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The present work focuses on the behavior of the stopping power of a polymer gel dosimetry system, known as PAGAT, infused with high atomic number nanoparticles formed by gold, with a 1 % mass concentration. The study is carried out for different energies of electron and proton beams within ranges of therapeutic applications, first by theoretical assessment, and then by simulation with Monte Carlo codes: PENELOPE in the case of electrons, and FLUKA in the case of protons. The results obtained analytically show promising behavior for gold nanoparticle infused tissue-equivalent systems, while the simulation results show better correspondence with models that consider the net path traveled, instead of models based on the thickness of the samples as typically done in experimental determinations.

Abstract Background The increasing birthweight trend stopped and even reversed in several high income countries in the last 20 years, however the reason for these changes is not well characterized. We aimed to describe birthweight trends of term deliveries in Hungary between 1999 and 2018 and to investigate potential maternal and foetal variables that could drive these changes. Methods We analysed data from the Hungarian Tauffer registry, a compulsory anonymized data collection of each delivery. We included all singleton term deliveries in 1999–2018 (n = 1,591,932). We modelled birthweight trends separately in 1999–2008 and 2008–2018 in hierarchical multiple linear regression models adjusted for calendar year, newborn sex, maternal age, gestational age at delivery, and other important determinants. Results Median birthweights increased from 3250/3400 g (girl/boy) to 3300/3440 g from 1999 to 2008 and decreased to 3260/3400 g in 2018. When we adjusted for gestational age at delivery the increase in the first period became more pronounced (5.4 g/year). During the second period, similar adjustment substantially decreased the rate of decline from 2.5 to 1.4 g/year. Further adjustment for maternal age halved the rate of increase to 2.4 g/year in the first period. During the second period, adjustment for maternal age had little effect on the estimate. Conclusions Our findings of an increasing birthweight trend (mostly related to the aging of the mothers) in 1999–2008 may forecast an increased risk of cardiometabolic diseases in offsprings born in this period. In contrast, the decreasing birthweight trends after 2008 may reflect some beneficial effects on perinatal morbidity. However, the long-term effect cannot be predicted, as the trend is mostly explained by the shorter pregnancies.

Our aim was to compare the performance of complementary clinical laboratory approaches to monitoring exposure to apixaban and rivaroxaban, the most prescribed direct-acting oral anticoagulants (DOAC’s): an automated commercial anti-Xa chromogenic assay suitable for emergency and pre-surgery testing and a laboratory-developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method employed for non-emergency analysis in plasma and in dried blood volumetric absorptive microsamples (VAMS) collectible by the patients in their homes. The full validation of the LC-MS/MS method was performed. Cross-validation of the methodologies was accomplished by processing 60 specimens collected for whole blood count and DOAC monitoring in a central clinical laboratory. For VAMS samples, dried plasma and whole blood calibrators were found to be suitable, and a cycle run for seven days could be implemented for rational and economic sample processing. The anti-Xa chromogrenic assay and the LC-MS/MS method delivered discordant plasma analyte concentrations. Moreover, the lack of agreement between plasma and VAMS concentrations was observed. Clinical laboratories must be aware of the differences between the performance of apixaban and rivaroxaban LC-MS/MS and anti-Xa assays. Hematocrit must always be measured along with VAMS samples to obtain accurate results.

Introduction The aim of this study was to identify low-risk traits of schizophrenia among healthy undergraduate student volunteers, and the investigation of these traits with regards to their specificity in contrast to individuals with a latent disposition towards bipolar disorder. Self-agency, as a phenomenon closely related to psychomotor functioning, provides a unique opportunity for the investigation of subjective self-perception. Objectives The implicit self-agency performances that are considered illness- (or risk state-) specific were compared between groups to find early markers of a specific schizotypic developmental path. Methods In a sample of 710 healthy university students, with the help of screening questionnaires, we were able to successfully form two risk groups, in one of them the emphasis on cyclothymia (CTF: Cyclothymia factor group, N=25), and in the other (PSF: Positive schizotypy factor group, N=26) the tendency to unusual experiences and paranoid thinking emphasis was typical. We assigned a properly matched control group (N=29) displaying both features on average. We focused on the implicit aspect of self-agency, using the well-known paradigm of intentional binding, as well as the self-developed device that exclusively tests the pre-reflexive feeling of movement initiation, the sense of self-agency. Results During the examination of intentional binding, although the specific predictive and retrospective component indicators did not show any significant difference for either group, the association of the sound alone could induce a binding effect in the control group. In the predictable frequency condition, there was a strong significant effect (W = 65.00, p = .007, rrb = -.60), and in the non-predictable condition a trend-level effect. Remarkably, this binding effect did not develop in either the CTF or PSF groups, indicating an implicit agency impairment in both risk groups. However, during the examination of sense of self-agency, we observed a disturbance specifically among healthy college students with positive schizotypal traits, in the form of falsely attributing their movement initiation to external influences. The percentage of this ‘miss’-type answering differed between groups, H(2) = 7.68, p = .021, ε2 = .10. The Dwass-SteelCritchlow-Fligner pairwise comparisons showed that this difference was due to the PSF Group showing a significant difference from the Control Group (W = -3.83, p = .019), but not from the CTF group, and the CTF Group also did not differ from the Control Group. Conclusions Thus, in premorbid conditions, in at-risk groups of non-help-seeking individuals, or in cases of early detection of prodromal abnormalities, objective confirmation of suspected susceptibility to schizophrenia may be aided by, among other things, instrumental assessment of self-agency. Disclosure of Interest None Declared

