A recurrent nova super-remnant in the Andromeda galaxy.

The accretion of hydrogen onto a white dwarf star ignites a classical nova eruption1,2-a thermonuclear runaway in the accumulated envelope of gas, leading to luminosities up to a million times that of the Sun and a high-velocity mass ejection that produces a remnant shell (mainly consisting of insterstellar medium). Close to the upper mass limit of a white dwarf3 (1.4 solar masses), rapid accretion of hydrogen (about 10-7 solar masses per year) from a stellar companion leads to frequent eruptions on timescales of years4,5 to decades6. Such binary systems are known as recurrent novae. The ejecta of recurrent novae, initially moving at velocities of up to 10,000 kilometres per second7, must 'sweep up' the surrounding interstellar medium, creating cavities in space around the nova binary. No remnant larger than one parsec across from any single classical or recurrent nova eruption is known8-10, but thousands of successive recurrent nova eruptions should be capable of generating shells hundreds of parsecs across. Here we report that the most frequently recurring nova, M31N 2008-12a in the Andromeda galaxy (Messier 31 or NGC 224), which erupts annually11, is indeed surrounded by such a super-remnant with a projected size of at least 134 by 90 parsecs. Larger than almost all known remnants of even supernova explosions12, the existence of this shell demonstrates that the nova M31N 2008-12a has erupted with high frequency for millions of years.

Current level of technology use, health and eHealth literacy in older Canadians with a recent fracture-a survey in orthopedic clinics.

Among older adults who have recently sustained a fracture, there is substantial adoption of mobile technology. Furthermore, health and eHealth literacy level reported by participants supports the development of interactive eHealth interventions toward fostering better patient engagement in skeletal health management. INTRODUCTION: Electronic health resources are increasingly used in the self-management of medical conditions. We aimed to identify the current level of technology adoption, health, and eHealth literacy among older adults with a recent fracture, to determine if the use of electronic interventions would be feasible and acceptable in this population. METHODS: Adults ≥ 50 years with recent fractures were invited to complete a self-administered survey composed of 21 questions, including an 8-item perceived eHealth literacy scale. RESULTS: A total of 401 participants completed the survey (women, 64%; ≥ 65 years, 59%; university education, 32%). Most participants reported no difficulty in reading printed health material (67%) and felt confident in filling out medical forms (65%). Younger age and higher levels of education were associated with higher health literacy. Most respondents (81%) owned at least one mobile device (smartphone, 49%; tablet, 45%). eHEALS scores were similar among men (29, IQR 24-32) and women (29, IQR 25-33), and between younger age group categories (50-64 years, 30; IQR 26-33; and 65-74 years, 29; IQR 25-32), but lower in the oldest age group (≥ 75 years, 24; IQR 21-29; p < 0.05). Compared with the youngest group, those ≥ 75 years had higher odds of an eHEALS < 26 (odds ratio, 4.2; 95% confidence interval 2.0-8.9) after adjusting for sex and education level. CONCLUSION: There is significant adoption of mobile technology among older adults. Health and eHealth literacy reported by this study population supports the development of interactive eHealth interventions toward fostering better patient engagement in skeletal health management.

A pilot study of surgical telementoring for leg fasciotomy.

INTRODUCTION: Acute extremity compartment syndrome requires rapid decompression. In remote locations, distance, weather and logistics may delay the evacuation of patients with extremity trauma beyond the desired timeline for compartment release. The aim of this study was to establish the feasibility of performing telementored surgery for leg compartment release and to identify methodological issues relevant for future research. METHODS: Three anaethetists and one critical care physician were recruited as operators. They were directed to perform a two-incision leg fasciotomy on a Thiel-embalmed cadaver under the guidance of a remotely located orthopaedic surgeon. The operating physician and the surgeon (mentor) were connected through software that allows for real-time supervision and the use of a virtual pointer overlaid onto the surgical field. Two experienced orthopaedic traumatologists independently assessed the adequacy of compartment decompression and the presence of iatrogenic complications. RESULTS: 14 of 16 compartments (in four leg specimens) were felt to have been completely released. The first evaluator considered that the deep posterior compartment was incompletely released in two specimens. The second evaluator considered that the superficial posterior compartment was incompletely released in two specimens. The only complication was a large laceration of the soleus muscle that occurred during a period of blurred video signal attributed to a drop in bandwidth. CONCLUSIONS: This study suggests that surgical telementoring may enable physicians to safely perform two-incision leg fasciotomy in remote environments. This could improve the chances of limb salvage when compartment syndrome occurs far from surgical care. We found interobserver variation in the assessment of compartment release, which should be considered in the design of future research protocols.

