Thoracic Epidural Abscesses: A Systematic Review.

Study Design: Systematic review. Objectives: Past research has demonstrated increased speed and severity of progression for spinal epidural abscesses (SEAs) of the thoracic level, specifically, when compared with SEAs of other spinal cord levels. Untreated, this infection can result in permanent neurological sequelae with eventual progression to death if inadequately managed. Despite the seriousness of this disease, no articles have focused on the presentation, diagnosis, and treatment of SEAs of the thoracic level. For this reason, specific focus on SEAs of the thoracic level occurred when researchers designed and implemented the following systematic review. Methods: A query of Ovid-Medline and EMBASE, Cochrane Central, and additional review sources was conducted. Search criteria focused on articles specific to thoracic epidural abscesses. Results: Twenty-five articles met inclusion criteria. The most commonly reported symptoms present on admission included back pain, paraparesis/paraplegia, fever, and loss of bowel/bladder control. Significant risk factors included diabetes, intravenous drug use, and advanced age ( Conclusions: For the first time researchers have focused specifically on SEAs of the thoracic level, as opposed to previously published general analysis of SEAs as a whole. Based on the results, investigators recommend early magnetic resonance imaging of the spine, laboratory workup (sedimentation rate/C-reactive protein, complete blood count), abscess culture followed by empiric antibiotics, and immediate surgical decompression when neurological deficits are present

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Bicaudal D2, Dynein, and Kinesin-1 Associate with Nuclear Pore Complexes and Regulate Centrosome and Nuclear Positioning during Mitotic Entry

Mammalian Bicaudal D2 is the missing molecular link between cytoplasmic motor proteins and the nucleus during nuclear positioning prior to the onset of mitosis

Almost All of Kepler's Multiple Planet Candidates are Planets

We present a statistical analysis that demonstrates that the overwhelming majority of Kepler candidate multiple transiting systems (multis) indeed represent true, physically-associated transiting planets. Binary stars provide the primary source of false positives among Kepler planet candidates, implying that false positives should be nearly randomly-distributed among Kepler targets. In contrast, true transiting planets would appear clustered around a smaller number of Kepler targets if detectable planets tend to come in systems and/or if the orbital planes of planets encircling the same star are correlated. There are more than one hundred times as many Kepler planet candidates in multi-candidate systems as would be predicted from a random distribution of candidates, implying that the vast majority are true planets. Most of these multis are multiple planet systems orbiting the Kepler target star, but there are likely cases where (a) the planetary system orbits a fainter star, and the planets are thus significantly larger than has been estimated, or (b) the planets orbit different stars within a binary/multiple star system. We use the low overall false positive rate among Kepler multis, together with analysis of Kepler spacecraft and ground-based data, to validate the closely-packed Kepler-33 planetary system, which orbits a star that has evolved somewhat off of the main sequence. Kepler-33 hosts five transiting planets with periods ranging from 5.67 to 41 days.Comment: 16 pages, 9 figure

Phosphorylation controls autoinhibition of cytoplasmic linker protein-170

Author Posting. © American Society for Cell Biology, 2010. This article is posted here by permission of American Society for Cell Biology for personal use, not for redistribution. The definitive version was published in Molecular Biology of the Cell 21 (2010): 2661-2673, doi:10.1091/mbc.E09-12-1036.Cytoplasmic linker protein (CLIP)-170 is a microtubule (MT) plus-end-tracking protein that regulates MT dynamics and links MT plus ends to different intracellular structures. We have shown previously that intramolecular association between the N and C termini results in autoinhibition of CLIP-170, thus altering its binding to MTs and the dynactin subunit p150Glued (J. Cell Biol. 2004: 166, 1003–1014). In this study, we demonstrate that conformational changes in CLIP-170 are regulated by phosphorylation that enhances the affinity between the N- and C-terminal domains. By using site-directed mutagenesis and phosphoproteomic analysis, we mapped the phosphorylation sites in the third serine-rich region of CLIP-170. A phosphorylation-deficient mutant of CLIP-170 displays an "open" conformation and a higher binding affinity for growing MT ends and p150Glued as compared with nonmutated protein, whereas a phosphomimetic mutant confined to the "folded back" conformation shows decreased MT association and does not interact with p150Glued. We conclude that phosphorylation regulates CLIP-170 conformational changes resulting in its autoinhibition.This work was supported by National Institutes of Health grant GM-25062 (to G.G.B.); Netherlands Organization for Scientific Research grants (to A. A. and N. G.); a Cancer Genomics Centre grant (to J.v.H.); and Presidential Program of Russian Academy of Sciences and RFBP grant 05-04-4915 (to E.S.N.)

