Estimated cumulative X-ray exposure and additional cancer risk during the evaluation and treatment of scoliosis in children and young people requiring surgery.

INTRODUCTION: Clinicians and patients must weigh the benefits of radiological imaging against the risks of radiation exposure in the diagnosis and treatment of scoliosis. This report aims to estimate the cumulative absorbed and equivalent dose of radiation in patients undergoing surgical treatment for scoliosis, and to present this as an estimated risk of cancer compared to background radiation levels. METHODS: Retrospective review of estimated absorbed dose on the Computerised Radiology Information System (CRIS®). Patients undergoing surgical correction of scoliosis (age ≤ 25) from August 2010 to August 2015 investigated. Estimated absorbed dose [milligrays (mGy)] recorded. Pedicle screws inserted using image intensification. Equivalent dose [millisieverts (mSv)] and additional cancer risk calculated from the National Research Council document 'Health risks from exposure to low levels of ionising radiation' (2006). RESULTS: 271 patients identified. Mean age 15 (range 2-25). Mean total absorbed dose 2136 mGy [standard deviation (SD) 1700 mGy]. Mean number of plain spine radiographs was 8 (SD 3) with total 1884 mGy exposure (SD 1609 mGy). Additional dose provided by CT (mean 0.17 episodes), plain chest and abdominal radiographs and image intensification. Mean number of image intensification episodes was 1.1 with mean estimated exposure 180 mGy (SD 238 mGy). Image intensification accounted for 8% of the estimated absorbed dose during treatment. Estimated mean effective dose delivered was 20.952 mSv equating to an additional cancer risk of 0.27-0.45%. CONCLUSION: Additional cancer risk from cumulative imaging is small and equivalent to approximately 8 years of natural background radiation. Use of image intensification for pedicle screw insertion is a minor contribution (8%) to the total patient dose.

A review on impedimetric immunosensors for pathogen and biomarker detection.

Since the discovery of antibiotics in the first quarter of the twentieth century, their use has been the principal approach to treat bacterial infection. Modernized medicine such as cancer therapy, organ transplantation or advanced major surgeries require effective antibiotics to manage bacterial infections. However, the irresponsible use of antibiotics along with the lack of development has led to the emergence of antimicrobial resistance which is considered a serious global threat due to the rise of multidrug-resistant bacteria (Wang et al. in Antibiotic resistance: a rundown of a global crisis, pp. 1645-1658, 2018). Currently employed diagnostics techniques are microscopy, colony counting, ELISA, PCR, RT-PCR, surface-enhanced Raman scattering and others. These techniques provide satisfactory selectivity and sensitivity (Joung et al. in Sens Actuators B Chem 161:824-831, 2012). Nevertheless, they demand specialized personnel and expensive and sophisticated machinery which can be labour-intensive and time-consuming, (Malvano et al. in Sensors (Switzerland) 18:1-11, 2018; Mantzila et al. in Anal Chem 80:1169-1175, 2008). To get around these problems, new technologies such as biosensing and lab-on-a-chip devices have emerged in the last two decades. Impedimetric immunosensors function by applying electrochemical impedance spectroscopy to a biosensor platform using antibodies or other affinity proteins such as Affimers (Tiede et al. in Elife 6(c):1-35, 2017) or other binding proteins (Weiss et al. in Electrochim Acta 50:4248-4256, 2005) as bioreceptors, which provide excellent sensitivity and selectivity. Pre-enrichment steps are not required and this allows miniaturization and low-cost. In this review different types of impedimetric immunosensors are reported according to the type of electrode and their base layer materials, either self-assembled monolayers or polymeric layers, composition and functionalization for different types of bacteria, viruses, fungi and disease biomarkers. Additionally, novel protein scaffolds, both antibody derived and non-antibody derived, used to specifically target the analyte are considered.

Current concepts in the surgical management of adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a complex 3D deformity of the spine. Its prevalence is between 2% and 3% in the general population, with almost 10% of patients requiring some form of treatment and up to 0.1% undergoing surgery. The cosmetic aspect of the deformity is the biggest concern to the patient and is often accompanied by psychosocial distress. In addition, severe curves can cause cardiopulmonary distress. With proven benefits from surgery, the aims of treatment are to improve the cosmetic and functional outcomes. Obtaining correction in the coronal plane is not the only important endpoint anymore. With better understanding of spinal biomechanics and the long-term effects of multiplanar imbalance, we now know that sagittal balance is equally, if not more, important. Better correction of deformities has also been facilitated by an improvement in the design of implants and a better understanding of metallurgy. Understanding the unique character of each deformity is important. In addition, using the most appropriate implant and applying all the principles of correction in a bespoke manner is important to achieve optimum correction. In this article, we review the current concepts in AIS surgery. Cite this article: Bone Joint J 2018;100-B:415-24.

