We present our perioperative minimally invasive spine surgery technique using intraoperative computed tomography image-guided navigation for the treatment of various lumbar spine pathologies. We present an illustrative case of a patient undergoing minimally invasive percutaneous posterior spinal fusion assisted by the O-arm system with navigation. We discuss the literature and the advantages of the technique over fluoroscopic imaging methods: lower occupational radiation exposure for operative room personnel, reduced need for postoperative imaging, and decreased revision rates. Most importantly, we demonstrate that use of intraoperative cone beam CT image-guided navigation has been reported to increase accuracy. Neurological sequelae may result from pedicle screw misplacement during spinal instrumentation and fusion, and inaccurate placement can be fairly frequent with conventional fluoroscopy –3. BecauThe drawbacks associated with conventional intraoperative imaging methods have increased the interest in improving navigation methods in spine surgery, evolving tremendously over the last few years –12. Use Most recently, introduction of the O-arm  has allowed spine surgeons to perform minimally invasive procedures accurately, safely, and more efficiently . The O-aIn a recent international, multicenter, prospective study over a 16-month period, 353 patients underwent 1922 pedicle screw placements using the O-arm [In this paper, we describe our perioperative MIS technique for placing percutaneous spinal instrumentation utilizing the O-arm with navigation.All O-arm MISS patients were placed prone on a Jackson radiolucent spinal operating table, and all pressure points were padded appropriately. The dorsal lumbar spine was sterilely prepped and care was taken to drape the entire lumbar spine as wide as possible. The authors recommend having a wide draping area as it allows for skin surface anatomy identification  and gives orientation during the entire procedure.Selection of ideal reference frame and placement are dependent on the goals of the surgeon and anatomy of the patient. A percutaneous reference pin was routinely placed in the left ilium inferior to the level of the posterior superior iliac spine for short-segment percutaneous pedicle screw instrumentation Figures . For MISThree-dimensional CT images were obtained using a cone beam mobile CT scanner  and were transferred to the computer-assisted StealthStation surgical navigation workstation. All navigated probes and instrumentation were calibrated. Although it is possible to keep the O-arm in the sterile surgical field during the entire procedure, it was our preference to remove the O-arm and station it in the operating room.Paramedian laterally based skin incisions were planned out using a navigated probe . PlanninIn our earlier experience with PSIS percutaneous reference frames, a Caspar pin was directly inserted through a percutaneous midline incision into one of the spinous processes within the acquired CT image. In MISS navigation surgery, there is oftentimes no clear anatomic point that can be referenced to determine navigation accuracy. Especially in morbidly obese patients, bony surface anatomy can be hard to palpate and assess. By obtaining a CT image with the Caspar pin inserted into the bony spinous process, the surgeon can reliably use this point as a check for accuracy for all navigated instruments .A navigated dilator was inserted through the Wiltse paraspinal muscle interval and docked onto the ideal pedicle screw starting point—lateral to the facet joint Figures . Serial In short-segment lumbar fixation, we inserted the rod under direct visualization using a rod holder Figures . For lonManagement of guide wires during navigated MISS is extremely critical. As there is no ability to navigate the tip of the guide wire in real time, there is a theoretical risk of inadvertently pushing the guide wire through the vertebral body and into the abdominal cavity. In our technique, during navigated MISS, we pay special attention to guide wire location. After a cannulated instrument or screw is started in the proximal pedicle, we recommend pulling the guide wire back several inches. This essentially eliminates the possibility of inadvertent guide wire advancement. “Guide wireless” navigated MISS techniques have also been previously described . The revIntraoperative confirmatory O-arm images and postoperative CT scans were analyzed for evidence of bony pedicle wall breach. The majority of postoperative CT scans were obtained in the outpatient setting for diagnosis purposes or to confirm evidence of bony fusion. Whenever possible, immediate postoperative CT scans were generally not obtained on asymptomatic patients secondary to concern for undue radiation exposure.The newest generation of navigation technology—intraoperative computed tomography image-guided navigation (CT-IGN) with the mobile O-arm scanner—has made a tremendous impact on spinal surgery and there is a wealth of literature on the topic , 11, 25.In a more recent study, Lau et al. investigated computer-guided intraoperative O-arm fluoroscopy in aiding the visualization of pedicle screw placement via minimally invasive transforaminal interbody fusion (MITLIF) . While pPark et al. were the first to publish a study to evaluate the O-arm alongside minimally invasive pedicle screw placement . In 11 pThree-dimensional image guidance has also been applied to the cervical spine. Because it offers a vast amount of anatomic information and allows safer approaches around complex anatomy, such technology can be quite helpful for navigating the cervical spine . Though Oertel et al. presented 50 patients that underwent spinal stabilization surgeries, 10 of which were through percutaneous pedicle screws . Of the P < 0.001) and the mean operative time was 200 versus 221 minutes (P < 0.03), respectively. The study builds upon the results of Oertel et al., reporting similar excellent outcomes with O-arm in MISS cases [The O-arm's application to MISS procedure was recently described in a major study by Houten et al. . They prThe cone beam O-arm system offers several advantages over prevailing imaging methods, especially for MISS which heavily benefits from use of navigation. There is the capacity for reduction in radiation exposure to the operating room staff that has been cited extensively in the literature , 31, 32.


During human brain development, cortical gyrification, which is believed to facilitate compact wiring of neural circuits, has been shown to follow an inverted U-shaped curve, coinciding with the two-stage neurodevelopmental process of initial synaptic overproduction with subsequent pruning. This trajectory allows postnatal experiences to refine the wiring, which may manifest as endophenotypic changes in cortical gyrification. Diving experts, typical elite athletes who commence intensive motor training at a very young age in their early childhood, serve ideal models for examining the gyrification changes related to long-term intensive diving training. Using local gyrification index (LGI), we compared the cortical gyrification between 12 diving experts and 12 controls. Compared with controls, diving experts showed widespread LGI reductions in regions relevant to diving performance. Negative correlations between LGIs and years of diving training were also observed in diving experts. Further exploratory network efficiency analysis of structural cortical networks, inferred from interregional correlation of LGIs, revealed comparable global and local efficiency in diving experts relative to controls. These findings suggest that gyrification reductions in diving experts may be the result of long-term diving training which could refine the neural circuitry (via synaptic pruning) and might be the anatomical substrate underlying their extraordinary diving performance. The human cerebral cortex is a highly complex structure with rich gyri and sulci. Gyrification, the process of gyrus and sulcus formation, allows a larger cortical surface area (therefore a greater number of neurons) to fit in the skull, facilitating the development of compact wiring for efficient information processingCortical gyrification of the human brain begins between 10 and 15 weeks of fetal life68101112131141617Diving is a competitive sport that greatly exceeds those of simple physical movement or locomotion and demands precise motor control, timing, coordination and excellent proprioceptive sensation during the execution of the motions. Diving experts are typical elite athletes that usually commence intensive motor training at a very young age in their early childhood, and therefore serve ideal models for examining the cerebral neuroplastic changes related to long-term intensive diving training. Of note, our previous studies found that diving experts had significant changes in gray matter volume and cortical thickness in multiple brain areas2124Using surface-based LGI, the present study aims to investigate cortical gyrification changes in diving experts compared with matched controls. Specifically, we fitted vertex-wise linear model to compare the LGI maps between 12 professional diving experts and 12 controls. We hypothesized that diving experts would show LGI changes in multiple brain regions in response to long-term intensive diving training, including some motor cortices and the parahippocampal cortex. Given structural covariance of LGI has been used to construct structural brain networksAll subjects of this study participated in our previous studies223. The scan time for the T1-weighted sequence was 486 s. During the scanning, each subject reclined in a supine position on the bed of the scanner and was asked to lie still during the imaging time. A foam head holder and padding were placed around the subject’s head. In addition, headphones were provided to block background noise.High-resolution anatomical images of the whole brain were acquired on a 3-tesla Trio system  with 12-channel head matrix coil using a magnetisation-prepared rapid-acquisition gradient echo sequence. The following parameters were used for the volumetric acquisition: repetition time = 2530 ms, echo time = 3.37 ms, flip angle = 7 degrees, slice thickness = 1.33 mm, FOV = 256 mm, 512 × 512- pixel matrix. The voxel size was 0.5 × 0.5 × 1.33 mmFreeSurfer ( http://surfer.nmr.mgh.harvard.edu/) to obtain the LGI. Briefly, the LGI map can be obtained in four stepsEach scan was processed using FreeSurfer, which includes 68 anatomical regions . The LGI for each cortical region was calculated as the average LGI of all vertices in that region. Secondly, the interregional correlation matrix C = [cij]  of each group was obtained by calculating the Pearson correlation coefficients across individuals between the LGIs of every pair of regionsB = [bij], where bij is 1 if the absolute value of the correlation coefficient cij between regions i and j is larger than a given correlation threshold, and 0 otherwise.Firstly, each individual LGI map was parcellated using the built-in Desikan atlas of G was represented by a binarized matrix B with N nodes and K edges, where nodes are cortical regions and edges indicate undirected links corresponding to its nonzero elements. To ensure the networks of two groups have the same number of edges and are comparable, the correlation matrix C of each group was thresholded into a binarized matrix with a fixed sparsity SK in a graph divided by the maximum possible number of edges N(N − 1)/2. Here, a wide range of sparsity thresholds 10% ≤ S ≤ 40% were used.The undirected network (graph) G with N nodes and K edges, the global efficiency Eglob (G) is defined as27In this study, we employed the network efficiency measurements to examine the global topological properties of the structural cortical networks obtained for the two groups. For a graph dij is the shortest path length between node i and node j in G. The local efficiency Eloc(G) is measured as27where Gi denotes the subgraph composed of the nearest neighbors of node i.where Vertex-by-vertex contrasts of LGI were performed between diving experts and controls. Specifically, each contrast was entered into a vertex-by-vertex GLM including diagnosis, sex, exact age and ICV as covariates. Subsequently, random field theory (RFT) was used to assess the significance of the statistical maps and to correct for multiple comparisonsWithin the diving experts, vertex-wise correlation analyses were performed to determine the associations between LGI and years of diving training, while removing the partial effect of age, sex and ICV. Then, the same procedures as the above between-group analysis on LGI were repeated to correct for multiple comparisons and to report the results