Heterotopic ossification, osteolysis and implant failure following cervical total disc replacement with the M6-C™ artificial disc.

INTRODUCTION: A recent study reported a 34% mid-term revision rate after M6-C™ cervical total disc replacement (CTDR) for wear-related osteolysis. Here, we aim to investigate the prevalence, risk factors, and radiographic characteristics of periprosthetic bony changes and implant failure of the M6-C™ artificial disc. METHODS: We retrospectively analysed radiographic (conventional X-ray, CT scan) and clinical outcomes (EQ-5D-5L, Neck Disability Index (NDI), and Visual Analog Scale (VAS) for neck and arm pain) data collected during routine follow-up of patients who underwent CTDR with the M6-C™ between 2011 and 2015. RESULTS: In total, 85 patients underwent CTDR with the M6-C™. Follow-up data were available for 43 patients (54% female, mean age 44 years) with 50 implants and a mean follow-up of 8.1 years (6.5-11 years). Implant failure with the presence of severe osteolysis was identified in 5 (12%) patients who were all male (p = 0.016) and implanted at the C5/6 level (p = 0.11). All failed implants required revision surgery. The overall prevalence of osteolysis was 44% (22/50 implants) and 34% (17/50 implants) for significant heterotopic ossification. Patients with high-grade osteolysis showed higher VAS arm pain (p = 0.05) and lower EQ-5D-VAS health VAS (p = 0.03). CONCLUSION: We report a lower reoperation rate for failed M6-C™ implants than previously published, but confirmed that osteolysis and heterotopic ossification are common following CTDR with the M6-C™ and may be asymptomatic. Therefore, we strongly recommend ongoing clinical and radiographic monitoring after CTDR with the M6-C™, particularly for male patients implanted at the C5/6 level.

Discerning the global phylogeographic distribution of Phyllosticta citricarpa by means of whole genome sequencing.

Phyllosticta citricarpa is a fungal pathogen causing citrus black spot (CBS). As a regulated pest in some countries, the presence of the pathogen limits the export of fruit and is therefore of agricultural and economic importance. In this study, we used high throughput sequencing data to infer the global phylogeographic distribution of this pathogen, including 71 isolates from eight countries, Argentina, Australia, Brazil, China, Cuba, Eswatini, South Africa and the United States of America. We assembled draft genomes and used a pairwise read mapping approach for the detection and enumeration of variants between isolates. We performed SSR marker discovery based on the assembled genome with the best assembly statistics, and generated genotype profiles for all isolates with 1987 SSR markers in silico. Furthermore, we identified 32,560 SNPs relative to a reference sequence followed by population genetic analyses based on the three datasets; pairwise variant counts, SSR genotypes and SNP genotypes. All three analysis approaches gave similar overall results. Possible pathways of dissemination among the populations from China, Australia, southern Africa and the Americas are postulated. The Chinese population is the most diverse, and is genetically the furthest removed from all other populations, and is therefore considered the closest to the origin of the pathogen. Isolates from Australia, Eswatini and the South African province Mpumalanga are closely associated and clustered together with those from Argentina and Brazil. The Eastern Cape, North West, and KwaZulu-Natal populations in South Africa grouped in another cluster, while isolates from Limpopo are distributed between the two aforementioned clusters. Southern African populations showed a close relationship to populations in North America, and could be a possible source of P. citricarpa populations that are now found in North America. This study represents the largest whole genome sequencing survey of P. citricarpa to date and provides a more comprehensive assessment of the population genetic diversity and connectivity of P. citricarpa from different geographic origins. This information could further assist in a better understanding of the epidemiology of the CBS pathogen, its long-distance dispersal and dissemination pathways, and can be used to refine phytosanitary regulations and management programmes for the disease.

Valproic acid interactions with the NavMs voltage-gated sodium channel.

