AP Axis Research Articles

Rate of polyethylene wear correlates with earlier glenoid implant failure in anatomic total shoulder arthroplasty with cemented all-polyethylene glenoid components

BackgroundGlenoid component loosening is the most common cause of anatomic total shoulder arthroplasty failure, and osteolysis is a common intraoperative and radiographic finding associated with these failed arthroplasties. While preclinical testing can estimate failure mode and wear rates in the laboratory, there is limited in vivo data measuring polyethylene wear rate and location. MethodsUsing an institutional review board–approved total joint arthroplasty retrieval collection, 56 cemented all-polyethylene glenoid components from eleven different manufacturers were analyzed for in vivo dimensional change. We used the differential thickness measurement between the anteroposterior and superoinferior axes of each radially symmetrical implant to determine the dimensional change along that axis. A physiologic wear vector was determined for each retrieved device. ResultsThe implants had a median dimensional change of 0.13 mm/year (range 0.01-1.01mm/year) and the 25th and 75th percentiles were 0.060 and 0.22 mm/year, respectively. The average time to revision of devices with <0.1mm/year of wear was 140.9 months, while the averages for devices between 0.1-0.2mm/year and ≥0.2mm/year were 80.7 and 54.0 months, respectively. Devices with ≥0.2mm/year of wear had significantly shorter time to revision than those with <0.1mm/year (P = .0006). The devices had a similar material loss distribution in both superior-inferior and anterior-posterior directions, with 29 (52%) devices having a greater material loss in the superior-inferior distribution and the remaining 27 (48%) devices in the anterior-posterior axis. The physiologic wear vector had a mean of 47.3 degrees, with a relatively even distribution across all angles, suggesting that glenoid component loosening can occur along multiple axes. ConclusionWe conclude that polyethylene wear is a contributing factor for early failure of cemented all-polyethylene glenoid implants and that anatomic total shoulder arthroplasty may benefit from advances in polyethylene processing. We also suggest that in vitro testing of new polymers and designs should incorporate motion vectors beyond the traditional IS rocking horse test.

Subject-specific sensitivity of several biomechanical features to fatigue during an exhaustive treadmill run

The aim of the present study was to examine the sensitivity of several movement features during running to exhaustion in a subject-specific setup adopting a cross-sectional design and a machine learning approach. Thirteen recreational runners, that systematically trained and competed, performed an exhaustive running protocol on an instrumented treadmill. Respiratory data were collected to establish the second ventilatory threshold (VT2) in order to obtain a reference point regarding the gradual accumulation of fatigue. A machine learning approach was adopted to analyze kinetic and kinematic data recorded for each participant, using a random forest classifier for the region pre and post the second ventilatory threshold. SHapley Additive exPlanations (SHAP) analysis was used to explain the models’ predictions and to provide insight about the most important variables. The classification accuracy value of the models adopted ranged from 0.853 to 0.962. The most important feature in six out of thirteen participants was the angular range in AP axis of upper trunk C7 (RTAPu) followed by maximum loading rate (RFDmaxD) and the angular range in the LT axis of the C7. SHAP dependence plots also showed an increased dispersion of predictions in stages around the second ventilatory threshold which is consistent with feature interactions. These results showed that each runner used the examined features differently to cope with the increase in fatigue and mitigate its effects in order to maintain a proper motor pattern.

Are liver contour and bone fusion comparable to fiducials for IGRT in liver SBRT?

