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1.
BMC Pediatr ; 24(1): 315, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714956

RESUMO

BACKGROUND: Ultrasound (US) is often the first method used to look for brain or cerebrospinal fluid (CSF) space pathologies. Knowledge of normal CSF width values is essential. Most of the available US normative values were established over 20 years ago, were obtained with older equipment, and cover only part of the age spectrum that can be examined by cranial US. This prospective study aimed to determine the normative values of the widths of the subarachnoid and internal CSF spaces (craniocortical, minimal and maximal interhemispheric, interventricular, and frontal horn) for high-resolution linear US probes in neurologically healthy infants and children aged 0-19 months and assess whether subdural fluid collections can be delineated. METHODS: Two radiologists measured the width of the CSF spaces with a conventional linear probe and an ultralight hockey-stick probe in neurologically healthy children not referred for cranial or spinal US. RESULTS: This study included 359 neurologically healthy children (nboys = 178, 49.6%; ngirls = 181, 50.4%) with a median age of 46.0 days and a range of 1-599 days. We constructed prediction plots, including the 5th, 50th, and 95th percentiles, and an interactive spreadsheet to calculate normative values for individual patients. The measurements of the two probes and the left and right sides did not differ, eliminating the need for separate normative values. No subdural fluid collection was detected. CONCLUSION: Normative values for the widths of the subarachnoid space and the internal CSF spaces are useful for evaluating intracranial pathology, especially when determining whether an increase in the subarachnoid space width is abnormal.


Assuntos
Espaço Subaracnóideo , Ultrassonografia , Humanos , Lactente , Estudos Prospectivos , Masculino , Feminino , Valores de Referência , Recém-Nascido , Ultrassonografia/métodos , Espaço Subaracnóideo/diagnóstico por imagem , Líquido Cefalorraquidiano/diagnóstico por imagem
2.
Neurology ; 102(1): e207977, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38165372

RESUMO

BACKGROUND AND OBJECTIVES: Cerebral small vessel disease (SVD) is the major cause of intracerebral hemorrhage (ICH). There is no comprehensive, easily applicable classification of ICH subtypes according to the presumed underlying SVD using MRI. We developed an MRI-based classification for SVD-related ICH. METHODS: We performed a retrospective study in the prospectively collected Swiss Stroke Registry (SSR, 2013-2019) and the Stroke InvestiGation in North And central London (SIGNAL) cohort. Patients with nontraumatic, SVD-related ICH and available MRI within 3 months were classified as Cerebral Amyloid angiopathy (CAA), Deep perforator arteriopathy (DPA), Mixed CAA-DPA, or Undetermined SVD using hemorrhagic and nonhemorrhagic MRI markers (CADMUS classification). The primary outcome was inter-rater reliability using Gwet's AC1. Secondary outcomes were recurrent ICH/ischemic stroke at 3 months according to the CADMUS phenotype. We performed Firth penalized logistic regressions and competing risk analyses. RESULTS: The SSR cohort included 1,180 patients (median age [interquartile range] 73 [62-80] years, baseline NIH Stroke Scale 6 [2-12], 45.6% lobar hematoma, systolic blood pressure on admission 166 [145-185] mm Hg). The CADMUS phenotypes were as follows: mixed CAA-DPA (n = 751 patients, 63.6%), undetermined SVD (n = 203, 17.2%), CAA (n = 154, 13.1%), and DPA (n = 72, 6.3%), with a similar distribution in the SIGNAL cohort (n = 313). Inter-rater reliability was good (Gwet's AC1 for SSR/SIGNAL 0.69/0.74). During follow-up, 56 patients had 57 events (28 ICH, 29 ischemic strokes). Three-month event rates were comparable between the CADMUS phenotypes. DISCUSSION: CADMUS, a novel MRI-based classification for SVD-associated ICH, is feasible and reproducible and may improve the classification of ICH subtypes in clinical practice and research.


