing for smaller but likewise powered studies, which particularly improves the ability to start clinical trials for rare neurological diseases. Moreover, the use of fluid biomarkers has the potential to support a targeted therapeutical intervention, as it is now emerging for the treatment of amyloid-beta deposition in patients suffering from Alzheimer’s disease. Here we review the knowledge that evolved from the measurement of fluid biomarker proteins in neurodegenerative conditions.
•Fluid biomarkers for neurodegenerative conditions are an urgent unmet need.•Technical advances enable a highly sensitive detection of biomarkers in blood.•Each biomarker is reflecting different aspects of CNS pathology.•Biomarkers can stratify patients based on biology rather than clinical phenotype.
Background and purpose
Neurofilament light chain is a cytoskeletal protein of neurons. Its levels are increasingly recognized as measures of neuroaxonal damage. The aim of this study was to explore ...serum neurofilament light chain (sNfL) levels in multiple sclerosis (MS) patients and healthy controls during pregnancy and puerperium.
Methods
This was a prospective, longitudinal, single‐center study. sNfL concentration was assessed using a highly sensitive single‐molecule array during pregnancy and in puerperium, in a cohort of 39 pregnant patients with relapsing multiple sclerosis (P‐MS). Twenty‐one healthy pregnant women (HPW) served as a control group. Eight P‐MS suffered relapses during pregnancy (P‐MS‐R) in the first or second trimesters.
Results
No differences in pregnancy and delivery data were observed between P‐MS and HPW. P‐MS showed higher sNfL values than HPW in the first trimester, independently of the presence (P = 0.002) or not (P = 0.02) of relapses during pregnancy. However, in the third trimester, only P‐MS‐R showed higher sNfL values than HPW (P = 0.001). These differences extended to the puerperium, where P‐MS‐R showed higher sNfL values than those with no relapses during gestation (P = 0.02).
Conclusion
These data strongly suggest that sNfL levels reflect MS activity during pregnancy. Additionally, the absence of relapses during pregnancy may have a beneficial effect on neurodegeneration during puerperium.
We report the case of a neonate with a new, previously undescribed, glucose-6-phosphate dehydrogenase (G6PD) gene mutation, which was revealed by severe cholestasis, hyperbilirubinemia, and transient ...liver dysfunction. The severity of the clinical phenotype with ongoing chronic hemolytic anemia suggests that this mutation belongs to class 1 G6PD deficiency. The hemizygous mutation «c.675G>c; p.Trp225Cys» was detected by genomic sequencing. Since severe G6PD deficiency can be revealed by cholestasis, it is important to check G6PD enzyme activity when faced with a case of liver dysfunction in the neonatal period.
Objective
Neurofilament light chains (NfL) are unique to neuronal cells, are shed to the cerebrospinal fluid (CSF), and are detectable at low concentrations in peripheral blood. Various diseases ...causing neuronal damage have resulted in elevated CSF concentrations. We explored the value of an ultrasensitive single‐molecule array (Simoa) serum NfL (sNfL) assay in multiple sclerosis (MS).
Methods
sNfL levels were measured in healthy controls (HC, n = 254) and two independent MS cohorts: (1) cross‐sectional with paired serum and CSF samples (n = 142), and (2) longitudinal with repeated serum sampling (n = 246, median follow‐up = 3.1 years, interquartile range IQR = 2.0–4.0). We assessed their relation to concurrent clinical, imaging, and treatment parameters and to future clinical outcomes.
Results
sNfL levels were higher in both MS cohorts than in HC (p < 0.001). We found a strong association between CSF NfL and sNfL (β = 0.589, p < 0.001). Patients with either brain or spinal (43.4pg/ml, IQR = 25.2–65.3) or both brain and spinal gadolinium‐enhancing lesions (62.5pg/ml, IQR = 42.7–71.4) had higher sNfL than those without (29.6pg/ml, IQR = 20.9–41.8; β = 1.461, p = 0.005 and β = 1.902, p = 0.002, respectively). sNfL was independently associated with Expanded Disability Status Scale (EDSS) assessments (β = 1.105, p < 0.001) and presence of relapses (β = 1.430, p < 0.001). sNfL levels were lower under disease‐modifying treatment (β = 0.818, p = 0.003). Patients with sNfL levels above the 80th, 90th, 95th, 97.5th, and 99th HC‐based percentiles had higher risk of relapses (97.5th percentile: incidence rate ratio = 1.94, 95% confidence interval CI = 1.21–3.10, p = 0.006) and EDSS worsening (97.5th percentile: OR = 2.41, 95% CI = 1.07–5.42, p = 0.034).
Interpretation
These results support the value of sNfL as a sensitive and clinically meaningful blood biomarker to monitor tissue damage and the effects of therapies in MS. Ann Neurol 2017;81:857–870
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