The Alterations of Serum N-glycome in Response to SARS-CoV-2 Vaccination.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a global concern since its outbreak in 2019, with one of the main solutions being vaccination. Altered glycosylation has been described in patients after SARS-CoV-2 infection, while the effect of vaccination on serum glycoproteins remained unexplored. In this study, total serum glycosylation was analyzed in patients after SARS-CoV-2 infection and/or mRNA vaccination in order to identify potential glycosylation-based alterations. Enzyme-linked immunosorbent assay was applied to identify post-COVID-19 and post-Vaccinated patients and rule out potential outliers. Serum samples were deglycosylated by PNGase F digestion, and the released glycans were fluorescently derivatized using procainamide labeling. Solid-phase extraction was used to purify the labeled glycans followed by the analysis of hydrophilic-interaction liquid chromatography with fluorescence and mass-spectrometric detection. Alterations of serum N-glycome in response to SARS-CoV-2 infection and mRNA vaccination were revealed by linear discriminant analysis.

Different Kinetics of Serum ADAMTS13, GDF-15, and Neutrophil Gelatinase-Associated Lipocalin in the Early Phase of Aneurysmal Subarachnoid Hemorrhage.

Growth differentiation factor 15 (GDF-15), neutrophil gelatinase-associated lipocalin (NGAL), and ADAMTS13 have previously been implicated in the pathophysiological processes of SAH. In the present study, we aim to examine their role in the early period of SAH and their relationship to primary and secondary outcomes. Serum samples were collected at five time periods after SAH (at 24 h (D1), at 72 h (D3), at 120 h (D5), at 168 h (D7) and at 216 h (D9), post-admission) and) were measured by using MILLIPLEX Map Human Cardiovascular Disease (CVD) Magnetic Bead Panel 2. We included 150 patients with SAH and 30 healthy controls. GDF-15 levels at D1 to D9 were significantly associated with a 3-month unfavorable outcome. Based on the ROC analysis, in patients with a good clinical grade at admission (WFNS I-III), the GDF-15 value measured at time point D3 predicted a 3-month unfavorable outcome (cut-off value: 3.97 ng/mL, AUC:0.833, 95%CI: 0.728-0.938, sensitivity:73.7%, specificity:82.6%, p < 0.001). Univariate binary logistic regression analysis showed that serum NGAL levels at D1-D5 and ADAMTS13 levels at D7-D9 were associated with MVS following SAH. GDF-15 is an early indicator of a poor 3-month functional outcome even in patients with mild clinical conditions at admission.

NH2-Functionalized Magnetic Nanoparticles for the N-Glycomic Analysis of Patients with Multiple Sclerosis.

Glycosylation is vital for well-functioning glycoproteins and is reportedly altered in chronic inflammatory disorders, including multiple sclerosis (MS). High-throughput quantitative measurement of protein glycosylation is challenging, as glycans lack fluorophore groups and require fluorescent labeling. The attachment of fluorescent tags to each glycan moiety necessitates sample clean-up for reliable quantitation. The use of magnetic particles in glycan sample preparation is reportedly an easy-to-use solution to accomplish large-scale biomarker discovery studies. In this study, NH2-funtionalized magnetic nanoparticles were synthetized, characterized and applied for the glycosylation analysis of serum samples from patients diagnosed with multiple sclerosis and corresponding healthy controls. Serum samples were PNGase F digested and labeled by procainamide via reductive amination, followed by magnetic nanoparticle-based purification. The prepared samples were analyzed by hydrophilic interaction liquid chromatography, allowing for the relative quantitation of the individual glycan species. Significant glycosylation alterations were detected between MS patients and healthy controls, especially when analyzing the different gender groups.

Are the Morphological Indices of the Vertebrobasilar System Heritable? A Twin Study Based on 3D Reconstructed Models.