Assuntos
Angiopatia Amiloide Cerebral , Acidente Vascular Cerebral , Humanos , Idoso , Reprodutibilidade dos Testes , Estudos Retrospectivos , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Angiopatia Amiloide Cerebral/diagnóstico por imagem
3.
Eur Radiol ; 34(3): 1556-1566, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37658140

RESUMO

OBJECTIVE: Bioabsorbable magnesium-based alloy screws release gas upon resorption. The resulting findings in the adjacent soft tissues and joints may mimic infection. The aim of the study was to evaluate the ultrasound (US) findings in soft tissues and joints during screw resorption. METHODS: Prospectively acquired US studies from pediatric patients treated with magnesium screws were evaluated for screw head visibility, posterior acoustic shadowing, twinkling artifact, foreign body granuloma, gas (soft tissue, intra-articular), alterations of the skin and subcutaneous fat, perifascial fluid, localized fluid collections, hypervascularization, and joint effusion. RESULTS: Sixty-six US studies of 28 pediatric patients (nfemale = 9, nmale = 19) were included. The mean age of the patients at the time of surgery was 10.84 years; the mean time between surgery and ultrasound was 128.3 days (range = 6-468 days). The screw head and posterior acoustic shadowing were visible in 100% of the studies, twinkling artifact in 6.1%, foreign body granuloma in 92.4%, gas locules in soft tissue in 100% and intra-articular in 18.2%, hyperechogenicity of the subcutaneous fat in 90.9%, cobblestoning of the subcutaneous fat in 24.2%, loss of normal differentiation between the epidermis/dermis and the subcutaneous fat in 57.6%, localized fluid collection in 9.9%, perifascial fluid in 12.1%, hypervascularization in 27.3%, and joint effusion in 18.2%. CONCLUSION: US findings in pediatric patients treated with magnesium screws strongly resemble infection, but are normal findings in the setting of screw resorption. CLINICAL RELEVANCE STATEMENT: Bioabsorbable magnesium-based alloy screws release gas during resorption. The resulting US findings in the adjacent soft tissues and joints in pediatric patients may mimic infection, but are normal findings. KEY POINTS: • Bioabsorbable magnesium-based alloy screws release gas upon resorption. • The resulting ultrasound findings in children's soft tissues and joints closely resemble those of soft tissue infection or osteosynthesis-associated infection. • Be familiar with these ultrasound findings in order to avoid inadvertently misdiagnosing a soft tissue infection or osteosynthesis-associated infection.


Assuntos
Fraturas Ósseas , Granuloma de Corpo Estranho , Infecções dos Tecidos Moles , Humanos , Masculino , Feminino , Criança , Magnésio , Implantes Absorvíveis , Granuloma de Corpo Estranho/etiologia , Infecções dos Tecidos Moles/etiologia , Fraturas Ósseas/etiologia , Ligas , Fixação Interna de Fraturas/métodos , Parafusos Ósseos/efeitos adversos
4.
Eur Radiol ; 2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38148406

RESUMO

OBJECTIVES: The purpose of this meta-analysis was to determine the diagnostic performance of conventional MRI and MR arthrography for tendinosis, and partial and complete tears of the long head of the biceps tendon (LHBT) using arthroscopy as the reference standard. MATERIALS AND METHODS: A systematic review was performed using predefined data fields in PubMed, and all articles published from January 2000 up to April 2022 were retrospectively pooled and reviewed. Six MRI studies on complete tear (n = 555) and ten studies on partial tear/tendinosis (n = 2487) were included in the analysis. Two of the included studies in each group investigated the use of MR arthrography. The data sets were analyzed using a univariate approach with the DerSimonian and Laird random effects model and the proportional hazards model. RESULTS: MRI shows high specificities in diagnosing complete tears of the LHBT ranging from 93.0 to 99.0%. Diagnostic sensitivity was more heterogeneous ranging from 55.9 to 90.0%. The overall negative likelihood ratio was 0.29 (95% CI: 0.17-0.50) and the overall positive likelihood ratio was 37.3 (95% CI: 11.9-117.4). The mean sensitivity in diagnosing partial tear/tendinosis of the LHBT was 67.8% (95% CI: 54.3-78.9%) and the specificity was 75.9% (95% CI: 63.6-85.0%), resulting in a balanced accuracy of 71.9%. The overall negative likelihood ratio was 0.44 (95% CI: 0.32-0.59) and the overall positive likelihood ratio was 2.64 (95% CI: 1.91-3.65). CONCLUSION: MRI is highly specific for the diagnosis of complete tears of the LHBT, whereas diagnostic sensitivity was more heterogeneous. The diagnosis of partial tears and/or tendinosis of the LHBT remains challenging on MRI, which may warrant complementary clinical examination or other imaging modalities to increase diagnostic confidence in equivocal cases. CLINICAL RELEVANCE STATEMENT: Conventional MRI and MR arthrography have high diagnostic performance for complete tendon tear when compared to arthroscopy. The diagnosis of tendinosis/partial tears remains challenging and may require comparison with clinical tests and other imaging modalities. KEY POINTS: •There is no clear consensus regarding the primary imaging modality for the evaluation of LHBT disorders. •Conventional MRI and MR arthrography are highly specific in diagnosing complete tears of the LHBT. •Diagnosis of partial tears/tendinosis of the LHBT on conventional MRI and MR arthrography remains a diagnostic challenge.

