Sonographic measurements of normal gallbladder sizes in children.

PurposeOur goal was to establish the range of sonographic measurements of normal gallbladders in children.MethodsSix hundred ten children aged 0-16 years (male:female ratio, 1.5:1) with normal clinical and laboratory findings were included in this study. The sonographic parameters were the length, width, and calculated volume of the gallbladder, and the clinical parameters were the age, height, weight, and body surface area of the children. Statistical significance was determined through correlation and regression analyses.ResultsThe length of the gallbladder showed significant positive correlations with age (r = 0.65), height (r = 0.67), weight (r = 0.63), and body surface area (r = 0.65; p < 0.01). The calculated volume of the gallbladder also showed moderate correlations with age (r = 0.53), height (r = 0.55), weight (r = 0.61), and body surface area (r = 0.57; p < 0.01). The gallbladder width showed modest but significant correlations with age (r = 0.48), height (r = 0.53), weight (r = 0.53), and body surface area (r = 0.55; p < 0.01). The highest correlation coefficients were found between the gallbladder length and subject age (r = 0.65; p < 0.01) and between the gallbladder length and subject height (r = 0.67; p < 0.01). For all correlations, statistical significance remained after regression analysis (p < 0.01).ConclusionsValues for the size of the normal pediatric gallbladder are defined and will be helpful in the diagnosis of gallbladder abnormalities

The first Irish genome and ways of improving sequence accuracy

Whole-genome sequencing of an Irish person reveals hundreds of thousands of novel genomic variants. Imputation using previous known information improves the accuracy of low-read-depth sequencing

Enzymatic analysis of the effect of naturally occurring Leu138Pro mutation identified in SHV β-lactamase on hydrolysis of penicillin and ampicillin

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to analyze the significance of leucine to proline substitution at position 138(Leu138Pro) on the hydrolysis of penicillin and ampicillin that we identified in the <it>bla</it>_SHVgene of clinical <it>Escherichia coli </it>swine isolate.</p> <p>Results</p> <p>Kinetic analysis of the mutant proteins showed that <it>K</it>_{<it>m </it>}value of the purified L138P mutant was comparatively higher than SHV-1, SHV-33 and SHV-33(L138P) enzyme for penicillin and ampicillin. Docking simulation of the SHV-1 and SHV-(L138P) enzymes also confirmed that β-lactamases preferred penicillin to ampicillin and the SHV-1 had a higher binding affinity for antibiotics compared to the SHV-(L138P) and other mutants.</p> <p>Conclusions</p> <p>Our result demonstrated that L138P has a reduced role in penicillin and ampicillin hydrolyzing properties of SHV β-lactamases. These naturally occurring mutations rendering reduced function of the existing protein could trigger the emergence or acquisition of more effective alternative mechanisms for β-lactam hydrolysis.</p

Implant selection for successful reverse total shoulder arthroplasty

Reverse total shoulder arthroplasty (RTSA) emerged as a new concept of arthroplasty that does not restore normal anatomy but does restore function. It enables the function of the torn rotator cuff to be performed by the deltoid and shows encouraging clinical outcomes. Since its introduction, various modifications have been designed to improve the outcome of the RTSA. From the original cemented baseplate with peg or keel, a cementless baseplate was designed that could be fixed with central and peripheral screws. In addition, a modular-type glenoid component enabled easier revision options. For the humeral component, the initial design was an inlay type of long stem with cemented fixation. However, loss of bone stock from the cemented stem hindered revision surgery. Therefore, a cementless design was introduced with a firm metaphyseal fixation. Furthermore, to prevent complications such as scapular notching, the concept of lateralization emerged. Lateralization helped to maintain normal shoulder contour and better rotator cuff function for improved external/internal rotation power, but excessive lateralization yielded problems such as subacromial notching. Therefore, for patients with pseudoparalysis or with risk of subacromial notching, a medial eccentric tray option can be used for distalization and reduced lateralization of the center of rotation. In summary, it is important that surgeons understand the characteristics of each implant in the various options for RTSA. Furthermore, through preoperative evaluation of patients, surgeons can choose the implant option that will lead to the best outcomes after RTSA.Level of evidence: IV

