Cervical spine metastases: techniques for anterior reconstruction and stabilization

pre-printThe surgical management of cervical spine metastases continues to evolve and improve. The authors provide an overview of the various techniques for anterior reconstruction and stabilization of the subaxial cervical spine after corpectomy for spinal metastases. Vertebral body reconstruction can be accomplished using a variety of materials such as bone autograft/allograft, polymethylmethacrylate, interbody spacers, and/or cages with or without supplemental anterior cervical plating. In some instances, posterior instrumentation is needed for additional stabilization

Measuring Channel Planform Change From Image Time Series: A Generalizable, Spatially Distributed, Probabilistic Method for Quantifying Uncertainty

Abstract Channels change in response to natural or anthropogenic fluctuations in streamflow and/or sediment supply and measurements of channel change are critical to many river management applications. Whereas repeated field surveys are costly and time‐consuming, remote sensing can be used to detect channel change at multiple temporal and spatial scales. Repeat images have been widely used to measure long‐term channel change, but these measurements are only significant if the magnitude of change exceeds the uncertainty. Existing methods for characterizing uncertainty have two important limitations. First, while the use of a spatially variable image co‐registration error avoids the assumption that errors are spatially uniform, this type of error, as originally formulated, can only be applied to linear channel adjustments, which provide less information on channel change than polygons of erosion and deposition. Second, previous methods use a level‐of‐detection (LoD) threshold to remove non‐significant measurements, which is problematic because real changes that occurred but were smaller than the LoD threshold would be removed. In this study, we present a new method of quantifying uncertainty associated with channel change based on probabilistic, spatially varying estimates of co‐registration error and digitization uncertainty that obviates a LoD threshold. The spatially distributed probabilistic (SDP) method can be applied to both linear channel adjustments and polygons of erosion and deposition, making this the first uncertainty method generalizable to all metrics of channel change. Using a case study from the Yampa River, Colorado, we show that the SDP method reduced the magnitude of uncertainty and enabled us to detect smaller channel changes as significant. Additionally, the distributional information provided by the SDP method allowed us to report the magnitude of channel change with an appropriate level of confidence in cases where a simple LoD approach yielded an indeterminate result

The long-lived queen : reproduction and longevity in female eusocial Damaraland mole-rats (Fukomys damarensis)

The inverse relationship between reproduction and lifespan is one of the main concepts of life history theory. This association has been observed in most taxa, although exceptions have been found in which a breeding female outlives her non-reproductive cohorts. This relationship is well known in social insects, and it has recently come to light that reproductive females of certain social mole-rat species also exhibit extended lifespans relative to non-breeders. We analysed mark–recapture data over 13 years in 12 colonies of Damaraland mole-rats (Fukomys damarensis) to assess if colony queens lived longer than non-reproductive adult females. Queens were recaptured up to 8.5 years after initial capture (X = 6.2 years); significantly longer than non-reproductive females (X = 1.3 years), suggesting that a colony queen lives longer than her non-reproductive subordinates. This difference may be attributed to both physiological and social factors which may relax reproductive costs in queens.C.M.S. acknowledges funding from the University of Pretoria, J.U.M.J. acknowledges funding from the University of Cape Town and N.C.B. acknowledges funding from the University of Pretoria and the National Research Foundation.http://africanzoology.journals.ac.za/am2013ab201

Reproduction is associated with a tissue-dependent reduction of oxidative stress in eusocial female Damaraland mole-rats (Fukomys damarensis)