Background and Objectives: The asymmetrical vertebral artery (VA) flow and diameter are common findings, which can result in an asymmetrical blood flow in the basilar artery (BA), leading to bending of the artery over time. This study investigated whether the variation of the different vertebrobasilar morphological indices that influence flow characteristics might be inherited. Materials and Methods: We analyzed 200 cerebral magnetic resonance imaging (MRI) scans of healthy Caucasian twins (100 pairs) who underwent time-of-flight MRI. From the scans, we reconstructed the 3D mesh of the posterior circulation from the start of the V4 segment to the basilar tip and subsequently analyzed the morphology of the vertebrobasilar system. The phenotypic covariances of the different morphological parameters were decomposed into heritability (A), shared (C), and unshared (E) environmental effects. Results: 39% of the twins had left dominant VA, while 32.5% had right dominant. In addition, 28.5% were classified as equal. The vertebral artery V4 segment diameter, curvature, and tortuosity were mainly influenced by shared (C) and unshared (E) environmental factors. A moderate heritability was found for the BA length (A: 63%; 95% CI: 45.7-75.2%; E: 37%; 95% CI: 24.8-54.3%) and volume (A: 60.1%; 95% CI: 42.4-73.2%; E: 39.9%; 95% CI: 26.8-57.6%), while the torsion of both arteries showed no heritability and were only influenced by the unshared environment. Conclusions: The length and volume of the BA show a moderate genetical influence. However, most of the measured morphological indices were influenced by shared and unshared factors, which highlight the role of the ever-changing hemodynamic influences shaping the geometry of the vertebrobasilar system.

[Treatment options for enormous carotid thrombus as a complication of SARS-CoV-2 infection]. / SARS-Cov-2-fertozés szövodményeként kialakult enormis nagyságú carotisthrombus kezelési lehetoségei.

In SARS-CoV-2 positive patients with corresponding neurological symptoms the presence of carotid bifurcation macrothrombus should always be considered. Hypercoagulopathy caused by viral endotheliitis, systemic inflammation and cytokine storm play an important role in its development. Here we present two patients treated with different treatment strategies because of carotid bifurcation macrothrombus as a complication of SARS-CoV-2 infection. In both cases, the soft macrothrombus was eliminated and the patients' neurological condition were improved. Intravenous thrombolysis, acute carotid stenting with embolic filter protection device and mechanical thrombectomy with aspiration are effective treatments.

Correction to: Assessment of cervical spine involvement in rheumatoid arthritis patients in the era of biologics: a real-life, cross-sectional MRI study.

In the original article, the first author's given name and family name were interchanged as provided by the authors in the original manuscript.

Assessment of cervical spine involvement in rheumatoid arthritis patients in the era of biologics: a real-life, cross-sectional MRI study.

Cervical spine involvement may lead to severe complications in rheumatoid arthritis (RA). In the era of modern therapies, atlantoaxial subluxation (AAS) may be rare; however, it may still be detected in asymptomatic patients. The onset of myelopathy can occur at any time. Altogether 49 female RA patients were included. Among them, 15 were methotrexate treated, biologic free, while 34 patients received biologics. The patients had no cervical pain or any neurological symptoms. We assessed the first (C1) and second (C2) cervical vertebrae by 3 T magnetic resonance imaging (MRI). In addition to AAS, we also determined odontoid erosion or periodontal soft tissue thickening. We associated our MRI findings with clinical, laboratory parameters, and hand radiography. We detected anterior AAS and soft tissue thickening in one-quarter, while odontoid erosions in eight (16%) of RA patients. There were no significant differences among the therapeutic subgroups. No posterior or vertical AAS was seen. Anterior AAS was associated with higher degree of inflammation, soft tissue thickening was seen at younger age, while odontoid erosions were associated with van der Heijde-Sharp scores of the hand. None of the patients had any lesions requiring surgery. The presence of cervical involvement in RA patients with 10-11 years of disease duration is still an important and frequent phenomenon. Higher disease activity and erosive disease are associated with atlantoaxial involvement. 3 T MRI is a sensitive method to assess AAS, as well as soft tissue lesions and odontoid erosions.

Assessment of cognitive function in female rheumatoid arthritis patients: associations with cerebrovascular pathology, depression and anxiety.