Lomerizine inhibits LPS-mediated neuroinflammation and tau hyperphosphorylation by modulating NLRP3, DYRK1A, and GSK3α/β

IntroductionLomerizine is a calcium channel blocker that crosses the blood–brain barrier and is used clinically in the treatment of migraines. However, whether lomerizine is beneficial in modulating neuroinflammatory responses has not been tested yet.MethodsTo assess the potential of lomerizine for repurposing as a treatment for neuroinflammation, we investigated the effects of lomerizine on LPS-induced proinflammatory responses in BV2 microglial cells, Alzheimer’s disease (AD) excitatory neurons differentiated from induced pluripotent stem cells (iPSCs), and in LPS-treated wild type mice.ResultsIn BV2 microglial cells, lomerizine pretreatment significantly reduced LPS-evoked proinflammatory cytokine and NLRP3 mRNA levels. Similarly, lomerizine pretreatment significantly suppressed the increases in Iba-1, GFAP, proinflammatory cytokine and NLRP3 expression induced by LPS in wild-type mice. In addition, lomerizine posttreatment significantly decreased LPS-stimulated proinflammatory cytokine and SOD2 mRNA levels in BV2 microglial cells and/or wild-type mice. In LPS-treated wild-type mice and AD excitatory neurons differentiated from iPSCs, lomerizine pretreatment ameliorated tau hyperphosphorylation. Finally, lomerizine abolished the LPS-mediated activation of GSK3α/β and upregulation of DYRK1A, which is responsible for tau hyperphosphorylation, in wild-type mice.DiscussionThese data suggest that lomerizine attenuates LPS-mediated neuroinflammatory responses and tau hyperphosphorylation and is a potential drug for neuroinflammation- or tauopathy-associated diseases

Prevalence of sarcopenia and sarcopenic obesity in Korean adults: The Korean Sarcopenic Obesity Study (KSOS)

*Context:* Sarcopenic obesity (SO), a combination of excess weight and reduced muscle mass and/or strength, is suggested to be associated with an increased risk of adverse health outcomes. &#xd;&#xa;*Objectives:* To examine the prevalence and characteristics of Sarcopenic and SO defined by using different indices such as Appendicular Skeletal muscle Mass (ASM)/height^2^ and Skeletal Muscle Index (SMI (%): skeletal muscle mass (kg)/weight (kg) &#xd7; 100) for Korean adults. &#xd;&#xa;*Methods:* 591 participants were recruited from the Korean Sarcopenic Obesity Study (KSOS) which is an ongoing prospective observational cohort study. Analysis was conducted in 526 participants (328 women, 198 men) who had complete data on body composition using Dual X-ray absorptiometry and computed tomography. &#xd;&#xa;*Results:* The prevalence of sarcopenia and SO increases with aging. Using two or more standard deviations (SD) of ASM/height^2^ below reference values from young, healthy adults as a definition of sarcopenia, the prevalence of sarcopenia and SO was 6.3% and 1.3% in men and 4.1% and 1.7% in women over 60 years of age. However, using two or more SD of SMI, the prevalence of sarcopenia and SO was 5.1% and 5.1% respectively in men and 14.2% and 12.5% respectively in women. As defined by SMI, subjects with SO had 3 times the risk of metabolic syndrome (OR = 3.03, 95% confidence interval (CI) = 1.26-7.26) and subjects with non-sarcopenic obesity had approximately 2 times the risk of metabolic syndrome (OR = 1.89, 95% CI = 1.18-3.02) compared with normal subjects. &#xd;&#xa;*Conclusion:* Obese subjects with relative sarcopenia were associated with a greater likelihood for metabolic syndrome. As Koreans were more obese and aging, the prevalence of SO and its impact on health outcomes are estimated to be rapidly grow. Further research is requested to establish the definition, cause and consequences of SO.&#xd;&#xa

The dual role of transforming growth factor-beta signatures in human B viral multistep hepatocarcinogenesis: early and late responsive genes