Liver stereotactic body radiotherapy (SBRT) is increasingly being used to treat tumours. The purpose of this study was to compare the differences in patient positioning when using implanted fiducials as surrogates compared to alternative methods based on liver contour or bone registration. Eighteen patients treated with SBRT who underwent a fiducial placement procedure were included. Fiducial guidance was our gold standard to guide treatment in this study. After recording the displacements, when fusing the planning CT and CBCT performed in the treatment unit using fiducials, liver contour and bone reference, the differences between fiducials and liver contour and bone reference were calculated. Data from 88 CBCT were analyzed. The correlation between the displacements found with fiducials and those performed based on the liver contour and the nearest bone structure as references was determined. The mean, median, variance, range and standard deviation of the displacements with each of the fusion methods were obtained. μ, Ʃ, and σ values and margins were obtained. Lateral displacements of less than 3mm with respect to the gold standard in 92% vs. 62.5% of cases using liver contour and bone references, respectively, with 93.2% vs. 65.9% in the AP axis and SI movement in 69.3% vs. 51.1%. The errors μ, σ and Ʃ of the fusions with hepatic contour and bone reference in SI were 0.26mm, 4mm and 3mm, and 0.8mm, 5mm and 3mm respectively. Our study showed that displacements were smaller with the use of hepatic contour compared to bone reference and comparable to those obtained with the use of fiducials in the lateral, AP and SI motion axes. This would justify that hepatic contouring can be a guide in the treatment of patients in the absence of fiducials.

A Case Study of Infantile Nystagmus Syndrome (Congenital)

Infantile nystagmus (IN), formerly known as congenital nystagmus, is an involuntary to-and-fro movement of the eyes that persists throughout life. IN is one of three types of early-onset nystagmus that first appear in infancy, alongside fusion maldevelopment nystagmus syndrome and spasmus nutans syndrome. Patients with acquired nystagmus may also be seen by optometrists. The features of IN overlap largely with those of fusion maldevelopment nystagmus syndrome, spasmus nutans syndrome, and acquired nystagmus, yet the management for each subtype is different. We report a case of bilateral congenital sensory nystagmus with bilateral megalocornea with left-sided relative afferent pupil defect with left eye global enlargement in ap axis with reduced caliber in left optic artery with pseudo polycorea with reduced visual acuity in the bilateral eye with buphthalmos with haab striae.

Lateral adherens junctions mediate a supracellular actomyosin cortex in drosophila trachea

Drosophila trachea is a classical model for analyzing epithelial, especially tubular epithelial biology. We identify lateral E-cadherin mediated junctions that encircle the cells just basal to the zonula adherens in the larval trachea. The lateral junction is associated with downstream adapters, including catenins, and has a distinct junctional actin cortex. The lateral cortex contributes to the development of a supracellular actomyosin mesh in the late larvae. Establishment of this cytoskeletal structure depends on lateral junction associated Rho1 and Cdc42 GTPases, and Arp and WASP pathways. The supracellular network takes the character of stress fibers along the AP axis in the early hours of pupation. It contributes to the shortening of the epithelial tube albeit in a manner redundant to ECM-mediated compression mechanism. In conclusion, we show the invivo existence of functional lateral adherens junction and suggest a role for it in mediating dynamic cytoskeletal events during tissue scale morphogenesis.

Elevated Neuropeptide Y in the Arcuate Nucleus of Young Obese Zucker Rats May Contribute to the Development of Their Overeating

Neuropeptide Y (NPY) mediates feeding behavior through a local hypothalamic network formed by the arcuate and paraventricular nuclei (the AP axis). In the hypothalamus, NPY is mainly synthesized in neurons of the arcuate nucleus. These neurons project to the paraventricular nucleus, the site where NPY has the strongest stimulatory effects on food intake of Sprague-Dawley rats. In the adult Zucker fatty rat (a genetic model of obesity with a well-established hyperphagia), NPY concentrations in these nuclei are higher than in its lean counterpart. We measured hypothalamic NPY before the appearance of altered eating behavior, e.g., in very young (16-d-old) lean and obese Zucker pups, and in pups at an age when overeating had begun, e.g., a few days after weaning at 30 d. At 30 d, NPY concentrations were significantly higher in obese than in lean rats in the arcuate nucleus (14.2 +/- 0.7 vs. 11.6 +/- 0.5 pmol/mg protein, P < 0.01). This difference was not observed at 16 d. A 160% increase was noted in the paraventricular nuclei of obese rats between 16 and 30 d of life compared with a 100% increase in the lean rats (P < 0.001). Neuropeptide Y concentration was greater in 30-d-old rats than in 16-d-old rats in other areas involved in the regulation of feeding behavior, such as the dorsomedian nuclei and lateral hypothalamus, but the values did not differ between genotypes. Higher NPY concentration was therefore detected early in young obese rats in the main hypothalamic site of NPY synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Age-Related Change of Head Control in Response to Postural Perturbations

