Marie Galligan

Novel glycan biomarkers for the detection of lung cancer

Lung cancer has a poor prognosis and a 5-year survival rate of 15%. Therefore, early detection is vital. Diagnostic testing of serum for cancer-associated biomarkers is a noninvasive detection method. Glycosylation is the most frequent post-translational modification of proteins and it has been shown to be altered in cancer. In this paper, high-throughput HILIC technology was applied to serum samples from 100 lung cancer patients, alongside 84 age-matched controls and significant alterations in N-linked glycosylation were identified. Increases were detected in glycans containing Sialyl Lewis X, monoantennary glycans, highly sialylated glycans and decreases were observed in core-fucosylated biantennary glycans, with some being detectable as early as in Stage I. The N-linked glycan profile of haptoglobin demonstrated similar alterations to those elucidated in the total serum glycome. The most significantly altered HILIC peak in lung cancer samples includes predominantly disialylated and tri- and tetra-antennary glycans. This potential disease marker is significantly increased across all disease groups compared to controls and a strong disease effect is visible even after the effect of smoking is accounted for. The combination of all glyco-biomarkers had the highest sensitivity and specificity. This study identifies candidates for further study as potential biomarkers for the disease.

Glycosylation status of serum in inflammatory arthritis in response to anti-TNF treatment

OBJECTIVE Glycosylation is the most common post-translational modification and is altered in disease. The typical glycosylation change in patients with inflammatory arthritis (IA) is a decrease in galactosylation levels on IgG. The aim of this study is to evaluate the effect of anti-TNF therapy on whole serum glycosylation from IA patients and determine whether these alterations in the glycome change upon treatment of the disease. METHODS Serum samples were collected from 54 IA patients before treatment and at 1 and 12 months after commencing anti-TNF therapy. N-linked glycans from whole serum samples were analysed using a high-throughput hydrophilic interaction liquid chromatography-based method. RESULTS Glycosylation on the serum proteins of IA patients changed significantly with anti-TNF treatment. We observed an increase in galactosylated glycans from IgG, also an increase in core-fucosylated biantennary galactosylated glycans and a decrease in sialylated triantennary glycans with and without outer arm fucose. This increase in galactosylated IgG glycans suggests a reversing of the N-glycome towards normal healthy profiles. These changes are strongly correlated with decreasing CRP, suggesting a link between glycosylation changes and decreases in inflammatory processes. CONCLUSION Glycosylation changes in the serum of IA patients on anti-TNF therapy are strongly associated with a decrease in inflammatory processes and reflect the effect of anti-TNF on the immune system.

Increase in Sialylation and Branching in the Mouse Serum N-glycome Correlates with Inflammation and Ovarian Tumour Progression

Ovarian cancer is the most lethal gynaecological cancer and is often diagnosed in late stage, often as the result of the unavailability of sufficiently sensitive biomarkers for early detection, tumour progression and tumour-associated inflammation. Glycosylation is the most common posttranslational modification of proteins; it is altered in cancer and therefore is a potential source of biomarkers. We investigated the quantitative and qualitative effects of anti-inflammatory (acetylsalicylic acid) and pro-inflammatory (thioglycolate and chlorite-oxidized oxyamylose) drugs on glycosylation in mouse cancer serum. A significant increase in sialylation and branching of glycans in mice treated with an inflammation-inducing compound was observed. Moreover, the increases in sialylation correlated with increased tumour sizes. Increases in sialylation and branching were consistent with increased expression of sialyltransferases and the branching enzyme MGAT5. Because the sialyltransferases are highly conserved among species, the described changes in the ovarian cancer mouse model are relevant to humans and serum N-glycome analysis for monitoring disease treatment and progression might be a useful biomarker.

The role of sports physiotherapy at the London 2012 Olympic Games

Background There is a lack of information on the utilisation of physiotherapy services at the Olympic Games. Aim To better understand the athlete and non-athlete requirements of the physiotherapy services at the Olympic Village Polyclinic during the London 2012 Olympic Games. Methods From 16 July to 14 August 2012, physiotherapy encounters for athletes and non-athletes (National Olympic Committee (NOC) team officials, coaches, team managers, workforce, Olympic family, technical officials and press) were recorded on the ATOS electronic medical records system at the polyclinic in the main Athletes’ Village in Stratford. Results Of the 1778 encounters, 1219 (69%) were administered to athletes and 559 (31%) to non-athletes. The anatomical areas most frequently recorded at the first visits for athletes were knee (15.4%), lumbar spine/lower back (15.2%) and upper leg (12.6%) and that for non-athletes were lumbar spine/lower back (19.8%), knee (15.8%) and neck/cervical spine. Muscle (33.3%) and joint injuries (24.8%) were the most common diagnoses in athletes and non-athletes (24.4% and 30.1%). The five most frequently used treatment modalities were therapeutic soft tissue techniques (23.3%), mobilisation techniques (21.8%), taping (8.9%), cryotherapy (6.9%) and exercise prescription (6.4%). The most common cause of athletes’ injuries was overuse (43.6%). Conclusions This study of the London 2012 Olympic Games workload highlights the physiotherapy needs of athletes as well as non-athletes and identifies the high numbers of pre-existing and overuse injuries in this setting, providing an insight into the reasons why the athletes seek physiotherapy support during the Olympic Games.

A longitudinal study of Staphylococcus aureus colonization in pigs in Ireland.