Oxidative stress has been implicated as both a physiological cost of reproduction and a driving force on an animal’s lifespan. Since increased reproductive effort is generally linked with a reduction in survival, it has been proposed that oxidative stress may influence this relationship. Support for this hypothesis is inconsistent, but this may, in part, be due to the type of tissues that have been analyzed. In Damaraland mole-rats the sole reproducing female in the colony is also the longest lived. Therefore, if oxidative stress does impact the trade-off between reproduction and survival in general, this species may possess some form of enhanced defense. We assessed this relationship by comparing markers of oxidative damage (malondialdehyde, MDA; protein carbonyls, PC) and antioxidants (total antioxidant capacity, TAC; superoxide dismutase, SOD) in various tissues including plasma, erythrocytes, heart, liver, kidney and skeletal muscle between wild-caught reproductive and non-reproductive female Damaraland mole-rats. Reproductive females exhibited significantly lower levels of PC across all tissues, and lower levels of MDA in heart, kidney and liver relative to non-reproductive females. Levels of TAC and SOD did not differ significantly according to reproductive state. The reduction in oxidative damage in breeding females may be attributable to the unusual social structure of this species, as similar relationships have been observed between reproductive and non-reproductive eusocial insects.A DST-NRF SARChI research chair for Behavioural Ecology and Physiology to NCB and a University of Pretoria postdoctoral fellowship to CMS.http://www.plosone.orgam201

The Expression of Epac2 and GluA3 in an Alzheimer's Disease Experimental Model and Postmortem Patient Samples

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by amyloid beta (Aβ) and hyperphosphorylated tau accumulation in the brain. Recent studies indicated that memory retrieval, rather than memory formation, was impaired in the early stage of AD. Our previous study reported that pharmacological activation of hippocampal Epac2 promoted memory retrieval in C57BL/6J mice. A recent study suggested that pharmacological inhibition of Epac2 prevented synaptic potentiation mediated by GluA3-containing AMPARs. In this study, we aimed to investigate proteins associated with Epac2-mediated memory in hippocampal postmortem samples of AD patients and healthy controls compared with the experimental AD model J20 and wild-type mice. Epac2 and phospho-Akt were downregulated in AD patients and J20 mice, while Epac1 and phospho-ERK1/2 were not altered. GluA3 was reduced in J20 mice and tended to decrease in AD patients. PSD95 tended to decrease in AD patients and J20. Interestingly, AKAP5 was increased in AD patients but not in J20 mice, implicating its role in tau phosphorylation. Our study points to the downregulation of hippocampal expression of proteins associated with Epac2 in AD. </p

Acid Sphingomyelinase Regulates Platelet Cell Membrane Scrambling, Secretion, and Thrombus Formation

Objective-Platelet activation is essential for primary hemostasis and acute thrombotic vascular occlusions. On activation, platelets release their prothrombotic granules and expose phosphatidylserine, thus fostering thrombin generation and thrombus formation. In other cell types, both degranulation and phosphatidylserine exposure are modified by sphingomyelinase-dependent formation of ceramide. The present study thus explored whether acid sphingomyelinase participates in the regulation of platelet secretion, phosphatidylserine exposure, and thrombus formation. Approach and Results-Collagen-related peptide-induced or thrombin-induced ATP release and P-selectin exposure were significantly blunted in platelets from Asm-deficient mice (Smpd1(-/-)) when compared with platelets from wild-type mice (Smpd1(+/+)). Moreover, phosphatidylserine exposure and thrombin generation were significantly less pronounced in Smpd1(-/-) platelets than in Smpd1(+/+) platelets. In contrast, platelet integrin alpha(IIb)beta(3) activation and aggregation, as well as activation-dependent Ca2+ flux, were not significantly different between Smpd1(-/-) and Smpd1(+/+) platelets. In vitro thrombus formation at shear rates of 1700 s(-1) and in vivo thrombus formation after FeCl3 injury were significantly blunted in Smpd1(-/-) mice while bleeding time was unaffected. Asm-deficient platelets showed significantly reduced activation-dependent ceramide formation, whereas exogenous ceramide rescued diminished platelet secretion and thrombus formation caused by Asm deficiency. Treatment of Smpd1(+/+) platelets with bacterial sphingomyelinase (0.01 U/mL) increased, whereas treatment with functional acid sphingomyelinase-inhibitors, amitriptyline or fluoxetine (5 mu mol/L), blunted activation-dependent platelet degranulation, phosphatidylserine exposure, and thrombus formation. Impaired degranulation and thrombus formation of Smpd1(-/-) platelets were again overcome by exogenous bacterial sphingomyelinase. Conclusions-Acid sphingomyelinase is a completely novel element in the regulation of platelet plasma membrane properties, secretion, and thrombus formation

