Factors associated with disease flare following SARS-CoV-2 vaccination in people with inflammatory rheumatic and musculoskeletal diseases: results from the physician-reported EULAR Coronavirus Vaccine (COVAX) Registry.

OBJECTIVES: To investigate the frequency and factors associated with disease flare following vaccination against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal diseases (I-RMDs). METHODS: Data from the European Alliance of Associations for Rheumatology Coronavirus Vaccine physician-reported registry were used. Factors associated with flare in patients with I-RMDs were investigated using multivariable logistic regression adjusted for demographic and clinical factors. RESULTS: The study included 7336 patients with I-RMD, with 272 of 7336 (3.7%) experiencing flares and 121 of 7336 (1.6%) experiencing flares requiring starting a new medication or increasing the dosage of an existing medication. Factors independently associated with increased odds of flare were: female sex (OR=1.40, 95% CI=1.05 to 1.87), active disease at the time of vaccination (low disease activity (LDA), OR=1.45, 95% CI=1.08 to 1.94; moderate/high disease activity (M/HDA), OR=1.37, 95% CI=0.97 to 1.95; vs remission), and cessation/reduction of antirheumatic medication before or after vaccination (OR=4.76, 95% CI=3.44 to 6.58); factors associated with decreased odds of flare were: higher age (OR=0.90, 95% CI=0.83 to 0.98), non-Pfizer/AstraZeneca/Moderna vaccines (OR=0.10, 95% CI=0.01 to 0.74; vs Pfizer), and exposure to methotrexate (OR=0.57, 95% CI=0.37 to 0.90), tumour necrosis factor inhibitors (OR=0.55, 95% CI=0.36 to 0.85) or rituximab (OR=0.27, 95% CI=0.11 to 0.66), versus no antirheumatic treatment. In a multivariable model using new medication or dosage increase due to flare as the dependent variable, only the following independent associations were observed: active disease (LDA, OR=1.47, 95% CI=0.94 to 2.29; M/HDA, OR=3.08, 95% CI=1.91 to 4.97; vs remission), cessation/reduction of antirheumatic medication before or after vaccination (OR=2.24, 95% CI=1.33 to 3.78), and exposure to methotrexate (OR=0.48, 95% CI=0.26 to 0.89) or rituximab (OR=0.10, 95% CI=0.01 to 0.77), versus no antirheumatic treatment. CONCLUSION: I-RMD flares following SARS-CoV-2 vaccination were uncommon. Factors associated with flares were identified, namely higher disease activity and cessation/reduction of antirheumatic medications before or after vaccination.

Attention impairment in motor functional neurological disorders: a neuropsychological study.

OBJECTIVE: Our objective was to assess cognitive functioning across multiple cognitive domains using a standardised neuropsychological battery in patients with motor functional neurological disorders (mFND). METHODS: Thirty patients with clinically established mFND and 30 age-, sex- and education-matched control subjects underwent a thorough neuropsychological assessment evaluating (1) attention including processing speed, (2) executive functions including working memory, (3) short-term memory, (4) speech and language and (5) visuospatial functions. Performance validity tests (PVT) and self-report measures of depression, anxiety and cognitive complaints were included in the assessment. Only patients with valid test performance were included in the analysis. RESULTS: Three patients scored below the cut-off scores in PVT. Patients performed significantly worse than controls in the following areas: (1) the attention domain which included a slow processing speed (p = 0.005, Cohen's d = 0.89), (2) executive functions (p = 0.01, Cohen's d = 0.88) and (3) speech and language domains (p = 0.025, Cohen's d = 0.77). Patients with mFND showed greater intra-individual variability in cognitive performance (p = 0.005, Cohen's d = 0.94). Cognitive impairments were independent of depressive symptoms, which were higher in mFND patients. CONCLUSION: This study revealed both subjective and objective cognitive impairment in patients with mFND. The neuropsychological profile in mFND was characterised primarily by attentional impairment including a slow processing speed and a high intra-individual variability in cognitive performance. Cognitive impairment was associated with a valid test performance, highlighting that the deficits observed were not likely to be explained by a lack of effort in the patient group. Attention is considered to play a key role in mFND pathophysiology, and the results suggest that such impairments are objectively measurable.

Proximate Chemical Composition, Amino Acids Profile and Minerals Content of Meat Depending on Carcass Part, Sire Genotype and Sex of Meat Rabbits.

