Cervical end of an occipitocervical fusion: a biomechanical evaluation of 3 constructs

Journal ArticleObject. Stabilization with rigid screw/rod fixation is the treatment of choice for craniocervical disorders requiring operative stabilization. The authors compare the relative immediate stiffness for occipital plate fixation in concordance with transarticular screw fixation (TASF), C-1 lateral mass and C-2 pars screw (C1L-C2P), and C-1 lateral mass and C-2 laminar screw (C1L-C2L) constructs, with and without a cross-link. Methods. Ten intact human cadaveric spines (Oc-C4) were prepared and mounted in a 7-axis spine simulator. Each specimen was precycled and then tested in the intact state for flexion/extension, lateral bending, and axial rotation. Motion was tracked using the OptoTRAK 3D tracking system. The specimens were then destabilized and instrumented with an occipital plate and TASF. The spine was tested with and without the addition of a cross-link. The C1L-C2P and C1L-C2L constructs were similarly tested. Results. All constructs demonstrated a significant increase in stiffness after instrumentation. The C1L-C2P construct was equivalent to the TASF in all moments. The C1L-C2L was significantly weaker than the C1L-C2P construct in all moments and significantly weaker than the TASF in lateral bending. The addition of a cross-link made no difference in the stiffness of any construct. Conclusions. All constructs provide significant immediate stability in the destabilized occipitocervical junction. Although the C1L-C2P construct performed best overall, the TASF was similar, and either one can be recommended. Decreased stiffness of the C1L-C2L construct might affect the success of clinical fusion. This construct should be reserved for cases in which anatomy precludes the use of the other two

Surgical treatment of occipitocervical instability

Journal ArticleOBJECTIVE: Instability of the occipitocervical junction can be a challenging surgical problem because of the unique anatomic and biomechanical characteristics of this region. We review the causes of instability and the development of surgical techniques to stabilize the occipitocervical junction. METHODS: Occipitocervical instrumentation has advanced significantly, and modern modular screw-based constructs allow for rigid short-segment fixation of unstable elements while providing the stability needed to achieve successful fusion in nearly 100% of patients. This article reviews the preoperative planning, the variety of instrumentation and surgical strategies, as well as the postoperative care of these patients. RESULTS: Current constructs use occipital plates that are rigidly fixed to the thick midline keel of the occipital bone, polyaxial screws that can be placed in many different trajectories, and rods that are bent to approximate the acute occipitocervical angle. These modular constructs provide a variety of methods to achieve fixation in the atlantoaxial complex, including transarticular screws or C1 lateral mass screws in combination with C2 pars, C2 pedicle, or C2 translaminar trajectories. CONCLUSION: Surgical techniques for occipitocervical instrumentation and fusion are technically challenging and require meticulous preoperative planning and a thorough understanding of the regional anatomy, instrumentation, and constructs. Modern screw-based techniques for occipitocervical fusion have established clinical success and demonstrated biomechanical stability, with fusion rates approaching 100%

Impact of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial

Background: Meningococcal conjugate vaccines protect individuals directly, but also confer herd protection by interrupting carriage transmission. This Phase III observer-blind, randomised, controlled study evaluated the effects of meningococcal quadrivalent (ACWY) glycoconjugate (MenACWY-CRM) or serogroup B (4CMenB) vaccination on meningococcal carriage rates in young adults. Methods: University students (aged 18–24 years) from ten sites in England were randomised to receive two vaccinations one month apart: two doses of Japanese Encephalitis vaccine (controls), two doses of 4CMenB (4CMenB), or one dose of MenACWY-CRM then placebo (MenACWY-CRM). Meningococci were isolated from oropharyngeal swabs collected before vaccination and at five scheduled intervals over one year. Primary analysis was cross-sectional carriage one month after the vaccine course; secondary analyses included comparison of carriage at any time point after primary analysis until study termination. Findings: 2954 subjects were randomised (control, n=987; 4CMenB, n=988; MenACWY-CRM, n=979); approximately one-third of each group was positive for meningococcal carriage at study entry. By one month, there was no significant difference in carriage between controls and 4CMenB (Odds Ratios (OR) [95% CI]; 1·2 [0·8−1·7]) or MenACWY-CRM (OR [95% CI], 0·9 [0·6–1·3]) groups. From three months after dose two, 4CMenB vaccination resulted in significantly lower carriage of any meningococcal strain (calculated efficacy 18·2% [95% CI: 3·4–30·8]) and capsular groups BCWY (calculated efficacy 26·6% [95% CI: 10·5–39·9]) compared to control vaccination. Significantly lower carriage rates were also observed in the MenACWY-CRM group compared with controls: calculated efficacies 39·0% [95%CI: 17·3-55·0] and 36.2% [95%CI: 15·6-51·7] for serogroups Y and CWY, respectively. Interpretation: MenACWY-CRM and 4CMenB vaccines reduced meningococcal carriage rates over 12 months post-vaccination and, therefore, may affect transmission where widely implemented

