How many different symptom combinations fulfil the diagnostic criteria for major depressive disorder? Results from the CRESCEND study.

PubMed

Park, Seon-Cheol; Kim, Jae-Min; Jun, Tae-Youn; Lee, Min-Soo; Kim, Jung-Bum; Yim, Hyeon-Woo; Park, Yong Chon

2017-04-01

The polythetic nature of major depressive disorder (MDD) in DSM- IV and DSM-5 inevitably leads to diagnostic heterogeneity. This study aimed to identify the number of depressive symptom combinations actually fulfilling the DSM-IV diagnostic criteria that can be found in Korean MDD patients and the relative frequencies of each combination. Using the data from the Clinical Research Center for Depression (CRESCEND) study in South Korea, we enrolled 853 MDD patients diagnosed using DSM-IV and scored as 8 or more on the Hamilton Depression Rating Scale (HAMD). Descriptive statistical analyses were performed to reveal the degree of diagnostic heterogeneity of the MDD. This study identified 119 different depressive symptom combinations. The most common combination consisted of all nine depressive symptom profiles, and nine different combinations were each present in more than 3% of the patients. The findings support the criticism that the diagnosis of MDD is not based on a single mental process, but on a set of 'family resemblances'.

[Rational combinations of antiepileptic drugs for refractory epilepsy].

PubMed

Yoshino, Aihide

2011-04-01

Although epilepsy surgery is most effective for patients with intractable epilepsy, a majority of them is not eligible for the surgery. Most of patients with refractory epilepsy are eventually treated with polypharmacy in hope of seizure control. Therefore, rational combinations of antiepileptic drugs are needed to control intractable seizures. Drug combinations should be rationally chosen based on the evidence of synergic efficacy and on avoidance of neurotoxicity. Several clinical studies suggest that the combination of valproate with lamotrigine has synergic antiepileptic effect. It has also been reported that the combination of carbamazepine with lamotrigine paradoxically decreases efficacy and increases toxicity. Animal studies using isobolography suggest that the combinations of topiramate with lamotrigine or levetiracetam are also promising on both seizure control and neurotoxicity. Clinical research is needed to examine these combinations.

Rocket Based Combined Cycle (RBCC) Propulsion Workshop, volume 2

NASA Technical Reports Server (NTRS)

Chojnacki, Kent T.

1992-01-01

The goal of the Rocket Based Combined Cycle (RBCC) Propulsion Technology Workshop, was to impart technology information to the propulsion community with respect to hypersonic combined cycle propulsion capabilities. The major recommendation resulting from this technology workshop was as follows: conduct a systems-level applications study to define the desired propulsion system and vehicle technology requirements for LEO launch vehicles. All SSTO and TSTO options using the various propulsion systems (airbreathing combined cycle, rocket-based combined cycle, and all rocket) must be considered. Such a study should be accomplished as soon as possible. It must be conducted with a consistent set of ground rules and assumptions. Additionally, the study should be conducted before any major expenditures on a RBCC technology development program occur.

Combination alpha-interferon and lamivudine therapy for alpha-interferon-resistant chronic hepatitis B infection: results of a pilot study.

PubMed

Mutimer, D; Naoumov, N; Honkoop, P; Marinos, G; Ahmed, M; de Man, R; McPhillips, P; Johnson, M; Williams, R; Elias, E; Schalm, S

1998-06-01

Alpha-interferon achieves seroconversion in about one third of naive patients. Attempts to achieve seroconversion in patients who have previously failed alpha-interferon have proved disappointing. Combination chemotherapy (alpha-interferon with a nucleoside analogue) might provide a treatment alternative for these patients. We have undertaken a phase 2 study in 20 patients who had previously failed at least one course of alpha-interferon. The study was designed to assess the safety, tolerability and efficacy of the combination. All patients were treated for 16 weeks with alpha-interferon in combination with 12 or 16 weeks of Lamivudine (3'TC). Patients were followed for 16 weeks post-treatment. Pharmacokinetic studies were performed to identify/exclude significant pharmacokinetic drug interaction. The combination was well tolerated, and side-effects of the combination were indistinguishable from the recognised side-effects of alpha-interferon. Pharmacokinetic studies performed on days 1 and 29 did not show any significant interaction. All patients achieved HBV DNA clearance during treatment, but 19 relapsed at the end of treatment. HBeAg/anti-HBe seroconversion was observed for four patients, but was sustained for a single patient (who also had sustained DNA clearance). Combination therapy with alpha-interferon and lamivudine given for 16 weeks appears safe and is well tolerated. However, for this group of patients who had previously failed interferon monotherapy, the efficacy of combination interferon/lamivudine therapy appears disappointing, and other treatment strategies should be investigated.

The Clinical Development of Molecularly Targeted Agents in Combination With Radiation Therapy: A Pharmaceutical Perspective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ataman, Ozlem U., E-mail: ouataman@hotmail.com; Sambrook, Sally J.; Wilks, Chris

2012-11-15

Summary: This paper explores historical and current roles of pharmaceutical industry sponsorship of clinical trials testing radiation therapy combinations with molecularly targeted agents and attempts to identify potential solutions to expediting further combination studies. An analysis of clinical trials involving a combination of radiation therapy and novel cancer therapies was performed. Ongoing and completed trials were identified by searching the (clinicaltrials.gov) Web site, in the first instance, with published trials of drugs of interest identified through American Society of Clinical Oncology, European CanCer Organisation/European Society for Medical Oncology, American Society for Radiation Oncology/European Society for Therapeutic Radiology and Oncology, andmore » PubMed databases and then cross-correlated with (clinicaltrials.gov) protocols. We examined combination trials involving radiation therapy with novel agents and determined their distribution by tumor type, predominant molecular mechanisms examined in combination to date, timing of initiation of trials relative to a novel agent's primary development, and source of sponsorship of such trials. A total of 564 studies of targeted agents in combination with radiation therapy were identified with or without concomitant chemotherapy. Most studies were in phase I/II development, with only 36 trials in phase III. The tumor site most frequently studied was head and neck (26%), followed by non-small cell lung cancer. Pharmaceutical companies were the sponsors of 33% of studies overall and provided support for only 16% of phase III studies. In terms of pharmaceutical sponsorship, Genentech was the most active sponsor of radiation therapy combinations (22%), followed by AstraZeneca (14%). Most radiation therapy combination trials do not appear to be initiated until after drug approval. In phase III studies, the most common (58%) primary endpoint was overall survival. Collectively, this analysis suggests that such trials are not given priority by pharmaceutical companies. The potential reasons for this and some challenges and possible solutions are discussed.« less

Improving Student Writing through Sentence Combining: A Literature Review. Technical Note.

ERIC Educational Resources Information Center

Lawlor, Joseph

The theoretical roots of sentence combining as a pedagogical strategy are discussed in this paper, along with recent studies of the development of written syntactic maturity. The paper examines several major sentence combining studies in detail and briefly summarizes additional relevant literature. The instructional implications of sentence…

Concurrent Drought Stress and Vascular Pathogen Infection Induce Common and Distinct Transcriptomic Responses in Chickpea

PubMed Central

Sinha, Ranjita; Gupta, Aarti; Senthil-Kumar, Muthappa

2017-01-01

Chickpea (Cicer arietinum); the second largest legume grown worldwide is prone to drought and various pathogen infections. These drought and pathogen stresses often occur concurrently in the field conditions. However, the molecular events in response to that are largely unknown. The present study examines the transcriptome dynamics in chickpea plants exposed to a combination of water-deficit stress and Ralstonia solanacearum infection. R. solanacearum is a potential wilt disease causing pathogen in chickpea. Drought stressed chickpea plants were infected with this pathogen and the plants were allowed to experience progressive drought with 2 and 4 days of R. solanacearum infection called short duration stress (SD stresses) and long duration stress (LD stresses), respectively. Our study showed that R. solanacearum multiplication decreased under SD-combined stress compared to SD-pathogen but there was no significant change in LD-combined stress compared to LD-pathogen. The microarray analysis during these conditions showed that 821 and 1039 differentially expressed genes (DEGs) were unique to SD- and LD-combined stresses, respectively, when compared with individual stress conditions. Three and fifteen genes were common among all the SD-stress treatments and LD-stress treatments, respectively. Genes involved in secondary cell wall biosynthesis, alkaloid biosynthesis, defense related proteins, and osmo-protectants were up-regulated during combined stress. The expression of genes involved in lignin and cellulose biosynthesis were specifically up-regulated in SD-combined, LD-combined, and LD-pathogen stress. A close transcriptomic association of LD-pathogen stress with SD-combined stress was observed in this study which indicates that R. solanacearum infection also exerts drought stress along with pathogen stress thus mimics combined stress effect. Furthermore the expression profiling of candidate genes using real-time quantitative PCR validated the microarray data. The study showed that down-regulation of defense-related genes during LD-combined stress resulted in an increased bacterial multiplication as compared to SD-combined stress. Overall, our study highlights a sub-set of DEGs uniquely expressed in response to combined stress, which serve as potential candidates for further functional characterization to delineate the molecular response of the plant to concurrent drought-pathogen stress. PMID:28382041

Cravings as a mediator and moderator of drinking outcomes in the COMBINE Study

PubMed Central

Lendle, Samuel; van der Laan, Mark; Kaskutas, Lee Ann; Ahern, Jennifer

2014-01-01

Aims Investigators of the COMBINE (Combining Medications and Behavioral Interventions for Alcoholism) Study examined whether combining medications with a behavioral intervention would improve outcomes over monotherapies. Unexpectedly, the combination did not offer any advantage over either treatment alone. This study aimed to explain the lack of incremental benefit offered by the combination over either monotherapy by assessing the role of cravings as a treatment mediator and moderator. Design Secondary mediation and moderation analyses of COMBINE study data. Setting Eleven United States academic sites. Participants 863 patients randomized to one of four treatment groups: naltrexone (100mg/d; n=209), the Combined Behavioral Intervention (CBI, n=236), naltrexone and CBI combined (n=213), and placebo naltrexone (n=205). Measurements Percent Days Abstinent (PDA) measured between 13 and 16 weeks post-baseline. Cravings, the potential mediator/moderator, was measured at baseline, week 4 and week 12 using the Obsessive-Compulsive Drinking Scale. Findings Compared to placebo, naltrexone, CBI, and the combination all increased PDA by an additional 6–10 percentage points for those with high cravings (p<0.05 for all three treatment groups). None had significant effects on PDA for those with low cravings. The effects of all three treatments were at least partially mediated by cravings; craving reduction explained 48–53% of treatment effects (p<0.05 for all three treatment groups). Furthermore, naltrexone appeared to reduce cravings at 4 weeks, while CBI did not reduce cravings until 12 weeks. Conclusions Naltrexone and the behavioral intervention both improved abstinence by reducing cravings and were no longer effective once cravings were low. Furthermore, naltrexone reduced cravings by 4 weeks, while the behavioral intervention took longer to affect cravings. The COMBINE naltrexone + CBI combination may not have been more beneficial than either monotherapy because craving reduction was a common mechanism of both, and neither worked when cravings were low. PMID:23668624

Combinations of Radiotherapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

PubMed Central

Barker, Christopher A.; Postow, Michael A.

2015-01-01

Radiotherapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiotherapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiotherapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiotherapy. The cytokines interferon-alpha and interleukin-2 have been combined with radiotherapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiotherapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested radiotherapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiotherapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study. PMID:24661650

Ulcerative colitis loci on chromosomes 1p36 and 12q15 identified by genome-wide association study

PubMed Central

Silverberg, Mark S.; Cho, Judy H.; Rioux, John D.; McGovern, Dermot P.B.; Wu, Jing; Annese, Vito; Achkar, Jean-Paul; Goyette, Philippe; Scott, Regan; Xu, Wei; Barmada, M. Michael; Klei, Lambertus; Daly, Mark J.; Abraham, Clara; Bayless, Theodore M.; Bossa, Fabrizio; Griffiths, Anne M.; Ippoliti, Andrew F.; Lahaie, Raymond G.; Latiano, Anna; Paré, Pierre; Proctor, Deborah D.; Regueiro, Miguel D.; Steinhart, A. Hillary; Targan, Stephan R.; Schumm, L. Philip; Kistner, Emily O.; Lee, Annette T.; Gregersen, Peter K.; Rotter, Jerome I.; Brant, Steven R.; Taylor, Kent D.; Roeder, Kathryn; Duerr, Richard H.

2008-01-01

Ulcerative colitis is a chronic inflammatory disease of the colon that presents as diarrhea and gastrointestinal bleeding. We performed a genome-wide association study using DNA samples from 1,052 individuals with ulcerative colitis and pre-existing data from 2,571 controls, all of European ancestry. In an analysis that controlled for gender and population structure, ulcerative colitis loci attaining genome-wide significance and subsequent replication in two independent populations were identified on chromosomes 1p36 (rs6426833, combined P = 5.1×10−13, combined OR = 0.73) and 12q15 (rs1558744, combined P = 2.5×10−12, combined OR = 1.35). In addition, combined genome-wide significant evidence for association was found in a region spanning BTNL2 to HLA-DQB1 on chromosome 6p21 (rs2395185, combined P = 1.0×10−16, combined OR = 0.66) and at the IL23R locus on chromosome 1p31 (rs11209026, combined P = 1.3×10−8, combined OR = 0.56; rs10889677, combined P = 1.3×10−8, combined OR = 1.29). PMID:19122664

U32: vehicle stability and dynamics longer combination vehicles final report.

DOT National Transportation Integrated Search

2011-09-01

This study investigated the safety and stability of longer combination vehicles (LCVs), in particular a triple trailer combination behind a commercial tractor, which has more complicated dynamics than the more common tractor in combination with a sin...

The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol

PubMed Central

2010-01-01

Background Ibuprofen and paracetamol differ in their mode of action and related therapeutic effects, suggesting that combined administration may offer improved analgesia. Reported here are the results of two studies on the pharmacokinetic properties of a novel ibuprofen (200 mg) and paracetamol (500 mg) fixed-dose combination tablet. Methods Both studies were open-label, randomised studies in healthy volunteers: Study 1 was a four-way crossover, single-dose study; Study 2 was a two-way cross-over, repeat-dose study. Results Pharmacokinetic parameters for ibuprofen and paracetamol were similar for the combination and monotherapy tablets (values falling within the 80% to 125% acceptable bioequivalence range) except for the rate of absorption of paracetamol from the combination (tmax), which was significantly faster compared with monotherapy (median difference 10 minutes; p < 0.05). Mean plasma concentrations of both drugs were higher, earlier, following administration of the combination tablet compared with monotherapy. Mean plasma levels at 10 and 20 minutes were 6.64 μg.mL-1 and 16.81 μg.mL-1, respectively, for ibuprofen from the combination, compared with 0.58 μg.mL-1 and 9.00 μg.mL-1, respectively, for monotherapy. For paracetamol, mean plasma levels at 10 and 20 minutes were 5.43 μg.mL-1 and 14.54 μg.mL-1, respectively, for the combination compared with 0.33 μg.mL-1 and 9.19 μg.mL-1, respectively, for monotherapy. The rate of absorption of both ibuprofen and paracetamol was significantly delayed when the combination tablet was administered in the fed versus fasted state; median delay was 25 minutes for ibuprofen (p > 0.05) and 55 minutes for paracetamol (p < 0.001). The pharmacokinetic parameters were comparable irrespective of whether the combination tablet was given twice or three times daily; systemic exposure was, however, approximately 1.4 times greater for both drugs when given three times daily. Conclusions Administration of ibuprofen and paracetamol in a fixed-dose combination tablet does not significantly alter the pharmacokinetic profiles of either drug, except for enhancing the rate of paracetamol absorption, offering potential therapeutic benefits in relation to the onset of analgesia. Concentrations of both drugs reached previously reported therapeutic levels when the combination tablet was administrated in the fed or fasted state. Three times daily dosing may offer enhanced therapeutic effect for longer than twice daily dosing. PMID:20602760

Experimental Design for Multi-drug Combination Studies Using Signaling Networks

PubMed Central

Huang, Hengzhen; Fang, Hong-Bin; Tan, Ming T.

