Environmentally associated chromosomal structural variation influences fine-scale population structure of Atlantic Salmon (Salmo salar).

Chromosomal rearrangements (e.g., inversions, fusions, and translocations) have long been associated with environmental variation in wild populations. New genomic tools provide the opportunity to examine the role of these structural variants in shaping adaptive differences within and among wild populations of non-model organisms. In Atlantic Salmon (Salmo salar), variations in chromosomal rearrangements exist across the species natural range, yet the role and importance of these structural variants in maintaining adaptive differences among wild populations remains poorly understood. We genotyped Atlantic Salmon (n = 1429) from 26 populations within a highly genetically structured region of southern Newfoundland, Canada with a 220K SNP array. Multivariate analysis, across two independent years, consistently identified variation in a structural variant (translocation between chromosomes Ssa01 and Ssa23), previously associated with evidence of trans-Atlantic secondary contact, as the dominant factor influencing population structure in the region. Redundancy analysis suggested that variation in the Ssa01/Ssa23 chromosomal translocation is strongly correlated with temperature. Our analyses suggest environmentally mediated selection acting on standing genetic variation in genomic architecture introduced through secondary contact may underpin fine-scale local adaptation in Placentia Bay, Newfoundland, Canada, a large and deep embayment, highlighting the importance of chromosomal structural variation as a driver of contemporary adaptive divergence.

Treatment of enterocutaneous fistula: a systematic review and meta-analysis.

BACKGROUND: Enterocutaneous fistula (ECF) is an abnormal communication between the gastrointestinal tract and skin, with a myriad of etiologies and therapeutic options. Management is influenced by etiology and specifics of the ECF, and patient-related factors. The aim of this study was to assess overall success, recurrence, and mortality rates of treatment for ECF. MATERIALS: A systematic search of PubMed and Google Scholar was performed through October 2021 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Case reports, reviews, animal studies, studies not reporting outcomes, had no available English text, included patients < 16 years old or those assessing other abdominocutaneous/internal fistulas were excluded. RESULTS: Fifty-three studies, between 1975 and 2020, incorporating 3078 patients were included. Patient age ranged between 16 and 87 years with a male:female ratio of 1.14:1. ECF developed postoperatively in 89.4%. Other common etiologies were inflammatory bowel disease, trauma, malignancy, and radiation. At least 28% of patients had complex fistulae (reported in 18 studies). Most common fistula site was small bowel. In 34 publications, 62.4% (n = 1371) patients received parenteral nutrition. In 45 publications, 72.5% underwent surgery to treat the fistula. Meta-analysis revealed an 89% healing rate; recurrence rate after initial successful treatment was 11.1%, and mortality rate was 8.5%. In a subgroup of patients who underwent combined ECF takedown and abdominal wall reconstructions (n = 315), 78% achieved fascial closure, mesh was used in 72%, hernia, and fistula recurrence rates were 19.7% and 7.6%, respectively. CONCLUSIONS: Treatment of ECF must be individualized according to specific etiology and location of the fistula and the patient's associated conditions.

The role of propeptide-mediated autoinhibition and intermolecular chaperone in the maturation of cognate catalytic domain in leucine aminopeptidase.

Leucyl aminopeptidase A from Aspergillus oryzae RIB40 (AO-LapA) is an exo-acting peptidase, widely utilised in food debittering applications. AO-LapA is secreted as a zymogen by the host and requires enzymatic cleavage of the autoinhibitory propeptide to reveal its full activity. Scarcity of structural data of zymogen aminopeptidases hampers a better understanding of the details of their molecular action of autoinhibition and how this might be utilised to improve the properties of such enzymes by recombinant methods for more effective bioprocessing. To address this gap in the literature, herein we report high-resolution crystal structures of recombinantly expressed AO-LapA precursor (AO-proLapA), mature LapA (AO-mLapA) and AO-mLapA complexed with reaction product l-leucine (AO-mLapA-Leu), all purified from Pichia pastoris culture supernatant. Our structures reveal a plausible molecular mechanism of LapA catalytic domain autoinhibition by propeptide and highlights the role of intramolecular chaperone (IMC). Our data suggest an absolute requirement for IMC in the maturation of cognate catalytic domain of AO-LapA. This observation is reinforced by our expression and refolding data of catalytic domain only (AO-refLapA) from Escherichia coli inclusion bodies, revealing a limited active conformation. Our work supports the notion that known synthetic aminopeptidase inhibitors and substrates mimic key polar contacts between propeptide and corresponding catalytic domain, demonstrated in our AO-proLapA zymogen crystal structure. Furthermore, understanding the atomic details of the autoinhibitory mechanism of cognate catalytic domains by native propeptides has wider reaching implications toward synthetic production of more effective inhibitors of bimetallic aminopeptidases and other dizinc enzymes that share an analogous reaction mechanism.