<h3>Research Objectives</h3> To explore if older adults, particularly those over 75 years, have more zero-crossings to restore head stabilization than young adults after postural perturbations. <h3>Design</h3> Cross-sectional study. <h3>Setting</h3> Laboratory setting. <h3>Participants</h3> A convenient sample of 57 healthy participants without a current or past history of neck-related dysfunction, trauma, deformities, and uncontrolled balance issues were recruited. They were grouped by age: Young (18-30 yrs, age: 22.3±3.8), Young-Old (60-74 yrs, age: 67.2±3.8), and Old-Old (>75+ yrs, age: 81.1±5.3). <h3>Interventions</h3> Not applicable. <h3>Main Outcome Measures</h3> Accelerometers (Delsys) were attached on the forehead and C7 of participants as they experienced the unexpected platform translations (Neurocom). A total of six trials were performed in random order including three anterior and posterior perturbations. The linear head acceleration in the vertical, anteroposterior, and mediolateral axis were extracted. A custom Matlab code computed the resultant head acceleration, detected the head re-stabilization time of each trail, and determined the number of zero-crossings during the head re-stabilization of three axes. <h3>Results</h3> Significant less zero-crossings in the Young group were noted in the vertical (p = 0.011, η2 = 0.07) and AP (p = 0.030, η2 = 0.05) axes of posterior platform translation. Despite no statistical differences found in other conditions, a trend of increased zero-crossing with aging was suggested. The Old-Old group consistently showed the greatest number of zero-crossings across all the conditions. <h3>Conclusions</h3> Older adults appear to recruit a different head stabilization strategy in response to postural perturbations. The oldest age group (over 75 years) seems to show more vigorous neuromuscular control to restore the postural stabilization in the head-neck segment after the perturbation than the younger counterparts. <h3>Author(s) Disclosures</h3> Authors declared that none of us had relevant or material financial interests that relate to the research described in this research project.

Effects of Fatigue on Postural Sway and Electromyography Modulation in Young Expert Acrobatic Gymnasts and Healthy Non-trained Controls During Unipedal Stance.

This study investigated whether expert acrobatic gymnasts respond differentially than their non-trained counterparts during a single-legged stance task performed before and after a protocol designed to induce fatigue in the ankle plantarflexor muscles in terms of (a) postural steadiness and (b) electromyography (EMG) activation. We hypothesized that neuromuscular adaptation due to training would lead to different behavior of center of pressure (COP) and EMG quantifiers after fatigue. Twenty eight female volunteers (aged 11 to 24 years) formed two groups: expert acrobatic gymnastics athletes (GYN, n = 14) and age-matched non-gymnasts [control (CTRL), n = 14]. Fatigue of the ankle plantarflexors (dominant leg) was induced by a sustained posture (standing on the toes) until exhaustion. Traditional COP parameters (area, RMS, mean velocity, and power spectrum at low and high frequency ranges) were obtained with a force plate, and time and frequency-domain EMG parameters were obtained by surface electrodes positioned on the tibialis anterior, soleus, lateral gastrocnemius, medial gastrocnemius, vastus lateralis, biceps femoris, spinal erector and rectus abdominis muscles. The main results showed that fatigue induced a significant increase in postural oscillations in the ML axis (including RMS, velocity and frequency components of the power spectrum), with no significant effects in the AP axis. In terms of postural sway parameters (i.e., COP quantifiers), no superior balance stability was found for the GYN group as compared to CTRL, irrespective of the fatigue condition. On the other hand, the modulation of EMG parameters (in both time and frequency domains) indicated that expert acrobatic gymnastics athletes (as compared to healthy untrained matched controls) used different neuromuscular control strategies to keep their postures on single-legged quiet standing after the fatiguing protocol. The present results improve our knowledge of the mechanisms behind the interplay between fatigue and postural performance associated with the neuromuscular adaptations induced by sport practice. The design of gymnastics training might consider strategies aimed at improving the performance of specific muscles (i.e., tibialis anterior, soleus, biceps femoris, spinal erector) for which particular activation patterns were used by the acrobatic gymnastics to control single-legged quiet standing.

