Novel scheelite‐type [Ca0.55(Nd1‐xBix)0.3]MoO4 (0.2 ≤ x ≤ 0.95) microwave dielectric ceramics with low sintering temperature

Novel scheelite‐type [Ca0.55(Nd1‐xBix)0.3]MoO4 (0.2 ≤ x ≤ 0.95) ceramics were prepared using the solid‐state reaction method. According to the X‐ray diffraction data, a solid solution was formed in 0.2 ≤ x ≤ 0.95 and all the samples belong to pure scheelite phase with the tetragonal structure. As revealed by Raman spectroscopy, the number of vibrational modes decreased with the increase in x value, which further indicated that Bi3+ ions occupied A‐site of scheelite structure. As the x value increased, the sintering temperature decreased from 740°C to 660°C; the permittivity increased from 12.6 to 20.3; the Qf value first decreased slightly and gradually remained stable. Based on the infrared reflectivity spectrum analysis, the calculated permittivity derived from the fitted data shared the same trend with the measured value. The [Ca0.55(Nd0.05Bi0.95)0.3]MoO4 ceramic sintered at 660 °C attained a near‐zero value temperature coefficient ~τf (−7.1 ppm/°C) and showed excellent microwave dielectric properties with a ɛr ~ 20.3 and a Qf ~ 33 860 GHz, making this system a promising candidate in the ultralow temperature cofired ceramic (ULTCC) technology

Treatment incidence of and medical utilization for hospitalized subjects with pathologic fractures in Taiwan-Survey of the 2008 National Health Insurance data

<p>Abstract</p> <p>Background</p> <p>Almost all studies of pathologic fractures have been conducted based on patients with tumours and hospital-based data; however, in the present study, a nationwide epidemiological survey of pathologic fractures in Taiwan was performed and the medical utilization was calculated.</p> <p>Methods</p> <p>All claimants of Taiwan's National Health Insurance (NHI) Program in 2008 were included in the target population of this descriptive cross-sectional study. The registration and inpatient expenditure claims data by admission of all hospitalized subjects of the target population were examined and the concomitant International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes were evaluated and classified into seven major categories of fracture.</p> <p>Results</p> <p>A total of 5,244 incident cases of pathologic fracture were identified from the 2008 hospitalized patient claims data. The incidence of pathologic fracture of the humerus, distal radius/ulna, vertebrae, femoral neck, other part of the femur, and tibia/fibula was 0.67, 0.08, 10.58, 1.11, 0.56, and 0.11 per 100,000 people, respectively, and patients with those fractures were hospitalized for 43.9 ± 42.9, 31.1 ± 32.9, 29. 4 ± 34.4, 43.3 ± 41.2, 42.4 ± 38.1, and 42.0 ± 32.8 days, respectively, incurring an average medical cost of US$11,049 ± 12,730, US$9,181 ± 12,115, US$6,250 ± 8,021, US$9,619 ± 8,906, US$10,646 ± 11,024, and US$9,403 ± 9,882, respectively. The percentage of patients undergoing bone surgery for pathologic fracture of the humerus, radius/ulna, vertebrae, femoral neck, other part of the femur, and tibia/fibula was 31.2%, 44.4%, 11.3%, 46.5%, 48.4%, and 52.5% respectively.</p> <p>Conclusions</p> <p>Comparing Taiwan to other countries, this study observed for Taiwan higher medical utilization and less-aggressive surgical intervention for patients hospitalized with pathologic fractures.</p