Atypical femur fractures: a survey of current practices in orthopedic surgery.

The results of a self-administered online survey demonstrate that orthopedic surgeons' management practices for AFF are variable. These data will inform the development of clinical practice guidelines. INTRODUCTION: We aimed to determine current AFF treatment practices of orthopedic surgeons to inform clinical practice guideline development. METHODS: A self-administered online survey was developed and sequentially posted on the Orthopaedic Trauma Association (OTA) website from July to August 2015 and the Canadian Orthopaedic Association (COA) website from December 2015 to January 2016. Level of confidence in diagnosis and treatment as well as treatment preferences between respondents who self-identified as trauma surgeons vs. non-trauma surgeons were compared. RESULTS: A total of 172 completed surveys were obtained (OTA, N = 100, 58%; COA, N = 72, 8%). Seventy-eight percent of respondents had treated ≥1 AFF in the previous 6 months. Seventy-six percent reported feeling extremely or very confident in diagnosing AFF (trauma 84% vs. non-trauma surgeons 70%, p = 0.04), and 63% reported feeling extremely or very confident in treating AFF (trauma 82%, non-trauma surgeons 50%, p < 0.01). Preferred management for complete and symptomatic incomplete AFFs was surgical fixation with a cephalomedullary nail (CMN) by 88 and 79%, respectively, while close follow-up was preferred for asymptomatic incomplete AFFs in 72% of respondents. Trauma surgeons used the CMN more frequently than non-trauma surgeons (90 vs. 76% p = 0.03). In patients with bilateral AFFs, with one side surgically treated, 56% were extremely likely to surgically treat the contralateral side, if symptomatic. Most felt guidelines (81%) and educational resources (73%) would be valuable. CONCLUSIONS: Current orthopedic treatment practices for AFFs are variable. The results of this survey will inform the development of practice guidelines and educational resources.

Ultrasound-assisted external fixation: a technique for austere environments.

INTRODUCTION: Ultrasound-assisted external fixation of long bones has the potential to enhance extremity damage control surgery in locations without fluoroscopy, such as forward surgical elements, the intensive care unit, and spacecraft. This pre-clinical study specifically sought to evaluate orthopaedic surgeons' ability to sonographically define fracture patterns and the associated zone of injury in order to improve surgical decision-making and safely insert Schanz pin percutaneously. METHODS: We encased small composite femurs in a cylindrical echogenic gelatin matrix to simulate a human thigh. Three orthopaedic trauma surgeons with no prior ultrasound experience were taught to use sonography to diagnose fractures and assist external fixation. The surgeons were then presented with five specimens in a randomized sequence: three diaphyseal fractures (32-A2, 32-C2 and 32-C3); a distal femur fracture (33-A1.2); and an intact femur, all encased in an opaque black gelatin matrix to blind the participants to the underlying pathology. If they diagnosed a diaphyseal fracture, the surgeons were instructed to insert two Schanz pins proximal and two distal to the fracture, no closer than 40 mm from the fracture edges. RESULTS: Fracture diagnosis and surgical decision-making were correct in all cases. All intact femurs were recognized as such. The need for a knee-spanning external fixator was recognized for all distal femur fractures. The three surgeons performed appropriate ultrasound-assisted pin placement in every case of diaphyseal fracture. The pins adjacent to the fracture site were on average 58 mm (SD ±11 mm) from the edge of the fracture. No pins were inserted in the fracture or in the knee joint. CONCLUSIONS: The current study results suggest that with minimal training, orthopaedic surgeons can use portable ultrasound to diagnose femur fractures, decide the appropriate external fixator configuration, and safely insert Schanz pins outside the zone of injury.

MSC-seeded dense collagen scaffolds with a bolus dose of VEGF promote healing of large bone defects.