The aim of the study was to assess the effects of the sire genotype, sex and carcass part on the composition of the meat of rabbits, which were fattened under conditions where no synthetic drugs were used. As for carcass parts, the higher content of both total amino acids (AA) and all essential AA (EAA) monitored was found in the Longissimus thoracis et lumborum (LTL) muscle as compared to hind leg meat (p ˂ 0.001). Significant effects of the rabbit sire genotype and the genotype x sex interaction on proportions of some AA in meat were found (p ˂ 0.001). Crossbreeding of the Mecklenburger Schecke (MS) sires with a commercial dam line of HYLA rabbits resulted in a lower proportion of the total AA and all EAA monitored in meats of MS sired males as compared to MS sired females and HYLA rabbits (p ˂ 0.05). The sex-related effect on AA profile was not so noticeable in final commercial crossbreds of HYLA rabbits when compared to MS sired progeny. These findings point to a possible risk of alterations in the nutritional quality of meat proteins when using different rabbit sire genotypes than those originally intended for the specific commercial crossbreeding scheme. However, on the contrary, higher contents of magnesium (p ˂ 0.05), manganese (p ˂ 0.001) and zinc (p ˂ 0.05) were found in meats of MS sired progeny as compared to HYLA rabbits.

Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry.

OBJECTIVES: To describe the safety of vaccines against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal disease (I-RMD). METHODS: Physician-reported registry of I-RMD and non-inflammatory RMD (NI-RMDs) patients vaccinated against SARS-CoV-2. From 5 February 2021 to 27 July 2021, we collected data on demographics, vaccination, RMD diagnosis, disease activity, immunomodulatory/immunosuppressive treatments, flares, adverse events (AEs) and SARS-CoV-2 breakthrough infections. Data were analysed descriptively. RESULTS: The study included 5121 participants from 30 countries, 90% with I-RMDs (n=4604, 68% female, mean age 60.5 years) and 10% with NI-RMDs (n=517, 77% female, mean age 71.4). Inflammatory joint diseases (58%), connective tissue diseases (18%) and vasculitis (12%) were the most frequent diagnostic groups; 54% received conventional synthetic disease-modifying antirheumatic drugs (DMARDs), 42% biological DMARDs and 35% immunosuppressants. Most patients received the Pfizer/BioNTech vaccine (70%), 17% AstraZeneca/Oxford and 8% Moderna. In fully vaccinated cases, breakthrough infections were reported in 0.7% of I-RMD patients and 1.1% of NI-RMD patients. I-RMD flares were reported in 4.4% of cases (0.6% severe), 1.5% resulting in medication changes. AEs were reported in 37% of cases (37% I-RMD, 40% NI-RMD), serious AEs in 0.5% (0.4% I-RMD, 1.9% NI-RMD). CONCLUSION: The safety profiles of SARS-CoV-2 vaccines in patients with I-RMD was reassuring and comparable with patients with NI-RMDs. The majority of patients tolerated their vaccination well with rare reports of I-RMD flare and very rare reports of serious AEs. These findings should provide reassurance to rheumatologists and vaccine recipients and promote confidence in SARS-CoV-2 vaccine safety in I-RMD patients.

Nutritional evaluation of commercial dry dog foods available on the Czech market.

The evaluation of the quality of commercial diets is a topic of interest to dog owners and veterinarians. The aims of the study were to determine proximate analysis, metabolizable energy and some amino acids in dry dog diets for different ages, divided into three groups G1 (low price, grains included), G2 (medium price, grains included) and G3 (high price, grain-free). The hypothesis was tested that there are significant differences in the analysed values between dry dog diets from different price categories and between grain-free and grain-containing diets. Furthermore, the analysed values were compared with AAFCO and FEDIAF recommendations and with label values guaranteed by manufacturers to see whether there are any deviations. We analysed 60 samples of complete dry dog diets purchased in the Czech Republic, using the standard AOAC methods of proximate analysis. Metabolizable energy was calculated using the NRC equation, and 30 samples were analysed for selected amino acids. The results showed that there are significant differences in protein and amino acid contents between grain-free (G3) and grain-containing (G1,2) dog diets. G3 diets had significantly (p < 0.01) higher crude protein and essential amino acid contents. No significant differences were found between grain-containing diets G1 and G2. The results may indicate a higher proportion of animal components and a lower content of carbohydrates in G3 diets. Most of the tested dog diets met the AAFCO and FEDIAF recommendations. There were only a few deviations in threonine in G1 and G2 diets for growing dogs.

Changes in activity of metabolic and regulatory pathways during germination of S. coelicolor.

