Citations

ABSTRACTThe objective of this study was to evaluate the correlations between deformation and displacement of median nerve and flexor tendons during finger motion in the carpal tunnel for both carpal tunnel syndrome (CTS) patients and healthy controls. Sixty‐two wrists of 31 asymptomatic volunteers and fifty‐one wrists of 28 idiopathic CTS patients were evaluated by ultrasound. The displacement of the median nerve and the middle finger flexor digitorum superficialis (FDS) tendon, as well as area, perimeter, aspect ratio of a minimum enclosing rectangle, and circularity of the median nerve were measured in finger extension and flexion positions. Deformation indices were defined as the ratios of indices in finger extension and flexion positions. The correlations between displacement and deformation indices were evaluated. There were significant correlations between nerve palmar–dorsal displacement and deformation indices (p < 0.05). The aspect ratio deformation index showed the strongest correlation to palmar–dorsal displacement of the nerve (−0.572, p < 0.01). This study showed that there is a relationship between median nerve deformation indices and nerve palmar–dorsal displacement in the carpal tunnel. Since the highest correlations were between palmar–dorsal nerve displacement direction and aspect ratio deformation index, these parameters may be helpful to understand the pathophysiology of CTS. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1876–1880, 2013

Objective Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. Design We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92×10 −4 was used to determine statistical significance of the associations. Results Two correlated SNPs—rs10090154 and rs4242382—in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p=1.74×10 −5 ), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. Conclusions This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.

Objectives/Hypothesis Pediatric obstructive sleep apnea syndrome ( OSAS ) is a common disorder with serious clinical implications if left untreated. The recommended initial treatment for pediatric patients with obstructive sleep apnea syndrome ( OSAS ) is adenotonsillectomy. However, recent reports have shown variable surgical results with adenotonsillectomy in the treatment of pediatric OSAS . Study Design Prospective, controlled study. Methods From April 2007 to August 2010, 24 participants were assigned alternatively to either adenotonsillectomy with pillar suturing (intervention group) or adenotonsillectomy alone (control group). Result The average improvement in apnea hypopnea index ( AHI ) was 42.6% in the control group and 79.9% in the intervention group ( P =0.037). The success rate was 50% in the control group and 91.6% in the intervention group ( P =0.034). Six patients (50%) in the intervention group achieved complete resolution of pediatric OSAS , as defined by an AHI <1/hour, compared to 2 patients (16.7%) in the control group ( P =0.097). Conclusion Adenotonsillectomy with pillar suturing showed significant improvement in treating pediatric patients with OSAS compared to adenotonsillectomy alone. The procedure is simple and safe. Level of Evidence 4. Laryngoscope , 123:2574–2578, 2013

ABSTRACTBackgroundVariants within the leucine‐rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine‐rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late‐onset sporadic disorders like Parkinson's disease.MethodsThe Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine‐rich repeat kinase 2 gene across 23 different sites in 15 countries.ResultsHerein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K‐R1398H‐K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups.ConclusionsEstablishing individual patient‐based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies. © 2013 International Parkinson and Movement Disorder Society

Key Points A continued monoclonal protein response after ASCT in the absence of further therapy is prognostic in MM patients.