HIF1A-Dependent Induction of Alveolar Epithelial PFKFB3 Dampens Acute Lung Injury

Acute lung injury (ALI) is a severe form of lung inflammation causing acute respiratory distress syndrome in patients. ALI pathogenesis is closely linked to uncontrolled alveolar inflammation. We hypothesize that specific enzymes of the glycolytic pathway could function as key regulators of alveolar inflammation. Therefore, we screened isolated alveolar epithelia from mice exposed to ALI induced by injurious ventilation to assess their metabolic responses. These studies pointed us toward a selective role for isoform 3 of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3). Pharmacologic inhibition or genetic deletion of Pfkfb3 in alveolar epithelia (Pfkfb3loxP/loxP SPC-ER-Cre+ mice) was associated with profound increases in ALI during injurious mechanical ventilation or acid instillation. Studies in genetic models linked Pfkfb3 expression and function to Hif1a. Not only did intratracheal pyruvate instillation reconstitute Pfkfb3loxP/loxP or Hif1aloxP/loxP SPC-ER-Cre+ mice, but pyruvate was also effective in ALI treatment of wild-type mice. Finally, proof-of-principle studies in human lung biopsies demonstrated increased PFKFB3 staining in injured lungs and colocalized PFKFB3 to alveolar epithelia. These studies reveal a specific role for PFKFB3 in counterbalancing alveolar inflammation and lay the groundwork for novel metabolic therapeutic approaches during ALI

Relationship between resident workload and self-perceived learning on inpatient medicine wards: a longitudinal study

BACKGROUND: Despite recent residency workload and hour limitations, little research on the relationship between workload and learning has been done. We sought to define residents' perceptions of the optimal patient workload for learning, and to determine how certain variables contribute to those perceptions. Our hypothesis was that the relationship between perceived workload and learning has a maximum point (forming a parabolic curve): that either too many or too few patients results in sub-optimal learning. METHODS: Residents on inpatient services at two academic teaching hospitals reported their team and individual patient censuses, and rated their perception of their learning; the patient acuity; case variety; and how challenged they felt. To estimate maximum learning scores, linear regression models with quadratic terms were fit on learning score. RESULTS: Resident self-perceived learning correlated with higher acuity and greater heterogeneity of case variety. The equation of census versus learning score, adjusted for perception of acuity and case mix scores, showed a parabolic curve in some cases but not in others. CONCLUSION: These data suggest that perceived resident workload is complex, and impacted by additional variables including patient acuity and heterogeneity of case variety. Parabolic curves exist for interns with regard to overall census and for senior residents with regard to new admissions on long call days

Pharmacological Inhibition of Epac1 Averts Ferroptosis Cell Death by Preserving Mitochondrial Integrity

Exchange proteins directly activated by cAMP (Epac) proteins are implicated in a wide range of cellular functions including oxidative stress and cell survival. Mitochondrial-dependent oxidative stress has been associated with progressive neuronal death underlying the pathology of many neurodegenerative diseases. The role of Epac modulation in neuronal cells in relation to cell survival and death, as well as its potential effect on mitochondrial function, is not well established. In immortalized hippocampal (HT-22) neuronal cells, we examined mitochondria function in the presence of various Epac pharmacological modulators in response to oxidative stress due to ferroptosis. Our study revealed that selective pharmacological modulation of Epac1 or Epac2 isoforms, exerted differential effects in erastin-induced ferroptosis conditions in HT-22 cells. Epac1 inhibition prevented cell death and loss of mitochondrial integrity induced by ferroptosis, while Epac2 inhibition had limited effects. Our data suggest Epac1 as a plausible therapeutic target for preventing ferroptosis cell death associated with neurodegenerative diseases