BACKGROUND: Bacterial spore germination is a developmental process during which all required metabolic pathways are restored to transfer cells from their dormant state into vegetative growth. Streptomyces are soil dwelling filamentous bacteria with complex life cycle, studied mostly for they ability to synthesize secondary metabolites including antibiotics. RESULTS: Here, we present a systematic approach that analyzes gene expression data obtained from 13 time points taken over 5.5 h of Streptomyces germination. Genes whose expression was significantly enhanced/diminished during the time-course were identified, and classified to metabolic and regulatory pathways. The classification into metabolic pathways revealed timing of the activation of specific pathways during the course of germination. The analysis also identified remarkable changes in the expression of specific sigma factors over the course of germination. Based on our knowledge of the targets of these factors, we speculate on their possible roles during germination. Among the factors whose expression was enhanced during the initial part of germination, SigE is though to manage cell wall reconstruction, SigR controls protein re-aggregation, and others (SigH, SigB, SigI, SigJ) control osmotic and oxidative stress responses. CONCLUSIONS: From the results, we conclude that most of the metabolic pathway mRNAs required for the initial phases of germination were synthesized during the sporulation process and stably conserved in the spore. After rehydration in growth medium, the stored mRNAs are being degraded and resynthesized during first hour. From the analysis of sigma factors we conclude that conditions favoring germination evoke stress-like cell responses.

Inference of sigma factor controlled networks by using numerical modeling applied to microarray time series data of the germinating prokaryote.

A computational model of gene expression was applied to a novel test set of microarray time series measurements to reveal regulatory interactions between transcriptional regulators represented by 45 sigma factors and the genes expressed during germination of a prokaryote Streptomyces coelicolor. Using microarrays, the first 5.5 h of the process was recorded in 13 time points, which provided a database of gene expression time series on genome-wide scale. The computational modeling of the kinetic relations between the sigma factors, individual genes and genes clustered according to the similarity of their expression kinetics identified kinetically plausible sigma factor-controlled networks. Using genome sequence annotations, functional groups of genes that were predominantly controlled by specific sigma factors were identified. Using external binding data complementing the modeling approach, specific genes involved in the control of the studied process were identified and their function suggested.

In vitro evaluation of the safety and probiotic properties of Lactobacilli isolated from chicken and calves.

A total of 73 chicken and calves isolates were diagnosed using matrix-assisted laser desorption ionization-time-of flight mass spectrometry (Maldi-Tof MS). After a preliminary subtractive screening based on the high acid tolerance at pH 2.5 and bile resistance at 0.3% oxgall, twenty isolates belonging to the species Lactobacillus salivarius, Lactobacillus agilis, Lactobacillus reuteri, Lactobacillus murinus and Lactobacillus amylovorus were in vitro screened for the safety assessment and probiotic properties, including antibiotics susceptibility patterns, biochemical activity and potential for competitive exclusion of biofilm producing pathogens determined by crystal violet and/or quantitative Fluorescent in situ Hybridisation (FISH) assays utilizing 5'Cy 3 labelled probe Enter1432 for enteric group. Antibiotic susceptibility testing was performed according to the ISO norm 10932. The sixteen strains were susceptible to certain antimicrobial agents, except for two chicken (L. salivarius 12K, L. agilis 13K) and two calves (L. reuteri L10/1, L. murinus L9) isolates with the presence non wild-type ECOFFs (epidemiological cut-off) for gentamicin (≥256 µg ml(-1)), tetracycline (≥128 µg ml(-1)), kanamycin (≥256 µg ml(-1)) and streptomycin (≥96 µg ml(-1)). The two referenced chicken isolates gave positive aac(6')Ie-aph(2″)Ia and tet(L) PCR results. The wild-type ECOFFs isolates were subjected to the apiZYM analysis for enzyme profile evaluation and amino acid decarboxylase activities determined by qualitative plate method and multiplex PCR for the detection of four genes involved in the production of histamine (histidine decarboxylase, hdc), tyramine (tyrosine decarboxylase, tyrdc) and putrescine (via eithers ornithine decarboxylase, odc, or agmatine deiminase, agdi). From examined strains only two chicken isolates (L. reuteri 14K; L. salivarius 15K) had no harmful ß-glucuronidase, ß-glucosidase activities connected with detrimental effects in the gastrointestinal tract and together no amino acid decarboxylase activities and no genes associated with biogenic amines production though only chicken L. salivarius 15K whole cells and acid supernatants shown strong suppressive potential against biofilm-forming Klebsiella and Escherichia coli. Our results highlight that above-mentioned isolate L. salivarius 15K fulfils the principle requirements of a qualified probiotic and may be seen as a reliable candidate for further validation studies in chicken.