Biosensor Regeneration: A Review of Common Techniques and Outcomes.

Biosensors are ideally portable, low-cost tools for the rapid detection of pathogens, proteins, and other analytes. The global biosensor market is currently worth over 10 billion dollars annually and is a burgeoning field of interdisciplinary research that is hailed as a potential revolution in consumer, healthcare, and industrial testing. A key barrier to the widespread adoption of biosensors, however, is their cost. Although many systems have been validated in the laboratory setting and biosensors for a range of analytes are proven at the concept level, many have yet to make a strong commercial case for their acceptance. Though it is true with the development of cheaper electrodes, circuits, and components that there is a downward pressure on costs, there is also an emerging trend toward the development of multianalyte biosensors that is pushing in the other direction. One way to reduce the cost that is suitable for certain systems is to enable their reuse, thus reducing the cost per test. Regenerating biosensors is a technique that can often be used in conjunction with existing systems in order to reduce costs and accelerate the commercialization process. This article discusses the merits and drawbacks of regeneration schemes that have been proven in various biosensor systems and indicates parameters for successful regeneration based on a systematic review of the literature. It also outlines some of the difficulties encountered when considering the role of regeneration at the point of use. A brief meta-analysis has been included in this review to develop a working definition for biosensor regeneration, and using this analysis only ∼60% of the reported studies analyzed were deemed a success. This highlights the variation within the field and the need to normalize regeneration as a standard process across the field by establishing a consensus term.

Systematic review of methods to predict and detect anastomotic leakage in colorectal surgery.

AIM: Anastomotic leakage is a serious complication of gastrointestinal surgery resulting in increased morbidity and mortality, poor function and predisposing to cancer recurrence. Earlier diagnosis and intervention can minimize systemic complications but is hindered by current diagnostic methods that are non-specific and often uninformative. The purpose of this paper is to review current developments in the field and to identify strategies for early detection and treatment of anastomotic leakage. METHOD: A systematic literature search was performed using the MEDLINE, Embase, PubMed and Cochrane Library databases. Search terms included 'anastomosis' and 'leak' and 'diagnosis' or 'detection' and 'gastrointestinal' or 'colorectal'. Papers concentrating on the diagnosis of gastrointestinal anastomotic leak were identified and further searches were performed by cross-referencing. RESULTS: Computerized tomography CT scanning and water-soluble contrast studies are the current preferred techniques for diagnosing anastomotic leakage but suffer from variable sensitivity and specificity, have logistical constraints and may delay timely intervention. Intra-operative endoscopy and imaging may offer certain advantages, but the ability to predict anastomotic leakage is unproven. Newer techniques involve measurement of biomarkers for anastomotic leakage and have the potential advantage of providing cheap real-time monitoring for postoperative complications. CONCLUSION: Current diagnostic tests often fail to diagnose anastomotic leak at an early stage that enables timely intervention and minimizes serious morbidity and mortality. Emerging technologies, based on detection of local biomarkers, have achieved proof of concept status but require further evaluation to determine whether they translate into improved patient outcomes. Further research is needed to address this important, yet relatively unrecognized, area of unmet clinical need.

Intra-operative tumour detection and staging in colorectal cancer surgery.

AIM: Surgical resection for colorectal cancer involves segmental resection and regional lymphadenectomy. The appropriateness of this 'one-size-fits-all' strategy is questioned as bowel cancer screening programmes result in a shift to earlier stage disease. Currently, the nodal status of a colorectal cancer can only be reliably determined by histopathological examination of the resected specimen. New methods of intra-operative staging are required to allow surgical resection to be tailored to the stage of the disease. METHOD: A literature search was performed of PubMed and Embase databases using the terms 'colon' OR 'colorectal' AND 'intra-operative detection' OR 'intra-operative staging' OR 'intra-operative detection' OR 'radioimmunoguided surgery'. Articles published between January 1980 and January 2012 were included. Technologies that have the potential to allow intra-operative staging and treatment stratification were identified and further searches performed. RESULTS: Established techniques such as sentinel lymph node mapping and radioimmunoguided surgery have benefited from combination with other technologies to allow real-time intra-operative staging. Intra-operative fluorescence, using naturally fluorescent biomarkers or fluorescent tumour probes, probably offers the most practical means of intra-operative lymph node staging and may be facilitated using nanotechnology. Optical coherence tomography and real-time elastography have the potential to provide an in vivo'virtual biopsy'. CONCLUSION: Technological advances may allow accurate intra-operative lymph node staging to facilitate tailored surgical resection. This may become the next paradigm shift in colorectal cancer surgery.