Research background. Protein A affinity chromatography is a well-established method currently used in the pharmaceutical industry. However, the high costs usually associated with chromatographic separation of protein A and the difficulties in continuous operation make the investigation of alternative purification methods very important. Experimental approach. In this study, extraction/back-extraction and precipitation/dissolution methods were developed and optimised. They were compared with protein A and cation exchange chromatography separations in terms of yield of monoclonal antibody (mAb) and amount of residual impurities, such as DNA and host cell proteins, and amount of mAb aggregates. For a comprehensive comparison of the different methods, experiments were carried out with the same cell-free fermentation broth containing adalimumab. Results and conclusions. Protein A and cation exchange chromatographic separations resulted in high yield and purity of adalimumab. The precipitation-based process resulted in high yield but with lower purity. The extraction-based purification resulted in low yield and purity. Thus, the precipitation-based method proved to be more promising than the extraction-based method for direct purification of adalimumab from harvested cell culture fluid. Novelty and scientific contribution. Although alternative purification methods may offer the advantages of simplicity and low-cost operation, further significant improvements are required to compete with the performance of chromatographic separations of adalimumab from true fermentation broth.

IntroductionIn 1989, the St Vincent declaration aimed to approximate pregnancy outcomes of diabetes to that of healthy pregnancies. We aimed to compare frequency and trends of outcomes of pregnancies affected by type 1 diabetes and controls in 1996–2018.MethodsWe used anonymized records of a mandatory nation-wide registry of all deliveries between gestational weeks 24 and 42 in Hungary. We included all singleton births (4,091 type 1 diabetes, 1,879,183 controls) between 1996 and 2018. We compared frequency and trends of pregnancy outcomes between type 1 diabetes and control pregnancies using hierarchical Poisson regression.ResultsThe frequency of stillbirth, perinatal mortality, large for gestational age, caesarean section, admission to neonatal intensive care unit (NICU), and low Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score was 2-4 times higher in type 1 diabetes compared to controls, while the risk of congenital malformations was increased by 51% and SGA was decreased by 42% (all p

We have developed a simple, rapid, high-throughput RBD-based ELISA to assess the humoral immunity against emerging SARS-CoV-2 virus variants. The cDNAs of the His-tagged RBD proteins of the virus variants were stably engineered into HEK cells secreting the protein into the supernatant, and RBD purification was performed by Ni-chromatography and buffer exchange by membrane filtration. The simplified assay uses single dilutions of sera from finger-pricked native blood samples, purified RBD in 96-well plates, and a chromogenic dye for development. The results of this RBD-ELISA were confirmed to correlate with those of a commercial immunoassay measuring antibodies against the Wuhan strain, as well as direct virus neutralization assays assessing the cellular effects of the Wuhan and the Omicron (BA.5) variants. Here, we document the applicability of this ELISA to assess the variant-specific humoral immunity in vaccinated and convalescent patients, as well as to follow the time course of selective vaccination response. This simple and rapid assay, easily modified to detect humoral immunity against emerging SARS-CoV-2 virus variants, may help to assess the level of antiviral protection after vaccination or infection.

This work reports on a computational modeling methodology through Monte Carlo simulations based on the FLUKAcode to describe the physical processes in proton therapy irradiations. The corresponding validation by comparisons with experimental data is shown and the SOBP generation procedure applied to intracranial irradiations is described. Promising peformance has been achieved in terms of the good agreements between experimental and simulation data, while the SOBP generation procedure has proved to attain acceptable dose concentration and uniformity, this constituting a promising issue for local control and protection of areas at risk for intracranial applications.