5.
ACS Med Chem Lett ; 14(6): 777-787, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37312859

RESUMO

The DNA methyltransferase 2 (DNMT2) is an RNA modifying enzyme associated with pathophysiological processes, such as mental and metabolic disorders or cancer. Although the development of methyltransferase inhibitors remains challenging, DNMT2 is not only a promising target for drug discovery, but also for the development of activity-based probes. Here, we present covalent SAH-based DNMT2 inhibitors decorated with a new type of aryl warhead. Based on a noncovalent DNMT2 inhibitor with N-benzyl substituent, the Topliss scheme was followed for optimization. The results showed that electron-deficient benzyl moieties highly increased affinity. By decorating the structures with strong electron-withdrawing moieties and leaving groups, we adjusted the electrophilicity to create covalent DNMT2 inhibitors. A 4-bromo-3-nitrophenylsulfonamide-decorated SAH derivative (80) turned out to be the most potent (IC50 = 1.2 ± 0.1 µM) and selective inhibitor. Protein mass spectrometry confirmed the covalent reaction with the catalytically active cysteine-79.

6.
Vaccines (Basel) ; 11(4)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37112632

RESUMO

Paediatric check-ups and vaccinations are provided and free of charge in Germany. Despite being hitherto generally well-received and adhered to, it is possible that the lockdown implemented due to the COVID-19 pandemic resulted in delays or even cancellations of critical paediatric visits with healthcare providers. This study attempts to quantify the rate and time to follow-up for check-ups in Germany using the retrospective IQVIATM Disease Analyzer database. Additionally, timely administration of 4 vaccines (Hexavalent, pneumococcal, MMR-V, Rotavirus) was analysed to examine the impact of pandemic restrictions on vaccine uptake. The timeframes which were compared to determine the effects of COVID-19 were June 2018-December 2019 and March 2020-September 2021. The follow-up rates for paediatric check-ups were consistently lower in the COVID-19 phase, but generally ~90%. Follow-up rates for the vaccinations were distinctly higher during COVID-19. The time between events was almost unchanged for check-ups during the pandemic. For check-ups, age at initial event differed by less than a week between the phases. For vaccinations, the age differences were slightly higher, but exceeded one week in only two cases. The results show that the COVID-19 pandemic had little effect on paediatric check-ups and vaccinations in Germany.

