Background
Some multiple sclerosis (MS) disease-modifying therapies (DMTs) impair responses to vaccines, emphasizing the importance of understanding COVID-19 vaccine immune responses in people with ...MS (PwMS) receiving different DMTs.
Methods
This prospective, open-label observational study enrolled 45 participants treated with natalizumab (
n
= 12), ocrelizumab (
n
= 16), fumarates (dimethyl fumarate or diroximel fumarate,
n
= 11), or interferon beta (
n
= 6); ages 18–65 years inclusive; stable on DMT for at least 6 months. Responder rates, anti-SARS-CoV-2 spike receptor-binding domain IgG (anti-RBD) geometric mean titers (GMTs), antigen-specific T cells, and vaccination-related adverse events were evaluated at baseline and 8, 24, 36, and 48 weeks after first mRNA-1273 (Moderna) dose.
Results
At 8 weeks post vaccination, all natalizumab-, fumarate-, and interferon beta-treated participants generated detectable anti-RBD IgG titers, compared to only 25% of the ocrelizumab cohort. At 24 and 36 weeks post vaccination, natalizumab-, fumarate-, and interferon beta-treated participants continued to demonstrate detectable anti-RBD IgG titers, whereas participants receiving ocrelizumab did not. Anti-RBD GMTs decreased 81.5% between 8 and 24 weeks post vaccination for the non-ocrelizumab-treated participants, with no significant difference between groups. At 36 weeks post vaccination, ocrelizumab-treated participants had higher proportions of spike-specific T cells compared to other treatment groups. Vaccine-associated side effects were highest in the ocrelizumab arm for most symptoms.
Conclusions
These results suggest that humoral response to mRNA-1273 COVID-19 vaccine is preserved and similar in PwMS treated with natalizumab, fumarate, and interferon beta, but muted with ocrelizumab. All DMTs had preserved T cell response, including the ocrelizumab cohort, which also had a greater risk of vaccine-related side effects.
To describe hand function among patients with multiple sclerosis (MS) and to examine the relationship between strength and self-reported abilities.
Cross-sectional study using a convenience sample.
...Outpatient department at a rehabilitation center.
Forty-four community-dwelling adults with MS (mean age, 49+/-9 y; range, 34-68 y) who were monitored by rehabilitation practitioners.
Not applicable.
Grip and pinch (tip, lateral, palmar) strengths and Manual Ability Measure (MAM-36).
When compared with the 50- to 54-year-old female norms, the pinch and grip strengths of the sample were lower. MAM-36 correlated moderately with right pinch (tip, lateral, palmar) strengths (r range, .51-.59; P<.01).
Manual ability seems to be more associated with pinch than grip strengths, probably because finger strength and dexterity are both needed to perform many hand tasks.
Abdominal aortic aneurysms (AAAs) are rupture-prone progressive dilations of the infrarenal aorta due to a loss of elastic matrix that lead to weakening of the aortic wall. Therapies to coax ...biomimetic regenerative repair of the elastic matrix by resident, diseased vascular cells may thus be useful to slow, arrest or regress AAA growth. Hyaluronan oligomers (HA-o) have been shown to induce elastic matrix synthesis by healthy and aneurysmal rat aortic smooth muscle cells (SMCs) in vitro but only via exogenous dosing, which potentially has side-effects and limitations to in vivo delivery towards therapy. In this paper, we describe the development of HA-o loaded poly(lactide-co-glycolide) nanoparticles (NPs) for targeted, controlled and sustained delivery of HA-o towards the elastogenic induction of aneurysmal rat aortic SMCs. These NPs were able to deliver HA-o over an extended period (>30days) at previously determined elastogenic doses (0.2–20μgml−1). HA-o released from the NPs led to dose-dependent increases in elastic matrix synthesis, and the recruitment and activity of lysyl oxidase, the enzyme which cross-links elastin precursor molecules into mature fibers/matrix. Therefore, we were able to successfully develop a nanoparticle-based system for controlled and sustained HA-o delivery for the in vitro elastogenic induction of aneurysmal rat aortic smooth muscle cells.
Treatment with natalizumab once every 4 weeks is approved for patients with relapsing-remitting multiple sclerosis, but is associated with a risk of progressive multifocal leukoencephalopathy. ...Switching to extended-interval dosing is associated with lower progressive multifocal leukoencephalopathy risk, but the efficacy of this approach is unclear. We aimed to assess the safety and efficacy of natalizumab once every 6 weeks compared with once every 4 weeks in patients with relapsing-remitting multiple sclerosis.