Valproic acid (VPA) is an anticonvulsant drug that is also used to treat migraines and bipolar disorder. Its proposed biological targets include human voltage-gated sodium channels, among other membrane proteins. We used the prokaryotic NavMs sodium channel, which has been shown to be a good exemplar for drug binding to human sodium channels, to examine the structural and functional interactions of VPA. Thermal melt synchrotron radiation circular dichroism spectroscopic binding studies of the full-length NavMs channel (which includes both pore and voltage sensor domains), and a pore-only construct, undertaken in the presence and absence of VPA, indicated that the drug binds to and destabilizes the channel, but not the pore-only construct. This is in contrast to other antiepileptic compounds that have previously been shown to bind in the central hydrophobic core of the pore region of the channel, and that tend to increase the thermal stability of both pore-only constructs and full-length channels. Molecular docking studies also indicated that the VPA binding site is associated with the voltage sensor, rather than the hydrophobic cavity of the pore domain. Electrophysiological studies show that VPA influences the block and inactivation rates of the NavMs channel, although with lower efficacy than classical channel-blocking compounds. It thus appears that, while VPA is capable of binding to these voltage-gated sodium channels, it has a very different mode and site of action than other anticonvulsant compounds.

Effect of parachute delivery on red blood cell (RBC) and plasma quality measures of blood for transfusion.

BACKGROUND: Parachute airdrop offers a rapid transfusion supply option for humanitarian aid and military support. However, its impact on longer-term RBC survival is undocumented. This study aimed to determine post-drop quality of RBCs in concentrates (RCC), and both RBCs and plasma in whole blood (WB) during subsequent storage. STUDY DESIGN AND METHODS: Twenty-two units of leucodepleted RCC in saline, adenine, glucose, mannitol (SAGM) and 22 units of nonclinical issue WB were randomly allocated for air transportation, parachute drop, and subsequent storage (parachute), or simply storage under identical conventional conditions (4 ± 2°C) (control). All blood products were 6-8 days post-donation. Parachute units were packed into Credo Cubes, (Series 4, 16 L) inside a PeliCase (Peli 0350) and rigged as parachute delivery packs. Packs underwent a 4-h tactical flight (C130 aircraft), then parachuted from 250 to 400 ft before ground recovery. The units were sampled aseptically before and after airdrop at weekly intervals. A range of assays quantified the RBC storage lesion and coagulation parameters. RESULTS: Blood units were maintained at 2-6°C and recovered intact after recorded ground impacts of 341-1038 m s-2 . All units showed a classical RBC storage lesion and increased RBC microparticles during 42 days of storage. Fibrinogen and clotting factors decreased in WB during storage. Nevertheless, no significant difference was observed between Control and Parachute groups. Air transportation and parachute delivery onto land did not adversely affect, or shorten, the shelf life of fresh RBCs or WB. DISCUSSION: Appropriately packaged aerial delivery by parachute can be successfully used for blood supply.

College and the "Culture War": Assessing Higher Education's Influence on Moral Attitudes.

Moral differences contribute to social and political conflicts. Against this backdrop, colleges and universities have been criticized for promoting liberal moral attitudes. However, direct evidence for these claims is sparse, and suggestive evidence from studies of political attitudes is inconclusive. Using four waves of data from the National Study of Youth and Religion, we examine the effects of higher education on attitudes related to three dimensions of morality that have been identified as central to conflict: moral relativism, concern for others, and concern for social order. Our results indicate that higher education liberalizes moral concerns for most students, but it also departs from the standard liberal profile by promoting moral absolutism rather than relativism. These effects are strongest for individuals majoring in the humanities, arts, or social sciences, and for students pursuing graduate studies. We conclude with a discussion of the implications of our results for work on political conflict and moral socialization.

Inoculum Dynamics and Infection of Citrus Fruit by Phyllosticta citricarpa.

Citrus black spot, caused by Phyllosticta citricarpa, is characterized by fruit blemishes and premature fruit drop, resulting in significant economic losses in summer rainfall areas. The pathogen forms both conidia and ascospores during its life cycle. However, the occurrence of these spores and their contributions to infection of fruit in field conditions are not well understood. Our research using direct leaf litter monitoring and volumetric spore trapping in Queensland orchards revealed that pseudothecia and ascospores in leaf litter as well as trapped ascospores had low abundance, while pycnidia and conidia were highly abundant. Both P. citricarpa and endophytic Phyllosticta spp. were identified, with P. citricarpa being dominant. In replicated field trials, we determined that infection of Imperial mandarin fruit by P. citricarpa occurred from fruit set until week 20 of fruit development, with the key infection events taking place between weeks 4 and 16 in Queensland subtropical conditions. These results demonstrate that protecting fruit during weeks 4 to 16 significantly reduced P. citricarpa infection. We found no significant correlation between the disease incidence in fruit and P. citricarpa conidial abundance in leaf litter or ascospore abundance measured by volumetric spore trapping. Therefore, it is suggested that inoculum sources in the tree canopy other than those detected by spore trapping and direct leaf litter monitoring may play a major role in the epidemiology of citrus black spot. Improved knowledge regarding epidemiology of P. citricarpa and an understanding of propagules causing infection may aid in development of more effective disease management strategies.

