Electroencephalogram pattern predicting neurological outcomes of children with seizures secondary to abusive head trauma.

BACKGROUND: The clinical presentations of abusive head trauma can abruptly worsen, so the occurrence of seizures and changes of EEG can be variable according to patients' conditions. Since the changes of EEG background waves reflect the cortical function of children, we aimed to find out whether the timing of EEG background, epileptiform discharges and seizure patterns were associated with the outcomes of patients with AHT. MATERIAL AND METHODS: Using seizure type and acute stage electroencephalographic (EEG) characteristics to assess adverse neurological outcomes in children with seizures secondary to abusive head trauma (AHT). Children who were hospitalized with AHT at a tertiary referral hospital from October 2000 to April 2010 were evaluated retrospectively. A total of 50 children below 6 years of age admitted due to AHT were included. KOSCHI outcome scale was used to evaluate the primary outcome and neurological impairment was used as secondary outcome after 6 months discharge. RESULTS: Children with apnea, cardiac arrest, reverse blood flow and skull fracture in clinic had a higher mortality rate even in the no-seizure group (3/5 [60%] vs. 3/45 [6.7%], odds ratio [OR] = 11; 95% CI = 2.3-52; p = 0.025). Seizure occurrence reduced mostly at the second day after admission in seizure groups; but children with persistent seizures for 1 week showed poor neurological outcomes. The occurrence of initial seizure was frequency associated with younger age; focal seizure, diffuse cortical dysfunction in acute-stage EEG, and low Glasgow Coma Scale (GCS) score were significantly related to poor outcomes after 6 months. Diffuse cortical dysfunction was also associated with motor, speech, and cognitive dysfunction. CONCLUSIONS: Diffuse cortical dysfunction in acute-stage EEG combined with low GCS score and focal seizure may related to poor outcomes and neurological dysfunctions in children with AHT.

Chronic cough relief by allosteric modulation of P2X3 without taste disturbance.

P2X receptors are cation channels that sense extracellular ATP. Many therapeutic candidates targeting P2X receptors have begun clinical trials or acquired approval for the treatment of refractory chronic cough (RCC) and other disorders. However, the present negative allosteric modulation of P2X receptors is primarily limited to the central pocket or the site below the left flipper domain. Here, we uncover a mechanism of allosteric regulation of P2X3 in the inner pocket of the head domain (IP-HD), and show that the antitussive effects of quercetin and PSFL2915 (our nM-affinity P2X3 inhibitor optimized based on quercetin) on male mice and guinea pigs were achieved by preventing allosteric changes of IP-HD in P2X3. While being therapeutically comparable to the newly licensed P2X3 RCC drug gefapixant, quercetin and PSFL2915 do not have an adverse effect on taste as gefapixant does. Thus, allosteric modulation of P2X3 via IP-HD may be a druggable strategy to alleviate RCC.

Comparison of active versus passive robotic-endoscope-holder-assisted unisurgeon uniportal thoracoscopic surgery in terms of surgical efficacy and patient safety.

Background: Few studies have compared robotic-arm-assisted unisurgeon uniportal surgeries with conventional human-assisted uniportal video-assisted thoracoscopic surgeries (VATSs) in terms of surgical efficacy and patient safety. In the present study, we compared the aforementioned surgeries. Methods: We explored two robotic endoscope holders-a passive robotic platform (ENDOFIXexo, EA group) and a pedal-controlled active robotic platform (MTG-100, MA group)-for unisurgeon uniportal surgeries and compared the surgical outcomes with those of human-assisted uniportal surgeries (HA group) in 228 patients with a lung lesion (size, <5 cm). The primary parameters for this comparison were surgical efficacy, patient safety, and short-term patient outcomes. Results: No significant differences were observed among the EA, MA, and HA groups. The success rate of robotic-arm-assisted unisurgeon uniportal wedge resection was 100%, regardless of the group. No major differences were noted in preparation time between the EA and MA groups. Segmentectomy was more favorable in the EA group than in the MA group. The rates of surgical conversion were 5% and 60% in the EA and MA groups, respectively. The EA and MA groups did not differ considerably from the HA group in terms of postoperative complications. Conclusions: Unisurgeon uniportal wedge resection may be effectively performed using a robotic endoscope holder, without the need for any human assistants with an expert hand. However, the rate of surgical conversion increases with the complexity of uniportal anatomic resections. The passive platform appears to be more suitable for unisurgeon uniportal surgery than the active pedal-controlled platform given the equipment in contemporary operating rooms.