of the correlation analysis.S ≤ 40%). Differences of the normalized integrals of each efficiency parameter were then calculated from two randomized groups to obtain a null distribution of differences, against which we can compute the P values of the actual difference of normalized integrals of the efficiency parameters between diving experts and controls.For group comparison of the network efficiency parameters, non-parametric permutation test with 1000 repetitions was adopted. For each iteration, we reassigned the LGIs of each participant randomly to one of two new groups with the sample size identical as the two groups. For each randomized group, we calculated the global efficiency and local efficiency as well as their normalized integrals  across a range of sparsity thresholds . This cluster involves the right inferior temporal gyrus, fusiform gyrus, parahippocampal gyrus and entorhinal cortex . Under aNon-parametric permutation test revealed no significant difference of the normalized integrals of the global efficiency (P = 0.37) and local efficiency (P = 0.48) between diving experts and controls.Using a surface-based LGI, the present study investigated the cortical gyrification changes in diving experts compared with matched controls. We also performed network efficiency analyses of structural cortical networks inferred from interregional correlation of LGIs to explore whether diving experts are more efficient in information processing. The first major finding was the widespread LGI reduction in diving experts. The cortical areas with LGI reductions were almost symmetrically distributed over both hemispheres, involving the bilateral premotor cortex, bilateral medial temporal lobe, bilateral prefrontal cortex, left precentral gyrus, superior parietal cortex, superior temporal sulcus, and the right inferior parietal cortex. Within the diving experts, vertex-wise correlation analyses revealed two clusters involving the right inferior temporal gyrus, fusiform gyrus, entorhinal cortex and premotor cortex where LGIs were negatively correlated with years of diving training. Next, we documented comparable global and local efficiency in diving experts relative to controls. Taken together, these findings indicate that cortical gyrification changes in diving experts may be the result of long-term diving training which could refine the neural circuitry and might be the anatomical substrate underlying their extraordinary diving performance.As demonstrated by many previous studies, long-term intensive training could influence brain structure and function along with the underlying connectivity. In the present study, we investigated the specific effect of long-term diving training on cortical gyrification by examining diving experts vs matched controls. Compared with controls, widespread LGI reductions were observed in diving experts. Among the regions showing significant LGI reductions, the differences seen in the posterior parietal cortex, medial temporal lobe and premotor cortex were of particular interest. These regions were shown to be directly or indirectly connected with the vestibular nuclei29313537393943Additional areas of LGI reductions were found in the medial prefrontal cortices  and lateral orbitofrontal cortex. The medial prefrontal cortex has been shown to play important roles in retrieval of both recent and remote memories5152To test whether diving experts are more efficient in information processing, we performed exploratory network efficiency analyses on the structural networks inferred from interregional correlation of LGI. Unexpectedly, we observed no significant difference in the normalized integrals of global efficiency and local efficiency between diving experts and controls. The negative result of the network efficiency analyses could be due to the small sample size of the current study, which resulted in low statistical power.Over the years, a number of studies have been conducted to investigate the developmental trajectory of cortical gyrification. Specifically, a longitudinal study on the cortical gyrification development of infants in the first 2 postnatal years reported that the cortical LGI has age-related and marked development with 16.1% increase in the first year and 6.6% increase in the second year14113In addition, the observed cortical gyrification alterations in diving experts can be explained by prevailing theories about the development of cortical gyrification24584215818This study had some limitations that should be addressed. First, due to the cross-sectional design of the current study, it is indefinite that the cortical gyrification reductions we found were directly caused by diving training. Hence, the major future challenge is to figure out whether the cortical gyrification changes in diving experts were actually induced by diving training, or whether they are inherent prerequisites for the beginning and continuation of diving. Second, the sample size of the current study is relatively small, making the findings of network analysis preliminary in nature. Moreover, the cortical networks were constructed by assessing the interregional structural covariance of cortical gyrification, which only provided an indirect measure of the anatomical networks. Therefore, more comprehensive network analyses with diffusion tensor imaging and also a larger sample size are warranted.Using a surface-based LGI, we found widespread cortical gyrification reductions in diving experts compared with controls. Within the diving experts, vertex-wise correlation analyses showed significant negative correlations between years of diving training and LGIs of a cluster in the medial temporal lobe. Meanwhile, graph-theoretic network analysis showed comparable global efficiency and local efficiency in diving experts relative to controls. These findings suggests that cortical gyrification reductions in diving experts may be the result of long-term diving training which could refine the neural circuitry (via synaptic pruning) and might be the anatomical substrate underlying their extraordinary diving performance.How to cite this article: Zhang, Y. et al. Effects of Long-term Diving Training on Cortical Gyrification. Sci. Rep.6, 28243; doi: 10.1038/srep28243 (2016).


Interestingly, changes in balance were unrelated to changes in the distance walked . For persons after stroke similar to those studied, improving balance may not be sufficient to improve long-distance walking function.Stroke survivors identify a reduced capacity to walk farther distances as a factor limiting their engagement at home and in community. Previous observational studies have shown that measures of balance ability and balance self-efficacy are strong predictors of long-distance walking function after stroke. Consequently, recommendations to target balance during rehabilitation have been put forth. The purpose of this study was to determine if the changes in balance and long-distance walking function observed following a 12-week poststroke walking rehabilitation program were related. For thirty-one subjects with hemiparesis after stroke, this investigation explored the cross-sectional  and longitudinal  relationships between measures of standing balance, walking balance, and balance self-efficacy versus long-distance walking function as measured via the 6-minute walk test (6MWT). A regression model containing all three balance variables accounted for 60.8% of the variance in 6MWT performance ( The recovery of walking function is an ultimate goal of rehabilitation after stroke . Indeed,Recent observational studies have shown balance to be a powerful predictor of poststroke walking function –13 and aThirty-one subjects with hemiparesis after stroke were studied. These subjects were those randomized to the treatment arms see  of a cliSubjects participated in a treadmill and overground walking retraining program at a frequency of 3 sessions per week for 12 weeks. On the treadmill, subjects walked five bouts of 6 minutes at the maximum walking speed they could maintain for four minutes. Subjects either walked with or without functional electrical stimulation applied to the paretic ankle plantarflexors during late stance and dorsiflexors during swing phase in an alternating pattern of one minute on to one minute off. The FES component of the intervention has previously been described . SubjectThe 6-minute walk test (6MWT) , 16 servP < 0.05. The Shapiro-Wilk test determined data normality. The paired t-test or the Wilcoxon signed rank test—pending data normality—was used to determine whether changes in each variable followed the intervention period. Individual subject changes were compared to known minimal detectable change (MDC) values. Pearson r or Spearman rho correlation analyses measured the cross-sectional and change-score relationships between each balance measure versus the 6MWT. Multiple regression was used to quantify the independent contribution to performance in the 6MWT or to changes in the 6MWT of the balance measures found to be significantly related in the correlation analyses.Statistical analyses were performed using the SPSS 21 and G Power 3.1 software packages. The threshold for significance was set to N = 31). An a priori power analysis revealed that with 31 subjects, at an alpha of 0.05, this investigation would be powered at a level of 80% to detect a significant r = 0.453 (R2 of 0.21).Complete data sets were available for all subjects  = 13.931; P < 0.001); however, only dynamic balance (FGA) independently predicted the distance walked during the 6MWT . It should be noted that balance self-efficacy (ABC) trended towards significance as an independent predictor , but interestingly standing balance (BERG) did not .Consistent with previous work, correlation analyses demonstrated that each balance construct strongly correlated with long-distance walking function .Improvements in long-distance walking function, standing balance, walking balance, and balance self-efficacy were observed following the 12-week intervention period see . Ten subThe development of effective targeted walking interventions depends on the valid identification of deficits that, when improved, will result in the recovery of walking function. The findings of this study suggest that basing the development of targeted interventions solely on the findings of cross-sectional analyses may not be appropriate. Indeed, despite being highly predictive of walking function before training, changes in balance did not relate to the changes in walking function observed after training. Moreover, to our knowledge, this is the first study to demonstrate that standing balance does not independently contribute to walking function if dynamic balance and balance self-efficacy are controlled.Consistent with the findings of the present investigation, Bowden and colleagues reported that changes in standing balance (BERG), balance confidence (ABC), and walking balance  did not correlate with changes in self-selected walking speed (SSWS) . Bowden Previous findings by Patterson and colleagues  and SchmPatient-specific characteristics should be considered when planning interventions. For those patients with a high fall risk or history of falls, balance may be the primary limiting factor to improved walking function and should thus be a target during rehabilitation. Indeed, for these individuals, walking may be optimized to prevent falls. For example, Blennerhassett and colleagues demonstrate that community-dwelling individuals after stroke were more likely to fall and walk less distance during the 6MWT if they were concerned about falling, had limited confidence, and performed worse on measures of dynamic balance . As suchThis study investigated the relationships between changes in balance and changes in walking function following activity-based interventions that did not directly target balance abilities. For subjects whose balance deficits are limiting walking function, specific balance training may be necessary to produce changes in balance sufficient to alter walking function. However, it should be noted that both the treadmill and overground portions of the interventions studied did indirectly challenge balance abilities and a number of subjects had meaningful improvements (larger than known MDCs) in each balance measure considered. Even when evaluating the relationships between improvements in walking function versus improvements in balance for just these subjects, the relationships were weak and not significant.For limited community ambulators in the chronic phase of stroke recovery, improving balance may be insufficient to improve long-distance walking function. Moreover, basing interventions on cross-sectional relationships may not be appropriate.


