A Biomechanical Analysis of Tibial Fixation Methods in Hamstring-Graft Anterior Cruciate Ligament Reconstruction.

Background: There are conflicting results on the biomechanical properties of tibial fixation devices in anterior cruciate ligament reconstruction. The objective of this study is to compare the initial biomechanical properties of tibial fixation in hamstring-graft ACL reconstruction with interference screw, suspension button, and Tape Locking ScrewTM devices. We hypothesized there are no differences in the initial biomechanical properties of these three tibial fixation techniques. Methods: Twenty-one fresh-frozen porcine tibiae were equally divided into three groups of seven tibiae to evaluate the fixation of human hamstring tendon grafts with interference screw, suspension button, or Tape Locking Screw fixation. Using a servohydraulic materials testing system, each graft was subjected to 500 cycles of loading followed by a monotonic failure test. Results: Interference screw fixation demonstrated significantly lower cyclic displacement (1.28 ± 0.73 mm) than the other groups fixated with either a suspension button device (2.54 ± 0.27 mm, p = 0.003) or a Tape Locking Screw (2.32 ± 0.42 mm, p = .009), and a significantly greater cyclic stiffness (212.19 ± 40.30 N/mm) than the Tape Locking Screw (137.64 ± 26.17 N/mm, p = 0.002). The interference screw also demonstrated significantly higher pullout stiffness (166.83 ± 23.22 N/mm) than the suspension button (112.78 ± 24.14 N/mm, P = 0.002) and Tape Locking Screw (109.11 ± 12.91 N/mm, P = 0.0002). Conclusions: Tibial fixation with an interference screw demonstrated superior biomechanical properties for cyclic testing compared to the suspension button and Tape Locking Screw. Load to failure did not differ between groups, and there were no significant biomechanical differences between the suspension button and Tape Locking Screw fixation devices. Clinical Relevance: Despite the initial biomechanical differences, all three fixation devices exhibited mean loads to failure and cyclic displacements below clinically relevant thresholds of failure. These data suggest all three fixation methods are viable options for achieving a functional ACL reconstruction.Level of Evidence: V.

Biologic therapies for refractory juvenile dermatomyositis: five years of experience of the Childhood Arthritis and Rheumatology Research Alliance in North America.

BACKGROUND: The prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960's with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from human genes) for inflammatory myositis has been reported. In 2011-2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA). METHODS: The JDM biologic study group developed a survey on the CARRA member experience using biologics for Juvenile DM utilizing Delphi consensus methods in 2011-2012. The survey was completed online by the CARRA members interested in JDM in 2012. A second survey was similarly developed that provided more opportunity to describe their experiences with biologics in JDM in detail and was completed by CARRA members in Feb 2013. During three CARRA meetings in 2013-2015, nominal group techniques were used for achieving consensus on the current choices of biologic drugs. A final survey was performed at the 2016 CARRA meeting. RESULTS: One hundred and five of a potential 231 pediatric rheumatologists (42%) responded to the first survey in 2012. Thirty-five of 90 had never used a biologic for Juvenile DM at that time. Fifty-five of 91 (denominators vary) had used biologics for JDM in their practice with 32%, 5%, and 4% using rituximab, etanercept, and infliximab, respectively, and 17% having used more than one of the three drugs. Ten percent used a biologic as monotherapy, 19% a biologic in combination with methotrexate (mtx), 52% a biologic in combination with mtx and corticosteroids, 42% a combination of a biologic, mtx, corticosteroids (steroids), and an immunosuppressive drug, and 43% a combination of a biologic, IVIG and mtx. The results of the second survey supported these findings in considerably more detail with multiple combinations of drugs used with biologics and supported the use of rituximab, abatacept, anti-TNFα drugs, and tocilizumab in that order. One hundred percent recommended that CARRA continue studying biologics for JDM. The CARRA meeting survey in 2016 again supported the study and use of these four biologic drug groups. CONCLUSIONS: Our CARRA JDM biologic work group developed and performed three surveys demonstrating that pediatric rheumatologists in North America have been using multiple biologics for refractory JDM in numerous scenarios from 2011 to 2016. These survey results and our consensus meetings determined our choice of four biologic therapies (rituximab, abatacept, tocilizumab and anti-TNFα drugs) to consider for refractory JDM treatment when indicated and to evaluate for comparative effectiveness and safety in the future. Significance and Innovations This is the first report that provides a substantial clinical experience of a large group of pediatric rheumatologists with biologics for refractory JDM over five years. This experience with biologic therapies for refractory JDM may aid pediatric rheumatologists in the current treatment of these children and form a basis for further clinical research into the comparative effectiveness and safety of biologics for refractory JDM.