2017-01-01

Summary Combinations of multiple drugs are an important approach to maximize the chance for therapeutic success by inhibiting multiple pathways/targets. Analytic methods for studying drug combinations have received increasing attention because major advances in biomedical research have made available large number of potential agents for testing. The preclinical experiment on multi-drug combinations plays a key role in (especially cancer) drug development because of the complex nature of the disease, the need to reduce development time and costs. Despite recent progresses in statistical methods for assessing drug interaction, there is an acute lack of methods for designing experiments on multi-drug combinations. The number of combinations grows exponentially with the number of drugs and dose-levels and it quickly precludes laboratory testing. Utilizing experimental dose-response data of single drugs and a few combinations along with pathway/network information to obtain an estimate of the functional structure of the dose-response relationship in silico, we propose an optimal design that allows exploration of the dose-effect surface with the smallest possible sample size in this paper. The simulation studies show our proposed methods perform well. PMID:28960231

Exploring the Interrelationship of Structure and Process in Family Child Care: The FCCERS-R and "Combined" CLASS

ERIC Educational Resources Information Center

Enns, Lionel

2012-01-01

This study examined the correlations between two prominent family child care environmental rating scales, the Family Child Care Environment Rating Scale - Revised (FCCERS-R) and the "Combined" Classroom Assessment Scoring System ("Combined" CLASS), both of which were used during the pilot study of Washington State's Quality…

A Conservative Inverse Normal Test Procedure for Combining P-Values in Integrative Research.

ERIC Educational Resources Information Center

Saner, Hilary

1994-01-01

The use of p-values in combining results of studies often involves studies that are potentially aberrant. This paper proposes a combined test that permits trimming some of the extreme p-values. The trimmed statistic is based on an inverse cumulative normal transformation of the ordered p-values. (SLD)

Enhanced antioxidant activity of gold nanoparticle embedded 3,6-dihydroxyflavone: a combinational study

NASA Astrophysics Data System (ADS)

Medhe, Sharad; Bansal, Prachi; Srivastava, Man Mohan

2014-02-01

The antioxidative effect of selected dietary compounds (3,6-dihydroxyflavone, lutein and selenium methyl selenocysteine) was determined in single and combination using DPPH (2,2-diphenyl-l-picrylhydrazyl), OH (hydroxyl), H2O2 (hydrogen peroxide) and NO (nitric oxide) radical scavenging assays. Radical scavenging effect of the dietary phytochemicals individually are found to be in the order: ascorbic acid (standard) > lutein > 3,6-dihydroxyflavone > selenium methyl selenocysteine, at concentration 100 μg/ml, confirmed by all the four bioassays (p < 0.05). Among the various combinations studied, the triplet combination of 3,6-dihydroxyflavone, lutein and selenium methyl selenocysteine (1:1:1), exhibited enhancement in the target activity at same concentration level. Synthesized gold nanoparticle embedded 3,6-dihydroxyflavone further enhanced the target antioxidant activity. The combinational study including gold nanoparticle embedded 3,6-dihydroxyflavone with other native dietary nutrients showed remarkable increase in antioxidant activity at the same concentration level. The present in vitro study on combinational and nanotech enforcement of dietary phytochemicals shows the utility in the architecture of nanoparticle embedded phytoproducts having a wide range of applications in medical science.

Perceived Costs of Combining Career and Family Roles: The Influence of Early Family History on Adult Role Decisions.

ERIC Educational Resources Information Center

Berson, Janet S.

This study attempts to clarify part of the decision-making process centering around combining family and career. There are two aspects of the study. In the first, perceived costs of combining roles are assessed and evaluated in light of mother's employment history. The subjects in this part of the study were 141 single women and 43 married women.…

Development of fat-reduced sausages: Influence of binary and ternary combinations of carrageenan, inulin, and bovine plasma proteins.

PubMed

Baracco, Yanina; Rodriguez Furlán, Laura T; Campderrós, Mercedes E

2017-04-01

The aim of this work was to study the influence of the binary and ternary combinations of bovine plasma proteins (BPP), inulin (I) and κ-carrageenan (C) in the overall quality of fat-reduced sausages. The influence of these components over different properties (chemical composition, weight loss after cooking, emulsion stability, texture profile and sensory analysis of fat-reduced sausages) was studied and compared against two samples, one without fat reduction and another a fat-reduced sample without addition of texturing agents. In this sense, a full factorial experimental design of two levels with central point was used. The samples containing BPP+I and BPP+C showed a synergy in which the binary combinations presented higher values of moisture and protein content than the samples containing the individual components. The reduction of fat content increases the values of hardness and decreases the values of springiness. Samples with 5% BPP (w/w) and binary combinations of BPP+C and BPP+I had the best stability values (low total fluid loss), demonstrating a significant synergistic effect by combining BPP+C. Similar results were obtained from the study of weight loss after cooking. However, both studies showed a destabilization of the sample BPP+I+C as emulsion stability decreased and weight loss increased after cooking compared to binary combinations ( P < 0.05). Samples with a binary combination of BPP+C and BPP+I do not present a statistically significant difference in the chewiness with respect to a not-fat-reduced commercial sample ( P > 0.05). The less acceptable sample for flavor and texture was the one containing only BPP. However, when BPP combined with I or C, a major acceptability was obtained, demonstrating the synergistic effect of these binary combinations. Therefore, our studies revealed that the binary combinations of BPP with I or C are good alternatives for the development of fat-reduced sausage.

Towards an understanding of adult judgments of synergistic health benefits.

PubMed

Dawson, Ian G J; Dohle, Simone

2016-02-01

Numerous scientific studies show that certain combinations of dietary and/or lifestyle factors produce health benefits which are greater than the sum of the benefits associated with each factor alone. To address an existing knowledge gap, we assessed the extent to which individuals understand that certain combinations present these 'synergistic health benefits'. Health benefit judgments were obtained from lay adults for a range of dietary and/or lifestyle combinations that have been found to present synergistic benefits. Association between these judgments and socio-cognitive characteristics such as numeracy, education, and health interest (HI) were examined. Three hundred and fifty-two Swiss adults were presented with a description of one of eight synergistically beneficial combinations. Each participant provided a categorical benefit judgment (i.e., subadditive, additive, or synergistic) for the combination and explained the cognitive reasoning underlying their judgment. Participants completed measures of numeracy and HI. The proportion of combinations judged to present a synergistic benefit was modest for 'macro-level' combinations (e.g., diet and exercise), but low for 'micro-level' combinations (e.g., two phytochemicals). Cognitive reasoning data showed that a higher proportion of judgments for micro-level (cf. macro-level) combinations were based on greater subjective epistemic uncertainty. Higher interest in health was associated with a better understanding of synergistic benefits, but numeracy and education level were not. There is considerable scope to improve the extent to which lay adults understand that specific combination of diet and lifestyle behaviours can synergistically benefit their health. Our results enable us to make informed recommendations for public health interventions. What is already known on this subject? Combining certain dietary and/or lifestyle factors can result in synergistic health benefits. People could maintain/enhance their health by combining these synergistic combinations. No previous studies have assessed the extent to which people understand that certain factors produce synergistic health benefits. What does this study add? This is the first study to identify that lay awareness of synergistic health benefits could be substantially improved. Neither education level nor numeracy moderate judgments of synergistic benefits, but health interest does. Individuals better understand that broad lifestyle behaviours (cf. specific foods and phytochemicals) are synergistic. © 2015 The British Psychological Society.

Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: A genome-wide interaction study

PubMed Central

Rudolph, Anja; Hein, Rebecca; Lindström, Sara; Beckmann, Lars; Behrens, Sabine; Liu, Jianjun; Aschard, Hugues; Bolla, Manjeet K.; Wang, Jean; Truong, Thérèse; Cordina-Duverger, Emilie; Menegaux, Florence; Brüning, Thomas; Harth, Volker; Severi, Gianluca; Baglietto, Laura; Southey, Melissa; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Eriksson, Mikael; Humpreys, Keith; Darabi, Hatef; Olson, Janet E.; Stevens, Kristen N.; Vachon, Celine M.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Webb, Penny M.; Guénel, Pascal; Brauch, Hiltrud; Giles, Graham; García-Closas, Montserrat; Czene, Kamila; Chenevix-Trench, Georgia; Couch, Fergus J.; Andrulis, Irene L.; Swerdlow, Anthony; Hunter, David J.; Flesch-Janys, Dieter; Easton, Douglas F.; Hall, Per; Nevanlinna, Heli; Kraft, Peter; Chang-Claude, Jenny

2013-01-01

Women using menopausal hormone therapy (MHT) are at increased risk to develop breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in eleven case-control studies. We used a case-only design to assess interactions between single nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2,920 cases (541 lobular) from four genome-wide association studies. The top 1,391 SNPs showing P-values for interaction (Pint) <3.0×10−03 were selected for replication using pooled case-control data from eleven studies of the Breast Cancer Association Consortium, including 7,689 cases (676 lobular) and 9,266 controls. Fixed effects meta-analysis was used to derive combined Pint. No SNP reached genome-wide significance in either the discovery or combined stage. We observed effect modification of current MHT use on overall BC risk by two SNPs on chr13 near POMP (combined Pint≤8.9×10−06), two SNPs in SLC25A21 (combined Pint≤4.8×10−05), and three SNPs in PLCG2 (combined Pint≤4.5×10−05). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined Pint≤2.7×10−05), one SNP in CD80 (combined Pint≤8.2×10−06), three SNPs on chr17 near TMEM132E (combined Pint≤2.2×10−06), and two SNPs on chr18 near SLC25A52 (combined Pint≤4.6×10−05). In conclusion, polymorphisms in genes related to solute transportation in mitochondria, transmembrane signaling and immune cell activation are potentially modifying BC risk associated with current use of MHT. These findings warrant replication in independent studies. PMID:24080446

Indentification and Analysis of Occludin Phosphosites: A Combined Mass Spectroscoy and Bioinformatics Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sundstrom, J.; Tash, B; Murakami, T

2009-01-01

The molecular function of occludin, an integral membrane component of tight junctions, remains unclear. VEGF-induced phosphorylation sites were mapped on occludin by combining MS data analysis with bioinformatics. In vivo phosphorylation of Ser490 was validated and protein interaction studies combined with crystal structure analysis suggest that Ser490 phosphorylation attenuates the interaction between occludin and ZO-1. This study demonstrates that combining MS data and bioinformatics can successfully identify novel phosphorylation sites from limiting samples.

Prevalence of Drug Combinations Increasing Bleeding Risk Among Warfarin Users With and Without Alzheimer's Disease.

PubMed

Taipale, Heidi; Vuorikari, Hanna; Tanskanen, Antti; Koponen, Marjaana; Tiihonen, Jari; Kettunen, Raimo; Hartikainen, Sirpa

2015-11-01

The aim of this study was to analyse the prevalence and predictors of drug combinations increasing bleeding risk among warfarin users with and without Alzheimer's disease (AD). This retrospective observational study utilised data from the Finnish MEDALZ-2005 cohort. The MEDALZ-2005 study included all community-dwelling persons with a clinically verified diagnosis of AD at the end of 2005, and one comparison person without AD for each case. Data on drug use was collected from the Prescription Register. We included persons who were warfarin users during the study period 2006-2009. Drug combinations increasing bleeding risk with warfarin included selective serotonin reuptake inhibitors (SSRIs), non-steroidal anti-inflammatory agents (NSAIDs), other antithrombotic drugs and tramadol. Factors associated with combination use were investigated with logistic regression. During the follow-up, 3385 persons with AD and 4830 persons without AD used warfarin. Drug combinations increasing bleeding risk were more common in warfarin users with AD than without AD [35.9 and 30.5%, respectively (p < 0.0001)]. The most common combination was SSRIs and warfarin, which was more common among persons with AD (23.8%) than among persons without AD (10.9%). NSAIDs and warfarin combination was more common among persons without AD. Combination use was associated with AD, female gender, younger age, diabetes mellitus, rheumatoid arthritis and asthma/chronic obstructive pulmonary disease (COPD). Use of drug combinations increasing bleeding risk was more common among warfarin users with AD. Special attention should be paid to minimise the duration of concomitant use and to find safer alternatives without increased bleeding risk.

Combination therapy for erectile dysfunction: an update review.

PubMed

Dhir, Rohit R; Lin, Hao-Cheng; Canfield, Steven E; Wang, Run

2011-05-01

The introduction of oral phosphodiesterase-5 inhibitors (PDE5Is) in the late 1990s and early 2000s revolutionized the field of sexual medicine and PDE5Is are currently first-line monotherapy for erectile dysfunction (ED). However, a significant proportion of patients with complex ED will be therapeutic non-responders to PDE5I monotherapy. Combination therapy has recently been adopted for more refractory cases of ED, but a critical evaluation of current combination therapies is lacking. A thorough PubMed and Cochrane Library search was conducted focusing on the effectiveness of combination therapies for ED in therapeutic non-responders to PDE5I therapy. Journal articles spanning the time period between January 1990 and December 2010 were reviewed. Criteria included all pertinent review articles, randomized controlled trials, cohort studies and retrospective analyses. References from retrieved articles were also manually scanned for additional relevant publications. Published combination therapies include PDE5I plus vacuum erectile device (VED), intraurethral medication, intracavernosal injection (ICI), androgen supplement, α-blocker or miscellaneous combinations. Based on this review, some of these combination treatments appeared to be quite effective in preliminary testing. Caution must be advised, however, as the majority of combination therapy articles in the last decade have numerous limitations including study biases and small subject size. Regardless of limitations, present combination therapy research provides a solid foundation for future studies in complex ED management.

ABA Is Required for Plant Acclimation to a Combination of Salt and Heat Stress.

PubMed

Suzuki, Nobuhiro; Bassil, Elias; Hamilton, Jason S; Inupakutika, Madhuri A; Zandalinas, Sara Izquierdo; Tripathy, Deesha; Luo, Yuting; Dion, Erin; Fukui, Ginga; Kumazaki, Ayana; Nakano, Ruka; Rivero, Rosa M; Verbeck, Guido F; Azad, Rajeev K; Blumwald, Eduardo; Mittler, Ron

2016-01-01

Abiotic stresses such as drought, heat or salinity are a major cause of yield loss worldwide. Recent studies revealed that the acclimation of plants to a combination of different environmental stresses is unique and cannot be directly deduced from studying the response of plants to each of the different stresses applied individually. Here we report on the response of Arabidopsis thaliana to a combination of salt and heat stress using transcriptome analysis, physiological measurements and mutants deficient in abscisic acid, salicylic acid, jasmonic acid or ethylene signaling. Arabidopsis plants were found to be more susceptible to a combination of salt and heat stress compared to each of the different stresses applied individually. The stress combination resulted in a higher ratio of Na+/K+ in leaves and caused the enhanced expression of 699 transcripts unique to the stress combination. Interestingly, many of the transcripts that specifically accumulated in plants in response to the salt and heat stress combination were associated with the plant hormone abscisic acid. In accordance with this finding, mutants deficient in abscisic acid metabolism and signaling were found to be more susceptible to a combination of salt and heat stress than wild type plants. Our study highlights the important role abscisic acid plays in the acclimation of plants to a combination of two different abiotic stresses.

ABA Is Required for Plant Acclimation to a Combination of Salt and Heat Stress

PubMed Central

Suzuki, Nobuhiro; Bassil, Elias; Hamilton, Jason S.; Inupakutika, Madhuri A.; Zandalinas, Sara Izquierdo; Tripathy, Deesha; Luo, Yuting; Dion, Erin; Fukui, Ginga; Kumazaki, Ayana; Nakano, Ruka; Rivero, Rosa M.; Verbeck, Guido F.; Azad, Rajeev K.; Blumwald, Eduardo; Mittler, Ron

2016-01-01

Abiotic stresses such as drought, heat or salinity are a major cause of yield loss worldwide. Recent studies revealed that the acclimation of plants to a combination of different environmental stresses is unique and cannot be directly deduced from studying the response of plants to each of the different stresses applied individually. Here we report on the response of Arabidopsis thaliana to a combination of salt and heat stress using transcriptome analysis, physiological measurements and mutants deficient in abscisic acid, salicylic acid, jasmonic acid or ethylene signaling. Arabidopsis plants were found to be more susceptible to a combination of salt and heat stress compared to each of the different stresses applied individually. The stress combination resulted in a higher ratio of Na+/K+ in leaves and caused the enhanced expression of 699 transcripts unique to the stress combination. Interestingly, many of the transcripts that specifically accumulated in plants in response to the salt and heat stress combination were associated with the plant hormone abscisic acid. In accordance with this finding, mutants deficient in abscisic acid metabolism and signaling were found to be more susceptible to a combination of salt and heat stress than wild type plants. Our study highlights the important role abscisic acid plays in the acclimation of plants to a combination of two different abiotic stresses. PMID:26824246

Simulation study on combination of GRACE monthly gravity field solutions

NASA Astrophysics Data System (ADS)

Jean, Yoomin; Meyer, Ulrich; Jäggi, Adrian

2016-04-01

The GRACE monthly gravity fields from different processing centers are combined in the frame of the project EGSIEM. This combination is done on solution level first to define weights which will be used for a combination on normal equation level. The applied weights are based on the deviation of the individual gravity fields from the arithmetic mean of all involved gravity fields. This kind of weighting scheme relies on the assumption that the true gravity field is close to the arithmetic mean of the involved individual gravity fields. However, the arithmetic mean can be affected by systematic errors in individual gravity fields, which consequently results in inappropriate weights. For the future operational scientific combination service of GRACE monthly gravity fields, it is necessary to examine the validity of the weighting scheme also in possible extreme cases. To investigate this, we make a simulation study on the combination of gravity fields. Firstly, we show how a deviated gravity field can affect the combined solution in terms of signal and noise in the spatial domain. We also show the impact of systematic errors in individual gravity fields on the resulting combined solution. Then, we investigate whether the weighting scheme still works in the presence of outliers. The result of this simulation study will be useful to understand and validate the weighting scheme applied to the combination of the monthly gravity fields.