Evolution of a New Function by Degenerative Mutation in Cephalochordate Steroid Receptors

Gene duplication is the predominant mechanism for the evolution of new genes. Major existing models of this process assume that duplicate genes are redundant; degenerative mutations in one copy can therefore accumulate close to neutrally, usually leading to loss from the genome. When gene products dimerize or interact with other molecules for their functions, however, degenerative mutations in one copy may produce repressor alleles that inhibit the function of the other and are therefore exposed to selection. Here, we describe the evolution of a duplicate repressor by simple degenerative mutations in the steroid hormone receptors (SRs), a biologically crucial vertebrate gene family. We isolated and characterized the SRs of the cephalochordate Branchiostoma floridae, which diverged from other chordates just after duplication of the ancestral SR. The B. floridae genome contains two SRs: BfER, an ortholog of the vertebrate estrogen receptors, and BfSR, an ortholog of the vertebrate receptors for androgens, progestins, and corticosteroids. BfSR is specifically activated by estrogens and recognizes estrogen response elements (EREs) in DNA; BfER does not activate transcription in response to steroid hormones but binds EREs, where it competitively represses BfSR. The two genes are partially coexpressed, particularly in ovary and testis, suggesting an ancient role in germ cell development. These results corroborate previous findings that the ancestral steroid receptor was estrogen-sensitive and indicate that, after duplication, BfSR retained the ancestral function, while BfER evolved the capacity to negatively regulate BfSR. Either of two historical mutations that occurred during BfER evolution is sufficient to generate a competitive repressor. Our findings suggest that after duplication of genes whose functions depend on specific molecular interactions, high-probability degenerative mutations can yield novel functions, which are then exposed to positive or negative selection; in either case, the probability of neofunctionalization relative to gene loss is increased compared to existing models

Assessment of postoperative outcomes in spinal epidural abscess following surgical decompression

© 2018 Elsevier Inc. Background context: A spinal epidural abscess (SEA)is a serious condition that may be managed with antibiotics alone or with decompressive surgery combined with antibiotics. Purpose: The objectives of this study were to assess the clinical outcomes of SEA after surgical management and to identify the patient-level factors that are associated with outcomes following surgical decompression and removal of SEA. Study design/setting: Retrospective chart review analysis. Patient sample: An analysis of 154 consecutive patients who initially presented to a tertiary-care, academic medical center with SEA, and were subsequently treated with surgery between 2010 and 2015 was performed. Outcome measures: Postoperative predischarge American Spinal Injury Association Impairment Scale (AIS)scores, 6-month follow-up encounter AIS scores, need for revision surgery, and mortality during SEA surgery were the primary outcomes.Physiological Measures: AIS scores. Method: Fisher\u27s exact and Wilcoxon rank-sum tests were used to assess the associations between patient-level factors and surgical outcomes. Moreover, an interactive, predictive model for postoperative predischarge AIS score was developed using a proportional odds regression model. There was no funding secured for this study and there is no conflict of interest-associated biases. Results: One hundred fifty-four patients (mean age of 58 years)were treated using surgical decompression in addition to antibiotics. The majority of patients were Caucasian (81%)and male (61%). No intraoperative mortality was reported. A second SEA surgery was performed in 8% of patients. A comparison of the preoperative and postoperative predischarge AIS scores showed that 49% of patients maintained a score of E or improved, while 45% remained at their preoperative status and 6% worsened. Among a subset of patients (n=36; 23%)for whom a 6-month follow-up encounter occurred, 75% maintained an AIS score of E or improved, 19% remained at their preoperative status, and 6% worsened. Both the presence and longer duration of preoperative paresis was associated with an increased risk of remaining at the same AIS score or worsening at the predischarge encounter (both p\u3c.001). A predictive model for predischarge AIS scores was developed based on several patient characteristics. Conclusions: Surgical decompression can contribute to improving or maintaining AIS scores in a high percentage of SEA patients. The presence and duration of preoperative paresis are prognostic for poorer outcomes and suggest that rapid surgical intervention before paresis develops may lead to improved postoperative outcomes. Our modeling tool enables an estimation of probabilities of patients’ predischarge condition

