Impact of a community-based diabetes self-management support program on adult self-care behaviors.

Diabetes is a chronic condition that has reached epidemic proportions in the United States, affecting nearly 34 million adults, and disproportionately affecting vulnerable populations, such as ethnic minorities, the elderly and individuals with low socioeconomic status. This study addresses the impact of the Health Extension for Diabetes (HED) program, a community-based diabetes self-management support program, on adult diabetes self-care behaviors. The Summary of Diabetes Self-Care Activities (SDSCA) was utilized to evaluate improvement in diabetes self-care behaviors. Descriptive statistics, univariate and multivariable regression models were conducted. Significant increases were observed among program participants (N = 149) in all five subscales of the SDSCA (general diet, specific diet, blood glucose testing, exercise and foot care; P-values < 0.001). A priority of this diabetes education program was helping underserved populations; over half (62%) of participants self-identified as Black/African Americans. After program participation, scores on all SDSCA subscales increased significantly among Black/African Americans (n = 93) by approximately 1 day per week. White/other races (n = 56) showed similar increases in four of the SDSCA subscales post-HED program participation. This study shows that increasing participation in community-based, diabetes self-management support programs, such as HED, can increase engagement in diabetes self-care behaviors among underserved groups.

Short-term effects of simulated microgravity on morphology and gene expression in human breast cancer cells.

INTRODUCTION: Microgravity has been shown to impose various effects on breast cancer cells. We exposed human breast cancer cells to simulated microgravity and studied morphology and alterations in gene expression. MATERIALS AND METHODS: Human breast cancer cells were exposed to simulated microgravity in a random positioning machine (RPM) for 24 h. Morphology was observed under light microscopy, and gene alteration was studied by qPCR. RESULTS: After 24 h, formation of three-dimensional structures (spheroids) occurred. BRCA1 expression was significantly increased (1.9×, p < 0.05) in the adherent cells under simulated microgravity compared to the control. Expression of KRAS was significantly decreased (0.6×, p < 0.05) in the adherent cells compared to the control. VCAM1 was significantly upregulated (6.6×, 2.0×, p < 0.05 each) in the adherent cells under simulated microgravity and in the spheroids. VIM expression was significantly downregulated (0.45×, 0.44×, p < 0.05 each) in the adherent cells under simulated microgravity and in the spheroids. There was no significant alteration in the expression of MAPK1, MMP13, PTEN, and TP53. CONCLUSIONS: Simulated microgravity induces spheroid formation in human breast cancer cells within 24 h and alters gene expression toward modified adhesion properties, enhanced cell repair, and phenotype preservation. Further insights into the underlying mechanisms could open up the way toward new therapies.

fcc-bcc phase transition in plasma crystals using time-resolved measurements.

Three-dimensional plasma crystals are often described as Yukawa systems for which a phase transition between the crystal structures fcc and bcc has been predicted. However, experimental investigations of this transition are missing. We use a fast scanning video camera to record the crystallization process of 70 000 microparticles and investigate the existence of the fcc-bcc phase transition at neutral gas pressures of 30, 40, and 50 Pa. To analyze the crystal, robust phase diagrams with the help of a machine learning algorithm are calculated. This work shows that the phase transition can be investigated experimentally and makes a comparison with numerical results of Yukawa systems. The phase transition is analyzed in dependence on the screening parameter and structural order. We suggest that the transition is an effect of gravitational compression of the plasma crystal. Experimental investigations of the fcc-bcc phase transition will provide an opportunity to estimate the coupling strength Γ by comparison with numerical results of Yukawa systems.

Expression of the CTLA-4 ligand CD86 on plasmacytoid dendritic cells (pDC) predicts risk of disease recurrence after treatment discontinuation in CML.

This corrects the article DOI: 10.1038/leu.2017.9.

Small-scale screening of novel biobased monomers: the curious case of 1,3-cyclopentanediol.