We assessed cognitive function of female rheumatoid arthritis (RA) patients and analyze the determinants, with special focus on cerebrovascular morphology. Sixty methotrexate (MTX-) or biologic-treated RA patients and 39 healthy controls were included in a cross-sectional study. Smoking habits, alcohol intake and time spent in education were recorded. Standard measures were performed to assess cognitive function (Montreal Cognitive Assessment, MOCA; Trail Making Test, TMT; Victoria Stroop Test, VST; Wechsler Adult Intelligence Scale, WAIS; Benton Visual Retention test, BVRT), depression (Beck Depression Inventory, BDI), anxiety (State-Trait Anxiety Inventory, STAIT/S) and general health status (Short Form 36, SF-36). Mean disease activity (28-joint Disease Activity Score, mDAS28; erythrocyte sedimentation rate, mESR; C-reactive protein, mCRP) of the past 12 months was calculated; anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF) were assessed. Cerebral vascular lesions and atrophy, carotid intima-media thickness (cIMT) and plaques, as well as median cerebral artery (MCA) circulatory reserve capacity (CRC) were assessed by brain magnetic resonance imaging (MRI), carotid ultrasound and transcranial Doppler, respectively. Cognitive function tests showed impairment in RA vs controls. Biologic- vs MTX-treated subgroups differed in TMT-A. Correlations were identified between cognitive function and depression/anxiety tests. WAIS, STAIS, STAIT and BDI correlated with most SF-36 domains. Numerous cognitive tests correlated with age and lower education. Some also correlated with disease duration, mESR and mDAS28. Regarding vascular pathophysiology, cerebral vascular lesions were associated with VST-A, carotid plaques with multiple cognitive parameters, while MCA and CRC with MOCA, BVRT and BDI. RA patients have significant cognitive impairment. Cognitive dysfunction may occur together with or independently of depression/anxiety. Older patients and those with lower education are at higher risk to develop cognitive impairment. Cognitive screening might be a useful tool to identify subgroups to be further investigated for cerebrovascular pathologies.

Care management of patients with high cardiovascular risk in Hungary an international and Hungarian longitudinal comparison of target level achievement.

BACKGROUND: Patients with high cardiovascular risk are usually cared for in primary care settings. Assessment of the effectiveness of long-time care was a subject of many European studies in the last two decades. This paper aims to present two Hungarian primary care cross sectional surveys and to compare their results to the primary care arms of the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) III. and IV. METHODS: Between 2010 and 2011, 679 patients with high cardiovascular risk were recruited in 20 Hungarian primary care practices and 628 patients were selected in 40 practices between 2015 and 2016. The actual national recommendations were used for classification, all based on European guidelines. Achievements of target levels for blood pressure, total-, LDL-and HDL-cholesterols, triglyceride, and HbA1c (in diabetics) were recorded and analyzed. Further cardiovascular risk factors, such as smoking, BMI, waist-circumference were also evaluated. RESULTS: There was a statistically significant improvement in the management of blood-pressure and plasma LDL-cholesterol levels among high risk patients, while there was no change in the plasma triglyceride values. The effectiveness of diabetes care deteriorated. In international relation, the management of blood pressure and plasma LDL-cholesterol values were better in Hungary when compared to the results of EUROASPIRE III-IV. studies, while the previous advantage in diabetes care disappeared. A higher proportion of diabetic patients was above the target values in Hungary than the means of the European surveys. There was a higher proportion of smokers in the Hungarian samples, while the proportion of obese and overweight patients was similar to the European sample. CONCLUSIONS: Primary care has a unique role in cardiovascular prevention. Although many of the patients are managed appropriately, there is a need to improve primary care services in Hungary, giving more competences to GPs in prescription and introducing structural changes in the healthcare system.

Are the Variants of the Circle of Willis Determined by Genetic or Environmental Factors? Results of a Twin Study and Review of the Literature.

BACKGROUND: Anatomic variants of the circle of Willis (CW) are commonly observed in healthy subjects. Genetic and environmental factors influencing these variants remain unclear. Our aim was to assess the genetic and environmental background affecting variant CW phenotypes. METHODS: A total of 122 adult healthy twins from the Hungarian Twin Registry (39 monozygotic (MZ) and 22 dizygotic (DZ) pairs, average age 49.7 ± 13.4 years) underwent Time-of-Flight magnetic resonance angiography and transcranial Doppler sonography. We investigated the anterior and posterior CW according to morphological categories. Prevalence and concordance rates of CW variants were calculated. MZ twins discordant for CW variants were analyzed for cardiovascular risk factors and altered blood flow. RESULTS: Complete CW (45.0%) and bilaterally absent posterior communicating artery (PCoA) (22.5%) were the most prevalent variants in the anterior and posterior CW, respectively. There was no significant difference regarding the prevalence of variants across zygosity except for bilaterally hypoplastic PCoA (p = .02). DZ concordance was higher compared to MZ twins regarding morphological categories of the CW. Cardiovascular risk factors were not significantly associated with variant CW in MZ twins discordant to CW morphology. Flow parameters did not differ significantly among MZ twins discordant to CW variants. CONCLUSION: CW variants may not be determined by substantial genetic effects and are not influenced by altered blood flow in healthy individuals. Further investigations are needed to identify potential environmental factors affecting these variants.

