Evaluation of a cooling/heating-assisted microextraction instrument using a needle trap device packed with aminosilica/graphene oxide nanocomposites, covalently attached to cotton.

A low-cost and reliable cooling/heating-assisted microextraction (CHaME) instrument was designed and fabricated for use in different modes of microextraction methods. The CHaME setup is able to cool down the sorbent and simultaneously heat the sample in a wide temperature range. Consequently, it can create a large thermal gap between the sorbent and the sample matrix, to promote the release of analytes from the sample tissue and enhance their effective trapping on the microextraction phase. The primary versions of the instrument have previously been evaluated, coupled with different modes of solid- and liquid-phase microextraction strategies. Compared with conventional microextraction systems, it is able to extract volatile organic compounds from complicated solid matrices more effectively, rapidly and without any need for a sample preparation step. In this research, the final and compact version of the CHaME instrument was fabricated and employed in a cooling/heating-assisted needle trap device (CHaME-NTD) for microextraction of polycyclic aromatic hydrocarbons (PAHs) in contaminated soil samples, prior to GC-FID determination. An aminosilica/graphene oxide nanocomposite was synthesized, covalently attached to cotton (Am-Si/GO/Cot), packed inside a needle, and applied as an effective sorbent for trapping of the analytes. The influence of experimental parameters on the extraction efficiency of the TC-NTD-GC-FID strategy was evaluated and optimized. Under the optimal conditions, linear dynamic ranges (LDRs), limits of detection (LODs), and relative standard deviations (RSDs) for the PAHs were 0.001-2.0 µg g-1, 5-38 pg g-1, and 6.2-9.8% (n = 6), respectively. The CHaME-NTD-GC-FID procedure was compared with the traditional NTD-GC-FID method. Additionally, the Am-Si/GO/Cot nanocomposite sorbent was compared with the most frequently used commercial sorbents. The results demonstrated the remarkable performance of the CHaME-NTD procedure and the Am-Si/GO/Cot composite sorbent. The developed setup was also used for the extraction and determination of PAHs in contaminated soil samples, through the CHaME-NTD-GC-FID procedure.

'Rail and Nail' bifocal management of atrophic femoral nonunion.

Aims: The management of a significant bony defect following excision of a diaphyseal atrophic femoral nonunion remains a challenge. We present the outcomes using a combined technique of acute femoral shortening, stabilized with a long retrograde intramedullary nail, accompanied by bifocal osteotomy compression and distraction osteogenesis with a temporary monolateral fixator. Patients and Methods: Eight men and two women underwent the 'rail and nail' technique between 2008 and 2016. Proximal locking of the nail and removal of the external fixator was undertaken once the length of the femur had been restored and prior to full consolidation of the regenerate. Results: The mean lengthening was 7 cm (3 to 11). The external fixator was removed at a mean of 127 days (57 to 220). The mean bone healing index was 28 days/cm and the mean external fixation index was 20 days/cm (11 to 18). There were no superficial or deep infections. Conclusion: This small retrospective study shows encouraging results for a combined technique, enabling compression of the femoral osteotomy, alignment, and controlled lengthening. Removal of the fixator and proximal locking of the nail reduces the risk of complications and stabilizes the femur with the maximum working length of the nail. Cite this article: Bone Joint J 2018;100-B:634-9.

Computer hexapod-assisted orthopaedic surgery provides a predictable and safe method of femoral deformity correction.

AIMS: Computer hexapod assisted orthopaedic surgery (CHAOS), is a method to achieve the intra-operative correction of long bone deformities using a hexapod external fixator before definitive internal fixation with minimally invasive stabilisation techniques. The aims of this study were to determine the reliability of this method in a consecutive case series of patients undergoing femoral deformity correction, with a minimum six-month follow-up, to assess the complications and to define the ideal group of patients for whom this treatment is appropriate. PATIENTS AND METHODS: The medical records and radiographs of all patients who underwent CHAOS for femoral deformity at our institution between 2005 and 2011 were retrospectively reviewed. Records were available for all 55 consecutive procedures undertaken in 49 patients with a mean age of 35.6 years (10.9 to 75.3) at the time of surgery. RESULTS: Patients were assessed at a mean interval of 44 months (6 to 90) following surgery. The indications were broad; the most common were vitamin D resistant rickets (n = 10), growth plate arrest (n = 6) and post-traumatic deformity (n = 20). Multi-planar correction was required in 33 cases. A single level osteotomy was performed in 43 cases. Locking plates were used to stabilise the osteotomy in 33 cases and intramedullary nails in the remainder. Complications included two nonunions, one death, one below-knee deep vein thrombosis, one deep infection and one revision procedure due to initial under-correction. There were no neurovascular injuries or incidence of compartment syndrome. CONCLUSION: This is the largest reported series of femoral deformity corrections using the CHAOS technique. This series demonstrates that precise intra-operative realignment is possible with a hexapod external fixator prior to definitive stabilisation with contemporary internal fixation. This combination allows reproducible correction of complex femoral deformity from a wide variety of diagnoses and age range with a low complication rate. Cite this article: Bone Joint J 2017;99-B:283-8.

Central nervous system niche involvement in the leukemia

Central nervous system (CNS) impairment is commonly involved in leukemia, as it can be observed upon onset or relapse of the disease. It is associated with poor prognosis and is a challenging clinical problem. The objective of this paper was to provide a characterization of the CNS niche in leukemia, to elucidate the culprits of CNS involvement, including diagnostic micro RNAs (miRs) and early leukemia prognosis. CNS niche is a proper location for homing of leukemic stem cells, thus representing a candidate target in the treatment of leukemia. Recent advances in the study of leukemia hallmarks have enlightened miRs as novel biomarkers for diagnosis and detection of CNS involvement in leukemia, thus providing the opportunity to develop novel therapeutic approaches. Given the importance of prognosis and early diagnosis of CNS involvement in leukemias as well as the severe side effects of current treatments, diagnostic and therapeutic approaches should focus on identification and inhibition of the factors contributing to CNS involvement, including CXCR3, P-selectin glycoprotein ligand-1 and MCP1. MiRs such as miR-221 and miR-222 are emerging as potential tools for an innovative non-invasive therapy of CNS in leukemia affected patients (AU)

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Assessment of penetration of dorsal screws after fixation of the distal radius using ultrasound: cadaveric study.

INTRODUCTION: Volar locking plates are used to treat unstable and displaced fractures of the distal radius. Potential advantages of stable anatomical reduction (eg early mobilisation) can be limited by penetration of dorsal screws, leading to synovitis and potential rupture of extensor tendons. Despite intraoperative imaging, penetration of dorsal screws continues to be a problem in volar plating of the distal radius. Ultrasound is a well recognised, readily available, diagnostic tool used to assess soft-tissue impingement by orthopaedic hardware. In this cadaveric study, we wished to ascertain the sensitivity and specificity of ultrasound for identification of protrusion of dorsal screws after volar plating of the distal radius. METHODS: Four adult, unpaired phenol-embalmed cadaveric distal radii were used. A VariAx™ Distal Radius Volar Locking Plate system (Stryker, Kalamazoo, MI, USA) was employed for instrumented fixation. A portable SIUI CTS 900 ultrasound machine (Providian Medical, Eastlake, OH, USA) was used to image the dorsal cortex to ascertain screw penetration. RESULTS: Specificity and sensitivity of ultrasound for detection of screw protrusion through the dorsal cortex was 100%. CONCLUSIONS: Ultrasound was found to be a safe and accurate method for assessment of dorsal-screw penetration through the dorsal cortex of the radius after volar plating of the distal radius. It also aids diagnosis of associated tendon disorders (eg tenosynovitis) that might cause pain and limit wrist function.

Central nervous system niche involvement in the leukemia.

Central nervous system (CNS) impairment is commonly involved in leukemia, as it can be observed upon onset or relapse of the disease. It is associated with poor prognosis and is a challenging clinical problem. The objective of this paper was to provide a characterization of the CNS niche in leukemia, to elucidate the culprits of CNS involvement, including diagnostic micro RNAs (miRs) and early leukemia prognosis. CNS niche is a proper location for homing of leukemic stem cells, thus representing a candidate target in the treatment of leukemia. Recent advances in the study of leukemia hallmarks have enlightened miRs as novel biomarkers for diagnosis and detection of CNS involvement in leukemia, thus providing the opportunity to develop novel therapeutic approaches. Given the importance of prognosis and early diagnosis of CNS involvement in leukemias as well as the severe side effects of current treatments, diagnostic and therapeutic approaches should focus on identification and inhibition of the factors contributing to CNS involvement, including CXCR3, P-selectin glycoprotein ligand-1 and MCP1. MiRs such as miR-221 and miR-222 are emerging as potential tools for an innovative non-invasive therapy of CNS in leukemia affected patients.

Acetabular fractures in children: a review of the literature.

Injury to the acetabular growth plate is rare. Accordingly, data on the incidence in the literature are controverse. Other difficulties include the clear definition of a pediatric acetabular injury. The modified classification according to Salter-Harris described by Bucholz is used in immature patients. The majority of these injuries can be treated conservatively. In severely displaced injuries or in the presence of intra-articular pathologies open procedures are recommended. The main long-term complication is the development of posttraumatic acetabular dysplasia which should be early detected by regular check-ups until the completion of growth. Overall, the long-term results are satisfactory.

Glucocorticoid-mediated BIM induction and apoptosis are regulated by Runx2 and c-Jun in leukemia cells.

Glucocorticoids (GCs) are common components of many chemotherapeutic regimens for lymphoid malignancies. GC-induced apoptosis involves an intrinsic mitochondria-dependent pathway. BIM (BCL-2-interacting mediator of cell death), a BCL-2 homology 3-only pro-apoptotic protein, is upregulated by dexamethasone (Dex) treatment in acute lymphoblastic leukemia cells and has an essential role in Dex-induced apoptosis. It has been indicated that Dex-induced BIM is regulated mainly by transcription, however, the molecular mechanisms including responsible transcription factors are unclear. In this study, we found that Dex treatment induced transcription factor Runx2 and c-Jun in parallel with BIM induction. Dex-induced BIM and apoptosis were decreased in cells harboring dominant-negative c-Jun and were increased in cells with c-Jun overexpression. Cells harboring short hairpin RNA for Runx2 also decreased BIM induction and apoptosis. On the Bim promoter, c-Jun bound to and activated the AP-1-binding site at about -2.7 kb from the transcription start site. Treatment with RU486, a GC receptor antagonist, blocked Dex-induced Runx2, c-Jun and BIM induction, as well as apoptosis. Furthermore, pretreatment with SB203580, a p38-mitogen-activated protein kinase (MAPK) inhibitor, decreased Dex-induced Runx2, c-Jun and BIM, suggesting that p38-MAPK activation is upstream of the induction of these molecules. In conclusion, we identified the critical signaling pathway for GC-induced apoptosis, and targeting these molecules may be an alternative approach to overcome GC-resistance in leukemia treatment.

Pelvic ring injuries in children. Part I: Epidemiology and primary evaluation. A review of the literature.

Pediatric pelvic injury is of major significance despite these injuries in children are rare with a suspected yearly rate of 3% of all pelvic injuries. The special pediatric bone anatomy of the pelvis is responsible for different fracture patterns, and overall, a bony or joint injury of the pelvis is an indicator of a severe trauma. The vast majority of pediatric pelvic fractures is the result of a high-energy trauma, especially after strucking by a car or injured as motor vehicle passengers. Additional injuries are common, but additional head injury is only present in 1/3 of patients. An adequate structured primary diagnosis must therefore be mandatory. The a.p. X-ray of the pelvis is still the gold standard to evaluate these injuries. The majority of injuries is mechanically stable with 85-90% expected type A- and B-injuries. Primary management of these injuries is orientated to that of adults. The standard emergency fixation procedure is the external fixator. Definitive treatment depends on the displacement of fractures and the instability of the pelvic ring. In displaced and unstable fractures, today, anatomic reconstruction of the pelvic ring by osteosynthesis is favoured. Due to the potential negative long term consequences of mal-healing child-adapted stabilization techniques should be used. Moratlity is related to concomitant injuries, e.g. severe head injury. Risk factors of mortality are the overall injury severity, additional complex pelvic trauma and the type of pelvic fracture. Nevertheless, growth disturbances occur in rare cases. Therefore, frequent clinical and radiological controls are proposed until the completion of growth. Overall, good and excellent long-term results can be expected in most patients, especially after type A-injuries. But several long-term sequelae can occur in unstable pelvic injuries depending on the instability of the child's pelvis at the time of injury. Overall, there is a good correlation between the clinical and radiological result. Risk factors for a worse result can be additional significant peripelvic injuries (complex pelvic trauma).

Is sparing the pronator quadratus muscle possible in volar plating of the distal radius?

We measured the length of the distal radius that can be exposed by mobilizing the distal edge of pronator quadratus (PQ) without detaching its radial attachment. Measurements were made in 20 cadaveric upper limbs from the distal margin of the radius in line with the scaphoid and lunate fossae to the distal margin of the PQ, before and after mobilization of the muscle from its distal attachment. The mean distance from the distal edge of the PQ to the scaphoid fossa was 13.1 mm and to the lunate fossa was 10.7 mm. This increased to a mean of 26.2 mm for the scaphoid and a mean of 23.8 mm for the lunate fossa following mobilization of PQ. Subperiosteal retrograde release of the PQ from its distal margin will allow for the placement of a volar plate and insertion of locking peri-articular screws in the great majority of volar locking plate systems on the market.

Does the anteromedial or anterolateral approach alter the rate of joint puncture in injection of the ankle?: A cadaver study.

Injection or aspiration of the ankle may be performed through either an anteromedial or an anterolateral approach for diagnostic or therapeutic reasons. We evaluated the success of an intra-articular puncture in relation to its site in 76 ankles from 38 cadavers. Two orthopaedic surgical trainees each injected methylene blue dye into 18 of 38 ankles through an anterolateral approach and into 20 of 38 through an anteromedial. An arthrotomy was then performed to confirm the placement of the dye within the joint. Of the anteromedial injections 31 of 40 (77.5%, 95% confidence interval (CI) 64.6 to 90.4) were successful as were 31 of 36 (86.1%, 95% CI 74.8 to 97.4) anterolateral injections. In total 62 of 76 (81.6%, 95% CI 72.9 to 90.3) of the injections were intra-articular with a trend towards greater accuracy with the anterolateral approach, but this difference was not statistically significant (p = 0.25). In the case of trainee A, 16 of 20 anteromedial injections and 14 of 18 anterolateral punctures were intra-articular. Trainee B made successful intra-articular punctures in 15 of 20 anteromedial and 17 of 18 anterolateral approaches. There was no significant difference between them (p = 0.5 and p = 0.16 for the anteromedial and anterolateral approaches, respectively). These results were similar to those of other reported studies. Unintended peri-articular injection can cause complications and an unsuccessful aspiration can delay diagnosis. Placement of the needle may be aided by the use of ultrasonographic scanning or fluoroscopy which may be required in certain instances.

GX15-070 (obatoclax) overcomes glucocorticoid resistance in acute lymphoblastic leukemia through induction of apoptosis and autophagy.

Glucocorticoids (GCs) are common components of many chemotherapeutic regimens for lymphoid malignancies including acute lymphoblastic leukemia (ALL). The BCL-2 family has an essential role in regulating GC-induced cell death. Here we show that downregulation of antiapoptotic BCL-2 family proteins, especially MCL-1, enhances GC-induced cell death. Thus we target MCL-1 by using GX15-070 (obatoclax) in ALL cells. Treatment with GX15-070 in both dexamethasone (Dex)-sensitive and -resistant ALL cells shows effective growth inhibition and cell death. GX15-070 induces caspase-3 cleavage and increases the Annexin V-positive population, which is indicative of apoptosis. Before the onset of apoptosis, GX15-070 induces LC3 conversion as well as p62 degradation, both of which are autophagic cell death markers. A pro-apoptotic molecule BAK is released from the BAK/MCL-1 complex following GX15-070 treatment. Consistently, downregulation of BAK reduces caspase-3 cleavage and cell death, but does not alter LC3 conversion. In contrast, downregulation of ATG5, an autophagy regulator, decreases LC3 conversion and cell death, but does not alter caspase-3 cleavage, suggesting that apoptosis and autophagy induced by GX15-070 are independently regulated. Downregulation of Beclin-1, which is capable of crosstalk between apoptosis and autophagy, affects GX15-070-induced cell death through apoptosis but not autophagy. Taken together, GX15-070 treatment in ALL could be an alternative regimen to overcome glucocorticoid resistance by inducing BAK-dependent apoptosis and ATG5-dependent autophagy.

Intra-articular injection of the acromioclavicular joint.

Intra-articular punctures and injections are performed routinely on patients with injuries to and chronic diseases of joints, to release an effusion or haemarthrosis, or to inject drugs. The purpose of this study was to investigate the accuracy of placement of the needle during this procedure. A total of 76 cadaver acromioclavicular joints were injected with a solution containing methyl blue and subsequently dissected to distinguish intra- from peri-articular injection. In order to assess the importance of experience in achieving accurate placement, half of the injections were performed by an inexperienced resident and half by a skilled specialist. The specialist injected a further 20 cadaver acromioclavicular joints with the aid of an image intensifier. The overall frequency of peri-articular injection was much higher than expected at 43% (33 of 76) overall, with 42% (16 of 38) by the specialist and 45% (17 of 38) by the resident. The specialist entered the joint in all 20 cases when using the image intensifier. Correct positioning of the needle in the joint should be facilitated by fluoroscopy, thereby guaranteeing an intra-articular injection.