We did a randomised, controlled, open-label, phase 3b trial (NOVA) at 89 multiple sclerosis centres across 11 countries in the Americas, Europe, and Western Pacific. Included participants were aged 18–60 years with relapsing-remitting multiple sclerosis and had been treated with intravenous natalizumab 300 mg once every 4 weeks with no relapses for at least 12 months before randomisation, with no missed doses in the previous 3 months. Participants were randomly assigned (1:1), using a randomisation sequence generated by the study funder and contract personnel with interactive response technology, to switch to natalizumab once every 6 weeks or continue with once every 4 weeks. The centralised MRI reader, independent neurology evaluation committee, site examining neurologists, site backup examining neurologists, and site examining technicians were masked to study group assignments. The primary endpoint was the number of new or newly enlarging T2 hyperintense lesions at week 72, assessed in all participants who received at least one dose of assigned treatment and had at least one postbaseline MRI, relapse, or neurological examination or efficacy assessment. Missing primary endpoint data were handled under prespecified primary and secondary estimands: the primary estimand included all data, regardless of whether participants remained on the assigned treatment; the secondary estimand classed all data obtained after treatment discontinuation or study withdrawal as missing. Safety was assessed in all participants who received at least one dose of study treatment. Study enrolment is closed and an open-label extension study is ongoing. This study is registered with EudraCT, 2018-002145-11, and ClinicalTrials.gov, NCT03689972.
Between Dec 26, 2018, and Aug 30, 2019, 605 patients were assessed for eligibility and 499 were enrolled and assigned to receive natalizumab once every 6 weeks (n=251) or once every 4 weeks (n=248). After prespecified adjustments for missing data, mean numbers of new or newly enlarging T2 hyperintense lesions at week 72 were 0·20 (95% CI 0·07–0·63) in the once every 6 weeks group and 0·05 (0·01–0·22) in the once every 4 weeks group (mean lesion ratio 4·24 95% CI 0·86–20·85; p=0·076) under the primary estimand, and 0·31 (95% CI 0·12–0·82) and 0·06 (0·01–0·31; mean lesion ratio 4·93 95% CI 1·05–23·20; p=0·044) under the secondary estimand. Two participants in the once every 6 weeks group with extreme new or newly enlarging T2 hyperintense lesion numbers (≥25) contributed most of the excess lesions. Adverse events occurred in 194 (78%) of 250 participants in the once every 6 weeks group and 190 (77%) of 247 in the once every 4 weeks group, and serious adverse events occurred in 17 (7%) and 17 (7%), respectively. No deaths were reported. There was one case of asymptomatic progressive multifocal leukoencephalopathy (without clinical signs) in the once every 6 weeks group, and no cases in the once every 4 weeks group; 6 months after diagnosis, the participant was without increased disability and remained classified as asymptomatic.
We found a numerical difference in the mean number of new or newly enlarging T2 hyperintense lesions at week 72 between the once every 6 weeks and once every 4 weeks groups, which reached significance under the secondary estimand, but interpretation of statistical differences (or absence thereof) is limited because disease activity in the once every 4 weeks group was lower than expected. The safety profiles of natalizumab once every 6 weeks and once every 4 weeks were similar. Although this trial was not powered to assess differences in risk of progressive multifocal leukoencephalopathy, the occurrence of the (asymptomatic) case underscores the importance of monitoring and risk factor consideration in all patients receiving natalizumab.
Biogen.
This study was designed to assess the possibility of tailoring waste papers and wood dust into composite materials with plaster of Paris (P.O.P) and also determine the suitability of using the ...developed composites as ceiling panels in building construction. Assorted un-used papers collected as waste materials were processed into waste paper ash (WPA) which was then after utilized like untreated wood dust (UWD) and treated wood dust (TWD) as filler materials to separately, but at similar volumetric proportions, fabricate test samples with P.O.P as matrix. Static angle of repose and major chemical constituents of the fillers were determined. The results of the tests performed on the samples revealed that increase in the proportion of each filler material resulted to decrease in bulk density, thermal conductivity, thermal diffusivity, and flexural strength but increase in percentage water absorption, specific heat capacity, thermal resistance, heat penetration time, and flaking concentration. Sample developed with 36.7 % of the WPA and the one containing 25.0 % of the TWD exhibited impressive performance ability similar to sample fabricated with 18.3 % of the UWD. Though the most significant improvement in thermal insulating ability over the pure P.O.P sample was observed in the case of samples developed with the UWD, it was found that the proportion of each filler material incorporated into the P.O.P matrix can be adjusted to achieve optimum performance desired of the resulting composite panel during its usage as a ceiling in building. From technical–economic point of view, utilizing waste papers and wood dust as raw materials in the production of new and value-added engineering materials, as in the present study, is a promising possibility of reducing the cost of P.O.P for enhancement of affordable housing, thereby meeting the needs of end-users and also ensure minimization of health hazards associated with paper and wood dust wastes.