Re-expression of miR-200s in claudin-low mammary tumor cells alters cell shape and reduces proliferation and invasion potentially through modulating other miRNAs and SUZ12 regulated genes.

BACKGROUND: MicroRNAs are a class of non-coding RNAs that regulate gene expression through binding to mRNAs and preventing their translation. One family of microRNAs known as the miR-200 family is an important regulator of epithelial identity. The miR-200 family consists of five members expressed in two distinct clusters; the miR-200c/141 cluster and the miR-200b/200a/429 cluster. We have found that murine and human mammary tumor cells with claudin-low characteristics are associated with very low levels of all five miR-200s. METHODS: To determine the impact of miR-200s on claudin-low mammary tumor cells, the miR-200c/141 cluster and the miR-200b/200a/429 cluster were stably re-expressed in murine (RJ423) and human (MDA-MB-231) claudin-low mammary tumor cells. Cell proliferation and migration were assessed using BrdU incorporation and transwell migration across Matrigel coated inserts, respectively. miRNA sequencing and RNA sequencing were performed to explore miRNAs and mRNAs regulated by miR-200 re-expression while Enrichr-based pathway analysis was utilized to identify cellular functions modified by miR-200s. RESULTS: Re-expression of the miR-200s in murine and human claudin-low mammary tumor cells partially restored an epithelial cell morphology and significantly inhibited proliferation and cell invasion in vitro. miRNA sequencing and mRNA sequencing revealed that re-expression of miR-200s altered the expression of other microRNAs and genes regulated by SUZ12 providing insight into the complexity of miR-200 function. SUZ12 is a member of the polycomb repressor complex 2 that suppresses gene expression through methylating histone H3 at lysine 27. Flow cytometry confirmed that re-expression of miR-200s increased histone H3 methylation at lysine 27. CONCLUSIONS: Re-expression of miR-200s in claudin-low mammary tumor cells alters cell morphology and reduces proliferation and invasion, an effect potentially mediated by SUZ12-regulated genes and other microRNAs.

Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity.

Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells. carCTL receptors associated with the synapse were found to be disrupted and formed a convoluted multifocal pattern of Lck microclusters. Both proximal and distal receptor signaling pathways were induced more rapidly and subsequently decreased more rapidly in carCTL than in tcrCTL. The functional consequence of this rapid signaling in carCTL cells included faster lytic granule recruitment to the immune synapse, correlating with faster detachment of the CTL from the target cell. This study provides a mechanism for how CAR-T cells can debulk large tumor burden quickly and may contribute to further refinement of CAR design for enhancing the quality of signaling and programming of the T cell.

Diabetes UK evidence-based nutrition guidelines for the prevention and management of diabetes.

A summary of the latest evidence-based nutrition guidelines for the prevention and management of diabetes is presented. These guidelines are based on existing recommendations last published in 2011, and were formulated by an expert panel of specialist dietitians after a literature review of recent evidence. Recommendations have been made in terms of foods rather than nutrients wherever possible. Guidelines for education and care delivery, prevention of Type 2 diabetes, glycaemic control for Type 1 and Type 2 diabetes, cardiovascular disease risk management, management of diabetes-related complications, other considerations including comorbidities, nutrition support, pregnancy and lactation, eating disorders, micronutrients, food supplements, functional foods, commercial diabetic foods and nutritive and non-nutritive sweeteners are included. The sections on pregnancy and prevention of Type 2 diabetes have been enlarged and the weight management section modified to include considerations of remission of Type 2 diabetes. A section evaluating detailed considerations in ethnic minorities has been included as a new topic. The guidelines were graded using adapted 'GRADE' methodology and, where strong evidence was lacking, grading was not allocated. These 2018 guidelines emphasize a flexible, individualized approach to diabetes management and weight loss and highlight the emerging evidence for remission of Type 2 diabetes. The full guideline document is available at www.diabetes.org.uk/nutrition-guidelines.

Alternative Locales for the Health Promotion of African American Men: A Survey of African American Men in Chicago Barbershops.