7.
J Clin Med ; 12(8)2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37109351

RESUMO

BACKGROUND: The resorption of magnesium-based alloy bioabsorbable screws results in the release of hydrogen gas, which can mimic infection and enter the growth plate. The screw itself and the released gas may also affect image quality. OBJECTIVE: The evaluation of magnetic resonance imaging (MRI) findings during the most active phase of screw resorption is the objective, with particular focus on the growth plate and to assess for the presence of metal-induced artifacts. MATERIAL AND METHODS: In total, 30 prospectively acquired MRIs from 17 pediatric patients with fractures treated with magnesium screws were assessed for the presence and distribution of intraosseous, extraosseous, and intra-articular gas; gas within the growth plate; osteolysis along the screw; joint effusion; bone marrow edema; periosteal reaction; soft tissue edema; and metal-induced artifacts. RESULTS: Gas locules were found in the bone and soft tissues in 100% of the examinations, intra-articular in 40%, and in 37% of unfused growth plates. Osteolysis and the periosteal reaction were present in 87%, bone marrow edema in 100%, soft tissue edema in 100%, and joint effusion in 50% of examinations. Pile-up artifacts were present in 100%, and geometric distortion in 0% of examinations. Fat suppression was not significantly impaired in any examination. CONCLUSIONS: Gas and edema in the bone and soft tissues are normal findings during the resorption of magnesium screws and should not be misinterpreted as infection. Gas can also be detected within growth plates. MRI examinations can be performed without metal artifact reduction sequences. Standard fat suppression techniques are not significantly affected.

8.
Int J Mol Sci ; 24(7)2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37047081

RESUMO

Targeting RNA methyltransferases with small molecules as inhibitors or tool compounds is an emerging field of interest in epitranscriptomics and medicinal chemistry. For two challenging RNA methyltransferases that introduce the 5-methylcytosine (m5C) modification in different tRNAs, namely DNMT2 and NSUN6, an ultra-large commercially available chemical space was virtually screened by physicochemical property filtering, molecular docking, and clustering to identify new ligands for those enzymes. Novel chemotypes binding to DNMT2 and NSUN6 with affinities down to KD,app = 37 µM and KD,app = 12 µM, respectively, were identified using a microscale thermophoresis (MST) binding assay. These compounds represent the first molecules with a distinct structure from the cofactor SAM and have the potential to be developed into activity-based probes for these enzymes. Additionally, the challenges and strategies of chemical space docking screens with special emphasis on library focusing and diversification are discussed.


Assuntos
Metiltransferases , RNA , Simulação de Acoplamento Molecular , RNA de Transferência/química , DNA (Citosina-5-)-Metiltransferases , tRNA Metiltransferases
9.
Neuroradiology ; 65(4): 729-736, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36633612

RESUMO

PURPOSE: To evaluate and compare which factors are relevant to the diagnostic decision-making and imaging workup of intracerebral hemorrhages in large, specialized European centers. METHODS: Expert neuroradiologists from ten large, specialized centers (where endovascular stroke treatment is routinely performed) in nine European countries were selected in cooperation with the European Society of Neuroradiology (ESNR). The experts were asked to describe how and when they would investigate specific causes in a patient who presented with an acute, atraumatic, intracerebral hemorrhage for two given locations: (1) basal ganglia, thalamus, pons or cerebellum; (2) lobar hemorrhage. Answers were collected, and decision trees were compared. RESULTS: Criteria that were considered relevant for decision-making reflect recommendations from current guidelines and were similar in all participating centers. CT Angiography or MR angiography was considered essential by the majority of centers regardless of other factors. Imaging in clinical practice tended to surpass guideline recommendations and was heterogeneous among different centers, e.g., in a scenario suggestive of typical hypertensive hemorrhage, recommendations ranged from no further follow-up imaging to CT angiography and MR angiography. In no case was a consensus above 60% achieved. CONCLUSION: In European clinical practices, existing guidelines for diagnostic imaging strategies in ICH evaluation are followed as a basis but in most cases, additional imaging investigation is undertaken. Significant differences in imaging workup were observed among the centers. Results suggest a high level of awareness and caution regarding potentially underlying pathology other than hypertensive disease.


Assuntos
Hemorragia Cerebral , Acidente Vascular Cerebral , Humanos , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/patologia , Acidente Vascular Cerebral/terapia , Europa (Continente) , Tomografia Computadorizada por Raios X , Hospitais
10.
J Chem Inf Model ; 62(17): 4134-4148, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-35994617