SIDE-EFFECTS OF COMBINED RADIATION AND CHEMOTHERAPY IN THE TREATMENT OF MALIGNANT TUMORS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ottoman, R.E.; Langdon, E.A.; Rochlin, D.B.

1963-12-01

A study was made of the effects of 5-fluorouracil (FU) and x irradiation, separately and in combination, upon multiple metastatic tumors within individual patients. Fourteen cases satisfied the criteria for a controlled study. In 4, the effects of irradiation alone were greater than the combination, in 4 the effects were equal, and in 6 the effects of irradiation were less than those of combination therapy. This study failed to demonstrate a significant alteration in the tumor response by the addition of FU to x irradiation. Four instances of unusual reactions in previously irradiated skin were noted following FU administration. (auth)

The antitumor efficacy of cisplatin in combination with triptorelin and exemestane therapy for an ovarian cancer ascites model in Wistar rats.

PubMed

Tkalia, I G; Vorobyova, L I; Grabovoy, A N; Svintsitsky, V S; Tarasova, T O

2015-03-01

To study antitumor activity of triptorelin - agonist of gonadotropin-releasing hormone and exemestane - inhibitor of aromatase in combination with cisplatin on the model of receptor-positive for estrogens and progesterone malignant transplantable ascites ovarian tumor (OT); to assess tumor response to treatment and VEGF expression in tumor cells under different combinations of cytostatic and hormonal drugs. 36 female Wistar rats, which underwent intraperitoneal transplantation of ascites OT (5×10(6) cells per animal), have been involved in the study. Rats were distributed into 4 groups (9 rats in each group): group 1 - animals, which received combination of cisplatin and triptorelin; group 2 - rats treated with combination of cisplatin and exemestane; group 3 - animals, which were administered with combination of cisplatin, triptorelin and exemestane; group 4 - rats, which received combination of triptorelin and exemestane. Histological study with assessment of treatment pathomorphosis in OT and immunohistochemical study have been carried out to analyze VEGF expression in OT cells. Survival of animals has been evaluated. Combination of cytostatic agent with triptorelin or exemestane has demonstrated significantly higher rates of treatment pathomorphosis (10.1 ± 0.1% and 16.2 ± 0.3%, respectively) and antiangiogenic activity in OT (21.4 ± 1.4% and 15.0 ± 1.3%, respectively), as well as the highest survival of animals (100.0 and 85.7%, respectively) as compared with the same in rats treated in regimen of monotherapy with cisplatin, triptorelin, exemestane or by combination of hormonal drugs. Among animals treated by combination of cytostatic drug with triptorelin, two were cured (22.2%), and among rats, which received cisplatin and exemestane, one animal (11.1%) was cured. Triptorelin and exemestane increase antitumor activity of cisplatin in respect to the transplantable malignant ascites OT and significantly increase survival of animals, especially when triptorelin and cisplatin are used in combination.

Berberine, a natural product, combined with cisplatin enhanced apoptosis through a mitochondria/caspase-mediated pathway in HeLa cells.

PubMed

Youn, Myung-Ja; So, Hong-Seob; Cho, Hea-Joong; Kim, Hyung-Jin; Kim, Yunha; Lee, Jeong-Han; Sohn, Jung Sook; Kim, Yong Kyu; Chung, Sang-Young; Park, Raekil

2008-05-01

Berberine, a main component of Coptidis Rhizoma, has been extensively studied and is known to exhibit multiple pharmacologic activities. In this study, we investigated whether the combination of berberine and cisplatin exhibited significant cytotoxicity in HeLa cells. Apoptosis was evaluated based on DNA fragmentation and cytofluorometrically with the annexin-V/propidium iodide labeling method. Combined treatment with berberine and cisplatin acted in concert to induce loss of mitochondrial membrane potential (Delta Psi m), release of cytochrome-c from mitochondria, and decreased expression of antiapoptotic Bcl-2, Bcl-x/L, resulting in activation of caspases and apoptosis. Further study showed that cell death induced by the combined treatment was associated with increased reactive oxygen species generation and lipid peroxidation. Moreover, we discovered that the combined treatment-induced apoptosis was mediated by the activation of the caspase cascade. These results indicated that the potential of cytotoxicity mediated through the mitochondria-caspase pathway is primarily involved in the combined treatment-induced apoptosis.

Combination Pharmacotherapies for Stimulant Use Disorder: A Review of Clinical Findings and Recommendations for Future Research

PubMed Central

Stoops, William W.; Rush, Craig R.

2014-01-01

Despite concerted efforts to identify a pharmacotherapy for managing stimulant use disorders, no widely effective medications have been approved. Innovative strategies are necessary to develop successful pharmacotherapies for stimulant use disorders. This manuscript reviews human laboratory studies and clinical trials to determine whether one such strategy, use of combination pharmacotherapies, holds promise. The extant literature shows that combination pharmacotherapy produced results that were better than placebo treatment, especially with medications shown to have efficacy as monotherapies. However, many studies did not compare individual constituents to the combination treatment, making it impossible to determine whether combination treatment is more effective than monotherapy. Future research should systematically compare combined treatments with individual agents using medications showing some efficacy when tested alone. PMID:24716825

Combined Effect of Fluid and Pressure on Middle Ear Function

PubMed Central

Dai, Chenkai; Wood, Mark W.; Gan, Rong Z.

2008-01-01

In our previous studies, the effects of effusion and pressure on sound transmission were investigated separately. The aim of this study is to investigate the combined effect of fluid and pressure on middle ear function. An otitis media with effusion model was created by injecting saline solution and air pressure simultaneously into the middle ear of human temporal bones. Tympanic membrane displacement in response to 90 dB SPL sound input was measured by a laser vibrometer and the compliance of the middle ear was measured by a tympanometer. The movement of the tympanic membrane at the umbo was reduced up to 17 dB by the combination of fluid and pressure in the middle ear over the auditory frequency range. The fluid and pressure effects on the umbo movement in the fluid-pressure combination are not additive. The combined effect of fluid and pressure on the umbo movement is different compared with that of only fluid or pressure change in the middle ear. Negative pressure in fluid-pressure combination had more effect on middle ear function than positive pressure. Tympanometry can detect the middle ear pressure of the fluid-pressure combination. This study provides quantitative information for analysis of the combined effect of fluid and pressure on tympanic membrane movement. PMID:18162348

Congenital combined deficiency of coagulation factors: a study of seven patients.

PubMed

Naderi, Majid; Tabibian, Shadi; Hosseini, Maryam Sadat; Alizadeh, Shaban; Hosseini, Soudabeh; Shamsizadeh, Morteza; Dorgalaleh, Akbar

2015-01-01

Combined deficiency of coagulation factors is considered as an extremely rare bleeding disorder (RBD) inherited in an autosomal recessive pattern. This disorder is more likely to occur in regions with a high rate of consanguineous marriages or in restricted communities. Sistan and Baluchistan, a province in southeast of Iran with a high rate of consanguinity, is a clear model of such regions with a very high prevalence of recessively inherited disorders. The aim of this study was to report the frequency of combined factor deficiency in this province. This descriptive study was conducted on 358 patients with RBD. Demographic information and medical history of each patient were recorded, and the patients were examined by a physician. Routine screening tests were carried out for all patients, and further coagulation tests including coagulation factor activity and antigen assays were subsequently performed for all suspected patients. Among 358 patients, four were found to be affected with combined factor (F)V and FVIII deficiency (F5F8D). In addition, one patient with combined deficiency of FVII-FXIII, one with combined FVII-FX and one with combined FVIII-FIX deficiency were identified. In Sistan and Baluchistan Province, coinheritance of recessively inherited disorders like combined coagulation factor deficiencies was surprisingly higher than expected.

Accuracy Evaluation of the Unified P-Value from Combining Correlated P-Values

PubMed Central

Alves, Gelio; Yu, Yi-Kuo

2014-01-01

Meta-analysis methods that combine -values into a single unified -value are frequently employed to improve confidence in hypothesis testing. An assumption made by most meta-analysis methods is that the -values to be combined are independent, which may not always be true. To investigate the accuracy of the unified -value from combining correlated -values, we have evaluated a family of statistical methods that combine: independent, weighted independent, correlated, and weighted correlated -values. Statistical accuracy evaluation by combining simulated correlated -values showed that correlation among -values can have a significant effect on the accuracy of the combined -value obtained. Among the statistical methods evaluated those that weight -values compute more accurate combined -values than those that do not. Also, statistical methods that utilize the correlation information have the best performance, producing significantly more accurate combined -values. In our study we have demonstrated that statistical methods that combine -values based on the assumption of independence can produce inaccurate -values when combining correlated -values, even when the -values are only weakly correlated. Therefore, to prevent from drawing false conclusions during hypothesis testing, our study advises caution be used when interpreting the -value obtained from combining -values of unknown correlation. However, when the correlation information is available, the weighting-capable statistical method, first introduced by Brown and recently modified by Hou, seems to perform the best amongst the methods investigated. PMID:24663491

Ergonomics, automation and logistics: practical and effective combination of working methods, a case study of a baking company.

PubMed

Quintana, Leonardo; Arias, Claudia; Cordoba, Jorge; Moroy, Magda; Pulido, Jean; Ramirez, Angela

2012-01-01

The aim of this study was to combine three different analytical methods from three different disciplines to diagnose the ergonomic conditions, manufacturing and supply chain operation of a baking company. The study explores a summary of comprehensive working methods that combines the ergonomics, automation and logistics study methods in the diagnosis of working conditions and productivity. The participatory approach of this type of study that involves the feelings and first-hand knowledge of workers of the operation are determining factors in defining points of action and ergonomic interventions, as well as defining opportunities in the automation of manufacturing and logistics, to cope with the needs of the company. The study identified an ergonomic situation (high prevalence of wrist-hand pain), and the combination of interdisciplinary techniques applied allowed to improve this condition in the company. This type of study allows a primary basis of the opportunities presented by the combination of specialized methods of different disciplines, for the definition of comprehensive action plans for the company. Additionally, it outlines opportunities for improvement and recommendations to mitigate the burden associated with occupational diseases and as an end result improve the quality of life and productivity of workers.

Effects of Physical Exercise Combined with Nutritional Supplements on Aging Brain Related Structures and Functions: A Systematic Review

PubMed Central

Schättin, Alexandra; Baur, Kilian; Stutz, Jan; Wolf, Peter; de Bruin, Eling D.

2016-01-01

Age-related decline in gray and white brain matter goes together with cognitive depletion. To influence cognitive functioning in elderly, several types of physical exercise and nutritional intervention have been performed. This paper systematically reviews the potential additive and complementary effects of nutrition/nutritional supplements and physical exercise on cognition. The search strategy was developed for EMBASE, Medline, PubMed, Cochrane, CINAHL, and PsycInfo databases and focused on the research question: “Is the combination of physical exercise with nutrition/nutritional supplementation more effective than nutrition/nutritional supplementation or physical exercise alone in effecting on brain structure, metabolism, and/or function?” Both mammalian and human studies were included. In humans, randomized controlled trials that evaluated the effects of nutrition/nutritional supplements and physical exercise on cognitive functioning and associated parameters in healthy elderly (>65 years) were included. The systematic search included English and German language literature without any limitation of publication date. The search strategy yielded a total of 3129 references of which 67 studies met the inclusion criteria; 43 human and 24 mammalian, mainly rodent, studies. Three out of 43 human studies investigated a nutrition/physical exercise combination and reported no additive effects. In rodent studies, additive effects were found for docosahexaenoic acid supplementation when combined with physical exercise. Although feasible combinations of physical exercise/nutritional supplements are available for influencing the brain, only a few studies evaluated which possible combinations of nutrition/nutritional supplementation and physical exercise might have an effect on brain structure, metabolism and/or function. The reason for no clear effects of combinatory approaches in humans might be explained by the misfit between the combinations of nutritional methods with the physical interventions in the sense that they were not selected on sharing of similar neuronal mechanisms. Based on the results from this systematic review, future human studies should focus on the combined effect of docosahexaenoic acid supplementation and physical exercise that contains elements of (motor) learning. PMID:27458371

Apatinib alone or combined with radiotherapy in metastatic prostate cancer: Results from a pilot, multicenter study.

PubMed

Zhao, Feng; Tian, Wei; Zeng, Ming; Xia, Jianling; Hu, Honglin; Hao, Xinbao; Han, Liangfu; Liu, Hao; He, Yangke; Zhu, Xueqiang; Liang, Liang; Ao, Rui; Wei, Min; Deng, Lili; Wei, Yuquan

2017-12-19

To study safety and efficacy of apatinib in combination of radiotherapy in patients with symptomatic bony disease prostate cancer(SBPC), based on the potential synergistic antitumor activity between apatinib and Radiation Therapy (RT). In phase I dose escalation part, 18 patients received apatinib dose at 250 mg every other day, 250 mg daily and 500 mg daily. In phase II part, the 250 mg daily cohorts were expanded to 20 patients in combination of RT (6 Gy/fraction, 5 fraction in total), one patient lost followed up and excluded the study, comparing with RT alone cohort with 10 patients, ratio of RT to RT + apatinib was 1 to 2. Evaluations included adverse events (AEs), prostate specific antigen (PSA) changes, radiographic evaluation and pain relief. In phase I study, common apatinib-related AEs (arAEs) were fatigue, anorexia, hand foot syndrome, proteinuria, and hypertension (HTN). Grade 3arAEs included HTN, proteinuria, liver dysfunction. In phase II study, combination apatinib with RT cohorts, AEs events increased comparing with either apatinib alone or RT alone; at the same time, combination cohorts showed PSA declines of ≥50% in 12 patients, and stable disease in 6 patients. Combination cohorts had pain control significantly improved in both level and duration comparing with RT alone. In SBPC patients, apatinib at less than 500 mg daily dose as mono-therapy had tolerable toxicity. Apatinib at dose of 250 mg daily in combining with RT synergized pain control, the overall AEs were manageable. Further studies are needed in large sample size future trials.

Early Combinations of Words and Actions.

ERIC Educational Resources Information Center

Shore, Cecilia

Previous research has shown a similar starting time for early combinations of words and play actions in children and has suggested that similar cognitive processes underlie the transition to combining activities in language, symbolic play, and manipulative play. A study was undertaken to investigate combining activities in these three domains and…

Anesthetic efficacy of ketamine-diazepam, ketamine-xylazine, and ketamine-acepromazine in Caspian Pond turtles (Mauremys caspica).

PubMed

Adel, Milad; Sadegh, Amin Bigham; Arizza, Vincenzo; Abbasi, Hossein; Inguglia, Luigi; Saravi, Hasan Nasrollahzadeh

2017-01-01

The objective of this study was to assess the efficacy of different anesthetic drug combinations on the Caspian Pond turtles ( Mauremys caspica ). Three groups of the Caspian Pond turtles ( n = 6) were anesthetized with three different drug combinations. Initially, a pilot study was conducted to determine the best drug doses for the anesthetization of the turtles, and according to these results, ketamine-diazepam (120 mg/kg ketamine hydrochloride [5%] and 2 mg/kg diazepam [5%]), ketamine-acepromazine (120 mg/kg ketamine hydrochloride [5%] and 1 mg/kg acepromazine [1%]), and ketamine-xylazine (120 mg/kg ketamine hydrochloride [5%] and 1 mg/kg xylazine [2%]) were injected intramuscularly. The onset times of anesthetization and the recovery time were measured. Statistical analysis of the data was performed using one-way analysis of variance followed by t -tests, and P < 0.05 was considered statistically significant. There were statistically significant differences in the mean of the onset times of anesthesia and recovery time among the three drug combinations depending on the treatment used. The onset of anesthesia of the animals treated with the ketamine-diazepam combination was 60% and 42% shorter, for male and female turtles, respectively, compared to that obtained with the ketamine-acepromazine combination and 64% (male turtles) and 50% (female turtles) shorter than that obtained with the ketamine-xylazine combination. Further, the recovery time, in male turtles, was 17% shorter in animals treated with the first drug combination than those treated with the ketamine-acepromazine combination and 37% shorter than those treated with the ketamine-xylazine combination. The recovery time, in female turtles, did not seem to be significantly different among treatments. The study showed that the ketamine-diazepam drug combination is the anesthetic combination with the fastest onset time and shortest recovery time.