The authors examined the physiochemical and microbiological properties of archived rusticles from World War II shipwrecks in the Gulf of Mexico. Rusticles, iron (Fe)-rich accumulations on shipwrecks ...in marine environments, have long been assumed to be the result of low alloy steel corrosion. In many cases the assumed corrosion has been attributed to biodeterioration because of the presence of specific types of bacteria associated with the rusticles. However, archived rusticles from WWII shipwrecks in the Gulf of Mexico (GOM) do not have the mineralogical layering typical of iron corrosion products. Moreover, spatial relationships between bacteria and rusticles cannot be interpreted as biodeterioration. The authors concluded that environmental Fe plays a role in rusticle formation and differences in Fe concentrations can be used to explain differences in rusticle size and distribution with depth in the GOM. Both biotic and abiotic mechanisms for Fe accumulation are provided.
•Rusticles are iron-rich accumulations found on shipwrecks in marine environments.•The spatial relationship between microorganisms and accumulated iron oxides cannot be interpreted as biodeterioration.•Rusticles from Gulf of Mexico shipwrecks are not consistent with mineralogical layering typical of iron corrosion products.•The role of environmental iron in rusticle formation and growth has been previously ignored.
This study was designed to examine the feasibility of recycling cassava effluent, sawdust, and unused paper products to enhance their utilization for beneficial purpose. Waste newspaper paste (WNP), ...Waste writing – paper paste (WWP), and Waste carton paper paste (WCP) were prepared and then used separately to similarly fabricate composite panels with Sawdust particle (SDP) proportioned at 0%, 25%, 50%, 75%, and 100% by weight. The binder used was cassava starch slurry prepared from the effluent. Bulk density, water absorption, thermal conductivity, specific heat capacity, thermal diffusivity, nailability, and flexural strength were determined for the developed samples. From the results obtained, the samples were found to be light-weight and their thermal insulation performance improved with increasing proportions of the SDP. Though samples containing the WCP exhibited the best satisfactory performance, it was found that all the studied samples could perform more effectively and efficiently as ceilings compared to some of those reported in the literature. From scientific-economic viewpoint, valorizing the above-mentioned wastes as described in this paper could help to protect the environment and also yield value-added insulation ceilings for enhancement of sustainable building construction especially in tropical areas.
Coconut husk is generated yearly as waste in large quantities but majorly under-utilized. Also, as a result of high embodied carbon, cement production is one of the largest contributors to ...construction sector carbon footprint. Since accumulation of unmanaged agro-waste like coconut husk has an increased environmental concern due to its pollution effect, recycling it into sustainable construction materials is a viable solution for future generation. In this study, experiments were performed to investigate the influence of coconut husk ash nanomaterial (CHAN) inclusion on electrical characteristics of plain cement paste (BCP) and mortar (CSM) samples at curing ages of 7 and 28 days. The results showed increase in electrical resistivity, thermal constant, and activation energy with curing duration for heating and cooling cycles of BCP and CSM. With inclusion of CHAN, the developed cement paste (CAP) and mortar (CASM) possessed lower values in all cases compared to their counterparts. Also, during heating at 28 days, both the CAP and CASM exhibited decrease in thermal constant. Though electrical resistance of all the samples varied inversely with temperature, CAP and CASM were found to possess greater potentials to make building structures intrinsically smart. Hence, in addition to solving disposal problems, utilization of coconut husks as described herein could enhance development of safe, inexpensive, and sustainable buildings that have large temperature sensing volume.
The literature is flooded with scientific information on most durability properties except water absorption coefficient of masonry units like sandcrete blocks. Also, while waste papers disposal is a ...systemic problem due to ineffectiveness of waste management system in developing countries, the price of cement is on the increase. This situation, ultimately, causes a bane in achievement of low-cost housing development considering the fact that sandcrete blocks are predominantly used as walling elements for such undertakings. In this study, solid core sandcrete blocks were produced with waste paper ash (WPA) utilized as partial replacement of cement at 5 % and 10 % volumetric levels. Chemically, the WPA was found to show similarity with cement in terms of SiO
, Al
, and CaO contents. Density and water absorption coefficient of the block samples were determined. While density ranged from 1682 to 1872 kg/m
, water absorption coefficient varied from 27.04 to 23.49 kg/m
. Statistically, no significant difference was revealed at
< 0.05 between experimentally-measured water absorption coefficients and those obtained using the model developed for prediction based on density of the samples. Thus, utilization of WPA as described herein could help to reduce the cost of procuring cement and in turn, enhance low-cost building construction. Also, with the developed model (showing dependence of water absorption coefficient on density), durability of sandcrete blocks exposed to moisture –prone environment could be easily predicted.
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