Radiographic Prediction of the Results of Long-term Treatment with the Pavlik Harness for Developmental Dislocation of the Hip

In 1957, Pavlik introduced the Pavlik harness as a useful treatment for developmental dislocation of the hip (DDH), and subsequent studies have documented favorable outcomes among patients treated with this device. However, there are only a few articles reporting how early radiographic measurements can be used to determine the prognosis after treatment with the Pavlik harness. In this study, 217 hips from 192 patients whose DDH treatment with the Pavlik harness was initiated before they were 6 months old and whose follow-up lasted at least 14 years (rate, 63.8%) were analyzed using measurements from radiographs taken immediately before and after harness treatment, and at 1, 2, and 3 years of age. Severin's classification at the final follow-up was I or II in 71.9% and III or IV in 28.1% of the hips, respectively. Avascular necrosis of the femoral head (AVN) was seen in 10% of the hips. Stepwise multiple regression analysis was performed to retrospectively determine whether any radiographic factors were related to the final classification as Severin I/II or III/IV. Receiver opera-ting characteristic (ROC) curves were drawn for these factors, and a Wiberg OE angle (Point O was the middle point of the proximal metaphyseal border of the femur) of 2 degrees on the 3-year radiographs was found to be the most useful screening value for judging the acetabular development of DDH cases after treatment with a Pavlik harness, with a sensitivity of 71% a specificity of 93%, and a likelihood ratio of 10.1.</p

Radiological and clinical results of rotational acetabular osteotomy combined with femoral intertrochanteric osteotomy for avascular necrosis following treatment for developmental dysplasia of the hip

This retrospective study assessed the radiographic results of 16 patients with avascular necrosis following treatment for developmental dislocation of the hip (DDH) who were subsequently treated between 1991 and 2005 by rotation acetabular osteotomy (RAO) combined with femoral intertrochan-teric osteotomy (FIO). Initial treatment was by Pavlik harness, cast fixation, or overhead traction. The parameters that showed consistent improvement were the index of centralization, the index of acetabular coverage, adequate reduction of the greater trochanter, and abductor sufficiency. The combined procedure appears to be effective in cases in which preoperative planning shows a reasonable expectation of congruency and osteoarthritis is limited to the early stages.</p

重症慢性肝疾患における高γク口ブリン血症の意義 : とくに血清グ口プリン/IgG とICG除去能との相聞に関連して

BACKGROUND/AIMS:Although hyperglobulinemia is frequently detected in severe chronic liver diseases (CLD) such as liver cirrhosis (LC), the mechanism for this is still uncertain. Hyperglobulinemia may represent a functional aspect of the liver.METHODOLOGY: The correlation between serum globulin (GLB) level and each of various liver function tests including the indocyanine green (ICG) retention rate at 15 min (ICGR15) was studied using 146 patients with liver dysfunction. The correlations among GLB, IgG and ICGR15 were also studied in other 32 patients with LC, in whom the glycosylation pattern of IgG was determined by enzyme-linked immunosorbent assay to detect terminal galactose (Gal) and neuraminic acid (NA) using biotinylated lectins.RESULTS:GLB level was predominantly correlated with ICGR15 (r = 0.449) among various liver function tests in 146 patients with liver dysfunction. In the 32 patients with LC, strong positive correlations between GLB and IgG (r = 0.875), between GLB and ICGR15 (r = 0.435), and between IgG and ICGR15 (r = 0.557) were evident. The glycosylation pattern of IgG showed that the proportions of both Gal and NA were inversely correlated with serum IgG levels (r = -0.516 and -0.390, respectively) in these patients. Significant decreases of the proportions were found in patients with IgG elevation (> 20 g/L, n = 13).CONCLUSIONS:The correlation between GLB and ICGR15 suggested that hyperglobulinemia is related to a common dysfunction estimated by ICG clearance, which represents mainly the liver's blood flow and removal capacity. The removal of immunoglobulins by the liver may be impaired in patients with severe liver dysfunction because the liver is a major catabolic site for immunoglobulins. The glycation pattern suggested that the proportions of asialo IgG and agalactosyl IgG were increased in the LC patients with IgG elevation possibly by deficient receptor-mediated removal in the liver. Although further investigations will be needed, hyperglobulinemia could be predictive for a certain impaired hepatic function estimated by ICG clearance in severe CLD such as LC.博士（医学）・乙第1301号・平成24年7月26日Hepato Gastroenterology © 200

Theobromine enhances the conversion of white adipocytes into beige adipocytes in a PPARγ activation-dependent manner