Medical residency can be a time of increased psychological stress and sleep disturbance. We examine the prospective associations between self-reported sleep quality and resident wellness across a single training year.N=69) resident physicians completed the Brief Resident Wellness Profile  and the Pittsburgh Sleep Quality Index  at multiple occasions in a single training year. We examined the 1-month lagged effect of sleep disturbances on residents’ self-reported wellness.Sixty-nine  and the lagged within-person effect of resident sleep disturbance  were significant predictors of decreased resident wellness. Increases in sleep disturbances are a leading indicator of resident wellness, predicting decreased well-being 1 month later.Accounting for residents’ overall level of sleep disturbance across the entire study period, both the concurrent (within-person) within-occasion effect of sleep disturbance (Sleep quality exerts a significant effect on self-reported resident wellness. Periodic evaluation of sleep quality may alert program leadership and the residents themselves to impending decreases in psychological well-being. For new physicians, residency training is a time to gain knowledge in their chosen specialty and hone clinical skills. Many resident physicians, however, also experience significant psychological stress and sleep deprivation, both of which have detrimental effects on learning and clinical performance. Among residents, feelings of burnout, fatigue, depression, sleepiness, and reduced quality of life are all independently associated with an increased risk of future self-perceived major medical errors . ReformsN=69) resident physicians at variable post-graduate years from a range of specialties completed the standardized, Brief Resident Wellness Profile  and the Pittsburgh Sleep Quality Index  at multiple occasions beginning in September of a single training year . The BRWP asked participants to rate items about their general levels of psychological stress, satisfaction with their residency and life in general, and enthusiasm for their career goals; the PSQI is a subjective measure of sleep disturbance, which asks participants to rate the quality of their sleep in the prior 30 days, including how often they have had trouble falling asleep, how often they have used sleep medication, and how often they have had trouble staying awake while performing activities of daily living. Both measures provide reliable and valid information in their respective domains . Accounting for residents’ overall level of sleep disturbance across the entire study period, both the concurrent (within-person) within-occasion effect of sleep disturbance  and the lagged within-person effect of resident sleep disturbance  were significant predictors of decreased resident wellness. Increases in sleep disturbances are a leading indicator of resident wellness, predicting decreased subjective well-being 1 month later (accounting for concurrent sleep problems). In a reverse model, with sleep disturbances as the outcome, lagged wellness does not predict future sleep disturbances, and these effects remained stable after accounting for residents’ medical specialty.A basic multilevel growth model revealed no systematic declines  in resident wellness across the training year , this change does not have a meaningful effect on their overall wellness . For residents who reported high levels of sleep disturbance across the study period (at or above 1 SD of the mean on PSQI scores across the entire study period), 2 months of sleep disturbances (relative to a person's own mean scores) have the effect of shifting wellness scores to the 30th percentile or below. Thus, from an intervention standpoint, residents at the highest risk for clinically meaningful decreases in their psychological well-being appear to be those who reported a worsening of already poor sleep.Fatigue and wellness clearly impact residents’ training and clinical performance. Papp et al.  found thand meaningful lagged effect on self-reported resident wellness. This finding was robust over a variety of specialties and all levels of training. Program directors may find this useful to predict and prevent declines in the wellness of their residents. It has been shown that people experiencing persistent sleep problems are 3.5 times more likely to experience a subsequent depressive episode than people without sleep problems  decreases in resident wellness, which suggests that poor sleep may presage declines in psychological well-being.


Sandblasting particles which remain on the surfaces of dental restorations are removed prior to cementation. It is probable that adhesive strength between luting material and sandblasting particle remnants might exceed that with restorative material. If that being the case, blasting particles adhere to sandblasted material surface could be instrumental to increasing adhesive strength like underlying bonding mechanism between luting material and silanized particles of tribochemical silica coating-treated surface. We hypothesize that ultrasonic cleaning of bonding surfaces, which were pretreated with sandblasting, may affect adhesive strength of a resin luting material to dental restorative materials.We therefore observed adhesive strength of resin luting material to aluminum oxide was greater than those to zirconia ceramic and cobalt-chromium alloy beforehand. To measure the shear bond strengths of resin luting material to zirconia ceramic and cobalt-chromium alloy, forty specimens of each restorative material were prepared. Bonding surfaces were polished with silicon abrasive paper and then treated with sandblasting. For each restorative material, 40 sandblasted specimens were equally divided into two groups: ultrasonic cleaning (USC) group and non-ultrasonic cleaning (NUSC) group. After resin luting material was polymerized on bonding surface, shear test was performed to evaluate effect of ultrasonic cleaning of bonding surfaces pretreated with sandblasting on bond strength.For both zirconia ceramic and cobalt-chromium alloy, NUSC group showed significantly higher shear bond strength than USC group.Ultrasonic cleaning of dental restorations after sandblasting should be avoided to retain improved bonding between these materials. The topic of bond strength between dental restorative material and luting materials has been extensively discussed. To date, sandblasting hails as one of the most effective methods of increasing bond strength between resin luting materials and dental restorative materials , 2. RougTribochemical silica coating (TBC) is another favored method of increasing the bond strength between resin luting materials and dental restorations , 6. AfteAfter sandblasting, some abrasive particles adhere to the blasted surface. It is probable that the adhesive strength between a luting material and the abrasive particle remnants might exceed that with the restorative material. If that being the case, abrasive particles which adhere to sandblasted material surface could be instrumental to increasing adhesive strength, like the underlying bonding mechanism between a luting material and silanized particles of TBC-treated surface. Therefore, routine cleaning and removal of abrasive particle remnants from the sandblasted surfaces of dental restorations might unwittingly reduce the adhesive strength of luting materials to restorations.Zirconia ceramics are becoming a favored choice for fixed prostheses because of their fracture toughness and esthetic appeal. However, they exhibit poor adhesive strength to resin luting materials, except with the use of special monomers such as 10-methacryloyloxydecyl dihydrogen phosphate (MDP) . For manAluminum oxide is a popular sandblasting abrasive medium. In this paper, the authors examined if the adhesive strength of a resin luting material to aluminum oxide was greater than those to zirconia ceramic and Co-Cr alloy. This leads to the hypothesis that rinsing aluminum oxide abrasive particles off the sandblasted surfaces of zirconia ceramics and Co-Cr alloy might decrease the adhesive strength of resin luting material to these restorative materials. The authors tested this hypothesis by examining the adhesive strengths of a resin luting material to alumina-blasted zirconia ceramic and Co-Cr alloy surfaces with and without ultrasonic cleaning. If the adhesive strength without ultrasonic cleaning was higher than that with ultrasonic cleaning, it would imply that sandblasting not only brings about morphological changes of material surface, but also increased adhesion efficiency.Three materials were tested: aluminum oxide , yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) ceramic , and Co-Cr alloy . These three materials were cut from blocks of each material. For each material, 11 slabs (approximately 6×6 mm) were prepared using a low-speed cutting machine and embedded in an epoxy resin .The bonding surface of each specimen slab was polished with #1200 silicon carbide abrasive paper  under water irrigation to remove pollutants and obtain a flat uniform surface as previously described , 10. Aftn = 11 per material), of 2.0 mm depth and 3.6 mm diameter, was placed on the polished and cleaned bonding surface and filled with the luting material using a syringe tip.A resin luting material  was polymerized on the bonding surface, in the form of a cylinder, using a Teflon mold. Teflon molds were used because Teflon does not react with the luting material. Each Teflon mold . Before applying curing light to the resin luting material, its irradiance was checked using a radiometer . During polymerization, light irradiance was maintained at 450 mW/cmShear bond strengths were measured after 24-hour storage in distilled water. For each material, specimens were mounted on a universal testing machine  and then shear stress was applied at a crosshead speed of 0.5 mm/minute. Data obtained for the three materials were statistically compared using one-way analysis of variance (ANOVA) and Fisher’s LSD method.For both Y-TZP ceramic  and Co-Cr alloy , 40 slabs (approximately 6×6 mm) were prepared for each material using a low-speed cutting machine and embedded in an epoxy resin. The bonding surface of each specimen slab was polished with #1200 silicon carbide abrasive paper as described in previous head. After polishing, the bonding surface was air-abraded using a laboratory sandblaster . Distance between nozzle and bonding surface was 5 mm, and sandblasting was performed at an air pressure of 0.4 MPa for 10 seconds.versus non-ultrasonic cleaning (NUSC) group. All USC specimens were cleaned with distilled water in an ultrasonic bath  at 40 kHz for 5 minutes, and then left to air-dry for 240 minutes. For NUSC specimens, their bonding surfaces were not cleaned ultrasonically but only with a soft air blow for 5 seconds.After sandblasting, 40 specimens of each material were equally divided into two groups: ultrasonic cleaning (USC) group n = 20 per group), of 2.0 mm depth and 3.6 mm diameter, was placed on the treated bonding surface