A review of issues and challenges of implementation of patient blood management.

INTRODUCTION: Patient blood management (PBM) is outlined as evidence-based medical and surgical concepts with a multidisciplinary method. AIMS AND OBJECTIVES: The aim of this article is to review the PBM implementation and analyses the issues, challenges, and opportunities. METHODOLOGY: In this article, we have an overview of PBM implementation in literature and our experience in one hospital in Iran. We used databases including Embase, CINAHL, Scopus, Google Scholar, Google, Science Direct, ProQuest, ISI Web of Knowledge, and PubMed to attain the related literature published in the English language. RESULTS: There are different barriers and challenges of implementation of PBM, such as hospital culture confrontation, reduced staff with restricted time, lack of interdisciplinary conversation, change of practice, the lack of experience with PBM, the feasibility to integrate PBM, electronic documentation and schedule budget for required instruments, resources, and personnel. Hospitals differ globally in the aspect of infrastructure, personnel and properties, and it is necessary to individualize according to the local situation. CONCLUSION: The review highlights the importance of PBM and its implementation for obtaining patient safety. PBM establishing in hospitals as a complex process have different challenges and barriers. Sharing experiences is essential to success in the PBM programs. Cooperation between countries will be useful in PBM spreading.

Metabolic therapies inhibit tumor growth in vivo and in silico.

In the recent years, cancer research succeeded with sensitive detection methods, targeted drug delivery systems, and the identification of a large set of genes differently expressed. However, although most therapies are still based on antimitotic agents, which are causing wide secondary effects, there is an increasing interest for metabolic therapies that can minimize side effects. In the early 20th century, Otto Warburg revealed that cancer cells rely on the cytoplasmic fermentation of glucose to lactic acid for energy synthesis (called "Warburg effect"). Our investigations aim to reverse this effect in reprogramming cancer cells' metabolism. In this work, we present a metabolic therapy specifically targeting the activity of specific enzymes of central carbon metabolism, combining the METABLOC bi-therapeutic drugs combination (Alpha Lipoic Acid and Hydroxycitrate) to Metformin and Diclofenac, for treating tumors implanted in mice. Furthermore, a dynamic metabolic model describing central carbon metabolism as well as fluxes targeted by the drugs allowed to simulate tumors progression in both treated and non-treated mice, in addition to draw hypotheses on the effects of the drugs on tumor cells metabolism. Our model predicts metabolic therapies-induced reversed Warburg effect on tumor cells.

A molecular modelling study of the effects of pivalate ligand substitutions on the magnetic properties of chromium-wheels host complexes.

In our recent article, we had a successful experience in applying binuclear chromium (III) model ([Cr2F(tBuCO2)2(H2O)2(OH)4]-1) instead of real chromium-wheel host complex ([Cr8F8(tBuCO2)16]) to calculate the effect of bridged-ligands substitution on the exchange coupling constants (J) values of the complexes. In this work our experienced procedure was used to evaluate the effect of pivalate (tBuCO2) ligands substitution on the J values of the complexes. For this, at first two new groups of complexes were designed based on the replacement of pivalate by X-tBuCO2 and X-iPrCO2 anionic ligands (where X represents F, Cl, Br and I halogens) and then their J values were calculated. Since the existence of two halogen atoms in the structures of complexes leads to form different conformers, at first step a conformational analysis was carried out to identify the stable conformers of each complex. In X-tBuCO2-containing complexes four stable conformers were recognized, while X-iPrCO2-containing complexes had three stable conformers. At next step the J values of each of these conformers were calculated for all complexes. It was found that depending on which conformer was formed, the effect of these substitutions in each complex could be different, leading to a decrease or increase in the antiferromagnetic property of the complex. In both types of complexes, the formation of the least stable conformer, Conf1, led to the strengthening of the antiferromagnetic property of the complex but the impacts of the substitutions in other conformers were diverse. These new designed complexes could be considered as novel synthetic targets with different magnetic properties.