In this work, we report on the small scale polycondensation and consecutive analysis of novel polyesters based on the potentially renewable 1,3-cyclopentanediol (CPdiol). To avoid evaporation of monomers during thin-film polymerization reactions, trimer pre-polyesters have been synthesized from the corresponding acid-chlorides with diol monomers. Polymerization of these trimers was explored by thermogravimetric analysis to identify potential side reactions, and to assess the ideal polymerization temperature. In general we observe that trans-1,3-cyclopentanediol exhibits good thermal stability up to 200 °C, whereas thermal dehydration of the alcohol end-groups occurs upon further heating. In contrast, for cis-1,3-cyclopentanediol, the ester bonds of the cyclopentane end-groups become labile, thereby generating carboxylic acid end-groups, and 3-cyclopentenol already at 180 °C. The thermal dehydration reactions yield double bond end-groups, which in turn facilitate cross-linking through cross-coupling and Diels-Alder reactions, leading to an increase in molecular weight. Despite the limited thermal stability of CPdiol, here we demonstrate that polymerization of CPdiol can successfully be achieved in thin-film polycondensation conditions at 180 °C, yielding molecular weights well above 10 kg mol-1.

Note: Sample holder with open area for increased deposition rate in plasma immersion ion implantation and deposition.

A sample holder with a large open area offers several benefits when used in the process of plasma immersion ion implantation and deposition in which the plasma is generated by a high voltage applied to the sample holder: The ignition voltage of the plasma is lower, and the deposition rate can be several times higher than in the case of a normal plate-like holder. There is a more pronounced edge effect regarding the film thickness. Other film properties are also affected; for diamond-like carbon films, the film structure exhibits more disorder. The hardness of the samples is similar, with the surfaces of the samples being very smooth.

Expression of the CTLA-4 ligand CD86 on plasmacytoid dendritic cells (pDC) predicts risk of disease recurrence after treatment discontinuation in CML.

It is unknown, why only a minority of chronic myeloid leukemia (CML) patients sustains treatment free remission (TFR) after discontinuation of tyrosine kinase inhibitor (TKI) therapy in deep molecular remission (MR). Here we studied, whether expression of the T-cell inhibitory receptor (CTLA-4)-ligand CD86 (B7.2) on plasmacytoid dendritic cells (pDC) affects relapse risk after TKI cessation. CML patients in MR displayed significantly higher CD86+pDC frequencies than normal donors (P<0.0024), whereas TFR patients had consistently low CD86+pDC (n=12). This suggested that low CD86+pDC might be predictive of TFR. Indeed, in a prospective analysis of 122 patients discontinuing their TKI within the EURO-SKI trial, the one-year relapse-free survival (RFS) was 30.1% (95% CI 15.6-47.9) for patients with >95 CD86+pDC per 105 lymphocytes, but 70.0% (95% CI 59.3-78.3) for patients with <95 CD86+pDC (hazard ratio (HR) 3.4, 95%-CI: 1.9-6.0; P<0.0001). Moreover, only patients with <95 CD86+pDC derived a significant benefit from longer (>8 years) TKI exposure before discontinuation (HR 0.3, 95% CI 0.1-0.8; P=0.0263). High CD86+pDC counts significantly correlated with leukemia-specific CD8+ T-cell exhaustion (Spearman correlation: 0.74, 95%-CI: 0.21-0.92; P=0.0098). Our data demonstrate that CML patients with high CD86+pDC counts have a higher risk of relapse after TKI discontinuation.

Machine-learning approach for local classification of crystalline structures in multiphase systems.

Machine learning is one of the most popular fields in computer science and has a vast number of applications. In this work we will propose a method that will use a neural network to locally identify crystal structures in a mixed phase Yukawa system consisting of fcc, hcp, and bcc clusters and disordered particles similar to plasma crystals. We compare our approach to already used methods and show that the quality of identification increases significantly. The technique works very well for highly disturbed lattices and shows a flexible and robust way to classify crystalline structures that can be used by only providing particle positions. This leads to insights into highly disturbed crystalline structures.