PCDDB: new developments at the Protein Circular Dichroism Data Bank.

The Protein Circular Dichroism Data Bank (PCDDB) has been in operation for more than 5 years as a public repository for archiving circular dichroism spectroscopic data and associated bioinformatics and experimental metadata. Since its inception, many improvements and new developments have been made in data display, searching algorithms, data formats, data content, auxillary information, and validation techniques, as well as, of course, an increase in the number of holdings. It provides a site (http://pcddb.cryst.bbk.ac.uk) for authors to deposit experimental data as well as detailed information on methods and calculations associated with published work. It also includes links for each entry to bioinformatics databases. The data are freely available to accessors either as single files or as complete data bank downloads. The PCDDB has found broad usage by the structural biology, bioinformatics, analytical and pharmaceutical communities, and has formed the basis for new software and methods developments.

A service evaluation of specialist nurse telephone follow-up of bowel cancer patients after surgery.

INTRODUCTION: the NHS Long Term Plan has called for a reduction in the number of outpatient appointments to reduce pressure on hospital services and increase ease of access for patients. This article presents a service evaluation of an innovative, nurse-led telephone follow-up service for a group of elective bowel cancer patients following surgery. METHODS: the records of patients who underwent surgery over a 2-year period were accessed to determine the number of telephone follow-ups and other investigations. This was used to model the potential cost saving for commissioners against traditional clinic follow-up. Patient satisfaction was assessed by the European Organisation for Research and Treatment of Cancer questionnaire on Outpatient Satisfaction in 30 patients. RESULTS: feedback on the service was overwhelmingly positive, with patients praising the care received from the specialist nurses, but also commenting on increased continuity of care, ease of access and convenience. The service also potentially creates significant savings for commissioners as the agreed tariff for nurse telephone follow-up is significantly less than the outpatient tariff. DISCUSSION: this innovative follow-up system is well liked by patients and should provide savings for commissioners. The hospital also benefits from an increase in capacity to see new or more unwell patients, and a reduction in carbon emissions. Such a service, however, is dependent on people, and although it has functioned effectively in this department for approximately 20 years, it would only be generalisable to other units if staff had appropriate expertise.

A service evaluation of specialist nurse telephone follow-up of bowel cancer patients after surgery.

INTRODUCTION: the NHS Long Term Plan has called for a reduction in the number of outpatient appointments to reduce pressure on hospital services and increase ease of access for patients. This article presents a service evaluation of an innovative, nurse-led telephone follow-up service for a group of elective bowel cancer patients following surgery. METHODS: the records of patients who underwent surgery over a 2-year period were accessed to determine the number of telephone follow-ups and other investigations. This was used to model the potential cost saving for commissioners against traditional clinic follow-up. Patient satisfaction was assessed by the European Organisation for Research and Treatment of Cancer questionnaire on Outpatient Satisfaction in 30 patients. RESULTS: feedback on the service was overwhelmingly positive, with patients praising the care received from the specialist nurses, but also commenting on increased continuity of care, ease of access and convenience. The service also potentially creates significant savings for commissioners as the agreed tariff for nurse telephone follow-up is significantly less than the outpatient tariff. DISCUSSION: this innovative follow-up system is well liked by patients and should provide savings for commissioners. The hospital also benefits from an increase in capacity to see new or more unwell patients, and a reduction in carbon emissions. Such a service, however, is dependent on people, and although it has functioned effectively in this department for approximately 20 years, it would only be generalisable to other units if staff had appropriate expertise.

Attenuation of Phosphorylation-dependent Activation of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) by Disease-causing Mutations at the Transmission Interface.