Effect of Le Fort I Maxillary Repositioning on Three-Dimensional Nasal Tip Rotation: A Comparative Study with Implication for the Asian Nose.

BACKGROUND: Le Fort I maxillary repositioning influences nasal morphology. In Asian cultures, upward nasal tip rotation with increased nostril exposure is considered aesthetically unpleasant and can have psychosocial consequences. This three-dimensional imaging-based study evaluated the effect of different Le Fort I maxillary movements on nasal tip rotation. METHODS: Consecutive patients who underwent two-jaw orthognathic surgery (n = 107) were enrolled. To achieve a standard head orientation, preoperative and 1-week and 12-month postoperative cone-beam computed tomography-derived three-dimensional craniofacial models were superimposed. Tip rotation angle was calculated according to the Frankfort horizontal plane for all three-dimensional digital models. The final tip rotation angle change was defined as 12-month postoperative value minus preoperative value. Translational maxillary movement types (advancement versus setback and intrusion versus extrusion), postoperative maxillary segment locations (anterosuperior, anteroinferior, posterosuperior, or posteroinferior), and actual linear maxillary changes were noted. RESULTS: Advancement (1.79 ± 5.20 degrees) and intrusion (2.23 ± 4.96 degrees) movements demonstrated significantly larger final tip rotation angle changes than setback (-0.88 ± 5.15 degrees) and extrusion (0.09 ± 5.44 degrees) movements (all p < 0.05). Postoperative anterosuperior location (2.95 ± 4.52 degrees) of the maxillary segment demonstrated a significantly larger final tip rotation angle change than anteroinferior (0.48 ± 5.65 degrees), posterosuperior (-1.08 ± 4.77 degrees), and posteroinferior (-0.64 ± 5.80 degrees) locations (all p < 0.05). Translational maxillary movement and actual linear maxillary change were not correlated with final tip rotation angle change. CONCLUSION: Effects of Le Fort I maxillary repositioning on nasal tip rotation depend on movement types and maxillary segment location. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Impact of the Different Types of Le Fort I Maxillary Surgical Movement on Nasal Width Changes: A Photogrammetric Analysis.

BACKGROUND: Le Fort I maxillary movements affect nasal width, but nasal width changes with specific movement types have not been formally addressed to date. OBJECTIVES: The purpose of this study was to analyze and compare the changes in nasal width with different maxillary movements. METHODS: A retrospective study was performed among consecutive patients who underwent bimaxillary orthognathic surgery (n = 138) and who were grouped based on the type of maxillary movement (ie, maxillary advancement with intrusion [MAI], maxillary advancement with extrusion [MAE], and maxillary setback with intrusion [MSI]). Preoperative and 12-month postoperative nasal widths were analyzed photogrammetrically by 2 blinded evaluators. RESULTS: Maxillary advancement with intrusion and MAE presented a significantly (P < 0.05) higher alar base widening than MSI did, with no significant (P > 0.05) differences between MAI and MAE. Maxillary advancement movements (MAI and MAE) showed significantly (P < 0.05) higher alar base widening than maxillary setback movement (MSI). However, no significant (P > 0.05) difference was observed between maxillary intrusion (MAI and MSI) and maxillary extrusion (MAE) movements. CONCLUSIONS: This study shows that the nasal width varies distinctly depending on the type of Le Fort I maxillary surgical movement.

Type of maxillary segment mobilization affects three-dimensional nasal morphology.

