Selective laser melting (SLM) is a useful technique for preparing three-dimensional porous bodies with complicated internal structures directly from titanium (Ti) powders without any intermediate ...processing steps, with the products being expected to be useful as a bone substitute. In this study the necessary SLM processing conditions to obtain a dense product, such as the laser power, scanning speed, and hatching pattern, were investigated using a Ti powder of less than 45μm particle size. The results show that a fully dense plate thinner than 1.8mm was obtained when the laser power to scanning speed ratio was greater than 0.5 and the hatch spacing was less than the laser diameter, with a 30μm thick powder layer. Porous Ti metals with structures analogous to human cancellous bone were fabricated and the compressive strength measured. The compressive strength was in the range 35–120MPa when the porosity was in the range 75–55%. Porous Ti metals fabricated by SLM were heat-treated at 1300°C for 1h in an argon gas atmosphere to smooth the surface. Such prepared specimens were subjected to NaOH, HCl, and heat treatment to provide bioactivity. Field emission scanning electron micrographs showed that fine networks of titanium oxide were formed over the whole surface of the porous body. These treated porous bodies formed bone-like apatite on their surfaces in a simulated body fluid within 3days. In vivo studies showed that new bone penetrated into the pores and directly bonded to the walls within 12weeks after implantation into the femur of Japanese white rabbits. The percentage bone affinity indices of the chemical- and heat-treated porous bodies were significantly higher than that of untreated implants.
Summary
Background
Work‐related psychosocial factors have been associated with metabolic syndrome. However, no systematic reviews or meta‐analyses have evaluated this association.
Methods
A ...systematic literature search was conducted, using PubMed, Embase, PsycINFO, PsycARTICLES and the Japan Medical s Society. Eligible studies included those that examined the previously mentioned association; had a longitudinal or prospective cohort design; were conducted among workers; provided sufficient data for calculating odds ratios, relative risks or hazard ratios with 95% confidence intervals; were original articles in English or Japanese; and were published no later than 2016. Study characteristics, exposure and outcome variables and association measures of studies were extracted by the investigators independently.
Results
Among 4,664 identified studies, 8 were eligible for review and meta‐analysis. The pooled risk of adverse work‐related stress on metabolic syndrome onset was significant and positive (RR = 1.47; 95% CI, 1.22–1.78). Sensitivity analyses limiting only the effects of job strain and shift work also indicated a significant positive relationship (RR = 1.75; 95% CI, 1.09–2.79; and RR = 1.59; 95% CI, 1.00–2.54, P = 0.049 respectively).
Conclusion
This study reveals a strong positive association between work‐related psychosocial factors and an elevated risk of metabolic syndrome onset. The effects of job strain and shift work on metabolic syndrome appear to be significant.
The differentiation of pure turbidites and contourites from mixed deposits —as the bottom current reworked sands (BCRS) — in sedimentary cores and outcrops from the modern or ancient records is still ...challenging. An accurate evaluation of facies associations calls for detailed understanding of processes controlling these deep-water systems and how they record interactions of along- and down-slope processes. Connecting features to processes is of particularly relevant in the study of contouritic drifts that include sandy deposits. This research describes and interprets BCRS within a Pleistocene contouritic drift located along the middle continental slope of the Gulf of Cadiz. Seismic, wireline, and sedimentological analyses of sediment samples were applied to core material representing a muddy drift that hosts sandy deposits. A sedimentary sequence, comprising five facies (F1 to F5) is defined here; it records background sedimentation influenced by the initial deposition of a gravity-driven flow followed by bottom current reworking. It is moderately bioturbated and contains distinctive trace fossil assemblages, often dominated by ichnofabrics of the Planolites and Thalassinoides. These assemblages represent intermittent deposition between down-slope and along-slope processes during relatively short time scales. The sequence is defined as a partial bi-gradational contourite sequence including BCRS reworked from underlying turbiditic deposits due to the interaction of down- and along- slope processes within the contouritic drift and its adjacent contouritic channel. Longer-term trends include an increase and subsequent decrease in both sediment supply and bottom currents. The sedimentary facies model presented here represents a new end member for a mixed turbiditic-contouritic system in which turbiditic flows influence a contourite drift. As such, it may support basic sedimentological interpretation and petroleum exploration strategies.