Tribenoside and lidocaine in the local treatment of hemorrhoids: an overview of clinical evidence.

PubMed

Lorenc, Z; Gökçe, Ö

2016-06-01

The combination of tribenoside+lidocaine (Procto-Glyvenol®) is a medical preparation for the local treatment of hemorrhoids, delivered as a suppository or rectal cream. This product has been used for decades in the therapy of hemorrhoids. This review discusses available evidence on the use of tribenoside/lidocaine in clinical practice. Papers were retrieved by a PubMed search, using different combinations of pertinent keywords (e.g. tribenoside AND hemorrhoids), without any limitations in terms of publication date and language. Documents from Authors' personal collection of literature could also be considered. Papers were selected for inclusion according to their relevance for the topic, as judged by the Authors. The efficacy of the combination of tribenoside+lidocaine in relieving symptoms caused by hemorrhoids and its safety have been assessed in several clinical studies on patients of either gender, either versus its two individual components (tribenoside and lidocaine) or versus steroids in the same setting. Five studies compared the combination treatment with each of its single components, and of these, three studies compared tribenoside+ lidocaine with a tribenoside-free semi-placebo preparation containing only lidocaine, and two studies compared this combination with lidocaine-free preparations containing only tribenoside. Tribenoside+lidocaine was compared with steroid-containing preparations in six studies. Last, two studies evaluated the efficacy and tolerability of the tribenoside+lidocaine combination in women with hemorrhoids as a consequence of pregnancy or delivery. All the above-mentioned studies were well-conducted and can provide a comprehensive evaluation of tribenoside+lidocaine in the treatment of hemorrhoids. Enough evidence exists to recommend the use of this combination therapy as a fast, effective and safe option for the local treatment of low-grade hemorrhoids.

Evaluating the incidence of leukopenia and neutropenia with valproate, quetiapine, or the combination in children and adolescents.

PubMed

Rahman, Aminur; Mican, Lisa M; Fischer, Charles; Campbell, Angela H

2009-05-01

At the Austin State Hospital, Austin, TX, a number of cases of neutropenia and leukopenia have been observed in children and adolescents who were treated with the combination of valproate and quetiapine. Use of this combination has raised concerns regarding an increased risk of hematologic toxicity. To evaluate the incidence of leukopenia and neutropenia associated with the use of valproate, quetiapine, or the combination in the child and adolescent population. This study was a retrospective evaluation of patients from the child and adolescent psychiatric service of the Austin State Hospital who were treated with valproate, quetiapine, or the combination. Subjects were selected from patients discharged between August 1, 2004, and August 31, 2007. Laboratory data were evaluated to determine the incidence and severity of leukopenia and neutropenia associated with valproate, quetiapine, and a combination of the 2. A total of 131 patients were included in the study. Analysis of the laboratory data revealed a combined incidence of neutropenia and/or leukopenia of 44%, 26%, and 6% in the combination group, valproate monotherapy group, and quetiapine monotherapy group, respectively. Differences in the incidence of neutropenia and/or leukopenia between the quetiapine monotherapy group and valproate monotherapy group, as well as the quetiapine monotherapy group and the combination group reached statistical significance. A significant difference was found among groups based on absolute neutrophil count Common Toxicity Criteria severity (p < 0.001). The combination group differed significantly in incidence of moderate-to-severe neutropenia (14 cases) from both the valproate (5 cases) and quetiapine (0 cases) monotherapy groups. A significantly greater number (44%) of African American patients experienced neutropenia and/or leukopenia than white (not Hispanic or Latino; 29%) or Hispanic or Latino (11%) patients. Patients treated with valproate or the combination of valproate and quetiapine should be monitored for the occurrence of leukopenia and neutropenia. Controlled studies are warranted to examine possible pharmacokinetic and pharmacodynamic interactions with the combination of valproate and quetiapine to further evaluate the hematologic findings of this study.

Comparison of cycle control with a combined contraceptive vaginal ring and oral levonorgestrel/ethinyl estradiol.

PubMed

Bjarnadóttir, Ragnheidur I; Tuppurainen, Marjo; Killick, Stephen R

2002-03-01

The purpose of this study was to compare cycle control and tolerability of the NuvaRing (NV Organon, Oss, The Netherlands), a novel combined contraceptive vaginal ring, with a standard combined oral contraceptive pill. Healthy women aged 18 to 40 years who requested contraception received either NuvaRing or a combined oral contraceptive containing 30 microg ethinyl estradiol and 150 microg levonorgestrel for 6 cycles in 3 similarly designed studies. Each cycle comprised 3 weeks of ring or pill use, followed by 1 ring- or pill-free week. Two hundred forty-seven women began the studies, 121 women with NuvaRing and 126 women with the combined oral contraceptive. Withdrawal bleeding occurred in virtually all cycles in both groups. In the NuvaRing groups, the incidence of irregular bleeding was < or =5% in all cycles; this was lower than the combined oral contraceptive groups (5.4%-38.8%). Furthermore, the incidence of a normal intended bleeding pattern was significantly higher in the NuvaRing groups than in the combined oral contraceptive groups (P <.01). Both contraceptives were well tolerated. NuvaRing has excellent cycle control and is well tolerated.

A study of the effects of physical dermabrasion combined with chemical peeling in porcine skin.

PubMed

Kang, Boo Kyoung; Choi, Jeong Hwee; Jeong, Ki Heon; Park, Jong Min; Suh, Dong Hye; Lee, Sang Jun; Shin, Min Kyung

2015-02-01

Many comparative studies of chemical peeling and dermabrasion have been reported. However, rare basic scientific data about the immediate effects after combined treatment with chemical peeling and dermabrasion have been confirmed. The aim of this study is to evaluate the effect of the application of physical abrasion in combination with chemical peels. Three pigs were treated with physical abrasion using a water jet device in combination with an α-hydroxy acid solution, and the skin samples of the control received chemical peeling solution alone. The levels of growth factors and neuropeptides were measured with a multiplex immunoassay. Skin treated with physical dermabrasion combined with chemical peeling showed prominent detachment and swelling of the stratum corneum (SC), and fluid collection in the hair follicles. The mean cell count of CD34 positive fibroblasts and mast cells, levels of epidermal growth factor, fibroblast growth factor-2, vascular endothelial growth factor, and neurotensin, were significantly increased in the tissue treated with physical abrasion combined with a chemical peeling agent, compared to the skin in the control. We concluded that physical dermabrasion combined with chemical peeling can be more effective than chemical peeling alone, for the approach through transfollicular routes.

How Combined Trip Purposes Are Associated with Transport Choice for Short Distance Trips. Results from a Cross-Sectional Study in the Netherlands

PubMed Central

Scheepers, Eline; Slinger, Minke; Wendel-Vos, Wanda; Schuit, Jantine

2014-01-01

Background One way to increase physical activity is to stimulate a shift from car use to walking or cycling. In single-purpose trips, purpose was found to be an important predictor of transport choice. However, as far as known, no studies have been conducted to see how trips with combined purposes affect this decision. This study was designed to provide insight into associations between combined purposes and transport choice. Methods An online questionnaire (N = 3,663) was used to collect data concerning transport choice for four primary purposes: shopping, going to public natural spaces, sports, and commuting. Per combination of primary trip purpose and transport choice, participants were asked to give examples of secondary purposes that they combine with the primary purpose. Logistic regression analyses were used to model the odds of both cycling and walking versus car use. Results Primary trip purposes combined with commuting, shopping, visiting private contacts or medical care were more likely to be made by car than by cycling or walking. Combinations with visiting catering facilities, trips to social infrastructure facilities, recreational outings, trips to facilities for the provision of daily requirements or private contacts during the trip were more likely to be made by walking and/or cycling than by car. Conclusion Combined trip purposes were found to be associated with transport choice. When stimulating active transport focus should be on the combined-trip purposes which were more likely to be made by car, namely trips combined with commuting, other shopping, visiting private contacts or medical care. PMID:25474653

The Relationship between a Linear Combination of Intelligence, Musical Background, Rhythm Ability and Tapping Ability to Typewriting Speed and Accuracy.

ERIC Educational Resources Information Center

Fante, Cheryl H.

This study was conducted in an attempt to identify any predictor or combination of predictors of a beginning typewriting student's success. Variables of intelligence, rhythmic ability, musical background, and tapping ability were combined to study their relationship to typewriting speed and accuracy. A sample of 109 high school students was…

Safety and efficacy of low-dose esterified estrogens and methyltestosterone, alone or combined, for the treatment of hot flashes in menopausal women: a randomized, double-blind, placebo-controlled study.

PubMed

Liu, James; Allgood, Adam; Derogatis, Leonard R; Swanson, Stephen; O'Mahony, Michael; Nedoss, Bertrand; Soper, Herbert; Zbella, Edward; Prokofieva, Svetlana Vladimirovna; Zipfel, Lisa; Guo, Chun-Yuan

2011-01-01

This study evaluated safety and efficacy of esterified estrogens and methyltestosterone administered alone or in combination for the treatment of hot flashes in menopausal women. The 0.30-mg esterified estrogens and 0.30-mg methyltestosterone combination was the lowest effective dose, and our results are consistent with the known safety profile of estrogen and androgen combination products. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

A Systematic Review of Combination Therapy with Stimulants and Atomoxetine for Attention-Deficit/Hyperactivity Disorder, Including Patient Characteristics, Treatment Strategies, Effectiveness, and Tolerability

PubMed Central

Gau, Susan Shur-Fen; Méndez, Luis; Montgomery, William; Monk, Julie A.; Altin, Murat; Wu, Shenghu; Lin, Chaucer C.H.; Dueñas, Héctor J.

2013-01-01

Abstract Objective The purpose of this article was to systematically review the literature on stimulant and atomoxetine combination therapy, in particular: 1) Characteristics of patients with attention-deficit/hyperactivity disorder (ADHD) given combination therapy, 2) treatment strategies used, 3) efficacy and effectiveness, and 4) safety and tolerability. Methods Literature databases (MEDLINE®, EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index Expanded, and SciVerse Scopus) were systematically searched using prespecified criteria. Publications describing stimulant and atomoxetine combination therapy in patients with ADHD or healthy volunteers were selected for review. Exclusion criteria were comorbid psychosis, bipolar disorder, epilepsy, or other psychiatric/neurologic diseases that could confound ADHD symptom assessment, or other concomitant medication(s) to treat ADHD symptoms. Results Of the 16 publications included for review, 14 reported findings from 3 prospective studies (4 publications), 7 retrospective studies, and 3 narrative reviews/medication algorithms of patients with ADHD. The other two publications reported findings from two prospective studies of healthy volunteers. The main reason for prescribing combination therapy was inadequate response to previous treatment. In the studies of patients with ADHD, if reported, 1) most patients were children/adolescents and male, and had a combined ADHD subtype; 2) methylphenidate was most often used in combination with atomoxetine for treatment augmentation or switch; 3) ADHD symptom control was improved in some, but not all, patients; and 4) there were no serious adverse events. Conclusions Published evidence of the off-label use of stimulant and atomoxetine combination therapy is limited because of the small number of publications, heterogeneous study designs (there was only one prospective, randomized controlled trial), small sample sizes, and geographic bias. Existing evidence suggests, but does not confirm, that this drug combination may benefit some, but not all, patients who have tried several ADHD medications without success. PMID:23560600

Synergistic antibacterial and antibiofilm efficacy of nisin in combination with p-coumaric acid against food-borne bacteria Bacillus cereus and Salmonella typhimurium.

PubMed

Bag, A; Chattopadhyay, R R

2017-11-01

The aim of the study was to evaluate possible antibacterial and antibiofilm efficacy of a bacteriocin, nisin with two essential oil components linalool and p-coumaric acid in combination against food-borne bacteria Bacillus cereus and Salmonella typhimurium. Their inhibition effects on planktonic cells and preformed biofilms were evaluated using microbroth dilution and checkerboard titration methods. Nisin/p-coumaric acid combination showed synergistic effects against planktonic cells of both the studied bacteria, whereas nisin/linalool combination showed synergistic activity against B. cereus and additive effect against S. typhimurium. In preformed biofilms, nisin by itself failed to show >50% antibiofilm efficacy against both the studied bacteria, but in combination with linalool and p-coumaric acid, it exerted >50% antibiofilm efficacy. On the basis of fractional inhibitory concentration indices values, nisin/p-coumaric acid combination exhibited synergistic antibiofilm activity, whereas nisin/linalool combination showed additive effects against preformed biofilms of studied bacteria. The results provide evidence that p-coumaric acid due to its synergistic interactions with nisin against planktonic cells and biofilms of both Gram-positive and Gram-negative food-borne bacteria enhanced the antibacterial spectrum of nisin, which subsequently may facilitate their use in the food industry. In the present work, synergistic interactions between a bacteriocin, nisin and essential oil component p-coumaric acid on planktonic cells as well as on biofilms of Gram-positive and Gram-negative food-borne bacteria have been reported. The results of this study provide evidence that nisin/p-coumaric acid combination can be considered as a promising source for development of more potent broad spectrum antimicrobial blend for food preservation, which subsequently may facilitate their use in the food industry. To the best of our knowledge, this is the first report of the antibacterial and antibiofilm efficacy of nisin in combination with essential oil components against food-borne bacteria. © 2017 The Society for Applied Microbiology.

Improving working memory in children with attention-deficit/hyperactivity disorder: the separate and combined effects of incentives and stimulant medication.

PubMed

Strand, Michael T; Hawk, Larry W; Bubnik, Michelle; Shiels, Keri; Pelham, William E; Waxmonsky, James G

2012-10-01

Working memory (WM) is considered a core deficit in Attention-Deficit/ Hyperactivity Disorder (ADHD), with numerous studies demonstrating impaired WM among children with ADHD. We tested the degree to which WM in children with ADHD was improved by performance-based incentives, an analog of behavioral intervention. In two studies, WM performance was assessed using a visuo-spatial n-back task. Study 1 compared children (ages 9-12 years) with ADHD-Combined type (n = 24) to a group of typically developing (TD) children (n = 32). Study 1 replicated WM deficits among children with ADHD. Incentives improved WM, particularly among children with ADHD. The provision of incentives reduced the ADHD-control group difference by approximately half but did not normalize WM. Study 2 examined the separate and combined effects of incentives and stimulant medication among 17 children with ADHD-Combined type. Both incentives and a moderate dose of long-acting methylphenidate (MPH; ~0.3 mg/kg t.i.d. equivalent) robustly improved WM relative to the no-incentive, placebo condition. The combination of incentives and medication improved WM significantly more than either incentives or MPH alone. These studies indicate that contingencies markedly improve WM among children with ADHD-Combined type, with effect sizes comparable to a moderate dose of stimulant medication. More broadly, this work calls attention to the role of motivation in studying cognitive deficits in ADHD and in testing multifactorial models of ADHD.

A designed screening study with prespecified combinations of factor settings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson-cook, Christine M; Robinson, Timothy J

2009-01-01

In many applications, the experimenter has limited options about what factor combinations can be chosen for a designed study. Consider a screening study for a production process involving five input factors whose levels have been previously established. The goal of the study is to understand the effect of each factor on the response, a variable that is expensive to measure and results in destruction of the part. From an inventory of available parts with known factor values, we wish to identify a best collection of factor combinations with which to estimate the factor effects. Though the observational nature of themore » study cannot establish a causal relationship involving the response and the factors, the study can increase understanding of the underlying process. The study can also help determine where investment should be made to control input factors during production that will maximally influence the response. Because the factor combinations are observational, the chosen model matrix will be nonorthogonal and will not allow independent estimation of factor effects. In this manuscript we borrow principles from design of experiments to suggest an 'optimal' selection of factor combinations. Specifically, we consider precision of model parameter estimates, the issue of replication, and abilities to detect lack of fit and to estimate two-factor interactions. Through an example, we present strategies for selecting a subset of factor combinations that simultaneously balance multiple objectives, conduct a limited sensitivity analysis, and provide practical guidance for implementing our techniques across a variety of quality engineering disciplines.« less

Failure mode effect analysis and fault tree analysis as a combined methodology in risk management

NASA Astrophysics Data System (ADS)

Wessiani, N. A.; Yoshio, F.

2018-04-01

There have been many studies reported the implementation of Failure Mode Effect Analysis (FMEA) and Fault Tree Analysis (FTA) as a method in risk management. However, most of the studies usually only choose one of these two methods in their risk management methodology. On the other side, combining these two methods will reduce the drawbacks of each methods when implemented separately. This paper aims to combine the methodology of FMEA and FTA in assessing risk. A case study in the metal company will illustrate how this methodology can be implemented. In the case study, this combined methodology will assess the internal risks that occur in the production process. Further, those internal risks should be mitigated based on their level of risks.

Toward a new approach to the study of personality in culture.

