Identification of new RAD51D-regulating microRNAs that also emerge as potent inhibitors of the Fanconi anemia/homologous recombination pathways.

The Fanconi anemia (FA) and homologous recombination (HR) pathways, which partially overlap and include RAD51 and its paralogs, are key for the repair of different types of DNA damage, such as DNA interstrand crosslinks. First, to broadly assess the impact of microRNA-mediated regulation, we examined microRNA expression profiles in five isogenic fibroblast cell pairs, either deficient in DNA repair due to germline mutations in FANCA, FANCB, FANCC, FANCI or BRIP1/FANCJ or proficient due to correction with retroviral vectors. In each pair, we observed lower abundance of specific microRNAs in the FA-deficient cells. From the list of microRNAs, we experimentally confirmed the effects of miR-141-3p and miR-369-3p targeting RAD51B and miR-15a-5p, miR-494-3p as well as miR-544a targeting RAD51D. However, by western blotting, only RAD51D protein was reduced by a mixture of its regulating microRNAs. Gene ontology analyses and identification of additional FA/HR factors as targets of miR-15a-5p, miR-494-3p and miR-544a strongly suggested the widespread influence of these microRNAs on HR. Interestingly, only miR-494-3p directly reduced RAD51 foci formation, while a mixture of miR-15a-5p, miR-494-3p and miR-544a strongly reduced HR activity in green fluorescent protein (GFP) repair assays. In summary, by successfully employing this novel loss- and gain-of-function strategy, we have identified new microRNAs strongly inhibiting HR in mammalian cells. Understanding and modulating such miRNA regulation of DNA repair genes/pathways might help to overcome the reduced repair capacity of FA patients with biallelic hypomorphic mutations or help to engineer synthetic lethality strategies for patients with mutations in cancer-associated FA/HR genes.

Immunoadsorption as a method of antibody donation during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: Initial therapeutic efforts to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) included the use of plasma from convalescent donors containing anti-SARS-CoV-2 antibodies. High-neutralizing antibody titres are required for therapeutic efficacy. This study aims to show that immunoadsorption followed by tangential flow filtration can be used to obtain antibody concentrates with high-neutralizing capacities. MATERIALS AND METHODS: Eligible donors (n = 10, five males and three females) underwent immunoadsorption using adsorber columns specific for human antibodies. Glycine-washed out eluates of 1.5 L volume were further concentrated by tangential flow filtration using 30 kDa ultrafiltration membranes. The same membranes were applied for diafiltrations to exchange residual glycine for 0.9% normal saline. RESULTS: Antibody concentrates were obtained within 8 h from the start of donation and had 4.58 ± 1.95, 3.28 ± 1.28 and 2.02 ± 0.92 times higher total IgG, IgA and IgM concentrations, 3.29 ± 1.62 and 3.74 ± 0.6 times higher SARS-CoV-2 N and S antibody concentrations and 3.85 ± 1.71 times higher SARS-CoV-2 S-specific IgG concentrations compared to the donors' peripheral blood. The specific SARS-CoV-2 virus neutralization capacities increased in all but one concentrate. All antibody concentrates (50-70 mL final volume) passed microbiological tests, were free of hazardous glycine levels and could be stored at -80°C and 4°C for 1 year with 20 ± 3% antibody loss. CONCLUSION: Immunoadsorption followed by tangential flow filtration is a feasible procedure to collect IgG, IgA and IgM as well as SARS-CoV-2 N- and S-specific antibody concentrates of low volume, free of albumin and coagulation factors. Whether these concentrates can be used as passive immunisation in infected patients remains to be elucidated.

Mass spectrometry coupling of chip-based supercritical fluid chromatography enabled by make-up flow-assisted backpressure regulation.

This work introduces a novel microfluidic backpressure pressure control developed for chip-based supercritical fluid chromatography (chipSFC). The presented on-chip pressure control mechanism involves the post-column addition of a viscous make-up stream, which enables pressure regulation within the range of 73 to 130 bar range. In contrast to approaches using mechanical backpressure regulators, this chip-based make-up-assisted pressure regulation offers a wear-free alternative that functions entirely through fluidic means and contributes minimally to extra column volume. It prevents phase separation of the supercritical mobile phase and, therefore, expands the analytical scope of chipSFC to detection systems with an ambient pressure interface. This was demonstrated by a proof-of-principle experiment, where a model mixture was separated within 30 s and detected using atmospheric pressure ionisation mass spectrometry.