Global features of gene expression on the proteome and transcriptome levels in S. coelicolor during germination.

Streptomycetes have been studied mostly as producers of secondary metabolites, while the transition from dormant spores to an exponentially growing culture has largely been ignored. Here, we focus on a comparative analysis of fluorescently and radioactively labeled proteome and microarray acquired transcriptome expressed during the germination of Streptomyces coelicolor. The time-dynamics is considered, starting from dormant spores through 5.5 hours of growth with 13 time points. Time series of the gene expressions were analyzed using correlation, principal components analysis and an analysis of coding genes utilization. Principal component analysis was used to identify principal kinetic trends in gene expression and the corresponding genes driving S. coelicolor germination. In contrast with the correlation analysis, global trends in the gene/protein expression reflected by the first principal components showed that the prominent patterns in both the protein and the mRNA domains are surprisingly well correlated. Analysis of the number of expressed genes identified functional groups activated during different time intervals of the germination.

Systems insight into the spore germination of Streptomyces coelicolor.

An example of bacterium, which undergoes a complex development, is the genus of Streptomyces whose importance lies in their wide capacity to produce secondary metabolites, including antibiotics. In this work, a proteomic approach was applied to the systems study of germination as a transition from dormancy to the metabolically active stage. The protein expression levels were examined throughout the germination time course, the kinetics of the accumulated and newly synthesized proteins were clustered, and proteins detected in each group were identified. Altogether, 104 2DE gel images at 13 time points, from dormant state until 5.5 h of growth, were analyzed. The mass spectrometry identified proteins were separated into functional groups and their potential roles during germination were further assessed. The results showed that the full competence of spores to effectively undergo active metabolism is derived from the sporulation step, which facilitates the rapid initiation of global protein expression during the first 10 min of cultivation. Within the first hour, the majority of proteins were synthesized. From this stage, the full capability of regulatory mechanisms to respond to environmental cues is presumed. The obtained results might also provide a data source for further investigations of the process of germination.

Possibilities of enhancing the colour of egg yolk.

BACKGROUND: This study attempts to compare two possibilities of enhancing the colour of egg yolk. One of them is based on the ecological rearing of laying hens on natural green grass whereas the other uses a feeding dose supplemented with natural pigments in laying hens reared in individual cages. Is it possible to distinguish these two technologies using yolk colour determination in the CIELAB system? RESULTS: Yolk colour parameters such as L*, a*, and b* in the group of grazed hens are significantly different (α = 0.001) from those observed in hens reared in cages. The yolk colour shows a darker, redder and more yellow colour. The greatest difference was seen in the red colour parameter, a*, that increased more than twice. Visually, this means a shift towards a more orange colour. Compared to grazing in the meadow (ΔE* = 13.257), the addition of artificial pigments in the feed resulted in a more significant increase in the parameter ΔE* (CIE total colour difference), with the greatest value of ΔE* being observed with the use of both pigments (ΔE* = 24.265). CONCLUSION: Grazing increases the parameter a* whereas the values of the parameter C*(ab) remain relatively low. The parameter ΔE* is significantly lower in the case of grazing as compared to the supplementation of the feed with pigments. However, colourity parameters cannot be used as a specific standard to identify a particular grazing technology as their values vary during the laying period.

Toxicological risk of melamine and cyanuric acid in food and feed.

From the toxicological point of view, in the last two years melamine and cyanuric acid have become matters of great interest. These substances, especially melamine, have been abused during food and feed adulteration by increasing the content of nitrogen compounds in these products. Melamine and cyanuric acid as individual substances do not pose any serious risk in terms of toxicology. From the point of view of toxicology, it is especially the complex of melamine with cyanuric acid that is important. This complex, also known as the melamine-cyanurate complex, is a cause of human and animal health problems. In this work we present two examples of the incidence of melamine and cyanuric acid in two feed products originating from China. They were rice and the pea concentrates intended for animal nutrition. Protein concentrates can be the main risk factor for food chain contamination with melamine and cyanuric acid, especially those of unknown origin. Feed with a high content of nitrogen compounds and low content of aminoacids can be regarded as particularly suspicious. A comparison of results for determining nitrogen compounds and amines can be used as proof of adulteration of protein feeds. These feeds must be subjected to further analysis to determine melamine and cyanuric acid.