Databases and Archiving for CryoEM.

CryoEM in structural biology is currently served by three public archives-EMDB for 3DEM reconstructions, PDB for models built from 3DEM reconstructions, and EMPIAR for the raw 2D image data used to obtain the 3DEM reconstructions. These archives play a vital role for both the structural community and the wider biological community in making the data accessible so that results may be reused, reassessed, and integrated with other structural and bioinformatics resources. The important role of the archives is underpinned by the fact that many journals mandate the deposition of data to PDB and EMDB on publication. The field is currently undergoing transformative changes where on the one hand high-resolution structures are becoming a routine occurrence while on the other hand electron tomography is enabling the study of macromolecules in the cellular context. Concomitantly the archives are evolving to best serve their stakeholder communities. In this chapter, we describe the current state of the archives, resources available for depositing, accessing, searching, visualizing and validating data, on-going community-wide initiatives and opportunities, and challenges for the future.

Exome sequencing in 32 patients with anophthalmia/microphthalmia and developmental eye defects.

Anophthalmia/microphthalmia (A/M) is a genetically heterogeneous birth defect for which the etiology is unknown in more than 50% of patients. We used exome sequencing with the ACE Exome(TM) (Personalis, Inc; 18 cases) and UCSF Genomics Core (21 cases) to sequence 28 patients with A/M and four patients with varied developmental eye defects. In the 28 patients with A/M, we identified de novo mutations in three patients (OTX2, p.(Gln91His), RARB, p.Arg387Cys and GDF6, p.Ala249Glu) and inherited mutations in STRA6 in two patients. In patients with developmental eye defects, a female with cataracts and cardiomyopathy had a de novo COL4A1 mutation, p.(Gly773Arg), expanding the phenotype associated with COL4A1 to include cardiomyopathy. A male with a chorioretinal defect, microcephaly, seizures and sensorineural deafness had two PNPT1 mutations, p.(Ala507Ser) and c.401-1G>A, and we describe eye defects associated with this gene for the first time. Exome sequencing was efficient for identifying mutations in pathogenic genes for which there is no clinical testing available and for identifying cases that expand phenotypic spectra, such as the PNPT1 and COL4A1-associated disorders described here.

Intradiscal Pressure Changes during Manual Cervical Distraction: A Cadaveric Study.

The objective of this study was to measure intradiscal pressure (IDP) changes in the lower cervical spine during a manual cervical distraction (MCD) procedure. Incisions were made anteriorly, and pressure transducers were inserted into each nucleus at lower cervical discs. Four skilled doctors of chiropractic (DCs) performed MCD procedure on nine specimens in prone position with contacts at C5 or at C6 vertebrae with the headpiece in different positions. IDP changes, traction forces, and manually applied posterior-to-anterior forces were analyzed using descriptive statistics. IDP decreases were observed during MCD procedure at all lower cervical levels C4-C5, C5-C6, and C6-C7. The mean IDP decreases were as high as 168.7 KPa. Mean traction forces were as high as 119.2 N. Posterior-to-anterior forces applied during manual traction were as high as 82.6 N. Intraclinician reliability for IDP decrease was high for all four DCs. While two DCs had high intraclinician reliability for applied traction force, the other two DCs demonstrated only moderate reliability. IDP decreases were greatest during moving flexion and traction. They were progressevely less pronouced with neutral traction, fixed flexion and traction, and generalized traction.

Computed tomography-based morphometric analysis of cervical pedicles in Indian population: a pilot study to assess feasibility of transpedicular screw fixation.

