Successful experience of tofacitinib treatment in patients with Fibrodysplasia Ossificans Progressiva.

Fibrodysplasia ossificans progressive (FOP) is an ultra-rare genetic disorder that is caused by a mutation in the ACVR1 gene and provokes severe heterotopic ossification. Since flares of the disease are associated with inflammation, it is assumed that JAK inhibitors can control active FOP due to blocking multiple signaling pathways.

Response to netakimab in radiographic axial spondyloarthritis patients with different baseline C-reactive protein, sacroiliitis evaluated by MRI and peripheral joint involvement status: a post-hoc analysis of the ASTERA study.

OBJECTIVES: Netakimab is a humanised camelid-derived monoclonal antibody targeting interleukin-17A. Here, we report the results of post-hoc analysis of the ASTERA phase 3 study (NCT03447704, February 27, 2018) in patients with active radiographic axial spondyloarthritis (r-axSpA) grouped by baseline C-reactive protein (CRP), baseline sacroiliac joint (SIJ) inflammation through magnetic resonance imaging (MRI) or presence of peripheral arthritis (PA). METHODS: In this double-blinded, multicentre, randomised, placebo-controlled, phase 3 ASTERA study, 228 adult patients with active r-axSpA received 120 mg of subcutaneous netakimab or placebo at weeks 0, 1, 2, and thereafter every other week. For the subanalysis, 16-week data of 114 netakimab-treated patients with the available baseline CRP and SIJ MRI were grouped by normal (<5 mg/L) or abnormal (≥5 mg/L) CRP, by the grade of sacroiliitis (SI) based on the SPARCC MRI score <2 (MRI-SI-) or ≥2 (MRI-SI+), or by the presence of PA. ASAS-recommended activity, spinal mobility, and function endpoints for r-axSpA were analysed. RESULTS: At week 16, an improvement in all the outcomes was similar for MRI-SI- and MRI-SI+ patients, except for a change in ASspi-MRI-a which was significantly greater in MRI-SI+. Netakimab was effective regardless of baseline CRP and PA. For patients with CRP ≥5 mg/L, a more pronounced decline in r-axSpA activity was observed with a trend towards the most prominent improvement in ASDAS-CRP and BASDAI for patients with CRP >20 mg/L. CONCLUSIONS: Subcutaneous netakimab is effective in patients with r-axSpA irrespective of baseline CRP and inflammation on SIJ MRI. The benefit in patients with high CRP (>20 mg/L) was more pronounced.

Ratio of Intensities of Blue and Red Light at Cultivation Influences Photosynthetic Light Reactions, Respiration, Growth, and Reflectance Indices in Lettuce.

LED illumination can have a narrow spectral band; its intensity and time regime are regulated within a wide range. These characteristics are the potential basis for the use of a combination of LEDs for plant cultivation because light is the energy source that is used by plants as well as the regulator of photosynthesis, and the regulator of other physiological processes (e.g., plant development), and can cause plant damage under certain stress conditions. As a result, analyzing the influence of light spectra on physiological and growth characteristics during cultivation of different plant species is an important problem. In the present work, we investigated the influence of two variants of LED illumination (red light at an increased intensity, the "red" variant, and blue light at an increased intensity, the "blue" variant) on the parameters of photosynthetic dark and light reactions, respiration rate, leaf reflectance indices, and biomass, among other factors in lettuce (Lactuca sativa L.). The same light intensity (about 180 µmol m-2s-1) was used in both variants. It was shown that the blue illumination variant increased the dark respiration rate (35-130%) and cyclic electron flow around photosystem I (18-26% at the maximal intensity of the actinic light) in comparison to the red variant; the effects were dependent on the duration of cultivation. In contrast, the blue variant decreased the rate of the photosynthetic linear electron flow (13-26%) and various plant growth parameters, such as final biomass (about 40%). Some reflectance indices (e.g., the Zarco-Tejada and Miller Index, an index that is related to the core sizes and light-harvesting complex of photosystem I), were also strongly dependent on the illumination variant. Thus, our results show that the red illumination variant contributes a great deal to lettuce growth; in contrast, the blue variant contributes to stress changes, including the activation of cyclic electron flow around photosystem I.

The Effect of Plant Growth Compensation by Adding Silicon-Containing Fertilizer under Light Stress Conditions.

The effects of different spectral compositions of light-emitting diode (LED) sources and fertilizer containing biologically active silicon (Si) in the nutrient solution on morphological and physiological plant response were studied. Qualitative indicators and the productivity of plants of a red-leaved and a green-leaved lettuce were estimated. Lettuce was grown applying low-volume hydroponics in closed artificial agroecosystems. The positive effect of Si fertilizer used as a microadditive in the nutrient solution on the freshly harvested biomass was established on the thirtieth day of vegetation under LEDs. Increase in productivity of the red-leaved lettuce for freshly harvested biomass was 26.6%, while for the green-leaved lettuce no loss of dry matter was observed. However, being grown under sodium lamps, a negative impact of Si fertilizer on productivity of both types of plants was observed: the amount of harvested biomass decreased by 22.6% and 30.3% for the green- and red-leaved lettuces, respectively. The effect of using Si fertilizer dramatically changed during the total growing period: up to the fifteenth day of cultivation, a sharp inhibition of the growth of both types of lettuce was observed; then, by the thirtieth day of LED lighting, Si fertilizer showed a stress-protective effect and had a positive influence on the plants. However, by the period of ripening there was no effect of using the fertilizer. Therefore, we can conclude that the use of Si fertilizers is preferable only when LED irradiation is applied throughout the active plant growth period.