[Endovascular treatment of complex vascular pathology in neck and brain region. Case report]. / Komplex nyaki és agyi érpatológia endovascularis kezelése.

Authors present complex multistage endovascular treatment of female patient with an intradural infiltrative, inoperable tumor of the glomus jugulare, a stenosis of the internal carotid artery and an aneurysm of middle cerebri artery. In the literature our case report is the first announcement in which three pathology coexist ipsilateral in one patient and the patient has been treated step by step by endovascular procedures. Beside the endovascular treatment steps they display glomus jugulare tumor's symptoms, staging, treatment options and also the current treatment guidelines of internal carotid artery stenosis and intracranial aneurysms. Orv Hetil. 2017; 158(18): 706-710.

[Nebivolol in treatment of multiple cerebral aneurysms]. / Nebivolol alkalmazása többszörös agyi aneurysmák esetén.

INTRODUCTION: We examined the effect of nebivolol on blood pressure control after subarachnoidal hemorrhage in three patients with multiple aneurysms. PATIENTS AND METHODS: Endovascular intervention was applied to treat the bleeding aneurysms of all patients, and the silent aneurysms were followed-up. In all patients nebivolol was used as long-term anti-hypertensive medication. RESULTS: With nebivolol treatment the blood pressure in our patients was maintained in the normal range with no unexpected shoot-ups. The size of the silent aneurysms did not increase and the endovascularly treated aneurysms demonstrated acceptable morphology on follow-up catheter-angiography. DISCUSSION: After endovascular treatment of the bleeding aneurysm, strict blood pressure control is essential in those with multiple aneurysms to prevent the rupture of silent aneurysms. Antihypertensive medications with a 24-hour effect are preferable. Nebivolol seemed to be an appropriate medication for this purpose in all of our patients.

The importance of chest CT severity score and lung CT patterns in risk assessment in COVID-19-associated pneumonia: a comparative study.

Introduction: Chest computed tomography (CT) is suitable to assess morphological changes in the lungs. Chest CT scoring systems (CCTS) have been developed and use in order to quantify the severity of pulmonary involvement in COVID-19. CCTS has also been correlated with clinical outcomes. Here we wished to use a validated, relatively simple CTSS to assess chest CT patterns and to correlate CTSS with clinical outcomes in COVID-19. Patients and methods: Altogether 227 COVID-19 cases underwent chest CT scanning using a 128 multi-detector CT scanner (SOMATOM Go Top, Siemens Healthineers, Germany). Specific pathological features, such as ground-glass opacity (GGO), crazy-paving pattern, consolidation, fibrosis, subpleural lines, pleural effusion, lymphadenopathy and pulmonary embolism were evaluated. CTSS developed by Pan et al. (CTSS-Pan) was applied. CTSS and specific pathologies were correlated with demographic, clinical and laboratory data, A-DROP scores, as well as outcome measures. We compared CTSS-Pan to two other CT scoring systems. Results: The mean CTSS-Pan in the 227 COVID-19 patients was 14.6 ± 6.7. The need for ICU admission (p < 0.001) and death (p < 0.001) were significantly associated with higher CTSS. With respect to chest CT patterns, crazy-paving pattern was significantly associated with ICU admission. Subpleural lines exerted significant inverse associations with ICU admission and ventilation. Lymphadenopathy was associated with all three outcome parameters. Pulmonary embolism led to ICU admission. In the ROC analysis, CTSS>18.5 significantly predicted admission to ICU (p = 0.026) and CTSS>19.5 was the cutoff for increased mortality (p < 0.001). CTSS-Pan and the two other CTSS systems exerted similar performance. With respect to clinical outcomes, CTSS-Pan might have the best performance. Conclusion: CTSS may be suitable to assess severity and prognosis of COVID-19-associated pneumonia. CTSS and specific chest CT patterns may predict the need for ventilation, as well as mortality in COVID-19. This can help the physician to guide treatment strategies in COVID-19, as well as other pulmonary infections.

Tocilizumab in Combination with Corticosteroids in COVID-19 Pneumonia: A Single-Centre Retrospective Controlled Study.