African American men (AA) carry unequal burdens of several conditions including cancer, diabetes, hypertension, and HIV. Engagement of diverse populations including AA men in research and health promotion practice is vital to examining the health disparities that continue to plague many racially and ethnically diverse communities. To date, there is little research on best practices that indicate locations, community areas and settings to engage AA men in research and health promotion. Traditionally, the AA church has been a key area to engage AA men and women. However, changing tides in attendance of AA parishioners require additional information to identify areas where AAs, particularly, AA men congregate. The AA barbershop has been identified as a place of social cohesion, cultural immersion and solidarity for AA men but specific sub-populations of AA men may be underrepresented. To further investigate additional locales where AA men congregate, this study engaged AA barbers and clients in several urban community barbershops in Chicago, Illinois. 127 AA men over age 18y/o receiving grooming services in 25 Chicago area barbershops across 14 predominantly AA communities were consented and recruited for a quantitative survey study. The self-administered surveys were completed in ~15 min and $10 compensation was provided to men. Descriptive statistics were reported for demographic variables and for frequency of responses for locations to find AA men of specific age ranges for health promotion and screening activities. Outside of the traditionally used churches or barbershops, the top recommended recruitment sites by age were: 18-29y/o- city park or a recreational center; 30-39y/o- gym, bars or the street; 40-49y/o- various stores, especially home improvement stores, and the mall; and 50y/o+- fast food restaurants in the mornings, such as McDonalds, and individual's homes. The study participants also reported that locations where AA men congregate vary by age. Findings from this study illustrate that AA barbers and barbershops remain a key stakeholder in health promotion among AA men. The findings also demonstrate the need for additional research to examine best practices for identifying locations where diverse groups of AA men that vary by age and sexual orientation may congregate in order to support increased health promotion among AA men.

Use of high-density SNP data to identify patterns of diversity and signatures of selection in broiler chickens.

The development of broiler chickens over the last 70 years has been accompanied by large phenotypic changes, so that the resulting genomic signatures of selection should be detectable by current statistical techniques with sufficiently dense genetic markers. Using two approaches, this study analysed high-density SNP data from a broiler chicken line to detect low-diversity genomic regions characteristic of past selection. Seven regions with zero diversity were identified across the genome. Most of these were very small and did not contain many genes. In addition, fifteen regions were identified with diversity increasing asymptotically from a low level. These regions were larger and thus generally included more genes. Several candidate genes for broiler traits were found within these 'regression regions', including IGF1, GPD2 and MTNR1AI. The results suggest that the identification of zero-diversity regions is too restrictive for characterizing regions under selection, but that regions showing patterns of diversity along the chromosome that are consistent with selective sweeps contain a number of genes that are functional candidates for involvement in broiler development. Many regions identified in this study overlap or are close to regions identified in layer chicken populations, possibly due to their shared precommercialization history or to shared selection pressures between broilers and layers.

The compliance of healthcare workers with universal precautions in the emergency room at the university hospital of the west indies.

OBJECTIVES: The study assessed compliance among health workers in the Emergency Room at the University Hospital of the West Indies with universal precautions. This was done by determining the knowledge, practices and perceptions of staff of universal precautions and by assessing compliance. Reported adherence with universal precautions was compared with observed practice. METHODS: This was a cross-sectional study conducted over a one-year period. It was approved by the University Hospital of the West Indies/University of the West Indies/Faculty of Medical Sciences Ethics Committee. Data were analysed using Stata version 11.1. RESULTS: During the study period, 67 persons gave consent for the study, data were obtained for 62 of these participants and 52 of the respondents were observed. All of the participants were aware that universal precautions related to blood. Eighty-six per cent erroneously thought that universal precautions apply to urine. Seventy-nine per cent of the participants reported always washing their hands after performing a procedure and 43.5% reported always washing their hands before a procedure. Just over half of the participants reported always wearing gloves while doing procedures (56.5%). Only 9% reported always using a gown with a trauma patient. However, 31% and 43.3% reported wearing a gown when placing a chest tube and when anticipating splashes, respectively. Of those participants who reported washing their hands often after a procedure, over 30% did not perform hand-washing when observed. Fifty per cent of persons that reported never recapping needles were observed to recap needles by hand. CONCLUSION: The study revealed that compliance among staff in the Emergency Room with universal precautions was unsatisfactory. The need for education in this area was recognized.

Age, Gender, and Liver Enzyme Impact Hospital Stay in COVID-19 Minority Patient with Cancer in the USA: Does Race Matters in the Pandemic?

