Search

Heat shock transcription factor 1 (HSF1) has been identified as a therapeutic target for pharmacological treatment of multiple myeloma (MM). However, direct therapeutic targeting of HSF1 function seems to be difficult due to the shortage of clinically suitable pharmacological inhibitors. We utilized the Ugi multicomponent reaction to create a small but smart library of α-acyl aminocarboxamides and evaluated their ability to suppress heat shock response (HSR) in MM cells. Using the INA-6 cell line as the MM model and the strictly HSF1-dependent HSP72 induction as a HSR model, we identified potential HSF1 inhibitors. Mass spectrometry-based affinity capture experiments with biotin-linked derivatives revealed a number of target proteins and complexes, which exhibit an armadillo domain. Also, four members of the tumor-promoting and HSF1-associated phosphatidylinositol 3-kinase-related kinase (PIKK) family were identified. The antitumor activity was evaluated, showing that treatment with the anti-HSF1 compounds strongly induced apoptotic cell death in MM cells. [ABSTRACT FROM AUTHOR]

Current iron supplementation practice in geriatric patients is erratic and lacks evidence-based recommendations. Despite potential benefits in this population, intravenous iron supplementation is often withheld due to concerns regarding pharmacy expense, perceived safety issues, and doubts regarding efficacy in elderly patients. This retrospective, observational cohort study aimed to evaluate the safety and efficacy of intravenous ferric carboxymaltose (FCM, Ferinject) in patients aged >75 years with iron deficiency anaemia (IDA). Within a twelve-month data extraction period, the charts of 405 hospitalised patients aged 65–101 years were retrospectively analysed for IDA, defined according to WHO criteria for anaemia (haemoglobin: <13.0 g/dL (m)/<12.0 g/dL (f)) in conjunction with transferrin saturation <20%. Of 128 IDA patients screened, 51 (39.8%) received intravenous iron. 38 patient charts were analysed. Mean cumulative dose of intravenous FCM was 784.4 ± 271.7 mg iron (1–3 infusions). 18 patients (47%) fulfilled treatment response criteria (≥1.0 g/dL increase in haemoglobin between baseline and hospital discharge). AEs were mild/moderate, most commonly transient increases of liver enzymes (n = 5/13.2%). AE incidence was comparable with that observed in patients <75 years. No serious AEs were observed. Ferric carboxymaltose was well tolerated and effective for correction of Hb levels and iron stores in this cohort of IDA patients aged over 75 years. [ABSTRACT FROM AUTHOR]

Abstract: Sphingolipids are implied in several regulatory processes, including cell death. Levels of the free sphingobase t18:0 (phytosphingosine) increase in Arabidopsis in response to the bacterial pathogen Pseudomonas syringae. To gain information on sphingobase-induced signaling, we determined kinetics of leaf reactive oxygen species (ROS) levels and cell death in response to specific sphingobases. t18:0, d18:0 and d17:1, but not d20:0, induced ROS and cell death within 1.5–2h. Early sphingobase-induced ROS production was independent of cell death induction and required the NADPH oxidase Respiratory Burst Oxidase Homolog D (RBOHD). Specific sphingobases can therefore induce cell death and require RBOHD for early ROS induction in plants. [Copyright &y& Elsevier]