Roles of Drosophila Hox Genes in the Assembly of Neuromuscular Networks and Behavior.

Hox genes have been known for specifying the anterior-posterior axis (AP) in bilaterian body plans. Studies in vertebrates have shown their importance in developing region-specific neural circuitry and diversifying motor neuron pools. In Drosophila, they are instrumental for segment-specific neurogenesis and myogenesis early in development. Their robust expression in differentiated neurons implied their role in assembling region-specific neuromuscular networks. In the last decade, studies in Drosophila have unequivocally established that Hox genes go beyond their conventional functions of generating cellular diversity along the AP axis of the developing central nervous system. These roles range from establishing and maintaining the neuromuscular networks to controlling their function by regulating the motor neuron morphology and neurophysiology, thereby directly impacting the behavior. Here we summarize the limited knowledge on the role of Drosophila Hox genes in the assembly of region-specific neuromuscular networks and their effect on associated behavior.

Extensive loss of Wnt genes in Tardigrada

BackgroundWnt genes code for ligands that activate signaling pathways during development in Metazoa. Through the canonical Wnt (cWnt) signaling pathway, these genes regulate important processes in bilaterian development, such as establishing the anteroposterior axis and posterior growth. In Arthropoda, Wnt ligands also regulate segment polarity, and outgrowth and patterning of developing appendages. Arthropods are part of a lineage called Panarthropoda that includes Onychophora and Tardigrada. Previous studies revealed potential roles of Wnt genes in regulating posterior growth, segment polarity, and growth and patterning of legs in Onychophora. Unlike most other panarthropods, tardigrades lack posterior growth, but retain segmentation and appendages. Here, we investigated Wnt genes in tardigrades to gain insight into potential roles that these genes play during development of the highly compact and miniaturized tardigrade body plan.ResultsWe analyzed published genomes for two representatives of Tardigrada, Hypsibius exemplaris and Ramazzottius varieornatus. We identified single orthologs of Wnt4, Wnt5, Wnt9, Wnt11, and WntA, as well as two Wnt16 paralogs in both tardigrade genomes. We only found a Wnt2 ortholog in H. exemplaris. We could not identify orthologs of Wnt1, Wnt6, Wnt7, Wnt8, or Wnt10. We identified most other components of cWnt signaling in both tardigrade genomes. However, we were unable to identify an ortholog of arrow/Lrp5/6, a gene that codes for a Frizzled co-receptor of Wnt ligands. Additionally, we found that some other animals that have lost several Wnt genes and are secondarily miniaturized, like tardigrades, are also missing an ortholog of arrow/Lrp5/6. We analyzed the embryonic expression patterns of Wnt genes in H. exemplaris during developmental stages that span the establishment of the AP axis through segmentation and leg development. We detected expression of all Wnt genes in H. exemplaris besides one of the Wnt16 paralogs. During embryo elongation, expression of several Wnt genes was restricted to the posterior pole or a region between the anterior and posterior poles. Wnt genes were expressed in distinct patterns during segmentation and development of legs in H. exemplaris, rather than in broadly overlapping patterns.ConclusionsOur results indicate that Wnt signaling has been highly modified in Tardigrada. While most components of cWnt signaling are conserved in tardigrades, we conclude that tardigrades have lost Wnt1, Wnt6, Wnt7, Wnt8, and Wnt10, along with arrow/Lrp5/6. Our expression data may indicate a conserved role of Wnt genes in specifying posterior identities during establishment of the AP axis. However, the loss of several Wnt genes and the distinct expression patterns of Wnt genes during segmentation and leg development may indicate that combinatorial interactions among Wnt genes are less important during tardigrade development compared to many other animals. Based on our results, and comparisons to previous studies, we speculate that the loss of several Wnt genes in Tardigrada may be related to a reduced number of cells and simplified development that accompanied miniaturization and anatomical simplification in this lineage.