and filled with the luting material using a syringe tip.A resin luting material  was polymerized on the bonding surface, in the form of a cylinder, using a Teflon mold. Each Teflon mold  and then shear stress was applied at a crosshead speed of 0.5 mm/minute. The edge of loading blade was applied just onon to the interface between luting material and test surface. Data of USC and NUSC groups of each material were statistically compared using the Mann-Whitney rank-sum test.Before the shear test, a scanning electron microscope  was used to detect and observe morphological changes in the bonding surface due to sandblasting and the presence of aluminum oxide particles with and without ultrasonic cleaning. For each material, the bonding surfaces of polished-only, USC, and NUSC specimens were observed.After specimens were dried in a desiccator for 24 hours, they were coated with a thin layer of osmium using Neo Osmium Coater  before SEM observation at 10 kV.Before the shear test, energy dispersive X-ray spectroscopy  analysis was carried out to determine the elemental compositions of the bonding surfaces of polished-only, USC, and NUSC specimens of both materials. Data were obtained using a SEM  with an EDS X-ray detector attached to a take-off angle of 31 degrees. Primary electron beam voltage varied from 10 kV for zirconia ceramic to 15 kV for Co-Cr alloy.The element distribution maps of zirconia ceramic and Co-Cr alloy specimens subjected to different surface treatments were obtained in the following conditions. The dwell time was 1 msec / 512 X 400 pixels frame, and 300 frames were captured. Semi-quantitative atomic percent maps were calculated by a standardless ZAF correction method.P = 0.021) and Co-Cr alloy (P = 0.031). However, there were no statistically significant differences between zirconia ceramic and Co-Cr alloy (P = 0.872).For NUSC specimens of zirconia ceramic, abrasive particle remnants were observed on the sandblasted surface. For the other NUSC and USC specimens of both materials, it was difficult to visually discern the abrasive particles from the SEM images.Bond strength of resin luting material (Panavias F 2.0) to alumina (VITA In-Ceram) was higher than those to zirconia ceramic and Cr-Cr alloy . VITA InFor both zirconia ceramic and C-Cr alloy, the bond strength of NUSC group was higher than that of USC group .In the SEM image of the NUSC specimen of zirconia ceramic, remnants of blasted aluminum oxide particles could be observed, further bolstering the claim that blasted aluminum oxide particles contributed to enhancing the adhesive strength. However, it was difficult to visually discern the aluminum oxide particles in the rest of the SEM images . Small aEDS analysis results clearly revealed the presence of aluminum oxide in NUSC specimens of both restorative materials Figs  and 3. EPhase transition of the blasted zirconia ceramic surface occurred during sandblasting . MateriaResults obtained in this study have shown that ultrasonic cleaning of the bonding surface after sandblasting decreased the adhesive strength of resin luting material, and therefore ultrasonic cleaning of sandblasted surfaces should be avoided. However, there was as yet insufficient data on the amount and magnitude of bond strength of alumina fragment of blasted particles adherent on the bonding surface.This study also examined the possibility of blasted aluminum oxide particles providing similar bonding mechanism as tribochemical silica coating. Results obtained suggested that aluminum oxide particles which remained on the bonding surface after sandblasting were effective in increasing bond strength. However, we could not definitively conclude that aluminum oxide particles adherent on zirconia ceramic surface was the only cause of and sole contributing factor to the increased bond strength. Other possible aspects, and hence effects, of sandblasting should be discussed.Aluminum oxide is an adsorbent for phosphoric acid , in thatSandblasting causes a new surface layer, underlying the top bonding surface, to be exposed. This new surface layer is high in purity and activity . By virtvia the ultrasonic cleaner or the drying period on the other hand, it was nearly impossible to achieve perfect contamination control. Therefore, it is reasonable to presume that contamination of sandblasted surfaces easily occurs in dental clinics and laboratories when ultrasonic cleaning is used.A highly active surface has high chemical affinity, which also means that it is particularly prone to contamination. Consequently, the new surface created by sandblasting loses its high activity because of contamination. It is highly probable that some contamination of the highly active surface occurs during the ultrasonic cleaning process, which then causes the bonding surface to lose its bonding ability. In this study, stringent contamination control measures were exercised in the handling of all equipment. However, with highly active—and hence highly contaminant-absorbent—bonding surfaces on the one hand, and introduction of contaminants In this study, increased bond strength was achieved between a phosphate monomer-containing resin luting material and zirconia ceramic and Co-Cr alloy. However, combinations of other luting materials and restorative materials may yield different bond strength results. Moreover in some clinical situations, ultrasonic cleaning is absolutely necessary from the hygiene perspective. These were some of the limitations of the present study, and further investigation is needed to reveal a fuller scope of the unnoticed effects of sandblasting on adhesive strength between resin luting materials and dental restorative materials.It could be concluded that sandblasting not only roughened the surfaces of restorative materials, but also increased the bond strength between a resin luting material and dental restorative materials. Ultrasonic cleaning of dental restorations after sandblasting should be avoided to retain the improved bond strength between these materials.


Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early-life stress can impact on later health but less is known about how early-life stress impairs HPA axis activity, contributing to maladaptation of the stress–response system. Early-life stress exposure  can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical, and experimental studies have demonstrated that early-life stress produces long term hyper-responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviors. Recently, evidence has emerged on early-life stress-induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early-life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1). We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early-life stress-induced maladaptation of the HPA axis, and its subsequent effects on energy utilization and expenditure. The effects of positive later environments as a means of ameliorating early-life stress-induced health deficits, and proposed mechanisms underpinning the interaction between early-life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early-life stress and later health outcomes will also be addressed. Stress can be defined as any condition including an adverse environment, experience, or perceived threat to alter an organism’s homeostasis, which elicits a physiological response involving both peripheral and central systems via the release of glucocorticoids from the adrenal cortex through activation of the hypothalamic–pituitary–adrenal (HPA) axis . GlucocoThere is longstanding recognition of the impact of stress during critical early developmental periods such as childhood and the consequential association with adverse mental health outcomes and changes in brain development –13, howeWhile studies aimed at exploring underlying mechanisms are difficult to achieve in humans, animal studies have shed some light into the effects of early-life stress induced during the prenatal and postnatal periods on metabolic hormones and on peripheral tissues involved in glucose/insulin and lipid metabolism –24. In aThis review will unravel how early-life stress induces metabolic derangements; an area that is less well explored. Despite the emergence of human data in the field, mechanisms elucidating the association between stress and adverse metabolic outcomes are lacking. Animal studies permit closer investigation of the stress system and through various manipulations, allow the mechanisms underlying effects of stress on metabolism to be explored. Of particular focus is exploring outcomes of stress during the perinatal and early-life period for later life metabolic outcomes.As direct examination of the prospective effects of early-life stress is not feasible in humans this had led to the development of numerous animal models to explore the question of whether early-life stress can affect risk for later life metabolic deficit. Animal models of early-life stress allow for controlled environmental manipulation throughout developmental periods and later life. With necessary caution these models can assist our understanding of the link between developmental and environment experiences and the conferred later life metabolic disease vulnerabilities. Inherent differences in human and rodent biological maturation and neuroendocrine development must be considered in study design and translation to human health. Humans give birth to mature young; with the final trimester of pregnancy being a period of rapid brain development , 28. RodHumans and rodents have a vital dependence on adequate nourishment and care to ensure normal development. This altricial nature and vulnerable perinatal period across both species means that models of maternal care can provide insight into how early support and sensitivity to offspring needs can impact development. Changes in maternal care have been shown to impact rodent development with mother–offspring interactions such as licking and feeding providing critical input for normal neurobiological development and HPA axis function , 33. AdeThree popular paradigms of postnatal early-life stress are maternal separation for varied periods of time from 15 min to 8 h, maternal deprivation (absence of the dam for a more extended period) and provision of only limiting nesting material. The maternal separation model has been studied for more than five decades, and is demonstrated in both mice and rats to affect the HPA axis, and behavioral responses in mothers and offspring in a sex dependant manner –39. MateRecently, early-life stress models in non-human primates have demonstrated a lasting health impact following adverse early experiences. Altering secure attachment relationships during early life in Rhesus macaques significantly elevated prevalence and frequency of illness and increased bodyweight trajectory . Stress Retrospective and observational studies in humans demonstrate that early-life experiences can influence later life metabolic outcome. Environmental changes during gestation and the early postnatal period may impact development and