Background/Aim Transforming growth factor-beta (TGF-β) has a dichotomous role, functioning as a tumor suppressor and tumor promoter. TGF-β signatures, explored in mouse hepatocytes, have been reported to predict the clinical outcomes of hepatocellular carcinoma (HCC) patients; HCCs exhibiting early TGF-β signatures showed a better prognosis than those with late TGF-β signatures. The expression status of early and late TGF-β signatures remains unclear in defined lesions of human B-viral multistep hepatocarcinogenesis. Methods The expression of TGF-β signatures, early and late responsive signatures of TGF-β were investigated and analyzed for their correlation in cirrhosis, low-grade dysplastic nodules (DNs), high-grade DNs, early HCCs and progressed HCCs (pHCCs) by real-time PCR and immunohistochemistry. Results The expression levels of TGF-β signaling genes (TGFB1, TGFBR1, TGFBR2 and SMAD4) gradually increased with the progression of hepatocarcinogenesis, peaking in pHCCs. The expression of early responsive genes of TGF-β (GADD45B, FBP1, CYP1A2 and CYP3A4) gradually decreased, and that of the late TGF-β signatures (TWIST and SNAI1) significantly increased according to the progression of multistep hepatocarcinogenesis. Furthermore, mRNA levels of TWIST and SNAI1 were well correlated with those of stemness markers, with upregulation of TGF-β signaling, whereas FBP1 expression was inversely correlated with that of stemness markers. Conclusions The enrichment of the late responsive signatures of TGF-β with induction of stemness is considered to be involved in the progression of the late stage of multistep hepatocarcinogenesis, whereas the early responsive signatures of TGF-β are suggested to have tumor-suppressive roles in precancerous lesions of the early stage of multistep hepatocarcinogenesis

A case study on swell correction of Chirp sub-bottom profiler (SBP) data using multi-beam echo sounder (MBES) data

High-resolution marine seismic data acquisition and subsequent analyses are highly influenced by sea conditions, directly affecting data quality and interpretation. Traditional swell effect correction methods are effective in improving reflector continuity; however, they are less useful for enhancing travel time consistency at intersection points of crossing lines. To develop a robust swell-removal technique for a set of crossing lines multi-beam echo sounder (MBES) data and Chirp sub-bottom profiler (SBP) data were acquired. After generation of a time structure map of the sea-bottom converted from the final processed multi-beam data, a moving average was used to improve the event continuity of the sea-bottom reflection of the Chirp SBP data. Using the position of the Chirp SBP data, the difference between the travel time of the sea-bottom from the smoothed map and the original travel time of the sea-bottom is calculated as a static correction. The static correction method based on the MBES data was compared and verified using three different cases: (i) simple 2D swell effect correction on a line-by-line basis, (ii) comparing the swell corrections at the crossing positions of 2D lines acquired from different dates, and (iii) comparison of ties of intersection points between 2D lines after new swell correction applied. Although a simple 2D swell correction showed great enhancement of reflector continuity, only the full static correction using the newly proposed method using MBES data produced completely corrected reflection events especially at the crossing points of 2D lines

Formyl-methionine as an N-degron of a eukaryotic N-end rule pathway

In bacteria, nascent proteins bear the pretranslationally generated N-terminal (Nt) formyl-methionine (fMet) residue. Nt-fMet of bacterial proteins is a degradation signal, termed fMet/N-degron. In contrast, proteins synthesized by cytosolic ribosomes of eukaryotes were presumed to bear unformylated Nt-Met. Here we found that the yeast formyltransferase Fmt1, although imported into mitochondria, could also produce Nt-formylated proteins in the cytosol. Nt-formylated proteins were strongly up-regulated in stationary phase or upon starvation for specific amino acids. This up-regulation strictly required the Gcn2 kinase, which phosphorylates Fmt1 and mediates its retention in the cytosol. We also found that the Nt-fMet residues of Nt-formylated proteins act as fMet/N-degrons, and identified the Psh1 ubiquitin ligase as the recognition component of this eukaryotic fMet/N-end rule pathway, which destroys Nt-formylated proteins