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) in livestock has refocused attention on S. aureus colonization and transmission in pigs. This study investigated the effect of the S. aureus colonization status of a sow on the colonization status of her piglets, and whether pigs carry the same strain of S. aureus throughout production. Nasal swabs were collected from the piglets of six healthy sows two days after birth and two days before and two days after they were moved into each production stage. The average prevalence of S. aureus colonization varied between 26% and 73%. The odds of being S. aureus positive were almost 12 times higher for piglets born to nasal-positive sows than for those born to nasal-negative sows, and three times higher again for piglets born to sows that were both nasal- and vaginal-positive. Isolates recovered from piglets immediately after birth were indistinguishable from those of the dam as determined by phenotypic and molecular typing, including microarray analysis and optical mapping. All isolates belonged to clonal complex 9 and the majority exhibited a novel spa type, t10449. The findings show that the S. aureus colonization status of the sow influences the colonization status of her piglets in the early production stages but strains carried by pigs change over time. Multiresistant S. aureus was detected, in particular post-weaning. Results suggest that sow status and management practices, including mixing of pigs and antimicrobial usage at weaning, should be considered when implementing control measures for S. aureus on a farm.

3T MRI of the knee with optimised isotropic 3D sequences: Accurate delineation of intra-articular pathology without prolonged acquisition times

ObjectivesTo investigate optimised isotropic 3D turbo spin echo (TSE) and gradient echo (GRE)-based pulse sequences for visualisation of articular cartilage lesions within the knee joint.MethodsOptimisation of experimental imaging sequences was completed using healthy volunteers (n=16) with a 3-Tesla (3T) MRI scanner. Imaging of patients with knee cartilage abnormalities (n=57) was then performed. Acquired sequences included 3D proton density-weighted (PDW) TSE (SPACE) with and without fat-suppression (FS), and T2*W GRE (TrueFISP) sequences, with acquisition times of 6:51, 6:32 and 5:35 min, respectively.ResultsOne hundred sixty-one confirmed cartilage lesions were detected and categorised (Grade II n=90, Grade III n=71). The highest sensitivity and specificity for detecting cartilage lesions were obtained with TrueFISP with values of 84.7% and 92%, respectively. Cartilage SNR mean for PDW SPACE-FS was the highest at 72.2. TrueFISP attained the highest CNR means for joint fluid/cartilage (101.5) and joint fluid/ligament (156.5), and the lowest CNR for cartilage/meniscus (48.5). Significant differences were identified across the three sequences for all anatomical structures with respect to SNR and CNR findings (p-value <0.05).ConclusionIsotropic TrueFISP at 3T, optimised for acquisition time, accurately detects cartilage defects, although it demonstrated the lowest contrast between cartilage and meniscus.Key points• Cartilage is better visualised with 3D TrueFISP than 3D SPACE sequences.• 3D TrueFISP is a reliable sequence for detecting low- and high-grade cartilage defects.• 3D TrueFISP at 3T provides excellent contrast between cartilage and joint fluid.

Factors Influencing Job Preferences of Health Workers Providing Obstetric Care: Results from Discrete Choice Experiments in Malawi, Mozambique and Tanzania.

BackgroundTask shifting from established health professionals to mid-level providers (MLPs) (professionals who undergo shorter training in specific procedures) is one key strategy for reducing maternal and neonatal deaths. This has resulted in a growth in cadre types providing obstetric care in low and middle-income countries. Little is known about the relative importance of the different factors in determining motivation and retention amongst these cadres.MethodsThis paper presents findings from large sample (1972 respondents) discrete choice experiments to examine the employment preferences of obstetric care workers across three east African countries.ResultsThe strongest predictors of job choice were access to continuing professional development and the presence of functioning human resources management (transparent, accountable and consistent systems for staff support, supervision and appraisal). Consistent with similar works we find pay and allowances significantly positively related to utility, but financial rewards are not as fundamental a factor underlying employment preferences as many may have previously believed. Location (urban vs rural) had the smallest average effect on utility for job choice in all three countries.ConclusionsThese findings are important in the context where efforts to address the human resources crisis have focused primarily on increasing salaries and incentives, as well as providing allowances to work in rural areas.

The impact of a supportive supervision intervention on health workers in Niassa, Mozambique: a cluster-controlled trial

BackgroundRegular supportive supervision is critical to retaining and motivating staff in resource-constrained settings. Previous studies have shown the particular contribution that supportive supervision can make to improving job satisfaction amongst over-stretched health workers in such settings.MethodsThe Support, Train and Empower Managers (STEM) study designed and implemented a supportive supervision intervention and measured its’ impact on health workers using a controlled trial design with a three-arm pre- and post-study in Niassa Province in Mozambique. Post-intervention interviews with a small sample of health workers were also conducted.ResultsThe quantitative measurements of job satisfaction, emotional exhaustion and work engagement showed no statistically significant differences between end-line and baseline. The qualitative data collected from health workers post the intervention showed many positive impacts on health workers not captured by this quantitative survey.ConclusionsHealth workers perceived an improvement in their performance and attributed this to the supportive supervision they had received from their supervisors following the intervention. Reports of increased motivation were also common. An unexpected, yet important consequence of the intervention, which participants directly attributed to the supervision intervention, was the increase in participation and voice amongst health workers in intervention facilities.

Response to letter re: Carotid atherosclerotic plaques standardized uptake values: methodological issues on reproducibility and accuracy

Background Dear Editor, We would like to thank Dr. Siamak Sabour for his letter and comments relating to our recently published article [1]. In the manuscript, an investigation was conducted on whether or not carotid atherosclerotic plaque standardized uptake values (SUVs) are consistent and reproducible across software packages; therefore, the purpose of the analysis performed was to measure the reproducibility, rather than validity, of SUV measurements between two software packages (OsiriX MD® version 6.5.2, Pixmeo© SARL, Geneva, Switzerland and AquariusNet iNtuitionTM version 4.4.11, TeraRecon, Foster City, CA, USA) (Table 1).