predict metabolic health outcomes. Manipulations of the early environment can affect the developing nervous system, shaping individual differences in physiological and behavioral responses to environmental insults. For example, disruption of the mother–infant relationship during early life contributes to neuroendocrine, neurochemical, and behavioral changes in the adult organism . ExperieBarker’s theory postulates that low birth weight predicts increased disease risk later in life, including metabolic vulnerability . Given tFamine exposure during pregnancy is a chronic early-life stress that is also known to affect birth weight and increase risk for metabolic disorders later in life. A well-documented period providing epidemiological evidence linking early-life adversity and health outcomes is the 1944–1945 Dutch Famine  during an oral glucose tolerance test (OGTT) , reducedThe mechanisms by which prenatal stress alters later life metabolic outcome remain unknown. Stress during pregnancy alters maternal hormones, including circulating glucocorticoid levels. Normal physiological levels of glucocorticoids during development are essential for tissue growth and maturation, however, excess levels of glucocorticoids, e.g., through pharmacological interventions, have been shown to affect maturation , 116. Elad libitum) showed significantly reduced locomotor activity with marked hyperphagia and hyperleptinemia when consuming either standard chow or a high caloric diet , increased non-esterified fatty acids (NEFA) –144, andGlucocorticoids exert tissue-specific metabolic effects, directly targeting tissues for insulin metabolism, and they regulate skeletal muscle, liver, and adipocyte insulin signaling . GlucocoMechanisms regulating intracellular glucocorticoid concentrations are critical to understand the impact of stress on energy metabolism including energy expenditure, storage, and utilization. Intracellular levels of glucocorticoids are influenced by 11β-HSD1 with the type-1 isoform predominantly expressed in the liver  and to aThus, liver 11β-HSD1-HPA axis is a potential pathway in early-life stress-mediated metabolic disturbances, particularly insulin sensitivity, glucose metabolism and lipid synthesis, and mobilization as outlined in Box Box 1Does chronic exposure to negative postnatal environments such as HFD and adulthood stressors lead to maladaptation following early-life stress?Is the stress-induced perturbation of metabolic profile mediated by the liver 11β-HSD1-HPA axis interaction?How can positive postnatal environments reverse the early-life stress-induced metabolic damage?What are the mechanism(s) underlying early-life stress-induced improvement of insulin sensitivity and improved glucose metabolism if rodents are maintained on chow diet?We propose that early-life stress may alter availability of tissue glucocorticoids and glucocorticoid signaling. Specifically, we propose that during the maladaptation period  early-life stress may exacerbate the risk of metabolic disease. One potential mechanism underlying early-life stress-induced metabolic deficits is the interaction between the HPA axis and liver 11β-HSD1. Positive later environments may modulate the negative impact of early-life stress not only on behavioral outcomes, but also on metabolism. Given the burgeoning issues of metabolic and mental health disorders, the question of how early-life stress impacts subsequent disease risk warrants further investigation.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Several relevant RBPs – FMRP; FUS/TLS; TDP-43; Staufen; Smaug; Pumilio; CPEB; HuD; ZBP1; and DDX6 among others – form granules that contain dormant mRNAs repressed by multiple pathways. Recent reports indicate that dendritic granules may contain stalled polysomes, and furthermore, active translation may occur in association with RNA granules. Here, we discuss the molecules and pathways involved in this continuum of RNA granules that contain masked mRNAs, mRNAs trapped in inactive polysomes or mRNAs engaged in translation.The transcriptome at the synapse consists of thousands of messengers encoding several cellular functions, including a significant number of receptors and ion channels and associated proteins. The concerted translational regulation of all these molecules contributes to the dynamic control of synaptic strength. Cumulative evidence supports that dendritic RNA granules and mRNA-silencing  Era como si brotaran del libro”“El número de páginas de este libro es exactamente infinito. Ninguna es la primera; ninguna, la última.”Several pages always lay between the cover and my hand. It was as if the pages sprouted from within the book. The number of pages in this book is no more or less than infinite. None is the first page, none the last.The book of sand”Jorge Luis Borges, “The transcriptome at the synapse comprises thousands of messengers encoding highly diverse proteins, which include an important proportion of the receptors and ion channels that modulate synaptic plasticity. The transcripts for several variants of the voltage-gated ion channels Kv1.1/Kcna1; Kcnab; Kcnama; Cacna; Cacnab; Cancng; Scn2a; Scn4b; 20 GABA receptor subunits and nine different glutamate receptors are present at dendrites and in the vicinity of synaptic contacts . The conThe presence of RNA granules at dendrites and synapses has been extensively documented. These higher-order assemblies of mRNAs and proteins are thought as units for mRNA transport and translational regulation. The molecular mechanisms for mRNA repression during granule movement are partially known and involve several RNA-binding proteins RBPs; . Dendritfoci are large multimolecular assemblies that contain silent mRNAs in association with repressor factors, including miRNAs and specific RBPs. The mRNA-silencing foci are, in general, highly dynamic and their dissolution correlates with translational activation. The processing bodies (PBs) are ubiquitous mRNA-silencing foci and specialized assemblies are formed under specific conditions, as for example the stress granules (SGs), which are induced upon cellular stress (N-Methyl-D-aspartate receptor (NMDAR) stimulation induces the dissolution of a specific type of PB that contains the Decapping Coactivator Protein 1a (DCP1a), putatively releasing transcripts to allow their translation , a signaling molecule that is key to synaptic plasticity, is repressed at the S-foci, and dissolution of the S-foci correlates with increased translation of CamKIIa mRNA . Upon neuron depolarization, the β-actin mRNA is reversibly released along with ribosome subunits, which are similarly masked .Another important mechanism for synaptic plasticity is the regulated translation of β-actin mRNA, which affects cytoskeleton remodeling at the post-synapse. By using single-molecule y masked . A temptfoci or masking granules is governed by signaling pathways downstream of synaptic activation. The unmasking of β-actin mRNA upon depolarization is mediated by MEK1/2, and the dissolution of the S-foci upon NMDAR stimulation requires calcium entrance and the activation of the PI3K/mTOR pathway .The proteins directing the formation of RNA granules are expected to contain oligomerization domains. In connection with this, low complexity regions (LCR) believed to mediate protein self-aggregation are frequent in the RBPs present in granules isolated from neural tissues . Among o pathway . These sin situ to demonstrate that a large proportion of dendritic RNA granules contain stalled polysomes, which switch into active translation upon metabotropic receptor stimulation . As described above for mRNA-silencing foci and masking granules, granules with stalled polysomes may respond to specific signals and dissolve to allow translation. Alternatively, they can rearrange to inactivate or release stalling factors, thus allowing translation at their periphery, as described in the next section .DDX6/RCK/p54/Me31B might be involved in FMRP-dependent polysome stalling, as the  binding . The recFMRP and ARC/Arg3.1 mRNAs and their encoded proteins using single-molecule approaches in living neurons. As anticipated, the injected mRNAs formed granules and unexpectedly, the polypeptides generated from these transcripts were detected near the granules .A number of recent reports demonstrated that translation occurs in the vicinity of dendritic mRNA granules and that polysomes are associated with PBs in several cell types and organisms. In a seminal work, granules . This sugranules . We propin situ metabolic labeling of proteins, they found that translation occurs in association with FUS/TLS granules. FUS/TLS form plastic granules at dendrites and the above observations open the possibility that synaptic FUS/TLS granules switch between states of silencing and active translation, involving granule reorganization. Pathogenic mutations on FUS/TLS enhance FUS/TLS aggregation and this may impair granule rearrangement and local production of proteins, thus affecting synaptic plasticity and homeostasis  and gurken (grk) mRNAs associate with embryo PBs with different localizations. Whereas grk mRNA concentrates at the edge of the PBs, bcd mRNA preferentially localizes at the PB core. This correlates with their translational status, and grk mRNA is actively translated whereas bcd mRNA is repressed. Moreover, bcd mRNA relocates to the PB periphery when its translation is triggered later during development .The question of where exactly in the granule translation takes place was approached by high-resolution electronic microscopy of elopment . More reIn addition to the above-described translational regulation pathways, the packaging of mRNAs in granules is believed to facilitate their transport, and recent findings in non-neuronal cells suggest that the presence of polysomes may help. Working with a fungal model system, The putative cross-talk and coordination between the above-described pathways, which may involve the exchange of factors among different granules, remain to be further investigated. Adding complexity, a given transcript may be regulated by multiple networks and in different granules, which may shift between translationally silent or active states, all these providing mechanisms for response diversity. The dynamics of mRNA storage and translation are linked to granule condensation, reorganization, and dissolution. These processes are analogous to phase transitions and depend on posttranslational modifications and physicochemical parameters . FurtherThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Post-traumatic long bone osteomyelitis (PTOM) is a relatively frequent occurrence in patients with severe open fractures and requires treatment to prevent limb-threatening complications. The Masquelet technique represents a length-independent, two-staged reconstruction that involves the induction of a periosteal membrane and use of an antibiotic-impregnated cement spacer for the treatment of segmental bone loss that result from bone infection. In this review, we summarize recent developments regarding