General dynamics of the URT microbiome and microbial signs of recovery in COVID-19 patients.

COVID-19 is caused by an airborne virus, SARS-CoV-2. The upper respiratory tract (URT) is, therefore, the first system to endure the attack. Inhabited by an assemblage of microbial communities, a healthy URT wards off the invasion. However, once invaded, it becomes destabilised, which could be crucial to the establishment and progression of the infection. We examined 696 URT samples collected from 285 COVID-19 patients at three time-points throughout their hospital stay and 100 URT samples from 100 healthy controls. We used 16S ribosomal RNA sequencing to evaluate the abundance of various bacterial taxa, α-diversity, and ß-diversity of the URT microbiome. Ordinary least squares regression was used to establish associations between the variables, with age, sex, and antibiotics as covariates. The URT microbiome in the COVID-19 patients was distinctively different from that of healthy controls. In COVID-19 patients, the abundance of 16 genera was significantly reduced. A total of 47 genera were specific to patients, whereas only 2 were unique to controls. The URT samples collected at admission differed more from the control than from the samples collected at later stages of treatment. The following four genera originally depleted in the patients grew significantly by the end of treatment: Fusobacterium, Haemophilus, Neisseria, and Stenotrophomonas. Our findings strongly suggest that SARS-CoV-2 caused significant changes in the URT microbiome, including the emergence of numerous atypical taxa. These findings may indicate increased instability of the URT microbiome in COVID-19 patients. In the course of the treatment, the microbial composition of the URT of COVID-19 patients tended toward that of controls. These microbial changes may be interpreted as markers of recovery.

Cognitive impairment in long-living adults: a genome-wide association study, polygenic risk score model and molecular modeling of the APOE protein.

Background: Cognitive impairment is an irreversible, aging-associated condition that robs people of their independence. The purpose of this study was to investigate possible causes of this condition and propose preventive options. Methods: We assessed cognitive status in long-living adults aged 90+ (n = 2,559) and performed a genome wide association study using two sets of variables: Mini-Mental State Examination scores as a continuous variable (linear regression) and cognitive status as a binary variable (> 24, no cognitive impairment; <10, impairment) (logistic regression). Results: Both variations yielded the same polymorphisms, including a well-known marker of dementia, rs429358in the APOE gene. Molecular dynamics simulations showed that this polymorphism leads to changes in the structure of alpha helices and the mobility of the lipid-binding domain in the APOE protein. Conclusion: These changes, along with higher LDL and total cholesterol levels, could be the mechanism underlying the development of cognitive impairment in older adults. However, this polymorphism is not the only determining factor in cognitive impairment. The polygenic risk score model included 45 polymorphisms (ROC AUC 69%), further confirming the multifactorial nature of this condition. Our findings, particularly the results of PRS modeling, could contribute to the development of early detection strategies for predisposition to cognitive impairment in older adults.

Dynamic contrast-enhanced magnetic resonance imaging for monitoring neovascularization during bone regeneration-a randomized in vivo study in rabbits.

OBJECTIVES: Micro-computed tomography (µ-CT) and histology, the current gold standard methods for assessing the formation of new bone and blood vessels, are invasive and/or destructive. With that in mind, a more conservative tool, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), was tested for its accuracy and reproducibility in monitoring neovascularization during bone regeneration. Additionally, the suitability of blood perfusion as a surrogate of the efficacy of osteoplastic materials was evaluated. MATERIALS AND METHODS: Sixteen rabbits were used and equally divided into four groups, according to the time of euthanasia (2, 3, 4, and 6 weeks after surgery). The animals were submitted to two 8-mm craniotomies that were filled with blood or autogenous bone. Neovascularization was assessed in vivo through DCE-MRI, and bone regeneration, ex vivo, through µ-CT and histology. RESULTS: The defects could be consistently identified, and their blood perfusion measured through DCE-MRI, there being statistically significant differences within the blood clot group between 3 and 6 weeks (p = 0.029), and between the former and autogenous bone at six weeks (p = 0.017). Nonetheless, no significant correlations between DCE-MRI findings on neovascularization and µ-CT (r =-0.101, 95% CI [-0.445; 0.268]) or histology (r = 0.305, 95% CI [-0.133; 0.644]) findings on bone regeneration were observed. CONCLUSIONS: These results support the hypothesis that DCE-MRI can be used to monitor neovascularization but contradict the premise that it could predict bone regeneration as well.