RUNX2 mutations in Taiwanese patients with cleidocranial dysplasia

Cleidocranial dysplasia (CCD) is an autosomal dominant human skeletal disorder comprising hypoplastic clavicles, wide cranial sutures, supernumerary teeth, short stature, and other skeletal abnormalities. It is known that mutations in the human RUNX2 gene mapped at 6p21 are responsible for CCD. We analyzed the mutation patterns of the RUNX2 gene by direct sequencing in six Taiwanese index cases with typical CCD. One of the patients was a familial case and the others were sporadic cases. Sequencing identified four mutations. Three were caused by single nucleotide substitutions, which created a nonsense (p.R391X), two were missense mutations (p.R190W, p.R225Q), and the forth was a novel mutation (c.1119delC), a one-base deletion. Real time quantitative PCR adapted to determine copy numbers of the promoter, all exons and the 3’UTR region of the RUNX2 gene detected the deletion of a single allele in a sporadic case. The results extend the spectrum of RUNX2 mutations in CCD patients and indicate that complete deletions of the RUNX2 gene should be considered in those CCD patients lacking a point mutation detected by direct sequencing

Regulation of Chemokine and Chemokine Receptor Expression by PPARγ in Adipocytes and Macrophages

PPARγ plays a key role in adipocyte biology, and Rosiglitazone (Rosi), a thiazolidinedione (TZD)/PPARγ agonist, is a potent insulin-sensitizing agent. Recent evidences demonstrate that adipose tissue inflammation links obesity with insulin resistance and that the insulin-sensitizing effects of TZDs result, in part, from their anti-inflammatory properties. However the underlying mechanisms are unclear.In this study, we establish a link between free fatty acids (FFAs) and PPARγ in the context of obesity-associated inflammation. We show that treatment of adipocytes with FFAs, in particular Arachidonic Acid (ARA), downregulates PPARγ protein and mRNA levels. Furthermore, we demonstrate that the downregulation of PPARγ by ARA requires the activation the of Endoplamsic Reticulum (ER) stress by the TLR4 pathway. Knockdown of adipocyte PPARγ resulted in upregulation of MCP1 gene expression and secretion, leading to enhanced macrophage chemotaxis. Rosi inhibited these effects. In a high fat feeding mouse model, we show that Rosi treatment decreases recruitment of proinflammatory macrophages to epididymal fat. This correlates with decreased chemokine and decreased chemokine receptor expression in adipocytes and macrophages, respectively.In summary, we describe a novel link between FAs, the TLR4/ER stress pathway and PPARγ, and adipocyte-driven recruitment of macrophages. We thus both describe an additional potential mechanism for the anti-inflammatory and insulin-sensitizing actions of TZDs and an additional detrimental property associated with the activation of the TLR4 pathway by FA

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Gastrin-Releasing Peptide Signaling Plays a Limited and Subtle Role in Amygdala Physiology and Aversive Memory

Links between synaptic plasticity in the lateral amygdala (LA) and Pavlovian fear learning are well established. Neuropeptides including gastrin-releasing peptide (GRP) can modulate LA function. GRP increases inhibition in the LA and mice lacking the GRP receptor (GRPR KO) show more pronounced and persistent fear after single-trial associative learning. Here, we confirmed these initial findings and examined whether they extrapolate to more aspects of amygdala physiology and to other forms of aversive associative learning. GRP application in brain slices from wildtype but not GRPR KO mice increased spontaneous inhibitory activity in LA pyramidal neurons. In amygdala slices from GRPR KO mice, GRP did not increase inhibitory activity. In comparison to wildtype, short- but not long-term plasticity was increased in the cortico-lateral amygdala (LA) pathway of GRPR KO amygdala slices, whereas no changes were detected in the thalamo-LA pathway. In addition, GRPR KO mice showed enhanced fear evoked by single-trial conditioning and reduced spontaneous firing of neurons in the central nucleus of the amygdala (CeA). Altogether, these results are consistent with a potentially important modulatory role of GRP/GRPR signaling in the amygdala. However, administration of GRP or the GRPR antagonist (D-Phe6, Leu-NHEt13, des-Met14)-Bombesin (6–14) did not affect amygdala LTP in brain slices, nor did they affect the expression of conditioned fear following intra-amygdala administration. GRPR KO mice also failed to show differences in fear expression and extinction after multiple-trial fear conditioning, and there were no differences in conditioned taste aversion or gustatory neophobia. Collectively, our data indicate that GRP/GRPR signaling modulates amygdala physiology in a paradigm-specific fashion that likely is insufficient to generate therapeutic effects across amygdala-dependent disorders