RESUMO

Targeting RNA with small molecules is an emerging field. While several ligands for different RNA targets are reported, structure-based virtual screenings (VSs) against RNAs are still rare. Here, we elucidated the general capabilities of protein-based docking programs to reproduce native binding modes of small-molecule RNA ligands and to discriminate known binders from decoys by the scoring function. The programs were found to perform similar compared to the RNA-based docking tool rDOCK, and the challenges faced during docking, namely, protomer and tautomer selection, target dynamics, and explicit solvent, do not largely differ from challenges in conventional protein-ligand docking. A prospective VS with the Bacillus subtilis preQ1-riboswitch aptamer domain performed with FRED, HYBRID, and FlexX followed by microscale thermophoresis assays identified six active compounds out of 23 tested VS hits with potencies between 29.5 nM and 11.0 µM. The hits were selected not solely based on their docking score but for resembling key interactions of the native ligand. Therefore, this study demonstrates the general feasibility to perform structure-based VSs against RNA targets, while at the same time it highlights pitfalls and their potential solutions when executing RNA-ligand docking.


Assuntos
Riboswitch , Ligantes , Estudos Prospectivos , Proteínas , Pirimidinonas , Pirróis , RNA
11.
Pediatr Radiol ; 52(13): 2584-2594, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35836016

RESUMO

BACKGROUND: Exposure of the eye lens to ionizing radiation results in cataract. Several dose optimization techniques to protect the lens are available for computed tomography (CT). OBJECTIVE: The radiation dose to the eye lens, volume CT dose index (CTDIvol) and image quality of various methods of dose optimization were evaluated for pediatric head CT: automated tube current modulation (ATCM), automated tube voltage selection (ATVS), organ-based tube current modulation (OBTCM) and bismuth shielding. MATERIALS AND METHODS: An anthropomorphic phantom of a 5-year-old child was scanned with nine protocols: no dose optimization technique and then adding different dose optimization techniques alone and in combination. Dose to the eye, thyroid and breast were estimated using metal oxide semiconductor field effect transistor (MOSFET) dosimetry. CTDIvol, influence of timing of shield placement, image noise and attenuation values in 13 regions of interest of the head and subjective image quality were compared. RESULTS: The eye shield significantly reduced the eye lens dose when used alone, to a similar degree as when using all software-based techniques together. When used in combination with software-based techniques, the shield reduced the eye lens dose by up to 45% compared to the no dose optimization technique. Noise was significantly increased by the shield, most pronounced in the anterior portion of the eye. CONCLUSION: The combination of ATCM, ATVS, OBTCM and a bismuth shield, with the shield placed after acquiring the localizer image, should be considered to reduce the radiation dose to the eye lens in pediatric head CT.


Assuntos
Bismuto , Proteção Radiológica , Criança , Humanos , Pré-Escolar , Doses de Radiação , Proteção Radiológica/métodos , Cabeça/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Imagens de Fantasmas
12.
Insights Imaging ; 13(1): 118, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35838922

RESUMO

BACKGROUND: Quantifying femoral and tibial torsion is crucial in the preoperative planning for derotation surgery in children and adolescents. The use of an ultra-low-dose computed tomography (CT) protocol might be possible for modern CT scanners and suitable for reliable torsion measurements even though the bones are not completely ossified. METHODS: This is a retrospective review of 77 children/adolescents (mean age 12.7 years) who underwent a lower extremity CT for torsion measurements on a 64-slice scanner. A stepwise dose reduction (70%, 50%, 30% of the original dose) was simulated. Torsion measurements were performed on all image datasets, and image noise, interrater agreement and subjective image quality were evaluated. Effective radiation dose of each original scan was estimated. As proof of concept, 24 children were scanned with an ultra-low-dose protocol, adapted from the 30% dose simulation, and the intra-class correlation coefficient (ICC) was determined. Ethics approval and informed consent were given. RESULTS: Torsion measurements at the simulated 30% dose level had equivalent interrater agreement compared to the 100% dose level (ICC ≥ 0.99 for all locations and dose levels). Image quality of almost all datasets was rated excellent, regardless of dose. The mean sum of the effective dose of the total torsion measurement was reduced by simulation from 0.460/0.490 mSv (boys/girls) at 100% dose to 0.138/0.147 mSv at 30%. The ICC of the proof-of-concept group was as good as that of the simulated 30% dose level. CONCLUSION: Pediatric torsion measurements of the lower extremities can be performed using an ultra-low-dose protocol without compromising diagnostic confidence.