Design of a novel antisymmetric coil array for parallel transmit cardiac MRI in pigs at 7 T.

The design, simulation, assembly and testing of a novel dedicated antisymmetric transmit/receive (Tx/Rx) coil array to demonstrate the feasibility of cardiac magnetic resonance imaging (cMRI) in pigs at 7 T was described. The novel antisymmetric array is composed of eight elements based on mirrored and reversed loop orientations to generate varying B1+ field harmonics for RF shimming. The central four loop elements formed together a pair of antisymmetric L-shaped channels to allow good decoupling between all neighboring elements of the entire array. The antisymmetric array was compared to a standard symmetric rectilinear loop array with an identical housing dimension. Both arrays were driven in the parallel transmit (pTx) mode forming an 8-channel transmit and 16-channel receive (8Tx/16Rx) coil array, where the same posterior array was combined with both anterior arrays. The hardware and imaging performance of the dedicated cardiac arrays were validated and compared by means of electromagnetic (EM) simulations, bench-top measurements, phantom, and ex-vivo MRI experiments with 46 kg female pig. Combined signal-to-noise ratio (SNR), geometry factor (g-factor), noise correlation maps, and high resolution ex-vivo cardiac images were acquired with an in-plane resolution of 0.3 mm × 0.3 mm using both arrays. The novel antisymmetric array enhanced the SNR within the heart by about two times and demonstrated good decoupling and improved control of the B1+ field distributions for RF shimming compared to the standard coil array. Parallel imaging with acceleration factor (R) up to 4 was possible using the novel antisymmetric coil array while maintaining the mean g-factor within the heart region of 1.13.

Continuous-flow DNP polarizer for MRI applications at 1.5 T.

Here we describe a new hyperpolarization approach for magnetic resonance imaging applications at 1.5 T. Proton signal enhancements of more than 20 were achieved with a newly designed multimode microwave resonator situated inside the bore of the imager and used for Overhauser dynamic nuclear polarization of the water proton signal. Different from other approaches in our setup the hyperpolarization is achieved continuously by liquid water flowing through the polarizer under continuous microwave excitation. With an available flow rate of up to 1.5 ml/min, which should be high enough for DNP MR angiography applications in small animals like mice and rats. The hyperpolarized liquid cooled to physiological temperature can be routed by a mechanical switch to a quartz capillary for injection into the blood vessels of the target object. This new approach allows hyperpolarization of protons without the need of an additional magnet and avoids the losses arising from the transfer of the hyperpolarized solution between magnets. The signal-to-noise improvement of this method is demonstrated on two- and three-dimensional phantoms of blood vessels.

Application unit for the administration of contrast gases for pulmonary magnetic resonance imaging: optimization of ventilation distribution for (3) He-MRI.

PURPOSE: MRI of lung airspaces using gases with MR-active nuclei ((3) He, (129) Xe, and (19) F) is an important area of research in pulmonary imaging. The volume-controlled administration of gas mixtures is important for obtaining quantitative information from MR images. State-of-the-art gas administration using plastic bags (PBs) does not allow for a precise determination of both the volume and timing of a (3) He bolus. METHODS: A novel application unit (AU) was built according to the requirements of the German medical devices law. Integrated spirometers enable the monitoring of the inhaled gas flow. The device is particularly suited for hyperpolarized (HP) gases (e.g., storage and administration with minimal HP losses). The setup was tested in a clinical trial (n = 10 healthy volunteers) according to the German medicinal products law using static and dynamic ventilation HP-(3) He MRI. RESULTS: The required specifications for the AU were successfully realized. Compared to PB-administration, better reproducibility of gas intrapulmonary distribution was observed when using the AU for both static and dynamic ventilation imaging. CONCLUSION: The new AU meets the special requirements for HP gases, which are storage and administration with minimal losses. Our data suggest that gas AU-administration is superior to manual modes for determining the key parameters of dynamic ventilation measurements.

[Cardiac angiosarcoma].

The paper outlines the authors'case of cardiac angiosarcoma. It provides the gross and microscopic characteristics of this tumor and procedures for its clinical and immunomorphological diagnosis.

Flip-angle measurement by magnetization inversion: Calibration of magnetization nutation angle in hyperpolarized (3) He magnetic resonance imaging lung experiments.