Cardiac Surgery 2023 Reviewed.

We reviewed the cardiac surgical literature for 2023. PubMed displayed almost 34,000 hits for the search term "cardiac surgery AND 2023." We used a PRISMA approach for a results-oriented summary. Key manuscripts addressed the mid- and long-term effects of invasive treatment options in patient populations with coronary artery disease (CAD), comparing interventional therapy (percutaneous coronary intervention [PCI]) with surgery (coronary artery bypass graft [CABG]). The literature in 2023 again confirmed the excellent long-term outcomes of CABG compared with PCI in patients with left main stenosis, specifically in anatomically complex chronic CAD, but even in elderly patients, generating further support for an infarct-preventative effect as a prognostic mechanism of CABG. For aortic stenosis, a previous trend of an early advantage for transcatheter (transcatheter aortic valve implantation [TAVI]) and a later advantage for surgical (surgical aortic valve replacement) treatment was also re-confirmed by many studies. Only the Evolut Low Risk trial maintained an early advantage of TAVI over 4 years. In the mitral and tricuspid field, the number of interventional publications increased tremendously. A pattern emerges that clinical benefits are associated with repair quality, making residual regurgitation not irrelevant. While surgery is more invasive, it currently generates the highest repair rates and longest durability. For terminal heart failure treatment, donor pool expansion for transplantation and reducing adverse events in assist device therapy were issues in 2023. Finally, the aortic diameter related to adverse events and technical aspects of surgery dominated in aortic surgery. This article summarizes publications perceived as important by us. It cannot be complete nor free of individual interpretation, but provides up-to-date information for patient-specific decision-making.

Coronary Artery Bypass Grafting versus Percutaneous Coronary Intervention in Patients with Chronic Total Occlusion.

OBJECTIVES: Mechanisms of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) differ as CABG provides surgical collateralization and may prolong life by preventing future myocardial infarctions (MIs). However, evidence for CABG in patients with chronic total occlusion (CTO) has not been fully elucidated and the impact of PCI is discussed controversially. METHODS: We performed a meta-analysis of studies comparing outcomes in patients with/without multivessel disease undergoing CABG or PCI for CTO. The primary outcome was long-term all-cause mortality (≥5 years). Secondary outcomes were MIs, repeat revascularization, cardiac mortality, major adverse cardiovascular events, and stroke, as well as short-term mortality (30 days/in-hospital) and stroke. A pooled Kaplan-Meier survival curve after reconstruction analysis was generated. Random-effects models were used. RESULTS: Six studies totaling 12,504 patients were included. In the pooled Kaplan-Meier analysis, PCI showed a significantly higher risk of death in the follow-up compared with CABG (hazard ratio [HR]: 2.12, 95% confidence interval [CI]: 1.88-2.38, p < 0.01). During the observation period, PCI was also associated with higher rates of MI (odds ratio [OR]: 2.86, 95% CI: 1.82-4.48, p < 0.01) and more repeat revascularization (OR: 4.88, 95% CI: 1.99-11.91, p = 0.0005). The other outcomes did not show significant differences. CONCLUSION: CABG is associated with superior survival to PCI over time in patients with CTO who are eligible for both PCI and CABG. This survival advantage is associated with fewer events of MI and repeat revascularization.

Delineating morbidity patterns in preterm infants at near-term age using a data-driven approach.