Investigation and improvement of three-dimensional plasma crystal analysis.

In this work, existing methods for plasma crystal analysis are investigated using artificial and simulated calibration data, which reproduce a multiphase system consisting of fcc, hcp, and bcc crystal data. Disturbances of the artificial data including Gaussian noise, stretching, and randomly missing particles are used to investigate the methods thoroughly. A popular method, called bond order parameter, has been repeatedly criticized as a structure analysis tool and will be improved with the help of a recent development. The method is called the bcc-sensitive Minkowski structure metric. It enhances robustness and consistency, while remaining compatible with previous bond-order-based results. Also, a promising method rooted in the molecular dynamics community is tested, yielding detailed insight of bond-order-specific drawbacks. With this investigation, the state of three-dimensional plasma crystal analysis will be significantly improved.

Development and evaluation of a secondary reference panel for BCR-ABL1 quantification on the International Scale.

Molecular monitoring of chronic myeloid leukemia patients using robust BCR-ABL1 tests standardized to the International Scale (IS) is key to proper disease management, especially when treatment cessation is considered. Most laboratories currently use a time-consuming sample exchange process with reference laboratories for IS calibration. A World Health Organization (WHO) BCR-ABL1 reference panel was developed (MR(1)-MR(4)), but access to the material is limited. In this study, we describe the development of the first cell-based secondary reference panel that is traceable to and faithfully replicates the WHO panel, with an additional MR(4.5) level. The secondary panel was calibrated to IS using digital PCR with ABL1, BCR and GUSB as reference genes and evaluated by 44 laboratories worldwide. Interestingly, we found that >40% of BCR-ABL1 assays showed signs of inadequate optimization such as poor linearity and suboptimal PCR efficiency. Nonetheless, when optimized sample inputs were used, >60% demonstrated satisfactory IS accuracy, precision and/or MR(4.5) sensitivity, and 58% obtained IS conversion factors from the secondary reference concordant with their current values. Correlation analysis indicated no significant alterations in %BCR-ABL1 results caused by different assay configurations. More assays achieved good precision and/or sensitivity than IS accuracy, indicating the need for better IS calibration mechanisms.

Safety and efficacy of imatinib in CML over a period of 10 years: data from the randomized CML-study IV.

Tyrosine kinase inhibitors (TKI) have changed the natural course of chronic myeloid leukemia (CML). With the advent of second-generation TKI safety and efficacy issues have gained interest. The randomized CML - Study IV was used for a long-term evaluation of imatinib (IM). 1503 patients have received IM, 1379 IM monotherapy. After a median observation of 7.1 years, 965 patients (64%) still received IM. At 10 years, progression-free survival was 82%, overall survival 84%, 59% achieved MR(5), 72% MR(4.5), 81% MR(4), 89% major molecular remission and 92% MR(2) (molecular equivalent to complete cytogenetic remission). All response levels were reached faster with IM800 mg except MR(5). Eight-year probabilities of adverse drug reactions (ADR) were 76%, of grades 3-4 22%, of non-hematologic 73%, and of hematologic 28%. More ADR were observed with IM800 mg and IM400 mg plus interferon α (IFN). Most patients had their first ADR early with decreasing frequency later on. No new late toxicity was observed. ADR to IM are frequent, but mostly mild and manageable, also with IM 800 mg and IM 400 mg+IFN. The deep molecular response rates indicate that most patients are candidates for IM discontinuation. After 10 years, IM continues to be an excellent initial choice for most patients with CML.

Velocity of early BCR-ABL transcript elimination as an optimized predictor of outcome in chronic myeloid leukemia (CML) patients in chronic phase on treatment with imatinib.