Noise reduction in diffusion weighted MRI of the pancreas using an L1-regularized iterative SENSE reconstruction

ObjectivesTo prospectively evaluate an L1 regularized iterative SENSE reconstruction (L1-R SENSE) to eliminate band-like artifacts frequently seen with parallel imaging (SENSE) at high acceleration factors in high resolution diffusion weighted magnetic resonance imaging of the pancreas. MethodsFourteen patients with pancreatic ductal adenocarcinoma (PDAC) underwent respiratory triggered DWI ss-EPI at a resolution of 2.5 × 2.5 × 3 mm3 with uniform undersampling in the phase encoding direction (AP axis) with an acceleration factor of 4. Data were reconstructed using the standard SENSE reconstruction routine of the vendor and an iterative SENSE reconstruction employing L1 regularization after a wavelet sparsifying transformation (L1-R SENSE). Retrospective reconstruction of the data with a lower number of averages was performed using both reconstruction methods. Two radiologists independently assessed noise artifacts, anatomical details and image quality (IQ) subjectively with a 4-point scale. Apparent diffusion coefficient (ADC) and covariance (CV) of ADC estimated from images reconstructed at a different number of averages for PDAC and the normal pancreas were assessed. ResultsL1-R SENSE resulted in higher IQ and less noise artifacts than SENSE. Anatomical details were significantly higher for SENSE in one reader. Mean ADC of PDAC and normal pancreas were significantly higher for L1-R SENSE than SENSE. L1-R SENSE revealed lower CV of ADC for normal pancreas compared to SENSE, whereas no difference was noted for PDAC. ConclusionCompared with traditional SENSE reconstruction, L1-R SENSE effectively reduces band-like noise and improves the robustness of the ADC estimation from acquisitions using single-shot DW-EPI of the pancreas.

Adult stem cells and niche cells segregate gradually from common precursors that build the adult Drosophila ovary during pupal development.

Production of proliferative follicle cells (FCs) and quiescent escort cells (ECs) by follicle stem cells (FSCs) in adult Drosophila ovaries is regulated by niche signals from anterior (cap cells, ECs) and posterior (polar FCs) sources. Here we show that ECs, FSCs, and FCs develop from common pupal precursors, with different fates acquired by progressive separation of cells along the AP axis and a graded decline in anterior cell proliferation. ECs, FSCs, and most FCs derive from intermingled cell (IC) precursors interspersed with germline cells. Precursors also accumulate posterior to ICs before engulfing a naked germline cyst projected out of the germarium to form the first egg chamber and posterior polar FC signaling center. Thus, stem and niche cells develop in appropriate numbers and spatial organization through regulated proliferative expansion together with progressive establishment of spatial signaling cues that guide adult cell behavior, rather than through rigid early specification events.