Patients with cancer are known to have a poor prognosis when infected with SARS-CoV-2 infection. We aimed in this study to assess health outcomes in COVID-19 patients with different cancers in comparison to non-cancer COVID-19 patients from different centers in the United States (US). We evaluated medical records of 1,943 COVID-19 Cancer patients from 3 hospitals admitted between December 2019 to October 2021 and compared them with non-cancer COVID-19 patients. Among 1,943 hospitalized COVID-19 patients, 18.7% (n=364) have an active or previous history of cancer. Among these 364 cancer patients, 222 were African Americans (61.7%) and 121 were Caucasians (33.2%). Cancer patients had significantly longer hospitalization compared to controls (8.24 vs 6.7 days). Overall, Lung cancer is associated with high mortality. Patients with a previous history of cancer were more prone to death (p=0.04) than active cancer patients. In univariate and multivariate analyses, predictors of death among cancer patients were male sex, older age, presence of dyspnea, elevated troponin, elevated AST (0.001) and ALT (0.05), low albumin (p=0.04) and mechanical ventilation (p=0.001). Patients with a previous history of cancer were more prone to death when compared to active cancer COVID-19 patients. Early recognition of cancer COVID-19 patients' death-associated risk factors can help determine appropriate treatment and management plans for better prognosis and outcome.

Long-term effects of the Diabetes Prevention Program interventions on cardiovascular risk factors: a report from the DPP Outcomes Study.

AIMS: Whether long-term cardiovascular risk is reduced by the Diabetes Prevention Program interventions is unknown. The aim of this study was to determine the long-term differences in cardiovascular disease risk factors and the use of lipid and blood pressure medications by the original Diabetes Prevention Program intervention group. METHODS: This long-term follow-up (median 10 years, interquartile range 9.0-10.5) of the three-arm Diabetes Prevention Program randomized controlled clinical trial (metformin, intensive lifestyle and placebo), performed on 2766 (88%) of the Diabetes Prevention Program participants (who originally had impaired glucose tolerance), comprised a mean of 3.2 years of randomized treatment, approximately 1-year transition (during which all participants were offered intensive lifestyle intervention) and 5 years follow-up (Diabetes Prevention Program Outcomes Study). During the study, participants were followed in their original groups with their clinical care being provided by practitioners outside the research setting. The study determined lipoprotein profiles and blood pressure and medication use annually. RESULTS: After 10 years' follow-up from Diabetes Prevention Program baseline, major reductions were seen for systolic (-2 to -3) and diastolic (-6 to -6.5 mmHg) blood pressure, and for LDL cholesterol (-0.51 to -0.6 mmol/l) and triglycerides (-0.23 to -0.25 mmol/l) in all groups, with no between-group differences. HDL cholesterol also rose significantly (0.14 to 0.15 mmol/l) in all groups. Lipid (P = 0.01) and blood pressure (P = 0.09) medication use, however, were lower for the lifestyle group during the Diabetes Prevention Program Outcomes Study. CONCLUSION: Overall, intensive lifestyle intervention achieved, with less medication, a comparable long-term effect on cardiovascular disease risk factors, to that seen in the metformin and placebo groups.

Feasibility of an obesity intervention for paediatric primary care targeting parenting and children: Helping HAND.

BACKGROUND: The primary care setting offers the opportunity to reach children and parents to encourage healthy lifestyle behaviours, and improve weight status among children. OBJECTIVE: Test the feasibility of Helping HAND (Healthy Activity and Nutrition Directions), an obesity intervention for 5- to 8-year-old children in primary care clinics. METHODS: A randomized controlled pilot study of Helping HAND, a 6-month intervention, targeted children with body mass index 85-99%tile and their parents. Intervention group attended monthly sessions and self-selected child behaviours and parenting practices to change. Control group received regular paediatric care and was wait-listed for Helping HAND. Session completion, participant satisfaction, child anthropometrics, dietary intake, physical activity, TV viewing and behaviour-specific parenting practices were measured pre and post intervention. RESULTS: Forty parent-child dyads enrolled: 82.5% were Hispanic, 80% had a girl and 65% reported income ≤ $30, 000/year. There was 20% attrition from Helping HAND (attended <4/6 sessions). Families self-selected 4.35 (SD 1.75) behaviours to target during the 6-month programme and each of the seven behaviours was selected by 45-80% of the families. There were no between group differences in the child's body mass index z-score, dietary intake or physical activity post intervention. Intervention group viewed 14.9 (SE 2.3) h/week of TV post intervention versus control group 23.3 (SE 2.4) h/week (P < 0.05). CONCLUSION: Helping HAND is feasible, due to low attrition, good programme attendance, and clinically relevant improvements in some child and parenting behaviours.