UNLABELLED: Early assessment of response at 3 months of tyrosine kinase inhibitor treatment has become an important tool to predict favorable outcome. We sought to investigate the impact of relative changes of BCR-ABL transcript levels within the initial 3 months of therapy. In order to achieve accurate data for high BCR-ABL levels at diagnosis, beta glucuronidase (GUS) was used as a reference gene. Within the German CML-Study IV, samples of 408 imatinib-treated patients were available in a single laboratory for both times, diagnosis and 3 months on treatment. In total, 301 of these were treatment-naïve at sample collection. RESULTS: (i) with regard to absolute transcript levels at diagnosis, no predictive cutoff could be identified; (ii) at 3 months, an individual reduction of BCR-ABL transcripts to the 0.35-fold of baseline level (0.46-log reduction, that is, roughly half-log) separated best (high risk: 16% of patients, 5-year overall survival (OS) 83% vs 98%, hazard ratio (HR) 6.3, P=0.001); (iii) at 3 months, a 6% BCR-ABL(IS) cutoff derived from BCR-ABL/GUS yielded a good and sensitive discrimination (high risk: 22% of patients, 5-year OS 85% vs 98%, HR 6.1, P=0.002). Patients at risk of disease progression can be identified precisely by the lack of a half-log reduction of BCR-ABL transcripts at 3 months.

Expression of transketolase-like gene 1 (TKTL1) depends on disease phase in patients with chronic myeloid leukaemia (CML).

PURPOSE: Overexpression of transketolase-like gene 1 (TKTL1) on RNA and protein level has been linked to tumour progression, metastasis and unfavourable patient outcome in many solid tumours. Chronic myeloid leukaemia (CML) cells show metabolic characteristics resembling deviations observed in TKTL1 overexpressing solid tumour cells. We therefore sought to evaluate TKTL1 gene expression in different phases of CML. METHODS: A total of 120 peripheral blood samples from 69 patients in various phases of CML and 21 healthy individuals were investigated. TKTL1 expression levels were determined by real-time quantitative polymerase chain reaction using LightCycler technology and normalised against beta-glucuronidase expression. RESULTS: A significantly lower TKTL1 expression was found in chronic phase (CP) CML patients compared to healthy controls. Lowest expression levels were observed in patients during blast crisis (BC). Baseline TKTL1 expression in CP patients did not have value in prognostication of subsequent favourable or dismal outcome. Further, more mature granulocytes showed significantly higher TKTL1 expression compared to immature CD34+ and CD34-/CD33+ cells both in healthy controls and in CML patients. CONCLUSION: TKTL1 expression levels appear to decline in the course of CML with lowest levels during BC. A potential reason is a shift of TKTL1-high-expressing mature granulocytes towards TKTL1-low-expressing immature cells and blasts.

Noninvasive protein structural flexibility mapping by bimodal dynamic force microscopy.

Mapping of the protein structural flexibility with sub-2-nm spatial resolution in liquid is achieved by combining bimodal excitation and frequency modulation force microscopy. The excitation of two cantilever eigenmodes in dynamic force microscopy enables the separation between topography and flexibility mapping. We have measured variations of the elastic modulus in a single antibody pentamer from 8 to 18 MPa when the probe is moved from the end of the protein arm to the central protrusion. Bimodal dynamic force microscopy enables us to perform the measurements under very small repulsive loads (30-40 pN).

[Cushing's syndrome with bilateral nodular adrenal enlargement]. / Cushing-Syndrom mit beidseitiger knotiger Nebennierenvergrösserung.

ACTH-independent macronodular bilateral adrenal hyperplasia (AIMAH) is a rare cause of endogenous Cushing's syndrome. Here, massive bilateral adrenal enlargement is accompanied by ACTH-independent hypercortisolism. The detection of ectopic hormone receptors which, according to a new concept, control the cortisol production in AIMAH, offers the opportunity of normalizing the hypercortisolism by pharmacologically influencing the receptor or its ligand. We here present the case of a 46 year old male patient. Using clinical and pharmacological tests we found evidence of ectopic receptors in the AIMAH. After suspicion was erroneously raised that a malignant lesion could be inside of the right adrenal mass, the decision was made to resect both adrenals instead of trying to treat the hypercortisolism by pharmacological means. This surgical approach (bilateral adrenalectomy) has been the standard way of treatment for AIMAH until the new concept of the ectopic receptors was developed.