Cystic fibrosis transmembrane conductance regulator (CFTR) is a multidomain membrane protein that functions as a phosphorylation-regulated anion channel. The interface between its two cytosolic nucleotide binding domains and coupling helices conferred by intracellular loops extending from the channel pore domains has been referred to as a transmission interface and is thought to be critical for the regulated channel activity of CFTR. Phosphorylation of the regulatory domain of CFTR by protein kinase A (PKA) is required for its channel activity. However, it was unclear if phosphorylation modifies the transmission interface. Here, we studied purified full-length CFTR protein using spectroscopic techniques to determine the consequences of PKA-mediated phosphorylation. Synchrotron radiation circular dichroism spectroscopy confirmed that purified full-length wild-type CFTR is folded and structurally responsive to phosphorylation. Intrinsic tryptophan fluorescence studies of CFTR showed that phosphorylation reduced iodide-mediated quenching, consistent with an effect of phosphorylation in burying tryptophans at the transmission interface. Importantly, the rate of phosphorylation-dependent channel activation was compromised by the introduction of disease-causing mutations in either of the two coupling helices predicted to interact with nucleotide binding domain 1 at the interface. Together, these results suggest that phosphorylation modifies the interface between the catalytic and pore domains of CFTR and that this modification facilitates CFTR channel activation.

Defunctioning Stomas Result in Significantly More Short-Term Complications Following Low Anterior Resection for Rectal Cancer.

BACKGROUND: Studies suggest that defunctioning stomas reduce the rate of anastomotic leakage and urgent reoperations after anterior resection. Although the magnitude of benefit appears to be limited, there has been a trend in recent years towards routinely creating defunctioning stomas. However, little is known about post-operative complication rates in patients with and without a defunctioning stoma. We compared overall short-term post-operative complications after low anterior resection in patients managed with a defunctioning stoma to those managed without a stoma. METHODS: A retrospective cohort study of patients undergoing elective low anterior resection of the rectum for rectal cancer. The primary outcome was overall 90-day post-operative complications. RESULTS: Two hundred and three patients met the inclusion criteria for low anterior resection. One hundred and forty (69%) had a primary defunctioning stoma created. 45% received neoadjuvant radiotherapy. Patients with a defunctioning stoma had significantly more complications (57.1 vs 34.9%, p = 0.003), were more likely to suffer multiple complications (17.9 vs 3.2%, p < 0.004) and had longer hospital stays (13.0 vs 6.9 days, p = 0.005) than those without a stoma. 19% experienced a stoma-related complication, 56% still had a stoma 1 year after their surgery, and 26% were left with a stoma at their last follow-up. Anastomotic leak rates were similar but there was a significantly higher reoperation rate among patients managed without a defunctioning stoma. CONCLUSION: Patients selected to have a defunctioning stoma had an absolute increase of 22% in overall post-operative complications compared to those managed without a stoma. These findings support the more selective use of defunctioning stomas. STUDY REGISTRATION: Registered at www.researchregistry.com (UIN: researchregistry3412).

Pathogenicity of Phyllosticta citricarpa Ascospores on Citrus spp.

Citrus black spot, caused by Phyllosticta citricarpa, is one of the most important fungal diseases in many citrus-growing regions with hot and humid summers. Ascospores and conidia are known to contribute to epidemic development of the disease. However, pathogenicity testing has never been done for pure ascospores produced from fully characterized P. citricarpa isolates, due to the inability to induce the sexual state in vitro. Recently, an in vitro mating technique was developed to readily produce pure P. citricarpa ascospores for use in host inoculation studies. To test the pathogenicity of P. citricarpa ascospores, we inoculated Troyer citrange leaves and Murcott tangor fruit with ascospores produced in vitro from characterized P. citricarpa isolates. Typical symptoms of citrus black spot occurred. Recovery of P. citricarpa isolates from symptomatic lesions and their characterization using genetic markers enabled us to identify recombinant genotypes among the isolates recovered from ascospore inoculations and, as such, fulfill Koch's postulates for ascospores. We have also identified Troyer citrange seedlings as a potential model system for citrus black spot inoculation studies, because it allows typical symptoms of citrus black spot to be expressed with a much shorter latent period than on fruit. This will facilitate future studies of epidemiological aspects of P. citricarpa ascospores relative to conidia and improve our understanding of the citrus black spot pathosystem. The susceptibility of Troyer citrange seedlings will also facilitate experimenting with disease management methods, aimed at reducing the impact of citrus black spot.

An expanded model of the moral self: Beyond care and justice.

