No abstract

Down syndrome, caused by trisomy 21, is characterized by congenital abnormalities as well as mental retardation. From the neonatal stage through adolescence, patients with Down syndrome often have several complications. Thus, it is important to attain knowledge of the prevalence of these comorbidities in children with Down syndrome. We, therefore, evaluated the biochemical data, thyroid function, and anthropometric parameters, and analyzed the association among them in Japanese children and early adolescents with Down syndrome. There was no difference in the prevalence of obesity and overweight between boys and girls. The level of uric acid was higher in boys than in girls. Moreover, the prevalence of hyperuricemia was also higher in boys than in girls (approximately 32% and 10%, respectively). The prevalence of subclinical hypothyroidism in children with Down syndrome was approximately 20%, with no significant sex differences. The levels of uric acid and dehydroepiandrosterone-sulfate were positively associated with age, while the levels of thyroid-stimulating hormone and free thyroxine had a negative association with age. Overall, children with Down syndrome, exhibit a higher incidence of hyperuricemia. Therefore, uric acid levels, as well as thyroid function, from childhood to early adulthood should be monitored in this patient cohort.

Background: Direct evidence of inflammatory activity in the atria of patients with atrial fibrillation (AF) is scarce. We assessed the capability of positron-emission tomography/computed tomography (PET/CT) to diagnose AF based on fluorodeoxyglucose (FDG) uptake in the atrial wall. Methods and results: Among 8233 patients who underwent FDG-PET/CT as work-up for malignancies, we identified 180 consecutive patients with AF (2.2%). Of those, we selected 137 patients who had fasted N12 h before FDG injection for inclusion in the experimental group (88 men and 49 women; age: 72.7 ± 8.9 years). Controls were 62 age-and sex-matched patients without AF. For visual analysis, we used a 4-point grading system. For quantitative analysis, we used the maximum standard uptake value (SUVmax) in the left (LA) and right atrial (RA) myocardium and the target-to-background ratio (TBR) of SUVmax to blood pool activity. The sensitivity, specificity, and positive-predictive value for detecting AF visually were 54.0%, 95.2%, and 96.1%, respectively; for quantitative analysis, the respective values were 65.7%, 75.8%, and 85.7%. Multivariable analysis of 11 clinical and imaging variables showed significant associations with RA SUVmax (odds ratio [OR]: 14.353, P = 0.026) and LA volume (OR: 1.371, P = 0.0001). The RA TBR was greater in cases with persistent AF than in those with paroxysmal AF (P b 0.0001). Pathological investigation of 4 autopsy hearts confirmed infiltration of extravascular macrophages and lymphocytes in the regions with FDG uptake. Conclusions: Higher atrial FDG uptake was associated with AF. PET/CT could be a useful tool for detecting local inflammation in the atria with AF.

Age at onset, presence of BZD-resistant SE, and AST are associated with a poor prognosis in AE.

Various walk supporting systems have been devised and developed. However, they have not been designed for supporting or evaluating the gait of parkinsonian patients, and not much consideration has been given to gait disturbances of parkinsonian patients. In this study: (a) We prepared a tentative model of walk supporting and monitoring system in consideration of typical symptoms of parkinsonism. (b) We conducted gait rehabilitation in a parkinsonian patient using the walk supporting and monitoring system and confirmed (i) the occurrence of frozen gait during walking, (ii) brachybasia, (iii) the absence of anterior tilting of the posture, pulsion symptom, and festination, and (iv) occurrence of hesitation to start walking. Therefore, typical symptoms of parkinsonism can be detected by the use of this system. (c) The medical staff can evaluate the state of recovery of patients on the basis of the data obtained from this system and use them for purposes such as guidance of rehabilitation.

No abstract

Myocardial ischemia is caused by a mismatch between myocardial oxygen consumption and oxygen delivery in coronary artery disease (CAD). Stratification and decision-making based on ischemia improves the prognosis in patients with CAD. Non-invasive tests used to evaluate myocardial ischemia include stress electrocardiography, echocardiography, single-photon emission computed tomography, and magnetic resonance imaging. Invasive fractional flow reserve is considered the reference standard for assessment of the hemodynamic significance of CAD. Computed tomography (CT) angiography has emerged as a first-line imaging modality for evaluation of CAD, particularly in the population at low to intermediate risk, because of its high negative predictive value; however, CT angiography does not provide information on the hemodynamic significance of stenosis, which lowers its specificity. Emerging techniques, e.g., CT perfusion and CT-fractional flow reserve, help to address this limitation of CT, by determining the hemodynamic significance of coronary artery stenosis. CT perfusion involves acquisition during the first pass of contrast medium through the myocardium following pharmacological stress. CTfractional flow reserve uses computational fluid dynamics to model coronary flow, pressure, and resistance. In this article, we review these two functional CT techniques in the evaluation of myocardial ischemia, including their principles, technology, advantages, limitations, pitfalls, and the current evidence.

Multiple myeloma (MM) is an incurable malignancy often associated with primary and acquired resistance to therapeutic agents, such as proteasome inhibitors. However, the mechanisms underlying the proteasome inhibitor resistance are poorly understood. Here, we elucidate the mechanism of primary resistance to bortezomib and ixazomib in the MM cell lines, KMS-20, KMS-26, and KMS-28BM. We find that low bortezomib and ixazomib concentrations induce cell death in KMS-26 and KMS-28BM cells. However, high bortezomib and ixazomib concentrations induce cell death only in KMS-20 cells. During Gene Expression Omnibus analysis, KMS-20 cells exhibit high levels of expression of various genes, including anti-phospho-fibroblast growth factor receptor 1 (FGFR1), chemokine receptor type (CCR2), and serum and glucocorticoid regulated kinase (SGK)1. The SGK1 inhibitor enhances the cytotoxic effects of bortezomib and ixazomib; however, FGFR1 and CCR2 inhibitors do not show such effect in KMS-20 cells. Moreover, SGK1 activation induces the phosphorylation of NF-κB p65, and an NF-κB inhibitor enhances the sensitivity of KMS-20 cells to bortezomib and ixazomib. Additionally, high levels of expression of SGK1 and NF-κB p65 is associated with a low sensitivity to bortezomib and a poor prognosis in MM patients. These results indicate that the activation of the SGK1/NF-κB pathway correlates with a low sensitivity to bortezomib and ixazomib, and a combination of bortezomib and ixazomib with an SGK1 or NF-κB inhibitor may be involved in the treatment of MM via activation of the SGK1/NF-κB pathway.