Background Ongoing education of health professionals in rheumatology (HPR) is critical for high-quality care. An essential factor is education readiness and a high quality of educational offerings. We explored which factors contributed to education readiness and investigated currently offered postgraduate education, including the European Alliance of Associations for Rheumatology (EULAR) offerings.Methods and participants We developed an online questionnaire, translated it into 24 languages and distributed it in 30 European countries. We used natural language processing and the Latent Dirichlet Allocation to analyse the qualitative experiences of the participants as well as descriptive statistics and multiple logistic regression to determine factors influencing postgraduate educational readiness. Reporting followed the Checklist for Reporting Results of Internet E-Surveys guideline.Results The questionnaire was accessed 3589 times, and 667 complete responses from 34 European countries were recorded. The highest educational needs were ‘professional development’, ‘prevention and lifestyle intervention’. Older age, more working experience in rheumatology and higher education levels were positively associated with higher postgraduate educational readiness. While more than half of the HPR were familiar with EULAR as an association and the respondents reported an increased interest in the content of the educational offerings, the courses and the annual congress were poorly attended due to a lack of awareness, comparatively high costs and language barriers.Conclusions To promote the uptake of EULAR educational offerings, attention is needed to increase awareness among national organisations, offer accessible participation costs, and address language barriers.

Cerebrovascular diseases are the leading cause of death and disability. The epidemiological background and predisposing factors have been the basis of many studies. We aimed to assess the effect of seasonal variability and meteorological factors on stroke incidence in Hungary. National and county-level secondary data were assessed for 2018–2019. We identified stroke with ICD codes I60, I61, I62 (hemorrhagic), I63, I65, and I66 (ischemic). The data were obtained from the University of Pécs Clinical Centre (number of patients per day according to sex and disease subtype, n = 1765). Daily average and maximum wind speed [m/s], precipitation [mm], temperature [°C], and frontal effect [warm/cold/mixed/no effect]) were provided by the Hungarian Meteorological Service. We found that 89.92% of the patients were hospitalized for ischemic and 10.08% for hemorrhagic stroke. We observed a significantly higher number of cases in the other months compared to winter (spring: +35.9%; p = 0.007, summer: +59.0%; p = 0.016, autumn: +36.5%; p = 0.01). In autumn, an increase in temperature increased the incidence of stroke (r = 0.210; p = 0.004). Temperature change affected ischemic stroke incidence (r = 0.112; p = 0.003). In contrast, the number of hemorrhagic stroke cases showed a mild but significant negative association with daily temperature change (r = −0.073; p = 0.049). Overall, a 1 °C temperature change compared to the previous day increased the daily number of admissions by 2.9% (p = 0.017). Air pressure change also affected hemorrhagic stroke incidence (r = 0.083; p = 0.025). Changes in temperature and frontal effects can increase the incidence of stroke. Modern forecasting technology can help the healthcare system prepare for possible increased workloads during critical periods. [ABSTRACT FROM AUTHOR]

Our aim was to compare the performance of complementary clinical laboratory approaches to monitoring exposure to apixaban and rivaroxaban, the most prescribed direct-acting oral anticoagulants (DOAC's): an automated commercial anti-Xa chromogenic assay suitable for emergency and pre-surgery testing and a laboratory-developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method employed for non-emergency analysis in plasma and in dried blood volumetric absorptive microsamples (VAMS) collectible by the patients in their homes. The full validation of the LC-MS/MS method was performed. Cross-validation of the methodologies was accomplished by processing 60 specimens collected for whole blood count and DOAC monitoring in a central clinical laboratory. For VAMS samples, dried plasma and whole blood calibrators were found to be suitable, and a cycle run for seven days could be implemented for rational and economic sample processing. The anti-Xa chromogrenic assay and the LC-MS/MS method delivered discordant plasma analyte concentrations. Moreover, the lack of agreement between plasma and VAMS concentrations was observed. Clinical laboratories must be aware of the differences between the performance of apixaban and rivaroxaban LC-MS/MS and anti-Xa assays. Hematocrit must always be measured along with VAMS samples to obtain accurate results. [ABSTRACT FROM AUTHOR]