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•Sedimentological study of the interaction between down- and along-slope processes;•A contourite drift containing reworked turbidites is described;•Turbidites are subjected to reworking and winnowing by bottom currents;•Contourite drifts are not only formed by contourite deposits;•The vertical trend in the sedimentary sequence presented records long- and short- term variation in turbidite-contourite interactions.
Pancreatic cancer has a poor prognosis because of its high refractoriness to chemotherapy and tumour recurrence, and these properties have been attributed to cancer stem cells (CSCs). MicroRNA ...(miRNA) regulates various molecular mechanisms of cancer progression associated with CSCs. This study aimed to identify the candidate miRNA and to characterise the clinical significance.
We established gemcitabine-resistant Panc1 cells, and induced CSC-like properties through sphere formation. Candidate miRNAs were selected through microarray analysis. The overexpression and knockdown experiments were performed by evaluating the in vitro cell growth and in vivo tumourigenicity. The expression was studied in 24 pancreatic cancer samples after laser captured microdissection and by immunohistochemical staining.
The in vitro drug sensitivity of pancreatic cancer cells was altered according to the miR-1246 expression via CCNG2. In vivo, we found that miR-1246 could increase tumour-initiating potential and induced drug resistance. A high expression level of miR-1246 was correlated with a worse prognosis and CCNG2 expression was significantly lower in those patients.
miR-1246 expression was associated with chemoresistance and CSC-like properties via CCNG2, and could predict worse prognosis in pancreatic cancer patients.
Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer deaths worldwide. While sorafenib, a multikinase inhibitor targeting the Raf/extracellular signal-regulated protein kinase ...(ERK) pathway, has been shown recently to provide a survival advantage to patients with advanced HCC, a predictive biomarker has not been developed. We studied whether c-Jun N-terminal kinase (JNK), which promotes liver carcinogenesis in mice, affects therapeutic response to sorafenib in HCC patients.
We collected pathological specimens from 39 patients with advanced HCC before starting sorafenib treatment, and measured JNK activity in HCCs.
In patients treated with sorafenib, the expression of phospho-c-Jun in HCC, as a read out of JNK activity, was significantly higher (P<0.001) in the non-responder group than in the responder group. c-Jun N-terminal kinase activation in HCC was associated with a decreased time to progression and a poor overall survival (P=0.0028 and P=0.0008, respectively).
In addition, JNK activity was significantly correlated with CD133 expression level. Correspondingly, high expression level of CD133 was linked to a poor response to sorafenib. Furthermore, D-JNKi, a specific JNK inhibitor, reduced the growth of xenografted CD133(+) cells in athymic mice. In conclusion, JNK activation was positively correlated with CD133 expression level and inversely correlated with the therapeutic response to sorafenib, suggesting that JNK activity may be considered as a new predictive biomarker for response to sorafenib treatment.
Many studies have shown that certain biomaterials with specific porous structures can induce bone formation in non-osseous sites without the need for osteoinductive biomolecules, however, the ...mechanisms responsible for this phenomenon (intrinsic osteoinduction of biomaterials) remain unclear. In particular, to our knowledge the type of pore structure suitable for osteoinduction has not been reported in detail. In the present study we investigated the effects of interconnective pore size on osteoinductivity and the bone formation processes during osteoinduction. Selective laser melting was employed to fabricate porous Ti implants (diameter 3.3
mm, length 15
mm) with a channel structure comprising four longitudinal square channels, representing pores, of different diagonal widths, 500, 600, 900, and 1200
μm (termed p500, p600, p900, and p1200, respectively). These were then subjected to chemical and heat treatments to induce bioactivity. Significant osteoinduction was observed in p500 and p600, with the highest observed osteoinduction occurring at 5
mm from the end of the implants. A distance of 5
mm probably provides a favorable balance between blood circulation and fluid movement. Thus, the simple architecture of the implants allowed effective investigation of the influence of the interconnective pore size on osteoinduction, as well as the relationship between bone quantity and its location for different pore sizes.
SIRT4, which is localised in the mitochondria, is one of the least characterised members of the sirtuin family of nicotinamide adenine dinucleotide-dependent enzymes that play key roles in multiple ...cellular processes such as metabolism, stress response and longevity. There are only a few studies that have characterised its function and assessed its clinical significance in human cancers.
We established colorectal cancer cell lines (SW480, HCT116, and HT29) overexpressing SIRT4 and investigated their effects on proliferation, migration and invasion, as well as E-cadherin expression, that negatively regulates tumour invasion and metastases. The associations between SIRT4 expression in colorectal cancer specimens and clinicopathological features including prognosis were assessed by immunohistochemistry.