BACKGROUND: Long-term survival after premature birth is significantly determined by development of morbidities, primarily affecting the cardio-respiratory or central nervous system. Existing studies are limited to pairwise morbidity associations, thereby lacking a holistic understanding of morbidity co-occurrence and respective risk profiles. METHODS: Our study, for the first time, aimed at delineating and characterizing morbidity profiles at near-term age and investigated the most prevalent morbidities in preterm infants: bronchopulmonary dysplasia (BPD), pulmonary hypertension (PH), mild cardiac defects, perinatal brain pathology and retinopathy of prematurity (ROP). For analysis, we employed two independent, prospective cohorts, comprising a total of 530 very preterm infants: AIRR ("Attention to Infants at Respiratory Risks") and NEuroSIS ("Neonatal European Study of Inhaled Steroids"). Using a data-driven strategy, we successfully characterized morbidity profiles of preterm infants in a stepwise approach and (1) quantified pairwise morbidity correlations, (2) assessed the discriminatory power of BPD (complemented by imaging-based structural and functional lung phenotyping) in relation to these morbidities, (3) investigated collective co-occurrence patterns, and (4) identified infant subgroups who share similar morbidity profiles using machine learning techniques. RESULTS: First, we showed that, in line with pathophysiologic understanding, BPD and ROP have the highest pairwise correlation, followed by BPD and PH as well as BPD and mild cardiac defects. Second, we revealed that BPD exhibits only limited capacity in discriminating morbidity occurrence, despite its prevalence and clinical indication as a driver of comorbidities. Further, we demonstrated that structural and functional lung phenotyping did not exhibit higher association with morbidity severity than BPD. Lastly, we identified patient clusters that share similar morbidity patterns using machine learning in AIRR (n=6 clusters) and NEuroSIS (n=8 clusters). CONCLUSIONS: By capturing correlations as well as more complex morbidity relations, we provided a comprehensive characterization of morbidity profiles at discharge, linked to shared disease pathophysiology. Future studies could benefit from identifying risk profiles to thereby develop personalized monitoring strategies. TRIAL REGISTRATION: AIRR: DRKS.de, DRKS00004600, 28/01/2013. NEuroSIS: ClinicalTrials.gov, NCT01035190, 18/12/2009.

Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysis.

The limited sensitivity of circulating tumor cell (CTC) detection in pancreatic adenocarcinoma (PDAC) stems from their extremely low concentration in the whole circulating blood, necessitating enhanced detection methodologies. This study sought to amplify assay-sensitivity by employing diagnostic leukapheresis (DLA) to screen large blood volumes. Sixty patients were subjected to DLA, with a median processed blood volume of ~ 2.8 L and approximately 5% of the resulting DLA-product analyzed using CellSearch (CS). Notably, DLA significantly increased CS-CTC detection to 44% in M0-patients and 74% in M1-patients, yielding a 60-fold increase in CS-CTC enumeration. DLA also provided sufficient CS-CTCs for genomic profiling, thereby delivering additional genomic information compared to tissue biopsy samples. DLA CS-CTCs exhibited a pronounced negative prognostic impact on overall survival (OS), evidenced by a reduction in OS from 28.6 to 8.5 months (univariate: p = 0.002; multivariable: p = 0.043). Additionally, a marked enhancement in sensitivity was achieved (by around 3-4-times) compared to peripheral blood (PB) samples, with positive predictive values for OS being preserved at around 90%. Prognostic relevance of CS-CTCs in PDAC was further validated in PB-samples from 228 PDAC patients, consolidating the established association between CTC-presence and reduced OS (8.5 vs. 19.0 months, p < 0.001). In conclusion, DLA-derived CS-CTCs may serve as a viable tool for identifying high-risk PDAC-patients and aiding the optimization of multimodal treatment strategies. Moreover, DLA enables comprehensive diagnostic profiling by providing ample CTC material, reinforcing its utility as a reliable liquid-biopsy approach. This high-volume liquid-biopsy strategy presents a potential pathway for enhancing clinical management in this malignancy.

Simultaneous T2 -weighted real-time MRI of two orthogonal slices.

PURPOSE: MR guidance is used during therapy to detect and compensate for lesion motion. T2 -weighted MRI often has a superior lesion contrast in comparison to T1 -weighted real-time imaging. The purpose of this work was to design a fast T2 -weighted sequence capable of simultaneously acquiring two orthogonal slices, enabling real-time tracking of lesions. METHODS: To generate a T2 contrast in two orthogonal slices simultaneously, a sequence (Ortho-SFFP-Echo) was designed that samples the T2 -weighted spin echo (S- ) signal in a TR-interleaved acquisition of two slices. Slice selection and phase-encoding directions are swapped between the slices, leading to a unique set of spin-echo signal conditions. To minimize motion-related signal dephasing, additional flow-compensation strategies are implemented. In both the abdominal breathing phantom and in vivo experiments, a time series was acquired using Ortho-SSFP-Echo. The centroid of the target was tracked in postprocessing steps. RESULTS: In the phantom, the lesion could be identified and delineated in the dynamic images. In the volunteer experiments, the kidney was visualized with a T2 contrast at a temporal resolution of 0.45 s under free-breathing conditions. A respiratory belt demonstrated a strong correlation with the time course of the kidney centroid in the head-foot direction. A hypointense saturation band at the slice overlap did not inhibit lesion tracking in the semi-automatic postprocessing steps. CONCLUSION: The Ortho-SFFP-Echo sequence delivers real-time images with a T2 -weighted contrast in two orthogonal slices. The sequence allows for simultaneous acquisition, which could be beneficial for real-time motion tracking in radiotherapy or interventional MRI.