Sensitivity of movement features to fatigue during an exhaustive treadmill run

ABSTRACT The objective of the present study was to examine the sensitivity of several movement variables during running to exhaustion adopting a cross-sectional design. Thirteen recreational runners, that systematically trained and competed, performed an exhaustive running protocol on an instrumented treadmill. Respiratory data were collected to establish the ventilatory threshold in order to obtain a reference point regarding the gradual accumulation of fatigue. A machine learning approach was adopted to analyse a set of 29,650 data points (individual steps) of kinetic and kinematic data, using a random forest classifier for the region pre and post the ventilatory threshold. The overall accuracy of the model was 0.914 (95% CI: 0.907–0.919). The four most important variables, and more sensitive in predictive ability, as it was concluded from the variable importance procedure and the partial dependence (PD), were the angular range in AP axis of upper trunk C7, the maximum loading rate, the angular range in LT axis of the C7 and the maximum value of the ground reaction force. Two-dimensional PD revealed considerable interactions for certain areas of the joint distributions between kinetic and kinematic data. These results provide a direction towards understanding the interconnections of kinetics and kinematics of the torso to maintain the coordinated running pattern under fatigue conditions. Highlights Trunk frontal plane kinematics is the most sensitive parameter to fatigue. Practitioners should consider this finding during endurance training. Kinetics exhibit a stable linear increase in mean values but a non-linear increase in variance during an exhaustive incremental treadmill run. This may affect training at a submaximal fatigued state. Specific areas in the joint distributions of kinetics and kinematics during treadmill running exhibit increased sensitivity in predicting fatigue state.

Calcification of Falx Cerebri between Male and Female Patients: A Comparative Study

Objectives: The aim of this paper is to study the calcification that occurs in the inter−hemispheric fissure to compare between male and female patients. Materials and Methods: The level of density and size of these calcifications were collected and analyzed in 30 patients randomly. Results: The result of this study showed that there is a relation between falx cerebri and gender since its more common in female patients. The density of the calcifications is higher in males and the calcifications are longer on the AP axis, while the falx cerebri calcifications are wider in the coronal axis in females. Conclusion: There is a relation between Calcification of falx cerebri and gender.

Mobility of Older Adults: Gait Quality Measures Are Associated With Life-Space Assessment Scores.

The relation of gait quality to real-life mobility among older adults is poorly understood. This study examined the association between gait quality, consisting of step variability, smoothness, regularity, symmetry, and gait speed, and the Life-Space Assessment (LSA). In community-dwelling older adults (N = 232, age 77.5 ± 6.6, 65% females), gait quality was derived from (i) an instrumented walkway: gait speed, variability, and walk ratio and (ii) accelerometer: signal variability, smoothness, regularity, symmetry, and time-frequency spatiotemporal variables during 6-minute walk. In addition to collecting LSA scores, cognitive functioning, walking confidence, and falls were recorded. Spearman correlations (speed as covariate) and random forest regression were used to assess associations between gait quality and LSA, and Gaussian mixture modeling (GMM) was used to cluster participants. Spearman correlations of ρ p = .11 (signal amplitude variability mediolateral [ML] axis), ρ p = .15 and ρ p = -.13 (symmetry anterior-posterior-vertical [AP-V] and ML-AP axes, respectively), ρ p = .16 (power V), and ρ = .26 (speed), all p <.05 and marginally related, ρ p = -.12 (regularity V), ρ p = .11 (smoothness AP), and ρ p = -.11 (step-time variability), all p <.1, were obtained. The cross-validated random forest model indicated good-fit LSA prediction error of 17.77; gait and cognition were greater contributors than age and gender. GMM indicated 2 clusters. Group 1 (n = 189) had better gait quality than group 2 (n = 43): greater smoothness AP (2.94 ± 0.75 vs 2.30 ± 0.71); greater similarity AP-V (.58 ± .13 vs .40 ± .19); lower regularity V (0.83 ± 0.08 vs 0.87 ± 0.10); greater power V (1.86 ± 0.18 vs 0.97 ± 1.84); greater speed (1.09 ± 0.16 vs 1.00 ± 0.16 m/s); lower step-time coefficient of variation (3.70 ± 1.09 vs 5.09 ± 2.37), and better LSA (76 ± 18 vs 67 ± 18), padjusted < .004. Gait quality measures taken in the clinic are associated with real-life mobility in the community.