BACKGROUND: Cervical transpedicular screw fixation is safe and is probably going to be the gold standard for cervical spine fixation. However, cervical transpedicular screw use in the Asian population can be limited as the transverse diameter in this group of patients may not be adequate to accommodate the 3.5-mm pedicular screw thus injuring the vital structures located in the close proximity of the pedicles. Thus lateral mass fixation remains the mainstay of treatment. The present study evaluated the transverse cervical pedicle diameter of C2-C7 vertebrae in a pilot study in 27 Indian subjects using computed tomography (CT) imaging and evaluated the feasibility of transpedicular screw fixation in them. AIMS: To evaluate the feasibility of transpedicular screw fixation in the Indian population. SETTINGS AND DESIGN: The cervical pedicle diameter size differs between the Asian and non-Asian population. The authors studied the transverse pedicle diameter of the C2-C7 of the cervical spine in the Indian population using CT measurements. This cross-sectional study was carried out at a tertiary care centre for a period of four months from October 2010 to December 2010. MATERIAL AND METHODS: Measurements of cervical pedicles in the subjects were performed on the CT workstation from the CT images taken at 2.5-mm interval. The transverse pedicle diameter was defined as the outermost diameter of the pedicle, taken perpendicular to the axis of the pedicle at the narrowest point and measured in millimeters±0.1 mm. STATISTICAL ANALYSIS: Descriptive statistics was used to represent percentage of transverse diameter of cervical pedicles less than 5 mm in male and female subjects at C2-C7 levels. Since there is no previous study done in India, we initiated the study with sample size of 27 as a pilot study. The statistical analysis was performed using SPSS software. RESULTS: The mean transverse diameters of the cervical pedicles of C2, C3, C4, C5, C6 and C7 in males were 5.3, 5.3, 5.3, 5.6, 5.6 and 6.1 mm respectively and ranged between 5.3 to 6.1 mm. The mean transverse diameters of the cervical pedicles of C2, C3, C4, C5, C6 and C7 in females were 5.1, 4.6, 4.7, 4.7, 5.3 and 5.6 mm respectively and ranged between 4.6 to 5.6 mm. Between 2.1% and 55.7% of pedicles in our male population and between 5.5% and 74.3% pedicles in our female population was smaller than 5.0 mm in transverse diameter and thus cannot have fixation with a 3.5 mm screw using this technique. CONCLUSIONS: We found that the transverse pedicle diameter of cervical pedicles in the Indian subjects is smaller compared to the Western population. Although transpedicular screw fixation has stronger pullout strength compared to lateral mass fixation, its use must be considered carefully and individually. Preoperative CT evaluation is a must before transpedicular fixation in the cervical spine, especially in the Indian female population. As an option 2.7-mm screws can be devised for the Indian population giving a wider safety margin.

Primary and coupled motions after cervical total disc replacement using a compressible six-degree-of-freedom prosthesis.

This study tested the hypotheses that (1) cervical total disc replacement with a compressible, six-degree-of-freedom prosthesis would allow restoration of physiologic range and quality of motion, and (2) the kinematic response would not be adversely affected by variability in prosthesis position in the sagittal plane. Twelve human cadaveric cervical spines were tested. Prostheses were implanted at C5-C6. Range of motion (ROM) was measured in flexion-extension, lateral bending, and axial rotation under ± 1.5 Nm moments. Motion coupling between axial rotation and lateral bending was calculated. Stiffness in the high flexibility zone was evaluated in all three testing modes, while the center of rotation (COR) was calculated using digital video fluoroscopic images in flexion-extension. Implantation in the middle position increased ROM in flexion-extension from 13.5 ± 2.3 to 15.7 ± 3.0° (p < 0.05), decreased axial rotation from 9.9 ± 1.7 to 8.3 ± 1.6° (p < 0.05), and decreased lateral bending from 8.0 ± 2.1 to 4.5 ± 1.1° (p < 0.05). Coupled lateral bending decreased from 0.62 ± 0.16 to 0.39 ± 0.15° for each degree of axial rotation (p < 0.05). Flexion-extension stiffness of the reconstructed segment with the prosthesis in the middle position did not deviate significantly from intact controls, whereas the lateral bending and axial rotation stiffness values were significantly larger than intact. Implanting the prosthesis in the posterior position as compared to the middle position did not significantly affect the ROM, motion coupling, or stiffness of the reconstructed segment; however, the COR location better approximated intact controls with the prosthesis midline located within ± 1 mm of the disc-space midline. Overall, the kinematic response after reconstruction with the compressible, six-degree-of-freedom prosthesis within ± 1 mm of the disc-space midline approximated the intact response in flexion-extension. Clinical studies are needed to understand and interpret the effects of limited restoration of lateral bending and axial rotation motions and motion coupling on clinical outcome.

Evaluation of nature and extent of injuries during Dahihandi festival.

