Characteristics of balance control in older persons who fall with injury – A prospective study

ObjectiveOlder adults who have recently fallen demonstrate increased postural sway compared with non-fallers. However, the differences in postural control between older adults who were seriously injured (SI) as a result of a fall, compared with those who fell but were not injured (NSI) and non-fallers (NFs), has not been investigated. The objective of the present study was to investigate the underlying postural control mechanisms related to injuries resulting from a fall.MethodsBoth traditional postural sway measures of foot center-of-pressure (CoP) displacements and fractal measures, the Stabilogram-Diffusion Analysis (SDA), were used to characterize the postural control. One hundred older adults aged 65–91 years were tested during narrow base upright stance in eyes closed condition; falls were monitored over a 1-year period.ResultsForty-nine older adults fell during the 1-year follow-up, 13 were seriously injured as a result of a fall (SI), 36 were not injured (NSI), and 49 were non-fallers (NFs); two passed away. The SDA showed significantly higher short-term diffusion coefficients and critical displacements in SI in the anterior–posterior direction compared with both NSI and NF. However, in the medio-lateral direction there were no statistically significant differences between groups. For the traditional measures of sway, the average anterior–posterior CoP range was also larger in SI individuals.ConclusionsThis work suggests that older fallers with a deterioration of anterior–posterior postural control may be at higher risk of serious injury following fall events.     

Cluster analysis of pressure pain threshold maps from the trapezius muscle

The aim of this study was to investigate and present a new mapping method to describe muscle pain sensitivity based on the assessment of pressure pain threshold (PPT) over the trapezius muscle. PPT data were recorded from 36 points in 20 healthy males using a standardised grid. Points were clustered using the K-means algorithm with a fixed initialisation procedure. The total number of clusters was determined on the basis of (1) R ² evaluation of the clustering outcome compared against a desired 95% reduction in variance criterion and (2) the number of empty clusters. A minimum of three clusters were found which fulfilled the criteria. The proposed method enables the identification of a relation between the muscle subdivisions and pressure pain sensitivity within the trapezius. Further, the cluster analysis will enable the study of differences in pain sensitivity distributions between patients and controls and quantify the effect of intervention (physical or pharmacological treatments).     

With or Without Sugar? (A)glycosylation of Therapeutic Antibodies

Antibodies and antibody-based drugs are currently the fastest-growing class of therapeutics. Over the last three decades, more than 30 therapeutic monoclonal antibodies and derivatives thereof have been approved for and successfully applied in diverse indication areas including cancer, organ transplants, autoimmune/inflammatory disorders, and cardiovascular disease. The isotype of choice for antibody therapeutics is human IgG, whose Fc region contains a ubiquitous asparagine residue (N₂₉₇) that acts as an acceptor site for N-linked glycans. The nature of these glycans can decisively influence the therapeutic performance of a recombinant antibody, and their absence or modification can lead to the loss of Fc effector functions, greater immunogenicity, and unfavorable pharmacokinetic profiles. However, recent studies have shown that aglycosylated antibodies can be genetically engineered to display novel or enhanced effector functions and that favorable pharmacokinetic properties can be preserved. Furthermore, the ability to produce aglycosylated antibodies in lower eukaryotes and bacteria offers the potential to broaden and simplify the production platforms and avoid the problem of antibody heterogeneity, which occurs when mammalian cells are used for production. In this review, we discuss the importance of Fc glycosylation focusing on the use of aglycosylated and glyco-engineered antibodies as therapeutic proteins.     

eScience and the need for data standards in the life sciences: in pursuit of objectivity rather than truth

Referring to European history of natural sciences as an example, I discuss the relation between development of standards and the emergence of new epistemic virtues. I distinguish standards relating to scientific argumentation from standards relating to data production. The former are based on truth-seeking epistemic virtues and use criteria of logical coherence and empirical grounding. They are important for the justification of an explanatory hypothesis. Data and metadata standards, on the other hand, concern the data record itself and all steps and actions taken during data production and are based on virtues of objectivity. In the second part I focus on data and metadata standards and argue that, in order to meet the requirements of eScience, the specification of the currently popular minimum information checklists should be complemented to cover four aspects: (i) content standards, which increase reproducibility and operational transparency of data production, (ii) concept standards, which increase the semantic transparency of the terms used in data records, (iii) nomenclatural standards, which provide stable and unambiguous links between the terms used and their underlying definitions or their real referents, and (iv) format standards, which increase compatibility and computer-parsability of data records. I discuss the role of scientific terminology for standardizing data and the need for using semantically standardized and formalized data-reporting languages in the form of controlled vocabularies and ontologies for establishing content standards for data in the life sciences. Finally I comment on the necessity of community participation in the development and application of standards and in making data openly available.     