13.
J Med Chem ; 65(14): 9750-9788, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35849534

RESUMO

Selective manipulation of the epitranscriptome could be beneficial for the treatment of cancer and also broaden the understanding of epigenetic inheritance. Inhibitors of the tRNA methyltransferase DNMT2, the enzyme catalyzing the S-adenosylmethionine-dependent methylation of cytidine 38 to 5-methylcytidine, were designed, synthesized, and analyzed for their enzyme-binding and -inhibiting properties. For rapid screening of potential DNMT2 binders, a microscale thermophoresis assay was established. Besides the natural inhibitors S-adenosyl-l-homocysteine (SAH) and sinefungin (SFG), we identified new synthetic inhibitors based on the structure of N-adenosyl-2,4-diaminobutyric acid (Dab). Structure-activity relationship studies revealed the amino acid side chain and a Y-shaped substitution pattern at the 4-position of Dab as crucial for DNMT2 inhibition. The most potent inhibitors are alkyne-substituted derivatives, exhibiting similar binding and inhibitory potencies as the natural compounds SAH and SFG. CaCo-2 assays revealed that poor membrane permeabilities of the acids and rapid hydrolysis of an ethylester prodrug might be the reasons for the insufficient activity in cellulo.


Assuntos
Metiltransferases , Neoplasias , Proteínas Arqueais , Células CACO-2 , DNA , Humanos , Neoplasias/tratamento farmacológico , S-Adenosil-Homocisteína/química , S-Adenosil-Homocisteína/metabolismo , S-Adenosil-Homocisteína/farmacologia , S-Adenosilmetionina/metabolismo
14.
Eur J Radiol Open ; 9: 100431, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35765661

RESUMO

Purpose: To compare temporal evolution of imaging features of coronavirus disease 2019 (COVID-19) and influenza in computed tomography and evaluate their predictive value for distinction. Methods: In this retrospective, multicenter study 179 CT examinations of 52 COVID-19 and 44 influenza critically ill patients were included. Lung involvement, main pattern (ground glass opacity, crazy paving, consolidation) and additional lung and chest findings were evaluated by two independent observers. Additional findings and clinical data were compared patient-wise. A decision tree analysis was performed to identify imaging features with predictive value in distinguishing both entities. Results: In contrast to influenza patients, lung involvement remains high in COVID-19 patients > 14 days after the diagnosis. The predominant pattern in COVID-19 evolves from ground glass at the beginning to consolidation in later disease. In influenza there is more consolidation at the beginning and overall less ground glass opacity (p = 0.002). Decision tree analysis yielded the following: Earlier in disease course, pleural effusion is a typical feature of influenza (p = 0.007) whereas ground glass opacities indicate COVID-19 (p = 0.04). In later disease, particularly more lung involvement (p < 0.001), but also less pleural (p = 0.005) and pericardial (p = 0.003) effusion favor COVID-19 over influenza. Regardless of time point, less lung involvement (p < 0.001), tree-in-bud (p = 0.002) and pericardial effusion (p = 0.01) make influenza more likely than COVID-19. Conclusions: This study identified differences in temporal evolution of imaging features between COVID-19 and influenza. These findings may help to distinguish both diseases in critically ill patients when laboratory findings are delayed or inconclusive.

15.
HardwareX ; 11: e00256, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35509940

RESUMO

Differential scanning fluorimetry (DSF) is a widely used biophysical technique with applications to drug discovery and protein biochemistry. DSF experiments are commonly performed in commercial real-time polymerase chain reaction (qPCR) thermal cyclers or nanoDSF instruments. Here, we report the construction, validation, and example applications of an open-source DSF system for 176 €, which, in addition to protein-DSF experiments, also proved to be a versatile biophysical instrument for less conventional RNA-DSF experiments. Using 3D-printed parts made of polyoxymethylene, we were able to fabricate a thermostable machine chassis for protein-melting experiments. The combination of blue high-power LEDs as the light source and stage light foil as filter components was proven to be a reliable and affordable alternative to conventional optics equipment for the detection of SYPRO Orange or Sybr Gold fluorescence. The ESP32 microcontroller is the core piece of this openDSF instrument, while the in-built I2S interface was found to be a powerful analog-to-digital converter for fast acquisition of fluorescence and temperature data. Airflow heating and inline temperature control by thermistors enabled high-accuracy temperature management in PCR tubes (±0.1 °C) allowing us to perform high-resolution thermal shift assays (TSA) from exemplary biological applications.