BACKGROUND: Surgical mobilization of the maxillary segment affects nasal morphology. This study assessed the impact of the type of maxillary mobilization on the three-dimensional (3D) nasal morphometry. METHODS: Pre- and postsurgery cone beam computed tomography-derived facial image datasets of consecutive patients who underwent two-jaw orthognathic surgery were reviewed. Using preoperative 3D facial models as the positional reference of the skeletal framework, 12-month postoperative 3D facial models were classified into four types of maxillary mobilizations (advancement [n = 83], setback [n = 24], intrusion [n = 55], and extrusion [n = 52]) and four types of final maxillary positions (anterosuperior [n = 44], anteroinferior [n = 39], posterosuperior [n = 11], and posteroinferior [n = 13]). Six 3D soft tissue nasal morphometric parameters were measured, with excellent intra- and interexaminer reliability scores (ICC>0.897) for all the measurements. The 3D nasal change for each nasal parameter was computed as the difference between postoperative and preoperative measurement values. RESULTS: The intrusion maxillary mobilization resulted in a significantly (all p<0.05) larger 3D nasal change in terms of alar width, alar base width, and nostril angle parameters, and a smaller change in terms of the nasal tip height parameter than the extrusion maxillary mobilization; however, no significant (all p>0.05) difference was observed between advancement and setback maxillary mobilizations. The anterosuperior and posterosuperior maxillary positions had a significantly (all p<0.05) larger 3D nasal change in terms of the alar base width and nostril angle than the anteroinferior and posteroinferior maxillary positions. CONCLUSION: The type of maxillary mobilization affects the 3D nasal morphometry.

Skeletal Muscle Is an Antigen Reservoir in Integrase-Defective Lentiviral Vector-Induced Long-Term Immunity.

We previously developed integrase-defective lentiviral vectors (IDLVs) as an antigen delivery system for inducing strong and prolonged immunity in animal models. Here, we examined the association between persistence of antigen expression and durability of immune response. Following a single intramuscular (i.m.) or subcutaneous (s.c.) injection of IDLV delivering GFP in mice, we evaluated antigen expression and inflammation at the site of injection and persistence of antigen-specific T cells at early and late time points. Durable antigen expression was detected up to 90 days only after i.m. immunization. Mononuclear inflammation was evident soon after IDLV injection in both i.m. and s.c. immunized mice, but remained detectable up to 30 days postinjection only in i.m. immunized mice. Similarly, GFP-specific T cells were more persistent in the i.m. immunized mice. Interestingly, GFP+ muscle fibers were co-expressing major histocompatibility complex (MHC) class I, suggesting that muscle cells are competent for presenting antigens to T cells in vivo. In in vitro experiments, we demonstrated that although both primary myoblasts and myocytes present the antigen to GFP-specific T cells through MHC class I, myoblasts are more resistant to Fas-dependent cytotoxic T lymphocyte (CTL) killing activity. Overall, these data indicate that muscle cells may serve as an antigen reservoir that contributes to the long-term immunity induced by IDLV vaccination.

Hydroxymethyl-Functionalized PEDOT-MeOH:PSS for Perovskite Solar Cells.

Poly(hydroxymethylated-3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT-MeOH:PSS) conducting polymers are synthesized and incorporated in inverted structured perovskite solar cells (PVSCs) as hole transport materials. The highest occupied molecular orbital of PEDOT-MeOH is lowered by adding a hydroxymethyl (-MeOH) functional group to ethylenedioxythiophene (EDOT), and thus, the work function of PEDOT-MeOH:PSS is increased. Additionally, hydrogen bonding can be formed among EDOT-MeOH monomers and between EDOT-MeOH monomers and sulfate groups on PSS, which promotes PEDOT-MeOH chain growth and enhances PSS doping. The electronic, microstructural, and surface morphological properties of PEDOT-MeOH:PSS are modified by changing the amounts of PSS and the ferric oxidizing agent used in the polymerization and by adding ethylene glycol in the postsynthesis treatment. The PVSCs based on ethylene-glycol-treated PEDOT-MeOH:PSS overperform the PVSCs based on commercial PEDOT:PSS because of the better energetic alignment and the enhancement of PEDOT-MeOH:PSS electrical conductivity. This work opens the way to develop new hole transport materials for highly efficient inverted PVSCs.