PubMed

Cheung, Fanny M; van de Vijver, Fons J R; Leong, Frederick T L

2011-10-01

We review recent developments in the study of culture and personality measurement. Three approaches are described: an etic approach that focuses on establishing measurement equivalence in imported measures of personality, an emic (indigenous) approach that studies personality in specific cultures, and a combined emic-etic approach to personality. We propose the latter approach as a way of combining the methodological rigor of the etic approach and the cultural sensitivity of the emic approach. The combined approach is illustrated by two examples: the first with origins in Chinese culture and the second in South Africa. The article ends with a discussion of the theoretical and practical implications of the combined emic-etic approach for the study of culture and personality and for psychology as a science.

Combined eating behaviors and overweight: Eating quickly, late evening meals, and skipping breakfast.

PubMed

Lee, Jung Su; Mishra, Gita; Hayashi, Kunihiko; Watanabe, Etsuko; Mori, Katsumi; Kawakubo, Kiyoshi

2016-04-01

Various eating behaviors have been linked with body weight management. However, combined effects of major eating behaviors are not fully understood. This study aimed to clarify the association of the combination of eating quickly (EQ), late evening meals (LEM), and skipping breakfast (SB) with being overweight. A cross-sectional study with standardized questions for EQ, LEM, and SB was conducted. Stratified random sampling of 5% of residents aged 20 to 80years was surveyed in a city in northeast Japan in 2011, and 4249 (84.9%) residents were analyzed. Association of combinations of eating behaviors on being overweight (BMI (kg/m(2)≥25.0)) was estimated by using logistic analysis, and odds ratio (OR) and 95% confidential interval were calculated after adjustment for potential covariates. LEM, SB, or a combination of LEM and SB was not significantly associated with being overweight. However, the combination of EQ or only EQ was significantly associated with being overweight. As the number of eating behavior practices increased, there was a linear increase in OR for being overweight. The OR of all three combined eating behaviors was higher than that of any combined two behaviors or of each behavior. This study result supports the evidence that EQ increases the risk of being overweight whether by itself or in combinations with LEM and/or SB. However, only LEM or only SB did not increase the risk of being overweight. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparative study of clozapine, electroshock and the combination of ECT with clozapine in treatment-resistant schizophrenic patients.

PubMed

Masoudzadeh, A; Khalilian, A R

2007-12-01

The aim of this study was to compare the results of treatment with clozapine alone, Electroshock (ECT) alone and the combination of clozapine with ECT in treatment-resistant schizophrenic patients. Eighteen treatment-resistant schizophrenic patients were assigned to three equal groups: one group was given clozapine; one group was treated with ECT and one group was treated with the combination of clozapine and ECT. The treatment response was evaluated using the PANSS criteria and the data were analyzed with ANOVA. Combination therapy was superior to single modality therapy. The reduction of PANSS scores was 46% in the clozapine group, 40% in the ECT groups and 71% in the combination group, the difference between the combination group and the other groups was statistically significant (p < 0.05). Patients had a quick response to combination treatment, which resulted in a higher cure rate of positive and negative symptoms and improved the patients general performance. There were no significant adverse effects with combination treatment. Combination treatment with clozapine and ECT was safe and effective in treatment-resistant schizophrenic patients. It should be considered for the treatment of treatment-resistant schizophrenic patients.

Evaluation of Ceftolozane-Tazobactam in Combination with Meropenem against Pseudomonas aeruginosa Sequence Type 175 in a Hollow-Fiber Infection Model.

PubMed

Montero, M; VanScoy, Brian D; López-Causapé, Carla; Conde, Haley; Adams, Jonathan; Segura, Concepción; Zamorano, Laura; Oliver, Antonio; Horcajada, Juan P; Ambrose, Paul G

2018-05-01

The aim of this study was to investigate the efficacy of ceftolozane-tazobactam in combination with meropenem against an extensively drug-resistant (XDR) Pseudomonas aeruginosa high-risk clone, sequence type 175, isolated in a Spanish university hospital. A 14-day hollow-fiber infection model was used to simulate clinical exposure of the two drug regimens alone and in combination, and serial samples were collected to determine drug concentrations and CFU counts. The untreated control failed, as did each study regimen when administered alone. However, when ceftolozane-tazobactam was administered in combination with meropenem, there was a >4-log 10 CFU/ml bacterial density reduction and suppression of resistance for the duration of the study. These data suggest that ceftolozane-tazobactam plus meropenem may be a useful combination for treating XDR P. aeruginosa . Copyright © 2018 American Society for Microbiology.

QUADAS and STARD: evaluating the quality of diagnostic accuracy studies.

PubMed

Oliveira, Maria Regina Fernandes de; Gomes, Almério de Castro; Toscano, Cristiana Maria

2011-04-01

To compare the performance of two approaches, one based on the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) and another on the Standards for Reporting Studies of Diagnostic Accuracy (STARD), in evaluating the quality of studies validating the OptiMal® rapid malaria diagnostic test. Articles validating the rapid test published until 2007 were searched in the Medline/PubMed database. This search retrieved 13 articles. A combination of 12 QUADAS criteria and three STARD criteria were compared with the 12 QUADAS criteria alone. Articles that fulfilled at least 50% of QUADAS criteria were considered as regular to good quality. Of the 13 articles retrieved, 12 fulfilled at least 50% of QUADAS criteria, and only two fulfilled the STARD/QUADAS criteria combined. Considering the two criteria combination (> 6 QUADAS and > 3 STARD), two studies (15.4%) showed good methodological quality. The articles selection using the proposed combination resulted in two to eight articles, depending on the number of items assumed as cutoff point. The STARD/QUADAS combination has the potential to provide greater rigor when evaluating the quality of studies validating malaria diagnostic tests, given that it incorporates relevant information not contemplated in the QUADAS criteria alone.

Diet or exercise interventions vs combined behavioral weight management programs: a systematic review and meta-analysis of direct comparisons.

PubMed

Johns, David J; Hartmann-Boyce, Jamie; Jebb, Susan A; Aveyard, Paul

2014-10-01

Weight loss can reduce the health risks associated with being overweight or obese. However, the most effective method of weight loss remains unclear. Some programs emphasize physical activity, others diet, but existing evidence is mixed as to whether these are more effective individually or in combination. We aimed to examine the clinical effectiveness of combined behavioral weight management programs (BWMPs) targeting weight loss in comparison to single component programs, using within study comparisons. We included randomized controlled trials of combined BWMPs compared with diet-only or physical activity-only programs with at least 12 months of follow-up, conducted in overweight and obese adults (body mass index ≥25). Systematic searches of nine databases were run and two reviewers extracted data independently. Random effects meta-analyses were conducted for mean difference in weight change at 3 to 6 months and 12 to 18 months using a baseline observation carried forward approach for combined BWMPs vs diet-only BWMPs and combined BWMPs vs physical activity-only BWMPs. In total, eight studies were included, representing 1,022 participants, the majority of whom were women. Six studies met the inclusion criteria for combined BWMP vs diet-only. Pooled results showed no significant difference in weight loss from baseline or at 3 to 6 months between the BWMPs and diet-only arms (-0.62 kg; 95% CI -1.67 to 0.44). However, at 12 months, a significantly greater weight-loss was detected in the combined BWMPs (-1.72 kg; 95% CI -2.80 to -0.64). Five studies met the inclusion criteria for combined BWMP vs physical activity-only. Pooled results showed significantly greater weight loss in the combined BWMPs at 3 to 6 months (-5.33 kg; 95% CI -7.61 to -3.04) and 12 to 18 months (-6.29 kg; 95% CI -7.33 to -5.25). Weight loss is similar in the short-term for diet-only and combined BWMPs but in the longer-term weight loss is increased when diet and physical activity are combined. Programs based on physical activity alone are less effective than combined BWMPs in both the short and long term. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Review of the contemporary cytotoxic and biologic combinations available for the treatment of metastatic breast cancer.

PubMed

Tkaczuk, Katherine H Rak

2009-01-01

Treatment of metastatic breast cancer (MBC) with > or =2 chemotherapeutic agents concurrently has been shown to increase response rates, often at the cost of a substantial increase in toxicity, and with minimal impact on the overall survival. However, some combinations of the newer cytotoxic agents, as well as combinations of chemotherapeutic agents and targeted biologic anticancer agents, can produce synergistic efficacy with a manageable toxicity profile. The aims of this work were to provide an overview of the currently approved combination regimens available for the treatment of MBC and to consider the clinical data supporting other drug combinations that may supplement the current therapeutic choices in the near future. Literature searches were performed using MEDLINE/PubMed, with a focus on combination therapies for the treatment of MBC that are approved by the US Food and Drug Administration (FDA) or in Phase III clinical trials. The National Institutes of Health's Clinical Trial Registry was searched for relevant ongoing clinical trials in specific areas. Bibliographies were also searched for additional relevant material. Preference was given to recently published, larger, well-designed clinical trials that influence current prescribing practices. Phase I and II studies, and/or studies older than 10 years (ie, published earlier than 1999), were afforded less emphasis or were disregarded. Combinations of taxanes with capecitabine or gemcitabine, and ixabepilone plus capecitabine, are approved by the FDA as combination regimens for the treatment of MBC. The use of targeted therapies such as trastuzumab, bevacizumab, or lapatinib in combination with taxanes (for the former two) or capecitabine (for lapatinib) is also approved. Several investigational drug combinations are also currently undergoing evaluation in clinical trials, including combinations of bevacizumab and gemcitabine with capecitabine or alternative taxanes. Although results from Phase I and II studies are largely encouraging so far, the data from ongoing Phase III studies will ultimately dictate changes in clinical practice. It seems unlikely that any single agent or combination regimen will emerge as superior in all patients with MBC, given the heterogeneous nature of the disease and patient population. New combination regimens for MBC may broaden the range of treatment options currently available to delay disease progression for as long as possible. Copyright 2009 Excerpta Medica Inc. All rights reserved.

Activity of Oxantel Pamoate Monotherapy and Combination Chemotherapy against Trichuris muris and Hookworms: Revival of an Old Drug

PubMed Central

Keiser, Jennifer; Tritten, Lucienne; Silbereisen, Angelika; Speich, Benjamin; Adelfio, Roberto; Vargas, Mireille

2013-01-01

Background It is widely recognized that only a handful of drugs are available against soil-transmitted helminthiasis, all of which are characterized by a low efficacy against Trichuris trichiura, when administered as single doses. The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations. Methodology We studied the activity of the veterinary drug oxantel pamoate against Trichuris muris, Ancylostoma ceylanicum and Necator americanus in vitro and in vivo. In addition, the dose-effect of oxantel pamoate combined with albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin was studied against T. muris in vitro and additive or synergistic combinations were followed up in vivo. Principal Findings We calculated an ED50 of 4.7 mg/kg for oxantel pamoate against T. muris in mice. Combinations of oxantel pamoate with pyrantel pamoate behaved antagonistically in vitro (combination index (CI) = 2.53). Oxantel pamoate combined with levamisole, albendazole or ivermectin using ratios based on their ED50s revealed antagonistic effects in vivo (CI = 1.27, 1.90 and 1.27, respectively). A highly synergistic effect (CI = 0.15) was observed when oxantel pamoate-mebendazole was administered to T. muris-infected mice. Oxantel pamoate (10 mg/kg) lacked activity against Ancylostoma ceylanicum and Necator americanus in vivo. Conclusion/Significance Our study confirms the excellent trichuricidal properties of oxantel pamoate. Since the drug lacks activity against hookworms it is necessary to combine oxantel pamoate with a partner drug with anti-hookworm properties. Synergistic effects were observed for oxantel pamoate-mebendazole, hence this combination should be studied in more detail. Since, of the standard drugs, albendazole has the highest efficacy against hookworms, additional investigations on the combination effect of oxantel pamoate-albendazole should be launched. PMID:23556013

Effect of benazepril, robenacoxib and their combination on glomerular filtration rate in cats.

PubMed

King, Jonathan N; Panteri, Alessandro; Graille, Melanie; Seewald, Wolfgang; Friton, Gabriele; Desevaux, Cyril

2016-06-23

Combined use of angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs may induce acute kidney injury in humans, especially when combined with diuretics. The objective of this investigation was to evaluate the effects of benazepril, robenacoxib and their combination in healthy cats. In each of two studies (study 1 followed by study 2), 32 healthy cats were randomised to one of four groups (n = 4 male and 4 female cats per group) in a parallel-group design. The groups received orally once daily for 7 days either placebo (control group), benazepril, robenacoxib or benazepril plus robenacoxib. In study 2, all groups received in addition 0.5 mg/kg furosemide twice daily by subcutaneous injection for 7 days. Benazepril, robenacoxib and their combination were well tolerated as evidenced from lack of clinical signs and no negative effects on body weight, feed consumption and clinical chemistry, haematology and urinalysis variables. The primary endpoint of the study was the glomerular filtration rate (GFR), which was estimated from the plasma clearance of iohexol. In the absence of furosemide, GFR was significantly higher in cats receiving the combination of benazepril plus robenacoxib compared to the other three groups, and was also significantly higher in females receiving only benazepril compared to the control. Administration of furosemide induced diuresis, reduced GFR and activated the renin-aldosterone-angiotensin system, evidenced from increased plasma renin activity and plasma aldosterone concentrations. Compared to the control group in cats treated with furosemide, GFR was increased by benazepril (females only) but decreased by robenacoxib (males only). Benazepril, robenacoxib and their combination significantly inhibited the increase in plasma aldosterone induced by furosemide. The combination of benazepril and robenacoxib was well tolerated and either increased or had a neutral effect on GFR in healthy cats without or with concomitant furosemide. The combination of benazepril and robenacoxib reduced plasma aldosterone concentrations increased by furosemide. It is recommended to test the efficacy and safety of the combined use of benazepril and robenacoxib in cats with clinical disease, notably proteinuric chronic kidney disease.

The efficacy of combined intra-articular and intravenous tranexamic acid for blood loss in primary total knee arthroplasty: A meta-analysis.

PubMed

Wang, Zhao; Shen, Xiaofei

2017-10-01

This meta-analysis aimed to illustrate the efficacy and safety of combined topical and intravenous (IV) tranexamic acid (TXA) for blood loss control in primary total knee arthroplasty (TKA) patients. In April 2017, a systematic computer-based search was conducted in PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, and Google database. Data on patients prepared for TKA surgery in studies that compared combined topical and IV TXA versus placebo, topical, or IV TXA alone were retrieved. The primary endpoint was the need for transfusion, total blood loss, hemoglobin drop, and the occurrence of deep venous thrombosis (DVT), pulmonary embolism (PE), and the infection. After testing for publication bias and heterogeneity between studies, data were aggregated for random-effects models when necessary. Seven clinical studies were ultimately included in the meta-analysis. Compared with IV TXA and control group, combined TXA was associated with less need for transfusion, blood loss, and hemoglobin drop (P < .05). There was no significant difference between the combined TXA and topical TXA in terms of the need for transfusion, total blood loss, and hemoglobin drop (P > .05). There was no significant difference between the complications (DVT, PE, and infection) between the combined TXA, IV TXA, topical TXA, and control group. Current meta-analysis suggests that the combined IV and topical TXA was superior than IV TXA or control group. There is still need for more studies to identify whether combined TXA was superior than topical TXA alone.

Design and characterization of diclofenac diethylamine transdermal patch using silicone and acrylic adhesives combination

PubMed Central

2013-01-01

Background and purpose of the study The objective of the study was to develop and characterize Diclofenac Diethylamine (DDEA) transdermal patch using Silicone and acrylic adhesives combination. Methods Modified solvent evaporation method was employed for casting of film over Fluoropolymer coated polyester release liner. Initial studies included solubilization of drug in the polymers using solubilizers. The formulations with combination of adhesives were attempted to combine the desirable features of both the adhesives. The effect of the permeation enhancers on the drug permeation were studied using pig ear skin. All the optimized patches were subjected to adhesion, dissolution and stability studies. A 7-day skin irritancy test on albino rabbits and an in vivo anti-inflammatory study on wistar rats by carrageenan induced paw edema method were also performed. Results The results indicated the high percent drug permeation (% CDP-23.582) and low solubility nature (1%) of Silicone adhesive and high solubility (20%) and low% CDP (10.72%) of acrylic adhesive. The combination of adhesives showed desirable characteristics for DDEA permeation with adequate % CDP and sufficient solubility. Release profiles were found to be dependent on proportion of polymer and type of permeation enhancer. The anti-inflammatory study revealed the sustaining effect and high percentage inhibition of edema of C4/OLA (99.68%). The acute skin irritancy studies advocated the non-irritant nature of the adhesives used. Conclusion It was concluded that an ideal of combination of adhesives would serve as the best choice, for fabrication of DDEA patches, for sustained effect of DDEA with better enhancement in permeation characteristics and robustness. PMID:23351568

Use of estetrol with other steroids for attenuation of neonatal hypoxic-ischemic brain injury: to combine or not to combine?