The adipocytes play an important role in driving the obese-state—white adipose tissue (WAT) stores the excess energy as fat, wherein brown adipose tissue (BAT) is responsible for energy expenditure via the thermoregulatory function of uncoupling protein 1 (UCP1)—the imbalance between these two onsets obesity. Moreover, the anti-obesity effects of brown-like-adipocytes (beige) in WAT are well documented. Browning, the process of transformation of energy-storing into energy-dissipating adipocytes, is a potential preventive strategy against obesity and its related diseases. In the present study, to explore an alternative source of natural products in the regulation of adipocyte transformation, we assessed the potential of theobromine (TB), a bitter alkaloid of the cacao plant, inducing browning in mice (in vivo) and primary adipocytes (in vitro). Dietary supplementation of TB significantly increased skin temperature of the inguinal region in mice and induced the expression of UCP1 protein. It also increased the expression levels of mitochondrial marker proteins in subcutaneous adipose tissues but not in visceral adipose tissues. The microarray analysis showed that TB supplementation upregulated multiple thermogenic and beige adipocyte marker genes in subcutaneous adipose tissue. Furthermore, in mouse-derived primary adipocytes, TB upregulated the expression of the UCP1 protein and mitochondrial mass in a PPARγ ligand-dependent manner. It also increased the phosphorylation levels of PPARγ coactivator 1α without affecting its protein expression. These results indicate that dietary supplementation of TB induces browning in subcutaneous WAT and enhances PPARγ-induced UCP1 expression in vitro, suggesting its potential to treat obesity.ArticleThe Journal of Nutritional Biochemistry. 100: 108898 (2021)journal articl

Intracellular cAMP contents regulate NAMPT expression via induction of C/EBPβ in adipocytes

A decline in intracellular nicotinamide adenine mononucleotide (NAD+) causes adipose tissue dysfunction. Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the rate-limiting step in the NAD+ biosynthesis pathway. However, the molecular mechanism that mediates regulation of NAMPT expression in adipocytes is yet to be elucidated. This study found that intracellular cAMP regulates NAMPT expression and promoter activity in 3T3-L1 adipocytes. cAMP-mediated Nampt promoter activity was suppressed by protein kinase A inhibitor H89, whereas AMP-activated protein kinase inhibitor compound C did not affect cAMP-mediated Nampt promoter activity. Intracellular cAMP induced CCAAT/enhancer-binding protein β (C/EBPβ) expression. Knockdown of C/EBPβ suppressed NAMPT expression and promoter activity. Furthermore, the Nampt promoter was activated by C/EBPβ, while LIP activated the dominant-negative form of C/EBPβ. Promoter sequence analysis revealed that the region from -96 to -76 on Nampt was required for C/EBPβ-mediated promoter activity. Additionally, chromatin immunoprecipitation assay demonstrated that C/EBPβ was bound to the promoter sequences of Nampt. Finally, NAMPT inhibitor FK866 suppressed adipogenesis in 3T3-L1 cells, and this suppressive effect was restored by nicotinamide mononucleotide treatment. These findings showed that intracellular cAMP increased NAMPT levels by induction of C/EBPβ expression and indicated that the induction of NAMPT expression was important for adipogenesis.ArticleBiochemical and Biophysical Research Communications. 522(3): 770-775. (2020)journal articl

Medaka: a promising model animal for comparative population genomics

<p>Abstract</p> <p>Background</p> <p>Within-species genome diversity has been best studied in humans. The international HapMap project has revealed a tremendous amount of single-nucleotide polymorphisms (SNPs) among humans, many of which show signals of positive selection during human evolution. In most of the cases, however, functional differences between the alleles remain experimentally unverified due to the inherent difficulty of human genetic studies. It would therefore be highly useful to have a vertebrate model with the following characteristics: (1) high within-species genetic diversity, (2) a variety of gene-manipulation protocols already developed, and (3) a completely sequenced genome. Medaka (<it>Oryzias latipes</it>) and its congeneric species, tiny fresh-water teleosts distributed broadly in East and Southeast Asia, meet these criteria.</p> <p>Findings</p> <p>Using <it>Oryzias </it>species from 27 local populations, we conducted a simple screening of nonsynonymous SNPs for 11 genes with apparent orthology between medaka and humans. We found medaka SNPs for which the same sites in human orthologs are known to be highly differentiated among the HapMap populations. Importantly, some of these SNPs show signals of positive selection.</p> <p>Conclusion</p> <p>These results indicate that medaka is a promising model system for comparative population genomics exploring the functional and adaptive significance of allelic differentiations.</p

Effects of a self-management program on antiemetic-induced constipation during chemotherapy among breast cancer patients: a randomized controlled clinical trial.