the diagnosis and treatment of long bone PTOM, with a special emphasis on the use of the Masquelet technique for reconstruction of wide diaphyseal defects. Osteomyelitis, or infection of the bone, represents a complex and challenging clinical entity in the field of orthopedics. In 1951, Gallie et al reported a case of recurring osteomyelitis following a period of 80 years since onset of initial infection. The patient was a 90-year-old woman with a Brodie’s abscess localized to the distal femur. Given a largely asymptomatic presentation throughout the patient’s lifetime, diagnosis and treatment was exceedingly delayed. This case is but one of many that illustrates the complex nature of osteomyelitis [The focus of this review will be on long bone posttraumatic osteomyelitis (PTOM), defined as infection of the bone in conjunction with recent fracture or traumatic insult. Long bone PTOM is a relatively frequent occurrence and may be involved in as many as 10 % of all open fractures and 1 % of all closed fractures . SeveralThe clinical diagnosis of long bone PTOM is challenging, in large measure, owing to the non-specific nature of its initial presentation. In addition to findings of localized pain, long bone PTOM classically presents with signs and symptoms of infection including low-grade fever, erythema, edema, and/or draining sinus tracts , 6. In pDiagnostic work-up of long bone PTOM traditionally involves a combination of imaging, tissue culture, and laboratory studies . Acute i. Magnetic resonance imaging (MRI) enables excellent visualization of soft-tissue pathology in as early as 3–5 days following initial onset of long bone PTOM [Following positive findings on culture and pathology suggestive of long bone PTOM, preoperative work-up must include an imaging series consisting of anteroposterior (AP) and lateral radiography, MRI, and/or CT. A multimodal imaging approach is employed to surmount the independent limitations of each imaging modality. In patients with long bone PTOM, AP and lateral radiographs traditionally demonstrate regional osteopenia, periosteal reaction (“Codman’s triangle”), and sequestrum (segments of necrotic bone with interspersed viable granulation tissue). However, sensitivity of plain radiography is quite poor during the initial two weeks of infection . Computeone PTOM  and is tone PTOM . The dowThe classification of long bone PTOM is done according duration  or disease stage  and may facilitate treatment planning . In the The management of long bone PTOM is complex and challenging. Therefore, patients must be prepared for a long course of multiple surgeries and counseled on the risks for postoperative complications that include nonunion, hardware failure and infection recurrence. Moreover, initial stages of preoperative planning must involve correction of modifiable co-morbidities and/or risk factors that portend poor postoperative wound healing. Indeed, a study by Brinkler et al showed that 31 of 37 patients (83 %) with fracture nonunion had one or more underlying metabolic or endocrine abnormalities such as vitamin D deficiency, calcium imbalances, central hypogonadism, thyroid disorders, and parathyroid hormone disorders. Eight of these patients (25 %) achieved bony union in an average of 7.6 months  following treatment of their metabolic or endocrine abnormalities without further operative treatment . Low socI.Control of the local infection with radical debridement and antibiotic therapyII.Fracture stabilization when instability occurs due to debridement or nonunionIII.Provision of adequate soft-tissue coverage to ensure wound healing , 5In severe cases of long bone PTOM, debridement of the infected tissue results in extended diaphyseal loss of bone that cannot be adequately managed by conventional methods of reconstruction. In particular, conventional methods often fail to satisfy at least one of the following goals of therapy:Radical debridement may further precipitate widening of the osseous defect in cases where segmental bone defects exceed 5 cm in size . ConventThe Masquelet technique represents a two-staged reconstructive procedure that overcomes several of the shortcomings in the treatment of osteomyelitis defects, particularly those located to the long bone and associated with infected and/or non-viable soft tissue . First dThe Masquelet technique is performed in two stages. In the setting of an unstable long bone with infected and/or non-viable soft tissue, the first stage involves radical debridement of all infected or non-viable bone and interposed fibrous tissue. Given that devitalized tissue serves as a nidus for recurrent infection and predisposes to increased risk of postoperative complications such as delayed union, nonunion, and vascular thrombosis, reconstruction of the bone defect (conducted in Stage 2) is only possible once complete eradication of infected and non-viable tissues has been achieved. The margins of debridement should extend until viable bony edges are encountered, determined intraoperatively using the “paprika sign” (punctate bleeding upon drilling with a 2.5 mm drill bit). Once the margins of debridement have been determined, an osteotome can be utilized to perform a corticotomy in order to prevent destruction of healthy surrounding tissues.Following debridement, stabilization must be achieved to maintain length, alignment and rotation prior to insertion of the cement spacer. Options include unilateral or ring external fixation, plate osteosynthesis, or IM nailing. The choice of stabilization is based on the location of the defect. For bone loss in the mid-diaphysis, an IM nail offers stable fixation that allows early weight bearing. A narrow diameter nail is used and coated with antibiotic-impregnated cement. For defects close to an articular surface, external fixation is preferred. Ring-fixators offer stable fixation and the ability to modify the bony alignment postoperatively. When placing external fixation, care must be taken to keep pins away from the site of definitive fixation so that the external fixator can be left in place until healing is achieved (during Stage 2 of the procedure) .In our experience, the preparation of an antibiotic IM interlocking carbon-fiber nail can be achieved using a simple and reproducible technique . PlasticThe next step following bony stabilization is the fashioning of a cement spacer, traditionally composed of polymethyl methacrylate (PMMA) cement, to fill the segmental bone defect. A cement spacer is preferable over other modalities of local antibiotic delivery primarily because it assumes the conjoint functions of inhibiting fibrous tissue ingrowth and maintaining dead space volume until time of reconstruction . For optStaphylococcus aureus, coagulase negative Staphylococci, Pseudomonas aeruginosa and Escherichia coli species. In another study performed in 15 mongrel dogs, Adams et al compared the elution characteristics of PMMA spacers loaded with cefazolin , ciprofloxacin , clindamycin , ticarcillin , tobramycin , and vancomycin . Clindamycin proved to have the best elution profile in seromas, granulation tissue, and bone. High concentrations of tobramycin were observed accumulating in bone and granulation tissue, compared to high concentrations of vancomycin occurring in bone alone [The appropriate choice of antibiotic therapy is predicated on the results of culture and pathology testing performed on direct wound and bone samples. Additionally, the chosen antibiotic must be thermostable to the exothermic polymerization (solidification) process of the PMMA cement. Aminoglycosides  and vancomycin represent good options given their thermostability, broad-spectrum of activity, high rates of elution, and relatively low incidence of anaphylactic reactions , 26. In ne alone . In an ine alone . This stne alone .; higher doses of antibiotic may impede cement molding [Of note, the largest permissible ratio is 8 g of antibiotic per 40 g of cement molding . During In the final phase of stage 1, there must be closure of the wound without tension. This may require treatments ranging from wet-to-dry dressings to a flap procedure to provide adequate soft-tissue coverage. As a guiding principle, the least technically demanding strategy that enables successful soft-tissue coverage should be chosen. For acute injuries, free-flaps are preferred over rotational muscle flaps, as the latter can potentially increase destruction of viable surrounding tissue . In a prWound vacuum-assisted closure (VAC) can also be used to promote tissue granulation, reduce tension required for wound closure, and minimize postoperative complications . This isOn a final note, a randomized control trial performed by Bouachour et al demonstrated potential benefit with treatment by hyperbaric oxygen therapy (HBO) in patients suffering severe crush injuries of the limbs . The stuFollowing completion of stage 1 of the Masquelet procedure, weight-bearing is determined based upon the stability of the defect size, location and implant. Patients with small and medium diaphyseal defects treated by IM nailing can bear weight as tolerated. The patient is then placed on a prolonged systemic antibiotic regimen for a period of 6-8 weeks. This is done in order to allow adequate time for a number of processes to occur: (1) epithelialization of free or pedicled muscle flaps in order to prevent surgical site contamination by bacterial skin flora, (2) revascularization of marginally viable tissue surrounding the bony defect, (3) formation of the self-induced periosteal membrane, and (4) treatment of any residual infection by systemic and/or local antibiotics , 23, 37.Complete eradication of infection is a prerequisite to reconstruction of bone defects due to osteomyelitis (Stage 2 of the Masquelet technique). Trending inflammatory markers before and after completion of systemic antibiotics can help confirm clearance. If there remains any doubt as to the presence of residual infection, then tissue specimens at the site of the segmental defect can be harvested for culture and pathology . SendingA single longitudinal incision is made centrally through the self-induced periosteal membrane. The cement spacer should be removed in one piece or a few small pieces created with a saw or osteotome. Particular care must be taken to avoid iatrogenic injury to the induced periosteal membrane so that it remains a self-contained compartment. The ends of the resected bone margins should be freshened with a drill bit or rasp to remove sclerotic bone and facilitate bone graft integration. The medullary canal should also be debrided to enable communicate with the graft. Definitive fixation can be revised at this point if necessary.The hollowed periosteal cavity is best filled with morcelized autogenous bone graft. A synergistic effect between the bone graft and the induced membrane promotes increased bone formation, angiogenesis, and consolidation of the bony defect through stimulating the release of growth factors such as VEGF, TGF-beta 1, and BMP-2 , 38–40.Bone graft can be