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The present study aimed to investigate the diagnostic performance of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the detection of bone marrow involvement (BMI) in paediatric Hodgkin lymphoma (HL) through a systematic review and meta-analysis.
PubMed, Cochrane, and EMBASE databases were searched from the earliest available date of indexing till March 31, 2020 for studies evaluating the diagnostic performance of F-18 FDG PET/CT in the detection of BMI in paediatric HL.
Across seven studies (1265 patients), the pooled sensitivity of F-18 FDG PET or PET/CT was 0.95 (95% confidence interval [CI] 0.87-0.98) with heterogeneity (I
= 86.2, p < 0.001), and the pooled specificity was 0.97 (95% CI 0.84-1.00) with heterogeneity (I
= 97.2, p < 0.001). Likelihood ratio syntheses provided an overall positive likelihood ratio of 37.8 (95% CI 5.2-274.9) and a negative likelihood ratio of 0.05 (95% CI 0.02-0.14). The pooled diagnostic odds ratio was 732 (95% CI 55-9806). The area under the summary receiver operating characteristic curve was 0.98 (95% CI 0.97-0.99).
The present meta-analysis revealed high sensitivity and specificity of F-18 FDG PET/CT for the detection of BMI in paediatric HL. Currently, the literature regarding the use of F-18 FDG PET/CT for the detection of BMI in paediatric HL is limited. Large multicentre studies are necessary to substantiate the diagnostic accuracy of F-18 FDG PET/CT in the detection of BMI in paediatric HL.
Through a meta-analysis, this study provided a more reliable assessment of the diagnostic utility of F-18 FDG PET/CT, which exhibited good diagnostic accuracy in the detection of BMI in paediatric HL.
Through a meta-analysis, this study provided a more reliable assessment of the diagnostic utility of F-18 FDG PET/CT, which exhibited good diagnostic accuracy in the detection of BMI in paediatric HL.The benzodiazepine midazolam (MDZ) is commonly used as first-line treatment in patients with acute seizures. This review summarizes the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of MDZ nasal spray (MDZ-NS), which can be administered by non-health care providers in the outpatient, ambulatory setting. Intranasal administration leads to rapid (tmax 9.0-21.5 min), consistent, and extensive absorption of MDZ, with fast distribution to the central nervous system (CNS), as demonstrated by the onset of sedation within 10 min after administration and the occurrence of peak psychomotor impairment at approximately 17-120 min after administration. Rapid plasma clearance of MDZ and its active metabolite 1-OH-MDZ (t½ 3.6-8.1 h) results in a return to baseline alertness and psychomotor functionality by approximately 240 min post dose. The lack of first-pass metabolism reduces the potential for drug-drug interactions compared with oral dosing. Age (≥ 12 years), sex, race, body weight, body mass index, normal to moderately impaired renal function, and concomitant administration of cytochrome P450 (CYP)3A-inducing drugs are not considered important factors for MDZ-NS dosing. However, coadministration of MDZ-NS with moderate or strong CYP3A4 inhibitors should be avoided, and MDZ-NS should be used with caution when coadministered with mild CYP3A4 inhibitors, as these may result in prolonged MDZ effects owing to a decrease in plasma clearance. Taken together, the PK and PD properties of MDZ-NS, with a short tmax that translates into rapid CNS PD effects of sedation and psychomotor impairment, demonstrate rapid CNS penetration and onset of action, supporting its use for acute treatment of seizure clusters.The hydrolysis of asparagine and glutamine by L-asparaginase has been used to treat acute lymphoblastic leukemia for over four decades. Each L-asparaginase monomer has a long loop that closes over the active site upon substrate binding, acting as a lid. Here we present a comparative study of two commercially available preparations of the drug containing Escherichia coli L-Asparaginase 2 (EcA2), performed by a comprehensive array of biophysical and biochemical approaches. We report the oligomeric landscape and conformational and dynamic plasticity of E. coli type 2 L-asparaginase present in two different formulations, and its relationship with L-aspartic acid, which is present in Aginasa, but not in Leuginase. The L-Asp present in Aginasa formulation was found to provide to EcA2 a resistance to in vitro proteolysis. EcA2 shows a composition of monomers and oligomers up to tetramers, which is mostly not altered in the presence of L-Asp. Ion-mobility spectrometry-mass spectrometry reveals two conformers for the monomeric EcA2, and that monomeric species has sufficient capacity for selective binding to L-Asp and L-Glu. The N-terminal loop of the EcA2 present in Leuginase, which is part of the active site is disordered, but it gets ordered in the presence of L-Asp, while L-Glu only does so to a limited extent. These data provide new insights on the mechanistic of ligand recognition by EcA2, and the impact of formulation in its conformational diversity landscape.
Isolated dysarthria caused by stroke is a rare condition and generally seen in infratentorial lesions, especially in cerebellar lesions. Isolated dysarthria associated with supratentorial ischemic lesions are also very rare and, these conditions were shown in only a few cases. In this study, six patients characterized by IHP due to supratentorial ischemic lesions are presented.
