Variables of host response in saliva of patients with periodontitis: A pilot study

Periodontitis is an infection that results from an imbalance between periodontopathic microorganisms and the local and systemic host defense. This study analyzed saliva samples of patients with periodontitis for several biomarkers of host response.

Patterns of molecular response to and relapse after combination of sorafenib, idarubicin, and cytarabine in patients with FLT3 mutant acute myeloid leukemia

BACKGROUND: FMS-like tyrosine kinase 3 (FLT3) is a class III receptor tyrosine kinase involved in hematopoietic progenitor cell development. Mutations of FLT3 have been reported in about a third of patients with acute myeloid leukemia (AML), and inhibitors of FLT3 are of clinical interest. Sorafenib is an orally active multikinase inhibitor with potent activity against FLT3 and the Raf/ERK/MEK kinase pathway. METHODS: We studied the patterns of molecular response and relapse in 18 patients with mutated FLT3 treated with the combination of sorafenib, idarubicin, and cytarabine. RESULTS: The median follow-up was 9 months. Sixteen patients achieved complete remission (CR), and the other 2 patients achieved CR but lacked platelet recovery for an overall response rate of 100%. Ten patients had their FLT3-mutated clone eradicated, with 6 patients who showed some residual FLT3-mutated cells, and 2 patients who showed persistent FLT3-mutated cells. The elimination of FLT3-mutated population at the time of morphologic CR, however, was not predictive of relapse. After a median follow-up of 9 months (range, 1-16 months), 10 (55%) patients had relapsed, with a median CR duration of 8.8 months (range, 1-9.5 months). By DNA sequencing, there was no evidence of an acquired FLT3 point mutation at the time of relapse in 7 patients tested, which suggested the presence of other mechanisms of sorafenib resistance. CONCLUSION: Sorafenib, combined with chemotherapy, is effective in attaining CR, but relapses still occur.

Sevoflurane remifentanil interaction: comparison of different response surface models

Various pharmacodynamic response surface models have been developed to quantitatively describe the relationship between two or more drug concentrations with their combined clinical effect. We examined the interaction of remifentanil and sevoflurane on the probability of tolerance to shake and shout, tetanic stimulation, laryngeal mask airway insertion, and laryngoscopy in patients to compare the performance of five different response surface models.

Methods to convert continuous outcomes into odds ratios of treatment response and numbers needed to treat: meta-epidemiological study

Clinicians find standardized mean differences (SMDs) calculated from continuous outcomes difficult to interpret. Our objective was to determine the performance of methods in converting SMDs or means to odds ratios of treatment response and numbers needed to treat (NNTs) as more intuitive measures of treatment effect.

Effective Length K-Factors For Flexural Buckling Strengths Of Web Members In Open Web Steel Joists

Open web steel joists are designed in the United States following the governing specification published by the Steel Joist Institute. For compression members in joists, this specification employs an effective length factor, or K-factor, in confirming their adequacy. In most cases, these K-factors have been conservatively assumed equal to 1.0 for compression web members, regardless of the fact that intuition and limited experimental work indicate that smaller values could be justified. Given that smaller K-factors could result in more economical designs without a loss in safety, the research presented in this thesis aims to suggest procedures for obtaining more rational values. Three different methods for computing in-plane and out-of-plane K-factors are investigated, including (1) a hand calculation method based on the use of alignment charts, (2) computational critical load (eigenvalue) analyses using uniformly distributed loads, and (3) computational analyses using a compressive strain approach. The latter method is novel and allows for computing the individual buckling load of a specific member within a system, such as a joist. Four different joist configurations are investigated, including an 18K3, 28K10, and two variations of a 32LH06. Based on these methods and the very limited number of joists studied, it appears promising that in-plane and out-of-plane K-factors of 0.75 and 0.85, respectively, could be used in computing the flexural buckling strength of web members in routine steel joist design. Recommendations for future work, which include systematically investigating a wider range of joist configurations and connection restraint, are provided.

Haemodynamic variables and functional outcome in hypothermic patients following out-of-hospital cardiac arrest

To evaluate the association between haemodynamic variables during the first 24h after intensive care unit (ICU) admission and neurological outcome in out-of-hospital cardiac arrest (OHCA) victims undergoing therapeutic hypothermia.

Multiple time scales of temporal response in pyramidal and fast spiking cortical neurons

Neural dynamic processes correlated over several time scales are found in vivo, in stimulus-evoked as well as spontaneous activity, and are thought to affect the way sensory stimulation is processed. Despite their potential computational consequences, a systematic description of the presence of multiple time scales in single cortical neurons is lacking. In this study, we injected fast spiking and pyramidal (PYR) neurons in vitro with long-lasting episodes of step-like and noisy, in-vivo-like current. Several processes shaped the time course of the instantaneous spike frequency, which could be reduced to a small number (1-4) of phenomenological mechanisms, either reducing (adapting) or increasing (facilitating) the neuron's firing rate over time. The different adaptation/facilitation processes cover a wide range of time scales, ranging from initial adaptation (<10 ms, PYR neurons only), to fast adaptation (<300 ms), early facilitation (0.5-1 s, PYR only), and slow (or late) adaptation (order of seconds). These processes are characterized by broad distributions of their magnitudes and time constants across cells, showing that multiple time scales are at play in cortical neurons, even in response to stationary stimuli and in the presence of input fluctuations. These processes might be part of a cascade of processes responsible for the power-law behavior of adaptation observed in several preparations, and may have far-reaching computational consequences that have been recently described.

DISSECTION OF STRESS RESPONSE NETWORKS REGULATING MULTIPLE STRESSES IN RICE

Important food crops like rice are constantly exposed to various stresses that can have devastating effect on their survival and productivity. Being sessile, these highly evolved organisms have developed elaborate molecular machineries to sense a mixture of stress signals and elicit a precise response to minimize the damage. However, recent discoveries revealed that the interplay of these stress regulatory and signaling molecules is highly complex and remains largely unknown. In this work, we conducted large scale analysis of differential gene expression using advanced computational methods to dissect regulation of stress response which is at the heart of all molecular changes leading to the observed phenotypic susceptibility. One of the most important stress conditions in terms of loss of productivity is drought. We performed genomic and proteomic analysis of epigenetic and miRNA mechanisms in regulation of drought responsive genes in rice and found subsets of genes with striking properties. Overexpressed genesets included higher number of epigenetic marks, miRNA targets and transcription factors which regulate drought tolerance. On the other hand, underexpressed genesets were poor in above features but were rich in number of metabolic genes with multiple co-expression partners contributing majorly towards drought resistance. Identification and characterization of the patterns exhibited by differentially expressed genes hold key to uncover the synergistic and antagonistic components of the cross talk between stress response mechanisms. We performed meta-analysis on drought and bacterial stresses in rice and Arabidopsis, and identified hundreds of shared genes. We found high level of conservation of gene expression between these stresses. Weighted co-expression network analysis detected two tight clusters of genes made up of master transcription factors and signaling genes showing strikingly opposite expression status. To comprehensively identify the shared stress responsive genes between multiple abiotic and biotic stresses in rice, we performed meta-analyses of microarray studies from seven different abiotic and six biotic stresses separately and found more than thirteen hundred shared stress responsive genes. Various machine learning techniques utilizing these genes classified the stresses into two major classes' namely abiotic and biotic stresses and multiple classes of individual stresses with high accuracy and identified the top genes showing distinct patterns of expression. Functional enrichment and co-expression network analysis revealed the different roles of plant hormones, transcription factors in conserved and non-conserved genesets in regulation of stress response.