Clinical implications of serum neurofilament in newly diagnosed MS patients: a longitudinal multicentre cohort study

BACKGROUND: We aim to evaluate serum neurofilament light chain (sNfL), indicating neuroaxonal damage, as a biomarker at diagnosis in a large cohort of early multiple sclerosis (MS) patients. METHODS: In a multicentre prospective longitudinal observational cohort, patients with newly diagnosed relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS) were recruited between August 2010 and November 2015 in 22 centers. Clinical parameters, MRI, and sNfL levels (measured by single molecule array) were assessed at baseline and up to four-year follow-up. FINDINGS: Of 814 patients, 54.7% (445) were diagnosed with RRMS and 45.3% (369) with CIS when applying 2010 McDonald criteria (RRMS[2010] and CIS[2010]). After reclassification of CIS[2010] patients with existing CSF analysis, according to 2017 criteria, sNfL levels were lower in CIS[2017] than RRMS[2017] patients (9.1 pg/ml, IQR 6.2-13.7 pg/ml, n = 45; 10.8 pg/ml, IQR 7.4-20.1 pg/ml, n = 213; p = 0.036). sNfL levels correlated with number of T2 and Gd+ lesions at baseline and future clinical relapses. Patients receiving disease-modifying therapy (DMT) during the first four years had higher baseline sNfL levels than DMT-naïve patients (11.8 pg/ml, IQR 7.5-20.7 pg/ml, n = 726; 9.7 pg/ml, IQR 6.4-15.3 pg/ml, n = 88). Therapy escalation decisions within this period were reflected by longitudinal changes in sNfL levels. INTERPRETATION: Assessment of sNfL increases diagnostic accuracy, is associated with disease course prognosis and may, particularly when measured longitudinally, facilitate therapeutic decisions

Endovascular Stroke Treatment and Risk of Intracranial Hemorrhage in Anticoagulated Patients.

Background and Purpose- We aimed to determine the safety and mortality after mechanical thrombectomy in patients taking vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). Methods- In a multicenter observational cohort study, we used multiple logistic regression analysis to evaluate associations of symptomatic intracranial hemorrhage (sICH) with VKA or DOAC prescription before thrombectomy as compared with no anticoagulation. The primary outcomes were the rate of sICH and all-cause mortality at 90 days, incorporating sensitivity analysis regarding confirmed therapeutic anticoagulation. Additionally, we performed a systematic review and meta-analysis of literature on this topic. Results- Altogether, 1932 patients were included (VKA, n=222; DOAC, n=98; no anticoagulation, n=1612); median age, 74 years (interquartile range, 62-82); 49.6% women. VKA prescription was associated with increased odds for sICH and mortality (adjusted odds ratio [aOR], 2.55 [95% CI, 1.35-4.84] and 1.64 [95% CI, 1.09-2.47]) as compared with the control group, whereas no association with DOAC intake was observed (aOR, 0.98 [95% CI, 0.29-3.35] and 1.35 [95% CI, 0.72-2.53]). Sensitivity analyses considering only patients within the confirmed therapeutic anticoagulation range did not alter the findings. A study-level meta-analysis incorporating data from 7462 patients (855 VKAs, 318 DOACs, and 6289 controls) from 15 observational cohorts corroborated these observations, yielding an increased rate of sICH in VKA patients (aOR, 1.62 [95% CI, 1.22-2.17]) but not in DOAC patients (aOR, 1.03 [95% CI, 0.60-1.80]). Conclusions- Patients taking VKA have an increased risk of sICH and mortality after mechanical thrombectomy. The lower risk of sICH associated with DOAC may also be noticeable in the acute setting. Improved selection might be advisable in VKA-treated patients. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03496064. Systematic Review and Meta-Analysis: CRD42019127464

Participation in education among older people

National random sample data on 4254 people in four adult age categories were analyzed with regard to enrollments in different kinds of education settings, enrollment motives, and barriers to enrollment. Further analysis compared participants to nonparticipants. Most adult enrollments were at the college or university level before age 40, in other settings thereafter, and instrumental motives were predominant across the lifespan. Lack of time and interest were major barriers to enrollment among older people, and those enrolled generally had higher prior educational attainments, were younger, and lived in urban or suburban locations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44538/1/10755_2005_Article_BF01080356.pd

Quantitative trait loci identified for resistance to Stagonospora Glume Blotch in wheat in the USA and Australia

Resistance to stagonospora nodorum blotch (SNB) in glumes of hexaploid wheat (Triticum aestivum L.), caused by Phaeosphaeria (Stagonospora anamorph) nodorum was investigated in a recombinant-inbred (RI) population. The Purdue University winter wheat breeding lines P91193D1 and P92201D5, unrelated by parentage but both exhibiting partial SNB resistance, were crossed to develop 254 RI lines by single-seed descent (SSD) from a random population of F2 plants, to identify quantitative trait loci (QTLs) controlling SNB resistance in wheat glumes. The RI population, together with parent lines, was phenotyped for glume resistance to SNB under field conditions in F8:10 at Evansville, Vincennes, and Lafayette, IN, in 2003; in F7:9 at South Perth, Australia, in 2004; and in F8:10 in greenhouse-grown inoculated tests at Lafayette in 2003 and 2004. Two QTLs for resistance to SNB in glumes were identified: QSng.pur-2DL.1 from P91193D1 and QSng.pur-2DL.2 from P92201D5. The QTL QSng.pur-2DL.1 explained from 12.3% of the phenotypic variation for resistance in southern Indiana (Evansville and Vincennes) to 38.1% at South Perth; QSng.pur-2DL.2 accounted for 6.9 and 11.2% of the phenotypic variation in Indiana and South Perth, respectively. This study is the first report of SNB glume blotch resistance in which the same QTLs were identified in tests on different continents where Stagonospora nodorum populations are probably genetically diverse

Langmuir-Blodgett and X-ray diffraction studies of isolated photosystem II reaction centers in monolayers and multilayers: Physical dimensions of the complex

The photosystem II (PSII) reaction center (RC) is a hydrophobic intrinsic protein complex that drives the water-oxidation process of photosynthesis. Unlike the bacterial RC complex, an X-ray crystal structure of the PSII RC is not available. In order to determine the physical dimensions of the isolated PSII RC complex, we applied Langmuir techniques to determine the cross-sectional area of an isolated RC in a condensed monolayer film. Low-angle X-ray diffraction results obtained by examining Langmuir-Blodgett multilayer films of alternating PSII RC/Cd stearate monolayers were used to determine the length (or height; z-direction, perpendicular to the plane of the original membrane) of the complex. The values obtained for a PSII RC monomer were 26 nm2 and 4.8 nm, respectively, and the structural integrity of the RC in the multilayer film was confirmed by several approaches. Assuming a cylindrical-type RC structure, the above dimensions lead to a predicted volume of about 125 nm3. This value is very close to the expected volume of 118 nm3, calculated from the known molecular weight and partial specific volume of the PSII RC proteins. This same type of comparison was also made with the Rhodobacter sphaeroides RC based on published data, and we conclude that the PSII RC is much shorter in length and has a more regular solid geometric structure than the bacterial RC. Furthermore, the above dimensions of the PSII RC and those of PSII core (RC plus proximal antenna) proteins protruding outside the plane of the PSII membrane into the lumenal space as imaged by scanning tunneling microscopy (Seibert, Aust. J. Pl. Physiol. 22, 161-166, 1995) fit easily into the known dimensions of the PSII core complex visualized by others as electron-density projection maps. From this we conclude that the in situ PSII core complex is a dimeric structure containing two copies of the PSII RC.Peer Reviewe