Physical examinations of patients were done by two different neurologists. The risk factors for stroke were determined. Localisations of lesions were identified by using magnetic resonance images(MRI). Corticolingual tract affection without sensorial and other corticospinal tract involvement was confirmed using Somatosensory evoked potentials(SEPs) and Transcranial Magnetic Stimulation(TMS).
Unilateral lingual paresis was detected in all of the patients. The lesions were demonstrated on MRI slices. All lesions were on the same localization. The affection of the corticolingual tract without any other motor and sensory tract involvement was proven electrophysiologically.
Corticospinal and corticobulbar fibers are very close to each other. Therefore common involvement is expected in cerebrovascular diseases. However, six patients with IHP caused by supratentorial ischemic lesions were reported in this study. Thus, a possible map of the corticolingual tract was drawn.
Corticospinal and corticobulbar fibers are very close to each other. Therefore common involvement is expected in cerebrovascular diseases. However, six patients with IHP caused by supratentorial ischemic lesions were reported in this study. Thus, a possible map of the corticolingual tract was drawn.Carnauba wax was used in salt encapsulation, allowing sodium reduction in fresh sausages while maintaining the salty taste due to the inhomogeneous salt distribution. Four treatments were made, as follows treatment C containing 2% non-encapsulated salt, and the treatments S2.0%, S1.5%, and S1.0% containing 2, 1.5, and 1% encapsulated salt, respectively. see more The physicochemical parameters were within the standard regulations for all treatments, with the lower hardness and cohesiveness observed for S1.0%. The treatments and the storage period (90 days) had no effect on aw and instrumental color. Although a decrease in pH and an increase in lipid oxidation were observed during storage, the results were within acceptable levels. Concerning the consumers' perception of saltiness, the assessors reported no differences among the treatments C, S2.0%, and S1.5%. Thus, it is possible to reduce 25% salt in fresh sausages using the taste contrast technology.
Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a rare neurological syndrome caused by pathogenic variants in the C19orf12 and is characterized by iron deposition in the basal ganglia and substantia nigra. Only a limited number of cohort studies were published to date and the prevalence of MPAN remains uncertain.
Recruited subjects with MPAN in Russia were diagnosed by whole-exome sequencing or Sanger sequencing of the C19orf12 gene. Data of over 14000 whole exome sequencing analyses was used to calculate the estimated disease frequency. RNA analysis was performed by RT-PCR. QSVanalyzer software was used to quantify the allelic disbalance.
We describe the clinical and molecular characterizations of 17 patients with MPAN. DNA analysis detected three previously undescribed pathogenic/likely pathogenic variants in the C19orf12 gene. The estimated disease frequency was calculated to be 1619150. We describe unusual clinical observations in several cases. One patient showed severe neurogenic muscle weakness along with a lack of marked spasticity or optic nerve atrophy. In another mild clinical case with the NM_001031726.3c.204_214del (p.(Gly69Argfs*10)) variant in a heterozygous state, a marked allelic disbalance was observed on the RNA level with reduced expression level of the wild-type allele. Thus, this case became the first one of a possible regulatory variant causing MPAN.
We reported a detailed clinical and molecular characterization of the third-largest MPAN cohort. We expanded the mutational and clinical spectrum of MPAN. Moreover, we calculated the estimated MPAN frequency in the Russian population for the first time.
We reported a detailed clinical and molecular characterization of the third-largest MPAN cohort. We expanded the mutational and clinical spectrum of MPAN. Moreover, we calculated the estimated MPAN frequency in the Russian population for the first time.
Adults with Parkinson's disease (PD) experience gait disturbances that can sometimes be improved with rhythmic auditory stimulation (RAS); however, the underlying physiological mechanism for this improvement is not well understood. We investigated brain activation patterns in adults with PD and healthy controls (HC) using functional magnetic resonance imaging (fMRI) while participants imagined gait with or without RAS.
Twenty-seven adults with PD who could walk independently and walked more smoothly with rhythmic auditory cueing than without it, and 25 age-matched HC participated in this study. Participants imagined gait in the presence of RAS or white noise (WN) during fMRI.
In the PD group, gait imagery with RAS activated cortical motor areas, including supplementary motor areas and the cerebellum, while gait imagery with WN additionally recruited the left parietal operculum. In HC, the induced activation was limited to cortical motor areas and the cerebellum for both the RAS and WN conditions. Within- and between-group analyses demonstrated that RAS reduced the activity of the left parietal operculum in the PD group but not in the HC group (condition-by-group interaction by repeated measures analysis of variance, p<0.05).
During gait imagery in adults with PD, the left parietal operculum was less activated by RAS than by WN, while no change was observed in HC, suggesting that rhythmic auditory stimulation may support the sensory-motor networks involved in gait, thus alleviating the overload of the parietal operculum and compensating for its dysfunction in these patients.
During gait imagery in adults with PD, the left parietal operculum was less activated by RAS than by WN, while no change was observed in HC, suggesting that rhythmic auditory stimulation may support the sensory-motor networks involved in gait, thus alleviating the overload of the parietal operculum and compensating for its dysfunction in these patients.
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