harvested from a number of locations, including the iliac crest, proximal tibia and calcaneus. Use of the RIA system from the femur is preferred and portends less morbidity than iliac crest bone graft harvesting –43. FurtWhile preparing for graft harvest using the RIA system, a few important considerations must be kept in mind. The reaming head size should not exceed the canal diameter at the isthmus of the femur  by more than 2 mm . ReamingHarvested bone graft should be loosely packed to bridge the osseous defect. It is important to avoid tight packing of bone graft when bridging the defect, as this can precipitate necrosis of the graft due to impaired angiogenesis. Large defects may require additional augmentation of autogenous bone graft with allograft or demineralized bone substitute at a ratio less than or equal to 1:3  to achieve sufficient graft volume or strength , 19, 46.Following surgery, the patient is encouraged to resume immediate weight-bearing as tolerated. Early weight-bearing stimulates secondary bone healing  and may help to reverse long-standing physical and psychological disability. The patient should be scheduled for routine follow-up postoperatively to evaluate for fracture alignment, osseous consolidation, and functionality.With careful planning and execution, reconstruction of long bone osteomyelitis defects using Masquelet technique can yield excellent long-term clinical outcomes. In a case series of 25 patients presenting with 27 segmental bone loss nonunions averaging 5.8 cm in size , 24 cases (90 %) demonstrated full clinical and radiographic healing within 1 year following reconstruction with Masquelet technique. No postoperative complications, including infection recurrence, were reported .The technique described here to treat long bone osteomyelitis is a feasible option for most orthopaedic surgeons. The materials required  are readily available at most centers. Carbon fiber products are becoming more popular and readily available, although a standard metallic nail can be substituted if necessary. Compared to alternative techniques such as bone transport and vascularized fibular grafting, the Masquelet technique is often technically easier and can produce good outcomes in a majority of patients.As an illustrative case example, we present a 33-year-old male who sustained an open (Gustilo IIIB) diaphyseal fracture of the right tibia following an occupational forklift accident. Initial treatment was performed at an outside facility and included multiple rounds of debridement followed by open reduction and internal fixation (ORIF) of a buttery fragment along the medial tibia with locking plate and IM nailing. The patient was placed on wound VAC therapy for three months and subsequently developed a chronic draining wound over the anterior tibia with concomitant osteomyelitis Fig. , promptiUpon initial presentation to our institution, the patient was noted to have a foul-smelling wound with inflammatory hypergranulation surrounding an open 3 × 2 cm bony defect. The patient reported a deep, throbbing pain localized to the right anterior tibia with an intensity of 7/10 at rest. Past medical and family history were not significant for any metabolic, endocrine, or chronic inflammatory conditions. The patient reported smoking one-half pack of cigarettes daily for the past 10 years.Staphylococcus aureus (MRSA) and Streptococcus anginosus. The patient was started on a 6-week course of Vancomycin (15 mg/kg IV q8 hr) and Metronidazole (500 mg PO q8 hr).On physical examination, the patient had decreased sensation to light touch over the cutaneous distribution of the superficial peroneal nerve and had drastically reduced strength of ankle dorsiflexion (1/5) in the right leg. Diagnostic imaging with anteroposterior (AP) and lateral radiographs revealed a mid-diaphyseal comminuted fracture nonunion of the right tibia with overlying soft-tissue swelling Fig. . Direct MRSA and Streptococcus milleri.Given the patient’s chronically infected nonunion and extensive necrosis of surrounding soft-tissue, a two-staged reconstruction using the Masquelet technique was performed. First, plate and screws were removed. Intraoperatively, absence of pinpoint bleeding was noted along an 11 cm segment of devitalized bone. Under fluoroscopic guidance, a Monotube multiplanar external fixator  was placed. Tibial osteotomy was carried out using an oscillating saw to resect necrotic bone, followed by radical debridement of all nonviable surrounding tissue. A PMMA cement spacer with 3.6 gm tobramycin and 3 gm vancomycin was prepared and placed into the bone defect. Soft-tissue coverage was provided using a rotational soleus flap. Incisional wound VAC therapy was applied for 1 week to promote tissue granulation and accelerated wound closure. The patient received a 6-week course of Vancomycin and Flagyl after direct tissue cultures grew Eight weeks post-operatively, the patient returned to undergo the second stage of reconstruction. Intraoperative bone and tissue samples were culture negative. A significant self-induced periosteal envelope was visible overlying the previously placed cement spacer Fig. . A centrThe patient was followed at 2, 8, 12, and 20 weeks postoperatively. The patient was able to resume full weight-bearing by 2 weeks postoperatively and was pain free at his 3 month follow-up visit. Radiographs at his 5 month visit showed consolidation of the defect without evidence of infection, osteolysis, or hardware failure . Use of an osteotome to perform corticotomy helps prevent damage to healthy surrounding tissue.✓ Following thorough debridement, an antibiotic-impregnated PMMA cement spacer is placed. Irrigation with cold saline during preparation of the antibiotic-cement mixture will help prevent skin burns.✓ Stabilization during the first stage can be achieved with an external fixator, plate or IM nail.✓ The cement spacer must be left in place for 6-8 weeks. Complete eradication of infection, confirmed by culture and pathology, is a prerequisite to the second stage of the procedure (reconstruction of the osseous defect).✓ In the second stage, we favor definitive fixation using an antibiotic-coated carbon fiber IM nail. This allows for artifact-free visualization on MRI, which is important for monitoring treatment response.✓ Autograft harvested using an RIA system should be loosely packed around the IM nail to permit angiogenesis. Bony margins should be freshened with a drill bit to facilitate graft integration.Obtained from patient.


Practitioners need more information about intimate partner violence (IPV) victims’ healthcare use trends. We used a novel data-linkage method and complaint categorization allowing us to evaluate IPV victims healthcare use trends compared to the date of their victimization.This was a retrospective case series using data-linking techniques cross-referencing databases of Medicaid-eligible women between the ages of 16 and 55 years, an IPV Case Database for 2007 and the Florida State Agency for Healthcare Administration, which tracks hospital inpatient, ambulatory and emergency department (ED) use within the State of Florida. We analyzed resulting healthcare visits 1.5 years before and 1.5 years after the women’s reported IPV offense. Using all available claims data a ‘complaint category’ representing categories of presenting chief complaints was assigned to each healthcare visit. Analysis included descriptive statistics, correlation coefficients between time of offense and visits, and a logistic regression analysis.The 695 victims were linked with 4,344 healthcare visits in the four-year study period. The victims were young (46% in the 16–25 age group and 79% were younger than 35). Healthcare visits were in the ED (83%) rather than other healthcare sites. In the ED, IPV victims mostly had complaint categories of obstetrics and gynaecology-related visits (28.7%), infection-related visits (18.9%), and trauma-related visits (16.3%). ED use escalated approaching the victim’s date of offense  compared to use of non-ED sites of healthcare use . ED use deescalated significantly after date of reported offense for ED visits  versus non-ED use . The victims’ age group more likely to use the ED than any other age group was the 36–45 age group .IPV victims use the ED increasingly approaching their date of offense. Presenting complaints were varied and did not reveal unique identifiers of IPV victims. This novel method of database matching between claims data and government records has been shown to be a valid way to evaluate healthcare utilization of at-risk populations. Intimate partner violence (IPV) occurs in two to five million intimate partner relationships in the United States each year.The practice of universal IPV screening during clinical encounters, however, remains controversial due to the extensive resources required to implement successful IPV screening tools and intervention programs. Such implementation is especially challenging in busy clinical environments such as the ED.The methodology used to generate contemporary reports of IPV epidemiology are limited and can suffer from bias. Investigations are frequently based on a single healthcare encounter, rely on victim self-report, or legal convictions used in victim identification.Visit-level information related to healthcare encounters with IPV victims is rarely reported: a critical factor in enhancing the recognition of IPV patients by advocates and healthcare providers. While analysis of diagnoses and population characteristics is important for recognizing healthcare use patterns, visit-level complaint data can assist physicians in recognition of IPV victims prior to final diagnosis. This study uses a complaint category-based assessment of IPV victims’ visits to provide a more relevant evaluation of their presentation patterns to healthcare providers. Knowing presentation patterns of IPV victims can help emergency physicians with pattern recognition of victims, as well as dispel myths about IPV victims. The objective was to characterize healthcare use patterns in female IPV victims who were Medicaid-eligible and between the ages of 16 and 55 identified by the Office of Victim Witness Services in the Florida State’s Attorney’s Office (SAO), Eighth Judicial Court using database-linking methods.We conducted a retrospective case series using data-linking techniques, cross-referencing databases of the Florida State Attorney’s Office (SAO) of Victim Witness Services 2009 IPV victim database, Medicaid-eligible women between the ages of 16 and 55 years, and the Florida State Agency for Healthcare Administration, which tracks hospital inpatient, hospital-based ambulatory, and ED use within Florida. The local institutional review committee approved this study.Our cohort included Medicaid-eligible female IPV victims identified through the State of Florida Attorney’s Office of Victim Services in northern Florida including a six-county area. The women in our cohort were females in the SAO’s adult IPV incident database whose IPV offense occurred