Mechanical stress increases brain amyloid ß, tau, and α-synuclein concentrations in wild-type mice.

INTRODUCTION: Exposure to traumatic brain injury is a core risk factor that predisposes an individual to sporadic neurodegenerative diseases. We provide evidence that mechanical stress increases brain levels of hallmark proteins associated with neurodegeneration. METHODS: Wild-type mice were exposed to multiple regimens of repetitive mild traumatic brain injury, generating a range of combinations of impact energies, frequencies, and durations of exposure. Brain concentrations of amyloid ß 1-42 (Aß1-42), total tau, and α-synuclein were measured by sandwich enzyme-linked immunosorbent assay. RESULTS: There was a highly significant main effect of impact energy, frequency, and duration of exposure on Aß1-42, tau, and α-synuclein levels (P < .001), and a significant interaction between impact energy and duration of exposure for Aß1-42 and tau (P < .001), but not for α-synuclein. DISCUSSION: Dose-dependent and cumulative influence of repetitive mild traumatic brain injury-induced mechanical stress may trigger and/or accelerate neurodegeneration by pushing protein concentration over the disease threshold.

Failure mode and effect analysis: improving intensive care unit risk management processes.

Purpose Failure modes and effects analysis (FMEA) is a practical tool to evaluate risks, discover failures in a proactive manner and propose corrective actions to reduce or eliminate potential risks. The purpose of this paper is to apply FMEA technique to examine the hazards associated with the process of service delivery in intensive care unit (ICU) of a tertiary hospital in Yazd, Iran. Design/methodology/approach This was a before-after study conducted between March 2013 and December 2014. By forming a FMEA team, all potential hazards associated with ICU services - their frequency and severity - were identified. Then risk priority number was calculated for each activity as an indicator representing high priority areas that need special attention and resource allocation. Findings Eight failure modes with highest priority scores including endotracheal tube defect, wrong placement of endotracheal tube, EVD interface, aspiration failure during suctioning, chest tube failure, tissue injury and deep vein thrombosis were selected for improvement. Findings affirmed that improvement strategies were generally satisfying and significantly decreased total failures. Practical implications Application of FMEA in ICUs proved to be effective in proactively decreasing the risk of failures and corrected the control measures up to acceptable levels in all eight areas of function. Originality/value Using a prospective risk assessment approach, such as FMEA, could be beneficial in dealing with potential failures through proposing preventive actions in a proactive manner. The method could be used as a tool for healthcare continuous quality improvement so that the method identifies both systemic and human errors, and offers practical advice to deal effectively with them.

Theoretical study of thieno-thiophene based low band gap copolymers and substituent effect on the optoelectronic properties of them.

This paper studies donor-acceptor systems which incorporate benzodithiophene (BDT), benzodifuran (BDF) and benzodipyrrole (BDP) units as the electron-rich monomer with TT unit representing the electron-deficient monomer. This research is based on employing density functional theory (DFT) and time-dependent DFT (TD-DFT). The highest occupied molecular orbitals (HOMO) and the lowest unoccupied molecular orbitals (LUMO), HOMO-LUMO gaps and dihedral-angles of these copolymers were calculated using oligomer extrapolation technique and periodic boundary condition (PBC) method. The optical band gaps and UV-vis absorption spectra of aforementioned copolymers were obtained by TD-DFT at the same level of theory. Based on the fair agreement between PBC-DFT calculated results and experimental data, the substituent effects of Cl, Br, CCH, COH, NO2, OH, SH and NH2 groups were investigated by PBC-DFT method. The difference between the ground and excited-states dipole moment (Δµge) of all derivatives were also calculated. Taking these results into account, a better understanding of the substituent effects on the photo-physical properties of the copolymers under study was achieved. Due to the shift of HOMO and LUMO energy levels, smaller band gaps and higher Δµge are observed in some derivatives. The calculation results demonstrate that the substitution of COH and NO2 by fluorine in BDF-TT and BDP-TT leads to higher maximum theoretical efficiencies (η).

The Redox Status of Cancer Cells Supports Mechanisms behind the Warburg Effect.

To better understand the energetic status of proliferating cells, we have measured the intracellular pH (pHi) and concentrations of key metabolites, such as adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NAD), and nicotinamide adenine dinucleotide phosphate (NADP) in normal and cancer cells, extracted from fresh human colon tissues. Cells were sorted by elutriation and segregated in different phases of the cell cycle (G0/G1/S/G2/M) in order to study their redox (NAD, NADP) and bioenergetic (ATP, pHi) status. Our results show that the average ATP concentration over the cell cycle is higher and the pHi is globally more acidic in normal proliferating cells. The NAD+/NADH and NADP+/NADPH redox ratios are, respectively, five times and ten times higher in cancer cells compared to the normal cell population. These energetic differences in normal and cancer cells may explain the well-described mechanisms behind the Warburg effect. Oscillations in ATP concentration, pHi, NAD+/NADH, and NADP+/NADPH ratios over one cell cycle are reported and the hypothesis addressed. We also investigated the mitochondrial membrane potential (MMP) of human and mice normal and cancer cell lines. A drastic decrease of the MMP is reported in cancer cell lines compared to their normal counterparts. Altogether, these results strongly support the high throughput aerobic glycolysis, or Warburg effect, observed in cancer cells.

Identification and prioritization of food insecurity and vulnerability indices in iran.

BACKGROUND: Food security is a multi-dimensional phenomenon. The objective of this study was to identify and prioritize major indices for determining food insecurity in Iran. METHODS: Descriptive study using the Delphi method was conducted through an email-delivered questionnaire. Forty-three senior experts at national or provincial level were selected based on their work experience and educational background through study panel consultation and snowballing from Tehran and other cities of Iran. During two rounds of Delphi, participants were asked to identify priority indicators for food security at provincial level in Iran. RESULTS: Sixty five percent of Delphi panel participated in the first round and eighty-nine percent of them participated in the second round of Delphi. Initially, 243 indices were identified through review of literature; after excluding indictors, which was not available or measurable at provincial level in Iran, 103 indictors remained. The results of study showed that experts identified "percentage of individuals receiving less than 70% of daily energy requirement" with a median score of 90, as the most influential index for determining food insecurity. "Food expenses as a proportion of the overall expenses of the family", "per capita of dietary energy supply", and "provision of micro-nutrient supply requirement per capita" with median of 80 were in the second rank of food security priority indicators. CONCLUSION: Out of 243 identified indicators for food security, 38 indicators were selected as the most priority indicators for food security at provincial level in Iran.

Density functional theory investigation of opto-electronic properties of thieno[3,4-b]thiophene and benzodithiophene polymer and derivatives and their applications in solar cell.

PTBs polymers with thieno[3,4-b]thiophene [TT] and benzodithiophene [BDT] units have particular properties, which demonstrate it as one of the best group of donor materials in organic solar cells. In the present work, density functional theory (DFT) is applied to investigate the optimized structure, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), band gap and dihedral angle of PTB7 at B3LYP/6-31G(d). Two different approaches are applied to carry out these investigations: Oligomer extrapolation technique and periodic boundary condition (PBC) method. The results obtained from PBC-DFT method are in fair agreement with experiments. Based on these reliable outcomes; the investigations continued to perform some derivatives of PTB7. In this study, sulfur is substituted by nitrogen, oxygen, silicon, phosphor or selenium atoms in pristine PTB7. Due to the shift of HOMO and LUMO levels, smaller band gaps are predicted to appear in some derivatives in comparison with PTB7. Maximum theoretical efficiencies, η, of the mentioned derivatives as well as local difference of dipole moments between the ground and excited states (Δµge) are computed. The results indicate that substitution of sulfur by nitrogen or oxygen in BDT unit, and silicon or phosphor in TT unit of pristine PTB7 leads to a higher η as well as Δµge.

Affinity-based target deconvolution of safranal.

BACKGROUND AND THE PURPOSE OF THE STUDY: Affinity-based target deconvolution is an emerging method for the identification of interactions between drugs/drug candidates and cellular proteins, and helps to predict potential activities and side effects of a given compound. In the present study, we hypothesized that a part of safranal pharmacological effects, one of the major constituent of Crocus sativus L., relies on its physical interaction with target proteins. METHODS: Affinity chromatography solid support was prepared by covalent attachment of safranal to agarose beads. After passing tissue lysate through the column, safranal-bound proteins were isolated and separated on SDS-PAGE or two-dimensional gel electrophoresis. Proteins were identified using MALDI-TOF/TOF mass spectrometry and Mascot software. RESULTS AND MAJOR CONCLUSION: Data showed that safranal physically binds to beta actin, cytochrome b-c1 complex sub-unit 1, trifunctional enzyme sub-unit beta and ATP synthase sub-unit alpha and beta. These interactions may explain part of safranal's pharmacological effects. However, phenotypic and/or biological relevance of these interactions remains to be elucidated by future pharmacological studies.

Tumor regression with a combination of drugs interfering with the tumor metabolism: efficacy of hydroxycitrate, lipoic acid and capsaicin.

Cellular metabolic alterations are now well described as implicated in cancer and some strategies are currently developed to target these different pathways. In previous papers, we demonstrated that a combination of molecules (namely alpha-lipoic acid and hydroxycitrate, i.e. Metabloc™) targeting the cancer metabolism markedly decreased tumor cell growth in mice. In this work, we demonstrate that the addition of capsaicin further delays tumor growth in mice in a dose dependant manner. This is true for the three animal model tested: lung (LLC) cancer, bladder cancer (MBT-2) and melanoma B16F10. There was no apparent side effect of this ternary combination. The addition of a fourth drug (octreotide) is even more effective resulting in tumor regression in mice bearing LLC cancer. These four compounds are all known to target the cellular metabolism not its DNA. The efficacy, the apparent lack of toxicity, the long clinical track records of these medications in human medicine, all points toward the need for a clinical trial. The dramatic efficacy of treatment suggests that cancer may simply be a disease of dysregulated cellular metabolism.

Adding a combination of hydroxycitrate and lipoic acid (METABLOC™) to chemotherapy improves effectiveness against tumor development: experimental results and case report.

Altered metabolism of cancer first highlighted by Otto Warburg has a long history. Although ignored for a considerable amount of time, it is now receiving substantial attention. We recently published results obtained with a combination of two drugs, lipoic acid and hydroxycitrate, targeting metabolic enzymes particularly affected in cancer: ATP citrate lyase and pyruvate dehydrogenase kinase. This treatment was as efficient as chemotherapy in the three mouse cancer models that were tested. In this work, we asked if our drug combination could be used in conjunction with standard cytotoxic chemotherapy, in particular cisplatin, to improve basic protocol efficacy. A combination of lipoic acid and hydroxycitrate was administered to mice implanted with syngeneic cancer cells, LL/2 lung carcinoma and MBT-2 bladder carcinoma, concommitantly with classical chemotherapy (cisplatin or methotrexate). We demonstrate that the triple combination lipoic acid + hydroxycitrate + cisplatin or methotrexate is more efficient than cisplatin or methotrexate used individually or the combination of lipoic acid and hydroxycitrate administered alone. Of particular note are the results obtained in the treatment of an 80 year-old female who presented with ductal adenocarcinoma of the pancreas accompanied by liver metastases. A treatment course using gemcitabine plus α-lipoic acid and hydroxycitrate gave highly promising results. The in vivo data, coupled with the case study results, suggest a possible advantage in using a treatment targeted at cancer metabolism in association with classical chemotherapy.

Screening of well-established drugs targeting cancer metabolism: reproducibility of the efficacy of a highly effective drug combination in mice.

Alterations in metabolic pathways are known to characterize cancer. In order to suppress cancer growth, however, multiple proteins involved in these pathways have to be targeted simultaneously. We have developed a screening method to assess the best drug combination for cancer treatment based on targeting several factors implicated in tumor specific metabolism. Following a review of the literature, we identified those enzymes known to be deregulated in cancer and established a list of sixty-two drugs targeting them. These molecules are used routinely in clinical settings for diseases other than cancer. We screened a first library in vitro against four cell lines and then evaluated the most promising binary combinations in vivo against three murine syngeneic cancer models, (LL/2, Lewis lung carcinoma; B16-F10, melanoma; and MBT-2, bladder cancer). The optimum result was obtained using a combination of α-lipoic acid and hydroxycitrate (METABLOC(TM)). In this study, a third agent was added by in vivo evaluation of a large number of combinations. The addition of octreotide strongly reduced tumor development (T/C% value of 30.2 to 34.5%; P < 0.001) in the same models and prolonged animal survival (P < 0.001) as compared to cisplatin. These results were confirmed in a different laboratory setting using a human xenograft model (NCI-H69, small cell lung cancer). None of these three molecules are known to target DNA. The effectiveness of this combination in several animal models, as well as the low toxicity of these inexpensive drugs, emphasizes the necessity of rapidly setting up a clinical trial.

Mycobacterium bovis Bacillus Calmette-Guérin killed by extended freeze-drying reduces colitis in mice.

BACKGROUND & AIMS: Mycobacterium bovis Bacillus Calmette-Guérin (BCG), killed by extended freeze-drying (EFD), induces secretion of interleukin-10 and reduces lung inflammation in a mouse model of asthma. We investigated the effects of EFD BCG in mouse models of inflammatory bowel disease. METHODS: EFD BCG was administered subcutaneously to mice with colitis induced by dextran sodium sulfate (DSS), oxazolone, or adoptive transfer of CD4(+)CD45RB(high)Foxp3(-) T cells from C57Bl/6 Foxp3GFP mice to RAG2(-/-) mice. RESULTS: EFD BCG, administered either before induction of DSS and oxazolone colitis or after development of acute or chronic DSS-induced colitis, reduced symptom scores, loss of body weight, and inflammation. Although transfer of CD4(+)CD45RB(high)Foxp3(-) cells induced colitis in RAG2(-/-) mice, administration of EFD BCG at the time of the transfer converted Foxp3(-) T cells to Foxp3(+) T cells and the mice did not develop colitis. EFD BCG protected mice from colitis via a mechanism that required expansion of T regulatory cells and production of interleukin-10 and transforming growth factor ß. EFD BCG activated the retinoid X receptor (RXR)-α-peroxisome proliferator-activated receptor (PPAR)-γ heterodimer, blocked translocation of nuclear factor κB to the nucleus, and reduced colonic inflammation; it did not increase the number of colon tumors that formed in mice with chronic DSS-induced colitis. CONCLUSIONS: EFD BCG controls severe colitis in mice by expanding T regulatory cell populations and PPAR-γ and might be developed to treat patients with inflammatory bowel disease.

Combination of PCA and undecimated wavelet transform for neural data processing.

Nervous system conveys information by electrical signals called 'spikes', therefore, spikes detection and sorting are challenging topics in the neural data processing. The principal component analysis (PCA) is a convenient tool for clustering spikes; however it has some disadvantages for closely shaped and overlapped spikes. For such the cases, an algorithm based on the combination of the principal component analysis and undecimated wavelet transform, is proposed to enhance the cluster formation from the spikes mapping. These results indicate that the principal component analysis used in combination with the undecimated wavelet has a better performance in the spike sorting. This can lead to more compact and separate clusters in comparison with the PCA clustering and more efficient spike sorting.

Extended Kalman filtering of point process observation.

A temporal point process is a stochastic time series of binary events that occurs in continuous time. In computational neuroscience, the point process is used to model neuronal spiking activity; however, estimating the model parameters from spike train is a challenging problem. The state space point process filtering theory is a new technique for the estimation of the states and parameters. In order to use the stochastic filtering theory for the states of neuronal system with the Gaussian assumption, we apply the extended Kalman filter. In this regard, the extended Kalman filtering equations are derived for the point process observation. We illustrate the new filtering algorithm by estimating the effect of visual stimulus on the spiking activity of object selective neurons from the inferior temporal cortex of macaque monkey. Based on the goodness-offit assessment, the extended Kalman filter provides more accurate state estimate than the conventional methods.

Cytosolic phospholipase A2alpha mediates Pseudomonas aeruginosa LPS-induced airway constriction of CFTR -/- mice.

BACKGROUND: Lungs of cystic fibrosis (CF) patients are chronically infected with Pseudomonas aeruginosa. Increased airway constriction has been reported in CF patients but underplaying mechanisms have not been elucidated. AIM: To examine the effect of P. aeruginosa LPS on airway constriction in CF mice and the implication in this process of cytosolic phospholipase A2alpha (cPLA2alpha), an enzyme involved in arachidonic acid (AA) release. METHODS: Mice were instilled intra-nasally with LPS. Airway constriction was assessed using barometric plethysmograph. MIP-2, prostaglandin E2 (PGE2), leukotrienes and AA concentrations were measured in BALF using standard kits and gas chromatography. RESULTS: LPS induced enhanced airway constriction and AA release in BALF of CF compared to littermate mice. This was accompanied by increased levels of PGE2, but not those of leukotrienes. However, airway neutrophil influx and MIP-2 production remained similar in both mouse strains. The cPLA2alpha inhibitor arachidonyl trifluoro-methyl-ketone (ATK), but not aspirin which inhibit PGE2 synthesis, reduced LPS-induced airway constriction. LPS induced lower airway constriction and PGE2 production in cPLA2alpha -/- mice compared to corresponding littermates. Neither aspirin nor ATK interfered with LPS-induced airway neutrophil influx or MIP-2 production. CONCLUSIONS: CF mice develop enhanced airway constriction through a cPLA2alpha-dependent mechanism. Airway inflammation is dissociated from airway constriction in this model. cPLA2alpha may represent a suitable target for therapeutic intervention in CF. Attenuation of airway constriction by cPLA2alpha inhibitors may help to ameliorate the clinical status of CF patients.

A combination of alpha lipoic acid and calcium hydroxycitrate is efficient against mouse cancer models: preliminary results.

The impact of metabolic dysregulation on tumor development has long been established. We have targeted two enzymes that are altered during carcinogenesis: pyruvate dehydrogenase (PDH), which is down-regulated, and ATP citrate lyase, which is overexpressed in cancer cells. Alpha lipoic acid is a cofactor of PDH, while hydroxycitrate is a known inhibitor of ATP citrate lyase. Our hypothesis is that a combination of these drugs may have antitumoral potential. The efficacy of these molecules was screened in vitro by treatment of different human cancer and murine cell lines. Lipoic acid reduced the cell number by 10-50% depending on concentrations (0.1-10 microM) and cell types. Calcium hydroxycitrate reduced the cell number by 5-60% at different concentrations (10-500 microM). When hydroxycitrate and lipoic acid were used together, there was a major cytotoxic effect: complete cell death was seen following 8 microM lipoic acid and 300 microM hydroxycitrate treatment for 72 h. The combination of alpha lipoic acid and hydroxycitrate was administered to healthy mice, at doses currently utilized for other indications than cancer; no demonstrable toxicity was observed. The combination was used to treat mouse syngenic cancer models: MBT-2 bladder transitional cell carcinoma, B16-F10 melanoma and LL/2 Lewis lung carcinoma. The efficacy of this combination appears similar to conventional chemotherapy (cisplatin or 5-fluorouracil) as it resulted in significant tumor growth retardation and enhanced survival. This preliminary study suggests that this combination of drugs is efficient against cancer cell proliferation both in vitro and in vivo. A clinical trial is warranted.

Mycobacterium bovis bacillus Calmette-Guérin killed by extended freeze-drying targets plasmacytoid dendritic cells to regulate lung inflammation.

We have previously shown that bacillus Calmette-Guérin (BCG) inactivated by extended freeze-drying (EFD) reduces airway hyperresponsiveness, whereas live and heat-killed BCG fail to do so. However, the cells involved in the protective effect and the signaling and transcriptional networks that could reprogram T cell commitment after EFD BCG treatment remained to be elucidated. We investigated whether EFD BCG targets plasmacytoid dendritic cells (pDCs) potentially involved in the polarization of regulatory T cells (Tregs) and the transcriptional factors that regulate allergic inflammation. OVA-sensitized mice were s.c. injected with EFD, live, or heat-killed BCG. We analyzed after the injection of the various BCG preparations: 1) pDCs recruited in the draining lymph nodes (day 4); 2) transcription factors involved in inflammation and T cell commitment in spleen and lungs after OVA challenge (day 28). Airway hyperresponsiveness and transcription factors were determined after in vivo depletion of pDCs or Tregs in EFD BCG-treated and OVA-challenged mice. EFD BCG reduced inflammation via the recruitment of pDCs polarizing the differentiation of naive CD4+ T lymphocytes into Tregs. In vivo, pDC or Treg depletion at the time of EFD BCG treatment abrogated the protection against inflammation. EFD BCG treatment upregulated Forkhead-winged helix transcription factor (Treg signature) and downregulated GATA-3 and RORgammat (Th2 and Th17 signatures) more efficiently than live and heat-killed BCG. Moreover, only EFD BCG enhanced peroxisome proliferator-activated receptor gamma expression and blocked NF-kappaB activation, cyclooxygenase expression, and p38 MAPK phosphorylation. EFD BCG reduced allergic inflammation by recruiting pDCs that promoted Tregs; EFD BCG acted as a peroxisome proliferator-activated receptor gamma agonist and thus could be used in asthma and other inflammatory diseases.

Optimized noninvasive monitoring of thermal changes on digital B-mode renal sonography during revascularization therapy.

OBJECTIVE: Noninvasive real-time thermal change monitoring of human internal organs can play a critical role in diagnosis and treatment of many disorders, including reperfusion of renal arteries during anticoagulation therapy. METHODS: This article focuses on tissue temperature detection using ultrasound velocity changes in different structures and their related speckle shift from their primary locations on high-quality B-mode digital sonography. We evaluated different speckle-tracking techniques and optimized them using appropriate motion estimation methods to determine the best algorithm and parameters. RESULTS: Performing thermal detection methods on simulated phantoms showed a good correlation between speckle shifts and the ground truth temperature. For the simulated images, average thermal error was 0.5 degrees C with an SD of 0.5 degrees C, where lower errors can be obtained in noiseless (motionless) data. The proposed technique was evaluated on real in vivo cases during surgical occlusion and reopening of the renal segmental artery and showed the potential of the algorithm for observation of internal organ changes using only digital ultrasound systems for diagnosis and therapy. CONCLUSIONS: The adaptive Rood pattern search proved to be the best block-matching technique, whereas the multiresolution Horn-Schunck technique was the best gradient optical flow method. The extracted thermal change during in vivo revascularization therapy is promising. In addition, we present an evaluation of several block-matching and optical flow motion estimation techniques.