Research on patient-reported outcomes indicates that constipation is a common adverse effect of chemotherapy, and the use of 5-hydroxytryptamine (serotonin; 5HT3) receptor antagonists aggravates this condition. As cancer patients take multiple drugs as a part of their clinical management, a non-pharmacological self-management (SM) of constipation would be recommended. We aimed to evaluate the effectiveness of a SM program on antiemetic-induced constipation in cancer patients. Thirty patients with breast cancer, receiving 5HT3 receptor antagonists to prevent emesis during chemotherapy were randomly assigned to the intervention or control group. The SM program consisted of abdominal massage, abdominal muscle stretching, and education on proper defecation position. The intervention group started the program before the first chemotherapy cycle, whereas patients in the wait-list control group received the program on the day before their second chemotherapy cycle. The primary outcome was constipation severity, assessed by the constipation assessment scale (CAS, sum of eight components). The secondary outcome included each CAS component (0-2 points) and mood states. A self-reported assessment of satisfaction with the program was performed. The program produced a statistically and clinically significant alleviation of constipation severity (mean difference in CAS, -3.00; P = 0.02), decrease in the likelihood of a small volume of stool (P = 0.03), and decrease in depression and dejection (P = 0.02). With regards to program satisfaction, 43.6 and 26.4 % patients rated the program as excellent and good, respectively. Our SM program is effective for mitigating the symptoms of antiemetic-induced constipation during chemotherapy

The Minimally Invasive Plate Osteosynthesis (MIPO) Technique with a Locking Compression Plate for Femoral Lengthening

A minimally invasive plate osteosynthesis technique using a locking compression plate (LCP) has been used widely in trauma cases. Its advantages are that the MIPO technique does not interfere with the fracture site and thus provides improved biological healing, and that the LCP has excellent angular stability. Its use in bone lengthening, however, has not been established. In such cases, it is desirable to shorten the external skeletal fixation period as much as possible. Here, the MIPO technique using an LCP was applied to femoral distraction osteogenesis in an attempt to shorten the external skeletal fixation period. For femoral lengthening, the MIPO technique was performed in 2 stages. Orthofix external fixators (Orthofix, England) were used to insert screws from the anterolateral side rather than from the lateral side of the femur for bone lengthening. When sufficient callus formation was detected postoperatively at the site of bone lengthening, and the absence of infection was ensured, limb draping was performed, including a whole external fixator, and then the MIPO technique was applied with an LCP. In 3 cases (5 limbs), the average duration of external skeletal fixation was 134days, the average external-fixation index was 24days/cm, and the average consolidation index was 22days/cm. The MIPO technique using an LCP made it possible to shorten the external skeletal fixation-wearing period in femoral lengthening.</p

Imaging Spectroscopy on Preflare Coronal Nonthermal Sources Associated with the 2002 July 23 Flare

We present a detailed examination on the coronal nonthermal emissions during the preflare phase of the X4.8 flare that occurred on 2002 July 23. The microwave (17 GHz and 34 GHz) data obtained with Nobeyama Radioheliograph, at Nobeyama Solar Radio Observatory and the hard X-ray (HXR) data taken with {\it Reuven Ramaty High Energy Solar Spectroscopic Imager} obviously showed nonthermal sources that are located above the flare loops during the preflare phase. We performed imaging spectroscopic analyses on the nonthermal emission sources both in microwaves and in HXRs, and confirmed that electrons are accelerated from several tens of keV to more than 1 MeV even in this phase. If we assume the thin-target model for the HXR emission source, the derived electron spectral indices ($\sim 4.7$) is the same value as that from microwaves ($\sim 4.7$) within the observational uncertainties, which implies that the distribution of the accelerated electrons follows a single power-law. The number density of the microwave-emitting electrons is, however, larger than that of the HXR-emitting electrons, unless we assume low ambient plasma density of about $1.0 \times 10^9$ cm$^{-3}$ for the HXR-emitting region. If we adopt the thick-target model for the HXR emission source, on the other hand, the electron spectral index ($\sim 6.7$) is much different, while the gap of the number density of the accelerated electrons is somewhat reduced.Comment: 21 pages, 6 figures, ApJ accepte

Quantitative Dynamics of Chromatin Remodeling during Germ Cell Specification from Mouse Embryonic Stem Cells

SummaryGerm cell specification is accompanied by epigenetic remodeling, the scale and specificity of which are unclear. Here, we quantitatively delineate chromatin dynamics during induction of mouse embryonic stem cells (ESCs) to epiblast-like cells (EpiLCs) and from there into primordial germ cell-like cells (PGCLCs), revealing large-scale reorganization of chromatin signatures including H3K27me3 and H3K9me2 patterns. EpiLCs contain abundant bivalent gene promoters characterized by low H3K27me3, indicating a state primed for differentiation. PGCLCs initially lose H3K4me3 from many bivalent genes but subsequently regain this mark with concomitant upregulation of H3K27me3, particularly at developmental regulatory genes. PGCLCs progressively lose H3K9me2, including at lamina-associated perinuclear heterochromatin, resulting in changes in nuclear architecture. T recruits H3K27ac to activate BLIMP1 and early mesodermal programs during PGCLC specification, which is followed by BLIMP1-mediated repression of a broad range of targets, possibly through recruitment and spreading of H3K27me3. These findings provide a foundation for reconstructing regulatory networks of the germline epigenome