Formulation and evaluation of multilamellar vesicles ropivacaine in pain management.

PURPOSE: The improvement of postoperative pain control plays an important role in recovery outcomes and patient satisfaction. Multilamellar vesicles ropivacaine, MVR, is being developed to sustain the release of ropivacaine in situ while maintaining the local concentration of ropivacaine within the therapeutic window. METHODS: These studies summarized the processes of MVR formulation development and the evaluation of its releasing profile in vitro and the pharmacokinetics and anesthetic effect in vivo. RESULTS: The MVR demonstrates a sustained-release profile in an in vitro serum environment model after 24 hrs of incubation which translates in the in vivo rat pharmacokinetic profile of ropivacaine as a prolonged half-life that is 10-fold longer in duration than plain ropivacaine solution. The anesthetic effect of single-dose MVR is apparent by providing a prolonged analgesia effect compared to plain ropivacaine solution in an in vivo guinea pig pin-prick wheal model after a single intracutaneous injection. From a safety evaluation, MVR is well tolerated after a subcutaneously injection at a dose level of 20 mg/kg in rats, with no observable changes in clinical observation, body weight, organ weight, hematology and serum chemistry analysis. CONCLUSION: These results suggest that single administration of MVR is a promising candidate in postoperative pain management.

Narrowband Ultraviolet Photodetectors Based on Nanocomposite Thin Films with High Gain and Low Driving Voltage.

Narrowband ultraviolet (UV) photodetectors are highly desired in multiple areas. Photodetectors based on organic-inorganic nanocomposites offer high sensitivity, widely adjustable response range, light weight, and low-temperature solution processibility. However, the broad absorption range of organic and inorganic semiconductor materials makes it difficult to achieve a narrowband detection feature for nanocomposite photodetectors. In this work, nanocomposite thin films containing the wide band gap conjugated polymer poly[(9,9-dioctylfluorenyl-2,7-diyl)- alt- co-(bithiophene)] (F8T2) blended with wide band gap ZnO nanoparticles (NPs) serve as the active layers of the photodetectors. Narrowband UV photodetectors with high gain and low driving voltage are demonstrated by adopting a symmetric device structure, controlling the active layer composition and microstructure, and manipulating the light penetration depth in the active layer. The fabricated photodetector exhibits a high external quantum efficiency of 782% at 358 nm under a low forward bias of 3 V with the full-width at half-maximum of 16 nm. Combined with a low dark current, a high specific detectivity of 8.45 × 1012 Jones is achieved. The impacts of the F8T2:ZnO NPs weight ratio and the device structure on the UV-selectivity and the device performance are investigated and discussed. Our method offers a pathway to design and fabricate narrowband UV photodetectors.

[Improving the Storage Integrity of Electroencephalography (EEG) Recordings in the Pediatric Ward].

BACKGROUND & PROBLEMS: A total of 20 cases of children with epilepsy implemented electroencephalography (EEG) recording examinations in our ward between January 1st and March 10th, 2016. Fifteen (75%) of the recordings were incompletely stored, indicating that the EEG recordings storage integrity in our unit was 25%. Incomplete storage of these recordings results in prolonged hospital stays and negatively affects the ability of doctors to provide accurate diagnoses. PURPOSE: This project was developed to increase the EEG recording storage integrity for epileptic children to 100%. RESOLUTIONS: Improvement plans included reinforcing related promotions, formulating a standard flowchart for EEG recording education, making "warm bear signs", designing simple cartoon health-education flashcards, and providing in-service education. RESULTS: The EEG recording storage integrity for epileptic children in our ward rose to 100% after implementation of the resolution measures, which achieved our purpose. CONCLUSIONS: We want to share this experience to improve the storage integrity of EEG recordings at other hospitals and clinics. The greatest benefit of this project was that the family members of children with epilepsy perceived more strongly the effort and care of the nursing staffs during examinations, which reduces the costs of healthcare.