AbstractObjectivesCompare healthcare resource utilization (HCRU) and costs between patients prescribed opioids (RxOP) and those who were not (NoRxOP) during an emergency department (ED) or inpatient visit.MethodsRetrospective cohort analysis was performed (January 2006 to September 2010). Continuously eligible RxOP patients in ED/inpatient settings (January 2007 to September 2009) were included if age was ≥ 12 years by initial prescription date (or random date between first ED/inpatient admission and September 30, 2009 [NoRxOP patients]).Healthcare resource utilization and costs for 12 months after initial prescription were compared. Univariate descriptive analyses were performed for baseline and outcome variables and compared using appropriate tests. Risk adjustment compared HCRU between RxOP and NoRxOP cohorts for the postindex period.ResultsOf 27,599 eligible patients, RxOP patients (n = 18,819) were younger, less likely to be male, more likely to reside in southern United States and to have Preferred Provider Organization health plans, and had lower comorbidity index scores, compared with NoRxOP patients (n = 8,780). RxOP patients were less likely to have nonpain‐related comorbidities and more frequently diagnosed with pain‐related comorbidities.Unmatched and propensity‐matched RxOP patients experienced higher HCRU and costs in all subcategories (total, inpatient, outpatient ED, physician, pharmacy, other outpatient settings). Opioid abuse frequency was low in patients with common diagnoses/procedures within 3 months before initial prescription (0.48%). Average time to abuse was < 1 year (201 days).ConclusionMost patients were prescribed opioids initially during ED/inpatient visits and incurred higher HCRU than those not prescribed opioids. Among those with diagnosed opioid abuse after initiating opioids, time to diagnosis was rapid (range: 14 to 260 days) for patients with common diseases and procedures.

The crystal structure of a pentameric α7 ligand-binding domain chimaera with bound α-btx (α-bungarotoxin) showed that of the five conserved aromatic residues in α7, only Tyr184 in loop C of the ligand-binding site was required for high-affinity binding. To determine whether the contribution of Tyr184 depends on local residues, we generated mutations in an α7/5HT3A (5-hydroxytryptamine type 3A) receptor chimaera, individually and in pairs, and measured 125I-labelled α-btx binding. The results show that mutations of individual residues near Tyr184 do not affect α-btx affinity, but pairwise mutations decrease affinity in an energetically coupled manner. Kinetic measurements show that the affinity decreases arise through increases in the α-btx dissociation rate with little change in the association rate. Replacing loop C in α7 with loop C from the α-btx-insensitive α2 or α3 subunits abolishes high-affinity α-btx binding, but preserves acetylcholine-elicited single channel currents. However, in both the α2 and α3 construct, mutating either residue that flanks Tyr184 to its α7 counterpart restores high-affinity α-btx binding. Analogously, in α7, mutating both residues that flank Tyr184 to the α2 or α3 counterparts abolishes high-affinity α-btx binding. Thus interaction between Tyr184 and local residues contributes to high-affinity subtype-selective α-btx binding.

To identify high-affinity interactions between long-chain α-neurotoxins and nicotinic receptors, we determined the crystal structure of the complex between α-btx (α-bungarotoxin) and a pentameric ligand-binding domain constructed from the human α7 AChR (acetylcholine receptor) and AChBP (acetylcholine-binding protein). The complex buries ~2000 Å2 (1 Å=0.1 nm) of surface area, within which Arg36 and Phe32 from finger II of α-btx form a π-cation stack that aligns edge-to-face with the conserved Tyr184 from loop-C of α7, while Asp30 of α-btx forms a hydrogen bond with the hydroxy group of Tyr184. These inter-residue interactions diverge from those in a 4.2 Å structure of α-ctx (α-cobratoxin) bound to AChBP, but are similar to those in a 1.94 Å structure of α-btx bound to the monomeric α1 extracellular domain, although compared with the monomer-bound complex, the α-btx backbone exhibits a large shift relative to the protein surface. Mutational analyses show that replacing Tyr184 with a threonine residue abolishes high-affinity α-btx binding, whereas replacing with a phenylalanine residue maintains high affinity. Comparison of the α-btx complex with that coupled to the agonist epibatidine reveals structural rearrangements within the binding pocket and throughout each subunit. The overall findings highlight structural principles by which α-neurotoxins interact with nicotinic receptors.

Genetic College Many genomic elements in humans are associated with behavior, including educational attainment. In a genome-wide association study including more than 100,000 samples, Rietveld et al. (p. 1467 , published online 30 May; see the Perspective by Flint and Munafò ) looked for genes related to educational attainment in Caucasians. Small genetic effects at three loci appeared to impact educational attainment.

Key PointsRadiation is appropriate primary therapy in approximately 25% of cases. Radiation provides long-term remissions in more than 50% of patients.