Low penetrance of retinoblastoma for p.V654L mutation of the RB1 gene

<p>Abstract</p> <p>Background</p> <p>Retinoblastoma is caused by compound heterozygosity or homozygosity of retinoblastoma gene (<it>RB1</it>) mutations. In germline retinoblastoma, mutations in the <it>RB1 </it>gene predispose individuals to increased cancer risks during development. These mutations segregate as autosomal dominant traits with high penetrance (90%).</p> <p>Methods</p> <p>We screened 30 family members from one family using high resolution melting assay and DNA direct sequencing for mutations in the <it>RB1 </it>gene. We evaluate the phenotype and penetrance of germline mutations of the <it>RB1 </it>gene in a large Taiwanese family.</p> <p>Results</p> <p>The molecular analysis and clinical details of this family showed phenotypic variability associated with the p.V654L mutation in exon 19 of the <it>RB1 </it>gene in 11 family members. The phenotype varied from asymptomatic to presence of a unilateral tumor. Only four individuals (2 males and 2 females) developed unilateral retinoblastoma, which resulted in calculated low penetrance of 36% (4/11). The four individuals with retinoblastoma were diagnosed before the age of three years. None of their relatives exhibited variable severity or bilateral retinoblastoma.</p> <p>Conclusions</p> <p>The diseased-eye ratio for this family was 0.36, which is lower than current estimates. This suggests that the <it>RB1 </it>p.V654L mutation is a typical mutation associated with low penetrance.</p

Lack of Association of SULT1A1 R213H Polymorphism with Colorectal Cancer: A Meta-Analysis

BACKGROUND: A number of case-control studies were conducted to investigate the association of SULT1A1 R213H polymorphisms with colorectal cancer (CRC) in humans. But the results were not always consistent. We performed a meta-analysis to examine the association between the SULT1A1 R213H polymorphism and CRC. METHODS AND FINDINGS: Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Excerpta Medica Database, and Chinese Biomedical Literature Database, with the last report up to September 2010. A total of 12 studies including 3,549 cases and 5,610 controls based on the search criteria were involved in this meta-analysis. Overall, no significant association of this polymorphism with CRC was found (H versus R: OR = 1.04, 95%CI = 0.94-1.16, P = 0.46; HR+HH versus RR: OR = 1.01, 95%CI = 0.92-1.11, P = 0.81; HH versus RR+HR: OR = 1.01, 95%CI = 0.74-1.38, P = 0.95; HH versus RR: OR = 1.00, 95%CI = 0.77-1.31, P = 0.98; HR versus RR: OR = 1.01, 95%CI = 0.92-1.11, P = 0.86). In subgroup analysis, we also did not find any significant association in Cauasians (H versus R: OR = 1.02, 95%CI = 0.92-1.15, P = 0.68; HR+HH versus RR: OR = 0.99, 95%CI = 0.91-1.09, P = 0.90; HH versus RR+HR: OR = 1.01, 95%CI = 0.73-1.39, P = 0.97; HH versus RR: OR = 0.99, 95%CI = 0.75-1.31, P = 0.94; HR versus RR: OR = 0.99, 95%CI = 0.90-1.09, P = 0.85). The results were not materially altered after the studies which did not fulfill Hardy-Weinberg equilibrium were excluded (H versus R: OR = 1.06, 95%CI = 0.95-1.19, P = 0.31; HR+HH versus RR: OR = 1.03, 95%CI = 0.93-1.13, P = 0.56; HH versus RR+HR: OR = 1.10, 95%CI = 0.78-1.56, P = 0.57; HH versus RR: OR = 1.09, 95%CI = 0.83-1.44, P = 0.53; HR versus RR: OR = 1.02, 95%CI = 0.92-1.13, P = 0.75). CONCLUSION: This meta-analysis demonstrates that there is no association between the SULT1A1 R213H polymorphism and CRC

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes