Wearable gait analysis systems: ready to be used by medical practitioners in geriatric wards?

PURPOSE: We assess feasibility of wearable gait analysis in geriatric wards by testing the effectiveness and acceptance of the system. METHODS: Gait parameters of 83 patients (83.34 ± 5.88 years, 58/25 female/male) were recorded at admission and/or discharge to/from two geriatric inpatient wards. Gait parameters were tested for statistically significant differences between admission and discharge. Walking distance measured by a wearable gait analysis system was correlated with distance assessed by physiotherapists. Examiners rated usability using the system usability scale. Patients reported acceptability on a five-point Likert-scale. RESULTS: The total distance measures highly correlate (r = 0.89). System Usability Scale is above the median threshold of 68, indicating good usability. Majority of patients does not have objections regarding the use of the system. Among other gait parameters, mean heel strike angle changes significantly between admission and discharge. CONCLUSION: Wearable gait analysis system is objectively and subjectively usable in a clinical setting and accepted by patients. It offers a reasonably valid assessment of gait parameters and is a feasible way for instrumented gait analysis.

An Extensive Quality Control and Quality Assurance (QC/QA) Program Significantly Improves Inter-Laboratory Concordance Rates of Flow-Cytometric Minimal Residual Disease Assessment in Acute Lymphoblastic Leukemia: An I-BFM-FLOW-Network Report.

Monitoring of minimal residual disease (MRD) by flow cytometry (FCM) is a powerful prognostic tool for predicting outcomes in acute lymphoblastic leukemia (ALL). To apply FCM-MRD in large, collaborative trials, dedicated laboratory staff must be educated to concordantly high levels of expertise and their performance quality should be continuously monitored. We sought to install a unique and comprehensive training and quality control (QC) program involving a large number of reference laboratories within the international Berlin-Frankfurt-Münster (I-BFM) consortium, in order to complement the standardization of the methodology with an educational component and persistent quality control measures. Our QC and quality assurance (QA) program is based on four major cornerstones: (i) a twinning maturation program, (ii) obligatory participation in external QA programs (spiked sample send around, United Kingdom National External Quality Assessment Service (UK NEQAS)), (iii) regular participation in list-mode-data (LMD) file ring trials (FCM data file send arounds), and (iv) surveys of independent data derived from trial results. We demonstrate that the training of laboratories using experienced twinning partners, along with continuous educational feedback significantly improves the performance of laboratories in detecting and quantifying MRD in pediatric ALL patients. Overall, our extensive education and quality control program improved inter-laboratory concordance rates of FCM-MRD assessments and ultimately led to a very high conformity of risk estimates in independent patient cohorts.

The hematopoietic stem cell marker VNN2 is associated with chemoresistance in pediatric B-cell precursor ALL.

Most relapses of acute lymphoblastic leukemia (ALL) occur in patients with a medium risk (MR) for relapse on the Associazione Italiana di Ematologia e Oncologia Pediatrica and Berlin-Frankfurt-Münster (AIEOP-BFM) ALL protocol, based on persistence of minimal residual disease (MRD). New insights into biological features that are associated with MRD are needed. Here, we identify the glycosylphosphatidylinositol-anchored cell surface protein vanin-2 (VNN2; GPI-80) by charting the cell surface proteome of MRD very high-risk (HR) B-cell precursor (BCP) ALL using a chemoproteomics strategy. The correlation between VNN2 transcript and surface protein expression enabled a retrospective analysis (ALL-BFM 2000; N = 770 cases) using quantitative polymerase chain reaction to confirm the association of VNN2 with MRD and independent prediction of worse outcome. Using flow cytometry, we detected VNN2 expression in 2 waves, in human adult bone marrow stem and progenitor cells and in the mature myeloid compartment, in line with proposed roles for fetal hematopoietic stem cells and inflammation. Prospective validation by flow cytometry in the ongoing clinical trial (AIEOP-BFM 2009) identified 10% (103/1069) of VNN2+ BCP ALL patients at first diagnosis, primarily in the MRD MR (48/103, 47%) and HR (37/103, 36%) groups, across various cytogenetic subtypes. We also detected frequent mutations in epigenetic regulators in VNN2+ ALLs, including histone H3 methyltransferases MLL2, SETD2, and EZH2 and demethylase KDM6A. Inactivation of the VNN2 gene did not impair leukemia repopulation capacity in xenografts. Taken together, VNN2 marks a cellular state of increased resistance to chemotherapy that warrants further investigations. Therefore, this marker should be included in diagnostic flow cytometry panels.