Most research on moral identities conceptualizes morality exclusively in terms of care and justice, but work from across the social sciences indicates that these represent only a corner of the moral landscape. Emphasizing care and justice alone severely restricts the scope of moral identity models, and risks under-estimating the influence of moral self-processes. To address this, we develop and validate measures of moral identity focused on group loyalty, authority, and purity, three additional facets of morality highlighted in Moral Foundations Theory. Although the loyalty identity is remarkably similar to the care/justice identity, the authority and purity identities are distinct, and demonstrate adequate convergent, divergent, and nomological validity. These identities also predict a wide range of behaviors that traditional care/justice focused moral identities miss. Taken together, our work indicates that the moral self is more complex - and has a much wider scope of influence - than previously supposed.

Socio-spatial mobilities and narratives of class identity in Britain.

In this article we carry out the most comprehensive analysis of social and spatial mobility in the UK to date and the first to directly link different dimensions of mobility to processes of social class formation. Using new analytical techniques in this field, we integrate quantitative and qualitative data from the 1958 Birth Cohort Study, combining text-mining and correspondence analysis in order to examine the intersection of geographical and social mobility with class identities. This work reflects a revival of interest in the spatialization of class inequalities, which is connected to policy concerns about the regional dimension of Britain's mobility 'crisis' that have intensified in the wake of the 'Brexit' vote. We find that the South's role as an 'escalator' region for upward mobility has continued and that the relationship between social and spatial mobility both confirms and qualifies the role of London and the South East in generating inequalities. We show that different migration-mobility transitions are associated with distinctive and contrasting class identity narratives. Those who move from North to South stand out in particular for the way their 'class talk' reveals the social disorientation that attends their success. The contrasting ways in which other groups express their social identities suggests that the interplay of geographical and social mobilities performs a significant role in regional cultural divisions.

Examining the Effects of Religious Attendance on Resilience for Older Adults.

Growing older often brings hardship, adversity, and even trauma. Resilience is a broad term used to describe flourishing despite adversity. To date, resilience and the connections to religion have not been well studied, despite compelling evidence that religious practice can promote psychological health. This research examines the role that religion plays in promoting resilience among older adults. Research questions include: (a) What is the relationship between religion and trait resilience? and (b) Does religion promote resilient reintegration following traumatic life events? Results indicate that religious service attendance is tied to higher levels of trait resilience and that both service attendance and trait resilience directly predict lower levels of depression and higher rates of resilient reintegration following traumatic life events. Findings suggest that religious service attendance has protective properties that are worthy of consideration when investigating resilience.

Mutagenesis of the NaChBac sodium channel discloses a functional role for a conserved S6 asparagine.

Asparagine is conserved in the S6 transmembrane segments of all voltage-gated sodium, calcium, and TRP channels identified to date. A broad spectrum of channelopathies including cardiac arrhythmias, epilepsy, muscle diseases, and pain disorders is associated with its mutation. To investigate its effects on sodium channel functional properties, we mutated the simple prokaryotic sodium channel NaChBac. Electrophysiological characterization of the N225D mutant reveals that this conservative substitution shifts the voltage-dependence of inactivation by 25 mV to more hyperpolarized potentials. The mutant also displays greater thermostability, as determined by synchrotron radiation circular dichroism spectroscopy studies of purified channels. Based on our analyses of high-resolution structures of NaChBac homologues, we suggest that the side-chain amine group of asparagine 225 forms one or more hydrogen bonds with different channel elements and that these interactions are important for normal channel function. The N225D mutation eliminates these hydrogen bonds and the structural consequences involve an enhanced channel inactivation.

Sexual Reproduction in the Citrus Black Spot Pathogen, Phyllosticta citricarpa.

Citrus black spot (Phyllosticta citricarpa) causes fruit blemishes and premature fruit drop, resulting in significant economic losses in citrus growing areas with summer rainfall across the globe. The mating type locus of P. citricarpa has recently been characterized, revealing the heterothallic nature of this pathogen. However, insight into the occurrence of mating and the impact of completing the sexual cycle of P. citricarpa was lacking. To investigate the occurrence and impact of sexual reproduction, we developed a method to reliably, and for the first time, produce ascospores of P. citricarpa on culture media. To demonstrate meiosis during the mating process, we identified recombinant genotypes through multilocus genotyping of single ascospores. Because the process of fertilization was not well understood, we experimentally determined that fertilization of P. citricarpa occurs via spermatization. Our results demonstrate that P. citricarpa is heterothallic and requires isolates of different MAT idiomorphs to be in direct physical contact, or for spermatia to fulfill their role as male elements to fertilize the receptive organs, in order to initiate the mating process. The impact of mating on the epidemiology of citrus black spot in the field is discussed.