KH-type splicing regulatory protein is a new component of chromatoid body.

The chromatoid body (CB) is a specific cloud-like structure in the cytoplasm of haploid spermatids. Recent findings indicate that CB is identified as a male germ cell-specific RNA storage and processing center, but its function has remained elusive for decades. In somatic cells, KH-type splicing regulatory protein (KSRP) is involved in regulating gene expression and maturation of select microRNAs (miRNAs). However, the function of KSRP in spermatogenesis remains unclear. In this study, we showed that KSRP partly localizes in CB, as a component of CB. KSRP interacts with proteins (mouse VASA homolog (MVH), polyadenylate-binding protein 1 (PABP1) and polyadenylate-binding protein 2 (PABP2)), mRNAs (Tnp2 and Odf1) and microRNAs (microRNA-182) in mouse CB. Moreover, KSRP may regulate the integrity of CB via DDX5-miRNA-182 pathway. In addition, we found abnormal expressions of CB component in testes of Ksrp-knockout mice and of patients with hypospermatogenesis. Thus, our results provide mechanistic insight into the role of KSRP in spermatogenesis.

Identifying genetic hypomethylation and upregulation of Toll-like receptors in Kawasaki disease.

Kawasaki disease (KD) is an acute febrile systemic vasculitis that occurs in children and is characterized by elevated levels of proinflammatory cytokines. Toll-like receptors (TLRs) serve as the sensor arm of the innate immune system and induce proinflammatory cytokine expressions.We recruited a total of 18 paired KD patients, before intravenous immunoglobulin (IVIG) and at least 3 weeks after IVIG treatment, 18 healthy controls, and 18 febrile controls. For TLR genes and their cytosine-phosphate-guanine (CpG) markers, we used Affymetrix GeneChip® Human Transcriptome Array 2.0 and Illumina HumanMethylation450 BeadChip to evaluate gene expression levels and methylation patterns, respectively.KD patients demonstrated a significantly differential expression of TLR mRNA levels compared to both the healthy and febrile controls, with only TLR 3 and 7 not differing between the KD patients and the controls. After patients underwent IVIG treatment, the TLR mRNA levels, except for TLR3, decreased significantly in KD patients. In contrast, the methylation status of the CpG sites of TLR1, 2, 4, 6, 8, and 9 demonstrated an opposite tendency between the two stages of both the KD samples and the controls.TLRs, particularly TLR1, 2, 4, 6, 8, and 9, may stimulate the immunopathogenesis of KD. These results are among the first to use TLRs to prove that a bacterial inflammatory response may trigger KD.

Phytoplasma SAP11 alters 3-isobutyl-2-methoxypyrazine biosynthesis in Nicotiana benthamiana by suppressing NbOMT1.

Phytoplasmas are bacterial phytopathogens that release virulence effectors into sieve cells and act systemically to affect the physiological and morphological state of host plants to promote successful pathogenesis. We show here that transgenic Nicotiana benthamiana lines expressing the secreted effector SAP11 from Candidatus Phytoplasma mali exhibit an altered aroma phenotype. This phenomenon is correlated with defects in the development of glandular trichomes and the biosynthesis of 3-isobutyl-2-methoxypyrazine (IBMP). IBMP is a volatile organic compound (VOC) synthesized by an O-methyltransferase, via a methylation step, from a non-volatile precursor, 3-isobutyl-2-hydroxypyrazine (IBHP). Based on comparative and functional genomics analyses, NbOMT1, which encodes an O-methyltransferase, was found to be highly suppressed in SAP11-transgenic plants. We further silenced NbOMT1 through virus-induced gene silencing and demonstrated that this enzyme influenced the accumulation of IBMP in N. benthamiana In vitro biochemical analyses also showed that NbOMT1 can catalyse IBHP O-methylation in the presence of S-adenosyl-L-methionine. Our study suggests that the phytoplasma effector SAP11 has the ability to modulate host VOC emissions. In addition, we also demonstrated that SAP11 destabilized TCP transcription factors and suppressed jasmonic acid responses in N. benthamiana These findings provide valuable insights into understanding how phytoplasma effectors influence plant volatiles.