Directed immobilization of reduced antibody fragments onto a novel SAM on gold for myoglobin impedance immunosensing.

The successful construction of an immunosensor depends on having an effective procedure for immobilising the bio-recognition element to the transducer surface. In the present study, an amino-terminated 4-aminothiophenol (ATP) self-assembled monolayer (SAM) was modified with heterobifunctional crosslinker sulfosuccinimidyl 4-[N-maleimidomethyl] cyclohexane-1-carboxylate to couple reduced anti-myoglobin half-antibody fragments. The disulphide groups present in the hinge region of IgG molecules were selectively cleaved by 2-mercaptoethylamine to produce reduced half-antibody fragments with free sulphydryl groups. The maleimide terminated 4-ATP SAM modified surface was coupled to these reduced antibody fragments to produce highly oriented immobilization of the half-antibody via its Fc domain and to allow free access to the Fv bindings sites. This represents an improvement by comparison with biotin/avidin mediated IgG attachment which is essentially randomly oriented. Functional immunosensors were able to detect myoglobin in both phosphate buffered saline and whole serum over the range of concentrations from 10(-13)M to 10(-6)M, and order of magnitude better than avidin/biotin linked immunosensors. In addition, atomic force microscopy (AFM) was carried out to elucidate the nanotopology of the immunosensor surface at different stages of fabrication; the images demonstrate that half antibodies bind as described and show structural changes on subsequent antigen binding.

Nanostructured transducer surfaces for electrochemical biosensor construction--interfacing the sensing component with the electrode.

For fabrication of effective electrochemical biosensors, interfacing the biomolecular receptor with the underlying transducer represents a critical step. The actual approach taken depends on the tethering layer covering the transducer, which is typically either a conducting polymeric matrix, or a thin film, such as an alkanethiol monolayer. Non-specific immobilisation methods can be either covalent, or non-covalent affinity attachment, with multipoint electrostatic attachment of the sensing biomolecule to either a polyanionic or polycationic layer representing the most common approach. Many specific affinity immobilisation strategies exist, but the majority make use of one of two binding systems. The first relies on the specific and strong affinity between biotin and proteins of the avidin family, with both bioreceptor and transducer bearing pendant biotins and avidin used as the crosslinker. The second approach employs a metal chelating group on the transducer to which can be bound a polyhistidine tag present on the N- or C-terminus of the receptor protein and which can be introduced genetically, when the expression sequence for a recombinant proteins is designed.

Parallel plate equipment for preparation of uniform gel sheets.

A method for the preparation of uniform gel-disks for enzyme and cell immobilisation, as well as for characterisation of gel mechanical stability, is described. The apparatus comprises a stainless steel base unit and glass parallel plates, designed to permit easy and fast production of multiple homogeneous gel sheets of variable thickness.

Personalised image-based templates for intra-operative guidance.

The high rate of unplanned perforation, poor fixation, and nerve injury with freehand pedicle screw insertion has led to the use of image-guided navigation systems. Although these improve accuracy, they have several drawbacks that could be overcome by using image-based drilling guide templates. The accuracy of such templates was tested in a cadaveric study of screw placement in the lumbar, thoracic, and cervical regions of the spine. The dimensional stability with autoclaving of duraform polyamide, to be used for manufacturing the guides, was first determined using test specimens. Computed tomography (CT) images were acquired of 4 cadaveric spines, and placement of 4 cervical, 32 thoracic, and 14 lumbar screws was planned. Eighteen personalized drilling guide templates, in four different designs, were built. Orthopaedic surgeons experienced in the freehand techniques used the templates. CT images were acquired to assess placement position with respect to the pedicle. Duraform polyamide was found to be unaffected by sterilization. Two of the template designs facilitated the placement of 20/20 screws without error. Templates can lead to successful screw placement, even in small pedicles, providing their design is optimized for the application area, e.g. with enhanced rotational stabilization.

Acetylecholinesterase-based biosensor electrodes for organophosphate pesticide detection. II. Immobilization and stabilization of acetylecholinesterase.

