Surgery for extraforaminal lumbar disc herniation: a single center comparative observational study

Background Surgery on extraforaminal lumbar disc herniation (ELDH) is a commonly performed procedure. Operating on this type of herniation is known to come with more difficulties than on the frequently seen paramedian lumbar disc herniation (PLDH). However, no comparative data are available on the effectiveness and safety of this operation. We sought out to compare clinical outcomes at 1 year following surgery for ELDH and PLDH. Methods Data were collected through the Norwegian Registry for Spine Surgery (NORspine). The primary outcome measure was change at 1 year in the Oswestry Disability Index (ODI). Secondary outcome measures were quality of life measured with EuroQol 5 dimensions (EQ-5D); and numeric rating scales (NRSs). Results Data of a total of 1750 patients were evaluated in this study, including 72 ELDH patients (4.1%). One year after surgery, there were no differences in any of the patient reported outcome measurements (PROMs) between the two groups. PLDH and ELDH patients experienced similar changes in ODI (- 30.92 vs. - 34.00, P = 0.325); EQ-5D (0.50 vs. 0.51, P = 0.859); NRS back (- 3.69 vs. - 3.83, P = 0.745); and NRS leg (- 4.69 vs. - 4.46, P = 0.607) after 1 year. The proportion of patients achieving a clinical success (defined as an ODI score of less than 20 points) at 1 year was similar in both groups (61.5% vs. 52.7%, P = 0.204). Conclusions Patients operated for ELDH reported similar improvement after 1 year compared with patients operated for PLDH.Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

Maternal Vitamin D Status and Delivery by Cesarean

We examined the association of vitamin D deficiency to risk of cesarean delivery using prospective data in a cohort of 1153 low income and minority gravidae. Circulating maternal 25-hydroxyvitamin D and intact parathyroid hormone were measured at entry to care 13.73 ± 5.6 weeks (mean ± SD). Intake of vitamin D and calcium was assessed at three time points during pregnancy. Using recent Institute of Medicine guidelines, 10.8% of the gravidae were at risk of vitamin D deficiency, and 23.8% at risk of insufficiency. Maternal 25-hydroxyvitamin D was related positively to vitamin D and calcium intakes and negatively to circulating concentrations of parathyroid hormone. Risk for cesarean delivery was increased significantly for vitamin D deficient women; there was no increased risk for gravidae at risk of insufficiency. When specific indications were examined, vitamin D deficiency was linked to a 2-fold increased risk of cesarean for prolonged labor. Results were the similar when prior guidelines for vitamin D deficiency (25(OH)D < 37.5nmol/L) and insufficiency (37.5–80 nmol/L) were utilized

Low BMI-1 expression is associated with an activated BMI-1-driven signature, vascular invasion, and hormone receptor loss in endometrial carcinoma

We studied the expression of polycomb group (PcG) protein BMI-1 in a large population-based patient series of endometrial carcinomas in relation to clinical and molecular phenotype. Also, 57 fresh frozen endometrial carcinomas were studied for the relationship between BMI-1 protein expression, BMI-1 mRNA level, and activation of an 11-gene signature reported to represent a BMI-1-driven pathway. BMI-1 protein expression was significantly weaker in tumours with vascular invasion (P<0.0001), deep myometrial infiltration (P=0.004), and loss of oestrogen receptor (ER) (P<0.0001) and progesterone receptors (PR) (P=0.03). Low BMI-1 protein expression was highly associated with low BMI-1 mRNA expression (P=0.002), and similarly low BMI-1 mRNA expression correlated significantly with vascular invasion, ER and PR loss, and histologic grade 3. In contrast, activation of the reported 11-gene signature, supposed to represent a BMI-1-driven pathway, correlated with low mRNA expression of BMI-1 (P<0.001), hormone receptor loss, presence of vascular invasion, and poor prognosis. We conclude that BMI-1 protein and mRNA expression are significantly correlated and that BMI-1 expression is inversely associated with activation of the 11-gene signature. Loss of BMI-1 seems to be associated with an aggressive phenotype in endometrial carcinomas

A Ubiquitin Ligase Complex Regulates Caspase Activation During Sperm Differentiation in Drosophila

In both insects and mammals, spermatids eliminate their bulk cytoplasm as they undergo terminal differentiation. In Drosophila, this process of dramatic cellular remodeling requires apoptotic proteins, including caspases. To gain further insight into the regulation of caspases, we screened a large collection of sterile male flies for mutants that block effector caspase activation at the onset of spermatid individualization. Here, we describe the identification and characterization of a testis-specific, Cullin-3–dependent ubiquitin ligase complex that is required for caspase activation in spermatids. Mutations in either a testis-specific isoform of Cullin-3 (Cul3Testis), the small RING protein Roc1b, or a Drosophila orthologue of the mammalian BTB-Kelch protein Klhl10 all reduce or eliminate effector caspase activation in spermatids. Importantly, all three genes encode proteins that can physically interact to form a ubiquitin ligase complex. Roc1b binds to the catalytic core of Cullin-3, and Klhl10 binds specifically to a unique testis-specific N-terminal Cullin-3 (TeNC) domain of Cul3Testis that is required for activation of effector caspase in spermatids. Finally, the BIR domain region of the giant inhibitor of apoptosis–like protein dBruce is sufficient to bind to Klhl10, which is consistent with the idea that dBruce is a substrate for the Cullin-3-based E3-ligase complex. These findings reveal a novel role of Cullin-based ubiquitin ligases in caspase regulation

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012