Gold and iron oxide hybrid nanocomposite materials.

This critical review provides an overview of current research activities that focused on the synthesis and application of multi-functional gold and iron oxide (Au-Fe(x)O(y)) hybrid nanoparticles and nanocomposites. An introduction of synthetic strategies that have been developed for generating Au-Fe(x)O(y) nanocomposites with different nanostructures is presented. Surface functionalisation and bioconjugation of these hybrid nanoparticles and nanocomposites are also reviewed. A variety of applications such as theranostics, gene delivery, biosensing, cell sorting, bio-separation, and catalysis is discussed and highlighted. Finally, future trends and perspectives of these sophisticated nanocomposites are outlined. Underpinning the fundamental requirements for effectively forming Au-Fe(x)O(y) hybrid nanocomposite materials would shed light on future development of nanotheranostics, nanomedicines, and chemical technologies. It would be interesting to investigate such multi-component composite nanomaterials with different novel morphologies in the near future to advance chemistry, biology, medicine, and engineering multi-disciplinary research (120 references).

Accuracy of genomic prediction using an evenly spaced, low-density single nucleotide polymorphism panel in broiler chickens.

One approach for cost-effective implementation of genomic selection is to genotype training individuals with a high-density (HD) panel and selection candidates with an evenly spaced, low-density (ELD) panel. The purpose of this study was to evaluate the extent to which the ELD approach reduces the accuracy of genomic estimated breeding values (GEBV) in a broiler line, in which 1,091 breeders from 3 generations were used for training and 160 progeny of the third generation for validation. All birds were genotyped with an Illumina Infinium platform HD panel that included 20,541 segregating markers. Two subsets of HD markers, with 377 (ELD-1) or 766 (ELD-2) markers, were selected as ELD panels. The ELD-1 panel was genotyped using KBiosciences KASPar SNP genotyping chemistry, whereas the ELD-2 panel was simulated by adding markers from the HD panel to the ELD-1 panel. The training data set was used for 2 traits: BW at 35 d on both sexes and hen house production (HHP) between wk 28 and 54. Methods Bayes-A, -B, -C and genomic best linear unbiased prediction were used to estimate HD-marker effects. Two scenarios were used: (1) the 160 progeny were ELD-genotyped, and (2) the 160 progeny and their dams (117 birds) were ELD-genotyped. The missing HD genotypes in ELD-genotyped birds were imputed by a Gibbs sampler, capitalizing on linkage within families. In scenario (1), the correlation of GEBV for BW (HHP) of the 160 progeny based on observed HD versus imputed genotypes was greater than 0.94 (0.98) with the ELD-1 panel and greater than 0.97 (0.99) with the ELD-2 panel. In scenario (2), the correlation of GEBV for BW (HHP) was greater than 0.92 (0.96) with the ELD-1 panel and greater than 0.95 (0.98) with the ELD-2 panel. Hence, in a pedigreed population, genomic selection can be implemented by genotyping selection candidates with about 400 ELD markers with less than 6% loss in accuracy. This leads to substantial savings in genotyping costs, with little sacrifice in accuracy.

Subclinical atherosclerosis, airflow obstruction and emphysema: the MESA Lung Study.

Airflow obstruction is an independent risk factor for cardiovascular events in the general population. The affected vascular bed and contribution of emphysema to cardiovascular risk are unclear. We examined whether an obstructive pattern of spirometry and quantitatively defined emphysema were associated with subclinical atherosclerosis in the carotid, peripheral and coronary circulations. The Multi-Ethnic Study of Atherosclerosis recruited participants aged 45-84 yrs without clinical cardiovascular disease. Spirometry, carotid intima-media thickness (IMT), ankle-brachial index (ABI) and coronary artery calcium (CAC) were measured using standard protocols. Percentage of emphysema-like lung was measured in the lung windows of cardiac computed tomography scans among 3,642 participants. Multiple linear regression was used to adjust for cardiac risk factors, including C-reactive protein. Decrements in forced expiratory volume in 1 s (FEV(1)) and FEV(1)/forced vital capacity ratio were associated with greater internal carotid IMT, particularly among smokers (p=0.03 and p<0.001, respectively) whereas percentage emphysema was associated with reduced ABI regardless of smoking history (p=0.004). CAC was associated with neither lung function (prevalence ratio for the presence of CAC in severe airflow obstruction 0.99, 95% CI 0.91-1.07) nor percentage emphysema. An obstructive pattern of spirometry and emphysema were associated distinctly and independently with subclinical atherosclerosis in the carotid arteries and peripheral circulation, respectively, and were not independently related to CAC.

