Gas-Filled Phospholipid Nanoparticles Conjugated with Gadolinium Play a Role as a Potential Theragnostics for MR-Guided HIFU Ablation

To develop a long-circulating theragnostics, meaning therapeutics and diagnostics for MR-guided HIFU ablation, we designed and prepared Gd-C5F12-phospholipid nanobubbles (PLNs) 30–100 nm in diameter. The biochemical and physical characterization of Gd-C5F12-PLNs were performed. Since Gd-C5F12-PLN-50 (Φ = 50 nm) and Gd-C5F12-PLN-100 (Φ = 100 nm) enhanced the hyperthermal effect of HIFU size- and concentration-dependently in a tissue-mimicking phantom, its circulation, distribution, tumor accumulation and tumor ablation were examined in tumor-bearing mice. The plasma-half life of Gd-C5F12-PLNs was longer than 1.5 hrs. Gd-C5F12-PLNs mainly accumulated in the liver and the spleen, suggesting that they are slowly secreted through the hepatobiliary pathway. Monitored by the T1 signal intensity of MR, Gd-C5F12-PLNs accumulated in tumor tissues for 8 hours in mice. HIFU with Gd-C5F12-PLN-100 showed the increased tumor ablation area as compared with HIFU alone. The results suggest that Gd-C5F12-PLNs exhibit a potential theragnostics for MR-guided HIFU ablation

Idiopathic severe hypermagnesemia in an extremely low birth weight infant on the first day of life

A preterm female infant born at 27 weeks of gestation with a birth weight of 990 g developed acute hypotonia, apnea, hypotension and bradycardia mimicking septic shock syndrome at 14h after birth. Laboratory tests indicated a severe hypermagnesemia of 45 mg/dL. The renal function, complete blood count and maternal blood concentrations of magnesium were normal, and the blood cultures were negative. The patient recovered with treatment including exchange transfusion. However, the etiology of the severe hypermagnesemia remains unknown

The validation of Implicit Association Test measures for smartphone and Internet addiction in at-risk children and adolescents

Background: Potential concerns are increasing that smartphone and Internet addictions may have deleterious effects on the mental health. Despite the recognition of the important role that implicit associations may have over explicit processes in addiction, such implicit associations have not been comprehensively investigated with respect to Internet addiction. Therefore, we modified the Implicit Association Test (IAT) for smartphone and Internet addictions and investigated its validity in children and adolescents. Methods: In this experimental study, 78 at-risk children and adolescents ranging in age from 7 to 17 years completed an IAT modified with pictures captured from the most popular Internet games among youth. Furthermore, measures of Internet and smartphone addictions, mental health and problem behaviors, impulsive tendencies, self-esteem, daily stress, and quality of life were assessed simultaneously. Results: Significant correlations were found between IAT D2SD scores and standardized scales for Internet (r = .28, p < .05) and smartphone (r = .33, p < .01) addictions. There were no significant correlations between IAT parameters and other scales measuring the constructs that are less relevant to the features of addiction, such as daily stress levels, impulsivity, and quality of life. Multiple regression analysis revealed that the IAT D2SD was independently and positively associated with smartphone addiction (p = .03) after controlling for other clinical correlates. Conclusions: This study demonstrated good convergent and discriminant validity of this IAT as a novel measurement relating to Internet and smartphone addictions. Further longitudinal and prospective studies are needed to evaluate its potential utility in clinical and community settings

Retropharyngeal abscess coinfected with and after rhinoviral infection in a 1-month-old infant

A retropharyngeal abscess is a rare disease entity in young infants but can develop after nasopharyngeal viral infection. Group B Streptococcus and Staphylococcus aureus are the most common pathogens in young infants, however, Mycobacterium tuberculosis is very rare. We report the case of retropharyngeal abscess and coinfection with S. aureus and M. tuberculosis in a very young infant presenting with respiratory symptoms due to upper airway obstruction. Usually tuberculous retropharyngeal abscesses are caused by the direct invasion of the bacteria from the spine via anterior longitudinal ligament of the spine. However, in this case, no associated spinal disease was observed

Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte

Background Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS. Methods Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform. Results Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB (n = 28), and followed by ANK1 (n = 19), SLC4A1 (n = 3), SPTA1 (n = 2), EPB41 (n = 1), and EPB42 (n = 1). Concurrent mutations of genes encoding RBC enzymes (ALDOB, GAPDH, and GSR) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations. Conclusions This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS.Support was provided by: the National Research Foundation of Korea (NRF) grant funded by the Korea government(MSIT) (NRF-2017R1A2A1A17069780) http://www.nrf.re.kr/

Role of annexin II heterotetramer in plasmin-dependent proteolysis

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Flightless-1, a novel transcriptional modulator of PPAR?? through competing with RXR??

Peroxisome proliferator-activated receptor ?? (PPAR??) is a member of the nuclear receptor family and plays key roles in glucose and lipid metabolism. Its transcriptional control of target genes is mediated by ligand-dependent recruitment of coactivators. In this study, we demonstrate that a novel transcriptional modulator of PPAR??, Flightless-I (FLII) binds directly to and suppresses the transcriptional activity of PPAR??. The LXXLL motif within the leucine-rich repeat (LRR) domain of FLII interacts directly with the DNA-binding domain of PPAR??. Interestingly, in the presence of PPAR?? ligands, such as rosiglitazone and SR1664, this interaction was abolished in vitro. When FLII was overexpressed, both the transcriptional activity of PPAR?? and adipogenesis were suppressed significantly, whereas specific knockdown of FLII reversed these effects. Furthermore, DNA occupancy of PPAR?? on its target gene promoters was enhanced by FLII knockdown, and the interaction between PPAR?? and retinoid X receptor ?? (RXR??) was blocked by FLII. Together, these findings strongly suggest that FLII functions in PPAR?? activation as a molecular switch to repress transcriptional activity by interrupting formation of the PPAR??/RXR?? complex, and FLII may serve as a novel therapeutic target in the treatment of adiposity-related metabolic syndromes.close01