Scalable and modular 8-channel transmit and 8-channel flexible receive coil array for 19 F MRI of large animals.

PURPOSE: To introduce an RF coil system consisting of an 8-channel transmit (Tx) and 8-channel receive (Rx) coil arrays for 19 F MRI of large animals. METHODS: The Tx efficiency and homogeneity of the 8-element loop coil array (loop size: 6 × 15 cm2 ) were simulated for two different pig models rendered from MR images. An 8-channel Rx coil array consisting of a flexible 6-channel posterior and a 2-channel planar anterior array was designed to fit on the abdomen of an average-sized pig in supine position. Measurements were performed in a grid phantom and ex vivo on a pig model with perfluoroctylbromide (PFOB)-filled tubes inserted in the thorax. RESULTS: Measured and simulated Tx efficiency and homogeneity for the 8-channel and 5-channel arrays were in good agreement: 1.87 ± 0.22µT/√kW versus 1.96 ± 0.29µT/√kW, and 2.29 ± 0.39µT/√kW versus 2.41 ± 0.37µT/√kW. An isolation of 38 ± 8 dB is achieved between the 19 F Tx and Rx elements, and over 30 dB between the 1 H and 19 F elements. The PFOB-filled vials could be clearly identified within the cadaver abdomen with an SNR of 275 ± 51 for a 3D gradient-echo sequence with 2-mm isotropic resolution and 12 averages, acquired in 9:52 min:s. Performance of the Tx array was robust against phase and amplitude mismatches at the input ports. CONCLUSIONS: A modular and scalable Tx array offers improved Tx efficiency in 19 F MRI of large animals with various sizes. Although conventional birdcage coils have superior Tx efficiency within the target region of interest, scalability of the Tx array to animal size is a major benefit. The described 19 F coil provides homogeneous excitation and high sensitivity detection in large pig models.

Formation of heterogeneous clusters in superfluid helium nanodroplets: phthalocyanine and water.

Clusters consisting of a single phthalocyanine molecule and a single water molecule are investigated by means of electronic spectroscopy in superfluid helium droplets. A recent spectroscopic study of those clusters [J. Fischer, F. Schlaghaufer, E.-M. Lottner, A. Slenczka, L. Christiansen, H. Stapelfeldt, M. Karra, B. Friedrich, T. Mullan, M. Schütz and D. Usvyat, J. Phys. Chem. A, 2019, 123, 10057-10064] which all exhibit a water induced electronic shift to the red is now complemented by the corresponding clusters exhibiting a water induced shift to the blue. These clusters will be analyzed by means of fluorescence excitation spectra, dispersed emission spectra, and additional experimental observations made feasible by helium droplets as cryogenic reactor. Together with the blue shifted clusters a total number of at least 6 isomeric variants could be identified in helium droplets. This contrasts to a number of only three isomeric variants obtained from quantum chemical calculations [J. Fischer, F. Schlaghaufer, E.-M. Lottner, A. Slenczka, L. Christiansen, H. Stapelfeldt, M. Karra, B. Friedrich, T. Mullan, M. Schütz and D. Usvyat, J. Phys. Chem. A, 2019, 123, 10057-10064] disregarding the helium environment and to a single isomer identified in a molecular beam experiment [J. Menapace and E. Bernstein, J. Chem. Phys., 1987, 87, 6877-6889]. The discrepancy in the number of isomers provides evidence of a profound involvement of helium in clustering. Moreover, the discrepancies between the gas phase experiment and quantum chemical calculations similarly reveal the influence of the dynamics of cluster formation on the population of global and local minima that are accessible as isomeric variants.