between January 1, 2007 and December 31, 2007, and were between 16 and 55 years old. Victims included in the database were identified by law enforcement officers or victim advocates. Responding officers or victim advocates evaluated daily “offenses”: sworn complaints, sexual assaults, arrests and IPV-related homicides. ”Sworn complaints” are calls police officers receive by victims or bystanders that warrant a visit. For example, if a neighbor calls that he hears yelling next door, and the police investigate and determine the situation to be IPV-related, this incident will be reported as an IPV-related sworn complaint, and added to the SAO’s IPV database. Each law enforcement interaction, within the six counties of the Eighth Circuit Court, that the responding officer or victim advocate suspects to be IPV-related, are submitted to the SAO Office of Victim Services. The SAO reviews all reports and deems the events to be IPV-related or not. Seeking out these officer- or advocate-identified incidents ensured a variety of types of IPV and severities of IPV-related victimization were included in the study rather than relying on higher-level court-determined incidents to validate IPV events. This created an inclusive population of the confirmed IPV victims recognized in this six-county region to study.This cohort of confirmed IPV victims were linked to their healthcare visits within the state of Florida through the state’s Agency for Healthcare Administration (AHCA) database records 1.5 years before and up to 1.5 years after the IPV victim’s first IPV incident (index event). Researchers used a third-party data management group which received the list of victims from the SAO and cross-linked the victim identifiers to government databases. Their techniques involved a software program matching IPV victims to Medicaid-eligible women by first name, last name, and date of birth. The Social Security number from this cohort of women was then used to query the AHCA claims database. De-identified data was then delivered to the researchers by assigning each victim a unique identifier. These linkages resulted in robust claims data for each of the linked IPV victims.The database includes financial, procedural and diagnostic data for all inpatient stays, ED visits, inpatient psychiatric visits, rehabilitations stays, and hospital-based ambulatory care medical records throughout the state. Each unique visit identified  was assigned a complaint category in order to evaluate trends in the women’s presenting complaints over time. To assign this complaint category, researchers reviewed the claims data for each visit including patient diagnostic codes, reason for admission codes, reason for injury codes, and procedure codes. Category assignments included trauma, infectious, obstetric, gynecologic, dental, ophthalmologic, hematologic, endocrine, cancer, psychiatric, pulmonary, cardiac, gastroenterologic, neurologic, drugs/intoxication, orthopedic, dermatologic, and ears/nose/throat. We categorized all reproductive-related complaints as obstetric- or gynecologic-related, including genital infections, instead of including these visits in the infectious category. Acute infectious complaints such as pneumonia, pharyngitis, or cellulitis were categorized to the infection-related complaints. For example, a visit with codes indicating vaginal bleeding would be categorized as a gynecology-related visit, and a visit with a diagnostic code indicating retinal tear would be categorized as an ophthalmology-related visit, while a visit indicating orbital cellulitis would be categorized under infectious. We constructed these categories to closer represent presenting complaints categories of ED patients to help identify trends in the undifferentiated patient as opposed to relying on the final diagnostic code evaluation. By tracking these complaint categories we hope to establish whether IPV victims present with complaints of one type prior to their date of offense more often than other complaints regardless of their traditional association with IPV.Outcome measures included healthcare use patterns. These specific variables included date of visit, site of visit, and reason for healthcare resource use, including complaint category of visit compared to date of offense.We performed descriptive analysis for all variables, and median and IQR were reported for quantitative measures. We classified date of healthcare visit in relation to the date of reported offense, by number of weeks prior to or after the occurrence. This allowed for comparison of overall trends in healthcare use across the cohort of patients. Researchers compared dates of healthcare visits to the time of offense by calculating correlation coefficients to compare time interval and type of visits to the date of offense. We performed a logistic regression analysis comparing victims who used the ED versus victims who used other healthcare sites. Data was analyzed using SAS version 9.4 , and a p-value less than 0.05 was considered significant.There were 695 separate IPV offenses identifying 695 unique IPV victims within the six-county area, aged 16–55 years old, identified as victims of IPV by the State of Florida Attorney’s Office in 2007. The cohort of 695 Medicaid-eligible IPV victims resulted in a total of 4,344 statewide healthcare visits found in 1.5 years before and after each victim’s identifying offense. The median number of healthcare visits per victim was four (IQR=6), and the median number of ED visits per victim was three (IQR=5). However, there was great variability among victims as indicated by the IQR. The number of healthcare visits per IPV victim ranged from one visit to 98 visits. Fifty-three percent of the visits were before the date of the victim’s offense versus 47% after the date of the victim’s offense. Many victims fell into the 16–25 year old age group (46% of the victims), indicating a relatively young study population. Overall, 79% of the victims were 35 years old or younger at the time of the healthcare use. Most victims were Caucasian (52%) or African American (46%), reflecting the population of the study state.Eighty-three percent of the total 4,344 healthcare visits by IPV victims occurred in the ED. Considering all healthcare visits, the most common complaint categories were obstetric-gynecology-related visits (28.7%), followed by infection-related visits (18.9%), and trauma-related visits (16.3%). Among only ED healthcare visits, the most common complaint categories of IPV victims were infection (22.4%), trauma (19.4%), and obstetric-gynecologic (18.8%).Overall healthcare use by victims escalated approaching their individual dates of reported offenses, with a moderately positive linear correlation . ED visits also demonstrated a strongly strong positive linear correlation of escalating visits approaching the date of reported offense  compared to non-ED healthcare visits . Both total healthcare visits , and ED visits  demonstrated a strong linear correlation with declining visits after the date of reported offense compared to non-ED healthcare visits  –3.Among all healthcare visits, those with the assigned complaint category of orthopedic  and trauma  had positive weak correlations with increasing number of visits up to the date of reported offense. Complaint categories with a weak correlation of declining visits following the day of the reported offense include trauma  and infection  . While iPsychiatric complaint category-related visits before  and after  date of reported offense, were not correlated with the time of reported IPV offenses. None of the other complaint categories had significant correlations to or from the time of reported offense.We compared victims who used the ED to victims who chose non-ED healthcare settings. Victims were 40% more likely to use ED healthcare settings after the date of reported offense versus before, with an OR of 1.41 . The age group more likely to use the ED versus non-ED healthcare settings was the 36–45 age group compared to the youngest group of women . There were no significant differences between races in presenting in the ED versus non-ED healthcare settings.This study offers healthcare providers insight into the healthcare use of IPV victims through an expanded analysis of a unique inclusive cohort of IPV victims’ healthcare use. Most studies are limited to retrospective reviews of court-identified or self reports of victims and small local populations.The third way in which our analysis is unique is the assignment of the complaint category to each visit. Assessing victims by complaint category can lead to more clinically relevant analysis when trying to identify trends in patient presentations, compared to use of discharge diagnoses. The unique data-linkage methods used here paired state law enforcement data to healthcare use and resulted in robust claims data for analysis.While victims used healthcare services frequently up to the date of the index offense and after, there was no single complaint category that successfully identified a majority of the victims. Ascending numbers of visits up to the date of IPV-related events is supported by a three-year county-wide study.Like most research using claims data, conclusions about the diagnostic categories and reasons for visits are limited to the researchers’ interpretation of and the strength of claims data. Retrospective data analysis also limited validity of results due to lack of control of confounding variables. The study also would have been able to make stronger conclusions about overall healthcare use had the claims data included primary care and private outpatient visits. The initial date of reported victimization in 2007 was chosen as the index offense, and it is possible that IPV occurred in prior years or after the index event in the same year. We did not analyze healthcare use trends associated with prior or repeat offenses, and this could have led to repeated measure bias. While Medicaid patients comprise an appropriate cohort for study, a larger study population across all socioeconomic categories would have strengthened external validity. Women who would not normally qualify for Medicaid can enroll when pregnant. This special population may have increased healthcare use associated with obstetric-gynecologic complaints.Female Medicaid-eligible IPV victims use the ED with increasing frequency as the date of the IPV abuse approaches. The women’s presenting complaints varied and did not reveal unique presenting complaints that would allow narrowing screening practices. Frequent ED use in women between the ages of 16–55 years of age should prompt healthcare providers to consider IPV.The successful cross-referencing of administrative and legal databases suggests this is a feasible methodology in investigating other use trends surrounding other types of victimization or criminal behavior. Identifying use patterns for child abuse victims, driving under the influence offenders or suicide victims may further assist practitioners on identifying at-risk patients.