The efficacy of intraoperative multimodal monitoring in pedicle subtraction osteotomies of the lumbar spine

© AANS 2019. OBJECTIVE Iatrogenic spine injury remains one of the most dreaded complications of pedicle subtraction osteotomies (PSOs) and spine deformity surgeries. Thus, intraoperative multimodal monitoring (IOM), which has the potential to provide real-time feedback on spinal cord signal transmission, has become the gold standard in such operations. However, while the benefits of IOM are well established in PSOs of the thoracic spine and scoliosis surgery, its utility in PSOs of the lumbar spine has not been robustly documented. The authors’ aim was to determine the impact of IOM on outcomes in patients undergoing PSO of the lumbar spine. METHODS All patients older than 18 years who underwent lumbar PSOs at the authors’ institution from 2007 to 2017 were analyzed via retrospective chart review and categorized into one of two groups: those who had IOM guidance and those who did not. Perioperative complications were designated as the primary outcome measure and postoperative quality of life (QOL) scores, specifically the Parkinson’s Disease Questionnaire–39 (PDQ-39) and Patient Health Questionnaire–9 (PHQ-9), were designated as secondary outcome measures. Data on patient demographics, surgical and monitoring parameters, and outcomes were gathered, and statistical analysis was performed to compare the development of perioperative complications and QOL scores between the two cohorts. In addition, the proportion of patients who reached minimal clinically important difference (MCID), defined as an increase of 4.72 points in the PDQ-39 score or a decrease of 5 points in the PHQ-9 score, in the two cohorts was also determined. RESULTS A total of 95 patients were included in the final analysis. IOM was not found to significantly impact the development of new postoperative deficits (p = 0.107). However, the presence of preoperative neurological comorbidities was found to significantly correlate with postoperative neurological complications (p = 0.009). Univariate analysis showed that age was positively correlated with MCID achievement 3 months after surgery (p = 0.018), but this significance disappeared at the 12-month postoperative time point (p = 0.858). IOM was not found to significantly impact MCID achievement at either the 3- or 12-month postoperative period as measured by PDQ-39 (p = 0.398 and p = 0.156, respectively). Similarly, IOM was not found to significantly impact MCID achievement at either the 3- or 12-month postoperative period, as measured by PHQ-9 (p = 0.230 and p = 0.542, respectively). Multivariate analysis showed that female sex was significantly correlated with MCID achievement (p = 0.024), but this significance disappeared at the 12-month postoperative time point (p = 0.064). IOM was not found to independently correlate with MCID achievement in PDQ-39 scores at either the 3- or 12-month postoperative time points (p = 0.220 and p = 0.097, respectively). CONCLUSIONS In this particular cohort, IOM did not lead to statistically significant improvement in outcomes in patients undergoing PSOs of the lumbar spine (p = 0.220). The existing clinical equipoise, however, indicates that future studies in this arena are necessary to achieve systematic guidelines on IOM usage in PSOs of the lumbar spine