Spatiotemporal contribution of neuromesodermal progenitor-derived neural cells in the elongation of developing mouse spinal cord

AimsDuring vertebrate development, the posterior end of the embryo progressively elongates in a head-to-tail direction to form the body plan. Recent lineage tracing experiments revealed that bi-potent progenitors, called neuromesodermal progenitors (NMPs), produce caudal neural and mesodermal tissues during axial elongation. However, their precise location and contribution to spinal cord development remain elusive. Main methodsHere we used NMP-specific markers (Sox2 and BraT) and a genetic lineage tracing system to localize NMP progeny in vivo. Key findingsSox2 and BraT double positive cells were initially located at the tail tip, but were later found in the caudal neural tube, which is a unique feature of mouse development. In the neural tube, they produced neural progenitors (NPCs) and contributed to the spinal cord gradually along the AP axis during axial elongation. Interestingly, NMP-derived NPCs preferentially contributed to the ventral side first and later to the dorsal side at the lumbar spinal cord level, which may be associated with atypical junctional neurulation in mice. SignificanceOur current observations detail the contribution of NMP progeny to spinal cord elongation and provide insights into how different species uniquely execute caudal morphogenesis.

A transgenic Alx4-CreER mouse to analyze anterior limb and nephric duct development.

Genetic tools to study gene function and the fate of cells in the anterior limb bud are very limited. We describe a transgenic mouse line expressing CreERT2 from the Aristaless-like 4 (Alx4) promoter that induces recombination in the anterior limb. Cre induction at embryonic day 8.5 revealed that Alx4-CreERT2 labeled cells using the mTmG Cre reporter contributed to anterior digits I to III as well as the radius of the forelimb. Cre activity is expanded further along the AP axis in the hindlimb than in the forelimb resulting in some Cre reporter cells contributing to digit IV. Induction at later time points labeled cells that become progressively restricted to more anterior digits and proximal structures. Comparison of Cre expression from the Alx4 promoter transgene with endogenous Alx4 expression reveals Cre expression is slightly expanded posteriorly relative to the endogenous Alx4 expression. Using Alx4-CreERT2 to induce loss of intraflagellar transport 88 (Ift88), a gene required for ciliogenesis, hedgehog signaling, and limb patterning, did not cause overt skeletal malformations. However, the efficiency of deletion, time needed for Ift88 protein turnover, and for cilia to regress may hinder using this approach to analyze cilia in the limb. Alx4-CreERT2 is also active in the mesonephros and nephric duct that contribute to the collecting tubules and ducts of the adult nephron. Embryonic activation of the Alx4-CreERT2 in the Ift88 conditional line results in cyst formation in the collecting tubules/ducts. Overall, the Alx4-CreERT2 line will be a new tool to assess cell fates and analyze gene function in the anterior limb, mesonephros, and nephric duct.

Fiducial-based image-guided SBRT for pancreatic adenocarcinoma: Does inter-and intra-fraction treatment variation warrant adaptive therapy?