SIRT4 upregulated E-cadherin expression and suppressed proliferation, migration and invasion through inhibition of glutamine metabolism in colorectal cancer cells. Moreover, SIRT4 expression in colorectal cancer decreased with the progression of invasion and metastasis, and a low expression level of SIRT4 was correlated with a worse prognosis.
SIRT4 has a tumour-suppressive function and may serve as a novel therapeutic target in colorectal cancer.
Recent data have linked hypoxia, a classic feature of the tumor microenvironment, to the function of specific microRNAs (miRNAs); however, whether hypoxia affects other types of noncoding transcripts ...is currently unknown. Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs). Interestingly, several hypoxia-upregulated T-UCRs, henceforth named 'hypoxia-induced noncoding ultraconserved transcripts' (HINCUTs), are also overexpressed in clinical samples from colon cancer patients. We show that these T-UCRs are predominantly nuclear and that the hypoxia-inducible factor (HIF) is at least partly responsible for the induction of several members of this group. One specific HINCUT, uc.475 (or HINCUT-1) is part of a retained intron of the host protein-coding gene, O-linked N-acetylglucosamine transferase, which is overexpressed in epithelial cancer types. Consistent with the hypothesis that T-UCRs have important function in tumor formation, HINCUT-1 supports cell proliferation specifically under hypoxic conditions and may be critical for optimal O-GlcNAcylation of proteins when oxygen tension is limiting. Our data gives a first glimpse of a novel functional hypoxic network comprising protein-coding transcripts and noncoding RNAs (ncRNAs) from the T-UCRs category.
Statistical imputation of classical human leukocyte antigen (HLA) alleles is becoming an indispensable tool for fine-mappings of disease association signals from case-control genome-wide association ...studies. However, most currently available HLA imputation tools are based on European reference populations and are not suitable for direct application to non-European populations. Among the HLA imputation tools, The HIBAG R package is a flexible HLA imputation tool that is equipped with a wide range of population-based classifiers; moreover, HIBAG R enables individual researchers to build custom classifiers. Here, two data sets, each comprising data from healthy Japanese individuals of difference sample sizes, were used to build custom classifiers. HLA imputation accuracy in five HLA classes (HLA-A, HLA-B, HLA-DRB1, HLA-DQB1 and HLA-DPB1) increased from the 82.5-98.8% obtained with the original HIBAG references to 95.2-99.5% with our custom classifiers. A call threshold (CT) of 0.4 is recommended for our Japanese classifiers; in contrast, HIBAG references recommend a CT of 0.5. Finally, our classifiers could be used to identify the risk haplotypes for Japanese narcolepsy with cataplexy, HLA-DRB1*15:01 and HLA-DQB1*06:02, with 100% and 99.7% accuracy, respectively; therefore, these classifiers can be used to supplement the current lack of HLA genotyping data in widely available genome-wide association study data sets.
A retrospective study.
Diffusion tensor imaging (DTI) reflects pathological change in the spinal cord more sensitively than conventional magnetic resonance imaging (MRI). Electrophysiological ...examination enables quantitative assessment of spinal cord function. Few studies have addressed the correlation between intraoperative spinal cord-evoked potentials (SCEPs) and DTI. The purpose of this study was to examine whether DTI is an objective index for the diagnosis of the segmental level of dysfunction in cervical spondylotic myelopathy (CSM).
Yamaguchi University Graduate School of Medicine, Japan.
Using 3.0-Tesla MRI, DTI values for the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured at the disc level C2/C3 through C6/C7 in 11 normal subjects and 10 subjects with CSM. Subjects with CSM were divided into two groups based on the extent of compression according to conventional MRI: single level (n=3) and multilevel (n=7). Intraoperative SCEPs were measured in subjects with CSM. For each group, the ADC and FA values were compared with SCEPs with respect to the segmental levels of dysfunction.
For all three subjects with single-level compression and six of seven with multilevel compression, the maximal ADC value was observed at the segmental level of dysfunction as per the SCEP. Minimum FA values were observed at those sites in two of three patients with single-level compression and in only two of seven with multi-level compression.
Our results suggest that ADC might serve as a supplementary diagnostic indicator of the segmental levels of dysfunction in CSM.
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