Automatization of nanotomography.

An approach for automated nanotomography, a layer-by-layer imaging technique based on scanning probe microscopy (SPM), is presented. Stepwise etching and imaging is done in situ in a liquid cell of an SPM. The flow of etching and rinsing solutions after each etching step is controlled with solenoid valves which allow for an automated measuring protocol. The thermal drift and the drift of the piezo scanner is corrected by applying offsets calculated from the cross correlation coefficients between successive images. As an example, we have imaged human bone with approximately 10 nm resolution using tapping mode SPM and successive etching with hydrochloric acid.

[Sexual medicine in primary care--development in the years 1980-1990-2004]. / Sexualmedizin in der ärztlichen Grundversorgung: Entwicklungen 1980-1990-2004.

Sexual disorders are common in community samples. Even so these problems are not often addressed by primary care physicians. In 1980, 1990, and 2004 three cohorts of primary care physicians in the German speaking part of Switzerland were asked to answer a questionnaire on the prevalence of sexual problems and disorders in their patients and their knowledge in sexual medicine. The prevalence of sexual disorders in primary care is underestimated by primary care physicians. Female doctors and female patients address sexual problems more often than male doctors and patients. Lack of sexual interest and erectile dysfunction are the most frequent sexual disorders in primary care. In 2004 the participating doctors assess their knowledge in sexual medicine at a higher level compared to 1980. The training of primary care physicians in primary care should further be improved.

Miniaturised selective pressurised liquid extraction of polychlorinated biphenyls from foodstuffs.

The feasibility of miniaturised pressurised liquid extraction (PLE) with in-cell purification and subsequent gas chromatography with micro-electron capture detection (GC-micro-ECD) for the determination of prioritary and toxic polychlorinated biphenyls (PCBs) in a variety of foodstuffs (fat contents in the range 22-49%, w/w, on a freeze-dried basis) has been investigated. After optimisation of the several experimental parameters affecting the efficiency of the selective PLE process, the developed method provided quantitative recoveries of the endogenous PCBs studied and complete fat elimination in a single step using n-hexane as extraction solvent. A total solvent volume of 3.5 mL was used for the two consecutive 7 min static PLEs of 100-mg samples. Detection limits using GC-micro-ECD were below 0.2 ng/g freeze dried sample for all 22 PCBs investigated in real-life foodstuffs, and the repeatability of the complete PLE plus GC-micro-ECD method as calculated for the analysis of the endogenous PCBs in general was better than 14%. Comparison of the miniaturised PLE method developed with either conventional Soxhlet extraction or matrix solid phase dispersion with subsequent (off-line) clean-up for the analysis of non-spiked samples showed that the efficiency of PLE was similar to or better (recoveries in the range 83-133%, as calculated for the endogenous analytes) than for the other two extraction methods assayed.

Evaluation of uridine metabolism in human and animal spermatozoa.

The objective of this study was to elucidate the role of uridine for spermatozoa, since this pyrimidine nucleoside was found in millimolar concentration in human seminal plasma. Here, the degradative activity of uridine-phosphorylase [EC 2.4.2.3] and the salvage activity of uridine kinase [EC 2.7.1.48] were detected in human spermatozoa. HPLC analysis depicted the uptake of exogeneous 14C-labelled adenine, but not of uridine and of hypoxanthine, into nucleotide pools of boar spermatozoa. On addition of uridine, the computer-assisted semen analysis (CASA) of human cells revealed a reduction of the percentage of motile spermatozoa in contrast to an elevation of some velocity parameters. It is concluded that exogeneous uridine could function as suppressor for early capacitation and as a substrate for phosphorolysis, if ribose is needed, rather than to satisfy a demand for intracellular pyrimidine nucleotides.