BACKGROUND: Injuries related to the Hindu festival of Dahihandi where a human pyramid is formed and a pot of money kept at a height is broken, celebrated in the state of Maharashtra, have seen a significant rise in the past few years. The human pyramid formed is multi-layered and carries with it a high risk of injury including mortality. AIMS: To evaluate the nature, extent and influencing factors of injuries related to Dahihandi festival. SETTINGS AND DESIGN: We present a retrospective analysis of patients who presented in a tertiary care center with injuries during the Dahihandi festival in the year 2010. MATERIALS AND METHODS: 124 patients' records were evaluated for timing of injury, height of the Dahihandi pyramid, position of the patient in the multi-layered pyramid, mode of pyramid collapse and mechanism of an injury. A binary regression logistic analysis for risk factors was done at 5% significance level. STATISTICAL ANALYSIS: Univariate and multi-variate binary logistic regression of the risk factors for occurrence of a major or minor injury was done using Minitab™ version 16.0 at 5% significance. RESULTS: Out of 139 patients presented to the center, 15 were not involved directly in the formation of pyramid, rest 124 were included in the analysis. A majority of the patients were above 15 years of age [110 (83.6%)]. 46 (37.1%) patients suffered major injuries. There were 39 fractures, 3 cases of chest wall trauma with 10 cases of head injuries and 1 death. More than half of the patients [78 (56.1%)] were injured after 1800 hours. 73 (58.9%) injured participants were part of the pyramid constructed to reach the Dahihandi placed at 30 feet or more above the ground. 72 (51.8%) participants were part of the middle layers of the pyramid. Fall of a participant from upstream layers on the body was the main mechanism of injury, and majority [101 (81.5%)] of the patients suffered injury during descent phase of the pyramid. CONCLUSIONS: There is a considerable risk of serious, life-threatening injuries inherent to human pyramid formation and descent in the Dahihandi festival. Safety guidelines are urgently needed to minimize risk and prevent loss of human life.

PDBe: Protein Data Bank in Europe.

The Protein Data Bank in Europe (PDBe; pdbe.org) is a partner in the Worldwide PDB organization (wwPDB; wwpdb.org) and as such actively involved in managing the single global archive of biomacromolecular structure data, the PDB. In addition, PDBe develops tools, services and resources to make structure-related data more accessible to the biomedical community. Here we describe recently developed, extended or improved services, including an animated structure-presentation widget (PDBportfolio), a widget to graphically display the coverage of any UniProt sequence in the PDB (UniPDB), chemistry- and taxonomy-based PDB-archive browsers (PDBeXplore), and a tool for interactive visualization of NMR structures, corresponding experimental data as well as validation and analysis results (Vivaldi).

Restoration of spinal alignment and disk mechanics following polyetheretherketone wafer kyphoplasty with StaXx FX.

BACKGROUND AND PURPOSE: EPFs sustained during VCFs degrade the disk's ability to develop IDP under load. This inability to develop pressure in combination with residual kyphotic deformity increases the risk for adjacent vertebral fractures. We tested the hypothesis that StaXx FX reduces kyphosis and endplate deformity following vertebral compression fracture, restoring disk mechanics. MATERIALS AND METHODS: Eight thoracolumbar, 5-vertebrae segments were tested. A void was selectively created in the middle vertebra. The specimens were compressed until EPF and to a grade I-II VCF. PEEK wafer kyphoplasty was then performed. The specimens were then tested in flexion-extension (±6 Nm) under 400-N preload intact, after EPF, VCF, and kyphoplasty. Endplate deformity, kyphosis, and IDP adjacent to the fractured body were measured. RESULTS: Vertebral body height at the point of maximal endplate deformity decreased after EPF and VCF and was partially corrected after StaXx FX, remaining less than intact (P = .047). Anterior vertebral height decreased after VCF (P = .002) and was partially restored with StaXx FX, remaining less than intact (P = .015). Vertebral kyphosis increased after VCF (P < .001) and reduced after StaXx FX, remaining greater than intact (P = .03). EPF reduced IDP in the affected disk in compression-flexion loading (P < .001), which was restored after StaXx FX (P = 1.0). IDP in the unaffected disk did not change during testing (P > .3). CONCLUSIONS: StaXx FX reduced endplate deformity and kyphosis, and significantly increased anterior height following VCF. Although height and kyphosis were not fully corrected, the disk's ability to pressurize under load was restored.

Production of camptothecin in cultures of Chonemorpha grandiflora.

BACKGROUND: Chonemorpha grandiflora (Syn. Chonemorpha fragrans (Apocynaceae) is an endangered medicinal plant. It is used in different preparations, such as sudarsanasavam and kumaryasavam used in Kerala Ayurvedic system. C. grandiflora is used for the treatment of fever and stomach disorders. Phytochemical investigations have revealed the presence of steroidal alkaloids, such as chonemorphine and funtumafrine in C. grandiflora. Camptothecin, a well-known anticancer alkaloid has been detected in ethanolic extracts of stem with bark and callus cultures derived from C. grandiflora. METHODS: Callus cultures of C. grandiflora were raised on Murashige and Skoog's medium supplemented with 2, 4-D. Stem with bark and callus were used for phytochemical analysis mainly the alkaloids. Detection and identification of camptothecin was carried out using thin-layer chromatography (TLC), high-performance thin-layer chromatography, (HPTLC) and high-performance liquid chromatography (HPLC). RESULTS: An important anticancer alkaloid, camptothecin was detected in ethanolic extracts of stem with bark and callus cultures of C. grandiflora. camptothecin content was 0.013 mg/g in stem with bark and 0.003 mg/g in callus. CONCLUSION: This is the first report on in vivo and in vitro production of camptothecin in C. grandiflora. Camptothecin is known to occur only in six plant sources so, alternative sources for camptothecin are needed. Thus of C. grandiflora could be a new promising alternative source of camptothecin.