[The Effect of Taking an Affectionate Approach to Discharge Education in the Pediatric Ward].

BACKGROUND & PROBLEMS: From January to March 2013, only 36.7% of pediatric patients in our hospital were given health education by nurses and only 47.1% of patient families indicated feeling "good" about the health education that they had received. After analyzing the situation, we identified the following key issues: (1) Lack of an SOP; (2) Inconsistent nursing guidelines; (3) Difficulties in comprehending health education tools; and (4) Poor caregiver adoption of TPN skills. PURPOSE: Our aim was to apply "impressive service" at our pediatric department to improve the effect of post-discharge health education in order to enhance the quality of care received by patients and their families. RESOLUTIONS: A variety of measures were implemented to improve the satisfaction rate of post-discharge health education. These measures included: reinforcing advocacy during hospitalization, developing an SOP on health education and an auditing system, manufacturing an "Impressive Service Card" and a "Pamphlet for hospitalized children", and employing a health education method and leaflets that were beneficial to the caregiver. RESULTS: The result of our practice increased the rate of health education to 100% and a rate of satisfaction of 99.4%. These significant improvements indicate that the "Impressive Service" program may be an effective strategy to improve the quality and effectiveness of post-discharge health education. CONCLUSIONS: This program was implemented as part of standard discharge procedures as a strategy to improve the attitudes of nursing staff, to enhance the satisfaction of pediatric patients and their family members, and the enhance the image of our hospital and nursing personnel.

KSRP is critical in governing hepatic lipid metabolism through controlling Per2 expression.

Hepatic lipid metabolism is controlled by integrated metabolic pathways. Excess accumulation of hepatic TG is a hallmark of nonalcoholic fatty liver disease, which is associated with obesity and insulin resistance. Here, we show that KH-type splicing regulatory protein (KSRP) ablation reduces hepatic TG levels and diet-induced hepatosteatosis. Expression of period 2 (Per2) is increased during the dark period, and circadian oscillations of several core clock genes are altered with a delayed phase in Ksrp(-/-) livers. Diurnal expression of some lipid metabolism genes is also disturbed with reduced expression of genes involved in de novo lipogenesis. Using primary hepatocytes, we demonstrate that KSRP promotes decay of Per2 mRNA through an RNA-protein interaction and show that increased Per2 expression is responsible for the phase delay in cycling of several clock genes in the absence of KSRP. Similar to Ksrp(-/-) livers, both expression of lipogenic genes and intracellular TG levels are also reduced in Ksrp(-/-) hepatocytes due to increased Per2 expression. Using heterologous mRNA reporters, we show that the AU-rich element-containing 3' untranslated region of Per2 is responsible for KSRP-dependent mRNA decay. These findings implicate that KSRP is an important regulator of circadian expression of lipid metabolism genes in the liver likely through controlling Per2 mRNA stability.

Biological characterization of cetuximab-conjugated gold nanoparticles in a tumor animal model.