Introduction: Interleukin 6 receptor inhibition by tocilizumab (TCZ) has been effectively used worldwide for the treatment of multisystem inflammatory syndrome (MIS) associated with COVID-19. In this single centre study, we compared the outcome of COVID-19 pneumonia in TCZ-treated vs. untreated (control) patients. We wished to compare TCZ administration in the general ward vs. in the intensive care unit (ICU). We also studied the role of a consulting rheumatologist in the management of severe COVID-19 pneumonia. Patients and methods: In our patients, COVID-19 pneumonia was confirmed by SARS-CoV-2 PCR, chest X-ray, and CT. We compared patients selected for TCZ treatment with TCZ-untreated age- and sex-matched controls. All patients received corticosteroids. In the TCZ-treated group, patients received one or two doses of TCZ 8 mg/kg IV in combination with corticosteroids. We recorded age, sex, symptom duration, oxygen saturation (SaO2), partial arterial oxygen pressure (PaO2), total white blood cell (WBC), absolute neutrophil, absolute lymphocyte and platelet counts, CRP, ferritin, IL-6, LDH, procalcitonin (PCT), and D-dimer. The primary outcome parameters were the need for ICU, ventilation, death, and time of hospitalisation. Results: Altogether, 104 patients, 52 TCZ-treated and 52 TCZ-untreated, were included in this study. At baseline, the TCZ-treated patient group indeed had more pronounced COVID-19-related MIS compared to controls. Consultation with a rheumatologist was performed in 60% vs. 40% of cases. Nineteen patients (37%) received one, while 33 (63%) received two TCZ doses. TCZ was administered to 28 patients (54%) in the general ward and to 24 (46%) in the ICU. TCZ treatment was found to be safe in our COVID-19 pneumonia patients. TCZ treatment favourably influenced MIS biomarkers, and was associated with better clinical outcomes compared to controls. Patients receiving TCZ treatment in combination with corticosteroids already in the general ward exerted much better outcomes than those treated in the ICU. Consultation with a rheumatologist also improved outcome. Conclusions: We successfully used TCZ in combination with corticosteroids in Hungarian COVID-19 pneumonia patients. We pointed out the importance of early treatment already in the general ward, and the involvement of a rheumatologist in making treatment decisions.

Role of anti-polyethylene glycol (PEG) antibodies in the allergic reactions to PEG-containing Covid-19 vaccines: Evidence for immunogenicity of PEG.

A small fraction of recipients who receive polyethylene-glycol (PEG)-containing COVID-19 mRNA-LNP vaccines (Comirnaty and Spikevax) develop hypersensitivity reactions (HSRs) or anaphylaxis. A causal role of anti-PEG antibodies (Abs) has been proposed, but not yet been proven in humans.We used ELISA for serial measurements of SARS-CoV-2 neutralizing Ab (anti-S) and anti-PEG IgG/IgM Ab levels before and after the first and subsequent booster vaccinations with mRNA-LNP vaccines in a total of 291 blood donors. The HSRs in 15 subjects were graded and correlated with anti-PEG IgG/IgM, just as the anti-S and anti-PEG Ab levels with each other. The impacts of gender, allergy, mastocytosis and use of cosmetics were also analyzed. Serial testing of two or more plasma samples showed substantial individual variation of anti-S Ab levels after repeated vaccinations, just as the levels of anti-PEG IgG and IgM, which were over baseline in 98-99 % of unvaccinated individuals. About 3-4 % of subjects in the strongly left-skewed distribution had 15-45-fold higher values than the median, referred to as anti-PEG Ab supercarriers. Both vaccines caused significant rises of anti-PEG IgG/IgM with >10-fold rises in about âˆ¼10 % of Comirnaty, and all Spikevax recipients. The anti-PEG IgG and/or IgM levels in the 15 vaccine reactors (3 anaphylaxis) were significantly higher compared to nonreactors. Serial testing of plasma showed significant correlation between the booster injection-induced rises of anti-S and anti-PEG IgGs, suggesting coupled anti-S and anti-PEG immunogenicity.Conclusions: The small percentage of people who have extremelevels of anti-PEG Ab in their blood may be at increased risk for HSRs/anaphylaxis to PEGylated vaccines and other PEGylated injectables. This risk might be further increased by the anti-PEG immunogenicity of these vaccines. Screening for anti-PEG Ab "supercarriers" may help predicting reactors and thus preventing these adverse phenomena.

Severity and prognostic factors of SARS-CoV-2-induced pneumonia: The value of clinical and laboratory biomarkers and the A-DROP score.

