Genetic association signal near NTN4 in Tourette syndrome

Tourette syndrome (TS) is a neurodevelopmental disorder with a complex genetic etiology. Through an international collaboration, we genotyped 42 single nucleotide polymorphisms (p < 10⁻³) from the recent TS genomewide association study (GWAS) in 609 independent cases and 610 ancestry‐matched controls. Only rs2060546 on chromosome 12q22 (p = 3.3 × 10⁻⁴) remained significant after Bonferroni correction. Meta‐analysis with the original GWAS yielded the strongest association to date (p = 5.8 × 10⁻⁷). Although its functional significance is unclear, rs2060546 lies closest to NTN4, an axon guidance molecule expressed in developing striatum. Risk score analysis significantly predicted case–control status (p = 0.042), suggesting that many of these variants are true TS risk alleles. Ann Neurol 2014;76:310–315     

Variable Significance of Brain MRI Findings in Infective Endocarditis and Its Effect on Surgical Decisions

ObjectiveTo determine how brain magnetic resonance imaging (MRI) findings impact clinical outcomes in patients with infective endocarditis (IE) and to propose a management algorithm for patients with neurologic symptoms who are candidates for valve surgery (VS).Patients and MethodsData from our center were retrospectively reviewed for patients hospitalized with IE between January 1, 2007, and December 31, 2014. Outcomes were postoperative intracerebral hemorrhage (ICH), 6-month mortality, and functional outcome at last follow-up as described by the modified Rankin Scale (mRS) score. Good outcome was defined as an mRS score of 2 or less.ResultsA total of 361 patients with IE were identified, including 127 patients (35%) who had MRI. One hundred twenty-six of 361 patients (35%) had neurologic symptoms, which prompted MRI in 79 of 127 patients (62%); 74 of 79 (94%) had acute or subacute MRI abnormalities. One patient with subarachnoid and multifocal ICH on MRI developed postoperative ICH. Patients with VS despite MRI abnormalities had lower 6-month mortality (odds ratio [OR], 0.17; 95% CI, 0.06-0.48; P<.001) and better functional outcome (OR, 4.43; 95% CI, 1.51-13.00; P=.005). Irrespective of VS, lobar or posterior fossa ICH on MRI was associated with 6-month mortality (OR, 3.58; 95% CI, 1.22-10.50; P=.02) and territorial ischemic stroke was inversely associated with good mRS (OR, 0.29; 95% CI, 0.13-0.66; P=.002). In neurologically asymptomatic patients who had VS, MRI findings did not impact 6-month mortality or functional outcomes.ConclusionMagnetic resonance imaging detects a large number of abnormalities in patients with IE. Preoperative lobar hematoma and large territorial stroke determine outcome irrespective of VS. When indicated, VS increases the odds of a good outcome despite MRI abnormalities.     

Anatomy of the pulmonary veins in patients with atrial fibrillation and effects of segmental ostial ablation analyzed by computed tomography

INTRODUCTION: The anatomic arrangement of pulmonary veins (PVs) is variable. No prior studies have quantitatively analyzed the effects of segmental ostial ablation on the PVs. The aim of this study was to determine the effect of segmental ostial radiofrequency ablation on PV anatomy in patients with atrial fibrillation (AF). METHODS AND RESULTS: Three-dimensional models of the PVs were constructed from computed tomographic (CT) scans in 58 patients with AF undergoing segmental ostial ablation to isolate the PVs and in 10 control subjects without a history of AF. CT scans were repeated approximately 4 months later. PV and left atrial dimensions were measured with digital calipers. Four separate PV ostia were present in 47 subjects; 3 ostia were present in 2 subjects; and 5 ostia were present in 9 subjects. The superior PVs had a larger ostium than the inferior PVs. Patients with AF had a larger left atrial area between the PV ostia and larger ostial diameters than the controls. Segmental ostial ablation resulted in a 1.5 +/- 3.2 mm narrowing of the ostial diameter. A 28% to 61% focal stenosis was present 7.6 +/- 2.2 mm from the ostium in 3% of 128 isolated PVs. There were no instances of symptomatic PV stenosis during a mean follow-up of 245 +/- 105 days. CONCLUSION: CT of the PVs allows identification of anatomic variants prior to catheter ablation procedures. Segmental ostial ablation results in a significant but small reduction in ostial diameter. Focal stenosis occurs infrequently and is attributable to delivery of radiofrequency energy within the PV.     