PubMed

Tskitishvili, Ekaterine; Pequeux, Christel; Munaut, Carine; Viellevoye, Renaud; Nisolle, Michelle; Noël, Agnes; Foidart, Jean-Michel

2016-06-07

Estetrol (E4), estradiol (E2) and progesterone (P4) have important antioxidative and neuroprotective effects in neuronal system. We aimed to study the consequence of combined steroid therapy in neonatal hypoxic-ischemic encephalopathy (HIE). In vitro the effect of E4 combined with other steroids on oxidative stress and the cell viability in primary hippocampal cultures was evaluated by lactate dehydrogenase and cell survival assays. In vivo neuroprotective and therapeutic efficacy of E4 combined with other steroids was studied in HIE model of immature rats. The rat pups rectal temperature, body and brain weights were evaluated.The hippocampus and the cortex were investigated by histo/immunohistochemistry: intact cell number counting, expressions of markers for early gray matter lose, neuro- and angiogenesis were studied. Glial fibrillary acidic protein was evaluated by ELISA in blood samples. In vitro E4 and combinations of high doses of E4 with P4 and/or E2 significantly diminished the LDH activity and upregulated the cell survival.In vivopretreatment or treatment by different combinations of E4 with other steroids had unalike effects on body and brain weight, neuro- and angiogenesis, and GFAP expression in blood. The combined use of E4 with other steroids has no benefit over the single use of E4.

Clinical trial studies a new form of vincristine in standard combination chemotherapy for children with relapsed ALL | Center for Cancer Research

Cancer.gov

A combination of chemotherapy drugs known by the regimen UK ALL R3 is one of the most successful treatments for patients with relapsed acute lymphoblastic leukemia (ALL). In this study, investigators hope to improve outcomes by combining the treatment with Marqibo, a new formulation of the drug vincristine. Learn more...

Search strategies for identifying qualitative studies in CINAHL.

PubMed

Wilczynski, Nancy L; Marks, Susan; Haynes, R Brian

2007-05-01

Nurses, allied health professionals, clinicians, and researchers increasingly use online access to evidence in the course of patient care or when conducting reviews on a particular topic. Qualitative research has an important role in evidence-based health care. Online searching for qualitative studies can be difficult, however, resulting in the need to develop search filters. The objective of this study was to develop optimal search strategies to retrieve qualitative studies in CINAHL for the 2000 publishing year. The authors conducted an analytic survey comparing hand searches of journals with retrievals from CINAHL for candidate search terms and combinations. Combinations of search terms reached peak sensitivities of 98.9% and peak specificities of 99.5%. Combining search terms optimized both sensitivity and specificity at 94.2%. Empirically derived search strategies combining indexing terms and textwords can achieve high sensitivity and high specificity for retrieving qualitative studies from CINAHL.

Developmental trajectories of DSM-IV symptoms of attention-deficit/hyperactivity disorder: genetic effects, family risk and associated psychopathology.

PubMed

Larsson, Henrik; Dilshad, Rezin; Lichtenstein, Paul; Barker, Edward D

2011-09-01

DSM-IV specifies three ADHD subtypes; the combined, the hyperactive-impulsive and the inattentive. Little is known about the developmental relationships underlying these subtypes. The objective of this study was to describe the development of parent-reported hyperactivity-impulsivity and inattention symptoms from childhood to adolescence and to study their associations with genetic factors, family risk, and later adjustment problems in early adulthood. Data in this study comes from 1,450 twin pairs participating in a population-based, longitudinal twin study. Developmental trajectories were defined using parent-ratings of hyperactivity-impulsivity and inattention symptoms at age 8-9, 13-14, and 16-17. Twin methods were used to explore genetic influences on trajectories. Family risk measures included low socioeconomic status, large family size and divorce. Self-ratings of externalizing and internalizing problems in early adulthood were used to examine adjustment problems related to the different trajectory combinations. We found two hyperactivity-impulsivity trajectories (low, high/decreasing) and two inattention trajectories (low, high/increasing). Twin modeling revealed a substantial genetic component underlying both the hyperactivity-impulsivity and the inattention trajectory. Joint trajectory analyses identified four groups of adolescents with distinct developmental patterns of hyperactivity-impulsivity and inattention: a low/low group, a primarily hyperactive, a primarily inattentive and a combined (high/high) trajectory type. These trajectory combinations showed discriminant relations to adjustment problems in early adulthood. The hyperactive, inattentive and combined trajectory subtypes were associated with higher rates of family risk environments compared to the low/low group. Study results showed that for those on a high trajectory, hyperactivity decreased whereas inattention increased. The combinations of these trajectories lend developmental insight into how children shift from (i) a combined to inattentive subtype, and (ii) a hyperactive-impulsive to a combined subtype. This study suggests that ADHD subtypes cannot be viewed as discrete and stable categories. © 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health.

The rationale of combination antifungal therapy in severely immunocompromised patients: empiricism versus evidence-based medicine.

PubMed

Chamilos, Georgios; Kontoyiannis, Dimitrios P

2006-08-01

Despite expansion of the antifungal armamentarium over the past decade, the mortality rate for invasive fungal infections remains high in severely immunocompromised patients. Furthermore, in recent years, difficult-to-treat invasive infections caused by rare molds and yeasts have emerged in high-risk patients receiving antifungal prophylaxis or empirical treatment. Antifungal combinations are increasingly used in clinical practice to improve outcomes for refractory mycoses because of the suboptimal efficacy of current antifungal agents. Herein we review recent advances in the area of antifungal combinations in high-risk patients to separate empiricism from evidence-based medicine. Thus far, the benefits of combination antifungal therapy have been difficult to prove for invasive fungal infections other than cryptococcal meningitis. The recent introduction of a new class of antifungal agents (the echinocandins) and extended-spectrum triazoles has rejuvenated interest in studying those combinations for difficult-to-treat aspergillosis, as recent observational studies show promise. In view of the evolving epidemiology of invasive fungal infections, combination antifungal therapy could be most valuable in preemptive management of carefully selected high-risk patients; however, this should be studied in appropriate trials.

Identification of Centella asiatica's Effective Ingredients for Inducing the Neuronal Differentiation.

PubMed

Jiang, Hui; Zheng, Guoshuai; Lv, Junwei; Chen, Heyu; Lin, Jinjin; Li, Yiyang; Fan, Guorong; Ding, Xianting

2016-01-01

Centella asiatica, commonly known as Gotu kola, has been widely used as a traditional herb for decades. Yet, the study on which compounds or compound combinations actually lead to its brain benefits remains scarce. To study the neuroprotection effects of Centella asiatica, neuronal differentiation of PC12 cells was applied. In our pilot study, we isolated 45 Centella asiatica fractions and tested their abilities for inducing neuronal differentiation on PC12 cells. The most effective fraction showed robust induction in neurite outgrowth and neurofilament expression. LC-MS fingerprint analysis of this fraction revealed asiatic acid and madecassic acid as the dominant components. A further investigation on the pure combination of these two compounds indicated that the combination of these two compounds extensively promoted nerve differentiation in vitro. Application of PD98059, a protein MEK inhibitor, attenuated combination-induced neurofilament expression, indicating the combination-induced nerve differentiation through activation of MEK signaling pathway. Our results support the use of combination of asiatic acid and madecassic acid as an effective mean to intervene neurodegenerative diseases in which neurotrophin deficiency is involved.

Identification of Centella asiatica's Effective Ingredients for Inducing the Neuronal Differentiation

PubMed Central

Jiang, Hui; Zheng, Guoshuai; Lv, Junwei; Chen, Heyu; Lin, Jinjin; Li, Yiyang; Fan, Guorong

2016-01-01

Centella asiatica, commonly known as Gotu kola, has been widely used as a traditional herb for decades. Yet, the study on which compounds or compound combinations actually lead to its brain benefits remains scarce. To study the neuroprotection effects of Centella asiatica, neuronal differentiation of PC12 cells was applied. In our pilot study, we isolated 45 Centella asiatica fractions and tested their abilities for inducing neuronal differentiation on PC12 cells. The most effective fraction showed robust induction in neurite outgrowth and neurofilament expression. LC-MS fingerprint analysis of this fraction revealed asiatic acid and madecassic acid as the dominant components. A further investigation on the pure combination of these two compounds indicated that the combination of these two compounds extensively promoted nerve differentiation in vitro. Application of PD98059, a protein MEK inhibitor, attenuated combination-induced neurofilament expression, indicating the combination-induced nerve differentiation through activation of MEK signaling pathway. Our results support the use of combination of asiatic acid and madecassic acid as an effective mean to intervene neurodegenerative diseases in which neurotrophin deficiency is involved. PMID:27446228

Feasibility Study Combining Art Therapy or Cognitive Remediation Therapy with Family-based Treatment for Adolescent Anorexia Nervosa.

PubMed

Lock, James; Fitzpatrick, Kathleen Kara; Agras, William S; Weinbach, Noam; Jo, Booil

2018-01-01

Adolescents with anorexia nervosa who have obsessive-compulsive (OC) features respond poorly to family-based treatment (FBT). This study evaluated the feasibility of combining FBT with either cognitive remediation therapy (CRT) or art therapy (AT) to improve treatment response in this at-risk group. Thirty adolescents with anorexia nervosa and OC features were randomized to 15 sessions of FBT + CRT or AT. Recruitment rate was 1 per month, and treatment attrition was 16.6% with no differences between groups. Suitability, expectancy and therapeutic relationships were acceptable for both combinations. Correlations between changes in OC traits and changes in cognitive inefficiencies were found for both combinations. Moderate changes in cognitive inefficiencies were found in both groups but were larger in the FBT + AT combination. This study suggests that an RCT for poor responders to FBT because of OC traits combining FBT with either CRT or AT is feasible to conduct. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Combination of psychotherapy and benzodiazepines versus either therapy alone for panic disorder: a systematic review

PubMed Central

Watanabe, Norio; Churchill, Rachel; Furukawa, Toshi A

2007-01-01

Background: The efficacy of combined psychotherapy and benzodiazepine treatment for panic disorder is still unclear despite its widespread use. The present systematic review aims to examine its efficacy compared with either monotherapy alone. Methods: All randomised trials comparing combined psychotherapy and benzodiazepine for panic disorder with either therapy alone were identified by comprehensive electronic search on the Cochrane Registers, by checking references of relevant studies and of other reviews, and by contacting experts in the field. Two reviewers independently checked eligibility of trials, assessed quality of trials and extracted data from eligible trials using a standardized data extraction form. Our primary outcome was "response" defined by global judgement. Authors of the original trials were contacted for further unpublished data. Meta-analyses were undertaken synthesizing data from all relevant trials. Results: Only two studies, which compared the combination with behaviour (exposure) therapy, met our eligibility criteria. Both studies had a 16-week intervention. Unpublished data were retrieved for one study. The relative risk for response for the combination was 1.25 (95%CI: 0.78 to 2.03) during acute phase treatment, 0.78 (0.45 to 1.35) at the end of treatment, and 0.62 (0.36 to 1.07) at 6–12 months follow-up. Some secondary outcomes hinted at superiority of the combination during acute phase treatment. One study was identified comparing the combination to benzodiazepine. The relative risk for response was 1.57 (0.83 to 2.98), 3.39 (1.03 to 11.21, statistically significant) and 2.31 (0.79 to 6.74) respectively. The superiority of the combination was observed on secondary outcomes at all the time points. No sub-group analyses were conducted due to the limited number of included trials. Conclusion: Unlike some narrative reviews in the literature, our systematic search established the paucity of high quality evidence for or against the combined psychotherapy plus benzodiazepine therapy for panic disorder. Based on limited available published and unpublished data, however, the combined therapy is probably to be recommended over benzodiazepine alone for panic disorder with agoraphobia. The combination might be superior to behaviour therapy alone during the acute phase, but afterwards this trend may be reversed. We know little from these trials about their adverse effects. PMID:17501985

The combined effect of administration of intravenous and topical tranexamic acid on blood loss and transfusion rate in total knee arthroplasty: Combined tranexamic acid for TKA.

PubMed

Yuan, Z F; Yin, H; Ma, W P; Xing, D L

2016-08-01

Tranexamic acid (TXA) is an antifibrinolytic agent used as a blood-sparing technique in total knee arthroplasty (TKA), and is routinely administered by intravenous (IV) or intra-articular (IA) injection. Recently, a novel method of TXA administration, the combined IV and IA application of TXA, has been applied in TKA. However, the scientific evidence of combined administration of TXA in TKA is still meagre. This meta-analysis aimed to investigate the efficacy and safety of combined IV and IA TXA in patients undergoing TKA. A systematic search was carried out in PubMed, the Cochrane Clinical Trial Register (Issue12 2015), Embase, Web of Science and the Chinese Biomedical Database. Only randomised controlled trials (RCT) evaluating the efficacy and safety of combined use TXA in TKA were identified. Two authors independently identified the eligible studies, extracted data and assessed the methodological quality of included studies. Meta-analysis was conducted using Review Manager 5.3 software. A total of ten RCTs (1143 patients) were included in this study. All the included studies were randomised and the quality of included studies still needed improvement. The results indicated that, compared with either placebo or the single-dose TXA (IV or IA) group, the combination of IV and IA TXA group had significantly less total blood loss, hidden blood loss, total drain output, a lower transfusion rate and a lower drop in haemoglobin level. There were no statistically significant differences in complications such as wound infection and deep vein thrombosis between the combination group and the placebo or single-dose TXA group. Compared with placebo or the single-dose TXA, the combined use of IV and IA TXA provided significantly better results with respect to all outcomes related to post-operative blood loss without increasing the risk of thromboembolic complications in TKA.Cite this article: Z. F. Yuan, H. Yin, W. P. Ma, D. L. Xing. The combined effect of administration of intravenous and topical tranexamic acid on blood loss and transfusion rate in total knee arthroplasty: combined tranexamic acid for TKA. Bone Joint Res 2016;5:353-361. DOI: 10.1302/2046-3758.58.BJR-2016-0001.R2. © 2016 Ma et al.

Thermodynamic Study of Multi Pressure HRSG in Gas/Steam Combined Cycle Power Plant

NASA Astrophysics Data System (ADS)

Sharma, Meeta; Singh, Onkar

2018-01-01

Combined cycle power plants have a combination of gas based topping cycle and steam based bottoming cycle through the use of Heat Recovery Steam Generator (HRSG). These HRSG may be either of single pressure (SP) or dual pressure (DP) or multiple pressure type. Here in this study thermodynamic analysis is carried out for optimal performance of HRSG using different types of HRSG layout for combined cycle efficiency improvement. Performance of single pressure HRSG and dual pressure HRSG, utilized in gas/steam combined cycle is analyzed and presented here. In comparison to single pressure, dual pressure HRSG offers 10 to 15% higher reduction in stack temperature due to greater heat recovery and thus improved plant efficiency.

In vitro evaluation of the activity of two doses of Levofloxacin alone and in combination with other agents against Pseudomonas aeruginosa.

PubMed

Burgess, David S; Hall, Ronald G; Hardin, Thomas C

2003-06-01

P. aeruginosa is one of the most difficult to treat pathogens that generally requires combination therapy to prevent the development of resistance. This study evaluated the in vitro activity of two concentrations of levofloxacin (modeled for the 500 mg and 750 mg daily dose) in combination with ceftazidime, cefepime, piperacillin/tazobactam, imipenem, and tobramycin against P. aeruginosa. MICs and time-kill studies were performed against 12 non-duplicate clinical isolates of P. aeruginosa. The percent susceptible for levofloxacin, ceftazidime, cefepime, piperacillin/tazobactam, imipenem, and tobramycin were 67%, 58%, 58%, 67%, 75%, and 100%, respectively. Tobramycin was the most active single agent, killing and maintaining > or =99.9% killing over a 24 h period against all isolates. Levofloxacin 4 microg/mL(750 mg/day) alone reached 99.9% killing and maintain this killing over the time period more often than levofloxacin 2 microg/mL (500 mg/day). No combination was antagonistic and all combinations with tobramycin were indifferent. Overall, levofloxacin 2 microg/mL plus a beta-lactam was synergistic (65%) more often than levofloxacin 4 microg/mL combinations (46%). This was not unexpected due to the increased activity of levofloxacin 4 microg/mL. However, levofloxacin 4 microg/mL combinations maintained a > or =99.9% killing over the entire 24 h period more often than levofloxacin 2 microg/mL combinations (94% vs 83%). The findings from this work suggest that levofloxacin 750 mg/day in combination with another agent active against P. aeruginosa may prove to be clinically beneficial and superior to combinations using lower doses of levofloxacin. In vivo studies are needed to evaluate the clinical significance of these findings.