16.
Cancers (Basel) ; 14(9)2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35565199

RESUMO

In this study. we aimed to detect vestibular schwannomas (VSs) in individual magnetic resonance imaging (MRI) slices by using a 2D-CNN. A pretrained CNN (ResNet-34) was retrained and internally validated using contrast-enhanced T1-weighted (T1c) MRI slices from one institution. In a second step, the model was externally validated using T1c- and T1-weighted (T1) slices from a different institution. As a substitute, bisected slices were used with and without tumors originating from whole transversal slices that contained part of the unilateral VS. The model predictions were assessed based on the categorical accuracy and confusion matrices. A total of 539, 94, and 74 patients were included for training, internal validation, and external T1c validation, respectively. This resulted in an accuracy of 0.949 (95% CI 0.935-0.963) for the internal validation and 0.912 (95% CI 0.866-0.958) for the external T1c validation. We suggest that 2D-CNNs might be a promising alternative to 2.5-/3D-CNNs for certain tasks thanks to the decreased demand for computational power and the fact that there is no need for segmentations. However, further research is needed on the difference between 2D-CNNs and more complex architectures.

17.
Insights Imaging ; 13(1): 91, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35551532

RESUMO

OBJECTIVES: The supraacetabular fossa (SAF) is an anatomical variant of the acetabular roof which may mimic a cartilage defect. Two different subtypes have been described: type 1 fluid-filled and type 2 cartilage-filled. The adult prevalence of SAF was reported between 10.5 and 12.6%. We aimed to determine SAF prevalence in a pediatric and young adult population and examine the potential remodeling of the subtypes over time. METHODS: A retrospective search of the institutional database for hip MRI of participants aged 4-25 years was carried out between 2010 and 2020. A total of 401 eligible MRIs of 323 participants were analyzed by two readers. The documented features were: existence of SAF, definition of subtype and measurements of the SAF in three dimensions. Logistic regression models were calculated to estimate the influence of age on the presence of SAF. RESULTS: Out of 323, 115 (35,6%) participants demonstrated a supraacetabular fossa. 63 (19.5%) participants presented subtype 1 and 51 (15.8%) type 2; one participant had both. The predicted probability for SAF increases until the age of 14, beyond 14 years, the combined predicted probability for both subtypes decreased again. In contrast to SAF type 1, SAF type 2 was more prevalent with older age. The size of the SAF decreased with aging. CONCLUSION: The supraacetabular fossa is most frequent in adolescents. With higher age, the prevalence and the size of the SAF decreased. This data supports the theory that the SAF is a developmental variant.

18.
Pediatr Radiol ; 52(12): 2368-2376, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35606529

RESUMO

BACKGROUND: Resorption of magnesium-based alloy bioabsorbable screws produces hydrogen gas, which can be mistaken as a sign of infection and may affect the physis or fixed bone fragment. OBJECTIVE: We evaluated the temporal and spatial occurrence of gas and the occurrence of a breakage of the fixed bone fragment or screw following magnesium screw fixation. MATERIALS AND METHODS: Radiographs of paediatric patients treated with magnesium screws were retrospectively reviewed. Temporal occurrence and distribution of gas in the bone, the physis and soft tissues, breakage of the screw or fixed bone fragment and joint effusion were assessed. RESULTS: One hundred and three radiographs in 35 paediatric patients were reviewed (mean age: 10.6 years). Follow-up ranged from 1 to 730 days. Gas in the bone increases up to week 5, remains constant up to week 16 and then decreases. Gas in soft tissues, intra-articular gas and joint effusions gradually reduce over time. In 1/23 (4.3%) patients with an open physis, gas intrusion into the physis occurred. Breakage of the bone fragment fixated by the screw was observed in 4/35 (11.4%) patients within the first 6 weeks. Screw breakage was observed in 16/35 (45.7%) patients, with a median time to first detection of 300 days. CONCLUSION: Gas bubbles in bone and soft tissue are normal findings in the context of screw resorption and should not be confused with soft-tissue infection or osteomyelitis. Gas is rarely visible in the physis. Breakage of the fixed bone fragment and/or screw can occur.