Directed transport of bacteria-based drug delivery vehicles: bacterial chemotaxis dominates particle shape

Several attenuated and non-pathogenic bacterial species have been demonstrated to actively target diseased sites and successfully deliver plasmid DNA, proteins and other therapeutic agents into mammalian cells. These disease-targeting bacteria can be employed for targeted delivery of therapeutic and imaging cargos in the form of a bio-hybrid system. The bio-hybrid drug delivery system constructed here is comprised of motile Escherichia coli MG1655 bacteria and elliptical disk-shaped polymeric microparticles. The transport direction for these vehicles can be controlled through biased random walk of the attached bacteria in presence of chemoattractant gradients in a process known as chemotaxis. In this work, we utilize a diffusion-based microfluidic platform to establish steady linear concentration gradients of a chemoattractant and investigate the roles of chemotaxis and geometry in transport of bio-hybrid drug delivery vehicles. Our experimental results demonstrate for the first time that bacterial chemotactic response dominates the effect of body shape in extravascular transport; thus, the non-spherical system could be more favorable for drug delivery applications owing to the known benefits of using non-spherical particles for vascular transport (e.g. relatively long circulation time).     

Mini-open thoracoscopically assisted thoracotomy versus video-assisted thoracoscopic surgery for anterior release in thoracic scoliosis and kyphosis: a comparison of operative and radiographic results

BACKGROUND CONTEXT: Combining anterior release and interbody fusion with posterior instrumented fusion is an accepted treatment for severe rigid spinal deformity. Video-assisted thoracoscopic surgery (VATS) and mini-open thoracoscopically assisted thoracotomy (MOTA) are two minimally invasive approaches to the thoracic spine. Both reduce surgical trauma, improve cosmesis and provide effective exposure for release and fusion. Published data and the authors' surgical experience have demonstrated that both techniques are equivalent in degree of release to traditional open thoracotomy, but no comparison between these two minimally invasive alternatives has been published to our knowledge. PURPOSE: This study compared MOTA and VATS under the hypothesis that both result in similar corrections and comparable operative parameters when used in conjunction with posterior instrumented fusion. STUDY DESIGN/SETTING: Retrospective chart review of consecutive case series by two surgeons. PATIENT SAMPLE: Twenty-one (13 female, 8 male) patients underwent MOTA and 24 patients (17 female, 7 male) underwent VATS for anterior release, discectomy and fusion prior to posterior instrumented fusion. OUTCOME MEASURES: Outcomes were measured at a minimum of 1-year follow-up and included radiographic Cobb measurements and operative parameters. METHODS: The indications for surgery included rigid and severe scoliosis or thoracic kyphosis. Data collection included preoperative demographics, number of levels released, primary curve correction, operative time and blood loss. Data were normalized per number of levels released anteriorly. Statistical analysis of results was done using a two-sample t test assuming equal variances with two-tail p values less than .05. RESULTS: More anterior levels were operated on average in the VATS group (6.33 vs. 4.38 levels). Curve correction per anterior level released was similar in both groups (8.7 and 8.8 degrees/level for MOTA and VATS, respectively). There was a significant difference in operative time with MOTA averaging 131.7 minutes and VATS averaging 162.8 minutes. However, a comparison of the operative time per anterior level operated, approached statistical significance in favor of VATS (33.0 vs. 28.4 minutes, p=.08). There was no significant difference in estimated blood loss during the anterior portion of the surgeries. There was a trend toward decreased blood loss per operated level favoring VATS (68.4 vs. 38.9 cc, p=.09). CONCLUSIONS: Both approaches resulted in corrections that compare favorably with open thoracotomy. We suggest that a factor in choosing between these two minimally invasive techniques is the number of thoracic levels requiring release. For four levels or less, MOTA provides an excellent alternative to standard thoracotomy. For five or more levels, VATS provides for excellent exposure of additional levels with the advantages of less operative time and blood loss per operated level.     

Immunohistochemical evaluation of endothelial nitric oxide synthase expression in primary breast cancer

To evaluate the clinical potential of endothelial nitric oxide synthase (e-NOS) in human breast cancer, we performed immunohistochemical (IHC) staining of paraffin-embedded primary breast cancer tissue of 163 patients for e-NOS using a monoclonal antibody. A correlation was found between e-NOS expression and both the classic prognostic factors and survival rates. Under half the patients were premenopausal (38.5%), 61.5% being postmenopausal. The median tumour size was 2 cm; in 41.7% of the patients there was involvement of the axillary lymph nodes. Most (84.1%) of the tumours were hormone receptor positive. e-NOS staining was positive in 62%, most of the positive tumours having weak (32.5%) or medium (21.5%) staining for e-NOS. The median follow-up time was 42 months, during which 46 (28%) patients had a local recurrence or metastatic disease. A positive correlation of e-NOS with the hormone receptor status was found (P=0.031). However, no impact on survival rates was observed.