Introduction: Numerous clinical and laboratory scores that include C-reactive protein (CRP), D-dimer, ferritin, lactate dehydrogenase (LDH), interleukin 6 (IL-6), procalcitonin (PCT), blood urea nitrogen (BUN), creatinine levels and oxygenation (PaO2 and SaO2) have been used for the prognosis of COVID-19. In addition, composite scores have been developed for the assessment of general state and risk in community-acquired pneumonia (CAP) that may be applied for COVID-19 as well. In this study, we assessed severity and potential prognostic risk factors for unfavorable outcome among hospitalized COVID-19 patients. We also applied the A-DROP general scoring system used in CAP to COVID-19. Patients and methods: Altogether 233 patients admitted to our center with COVID-19 were included in the study. Clinical status, several laboratory biomarkers described above, indicators of oxygenation were determined at hospital admission. We also applied the A-DROP composite scoring system that includes Age (≥ 70 years in males and ≥ 75 years in females), Dehydration (BUN ≥ 7.5 mmol/l), Respiratory failure (SaO2 ≤ 90% or PaO2 ≤ 60 mmHg), Orientation disturbance (confusion) and low blood Pressure (systolic BP ≤ 90 mmHg) to COVID-19. Results: At the time of admission, most patients had elevated CRP, LDH, ferritin, D-dimer, and IL-6 levels indicating multisystemic inflammatory syndrome (MIS). Altogether 49 patients (21.2%) required admission to ICU, 46 (19.7%) needed ventilation and 40 patients (17.2%) died. In the binary analysis, admission to ICU, the need for ventilation and death were all significantly associated with the duration of hospitalization, history of hypertension or obesity, confusion/dizziness, as well as higher absolute leukocyte and neutrophil and lower lymphocyte counts, elevated CRP, PCT, LDH, ferritin, IL-6, BUN, and creatinine levels, low PaO2 and SaO2 and higher A-DROP score at the time of admission (p < 0.05). Conclusion: Numerous laboratory biomarkers in addition to obesity, dizziness at the time of admission and the history of hypertension may predict the need for ICU admission and ventilation, as well as mortality in COVID-19. Moreover, A-DROP may be a suitable scoring system for the assessment of general health and disease outcome in COVID-19.

Functional Yogurt Fortified with Honey Produced by Feeding Bees Natural Plant Extracts for Controlling Human Blood Sugar Level.

The human blood sugar level is important and should be controlled to avoid any damage to nerves and blood vessels which could lead to heart disease and many other problems. Several market-available treatments for diabetes could be used, such as insulin therapy, synthetic drugs, herbal drugs, and transdermal patches, to help control blood sugar. In a double-blind human study, four kinds of honey from bees fed on acacia, sea buckthorn, chlorella alga, and green walnut extracts were used in fortifying yogurt for controlling human blood sugar. The impact of a previously fortified honey was investigated on blood levels and other parameters of healthy individuals in a human study with 60 participants. The participants received 150 mL of yogurt mixed with 30 g of honey every morning for 21 days. Before and after the study period, the basic blood parameters were tested, and the participants filled out standardized self-report questionnaires. Acacia honey was the traditional honey used as a control; the special honey products were produced by the patented technology. The consumption of green walnut honey had a significant effect on the morning blood sugar level, which decreased for every participant in the group (15 people). The average blood sugar level at the beginning in the walnut group was 4.81 mmol L-1, whereas the value after 21 days was 3.73 mmol L-1. The total decrease level of the individuals was about 22.45% (1.08 mmol L-1). Concerning the sea buckthorn and chlorella alga-based honey product groups, there was no significant change in the blood sugar level, which were recorded at 4.91 and 5.28 mmol L-1 before treatment and 5.28 and 5.07 mmol L-1 after, respectively. In the case of the acacia honey group, there was a slight significant decrease as well, it was 4.77 mmol L-1 at the beginning and 4.27 mmol L-1 at the end with a total decrease rate of 10.48%. It could thus be concluded that the active ingredients of green walnut can significantly decrease the blood sugar level in humans. This study, as a first report, is not only a new innovative process to add herbs or healthy active ingredients to honey but also shows how these beneficial ingredients aid the honey in controlling the human blood sugar level.

A naturally hypersensitive porcine model may help understand the mechanism of COVID-19 mRNA vaccine-induced rare (pseudo) allergic reactions: complement activation as a possible contributing factor.