CASEPLUS-SimPat: An Intersectoral Web-Based Case Management System for Multimorbid Dementia Patients.

One main challenge of health care systems in future will be the care and treatment of dementia patients. To their advanced age, dementia patients do not only have limitations in cognition, perception, and articulation, but also suffer from several other diseases (multimorbidity). These patients have sophisticated needs for assistance, care, and treatment relying on different health care sectors. Well-known communication and coordination deficits between sectors are intensified in the case of dementia, to the above described limitations. Coordination processes concerning the transition of patients from hospitals to inpatient or outpatient aftercare pose particularly difficult. To show a possible future direction for improving intersectoral care of dementia patients, we developed the web-based case management system CASEPLUS-SimPat as part of the project SimPat "Securing Integrated Care for Multi-morbid Patients with Dementia using an IT-based Service Concept". CASEPLUS-SimPat allows health care professionals, hospital employees and general practitioners, to jointly access patient data and exchange information about the treatment of patients. The case management system was implemented in a three-tier architecture with a role-based authorization concept. A portal for relatives complements the system. By providing precise information and e-learning services, caring relatives are integrated into the care process. In a pilot test, CASEPLUS-SimPat shows a good usability. Adapting aspects, such as keywords used to structure entries will make it easier to find required information, and thus will increase usability. Next steps comprise integration of further health care professionals and care facilities as well as real-life testing in terms of feasibility and effectiveness.

Arabidopsis 14-3-3 epsilon members contribute to polarity of PIN auxin carrier and auxin transport-related development.

Eukaryotic 14-3-3 proteins have been implicated in the regulation of diverse biological processes by phosphorylation-dependent protein-protein interactions. The Arabidopsis genome encodes two groups of 14-3-3s, one of which - epsilon - is thought to fulfill conserved cellular functions. Here, we assessed the in vivo role of the ancestral 14-3-3 epsilon group members. Their simultaneous and conditional repression by RNA interference and artificial microRNA in seedlings led to altered distribution patterns of the phytohormone auxin and associated auxin transport-related phenotypes, such as agravitropic growth. Moreover, 14-3-3 epsilon members were required for pronounced polar distribution of PIN-FORMED auxin efflux carriers within the plasma membrane. Defects in defined post-Golgi trafficking processes proved causal for this phenotype and might be due to lack of direct 14-3-3 interactions with factors crucial for membrane trafficking. Taken together, our data demonstrate a fundamental role for the ancient 14-3-3 epsilon group members in regulating PIN polarity and plant development.

Polarized Defense Against Fungal Pathogens Is Mediated by the Jacalin-Related Lectin Domain of Modular Poaceae-Specific Proteins.

Modular proteins are an evolutionary answer to optimize performance of proteins that physically interact with each other for functionality. Using a combination of genetic and biochemical experiments, we characterized the rice protein OsJAC1, which consists of a jacalin-related lectin (JRL) domain predicted to bind mannose-containing oligosaccharides, and a dirigent domain which might function in stereoselective coupling of monolignols. Transgenic overexpression of OsJAC1 in rice resulted in quantitative broad-spectrum resistance against different pathogens including bacteria, oomycetes, and fungi. Overexpression of this gene or its wheat ortholog TAJA1 in barley enhanced resistance against the powdery mildew fungus. Both protein domains of OsJAC1 are required to establish resistance as indicated by single or combined transient expression of individual domains. Expression of artificially separated and fluorescence-tagged protein domains showed that the JRL domain is sufficient for targeting the powdery mildew penetration site. Nevertheless, co-localization of the lectin and the dirigent domain occurred. Phylogenetic analyses revealed orthologs of OsJAC1 exclusively within the Poaceae plant family. Dicots, by contrast, only contain proteins with either JRL or dirigent domain(s). Altogether, our results identify OsJAC1 as a representative of a novel type of resistance protein derived from a plant lineage-specific gene fusion event for better function in local pathogen defense.