Challenges for synthesising data in a network of registries for systemic psoriasis therapies.

BACKGROUND: Large disease registries are the preferred method to assess long-term treatment safety. If psoriasis registries collaborate in a network, their power to assess safety is increased. OBJECTIVE: To identify heterogeneity in psoriasis registries and methodological challenges for synthesising the data they provide. METHODS: We surveyed the registries in PSONET and identified and addressed the challenges to collaborative analysis for the network in several round table meetings. RESULTS: Eight out of 10 registries had a prospective comparator cohort with similar disease characteristics but not on biologics. Registries differed in the coding and validation or follow-up of adverse events and in the way they sampled their population. Fifteen challenges to registries collaborating were identified in the areas of operational governance, structural conduct, bias and analysis. CONCLUSIONS: Participation in PSONET, a network of psoriasis registries, helps identify and solve common issues, enhancing the individual registries, and provides larger sets of more powerful safety data in a diverse population. Challenges to interpreting data collectively include heterogeneity in sampling, variable penetration of biologics and compatibility of different datasets.

Strategies for the removal of halides from drinking water sources, and their applicability in disinfection by-product minimisation: a critical review.

The presence of bromide (Br(-)) and iodide (I(-)) in source waters leads to the formation of brominated and iodinated disinfection by-products (DBPs), which are often more toxic than their chlorinated analogues. The increasing scarcity of water resources in Australia is leading to use of impaired and alternative water supplies with high bromide and iodide levels, which may result in the production of more brominated and iodinated DBPs. This review aims to provide a summary of research into bromide and iodide removal from drinking water sources. Bromide and iodide removal techniques have been broadly classified into three categories, namely; membrane, electrochemical and adsorptive techniques. Reverse osmosis, nanofiltration and electrodialysis membrane techniques are reviewed. The electrochemical techniques discussed are electrolysis, capacitive deionization and membrane capacitive deionization. Studies on bromide and iodide removal using adsorptive techniques including; layered double hydroxides, impregnated activated carbons, carbon aerogels, ion exchange resins, aluminium coagulation and soils are also assessed. Halide removal techniques have been compared, and areas for future research have been identified.

Risk of septic arthritis in patients with rheumatoid arthritis and the effect of anti-TNF therapy: results from the British Society for Rheumatology Biologics Register.

OBJECTIVES: To evaluate the risk of septic arthritis (SA) in patients with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) therapy. METHODS: Using data from the British Society for Rheumatology Biologics Register, a prospective observational study, the authors compared the risk of SA between 11 881 anti-TNF-treated and 3673 non-biological disease-modifying antirheumatic drug (nbDMARD)-treated patients. RESULTS: 199 patients had at least one episode of SA (anti-TNF: 179, nbDMARD: 20). Incidence rates were: anti-TNF 4.2/1000 patient years (pyrs) follow-up (95% CI 3.6 to 4.8), nbDMARD 1.8/1000 pyrs (95% CI 1.1 to 2.7). The adjusted HR for SA in the anti-TNF cohort was 2.3 (95% CI 1.2 to 4.4). The risk did not differ significantly between the three agents: adalimumab, etanercept and infliximab. The risk was highest in the early months of therapy. The patterns of reported organisms differed in the anti-TNF cohort. Prior joint replacement surgery was a risk factor for SA in all patients. The rate of postoperative joint infection (within 90 days of surgery) was 0.7%. This risk was not significantly influenced by anti-TNF therapy. CONCLUSIONS: Anti-TNF therapy use in RA is associated with a doubling in the risk of SA. Physicians and surgeons assessing the RA patient should be aware of this potentially life-threatening complication.

Synthesis of Functional Building Blocks for Type III-B Rotaxane Dendrimer.

Second-generation type III-B rotaxane dendrons, equipped with succinimide and acetylene functional groups, were synthesized successfully and characterized by NMR spectroscopy and mass spectrometry. A cell viability study of a dendron with a normal cell line of L929 fibroblast cells revealed no obvious cytotoxicity at a range of 5 to 100 µM. The nontoxic properties of the sophisticated rotaxane dendron building blocks provided a choice of bio-compatible macromolecular machines that could be potentially developed into polymeric materials.