Clinical Outcomes and Return to Sport After Arthroscopic Anterior, Posterior, and Combined Shoulder Stabilization

PubMed Central

Kraeutler, Matthew J.; Aberle, Nicholas S.; Brown, Colin C.; Ptasinski, Joseph J.; McCarty, Eric C.

2018-01-01

Background: Glenohumeral instability is a common abnormality, especially among athletes. Previous studies have evaluated outcomes after arthroscopic stabilization in patients with anterior or posterior shoulder instability but have not compared outcomes between groups. Purpose: To compare return-to-sport and other patient-reported outcomes in patients after primary arthroscopic anterior, posterior, and combined anterior and posterior shoulder stabilization. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent primary arthroscopic anterior, posterior, or combined anterior and posterior shoulder stabilization were contacted at a minimum 2-year follow-up. Patients completed a survey that consisted of return-to-sport outcomes as well as the Western Ontario Shoulder Instability Index (WOSI), Single Assessment Numeric Evaluation (SANE), American Shoulder and Elbow Sur’geons (ASES) score, and Shoulder Activity Scale. Results: A total of 151 patients were successfully contacted (anterior: n = 81; posterior: n = 22; combined: n = 48) at a mean follow-up of 3.6 years. No significant differences were found between the groups with regard to age at the time of surgery or time to follow-up. No significant differences were found between the groups in terms of WOSI (anterior: 76; posterior: 70; combined: 78; P = .28), SANE (anterior: 87; posterior: 85; combined: 87; P = .79), ASES (anterior: 88; posterior: 83; combined: 91; P = .083), or Shoulder Activity Scale (anterior: 12.0; posterior: 12.5; combined: 12.5; P = .74) scores. No significant difference was found between the groups in terms of the rate of return to sport (anterior: 73%; posterior: 68%; combined: 75%; P = .84). Conclusion: Athletes undergoing arthroscopic stabilization of anterior, posterior, or combined shoulder instability can be expected to share a similar prognosis. High patient-reported outcome scores and moderate to high rates of return to sport were achieved by all groups. PMID:29637085

Assessing the clinical utility of combined movement examination in symptomatic degenerative lumbar spondylosis.

PubMed

Monie, A P; Price, R I; Lind, C R P; Singer, K P

2015-07-01

The aim of this study is to report the development and validation of a low back computer-aided combined movement examination protocol in normal individuals and record treatment outcomes of cases with symptomatic degenerative lumbar spondylosis. Test-retest, following intervention. Self-report assessments and combined movement examination were used to record composite spinal motion, before and following neurosurgical and pain medicine interventions. 151 normal individuals aged from 20 years to 69 years were assessed using combined movement examination between L1 and S1 spinal levels to establish a reference range. Cases with degenerative low back pain and sciatica were assessed before and after therapeutic interventions with combined movement examination and a battery of self-report pain and disability questionnaires. Change scores for combined movement examination and all outcome measures were derived. Computer-aided combined movement examination validation and intraclass correlation coefficient with 95% confidence interval and least significant change scores indicated acceptable reliability of combined movement examination when recording lumbar movement in normal subjects. In both clinical cases lumbar spine movement restrictions corresponded with self-report scores for pain and disability. Post-intervention outcomes all showed significant improvement, particularly in the most restricted combined movement examination direction. This study provides normative reference data for combined movement examination that may inform future clinical studies of the technique as a convenient objective surrogate for important clinical outcomes in lumbar degenerative spondylosis. It can be used with good reliability, may be well tolerated by individuals in pain and appears to change in concert with validated measures of lumbar spinal pain, functional limitation and quality of life. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinically Relevant Plasma Concentrations of Colistin in Combination with Imipenem Enhance Pharmacodynamic Activity against Multidrug-Resistant Pseudomonas aeruginosa at Multiple Inocula▿†

PubMed Central

Bergen, Phillip J.; Forrest, Alan; Bulitta, Jürgen B.; Tsuji, Brian T.; Sidjabat, Hanna E.; Paterson, David L.; Li, Jian; Nation, Roger L.

2011-01-01

The use of combination antibiotic therapy may be beneficial against rapidly emerging resistance in Pseudomonas aeruginosa. The aim of this study was to systematically investigate in vitro bacterial killing and resistance emergence with colistin alone and in combination with imipenem against multidrug-resistant (MDR) P. aeruginosa. Time-kill studies were conducted over 48 h using 5 clinical isolates and ATCC 27853 at two inocula (∼106 and ∼108 CFU/ml); MDR, non-MDR, and colistin-heteroresistant and -resistant strains were included. Nine colistin-imipenem combinations were investigated. Microbiological response was examined by log changes at 6, 24, and 48 h. Colistin combined with imipenem at clinically relevant concentrations increased the levels of killing of MDR and colistin-heteroresistant isolates at both inocula. Substantial improvements in activity with combinations were observed across 48 h with all colistin concentrations at the low inoculum and with colistin at 4× and 16× MIC (or 4 and 32 mg/liter) at the high inoculum. Combinations were additive or synergistic against imipenem-resistant isolates (MICs, 16 and 32 mg/liter) at the 106-CFU inoculum in 9, 11, and 12 of 18 cases (i.e., 9 combinations across 2 isolates) at 6, 24, and 48 h, respectively, and against the same isolates at the 108-CFU inoculum in 11, 7, and 8 cases, respectively. Against a colistin-resistant strain (MIC, 128 mg/liter), combinations were additive or synergistic in 9 and 8 of 9 cases at 24 h at the 106- and 108-CFU inocula, respectively, and in 5 and 7 cases at 48 h. This systematic study provides important information for optimization of colistin-imipenem combinations targeting both colistin-susceptible and colistin-resistant subpopulations. PMID:21876058

Use of Neoadjuvant Chemotherapy Plus Molecular Targeted Therapy in Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

PubMed

Sabanathan, Dhanusha; Eslick, Guy D; Shannon, Jenny

2016-12-01

Surgery remains the standard of care for patients with colorectal liver metastases (CLMs), with a 5-year survival rate approaching 35%. Perioperative chemotherapy confers a survival benefit in selected patients with CLMs. The use of molecular targeted therapy combined with neoadjuvant chemotherapy for CLMs, however, remains controversial. We reviewed the published data on combination neoadjuvant chemotherapy and molecular targeted therapy for resectable and initially unresectable CLMs. A literature search of the Medline and PubMed databases was conducted to identify studies of neoadjuvant chemotherapy plus molecular targeted therapy in the management of resectable or initially unresectable CLMs. We calculated the pooled proportion and 95% confidence intervals using a random effects model for the relationship of the combination neoadjuvant treatment on the overall response rate and performed a systematic review of all identified studies. The analysis was stratified according to the study design. The data from 11 studies of 908 patients who had undergone systemic chemotherapy plus targeted therapy for CLM were analyzed. The use of combination neoadjuvant therapy was associated with an overall response rate of 68% (95% confidence interval, 63%-73%), with significant heterogeneity observed in the studies (I 2  = 89.35; P < .001). Of the 11 studies, 4 used a combination that included oxaliplatin, 2 included irinotecan, and 5 included a combination of both. Also, 7 studies used cetuximab and 4 bevacizumab. The overall progression-free survival was estimated at 14.4 months. Current evidence suggests that neoadjuvant chemotherapy plus molecular targeted agents for CLM confers high overall response rates. Combination treatment might also increase the resectability rates in initially unresectable CLM. Further studies are needed to examine the survival outcomes, with a focus on the differential role of molecular targeted therapy in the neoadjuvant versus adjuvant setting. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Statistical approaches to assessing single and multiple outcome measures in dry eye therapy and diagnosis.

PubMed

Tomlinson, Alan; Hair, Mario; McFadyen, Angus

2013-10-01

Dry eye is a multifactorial disease which would require a broad spectrum of test measures in the monitoring of its treatment and diagnosis. However, studies have typically reported improvements in individual measures with treatment. Alternative approaches involve multiple, combined outcomes being assessed by different statistical analyses. In order to assess the effect of various statistical approaches to the use of single and combined test measures in dry eye, this review reanalyzed measures from two previous studies (osmolarity, evaporation, tear turnover rate, and lipid film quality). These analyses assessed the measures as single variables within groups, pre- and post-intervention with a lubricant supplement, by creating combinations of these variables and by validating these combinations with the combined sample of data from all groups of dry eye subjects. The effectiveness of single measures and combinations in diagnosis of dry eye was also considered. Copyright © 2013. Published by Elsevier Inc.

A combined system for measuring animal motion activities.

PubMed

Young, M S; Young, C W; Li, Y C

2000-01-31

In this study, we have developed a combined animal motion activity measurement system that combines an infrared light matrix subsystem with an ultrasonic phase shift subsystem for animal activity measurement. Accordingly, in conjunction with an IBM PC/AT compatible personal computer, the combined system has the advantages of both infrared and ultrasonic subsystems. That is, it can at once measure and directly analyze detailed changes in animal activity ranging from locomotion to tremor. The main advantages of this combined system are that it features real time data acquisition with the option of animated real time or recorded display/playback of the animal's motion. Additionally, under the multi-task operating condition of IBM PC, it can acquire and process behavior using both IR and ultrasound systems simultaneously. Traditional systems have had to make separate runs for gross and fine movement recording. This combined system can be profitably employed for normative behavioral activity studies and for neurological and pharmacological research.

Low thrust chemical orbit to orbit propulsion system propellant management study

NASA Technical Reports Server (NTRS)

Dergance, R. H.; Hamlyn, K. M.; Tegart, J. R.

1981-01-01

Low thrust chemical propulsion systems were sized for transfer of large space systems from LEO to GEO. The influence of propellant combination, tankage and insulation requirements, and propellant management techniques on the LTPS mass and volume were studied. Liquid oxygen combined with hydrogen, methane or kerosene were the propellant combinations. Thrust levels of 445, 2230, and 4450 N were combined with 1, 4 and 8 perigee burn strategies. This matrix of systems was evaluated using multilayer insulation and spray-on-foam insulation systems. Various combinations of toroidal, cylindrical with ellipsoidal domes, and ellipsoidal tank shapes were investigated. Results indicate that low thrust (445 N) and single perigee burn approaches are considerably less efficient than the higher thrust level and multiple burn strategies. A modified propellant settling approach minimized propellant residuals and decreased system complexity, in addition, the toroid/ellipsoidal tank combination was predicted to be shortest.

Synergistic activity profile of carbosilane dendrimer G2-STE16 in combination with other dendrimers and antiretrovirals as topical anti-HIV-1 microbicide.

PubMed

Sepúlveda-Crespo, Daniel; Lorente, Raquel; Leal, Manuel; Gómez, Rafael; De la Mata, Francisco J; Jiménez, José Luis; Muñoz-Fernández, M Ángeles

2014-04-01

Polyanionic carbosilane dendrimers represent opportunities to develop new anti-HIV microbicides. Dendrimers and antiretrovirals (ARVs) acting at different stages of HIV replication have been proposed as compounds to decrease new HIV infections. Thus, we determined the potential use of our G2-STE16 carbosilane dendrimer in combination with other carbosilane dendrimers and ARVs for the use as topical microbicide against HIV-1. We showed that these combinations obtained 100% inhibition and displayed a synergistic profile against different HIV-1 isolates in our model of TZM.bl cells. Our results also showed their potent activity in the presence of an acidic vaginal or seminal fluid environment and did not activate an inflammatory response. This study is the first step toward exploring the use of different anionic carbosilane dendrimers in combination and toward making a safe microbicide. Therefore, our results support further studies on dendrimer/dendrimer or dendrimer/ARV combinations as topical anti-HIV-1 microbicide. This paper describes the first steps toward the use of anionic carbosilane dendrimers in combination with antivirals to address HIV-1, paving the way to further studies on dendrimer/dendrimer or dendrimer/ARV combinations as topical anti-HIV-1 microbicides. © 2014.

Combination of α-Tomatine and Curcumin Inhibits Growth and Induces Apoptosis in Human Prostate Cancer Cells

PubMed Central

Li, Dongli; He, Yan; Li, Yu; Du, Zhiyun; Zhang, Kun; DiPaola, Robert; Goodin, Susan; Zheng, Xi

2015-01-01

α-Tomatine is a glycoalkaloid found in tomatoes and curcumin is a major yellow pigment of turmeric. In the present study, the combined effect of these two compounds on prostate cancer cells was studied. Treatment of different prostate cancer cells with curcumin or α-tomatine alone resulted in growth inhibition and apoptosis in a concentration-dependent manner. Combinations of α-tomatine and curcumin synergistically inhibited the growth and induced apoptosis in prostate cancer PC-3 cells. Effects of the α-tomatine and curcumin combination were associated with synergistic inhibition of NF-κB activity and a potent decrease in the expression of its downstream gene Bcl-2 in the cells. Moreover, strong decreases in the levels of phospho-Akt and phosphor-ERK1/2 were found in PC-3 cells treated with α-tomatine and curcumin in combination. In animal experiment, SCID mice with PC-3 xenograft tumors were treated with α-tomatine and curcumin. Combination of α-tomatine and curcumin more potently inhibited the growth of PC-3 tumors than either agent alone. Results from the present study indicate that α-tomatine in combination with curcumin may be an effective strategy for inhibiting the growth of prostate cancer. PMID:26630272

Combination of hemostatic therapies for treatment of patients with hemophilia A and inhibitors.

PubMed

Livnat, Tami; Budnik, Ivan; Levy-Mendelovich, Sarina; Avishai, Einat; Misgav, Mudi; Barg, Assaf Arie; Lubetsky, Aharon; Brutman-Barazani, Tami; Kenet, Gili

2017-07-01

Therapy application and monitoring of patients with hemophilia A (HA) and inhibitors are challenging. In the current study, combined FVIII - bypass therapy was implemented for a cohort of severe HA patients with inhibitors. Plasma of 15 HA patients with inhibitors was spiked ex vivo with FVIII, rFVIIa, FEIBA and their combinations and thrombin generation (TG) was studied. Some patients who experienced hemarthroses or required minor surgeries were treated by a combined concomitant administration of FVIII+FEIBA as IV bolus doses. TG spiking studies showed individual responses not correlated to inhibitor titer. Combinations of agents augmented TG as compared to any single agent, while combined FVIII+FEIBA yielded the highest TG, supporting it as a potential treatment. Following emergent successful surgery of child treated by concomitant FVIII+FEIBA, a total of 396 episodes in 7/15 patients were treated with concomitant FVIII+FEIBA. Five patients were treated for bleeding episodes only, whereas 2 were children undergoing immune tolerance induction (ITI) with FEIBA prophylaxis. Four minor surgeries were performed on FVIII+FEIBA repeated infusions. Neither thrombosis nor any other adverse events were documented. A combination of FVIII+FEIBA may be effective and safe as an alternative treatment option for some high-responding inhibitor patients. Copyright © 2017 Elsevier Inc. All rights reserved.

The combination of aricept with a traditional Chinese medicine formula, smart soup, may be a novel way to treat Alzheimer's disease.

PubMed

Wang, Ying; Wang, Ying; Sui, Yi; Yu, Hongshuang; Shen, Xiaoheng; Chen, Shengdi; Pei, Gang; Zhao, Jian; Ding, Jianqing

2015-01-01

Alzheimer's disease (AD) is a common neurodegenerative disease affecting cognitive function in the elderly, which is characterized by the presence of extracellular deposits of insoluble amyloid-β plaques and neuronal loss. Modern pharmacology and drug development usually follow a single-target principle, which might contribute to the failure of most compounds in clinical trials against AD. Considering AD is a multifactorial disease, a combination therapeutic strategy that applies drugs with different mechanisms would be an alternative way. Smart Soup (SS), a Traditional Chinese Medicine formula, is composed of three herbaceous plants and has been applied in the treatment of amnesia in China for hundreds of years. In this work, we studied the clinical potency of the combination of SS and Aricept in AD therapy. In the in vivo model, both longevity and locomotive activity of AD transgenic Drosophila were improved remarkably in the combined medicine treated group. We also observed less amyloid-β deposition and retarded neuronal loss following the combined drug treatment. In the retrospective cohort study, we found the combination therapy exerted better therapeutic effect on AD patients. Our study revealed that combination therapy with multiple drug targets did have a better therapeutic outcome. It provides a new strategy to develop an optimum pharmaceutical approach against AD.

Antifungal activity of silver nanoparticles in combination with nystatin and chlorhexidine digluconate against Candida albicans and Candida glabrata biofilms.