The functional repair of large skeletal defects remains a significant challenge to orthopaedic surgeons due to the lack of effective strategies to promote bone regeneration, particularly in the elderly. This study investigated the potential use of bone marrow derived mesenchymal stromal cells (MSC) in a dense collagen scaffold with a bolus dose of vascular endothelial growth factor (VEGF) to repair a defect in the femoral diaphysis of mice. MSC isolated from bone marrow of 4-month-old donor mice were seeded in type I collagen gels that were then compressed to form scaffolds with a fibrillar density similar to osteoid. The cells remained metabolically active in scaffolds incubated in vitro for up to 15 days and differentiated into osteoblasts that deposited calcium-phosphate mineral into the scaffold, which was quantified using micro-computed tomographic (micro-CT) imaging. When implanted in a 1 mm x 3 mm unicortical defect the MSC-loaded scaffolds were rapidly mineralised and integrated into host bone with administration of 10 ng of recombinant VEGF injected into the femoral canal at 4 days postoperative. Empty scaffolds and MSC-seeded scaffolds implanted in defects that did not receive a bolus dose of VEGF did not mineralise or integrate with native bone. The approach with MSC, hydrogels and a biologic factor already approved for human use warrants further pre-clinical investigation with a large animal model.

FGF18 augments osseointegration of intra-medullary implants in osteopenic FGFR3(-/-) mice.

Enhancement of endogenous bone regeneration is a priority for integration of joint replacement hardware with host bone for stable fixation of the prosthesis. Fibroblast Growth Factor (FGF) 18 regulates skeletal development and could therefore have applications for bone regeneration and skeletal repair. This study was designed to determine if treatment with FGF 18 would promote bone regeneration and integration of orthopedic hardware in FGF receptor 3 deficient (FGFR3(-/-)) mice, previously characterized with impaired bone formation. Rigid nylon rods coated with 200 nm of titanium were implanted bilaterally in the femora of adult FGFR3(-/-) and FGFR3(+/+) mice to mimic human orthopedic hardware. At the time of surgery, LEFT femora received an intramedullary injection of 0.5 µg FGF18 (Merck Serono) and RIGHT femora received PBS as a control. Treatment with FGF18 resulted in a significant increase in peri-implant bone formation in both FGFR3(+/+) and FGFR3(-/-) mice, with the peri-implant fibrous tissue frequently seen in FGFR3(-/-) mice being largely replaced by bone. The results of this pre-clinical study support the conjecture that FGF18 could be used in the clinical setting to promote integration of orthopedic hardware in poor quality bone.

Detecting the PEX Like Domain of Matrix Metalloproteinase-14 (MMP-14) with Therapeutic Conjugated CNTs.

Matrix metalloproteinases (MMPs) are essential proteins acting directly in the breakdown of the extra cellular matrix and so in cancer invasion and metastasis. Given its impact on tumor angiogenesis, monitoring MMP-14 provides strategic insights on cancer severity and treatment. In this work, we report a new approach to improve the electrochemical interaction of the MMP-14 with the electrode surface while preserving high specificity. This is based on the detection of the hemopexin (PEX) domain of MMP-14, which has a greater availability with a stable and low-cost commercial molecule, as a recognition element. This molecule, called NSC-405020, is specific of the PEX domain of MMP-14 within the binding pocket. Through the covalent grafting of the NSC-405020 molecule on carbon nanotubes (CNTs), we were able to detect and quantify MMP-14 using electrochemical impedance spectroscopy with a linear range of detection of 10 ng⋅mL-1 to 100 ng⋅mL-1, and LOD of 7.5 ng⋅mL-1. The specificity of the inhibitory small molecule was validated against the PEX domain of MMP-1. The inhibitor loaded CNTs system showed as a desirable candidate to become an alternative to the conventional recognition bioelements for the detection of MMP-14.

Non-traumatic necrosis of bone (osteonecrosis) is associated with endothelial cell activation but not thrombophilia.

OBJECTIVE: The pathophysiology of non-traumatic osteonecrosis (ON) or avascular necrosis (AVN) of the femoral head remains poorly understood. Some studies have suggested the contribution of underlying thrombophilia as a mechanism; however, no specific thrombophilic factor has been consistently found in association with the disease. We are presenting data suggesting a role for endothelial cell activation rather than thrombophilia in ON. METHODS: A prospective consecutive cohort of 49 patients with a diagnosis of ON. The disease was considered idiopathic in five and secondary in 44 patients. The investigation included a coagulation and thrombophilia profile, endothelial cell activation and non-specific inflammatory markers as well as a biochemical profile. Statistical analysis using Fisher's exact test was obtained to assess correlation between endothelial cell markers and variables of inflammation. RESULTS: Patients with non-traumatic ON were not found to have a specific underlying thrombophilic factor compared with the general population. Out of 49 patients,19 had elevation of at least one endothelial cell markers. We found that activation of endothelial cell markers was independently correlated to ON but not correlated to the presence of inflammation (P = 1.0000). CONCLUSION: These results suggest that non-traumatic ON is not associated with a specific thrombophilic abnormality in those affected. This study demonstrates a potential association between regional endothelial dysfunction and ON. More studies are needed at a molecular level to further investigate the specific role of endothelium in the physiopathology of ON. A better understanding of the underlying mechanism could lead to potential preventive and therapeutic strategies of this devastating disease.

A physical vapor deposition method for controlled evaluation of biological response to biomaterial chemistry and topography.

The purpose of this study was to characterize a technique to effectively mask surface chemistry without modifying surface topography. A thin layer of titanium was deposited by physical vapor deposition (PVD) onto different biomaterial surfaces. Commercially pure titanium disks were equally divided into three groups. Disks were either polished to a mirror finish, grit blasted with alumina particles, or grit blasted and subsequently plasma sprayed with a commercial grade of hydroxyapatite (HA). A subgroup of each of these treatment types was further treated by masking the entire disk surface with a thin layer of commercially pure titanium deposited by PVD. A comparison of surface topography and chemical composition was carried out between disks within each treatment group. Canine marrow cells were seeded on all disk surfaces to determine the stability of the PVD Ti mask under culture conditions. The PVD process did not significantly alter the surface topography of any samples. The thin titanium layer completely masked the underlying chemistry of the plasma sprayed HA surface and the chemistry of the plasma vapor deposited titanium layer did not differ from that of the commercially pure titanium disks. Aliquots obtained from the media during culture did not indicate any significant differences in Ti concentration amongst the Ti and Ti-masked surfaces. The PVD application of a Ti layer on HA coatings formed a stable, durable, and homogenous layer that effectively masked the underlying surface chemistry without altering the surface topography.

Photodynamic therapy induces rapid cell death by apoptosis in L5178Y mouse lymphoma cells.

The mode of cell death of two strains of mouse lymphoma L5178Y cells was studied following photodynamic therapy (PDT) sensitized by chloroaluminum phthalocyanine. Strains LY-R and LY-S differ in their relative sensitivities to UVC radiation, X-radiation, and PDT; both responded to PDT by undergoing apoptosis. The DNA was degraded into fragments with lengths which are multiples of approximately 180-190 base pairs (i.e., oligonucleosome size), a biochemical marker of apoptosis. The DNA fragmentation was dose and time dependent which indicates this response to be an enzymic process related to cell killing. Cycloheximide, a protein synthesis inhibitor, and actinomycin D, an RNA synthesis inhibitor, enhanced the endonucleolytic DNA fragmentation. Transmission electron microscopy revealed chromatin condensation around the periphery of the nucleus, which is also characteristic of apoptosis. The induction of apoptosis in L5178Y cells by PDT was rapid, with marked degradation of DNA occurring in as little as 30 min. The rapidity of the response to PDT suggests that cellular damage produced by PDT can directly activate endonucleolysis and chromatin condensation, thereby by-passing many of the early steps in the signal transduction program which are acted upon by other agents causing apoptosis.

Zoledronic acid causes enhancement of bone growth into porous implants.

The effect of zoledronic acid on bone ingrowth was examined in an animal model in which porous tantalum implants were placed bilaterally within the ulnae of seven dogs. Zoledronic acid in saline was administered via a single post-operative intravenous injection at a dose of 0.1 mg/kg. The ulnae were harvested six weeks after surgery. Undecalcified transverse histological sections of the implant-bone interfaces were imaged with backscattered scanning electron microscopy and the percentage of available pore space that was filled with new bone was calculated. The mean extent of bone ingrowth was 6.6% for the control implants and 12.2% for the zoledronic acid-treated implants, an absolute difference of 5.6% (95% confidence interval, 1.2 to 10.1) and a relative difference of 85% which was statistically significant. Individual islands of new bone formation within the implant pores were similar in number in both groups but were 69% larger in the zoledronic acid-treated group. The bisphosphonate zoledronic acid should be further investigated for use in accelerating or enhancing the biological fixation of implants to bone.