The dry and wet stability of Drosophila acetylcholinesterase non-covalently immobilized onto polyethyleneimine modified screen-printed carbon electrodes was improved when compared to non-immobilized acetylcholinesterase, and acetylcholinesterase covalently immobilized onto dialdehyde and polyethyleneimine modified electrodes. Stabilizer mixtures were characterized for additional stabilization of acetylcholinesterase during storage in the dry state, with dextran-sulphate/sucrose and polygalacturonic acid/sucrose mixtures proving highly effective for long-term storage of biosensor electrodes.

Acetylcholinesterase-based biosensor electrodes for organophosphate pesticide detection. I. Modification of carbon surface for immobilization of acetylcholinesterase.

Screen-printed carbon electrodes modified with the dialdehydes, glutaraldehyde and terephthaldicarboxaldehyde, and then polyethyleneimine have been utilized for production of pesticide biosensors based on acetylcholinesterase. To improve the extent of dialdehyde modification, the electrodes were NH2-derivatized, initially by electrochemical reduction of 4-nitrobenzenediazonium to a nitroaryl radical permitting attachment to the carbon surface. Subsequent reduction of the 4-nitrobenzene yields a 4-aminobenzene modified carbon surface. Drosophila melanogaster acetylcholinesterase was immobilized either covalently onto dialdehyde modified electrodes or non-covalently onto polyethyleneimine modified electrodes. Internal diffusion limitations due to the dialdehyde and polyethyleneimine modifications increased the apparent Km of the immobilized enzyme. The thiocholine sensitivity was about 90% for dialdehyde modified electrodes and about 10% for polyethyleneimine modified electrodes as compared with non-modified carbon electrodes. The detection limit of the biosensors produced by non-covalent immobilization of acetylcholinesterase onto polyethyleneimine modified carbon electrodes was found to be about 10(-10) M for the organophosphate pesticide dichlorvos.

Therapeutic impact of percutaneous spinal biopsy in spinal infection.

OBJECTIVE: To investigate the therapeutic impact of percutaneous spinal biopsy in patients with suspected spinal infection. DESIGN AND PATIENTS: A review of the case notes and imaging features of 36 patients who underwent percutaneous spinal biopsy was performed. From this group 20 patients with a prebiopsy diagnosis of spinal osteomyelitis were identified. Management before biopsy was noted including the use of antimicrobial therapy. The results of the histology and microbiology were noted along with the subsequent diagnosis and management. RESULTS: Eight of the 20 patients (40%) had received antibiotics before the biopsy. An organism was isolated in 8/20 cases (40%). Of the eight patients on antibiotics, two grew an organism (25%), including one case of candida in a patient receiving flucloxacillin. Out of 12 patients not on antibiotics there were six cases where an organism was isolated (50%). The result of the biopsy led to a change in management in seven of the 20 patients (35%). CONCLUSIONS: Many clinicians are treating spinal osteomyelitis empirically with antibiotics before biopsy, but this reduces the chance of isolating an organism and determining antibiotic sensitivity. Despite this biopsy led to a change in management in 35% of cases.

Scoliosis in cystic fibrosis: is it idiopathic?

STUDY DESIGN: This is a retrospective study of all the patients registered with the Yorkshire Regional Cystic Fibrosis unit from 1982 to 1997. Of the 316 patients, there were 184 adults (age 17 years and above) and 132 children (age 0-6 years). OBJECTIVES: This study was aimed at determining the prevalence of scoliosis in people with cystic fibrosis and describes the characteristics and progression of scoliosis in these patients and highlights predictive factors, which account for high prevalence of scoliosis in this condition. SUMMARY OF THE BACKGROUND DATA: Two previous North American studies (1978 and 1982) have indicated a high prevalence of scoliosis in patients with cystic fibrosis. METHODS: The patients were divided into 3 groups based on their chronologic age as on January 1998. Chest, abdomen, and whole spine radiographs were studied for the presence of any spinal deformity, and measurements were made using the Oxford Cobbmeter (Oxford Metrics). The extent, apex, and the side of the curves were described. The disease-specific scores, ie, Chrispin-Norman score (score for radiologic severity of lung disease) and Shwachman score (score for general condition), were noted from the patient follow-up database maintained by the Regional Cystic Fibrosis Unit. Multiple linear regression analysis was used to study the correlation between Cobb angle and the previously mentioned scores. RESULTS: In the 4- to 16-year age group, the prevalence of scoliosis was 15.6%, which is 20 times the prevalence in 15,793 school children with a similar age and sex distribution from the same geographic area. The majority of curves were single-thoracic, apical around T6-T8 with no side predilection. In the adult population (above 16 years), the prevalence was 9.8%, which is higher than that of the general population. These curves were thoracic, apical around T7-T8, and approximately two thirds of them were right-sided. Infantile curves are described for the first time in our study; these tend to be nonprogressive, right-sided, upper thoracic curves. CONCLUSION: Our study shows a high prevalence of scoliosis in people with cystic fibrosis. These are benign short midthoracic curves, apical between T6-T8 with no side predilection.