PurposeVariation in target positioning represents a challenge to set-up reproducibility and reliability of dose delivery with stereotactic body radiation therapy (SBRT) for pancreatic adenocarcinoma (PDAC). While on-board imaging for fiducial matching allows for daily shifts to optimize target positioning, the magnitude of the shift as a result of inter- and intra-fraction variation may directly impact target coverage and dose to organs-at-risk. Herein, we characterize the variation patterns for PDAC patients treated at a high-volume institution with SBRT.MethodsWe reviewed 30 consecutive patients who received SBRT using active breathing coordination (ABC). Patients were aligned to bone and then subsequently shifted to fiducials. Inter-fraction and intra-fraction scans were reviewed to quantify the mean and maximum shift along each axis, and the shift magnitude. A linear regression model was conducted to investigate the relationship between the inter- and intra-fraction shifts.ResultsThe mean inter-fraction shift in the LR, AP, and SI axes was 3.1 ± 1.8 mm, 2.9 ± 1.7 mm, and 3.5 ± 2.2 mm, respectively, and the mean vector shift was 6.4 ± 2.3 mm. The mean intra-fraction shift in the LR, AP, and SI directions were 2.0 ± 0.9 mm, 2.0 ± 1.3 mm, and 2.3 ± 1.4 mm, respectively, and the mean vector shift was 4.3 ± 1.8 mm. A linear regression model showed a significant relationship between the inter- and intra-fraction shift in the AP and SI axis and the shift magnitude.ConclusionsClinically significant inter- and intra-fraction variation occurs during treatment of PDAC with SBRT even with a comprehensive motion management strategy that utilizes ABC. Future studies to investigate how these variations could lead to variation in the dose to the target and OAR should be investigated. Strategies to mitigate the dosimetric impact, including real time imaging and adaptive therapy, in select cases should be considered.

The Cdx transcription factors and retinoic acid play parallel roles in antero-posterior position of the pectoral fin field during gastrulation

The molecular regulators that determine the precise position of the vertebrate limb along the anterio-posterior axis have not been identified. One model suggests that a combination of hox genes in the lateral plate mesoderm (LPM) promotes formation of the limb field, however redundancy among duplicated paralogs has made this model difficult to confirm. In this study, we identify an optimal window during mid-gastrulation stages when transient mis-regulation of retinoic acid signaling or the caudal related transcription factor, Cdx4, both known regulators of hox genes, can alter the position of the pectoral fin field. We show that increased levels of either RA or Cdx4 during mid-gastrulation are sufficient to rostrally shift the position of the pectoral fin field at the expense of surrounding gene expression in the anterior lateral plate mesoderm (aLPM). Alternatively, embryos deficient for both Cdx4 and Cdx1a (Cdx-deficient) form pectoral fins that are shifted towards the posterior and reveal an additional effect on size of the pectoral fin buds. Prior to formation of the pectoral fin buds, the fin field in Cdx-deficient embryos is visibly expanded into the posterior LPM (pLPM) region at the expense of surrounding gene expression. The effects on gene expression immediately post-gastrulation and during somitogenesis support a model where RA and Cdx4 act in parallel to regulate the position of the pectoral fin. Our transient method is a potentially useful model for studying the mechanisms of limb positioning along the AP axis.

The tibial lateral axis is a novel extraarticular landmark for detection of the tibial anteroposterior axis.

Although the tibial rotation axis is significant in knee arthroplasty, no reliable extraarticular landmark has been proposed. We hypothesized that the tibial lateral axis (TLA), a tangential line of the lateral tibial surface, is perpendicular to the surgical epicondylar axis (SEA) and compared it to other existing landmarks by 3D-CT. Fifty legs in 25 consecutive patients were studied. Using their preoperative CT, the TLAs were identified on slices at 10-50% of the total length of the tibia and the measured differences of angles against the line perpendicular to the SEA (the tibial AP axis) were calculated. The differences between the SEA and the femoral and tibial posterior condylar axis, Akagi's line and the line between the medial intercondylar spine and the medial border of the patellar tendon (sAP line)(intraarticular), the ankle axis, and the transmalleolar axis (extraarticular) were also calculated and compared. The mean values of TLA at 10%, 20%, 30% were virtually parallel to the SEA (0.97° ± 4.84°, 0.02° ± 4.61°, 1.10° ± 4.97°, respectively). They were equivalent to existing intraarticular landmarks and superior to existing extraarticular landmarks, and these levels corresponded to the tip to the lower end of the tibial tubercle (at 10.8% and 17.0% of total tibial length). The proximal TLAs can be an extraarticular bony landmark that indicates the line perpendicular to the SEA. A prospective study is needed to prove the validity and accuracy of the axes clinically.