Gender-Associated Variation in DOAC Levels.

BACKGROUND: Direct oral anticoagulants (DOAC) such as Xa inhibitors rivaroxaban (riva) and apixaban (apix) are increasingly replacing Vitamin K antagonists in prophylaxis and treatment of venous thromboembolism (VTE). Measurements of DOAC plasma levels may be necessary in certain clinical conditions to determine the further dosage. Making decisions is made more difficult by the fact that the peak and trough plasma levels are subject to strong inter-individual fluctuations with overlapping reference ranges. We wanted to find out whether the peak and trough levels can be narrowed if they are determined based on age and gender. METHODS: Therefore, we collected data on peak and trough anti-Xa concentrations in patients treated with either rivaroxaban (n = 93) or apixaban (n = 51) in one center. After exclusion of blood samples of uncertain oral intake, 83 samples for rivaroxaban and 49 samples for apixaban remained for further analysis. Differences between male (riva n = 42, apix n = 28) and female (riva n = 41 and apix n = 21) as well as young (≤ 60 years, riva n = 44, apix n = 23) and elder (> 60 years) patients (riva n = 39 and apix n = 26) were analyzed by Student`s t-test and retrospective regression. RESULTS: We found no differences in age and gender for the apix peak levels. But women had significantly higher riva peak concentrations than men (308.8 ± 178.1 ng/mL versus 206.4 ± 80 ng/mL, p = 0.013). Patients older than 60 years had significantly higher riva peak levels than those younger than 60 (293.7 ± 126.7 ng/mL versus 211.7 ± 158.4 ng/mL, p = 1.29 x 10-8). CONCLUSIONS: In search of narrowing standard peak and trough levels in patients' sera we found significant differ-ences between patients below and above sixty years of age. Gender-associated differences were found in rivaroxa-ban levels possibly explaining DOAC associated hypermenorrhea. In conclusion, gender and age should be included in the determination of peak blood concentration references.

Dental plaque and gingival bleeding in adolescents with juvenile idiopathic arthritis and controls: a multilevel analysis.

OBJECTIVE: To explore whether plaque and gingival bleeding are more frequently experienced by adolescents with juvenile idiopathic arthritis (JIA) compared to matched controls without JIA; explore whether surface- and site-specific periodontal outcomes vary between the two groups; and for participants with JIA, investigate associations between disease-specific features and periodontal outcomes. MATERIAL AND METHODS: In this comparative cross-sectional study, selected surfaces, and sites of index teeth in 10-16-year-olds with JIA and matched controls were examined by modified versions of Simplified Oral Hygiene Index (OHI-S) and Gingival Bleeding Index (GBI). Mixed-effects logistic regressions, reporting odds ratios (OR) with 95% confidence interval (CI), were applied. Intra-class correlation coefficients (ICCs) were calculated to quantify the degree of dependency of measures within the same individual. RESULTS: 144 and 159 adolescents with JIA were evaluated according to OHI-S and GBI; corresponding numbers of controls were 154 and 161. Plaque and gingival bleeding were more frequent in individuals with JIA than controls. Adjusted analyses showed association between JIA status and OHI-S > 0 (OR = 2.33, 95% CI: 1.47 - 3.67, ICC = 0.45) and GBI > 0 (OR = 1.54, 95% CI: 1.10 - 2.16, ICC = 0.41 and 0.30). Surface-specific distribution of plaque varied among the two groups. CONCLUSIONS: Our results highlight the importance of increased awareness of oral health care in patients with JIA and that surface- and site-specific differences in periodontal outcomes exist between individuals with JIA and controls. Few JIA disease-specific variables associated with plaque or gingival bleeding.

High-Throughput Next-Generation Sequencing of the Kidd Blood Group: Unexpected Antigen Expression Properties of Four Alleles and Detection of Novel Variants.