Toxoplasma gondii major surface antigen (SAG1): in vitro analysis of host cell binding.

Previous studies have indicated that SAG1, the major surface molecule of the protozoan parasite Toxoplasma gondii, is an important attachment ligand for the host cell. However, the research data that supports this claim comes largely from studies investigating tachyzoite binding, and not SAG1 binding per se. In this study we successfully developed an in vitro attachment assay to directly evaluate the mechanism of SAG1-host cell binding. Competition experiments were then performed using SAG1 that had been pre-treated with the neoglycoprotein BSA-glucosamide or with antibody. Soluble BSA-glucosamide blocked SAG1 attachment to MDBK cells in a dose-dependent manner, implying that SAGI binding is mediated, in part, via attachment to host cell surface glucosamine. Interestingly, pre-incubation of SAG1 in polyclonal sera from chronically infected mice failed to block binding. This challenges the assumption that anti-SAG1 antibodies block parasite attachment through the masking of SAG1 host cell binding domains. Taken together, this evidence presents new strategies for understanding SAG1-mediated attachment.

The removal of indicator microorganisms from primary treated wastewater in subsurface reed beds using different substrates.

Subsurface, horizontal flow, experimental reed beds, were designed and built based on a combination of two design methodologies, that of the WRc and Severn Trent Water Plc and that of the USA, EPA. Four different growing media were used with a combination of top soil, gravel, river sand and mature sewage sludge compost, aiming to determine the best substrate for enteric pathogen removal. Eight units were constructed, two for each material. One bed for each pair was planted with Typha latifolia plants commonly known as cattails. Primary treated domestic wastewater, was continuously fed in to the bed for more than six months. All beds achieved a high reduction of Escherichia coli and faecal coliforms with the best results recorded in the gravel reed beds with an average removal above 3.3 log for E. coli and 3.0 for faecal coliforms. There was no significance difference in the performance of planted and unplanted reed beds.

Indications of disordered eating behaviour in adolescent patients with idiopathic scoliosis.

We have investigated whether patients with adolescent-onset idiopathic scoliosis (AIS) are more likely to have a low body-weight. Measurements of weight, height and body mass index (BMI) were made in 44 young women with AIS and compared with age- and gender-adjusted normative data. The body mass criteria of the International Classification of Diseases for eating disorders was used to determine how many patients were within the range considered to be 'eating disordered'. Compared with the normative data, the AIS group did not differ significantly in terms of height, (p = 0.646), but they were significantly lighter (p < 0.001) and had significantly lower BMI scores (p < 0.001); 25% of the series had BMI scores which were within the range considered to be anorexic. The relationship between a diagnosis of AIS and low body-weight may indicate disordered eating and is thus a cause for concern, particularly in the light of the well-established relationship between eating psychopathology and osteoporosis. Aspects of organic health may need to be considered in addition to the cosmetic deformity.

Biochemical characteristics of guanine nucleotide binding protein alpha-subunit recombinant protein and three mutants: investigation of a domain motion involved in GDP-GTP exchange.

Our previous studies using molecular dynamics have shown a hinge bending motion between the helical and the GTPase domains of GalphaT (Mello et al., 1998). The hypothesis that this motion is allowed by residues Gly56 and Gly179 and that this motion may affect the ligand exchange was tested in this work. Mutations of Gly 56 were carried out and the mutant proteins were expressed in Sf9 cells using the Baculovirus expression system. The recombinant proteins were purified using Ni-NTA affinity chromatography. The results for the (GDP/GTP) exchange assays showed that G56S and double mutants (D55G/G56S) proteins differ significantly from the wild type and D55G mutant forms. The Kd values for GTPgammaS binding of those mutants have decreased by approximately 10-fold. No difference in the GTPase activity was detected for the mutants. Thus, the biochemical results obtained support the conclusions of the computational studies.

Non-invasive ventilation in the treatment of ventilatory failure following corrective spinal surgery.

Non-invasive positive pressure ventilation has previously been used successfully to treat both acute and chronic ventilatory failure secondary to a number of conditions, including scoliosis. We report two patients in whom it was used, on three separate occasions, to treat acute ventilatory failure following corrective spinal surgery. Non-invasive positive pressure ventilation may be useful postoperatively in high-risk patients undergoing major spinal surgery in an attempt to prevent intubation and its attendant complications.