Gold nanoparticles (AuNPs) are widely applied to the diagnosis and treatment of cancer and can be modified to contain target-specific ligands via gold-thiolate bonding. This study investigated the pharmacokinetics and microdistribution of antibody-mediated active targeting gold nanoparticles in mice with subcutaneous lung carcinoma. We conjugated AuNPs with cetuximab (C225), an antibody-targeting epidermal growth factor receptor (EGFR), and then labeled with In-111, which created EGFR-targeted AuNPs. In vitro studies showed that after a 2 h incubation, the uptake of C225-conjugated AuNPs in high EGFR-expression A549 cells was 14.9-fold higher than that of PEGylated AuNPs; furthermore, uptake was also higher at 3.8-fold when MCF7 cells with lower EGFR-expression were used. MicroSPECT/CT imaging and a biodistribution study conducted by using a A549 tumor xenograft mouse model provided evidence of elevated uptake of the C225-conjugated AuNPs into the tumor cells as a result of active targeting. Moreover, the microdistribution of PEGylated AuNPs revealed that a large portion of AuNPs remained in the tumor interstitium, whereas the C225-conjugated AuNPs displayed enhanced internalization via antibody-mediated endocytosis. Our findings suggest that the anti-EGFR antibody-conjugated AuNPs are likely to be a plausible nano-sized vehicle for drug delivery to EGFR-expressing tumors.

KSRP and MicroRNA 145 are negative regulators of lipolysis in white adipose tissue.

White adipose tissue (WAT) releases fatty acids from stored triacylglycerol for an energy source. Here, we report that targeted deletion of KH-type splicing regulatory protein (KSRP), an RNA-binding protein that regulates gene expression at multiple levels, enhances lipolysis in epididymal WAT (eWAT) because of the upregulation of genes promoting lipolytic activity. Expression of microRNA 145 (miR-145) is decreased because of impaired primary miR-145 processing in Ksrp(-/-) eWAT. We show that miR-145 directly targets and represses Foxo1 and Cgi58, activators of lipolytic activity, and forced expression of miR-145 attenuates lipolysis. This study reveals a novel in vivo function of KSRP in controlling adipose lipolysis through posttranscriptional regulation of miR-145 expression.

KSRP ablation enhances brown fat gene program in white adipose tissue through reduced miR-150 expression.

Brown adipose tissue oxidizes chemical energy for heat generation and energy expenditure. Promoting brown-like transformation in white adipose tissue (WAT) is a promising strategy for combating obesity. Here, we find that targeted deletion of KH-type splicing regulatory protein (KSRP), an RNA-binding protein that regulates gene expression at multiple levels, causes a reduction in body adiposity. The expression of brown fat-selective genes is increased in subcutaneous/inguinal WAT (iWAT) of Ksrp(-/-) mice because of the elevated expression of PR domain containing 16 and peroxisome proliferator-activated receptor gamma coactivator 1α, which are key regulators promoting the brown fat gene program. The expression of microRNA (miR)-150 in iWAT is decreased due to impaired primary miR-150 processing in the absence of KSRP. We show that miR-150 directly targets and represses Prdm16 and Ppargc1a, and that forced expression of miR-150 attenuates the elevated expression of brown fat genes caused by KSRP deletion. This study reveals the in vivo function of KSRP in controlling brown-like transformation of iWAT through post-transcriptional regulation of miR-150 expression.

A pharmacokinetics study of radiolabeled micelles of a poly(ethylene glycol)-block-poly(caprolactone) copolymer in a colon carcinoma-bearing mouse model.

A copolymer of poly(ethylene glycol)-b-poly(caprolactone) (PEG-PCL) was modified with a benzyl moiety and labeled with I-131. A micelle system, (131)I-benzyl-micelles, formed from (131)I-benzyl-PEG-PCL and PEG-PCL-PC, was created and used for in vitro characterization and in vivo evaluation. Administration of (131)I-benzyl-micelles to a colon carcinoma-bearing mouse model gives a 4.9-fold higher tumor-to-muscle ratio at 48 h post-injection than treatment with the unimer (131)I-benzyl-PEG-PCL. Scintigraphic imaging, biodistribution results and pharmacokinetical evaluation all demonstrated that (131)I-benzyl-micelles are a plausible radioactive surrogate for PEG-PCL copolymer micelles. Modifying the amphiphilic copolymer with a benzyl moiety and labeled it with iodine-131 should make possible the real-time and noninvasive evaluation of the pharmacokinetics of copolymer micelles in vivo.