Separation of cobalt and nickel by solvent extraction with two mutually immiscible ionic liquids.

The proof-of-principle for the separation of metals by solvent extraction using two mutually immiscible ionic liquids is given. Cobalt was extracted from the ionic liquid 1-ethyl-3-methylimidazolium chloride to the ionic liquid trihexyl(tetradecyl)phosphonium bis(2,4,4-trimethylpentyl)phosphinate. A distribution ratio of 44 was obtained. Cobalt could be selectively separated from nickel, with a separation factor of 207. The extraction mechanism was elucidated using UV-VIS absorption measurements. The mutual solubility between the two ionic liquids was determined by (1)H NMR. Processing steps such as washing, stripping and regeneration of the ionic liquid phases are discussed.

Production of yoghurt with mild taste by a Lactobacillus delbrueckii subsp. bulgaricus mutant with altered proteolytic properties.

In this communication, we describe the isolation of a Lactobacillus delbrueckii subsp. bulgaricus 92063 mutant strain named pH-P11, which differed from the parent strain by low proteolytic activity and altered regulation of expression of lacZ in the presence of glucose or lactose. In the presence of lactose, beta-galactosidase activity was approximately twice as high in pH-P11 than in the wild type. pH-P11 exhibited protosymbiosis together with Streptococcus thermophilus. Yoghurt produced with pH-P11 was characterized by low acidity and little post-acidification during storage. The organoleptic properties (absence of bitterness and other off-flavors, weak sourness, and clear yoghurt taste) were those of a typical "yoghurt mild". This mild flavor was achieved at rather high cell counts of lactobacilli even at the end of shelf-life. High cell counts in conjunction with high beta-galactosidase activity make pH-P11 an interesting strain for application in yoghurt especially designed for consumers with lactose malabsorption. In contrast to "yoghurt mild", which is predominantly produced with Lactobacillus acidophilus together with Streptococcus thermophilus, the product obtained by fermentation with pH-P11 and Streptococcus thermophilus concurs with international standards for yoghurt. During frequent sub-culturing, strain pH-P11, which is supposed to differ from the wild type by one or a few so-far-not-characterized mutations, showed sufficient stability for application in industrial production.

The interaction of DOF transcription factors with nucleosomes depends on the positioning of the binding site and is facilitated by maize HMGB5.

The expression of genes involved in C(4) photosynthesis in maize is under tight tissue-specific and light-dependent control. There is strong evidence that this control is at least in part brought about by DOF transcription factors binding to the respective promoters. We analyzed the interaction of DOF1 and DOF2 proteins with a functional and a cryptic endogenous binding site derived from the maize phosphoenolpyruvate carboxylase promoter (-300 bp region) in the nucleosomal context. Various DNA fragments comprising this promoter region were reconstituted into mononucleosomes from purified components, resulting in different positions of the DOF binding sites on the nucleosome surface. Binding of recombinant transcription factors to the different types of nucleosomes was examined using electrophoretic mobility shift assays. Changing the translational position of the binding site on the nucleosome surface strongly affected the efficiency of the interaction with the DOF factors. Deletion of individual recognition motifs revealed a positive impact of DOF protein binding to the main binding site on interactions with the cryptic binding site. The addition of the chromosomal high-mobility group (HMG) protein HMGB5 to the binding reaction mixture facilitated nucleosome binding of the transcription factor independent from the position of the recognition sites. The relevance of the data for the activation of the promoter in vivo is discussed.