How do nematodes transfer phosphorylcholine to carbohydrates?

An unusual aspect of the biology of nematodes is the attachment of phosphorylcholine (PC) to carbohydrate. The attachment appears to play an important role in nematode development and, in some parasitic species, in immunomodulation. This article considers the nature of the biosynthetic pathway of nematode PC-containing glycoconjugates and, in particular, the identity of the final component in the pathway - the enzyme that transfers PC to carbohydrate (the 'PC transferase'). We offer the opinion that the PC transferase could be a member of the fukutin family (fukutin refers to the mutated gene product that causes Fukuyama congenital muscular dystrophy), a group of enzymes with apparent phosphoryl-ligand transferase activity that are found in organisms ranging from bacteria to humans

Impact of Continuous Flow Left Ventricular Assist Device Therapy on Chronic Kidney Disease: A Longitudinal Multicenter Study

Background: Many patients undergoing durable left ventricular assist device (LVAD) implantation suffer from chronic kidney disease (CKD). Therefore, we investigated the effect of LVAD support on CKD. Methods: A retrospective multicenter cohort study, including all patients undergoing LVAD (HeartMate II (n = 330), HeartMate 3 (n = 22) and HeartWare (n = 48) implantation. In total, 227 (56.8%) patients were implanted as bridge-to-transplantation; 154 (38.5%) as destination therapy; and 19 (4.7%) as bridge-to-decision. Serum creatinine measurements were collected over a 2-year follow-up period. Patients were stratified based on CKD stage. Results: Overall, 400 patients (mean age 53 ± 14 years, 75% male) were included: 186 (46.5%) patients had CKD stage 1 or 2; 93 (23.3%) had CKD stage 3a; 82 (20.5%) had CKD stage 3b; and 39 (9.8%) had CKD stage 4 or 5 prior to LVAD implantation. During a median follow-up of 179 days (IQR 28–627), 32,629 creatinine measurements were available. Improvement of kidney function was noticed in every preoperative CKD-stage group. Following this improvement, estimated glomerular filtration rates regressed to baseline values for all CKD stages. Patients showing early renal function improvement were younger and in worse preoperative condition. Moreover, survival rates were higher in patients showing early improvement (69% vs 56%, log-rank P = 0.013). Conclusions: Renal function following LVAD implantation is characterized by improvement, steady state and subsequent deterioration. Patients who showed early renal function improvement were in worse preoperative condition, however, and had higher survival rates at 2 years of follow-up

Global Research Priorities to Better Understand the Burden of Iatrogenic Harm in Primary Care: An International Delphi Exercise

There is a need to identify and reach agreement on key foci for patient safety research in primary care contexts and understand how these priorities differ between low-, middle-, and high-income settings. We conducted a modified Delphi exercise, which was distributed to an international panel of experts in patient safety and primary care. Family practice and pharmacy were considered the main contexts on which to focus attention in order to advance patient safety in primary care across all income categories. Other clinical contexts prioritised included community midwifery and nursing in low-income countries and care homes in high-income countries. The sources of patient safety incidents requiring further study across all economic settings that were identified were communication between health care professionals and with patients, teamwork within the health care team, laboratory and diagnostic imaging investigations, issues relating to data management, transitions between different care settings, and chart/patient record com- pleteness. This work lays the foundation for a range of research initiatives that aim to promote a more comprehensive appreciation of the burden of unsafe primary care, develop understanding of the main areas of risk, and identify interventions that can enhance the safety of primary care provision internationall

A simplified (modified) Duke Activity Status Index (M-DASI) to characterise functional capacity: A secondary analysis of the Measurement of Exercise Tolerance before Surgery (METS) study

Background Accurate assessment of functional capacity, a predictor of postoperative morbidity and mortality, is essential to improving surgical planning and outcomes. We assessed if all 12 items of the Duke Activity Status Index (DASI) were equally important in reflecting exercise capacity. Methods In this secondary cross-sectional analysis of the international, multicentre Measurement of Exercise Tolerance before Surgery (METS) study, we assessed cardiopulmonary exercise testing and DASI data from 1455 participants. Multivariable regression analyses were used to revise the DASI model in predicting an anaerobic threshold (AT) >11 ml kg −1 min −1 and peak oxygen consumption (VO 2 peak) >16 ml kg −1 min −1, cut-points that represent a reduced risk of postoperative complications. Results Five questions were identified to have dominance in predicting AT>11 ml kg −1 min −1 and VO 2 peak>16 ml.kg −1min −1. These items were included in the M-DASI-5Q and retained utility in predicting AT>11 ml.kg −1.min −1 (area under the receiver-operating-characteristic [AUROC]-AT: M-DASI-5Q=0.67 vs original 12-question DASI=0.66) and VO 2 peak (AUROC-VO2 peak: M-DASI-5Q 0.73 vs original 12-question DASI 0.71). Conversely, in a sensitivity analysis we removed one potentially sensitive question related to the ability to have sexual relations, and the ability of the remaining four questions (M-DASI-4Q) to predict an adequate functional threshold remained no worse than the original 12-question DASI model. Adding a dynamic component to the M-DASI-4Q by assessing the chronotropic response to exercise improved its ability to discriminate between those with VO 2 peak>16 ml.kg −1.min −1 and VO 2 peak<16 ml.kg −1.min −1. Conclusions The M-DASI provides a simple screening tool for further preoperative evaluation, including with cardiopulmonary exercise testing, to guide perioperative management

Variation in the nature of attachment of phosphorylcholine to excretory–secretory products of adult Brugia pahangi

The mechanism of linkage of phosphorylcholine (PC) to excretory–secretory products (ES) of adult Brugia pahangi has been investigated. Biosynthetic radio-isotope labelling of ES with [3H]choline followed by SDS–PAGE/fluorography revealed a smear of molecular weight approximately 40–100 kDa which loses its radiolabel following exposure to N-glycosidase F, but not mild alkali. PC is thus attached to this smear of molecules via N-type glycans, a mechanism of linkage previously observed with respect to PC–ES of Acanthocheilonema viteae. Western blotting analysis of non-radiolabelled ES demonstrated the existence of additional PC–ES which were insensitive to N-glycosidase F, but not to alkali. This second group of molecules is therefore likely to contain PC linked to O-glycans. Filarial nematodes may thus utilize 2 classes of glycan for attachment of PC. Examination of B. pahangi and A. viteae whole worm extracts by Western blotting indicated that their PC content could not be cleaved by N-glycosidase F and hence the use of N-type glycans may be restricted to a subset of ES products. The implications of these findings with respect to developing inhibitors of PC attachment for use as anti-filarial drugs are discussed

Some preliminary data on the nature/structure of the PC-glycan of the major excretory-secretory product of

The structure of the PC-glycan of the major excretory-secretory product (ES-62) of Acanthocheilonema viteae has been investigated using endoglycosidases and lectins. Results obtained raise the possibility that it may be of the high mannose type. This, and the insensitivity of the PC-glycan to treatments which remove PC or choline from bacterial PC-glycans, suggests that it may be more analogous to fungal, than to bacterial PC-containing glycans

Preliminary data on the nature/structure of the pc-glycan of the major excretory-secretory product of

The structure of the PC-glycan of the major excretory-secretory product (ES-62) of Acanthocheilonema viteae has been investigated using endoglycosidases and lectins. Results obtained raise the possibility that it may be of the high mannose type. This, and the insensitivity of the PC-glycan to treatments which remove PC or choline from bacterial PC-glycans, suggests that it may be more analogous to fungal, than to bacterial PC-containing glycans