Assuntos
Fraturas Ósseas , Magnésio , Humanos , Criança , Implantes Absorvíveis , Estudos Retrospectivos , Parafusos Ósseos , Ligas , Fraturas Ósseas/etiologia
19.
Diagnostics (Basel) ; 12(5)2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35626356

RESUMO

BACKGROUND: COVID-19 superinfection by Aspergillus (COVID-19-associated aspergillosis, CAPA) is increasingly observed due to increased awareness and use of corticosteroids. The aim of this study is to compare clinical and imaging features between COVID-19 patients with and without associated pulmonary aspergillosis. MATERIAL AND METHODS: In this case-control study, hospitalized patients between March 2020 and March 2021 were evaluated. Two observers independently compared 105 chest CTs of 52 COVID-19 patients without pulmonary aspergillosis to 40 chest CTs of 13 CAPA patients. The following features were evaluated: lung involvement, predominant main pattern (ground glass opacity, crazy paving, consolidation) and additional lung and chest findings. Chronological changes in the abnormal extent upon CT and chronological changes in the main patterns were compared with mixed models. Patient-wise comparisons of additional features and demographic and clinical data were performed using Student's t-test, Chi-squared test, Fisher's exact tests and Wilcoxon rank-sum tests. RESULTS: Compared to COVID-19 patients without pulmonary aspergillosis, CAPA patients were older (mean age (±SD): 70.3 (±7.8) versus 63.5 (±9.5) years (p = 0.01). The time-dependent evolution rates for consolidation (p = 0.02) and ground glass (p = 0.006) differed. In early COVID-19 disease, consolidation was associated with CAPA, whereas ground glass was less common. Chronological changes in the abnormal extent upon CT did not differ (p = 0.29). Regardless of the time point, bronchial wall thickening was observed more frequently in CAPA patients (p = 0.03). CONCLUSIONS: CAPA patients showed a tendency for consolidation in early COVID-19 disease. Bronchial wall thickening and higher patient age were associated with CAPA. The overall lung involvement was similar between both groups.

20.
Front Neurol ; 13: 856219, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432148

RESUMO

Introduction and Objectives: Noise-induced hearing loss (NIHL) and tinnitus are common problems that can be prevented with hearing protection measures. Sound level meters and noise dosimeters enable to monitor and identify health-threatening occupational or recreational noise, but are limited in their daily application because they are usually difficult to operate, bulky, and expensive. Smartwatches, which are becoming increasingly available and popular, could be a valuable alternative to professional systems. Therefore, the aim of this study was to evaluate the applicability of smartwatches for accurate environmental noise monitoring. Methods: The A-weighted equivalent continuous sound pressure level (L Aeq ) was recorded and compared between a professional sound level meter and a popular smartwatch. Noise exposure was assessed in 13 occupational and recreational settings, covering a large range of sound pressure levels between 35 and 110 dBA. To assess measurement agreement, a Bland-Altman plot, linear regression, the intra-class correlation coefficient, and descriptive statistics were used. Results: Overall, the smartwatch underestimated the sound level meter measurements by 0.5 dBA (95% confidence interval [0.2, 0.8]). The intra-class correlation coefficient showed excellent agreement between the two devices (ICC = 0.99), ranging from 0.65 (music club) to 0.99 (concert) across settings. The smartwatch's sampling rate decreased significantly with lower sound pressure levels, which could have introduced measurement inaccuracies in dynamic acoustic environments. Conclusions: The assessment of ambient noise with the tested smartwatch is sufficiently accurate and reliable to improve awareness of hazardous noise levels in the personal environment and to conduct exploratory clinical research. For professional and legally binding measurements, we recommend specialized sound level meters or noise dosimeters. In the future, smartwatches will play an important role in monitoring personal noise exposure and will provide a widely available and cost-effective measure for otoprotection.

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