BackgroundDistal symmetric polyneuropathy (DSPN) is a common microvascular complication of both type 1 and 2 diabetes with substantial morbidity burden and reduced quality of life. Its association with mortality is equivocal.PurposeTo describe the association between DSPN and all-cause mortality in people with diabetes and further stratify by the type of diabetes based on a meta-analysis of published observational studies.Data SourcesWe searched Medline from inception to May 2021.Study SelectionOriginal data were collected from case-control and cohort studies that reported on diabetes and DSPN status at baseline and all-cause mortality during follow-up.Data Extractionwas completed by diabetes specialists with clinical experience in neuropathy assessment.Data SynthesisData was synthesized using random-effects meta-analysis. The difference between type 1 and 2 diabetes was investigated using meta-regression.ResultsA total of 31 cohorts (n=155,934 participants, median 27.4% with DSPN at baseline, all-cause mortality 12.3%) were included. Diabetes patients with DSPN had an almost twofold mortality (HR: 1.96, 95%CI: 1.68-2.27, I2 = 91.7%), I2 = 91.7%) compared to those without DSPN that was partly explained by baseline risk factors (adjusted HR: 1.60, 95%CI: 1.37-1.87, I2 = 78.86%). The association was stronger in type 1 compared to type 2 diabetes (HR: 2.22, 95%CI: 1.43-3.45). Findings were robust in sensitivity analyses without significant publication bias.LimitationsNot all papers reported multiple adjusted estimates. The definition of DSPN was heterogeneous.ConclusionsDSPN is associated with an almost twofold risk of death. If this association is causal, targeted therapy for DSPN could improve life expectancy of diabetic patients.

BackgroundMetabolic Syndrome (MetS) increases the risk of cardiovascular diseases (CVD) and affects around one fourth of the population worldwide. In the prevention and treatment regular exercise trainings are inevitable. Providing personal supervision in out/inpatient care settings for such a large target population challenges the healthcare systems, but using telemonitoring of the home-performed trainings could be a promising and widely available option.ObjectivesThe aim of this study was to evaluate the physiological and psychological effects of a 12-week home-based physical training program, telemonitored by widely available fitness devices on parameters of MetS patients.MethodsA total of 55 MetS patients (mean age 49.19 ± 7.93 years) were involved in the study. They were asked to perform 3–5 sessions of exercise activity (min. 150 min) each week for 12 weeks. Trainings were monitored off-line by heart rate sensors, a fitness application and a cloud-based data transfer system. Physiotherapists supervised, coached, and feedback the trainings through an online coach system. We investigated different anthropometric parameters, maximum exercise and functional capacity levels, laboratory parameters, the level of depression, insomnia, vital exhaustion, and wellbeing as well.ResultsThe average weekly training time was 152.0 ± 116.2 min. Out of the 55 participants who completed the program, 22 patients (40%) performed the recommended 150 min or more weekly. Patients showed statistically significant changes in: all the measured waist and hip circumferences; 6-min walk distance (6MWD; from 539.69 ± 78.62 to 569.72 ± 79.96 m, p < 0.001); maximal exercise capacity (11.02 ± 2.6 to 12.14 ± 2 MET, p < 0.001), stress-electrocardiogram duration time (13.74 ± 3.29 to 15.66 ± 2.64 min, p < 0.001); body weight (98.72 ± 21.7 to 97.45 ± 21.76 kg, p = 0.004); high-density lipoprotein cholesterol (n = 45, 1.28 ± 0.31 to 1.68 ± 0.36 mmol/L, p < 0.001); fasting plasma glucose (FPG; n = 47, 6.16 ± 1.26 to 5.44 ± 1.31 mmol/L, p = 0.001); glycated hemoglobin A1c (HbA1c; n = 41, 6.22 ± 0.68 to 5.87 ± 0.78%, p = 0.01). Out of the 55 patients who finished the program 38 patients (70%) completed all the psychological questionnaires. We found statistically significant decrease of the overall scores of the Maastricht Vital Exhaustion Questionnaire, from 3.37 ± 2.97 points to 2.63 ± 2.70 points (p < 0.05) and a significant increase of the overall scores of the WHO Wellbeing Scale from 9.92 ± 2.59 points to 10.61 ± 2.76 points (p < 0.05). We have not found any statistically significant changes in the scores of the Beck Depression Inventory and the Athens Insomnia Scale.ConclusionA 12-week home-based telemonitored training supported by an affordable, commonly available device system produces positive, statistically significant changes in many core components in MetS patients. Telemonitoring is a cheap method for coaching and feeding back the home-based interventions.