The aim of this work was to establish a new, fast, and robust method of flip-angle calibration for magnetic resonance imaging of hyperpolarized (3) He. The method called flip-angle measurement with magnetization inversion is based on acquiring images from periodically inverted longitudinal magnetization created using the spatial modulation of magnetization technique. By measuring the width of the area where the magnetization was inverted by the spatial modulation of magnetization preparation in phase images, the flip angle can be generated using a simple equation. To validate and establish the limits of the proposed method, flip-angle measurement with magnetization inversion acquisitions were simulated and applied to proton and hyperpolarized (3) He phantoms. Then, the calibration procedure was applied during hyperpolarized (3) He magnetic resonance imaging in a healthy volunteer. The advantage of the flip-angle measurement with magnetization inversion method compared with the conventional method based on the assessment of radiofrequency-decay is that it is free of errors induced by relaxation due to oxygen, by imperfect excitation slice profile and by any diffusion of (3) He into and out of the slice. Another advantage is that it does not require image processing with external software and therefore can be performed using the implemented tools on the magnetic resonance workstation.

NMR measurements of gaseous sulfur hexafluoride (SF6) to probe the cross-linking of EPDM rubber.

The effects of embedding gaseous SF6 into EPDM rubber were investigated using NMR methods. It was found that observed sorption and desorption processes follow the behavior of the dual mode sorption model. A strong correlation was found between EPDM cross-linking and transversal relaxation time of embedded SF6. EPDM samples with different cross-link densities, preliminarily determined by 1H transversal relaxation using the Gotlib model and Litvinov's method, were investigated using embedded SF6. The sensitivity of the 19F transversal relaxation rate of SF6 to the EPDM cross-link density variation was found to be at least 10 times higher than for 1H in the polymer chain. First experiments on probing the swelling effects in EPDM due to its contact with polar liquids have been performed.

MRI with the dipolar interaction refocusing techniques: analysis of the effectiveness for the solid-state polymers.

The effectiveness of solid-echo and magic-echo phase-encoding solid-state magnetic resonance imaging methods was tested to determine possible improvement of sensitivity and spatial resolution for investigation of various types of solid polymers. The dipolar interaction refocusing pulse sequences have been used to elongate the possible phase-encoding period and to improve the signal sensitivity. The comparison of both dipolar refocusing techniques with conventional single point imaging method was made. The optimization of the phase-encoding time and magnetization recovery periods were performed basing on (1)H spectra and longitudinal relaxation measurements, respectively. The influence of imaging artifacts (intrinsic for each technique) on image quality was investigated. The effectiveness of the artifacts suppression methods was tested.

Magnetic Resonance Imaging (MRI) of fingers with a high spatial resolution using a low-field magnetic system.

For our low-field resistive MRI-System we have developed suitable rf-probes to be able to image fingers with a possibly high spatial resolution. To reduce the measurement time and to improve the signal/noiseratio, which is inherently bad in a low field system, we used a multi-echo sequence, accumulating up to six echo signals for each image. For a 256 x 256 pixel matrix we achieved with this technique a spatial resolution of 176 microns/pixel in measuring times between 4 and 5 minutes. In comparison to healthy persons also first MR-images of patients suffering on arthrosis at the fingers and small joint injures were acquired. Using a 512 x 512 pixel matrix and a field of view of 5 cm images with a resolution of 80 microns/pixel were recorded in a total measuring time of less than 10 minutes.

[Diagnosis and treatment of stenosis of the major duodenal papilla after cholecystectomy]. / Diagnostika i lechenie stenoza bol'shogo sosochka dvenadtsati- perstnoi kishki posle kholetsistéktomii.

The data of diagnosis and treatment of 59 patients with stenosis of the major duodenal papilla (MDP) revealed at different periods after cholecystectomy are analysed. In diagnosis of MDP stenosis, the following methods were employed: ultrasounds scanning of the liver and bile ducts, intravenous cholangiography, endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography. The surgical method of treatment was used in 24, an endoscopic method--in 28, a combined one--in 7 patients. The indications and contraindications for the use of different methods of treatment are presented. It is noted that the use of a complex of modern methods of diagnosis and treatment will permit to establish precisely MDP stenosis after previously performed cholecystectomy and eliminate it with minimal lethality.