Simulation of Field Assisted Sintering of Silicon Germanium Alloys.

We report a numerical study of the field assisted sintering of silicon germanium alloys by a finite element method, which takes into account contact resistances, thermal expansion and the thermoelectric effect. The distribution of electrical and thermal fields was analyzed numerically, based on the experimental data collected from spark plasma sintering (SPS) apparatus. The thermoelectric properties of Si-Ge used within the simulation were considered as the function of density and the sintering temperature. Quantitative estimation of the temperature distribution during the sintering pointed to a significant, up to 60 °C, temperature difference within the specimen volume for the case of the sintering temperature at 1150 °C.

CSF amyloid-beta-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia.

As the differential diagnosis of dementias based on established clinical criteria is often difficult, biomarkers for applicable diagnostic testing are currently under intensive investigation. Amyloid plaques deposited in the brain of patients suffering from Alzheimer's disease, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) mainly consist of carboxy-terminally elongated forms of amyloid-beta (Abeta) peptides, such as Abeta1-42. Absolute Abeta1-42 levels in CSF have shown diagnostic value for the diagnosis of Alzheimer's disease, but the discrimination among Alzheimer's disease, DLB and PDD was poor. A recently established quantitative urea-based Abeta-sodium-dodecylsulphate-polyacrylamide-gel-electrophoresis with Western immunoblot (Abeta-SDS-PAGE/immunoblot) revealed a highly conserved Abeta peptide pattern of the carboxy-terminally truncated Abeta peptides 1-37, 1-38, 1-39 in addition to 1-40 and 1-42 in human CSF. We used the Abeta-SDS-PAGE/immunoblot to investigate the CSF of 23 patients with Alzheimer's disease, 21 with DLB, 21 with PDD and 23 non-demented disease controls (NDC) for disease-specific alterations of the Abeta peptide patterns in its absolute and relative quantities. The diagnostic groups were matched for age and severity of dementia. The present study is the first attempt to evaluate the meaning of Abeta peptide patterns in CSF for differential diagnosis of the three neurodegenerative diseases--Alzheimer's disease, DLB and PDD. The Abeta peptide patterns displayed disease-specific variations and the ratio of the differentially altered Abeta1-42 to the Abeta1-37 levels subsequently discriminated all diagnostic groups from each other at a highly significant level, except DLB from PDD. Additionally, a novel peptide with Abeta-like immunoreactivity was observed constantly in the CSF of all 88 investigated patients. The pronounced percentage increase of this peptide in DLB allowed a highly significant discrimination from PDD. Using a cut-off point of 0.954%, this marker yielded a diagnostic sensitivity and specificity of 81 and 71%, respectively. From several lines of indication, we consider this peptide to represent an oxidized alpha-helical form of Abeta1-40 (Abeta1-40*). The increased abundance of Abeta1-40* probably reflects a disease-specific alteration of the Abeta1-40 metabolism in DLB. We conclude that Abeta peptide patterns reflect disease-specific pathophysiological pathways of different dementia syndromes as distinct neurochemical phenotypes. Although Abeta peptide patterns failed to fulfil the requirements for a sole biomarker, their combined evaluation with other biomarkers is promising in neurochemical dementia diagnosis. It is noteworthy that DLB and PDD exhibit distinct clinical temporal courses, despite their similar neuropathological appearance. Their distinct molecular phenotypes support the view of different pathophysiological pathways for each of these neurodegenerative diseases.

Electrophoretic separation of amyloid beta peptides in plasma.

In this prospective study, for the first time we have separated and quantified amyloid beta (Abeta) peptides in the plasma of patients with Alzheimer's disease (AD, n = 8) and age- and environment-matched healthy controls (n = 9) with urea-based Abeta-sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)/immunoblot. In addition to the Abeta peptides 1-37/38/39/40/42, which we recently identified as regular constituents of human cerebrospinal fluid (CSF), we have observed a novel electrophoretic band migrating slightly cathodically to Abeta1-42. Since a standard peptide with the amino acid sequence Abeta2-40 migrates in the same position, we hypothesize that this plasma-specific band may correspond to Abeta2-40. The concentration of Abeta peptides in the plasma has been approximately 100-fold lower compared to the CSF. Interestingly, the concentration of the two shortest peptides and the longest one of these considered here (i.e., Abeta1-37/38/42) have increased significantly when the samples have been frozen at -80 degrees C before immunoprecipitation, while the 'middle-length' peptides (i.e., Abeta1-39/40) have not been affected by this procedure. We have not observed significant differences of the Abeta peptides concentrations between AD and control subjects. Our method can be used to investigate the significance of plasma Abeta peptides in neurodegenerative disorders, and to monitor the efficiency of drugs with beta/gamma-secretase inhibitory potency.