Needs of family caregivers in chronic schizophrenia.

The goals of the study were to describe (1) the tasks undertaken by people who care for a relative with chronic schizophrenia, according to their level of contact with the patient; and (2) any needs for further help that these caregivers might experience. Interviews and standardized questionnaires were used to collect information from 121 family caregivers whose relatives had been diagnosed an average of 14 years previously. Burden in the sense of interference in caregivers' daily lives was most marked for caregivers in high contact with the patients. Patients whom the caregivers regarded as enjoyable to live with had greater self-care and communication skills. Caregivers preferred that patients low in these skills or high in disruptive behavior live in supervised settings. Caregivers expressed particular support for earlier professional intervention in episodes of illness, information about how to lobby politicians for resources, and information about schizophrenia. These results can be used to plan interventions to reduce caregiver stress.

Determinants of psychological distress in relatives of people with chronic schizophrenia.

Research shows that the relatives of people with chronic schizophrenia suffer psychological distress and interference in daily life from the burdens of caregiving. In this study, members of a self-help group for the relatives of schizophrenia sufferers provided information through a mail survey, using standardized measures of psychological distress and burden, and severity of the sufferer's illness. Caregiver psychological distress was high compared with test norms, and the level of behavioral disturbance in the sufferer was found to contribute to caregiver distress after controlling for the caregiver's age, sex, and social supports. An unexpected finding was that those caring for female sufferers reported greater distress than those caring for males.

Effect of flexibility of the femoral stem on bone-remodeling and fixation of the stem in a canine total hip arthroplasty model without cement.

The purpose of this study was to compare, with regard to fixation of the implant and femoral bone resorption, two fully porous-coated stems of different stiffnesses in a canine total hip arthroplasty model. A bilateral arthroplasty was carried out with insertion of a titanium-alloy stem (which had stiffness properties comparable with those of the canine femur) on one side and with insertion of a composite stem (which was three to fivefold more flexible than the canine femur) on the contralateral side. Eight femora were evaluated at six months and eight, at eighteen months after the operation, to determine the extent of bone ingrowth, periprosthetic cortical area, intracortical porosity, and bone-remodeling. Despite the markedly greater flexibility of the composite stems, no significant difference could be detected (with the numbers available), with regard to the overall degree of femoral stress-shielding, cortical area, or cortical porosity, between these stems and the stiffer, titanium-alloy stems at either time-period. However, the composite stems had less bone ingrowth and more formation of radiopaque lines than did the titanium-alloy stems. At eighteen months, the values for bone ingrowth were 9.7 +/- 5.38 percent (mean and standard deviation) for the composite stems compared with 28.1 +/- 5.31 percent for the titanium-alloy stems (p = 0.003). Furthermore, the histological sections from the femora containing a composite stem showed radiopaque lines indicative of fibrous ingrowth approximately threefold more often than did those from the femora containing a titanium-alloy stem (p = 0.02).

The effect of fibrin sealant on spinal fusions using allograft in dogs.

STUDY DESIGN: This study investigated the use of Tisseel (immuno [Canada], Toronto, Ontario) as an adjunct to allograft spinal fusion. Thirteen mongrel, dogs were fused bilaterally with morcellized graft from a separate dog. OBJECTIVES: To evaluate whether fibrin sealant had an effect on bone volume of fusion mass in allograft fusions of the spine. SUMMARY OF BACKGROUND DATA: Fibrin sealant has been promoted for use in many orthopedic applications. There is controversy about its effectiveness in augmenting bone graft healing. However, some surgeons make routine use of the sealant in augmentation of bone grafting procedures. METHODS: To test the usefulness of this material in augmenting allograft fusions, the authors carried out bilateral posterolateral fusions in 13 mongrel dogs. At surgery, 15 cm3 of allograft was placed into a posterolateral position at the L5-L6 region on both sides of the spine. Fibrin sealant (Tisseel) was allocated randomly to one side only. Fusion mass was tested 6 months after the initial operation by computed tomographic scan imaging and mechanical testing. RESULTS: A significantly smaller bone volume mass, as illustrated by computed tomographic measurement, was seen on the Tisseel side (P = 0.03). Biomechanical testing indicated that there was a trend for the Tisseel side to be stiffer than the untreated side, particularly at lower weights, but statistical significance was not achieved. Computed tomographic volumetric analysis showed that Tisseel-treated allograft led to a significantly smaller fusion volume. CONCLUSIONS: This study refutes the belief that Tisseel is a good material for accomplishing or augmenting intervertebral arthrodesis. Fibrin sealant significantly retards allograft fusion mass formation in dogs.