OBJECTIVES: To evaluate the effect of an intervention by a multidisciplinary team to reduce falls in older people's homes. DESIGN: Randomized, controlled trial with follow-up of subjects for 1 year. SETTING: University-affiliated geriatric hospital and older patients' homes. PARTICIPANTS: Three hundred sixty subjects (mean age ± standard deviation = 81.5 ± 6.4) admitted from home to a geriatric hospital and showing functional decline, especially in mobility. INTERVENTION: The participants were randomly assigned to receive a comprehensive geriatric assessment followed by a diagnostic home visit and home intervention or a comprehensive geriatric assessment with recommendations and usual care at home. The home intervention included a diagnostic home visit, assessing the home for environmental hazards, advice about possible changes, offer of facilities for any necessary home modifications, and training in the use of technical and mobility aids. An additional home visit was made after 3 months to reinforce the recommendations. After 12 months of follow-up, a home visit was made to all study participants. MEASUREMENTS: Number of falls, type of recommended home modifications, and compliance with recommendations. RESULTS: After 1 year, there were 163 falls in the intervention group and 204 falls in the control group. The intervention group had 31% fewer falls than the control group (incidence rate ratio (IRR) = 0.69, 95% confidence interval (CI) = 0.51–0.97). The intervention was most effective in a subgroup of participants who reported having had two or more falls during the year before recruitment into the study. In this subgroup, the proportion of frequent fallers and the rate of falls was significantly reduced for the intervention group compared with the control group (21 vs 36 subjects with recurrent falls, P = .009; IRR = 0.63, 95% CI = 0.43–0.94). The compliance rate varied with the type of change recommended from 83% to 33% after 12... [ABSTRACT FROM AUTHOR]

This article discusses a study which examined the extent to which walker use by geriatric rehabilitation patients affects functional outcome measures used to assess motor performance or rehabilitation progress. The study involved 28 patients aged 71-92. The Timed Up and Go (TUG) Test was performed using a standard armchair. Results of the study show that changes in mobility function could to some extent be attributed to the walker use experience.

The N,C-coupled naphthylisoquinoline alkaloid ancistrocladinium A belongs to a novel class of natural products with potent antiprotozoal activity. Its effects on tumor cells, however, have not yet been explored. We demonstrate the antitumor activity of ancistrocladinium A in multiple myeloma (MM), a yet incurable blood cancer that represents a model disease for adaptation to proteotoxic stress. Viability assays showed a potent apoptosis-inducing effect of ancistrocladinium A in MM cell lines, including those with proteasome inhibitor (PI) resistance, and in primary MM cells, but not in non-malignant blood cells. Concomitant treatment with the PI carfilzomib or the histone deacetylase inhibitor panobinostat strongly enhanced the ancistrocladinium A-induced apoptosis. Mass spectrometry with biotinylated ancistrocladinium A revealed significant enrichment of RNA-splicing-associated proteins. Affected RNA-splicing-associated pathways included genes involved in proteotoxic stress response, such as PSMB5-associated genes and the heat shock proteins HSP90 and HSP70. Furthermore, we found strong induction of ATF4 and the ATM/H2AX pathway, both of which are critically involved in the integrated cellular response following proteotoxic and oxidative stress. Taken together, our data indicate that ancistrocladinium A targets cellular stress regulation in MM and improves the therapeutic response to PIs or overcomes PI resistance, and thus may represent a promising potential therapeutic agent. [ABSTRACT FROM AUTHOR]

Assesses the manual dexterity and cognitive capacity of 78 geriatric patients using the Timed Test of Money Counting (TTMC). Other assessment tests; Reliability of the TTMC; Validity; Simplicity and lack of special equipment needed for application.

High Performance Linpack can maximize requirements throughout a computer system. An efficient multi-GPU double-precision general matrix multiply (DGEMM), together with adjustments to the HPL, is required to utilize a heterogeneous computer to its full extent. The authors present the resulting energy-efficiency measurements and suggest a cluster design that can utilize multiple GPUs. [ABSTRACT FROM PUBLISHER]