Unnatural Amino Acid Incorporation into Virus-Like Particles

Virus-like particles composed of hepatitis B virus (HBV) or bacteriophage Qβ capsid proteins have been labeled with azide- or alkyne-containing unnatural amino acids by expression in a methionine auxotrophic strain of E. coli. The substitution does not affect the ability of the particles to self-assemble into icosahedral structures indistinguishable from native forms. The azide and alkyne groups were addressed by Cu(I)-catalyzed [3 + 2] cycloaddition: HBV particles were decomposed by the formation of more than 120 triazole linkages per capsid in a location-dependent manner, whereas Qβ suffered no such instability. The marriage of these well-known techniques of sense-codon reassignment and bioorthogonal chemical coupling provides the capability to construct polyvalent particles displaying a wide variety of functional groups with near-perfect control of spacing

Analysis of Abrupt Transitions in Ecological Systems

The occurrence and causes of abrupt transitions, thresholds, or regime shifts between ecosystem states are of great concern and the likelihood of such transitions is increasing for many ecological systems. General understanding of abrupt transitions has been advanced by theory, but hindered by the lack of a common, accessible, and data-driven approach to characterizing them. We apply such an approach to 30–60 years of data on environmental drivers, biological responses, and associated evidence from pelagic ocean, coastal benthic, polar marine, and semi-arid grassland ecosystems. Our analyses revealed one case in which the response (krill abundance) linearly tracked abrupt changes in the driver (Pacific Decadal Oscillation), but abrupt transitions detected in the three other cases (sea cucumber abundance, penguin abundance, and black grama grass production) exhibited hysteretic relationships with drivers (wave intensity, sea-ice duration, and amounts of monsoonal rainfall, respectively) through a variety of response mechanisms. The use of a common approach across these case studies illustrates that: the utility of leading indicators is often limited and can depend on the abruptness of a transition relative to the lifespan of responsive organisms and observation intervals; information on spatiotemporal context is useful for comparing transitions; and ancillary information from associated experiments and observations aids interpretation of response-driver relationships. The understanding of abrupt transitions offered by this approach provides information that can be used to manage state changes and underscores the utility of long-term observations in multiple sentinel sites across a variety of ecosystems.Organismic and Evolutionary Biolog

“A Case of Telecommunications (Mis)Management” Case Analyses

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68983/2/10.1177_0893318999124005.pd

The structure of BVU2987 from Bacteroides vulgatus reveals a superfamily of bacterial periplasmic proteins with possible inhibitory function.

Proteins that contain the DUF2874 domain constitute a new Pfam family PF11396. Members of this family have predominantly been identified in microbes found in the human gut and oral cavity. The crystal structure of one member of this family, BVU2987 from Bacteroides vulgatus, has been determined, revealing a β-lactamase inhibitor protein-like structure with a tandem repeat of domains. Sequence analysis and structural comparisons reveal that BVU2987 and other DUF2874 proteins are related to β-lactamase inhibitor protein, PepSY and SmpA_OmlA proteins and hence are likely to function as inhibitory proteins

NuSTAR Observations of the State Transition of Millisecond Pulsar Binary PSR J1023+0038

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GLA-modified RNA treatment lowers GB3 levels in iPSC-derived cardiomyocytes from Fabry-affected individuals

Recent studies in non-human model systems have shown therapeutic potential of nucleoside-modified messenger RNA (modRNA) treatments for lysosomal storage diseases. Here, we assessed the efficacy of a modRNA treatment to restore the expression of the galactosidase alpha (GLA), which codes for α-Galactosidase A (α-GAL) enzyme, in a human cardiac model generated from induced pluripotent stem cells (iPSCs) derived from two individuals with Fabry disease. Consistent with the clinical phenotype, cardiomyocytes from iPSCs derived from Fabry-affected individuals showed accumulation of the glycosphingolipid Globotriaosylceramide (GB3), which is an α-galactosidase substrate. Furthermore, the Fabry cardiomyocytes displayed significant upregulation of lysosomal-associated proteins. Upon GLA modRNA treatment, a subset of lysosomal proteins were partially restored to wild-type levels, implying the rescue of the molecular phenotype associated with the Fabry genotype. Importantly, a significant reduction of GB3 levels was observed in GLA modRNA-treated cardiomyocytes, demonstrating that α-GAL enzymatic activity was restored. Together, our results validate the utility of iPSC-derived cardiomyocytes from affected individuals as a model to study disease processes in Fabry disease and the therapeutic potential of GLA modRNA treatment to reduce GB3 accumulation in the heart.</p

Childhood socioeconomic position and objectively measured physical capability levels in adulthood: a systematic review and meta-analysis

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and Findings:&lt;/b&gt; Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.&lt;/p&gt