Acid-etched microtexture for enhancement of bone growth into porous-coated implants.

We designed an in vivo study to determine if the superimposition of a microtexture on the surface of sintered titanium beads affected the extent of bone ingrowth. Cylindrical titanium intramedullary implants were coated with titanium beads to form a porous finish using commercial sintering techniques. A control group of implants was left in the as-sintered condition. The test group was etched in a boiling acidic solution to create an irregular surface over the entire porous coating. Six experimental dogs underwent simultaneous bilateral femoral intramedullary implantation of a control implant and an acid etched implant. At 12 weeks, the implants were harvested in situ and the femora processed for undecalcified, histological examination. Eight transverse serial sections for each implant were analysed by backscattered electron microscopy and the extent of bone ingrowth was quantified by computer-aided image analysis. The extent of bone ingrowth into the control implants was 15.8% while the extent of bone ingrowth into the etched implants was 25.3%, a difference of 60% that was statistically significant. These results are consistent with other research that documents the positive effect of microtextured surfaces on bone formation at an implant surface. The acid etching process developed for this study represents a simple method for enhancing the potential of commonly available porous coatings for biological fixation.

HPLC of basic drugs on microparticulate strong cation-exchange materials - a review.

Propylsulphonic acid (SCX)-modified silica HPLC columns used with methanol or aqueous methanol eluents of appropriate pH and ionic strength can give good retention and peak shape for basic drugs. In the system studied, eluent pH influenced retention via protonation of basic analytes, the pK(a) of the analyte indicating the pH where retention begins to decrease at constant ionic strength. At constant pH, retention is inversely proportional to ionic strength for protonated bases and quaternary ammonium compounds. The underlying retention mechanism appears to be ion-exchange with the SCX moieties, although ionized surface silanols may also contribute to retention at higher eluent pH values. In capillary electrochromatography (CEC) unprecedented efficiencies, but similar selectivity, to that observed in conventional HPLC have been obtained for a standard range of basic drugs using Waters Spherisorb S3SCX.SCX-modified silica columns can be used in the HPLC of many basic drugs, including some compounds that are poorly retained on unmodified silica using methanol-rich eluents. N-Desalkyl and sulphoxide metabolites are often resolved at an appropriate eluent pH. Even analogues differing by a methylene unit in a side-chain remote from a basic centre are often resolved. Applications of Waters Spherisorb S5SCX columns include HPLC of antimalarials such as chloroquine and quinine, cardioactive drugs, for example amiodarone and flecainide, antipsychotics (clozapine, olanzapine), and antidepressants (amitriptyline, clomipramine, dothiepin, fluoxetine) and their N-desalkyl metabolites. Major practical features of these systems are that (i) acidic and neutral compounds are not retained, (ii) solvent extracts can be injected directly, and (iii) eluent recycling can be performed routinely.

Revascularization of the femoral head in osteonecrosis.

Osteonecrosis of the femoral head accounts for as many as 18% of total hip arthroplasties performed in western countries. The young age of affected patients and the potentially poor outcome have sparked an interest in alternative treatment modalities. Extracapsular placement of a vascularized fibular graft in the subchondral region of the femoral head has shown great promise as a treatment option. The authors have used this procedure in the treatment of 646 symptomatic hips, of all grades of osteonecrosis, with a follow-up of 1 to 17 years. The resultant 10-year survival rate of greater than 80% suggests that this procedure may be preferable to total hip arthroplasty for the young patient with osteonecrosis of the femoral head.