In a quasi-experimental pre- and postdesign, we examined the effect of rollator use on functional rehabilitation outcome in geriatric patients. From a sample of 458 geriatric inpatients, we matched 30 subjects who were not using assistive devices in their everyday lives but received a wheeled walker at the time of hospital admission (first-time user group) according to their admission scores on three motor performance tests (Timed Up-and-Go, Five-Times-Sit-to-Stand, and Performance-Oriented Mobility Assessment-Balance) with 30 patients who were actively using rollators as their primary walking aid for at least 3 months (long-term user group) and 30 control subjects without walking-aid assistance. Measurementswere repeated after the inpatient rehabilitation regimen. The Kruskal-Wallis test did not reveal significant group differences in rehabilitation progress. Controls and device users, regardless of walking-aid experience, demonstrated nearly comparable mobility, strength, and balance improvements. More than half of each cohort (controls, n = 22; first-time, n = 17; long-term, n =18) achieved functional gains in all three motor tests. The study showed that rollator assistance does not interfere with rehabilitation outcome and, to some extent, legitimates the prescription of assistive devices to improve confidence and restore or maintain motor ability at the highest possible level. [ABSTRACT FROM AUTHOR]

Background. Anemia is a common condition in the elderly and a significant risk factor for increased morbidity and mortality, reducing not only functional capacity and mobility but also quality of life. Currently, few data are available regarding anemia in hospitalized geriatric patients. Our retrospective study investigated epidemiology and causes of anemia in 405 hospitalized geriatric patients. Methods. Data analysiswas performed using laboratory parameters determined during routine hospital admission procedures (hemoglobin, ferritin, transferrin saturation, C-reactive protein, vitamin B12, folic acid, and creatinine) in addition to medical history and demographics. Results. Anemia affected approximately two-thirds of subjects. Of 386 patients with recorded hemoglobin values, 66.3% were anemic according to WHO criteria, mostly (85.1%) in a mild form. Anemia was primarily due to iron deficiency (65%), frequently due to underlying chronic infection (62.1%), or of mixed etiology involving a combination of chronic disease and iron deficiency, with absolute iron deficiency playing a comparatively minor role. Conclusion. Greater awareness of anemia in the elderly is warranted due to its high prevalence and negative effect on outcomes, hospitalization duration, and mortality. Geriatric patients should be routinely screened for anemia and etiological causes of anemia individually assessed to allow timely initiation of appropriate therapy. [ABSTRACT FROM AUTHOR]

The on-line event reconstruction in ALICE is performed by the High Level Trigger, which should process up to 2000 events per second in proton-proton collisions and up to 300 central events per second in heavy-ion collisions, corresponding to an input data stream of 30 GB/s. In order to fulfill the time requirements, a fast on-line tracker has been developed. The algorithm combines a Cellular Automaton method being used for a fast pattern recognition and the Kalman Filter method for fitting of found trajectories and for the final track selection. The tracker was adapted to run on Graphics Processing Units (GPU) using the NVIDIA Compute Unified Device Architecture (CUDA) framework. The implementation of the algorithm had to be adjusted at many points to allow for an efficient usage of the graphics cards. In particular, achieving a good overall workload for many processor cores, efficient transfer to and from the GPU, as well as optimized utilization of the different memories the GPU offers turned out to be critical. To cope with these problems a dynamic scheduler was introduced, which redistributes the workload among the processor cores. Additionally a pipeline was implemented so that the tracking on the GPU, the initialization and the output processed by the CPU, as well as the DMA transfer can overlap. The GPU tracking algorithm significantly outperforms the CPU version for large events while it entirely maintains its efficiency. [ABSTRACT FROM PUBLISHER]

Abstract: The present study investigated the relative slip resistance of commercially available non-slip socks during gait. Twenty-four healthy subjects (29.3±10.4 years) participated in the study. Each subject completed 4 different test conditions (barefoot, non-slip socks, conventional socks, backless slippers) in a randomized, balanced order. The slip resistance was estimated by measuring the heel deceleration time using a heel-mounted accelerometer. Repeated measures ANOVA and post hoc paired-sample t-test with Bonferroni correction were used for statistical analysis. Compared to barefoot walking absolute deceleration times [ms] were significantly increased when wearing conventional socks or slippers. No significant differences were observed between the barefoot and non-slip socks conditions. The present study shows that non-slip socks improved slip-resistance during gait when compared to conventional socks and slippers. Future investigations should verify the present findings in hospital populations prone to slip-related falls. [Copyright &y& Elsevier]