Clinical-scale generation of multi-specific anti-fungal T cells targeting Candida,Aspergillus and mucormycetes

Background aimsInvasive fungal infections, in particular, infections caused by Candida, Aspergillus and mucormycetes, are a major cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation. Adoptive transfer of donor-derived anti-fungal T cells shows promise to restore immunity and to offer a cure. Because T cells recognize only specific epitopes, the low rate of patients in which the causal fungal pathogen can be identified and the considerable number of patients with co-infection with several genera or species of fungi significantly limit the application of adoptive immunotherapy.MethodsUsing the interferon-γ secretion assay, we isolated multi-specific human anti-fungal T cells after simultaneous stimulation with cellular extracts of Aspergillus fumigatus, Candida albicans and Rhizopus oryzae. Cells were phenotypically and functionally characterized by flow cytometry.ResultsOf a total of 1.1 × 10⁹ peripheral blood mononuclear cells, a median number of 5.2 × 10⁷ CD3⁺CD4⁺ T cells was generated within 12 days. This cell population consisted of activated memory T_H1 cells and reproducibly responded to a multitude of Aspergillus spp., Candida spp. and mucormycetes with interferon-γ production. On re-stimulation, the generated T cells proliferated and enhanced anti-fungal activity of phagocytes and showed reduced alloreactivity compared with the original cell fraction.ConclusionsOur rapid and simple method of simultaneously generating functionally active multi-specific T cells that recognize a wide variety of medically relevant fungi may form the basis for future clinical trials investigating adoptive immunotherapy in allogeneic hematopoietic stem cell transplantation recipients with invasive fungal infection.     

Studying Biomolecule Localization by Engineering Bacterial Cell Wall Curvature

In this article we describe two techniques for exploring the relationship between bacterial cell shape and the intracellular organization of proteins. First, we created microchannels in a layer of agarose to reshape live bacterial cells and predictably control their mean cell wall curvature, and quantified the influence of curvature on the localization and distribution of proteins in vivo. Second, we used agarose microchambers to reshape bacteria whose cell wall had been chemically and enzymatically removed. By combining microstructures with different geometries and fluorescence microscopy, we determined the relationship between bacterial shape and the localization for two different membrane-associated proteins: i) the cell-shape related protein MreB of Escherichia coli, which is positioned along the long axis of the rod-shaped cell; and ii) the negative curvature-sensing cell division protein DivIVA of Bacillus subtilis, which is positioned primarily at cell division sites. Our studies of intracellular organization in live cells of E. coli and B. subtilis demonstrate that MreB is largely excluded from areas of high negative curvature, whereas DivIVA localizes preferentially to regions of high negative curvature. These studies highlight a unique approach for studying the relationship between cell shape and intracellular organization in intact, live bacteria.     

The Use of Molecular Analyses in Voided Urine for the Assessment of Patients with Hematuria

Introduction

Patients presenting with painless hematuria form a large part of the urological patient population. In many cases, especially in younger patients, the cause of hematuria is harmless. Nonetheless, hematuria could be a symptom of malignant disease and hence most patients will be subject to cystoscopy. In this study, we aimed to develop a prediction model based on methylation markers in combination with clinical variables, in order to stratify patients with high risk for bladder cancer.

Material and Methods

Patients (n=169) presenting with painless hematuria were included. 54 patients were diagnosed with bladder cancer. In the remaining 115 patients, the cause of hematuria was non-malignant. Urine samples were collected prior to cystoscopy. Urine DNA was analyzed for methylation of OSR1, SIM2, OTX1, MEIS1 and ONECUT2. Methylation percentages were calculated and were combined with clinical variables into a logistic regression model.

Results

Logistic regression analysis based on the five methylation markers, age, gender and type of hematuria resulted in an area under the curve (AUC) of 0.88 and an optimism corrected AUC of 0.84 after internal validation by bootstrapping. Using a cut-off value of 0.307 allowed stratification of patients in a low-risk and high-risk group, resulting in a sensitivity of 82% (44/54) and a specificity of 82% (94/115). Most aggressive tumors were found in patients in the high-risk group. The addition of cytology to the prediction model, improved the AUC from 0.88 to 0.89, with a sensitivity and specificity of 85% (39/46) and 87% (80/92), retrospectively.

Conclusions

This newly developed prediction model could be a helpful tool in risk stratification of patients presenting with painless hematuria. Accurate risk prediction might result in less extensive examination of low risk patients and thereby, reducing patient burden and costs. Further validation in a large prospective patient cohort is necessary to prove the true clinical value of this model.