Significant associations of PAI-1 genetic polymorphisms with osteonecrosis of the femoral head

<p>Abstract</p> <p>Background</p> <p>The pathogenesis of osteonecrosis of the femoral head (ONFH) has been implicated in hypofibrinolysis and blood supply interruption. Previous studies have demonstrated that decreased fibrinolytic activity due to elevated plasminogen activator inhibitor-1 (PAI-1) levels correlates with ONFH pathogenesis. The -675 4G/5G single nucleotide polymorphism (SNP rs1799889) in the PAI-1 gene promoter is associated with PAI-1 plasma level. We investigated whether rs1799889 and two other SNPs of the PAI-1 gene (rs2227631, -844 G/A in the promoter; rs11178, +10700 C/T in the 3'UTR) are associated with increased ONFH risk.</p> <p>Methods</p> <p>Three SNPs in PAI-1 were genotyped in 206 ONFH patients and 251 control subjects, using direct sequencing and a TaqMan^®5' allelic discrimination assay. We performed association analysis for genotyped SNPs and haplotypes with ONFH.</p> <p>Results</p> <p>The 4G allele of rs1799889, A allele of rs2227631, and C allele of rs11178 were significantly associated with increased ONFH risk (p = 0.03, p = 0.003, and p = 0.002, respectively). When we divided the population according to gender, an association between the three SNPs and increased risk of ONFH was found only in men. In another subgroup analysis based on the etiology of ONFH, rs2227631 (A allele) and rs11178 (C allele) in the idiopathic subgroup (p = 0.007 and p = 0.021) and rs1799889 (4G allele) and rs11178 (C allele) in the alcohol-induced subgroup (p = 0.042 and p = 0.015) were associated with increased risk of ONFH. In addition, a certain haplotype (A-4G-C) of PAI-1 was also significantly associated with ONFH (p < 0.001).</p> <p>Conclusion</p> <p>Our findings demonstrated that three SNPs (rs1799889, rs2227631, and rs11178) of the PAI-1 gene were associated with ONFH risk. This study also suggests that PAI-1 SNPs may play an important role in ONFH.</p

Defective lymphoid organogenesis underlies the immune deficiency caused by a heterozygous S32I mutation in IκBα.

Patients with ectodermal dysplasia with immunodeficiency (ED-ID) caused by mutations in the inhibitor of NF-κB α (IκBα) are susceptible to severe recurrent infections, despite normal T and B cell numbers and intact in vitro lymphocyte function. Moreover, the outcome of hematopoietic stem cell transplantation (HSCT) in these patients is poor despite good engraftment. Mice heterozygous for the IκBα S32I mutation found in patients exhibited typical features of ED-ID. Strikingly, the mice lacked lymph nodes, Peyer's patches, splenic marginal zones, and follicular dendritic cells and failed to develop contact hypersensitivity (CHS) or form germinal centers (GCs), all features not previously recognized in patients and typical of defective noncanonical NF-κB signaling. Lymphotoxin β receptor (LTβR)-driven induction of chemokines and adhesion molecules mediated by both canonical and noncanonical NF-κB pathways was impaired, and levels of p100 were markedly diminished in the mutant. IκBα mutant → Rag2(-/-), but not WT→IκBα mutant, bone marrow chimeras formed proper lymphoid organs and developed CHS and GCs. Defective architectural cell function explains the immunodeficiency and poor outcome of HSCT in patients with IκBα deficiency and suggests that correction of this niche is critical for reconstituting their immune function

Cosmological Parameter Constraints from the SDSS Density and Momentum Power Spectra

We extract the galaxy density and momentum power spectra from a subset of early-type galaxies in the Sloan Digital Sky Survey (SDSS) DR7 main galaxy catalog. Using galaxy distance information inferred from the improved fundamental plane described in Yoon and Park, we reconstruct the peculiar velocities of the galaxies and generate number density and density-weighted velocity fields, from which we extract the galaxy density and momentum power spectra. We compare the measured values to the theoretical expectation of the same statistics, assuming an input Λ cold dark matter (CDM) model and using a third-order perturbative expansion. After validating our analysis pipeline with a series of mock data sets, we apply our methodology to the SDSS data and arrive at constraints $f{\sigma }_{8}={0.471}_{-0.080}^{+0.077}$ and ${b}_{1}{\sigma }_{8}={0.920}_{-0.070}^{+0.070}$ at a mean redshift $\bar{z}=0.04$ . Our result is consistent with the Planck cosmological best-fit parameters for the ΛCDM model. The momentum power spectrum is found to be strongly contaminated by small-scale velocity dispersion, which suppresses power by $\sim { \mathcal O }(30 \% )$ on intermediate scales k ∼ 0.05 h Mpc ^−1

Pregnancy outcomes after living kidney donation from a nationwide population-based cohort study from Korea

Abstract While most living kidney donors experience good outcomes and high rates of satisfaction, kidney donation can increase the risk of gestational hypertension or preeclampsia. However, pregnancy outcomes in non-white donors are limited. We conducted a nationwide cohort study of 112 living kidney donors and 672 matched healthy non-donors using the Korean National Health Insurance Claims Database. Donors and healthy non-donors were matched according to age, year of cohort entry, residency, income, number of pregnancies, and the time to the first pregnancy after cohort entry. We assessed pregnancy outcomes of live kidney donors compared with matched healthy non-donors using the nationwide database. Gestational hypertension or preeclampsia was more common in kidney donors than in non-donors (8.9% vs. 1.8%; adjusted odds ratio, 2.68; 95% confidence interval, 1.11–6.50). However, the incidence of severe gestational hypertension or preeclampsia that required antihypertensive medication was comparable (2.7% vs. 0.9%; P = 0.121). The time from donation to delivery within 5 years and primiparity were risk factors for preeclampsia in donors. Low birth weight, stillbirth, and ectopic pregnancy were not significantly different between the two groups. Maternal death occurred in two non-donor cases, but none occurred in donors compared to non-donors. Our findings indicate that kidney donors are associated with an increased risk of gestational hypertension or preeclampsia than matched healthy non-donors. However, the probabilities of serious maternal and fetal outcomes remained low and are not increased significantly after kidney donation

Atypical presentation of complex regional pain syndrome: neuropathic itching - A case report -

Background In some patients with neuropathic pain (NP), such as complex regional pain syndrome (CRPS), itching rather than pain is the main symptom making diagnosis and treatment difficult. Case We report a case of a 23-year-old male with a history of hypoxic brain damage who presented with pruritus of the left foot and ankle. His left foot was fractured, and he underwent surgery 6 months previously. After the operation and cast application, he developed uncontrolled pruritus, swelling, sweating, and flushing of the left foot skin with limping. On examination, he showed well-known features of CRPS without pain. He was diagnosed with an atypical CRPS with neuropathic itching (NI). With treatment modalities used for NP and CRPS, his pruritus subsided gradually, and the his ankle mobility improved. Conclusions Unexplained itching can be the main symptom in some CRPS patients. Treatment according to NP can improve symptoms of NI in CRPS patients