Background: The blood supply for patients with foreign ethnic backgrounds can be challenging, as they often have blood group and HPA patterns that differ from the variants prevalent in the German population. In addition, hemoglobinopathies requiring regular blood transfusion may be more common in such populations. High-throughput genotyping tests can facilitate the identification of the most compatible blood products, thereby reducing the risk of transfusion reactions. The present study reports the results of a molecular study for the Kidd (JK) blood group. Allele frequencies and antigen prevalence data are presented for >8,000 individuals of various origins. Material and Methods: More than 8,000 blood donors were genotyped for 22 blood group systems and 5 HPA genes using an amplicon-based next-generation sequencing (NGS) approach. As part of the test system, we focused on the JK system in more detail. Double-ARMS PCR analysis was performed for the haplotype phasing of the JK1/JK2 and two more common synonymous polymorphisms. We performed transcript analysis to detect potential alternative splice products. For a subset of samples, a comparison between serotype and red cell genotype was conducted. Allele frequencies were determined for geographically different panels of individuals. Results: We successfully genotyped the JK blood group for 99.6% of the samples. Haplotype phasing revealed 96 different alleles. For several alleles that carry one of the synonymous SNVs c.588A>G and c.810G>A, we could not confirm the reported JK phenotypes. We found a higher frequency of JK:1 alleles for all populations except Iraqis. JK*01W.01 alleles were more common in the Asian groups and sub-Saharan Africans. A variant of the allele JK*02N.01 was present exclusively in Southeast Asians. Conclusion: Genotyping for JK antigens with a targeted NGS assay can easily be performed in routine. The interpretation that c.588A>G leads to a weak phenotype and c.810G>A to a null phenotype is questionable. IDs as well as the descriptions of alleles carrying these SNVs should be revised in the ISBT JK table.

The Effect of Renal Denervation on T Cells in Patients with Resistant Hypertension.

(1) Background: Sympathetic overactivity is a major contributor to resistant hypertension (RH). According to animal studies, sympathetic overactivity increases immune responses, thereby aggravating hypertension and cardiovascular outcomes. Renal denervation (RDN) reduces sympathetic nerve activity in RH. Here, we investigate the effect of RDN on T-cell signatures in RH. (2) Methods: Systemic inflammation and T-cell subsets were analyzed in 17 healthy individuals and 30 patients with RH at baseline and 6 months after RDN. (3) Results: The patients with RH demonstrated higher levels of pro-inflammatory cytokines and higher frequencies of CD4+ effector memory (TEM), CD4+ effector memory residential (TEMRA) and CD8+ central memory (TCM) cells than the controls. After RDN, systolic automated office blood pressure (BP) decreased by -17.6 ± 18.9 mmHg. Greater BP reductions were associated with higher CD4+ TEM (r -0.421, p = 0.02) and CD8+ TCM (r -0.424, p = 0.02) frequencies at baseline. The RDN responders, that is, the patients with ≥10mmHg systolic BP reduction, showed reduced pro-inflammatory cytokine levels, whereas the non-responders had unchanged inflammatory activity and higher CD8+ TEMRA frequencies with increased cellular cytokine production. (4) Conclusions: The pro-inflammatory state of patients with RH is characterized by altered T-cell signatures, especially in non-responders. A detailed analysis of T cells might be useful in selecting patients for RDN.

Cone beam computed tomography in the assessment of TMJ deformity in children with JIA: repeatability of a novel scoring system.

BACKGROUND: The temporomandibular joint (TMJ) is frequently involved in juvenile idiopathic arthritis (JIA). Diagnostic imaging is necessary to correctly diagnose and evaluate TMJ involvement, however, hitherto little has been published on the accuracy of the applied scoring systems and measurements. The present study aims to investigate the precision of 20 imaging features and five measurements based on cone beam computed tomography (CBCT). METHODS: Imaging and clinical data from 84 participants in the Norwegian study on juvenile idiopathic arthritis, the NorJIA study, were collected. Altogether 20 imaging features and five measurements were evaluated independently by three experienced radiologists for intra- and interobserver agreement. Agreement of categorical variables was assessed by Fleiss', Cohen's simple or weighted Kappa as appropriate. Agreement of continuous variables was assessed with 95% limits of agreement as advised by Bland and Altman. RESULTS: "Overall impression of TMJ deformity" showed almost perfect intraobserver agreement with a kappa coefficient of 0.81 (95% CI 0.69-0.92), and substantial interobserver agreement (Fleiss' kappa 0.70 (0.61-0.78)). Moreover, both "flattening" and "irregularities" of the eminence/fossa and condyle performed well, with intra- and interobserver agreements of 0.66-0.82 and 0.55-0.76, respectively. "Reduced condylar volume" and "continuity" of the fossa/eminence had moderate intra- and interobserver Kappa values, whereas continuity of the condyle had Kappa values above 0.55. Measurements of distances and angles had limits of agreement of more than 15% of the sample mean. CONCLUSIONS: We propose a CBCT-based scoring system of nine precise imaging features suggestive of TMJ deformity in JIA. Their clinical validity must be tested.

Oral health-related quality of life, impaired physical health and orofacial pain in children and adolescents with juvenile idiopathic arthritis - a prospective multicenter cohort study.

BACKGROUND: Knowledge on oral health-related quality of life (OHRQoL) in children and adolescents with juvenile idiopathic arthritis (JIA) is limited, and longitudinal studies are lacking. We aimed to describe OHRQoL in children and adolescents with JIA compared to controls, and to explore the validity and internal consistency of the Early Childhood Oral Health Impact Scale (ECOHIS) and the Child Oral Impact on Daily Performance (Child-OIDP). Furthermore, we wanted to investigate associations between OHRQoL and orofacial pain, physical health, disease activity, and temporomandibular joint (TMJ) involvement in JIA. METHODS: The Norwegian prospective, multicenter cohort study recruited participants with JIA between 4 and 16 years of age and corresponding controls from three pediatric university hospital departments and public dental health services. In the present study, we analyzed OHRQoL in all children < 12 years with the ECOHIS and adolescents ≥ 12 years with the Child-OIDP at the first visit and the two-year follow-up. Associations between OHRQoL and JIA characteristics, collected in clinical exam and questionnaires, were analyzed in logistic regressions. RESULTS: The same OHRQoL questionnaire was completed both at first visit and two-year follow-up in 101 children < 12 years (47 JIA, 54 controls) and 213 adolescents ≥ 12 years (111 JIA, 102 controls). The frequency of OHRQoL impacts in children was similar at the first visit and the two-year follow-up (ECOHIS > 0: JIA group 81% and 85%, p = 0.791; control group 65% and 69%, p = 0.815), while adolescents with JIA reported fewer impacts at the two-year follow-up (Child OIDP > 0: JIA group 27% and 15%, p = 0.004; control group 21% and 14%, p = 0.230). The internal consistency of the OHRQoL instruments was overall acceptable and the criterion validity indicated that the instruments were valid at both visits. Orofacial pain was more frequent in children and adolescents with JIA than in controls. We found associations between OHRQoL impacts and orofacial pain, impaired physical health, disease activity, and TMJ involvement. CONCLUSIONS: Children and adolescents with orofacial pain or impaired physical health were more likely to report impacts on daily life activities than those without. Pediatric rheumatologists and dentists should be aware of impaired OHRQoL in individuals with JIA with active disease or temporomandibular joint involvement. TRIAL REGISTRATION: Registered on clinicaltrials.gov (NCT03904459, 05/04/2019).

Radio-frequency induced heating of intra-cranial EEG electrodes: The more the colder?

Many neurological disorders are analyzed and treated with implantable electrodes. Many patients with such electrodes have to undergo MRI examinations - often unrelated to their implant - at the risk of radio-frequency induced heating. The number of electrode contact sites of these implants keeps increasing due to improvements in manufacturing and computational algorithms. Electrode grids with multiple receive channels couple to the RF fields present in MRI, but, due to their proximity, a combination of leads has a coupling response which is not a superposition of the individual leads' response. To investigate the problem of RF-induced heating of coupled multi-lead implants, temperature mapping was performed on a set of intra-cranial electroencephalogram (icEEG) electrode grid prototypes with increasing number of contact sites (1-16). Additionally, electric field measurements were used to investigate the radio-frequency heating characteristics of the implants in different media combinations, simulating the device being partially immersed inside the patient. MR measurements show RF-induced heating up to 19.6 K for the single electrode, reducing monotonically with larger number of contact sites to a minimum of 0.9 K for the largest grid. The SAR calculated from temperature measurements agrees well with electric field mapping: The same trend is visible for different insertion lengths, however, the energy dissipated by the whole implant varies with the grid size and insertion length. Thus, in the tested circumstances, a larger electrode number either reduced or had a similar risk of RF induced heating, indicating, that the size of electrode grids is a design parameter, which can be used to change an implants RF response and in turn to reduce the risk of RF induced heating and improve the safety of patient with neuro-implants undergoing MRI examinations.