Equilibrium studies on hydrolysis of urea in a semi-batch reactor for production of ammonia to reduce hazardous pollutants from flue gases.

The increasing environmental awareness and the mandate of the pollution control agencies in various part of country for lowering emission of air pollutants such as CO(2), NO(x), SO(2) and fly ash emissions, has increased the urgency for reviewing options and alternatives to accomplish the above objective. The addition of ammonia into the flue gas stream as a conditioning agent is found to be used in recent years for the reduction of air pollutants. Flue gas conditioning requires in situ generation of ammonia as the transportation and storage of anhydrous ammonia is hazardous in nature. The equilibrium study on hydrolysis of urea was done in a semi-batch glass reactor to investigate the effect of reaction temperature, initial feed concentration and stirring speed on ammonia production. Few experiments were carried out in a semi-batch reactor at atmospheric pressure by using different concentration of urea solution from 10 to 40 wt% of urea to water and equilibrium study has been done. The study reveals that conversion increases exponentially with an increase in temperature but the conversion decreases with increase in the inlet feed concentration of urea solution. Furthermore, the effect of stirring speed on conversion has also been studied and it found that conversion increases with increase in stirring speed.

Relationship of growth parameters and nutrients uptake with canola (Brassica napus L.) yield and yield contribution at different nutrients availability.

A field experiment was conducted to evaluate the effect of different nutrients on canola (Brassica napus L.) growth parameters, nutrient uptake and ultimately on seed yield. For this purpose a split plot experimental design, with 10 treatments in 4 replications was carried out in 2004-2005, in silt-clay soil at Baiecola Agricultural Research Station, Mazandaran Iran. Canola seed yield, growth parameters (CGR, LAI, RGR and NAR), dry matter accumulation and HI and nutrient content of the leaf were examined. NPK fertilizers together with S and Zn, singly or in combination were applied. The results showed that at treatments T5 (NP), T8 (NPK), T9 (NPKS) and T10 (NPKZn) the higher seed yield (> 2600 kg ha(-1)) coincided with TDM > 880 g m(-2) the peak CGR > or = 13.9 g m(-2) day(-1) and the maximum LAI > or = 4.1. The higher seed yield at T5, T8, T9 and T10 coincided with higher concentrations of nutrients: N, P, K, S and Zn in leaf at flowering having > or = 3.40%, > or = 0.25%, > or = 1.53%, > or = 110 ppm and > or = 22.7 ppm, indicating substantial levels of translocation of nutrients at various stages of plant growth and higher number of pods per plant (> or = 179). Combined application of NPKZn at T10 resulted in maximum seed yield (3090 kg ha(-1)), coinciding with the maximum number of pods per plant (230), maximum TDM (1043 kg ha(-1)), maximum CGR (20.09 g m(-2) day(-1)) and maximum LAI (4.69).

Trigeminal nociceptors express prostaglandin receptors.

Orofacial inflammation is associated with prostaglandin release and the sensitization of nociceptive receptors such as the transient receptor potential subtype V(1) (TRPV(1)). We hypothesized that certain PGE(2) receptor subtypes (EP1-EP4) are co-expressed with TRPV(1) in trigeminal nociceptors and sensitize responses to a TRPV(1) agonist, capsaicin. Accordingly, combined in situ hybridization was performed with immunohistochemistry on rat trigeminal ganglia. We next evaluated the effects of specific EP2 and EP3 agonists (butaprost and sulprostone) in cultured trigeminal ganglia neurons. The results showed that EP2 and EP3 are expressed in trigeminal neurons (58% and 53% of total neurons, respectively) and are co-expressed in TRPV(1)-positive neurons (64% and 67 % of TRPV(1)-positive neurons, respectively). Moreover, most of the cells expressing EP2 or EP3 mRNA were of small to medium diameter (< 30 microm). The application of butaprost and sulprostone triggered neuropeptide exocytosis, and butaprost sensitized capsaicin responses. Analysis of these data, collectively, supports the hypothesis that prostaglandins regulate trigeminal TRPV(1) nociceptors via activation of the EP2 and EP3 receptors.