A tiny fraction of people immunized with lipid nanoparticle (LNP)-enclosed mRNA (LNP-mRNA) vaccines develop allergic symptoms following their first or subsequent vaccinations, including anaphylaxis. These reactions resemble complement (C) activation-related pseudoallergy (CARPA) to i.v. administered liposomes, for which pigs provide a naturally oversensitive model. Using this model, we injected i.v. the human vaccination dose (HVD) of BNT162b2 (Comirnaty, CMT) or its 2-fold (2x) or 5-fold (5x) amounts and measured the hemodynamic changes and other parameters of CARPA. We observed in 6 of 14 pigs transient pulmonary hypertension along with thromboxane A2 release into the blood and other hemodynamic and blood cell changes, including hypertension, granulocytosis, lymphopenia, and thrombocytopenia. One pig injected with 5x CMT developed an anaphylactic shock requiring resuscitation, while a repeat dose failed to induce the reaction, implying tachyphylaxis. These typical CARPA symptoms could not be linked to animal age, sex, prior immune stimulation with zymosan, immunization of animals with Comirnaty i.v., or i.m. 2 weeks before the vaccine challenge, and anti-PEG IgM levels in Comirnaty-immunized pigs. Nevertheless, IgM binding to the whole vaccine, used as antigen in an ELISA, was significantly higher in reactive animals compared to non-reactive ones. Incubation of Comirnaty with pig serum in vitro showed significant elevations of C3a anaphylatoxin and sC5b-9, the C-terminal complex. These data raise the possibility that C activation plays a causal or contributing role in the rare HSRs to Comirnaty and other vaccines with similar side effects. Further studies are needed to uncover the factors controlling these vaccine reactions in pigs and to understand their translational value to humans.

The Analysis of Human Serum N-Glycosylation in Patients with Primary and Metastatic Brain Tumors.

The identification of patients with different brain tumors is solely built on imaging diagnostics, indicating the need for novel methods to facilitate disease recognition. Glycosylation is a chemical modification of proteins, reportedly altered in several inflammatory and malignant diseases, providing a potential alternative route for disease detection. In this paper, we report the quantitative analysis of serum N-glycosylation of patients diagnosed with primary and metastatic brain tumors. PNGase-F-digested and procainamide-labeled serum glycans were purified by magnetic nanoparticles, followed by quantitative liquid chromatographic analysis. The glycan structures were identified by the combination of single quad mass spectrometric detection and exoglycosidase digestions. Linear discriminant analysis provided a clear separation of different disease groups and healthy controls based on their N-glycome pattern. Altered distribution of biantennary neutral, sialylated but nonfucosylated, and sialylated-fucosylated structures were found to be the most significant changes. Our results demonstrate that serum glycosylation monitoring could improve the detection of malignancy.

The personalized Berger method is usable to solve the problem of tibial rotation.

PURPOSE: The revision of any total knee replacement is carried out in a significant number of cases, due to the excessive internal rotation of the tibial component. The goal was to develop a personalized method, using only the geometric parameters of the tibia, without the femoral guidelines, to calculate the postoperative rotational position of tibial component malrotation within a tolerable error threshold in every case. METHODS: Preoperative CT scans of eighty-five osteoarthritic knees were examined by three independent medical doctors twice over 7 weeks. The geometric centre of the tibia was produced by the ellipse annotation drawn 8 mm below the tibial plateau, the sagittal and frontal axes of the ellipse were transposed to the slice of the tibial tuberosity. With the usage of several guide lines, a right triangle was drawn within which the personalized Berger angle was calculated. RESULTS: A very good intra-observer (0.89-0.925) and inter-observer (0.874) intra-class correlation coefficient (ICC) was achieved. Even if the average of the personalized Berger values were similar to the original 18° (18.32° in our case), only 70.6% of the patients are between the clinically tolerable thresholds (12.2° and 23.8°). CONCLUSION: The method, measured on the preoperative CT scans, is capable of calculating the required correction during the planning of revision arthroplasties which are necessary due to the tibial component malrotation. The personalized Berger angle isn't altered during arthroplasty, this way it determines which one of the anterior reference points of the tibia (medial 1/3 or the tip of the tibial tuberosity, medial border or 1/6 or 1/3 or the centre of the patellar tendon) can be used during the positioning of the tibial component. LEVEL OF EVIDENCE: Level II, Diagnostic Study (Methodological Study).