Single point imaging with radial acquisition and compressed sensing.

PURPOSE: To accelerate the Pointwise Encoding Time Reduction with Radial Acquisition (PETRA) sequence using compressed sensing while preserving the image quality for high-resolution MRI of tissue with ultra-short T2∗ values. METHODS: Compressed sensing was introduced in the PETRA sequence (csPETRA) to accelerate the time-consuming single point acquisition of the k-space center data. Random undersampling was applied to achieve acceleration factors up to Acc = 32. Phantom and in vivo images of the knee joint of six volunteers were measured at 3T using csPETRA sequence with Acc = 4, 8, 12, 16, 24, and 32. Images were compared against fully sampled PETRA data (Acc = 1) for structural similarity and normalized-mean-square-error. Qualitative and semi-quantitative analyses were performed to assess the effect of the acceleration on image artifacts, image quality, and delineation of anatomical structures at the knee. RESULTS: Even at high acceleration factors of Acc = 16 no aliasing artifacts were observed, and the anatomical details were preserved compared with the fully sampled data. The normalized-mean-square-error was less than 1% for Acc = 16, in which single point imaging acquisition time was reduced from 165 to 10 s, reducing the total scan time from 7.8 to 5.2 min. Semi-quantitative analyses suggest that Acc = 16 yields comparable diagnostic quality as the fully sampled data for knee imaging at a scan time of 5.2 min. CONCLUSION: csPETRA allows for ultra-short T2∗ imaging of the knee joint in clinically acceptable scan times while maintaining the image quality of original non-accelerated PETRA sequence.

Humoral response to SARS-CoV-2 and seasonal coronaviruses in COVID-19 patients.

We used enzyme-linked immunoassay methods to measure the prevalence and the levels of antibody responses to the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and four seasonal human coronaviruses (HCoV-OC43, HCoV-HKU1, HCoV 229E, and HCoV-NL63) in a cohort of 115 convalescent plasma donors infected with SARS-CoV-2 (1-61 days after symptom onset) compared to antibody levels in 114 individuals with no evidence of a recent infection with SARS-CoV-2. In the humoral response to the four seasonal coronaviruses, only HCoV-HKU1- and HCoV-229E-assays showed slightly elevated antibody levels in the COVID group compared to the control group. While in the COVID-group the levels of SARS-CoV-2 antibodies correlated significantly with disease severity, no association was found in the levels of antibodies against the seasonal coronaviruses. The most striking result in both groups was that the levels of antibodies against all tested coronaviruses, including the new SARS-CoV-2 showed a highly significant correlation with each other. There seems to be an individual predisposition to a weaker or stronger humoral immune response against all known seasonal human coronaviruses including the new SARS-CoV-2, which could lead to a definition of low and high responders against human coronaviruses with potential impact on the assessment of postinfection antibody levels and protection.

Sub-millisecond 2D MRI of the vocal fold oscillation using single-point imaging with rapid encoding.

OBJECTIVE: The slow spatial encoding of MRI has precluded its application to rapid physiologic motion in the past. The purpose of this study is to introduce a new fast acquisition method and to demonstrate feasibility of encoding rapid two-dimensional motion of human vocal folds with sub-millisecond resolution. METHOD: In our previous work, we achieved high temporal resolution by applying a rapidly switched phase encoding gradient along the direction of motion. In this work, we extend phase encoding to the second image direction by using single-point imaging with rapid encoding (SPIRE) to image the two-dimensional vocal fold oscillation in the coronal view. Image data were gated using electroglottography (EGG) and motion corrected. An iterative reconstruction with a total variation (TV) constraint was used and the sequence was also simulated using a motion phantom. RESULTS: Dynamic images of the vocal folds during phonation at pitches of 150 and 165 Hz were acquired in two volunteers and the periodic motion of the vocal folds at a temporal resolution of about 600 µs was shown. The simulations emphasize the necessity of SPIRE for two-dimensional motion encoding. DISCUSSION: SPIRE is a new MRI method to image rapidly oscillating structures and for the first time provides dynamic images of the vocal folds oscillations in the coronal plane.