PubMed

Monteiro, Douglas R; Silva, Sónia; Negri, Melyssa; Gorup, Luiz F; de Camargo, Emerson R; Oliveira, Rosário; Barbosa, Debora B; Henriques, Mariana

2013-11-01

Although silver nanoparticles (SN) have been investigated as an alternative to conventional antifungal drugs in the control of Candida-associated denture stomatitis, the antifungal activity of SN in combination with antifungal drugs against Candida biofilms remains unknown. Therefore, the aim of this study was to evaluate the antifungal efficacy of SN in combination with nystatin (NYT) or chlorhexidine digluconate (CHG) against Candida albicans and Candida glabrata biofilms. The drugs alone or combined with SN were applied on mature Candida biofilms (48 h), and after 24 h of treatment their antibiofilm activities were assessed by total biomass quantification (by crystal violet staining) and colony forming units enumeration. The structure of Candida biofilms was analysed by scanning electron microscopy (SEM) images. The data indicated that SN combined with either NYT or CHG demonstrated synergistic antibiofilm activity, and this activity was dependent on the species and on the drug concentrations used. SEM images showed that some drug combinations were able to disrupt Candida biofilms. The results of this study suggest that the combination of SN with NYT or CHG may have clinical implications in the treatment of denture stomatitis. However, further studies are needed before recommending the use of these drugs safely in clinical situations. © 2013 Blackwell Verlag GmbH.

Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models.

PubMed

Lehmann, Christian; Friess, Thomas; Birzele, Fabian; Kiialainen, Anna; Dangl, Markus

2016-06-28

Venetoclax, a small molecule BH3 mimetic which inhibits the anti-apoptotic protein Bcl-2, and idasanutlin, a selective MDM2 antagonist, have both shown activity as single-agent treatments in pre-clinical and clinical studies in acute myeloid leukemia (AML). In this study, we deliver the rationale and molecular basis for the combination of idasanutlin and venetoclax for treatment of p53 wild-type AML. The effect of idasanutlin and venetoclax combination on cell viability, apoptosis, and cell cycle progression was investigated in vitro using established AML cell lines. In vivo efficacy was demonstrated in subcutaneous and orthotopic xenograft models generated in female nude or non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Mode-of-action analyses were performed by means of cell cycle kinetic studies, RNA sequencing as well as western blotting experiments. Combination treatment with venetoclax and idasanutlin results in synergistic anti-tumor activity compared with the respective single-agent treatments in vitro, in p53 wild-type AML cell lines, and leads to strongly superior efficacy in vivo, in subcutaneous and orthotopic AML models. The inhibitory effects of idasanutlin were cell-cycle dependent, with cells arresting in G1 in consecutive cycles and the induction of apoptosis only evident after cells had gone through at least two cell cycles. Combination treatment with venetoclax removed this dependency, resulting in an acceleration of cell death kinetics. As expected, gene expression studies using RNA sequencing showed significant alterations to pathways associated with p53 signaling and cell cycle arrest (CCND1 pathway) in response to idasanutlin treatment. Only few gene expression changes were observed for venetoclax treatment and combination treatment, indicating that their effects are mediated mainly at the post-transcriptional level. Protein expression studies demonstrated that inhibition of the anti-apoptotic protein Mcl-1 contributed to the activity of venetoclax and idasanutlin, with earlier inhibition of Mcl-1 in response to combination treatment contributing to the superior combined activity. The role of Mcl-1 was confirmed by small hairpin RNA gene knockdown studies. Our findings provide functional and molecular insight on the superior anti-tumor activity of combined idasanutlin and venetoclax treatment in AML and support its further exploration in clinical studies.

Vascular Disruption in Combination with mTOR Inhibition in Renal Cell Carcinoma

PubMed Central

Ellis, Leigh; Shah, Preeti; Hammers, Hans; Lehet, Kristin; Sotomayor, Paula; Azabdaftari, Gissou; Seshadri, Mukund; Pili, Roberto

2013-01-01

Renal cell carcinoma (RCC) is an angiogenesis-dependent and hypoxia-driven malignancy. As a result, there has been an increased interest in the use of antiangiogenic agents for the management of RCC in patients. However, the activity of tumor-vascular disrupting agents (tumor-VDA) has not been extensively examined against RCC. In this study, we investigated the therapeutic efficacy of the tumor-VDA ASA404 (DMXAA, 5,6-dimethylxanthenone-4-acetic acid, or vadimezan) in combination with the mTOR inhibitor everolimus (RAD001) against RCC. In vitro studies were carried out using human umbilical vein endothelial cells and in vivo studies using orthotopic RENCA tumors and immunohistochemical patient tumor-derived RCC xenografts. MRI was used to characterize the vascular response of orthotopic RENCA xenografts to combination treatment. Therapeutic efficacy was determined by tumor growth measurements and histopathologic evaluation. ASA404/everolimus combination resulted in enhanced inhibition of endothelial cell sprouting in the 3-dimensional spheroid assay. MRI of orthotopic RENCA xenografts revealed an early increase in permeability 4 hours posttreatment with ASA404, but not with everolimus. Twenty-four hours after treatment, a significant reduction in blood volume was observed with combination treatment. Correlative CD31/NG2 staining of tumor sections confirmed marked vascular damage following combination therapy. Histologic sections showed extensive necrosis and a reduction in the viable rim following combination treatment compared with VDA treatment alone. These results show the potential of combining tumor-VDAs with mTOR inhibitors in RCC. Further investigation into this novel combination strategy is warranted. PMID:22084164

Triple combination antibiotic therapy for carbapenemase-producing Klebsiella pneumoniae: a systematic review.

PubMed

Jacobs, David M; Safir, M Courtney; Huang, Dennis; Minhaj, Faisal; Parker, Adam; Rao, Gauri G

2017-11-25

The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections. The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy. Articles were stratified into two tiers depending on the level of clinical detail provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome, patient status at onset of infection, and source of infection. Articles not reaching these criteria were considered tier 2. Thirty-three studies were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were included in this analysis. The most common infection was pneumonia (31%) followed by primary or catheter-related bacteremia (21%) and urinary tract infection (17%). Different combinations of antibiotic classes were utilized in triple combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%), tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients (52.4%), respectively. Overall mortality for patients treated with triple combination therapy was 35.8% (19/53 patients). Triple combination therapy is being considered as a treatment option for CPKP. Polymyxin-based therapy is the backbone antibiotic in these regimens, but its effectiveness needs establishing in prospective clinical trials.

Ankle foot orthosis-footwear combination tuning: an investigation into common clinical practice in the United Kingdom.

PubMed

Eddison, Nicola; Chockalingam, Nachiappan; Osborne, Stephen

2015-04-01

Ankle foot orthoses are used to treat a wide variety of gait pathologies. Ankle foot orthosis-footwear combination tuning should be routine clinical practice when prescribing an ankle foot orthosis. Current research suggests that failure to tune ankle foot orthosis-footwear combinations can lead to immediate detrimental effect on function, and in the longer term, it may actually contribute to deterioration. The purpose of this preliminary study was to identify the current level of knowledge clinicians have in the United Kingdom regarding ankle foot orthosis-footwear combination tuning and to investigate common clinical practice regarding ankle foot orthosis-footwear combination tuning among UK orthotists. Cross-sectional survey. A prospective study employing a multi-item questionnaire was sent out to registered orthotists and uploaded on to the official website of British Association of Prosthetists and Orthotists to be accessed by their members. A total of 41 completed questionnaires were received. The results demonstrate that only 50% of participants use ankle foot orthosis-footwear combination tuning as standard clinical practice. The most prevalent factors preventing participants from carrying out ankle foot orthosis-footwear combination tuning are a lack of access to three-dimensional gait analysis equipment (37%) and a lack of time available in their clinics (27%). Although, ankle foot orthosis-footwear combination tuning has been identified as an essential aspect of the prescription of ankle foot orthoses, the results of this study show a lack of understanding of the key principles behind ankle foot orthosis-footwear combination tuning. © The International Society for Prosthetics and Orthotics 2014.

Design and characterization of diclofenac diethylamine transdermal patch using silicone and acrylic adhesives combination.

PubMed

Panchaxari, Dandigi M; Pampana, Sowjanya; Pal, Tapas; Devabhaktuni, Bhavana; Aravapalli, Anil Kumar

2013-01-07

The objective of the study was to develop and characterize Diclofenac Diethylamine (DDEA) transdermal patch using Silicone and acrylic adhesives combination. Modified solvent evaporation method was employed for casting of film over Fluoropolymer coated polyester release liner. Initial studies included solubilization of drug in the polymers using solubilizers. The formulations with combination of adhesives were attempted to combine the desirable features of both the adhesives. The effect of the permeation enhancers on the drug permeation were studied using pig ear skin. All the optimized patches were subjected to adhesion, dissolution and stability studies. A 7-day skin irritancy test on albino rabbits and an in vivo anti-inflammatory study on wistar rats by carrageenan induced paw edema method were also performed. The results indicated the high percent drug permeation (% CDP-23.582) and low solubility nature (1%) of Silicone adhesive and high solubility (20%) and low% CDP (10.72%) of acrylic adhesive. The combination of adhesives showed desirable characteristics for DDEA permeation with adequate % CDP and sufficient solubility. Release profiles were found to be dependent on proportion of polymer and type of permeation enhancer. The anti-inflammatory study revealed the sustaining effect and high percentage inhibition of edema of C4/OLA (99.68%). The acute skin irritancy studies advocated the non-irritant nature of the adhesives used. It was concluded that an ideal of combination of adhesives would serve as the best choice, for fabrication of DDEA patches, for sustained effect of DDEA with better enhancement in permeation characteristics and robustness.

Discriminative and Reinforcing Stimulus Effects of Nicotine, Cocaine, and Cocaine + Nicotine Combinations in Rhesus Monkeys

PubMed Central

Mello, Nancy K.; Newman, Jennifer L.

2011-01-01

Concurrent cigarette smoking and cocaine use is well documented. However, the behavioral pharmacology of cocaine and nicotine combinations is poorly understood, and there is a need for animal models to examine this form of polydrug abuse. The purpose of this study was two-fold: first to assess the effects of nicotine on the discriminative stimulus effects of cocaine, and second, to study self-administration of nicotine/cocaine combinations in a novel polydrug abuse model. In drug discrimination experiments, nicotine increased the discriminative stimulus effects of low cocaine doses in two of three monkeys, but nicotine did not substitute for cocaine in any monkey. Self-administration of cocaine and nicotine alone, and cocaine + nicotine combinations was studied under a second-order fixed ratio 2, variable ratio 16 (FR2[VR16:S]) schedule of reinforcement. Cocaine and nicotine alone were self-administered in a dose-dependent manner. The combination of marginally reinforcing doses of cocaine and nicotine increased drug self-administration behavior above levels observed with the same dose of either cocaine or nicotine alone. These findings indicate that nicotine may increase cocaine’s discriminative stimulus and reinforcing effects in rhesus monkeys, and illustrate the feasibility of combining cocaine and nicotine in a preclinical model of polydrug abuse. Further studies of the behavioral effects of nicotine + cocaine combinations will contribute to our understanding the pharmacology of dual nicotine and cocaine dependence, and will be useful for evaluation of new treatment medications. PMID:21480727

Bactericidal Effect of Pterostilbene Alone and in Combination with Gentamicin against Human Pathogenic Bacteria.

PubMed

Lee, Wee Xian; Basri, Dayang Fredalina; Ghazali, Ahmad Rohi

2017-03-17

The antibacterial activity of pterostilbene in combination with gentamicin against six strains of Gram-positive and Gram-negative bacteria were investigated. The minimum inhibitory concentration and minimum bactericidal concentration of pterostilbene were determined using microdilution technique whereas the synergistic antibacterial activities of pterostilbene in combination with gentamicin were assessed using checkerboard assay and time-kill kinetic study. Results of the present study showed that the combination effects of pterostilbene with gentamicin were synergistic (FIC index < 0.5) against three susceptible bacteria strains: Staphylococcus aureus ATCC 25923 , Escherichia coli O157 and Pseudomonas aeruginosa 15442 . However, the time-kill study showed that the interaction was indifference which did not significantly differ from the gentamicin treatment. Furthermore, time-kill study showed that the growth of the tested bacteria was completely attenuated with 2 to 8 h treatment with 0.5 × MIC of pterostilbene and gentamicin. The identified combinations could be of effective therapeutic value against bacterial infections. These findings have potential implications in delaying the development of bacterial resistance as the antibacterial effect was achieved with the lower concentrations of antibacterial agents.

Why is working memory capacity related to matrix reasoning tasks?

PubMed

Harrison, Tyler L; Shipstead, Zach; Engle, Randall W

2015-04-01

One of the reasons why working memory capacity is so widely researched is its substantial relationship with fluid intelligence. Although this relationship has been found in numerous studies, researchers have been unable to provide a conclusive answer as to why the two constructs are related. In a recent study, researchers examined which attributes of Raven's Progressive Matrices were most strongly linked with working memory capacity (Wiley, Jarosz, Cushen, & Colflesh, Journal of Experimental Psychology: Learning, Memory, and Cognition, 37, 256-263, 2011). In that study, Raven's problems that required a novel combination of rules to solve were more strongly correlated with working memory capacity than were problems that did not. In the present study, we wanted to conceptually replicate the Wiley et al. results while controlling for a few potential confounds. Thus, we experimentally manipulated whether a problem required a novel combination of rules and found that repeated-rule-combination problems were more strongly related to working memory capacity than were novel-rule-combination problems. The relationship to other measures of fluid intelligence did not change based on whether the problem required a novel rule combination.

Phase I study of the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 with 5-fluorouracil and leucovorin: a safe combination.

PubMed

Hoekstra, R; de Vos, F Y F L; Eskens, F A L M; de Vries, E G E; Uges, D R A; Knight, R; Carr, R A; Humerickhouse, R; Verweij, J; Gietema, J A

2006-03-01

We performed a phase I study with the thrombospondin-1-mimetic angiogenesis inhibitor ABT-510 combined with 5-fluorouracil and leucovorin (5-FU/LV) to determine safety profile and assess pharmacokinetic interactions. Patients with advanced solid malignancies received LV 20 mg/m(2) followed by 5-FU 425 mg/m(2) both administered intravenously in 15 min daily for 5 days every 4 weeks. ABT-510 was administered subcutaneously twice daily continuously from day 2 onwards. Blood and urine samples for pharmacokinetic analyses were collected at days 1, 5 and 22. Twelve patients received a total of 45 cycles of 5-FU/LV combined with ABT-510. ABT-510 dose levels studied were 50 and 100 mg. The combination was well tolerated, with a toxicity profile comparable to that of 5-FU/LV alone. At the dose levels studied no significant pharmacokinetic interactions were observed. These data indicate that ABT-510 administered twice daily subcutaneously can be safely combined with 5-FU/LV administered daily for 5 days, every 4 weeks.

A phase I study of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors potentially responsive to mitoxantrone

PubMed Central

Resta, Lee P.; Pili, Roberto; Eisenberger, Mario A.; Spitz, Avery; King, Serina; Porter, Jennifer; Franke, Amy; Boinpally, Ramesh; Sweeney, Christopher J.

2010-01-01

Purpose To find the maximum tolerated dose (MTD) of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors. Methods This was a Phase I study using cohort dose escalation of OSI-461 dosed orally twice daily in combination with mitoxantrone 12 mg/m2 given on Day 1 of each 21-day cycle. Results OSI-461 dose was escalated to 1,000 mg po bid. One patient experienced a dose-limiting toxicity (DLT). Three patients discontinued the study due to adverse events (AE). Two patients (10%) had a partial response, and ten patients (50%) had stable disease as best response. Conclusion The combination of OSI-461 and mitoxantrone was well tolerated. Dose escalation was stopped because of toxicities in a concurrent Phase I trial. The response rate seen in patients with prostate cancer was comparable to response rates seen in trials of mitoxantrone and prednisone alone, and further studies of the combination of OSI-461 and mitoxantrone were not pursued. PMID:20445979

Phase II study of docetaxel in combination with epirubicin and protracted venous infusion 5-fluorouracil (ETF) in patients with recurrent or metastatic breast cancer. A Yorkshire breast cancer research group study.

PubMed

Humphreys, A C; Dent, J; Rodwell, S; Crawford, S M; Joffe, J K; Bradley, C; Dodwell, D; Perren, T J

2004-06-01

This study was originally designed as a phase I/II study, with a dose escalation of docetaxel in combination with epirubicin 50 mg m(-2) and 5-fluorouracil (5-FU) 200 mg m(-2) day(-1). However, as dose escalation was not possible, the study is reported as a phase II study of the combination to assess response and toxicity. A total of 51 patients with locally advanced or metastatic breast cancer were treated on this phase II study, with doses of docetaxel 50 mg m(-2), epirubicin 50 mg m(-2) and infusional 5-FU 200 mg m(-2) day(-1) for 21 days. The main toxicity of this combination was neutropenia with 89% of patients having grade 3 and 4 neutropenia, and 39% of patients experiencing febrile neutropenia. Nonhaematological toxicity was mild. The overall response rate in the assessable patients was 64%, with median progression-free survival of 38 weeks, and median survival of 70 weeks. The ETF regimen was found to be toxic, and it was not possible to escalate the dose of docetaxel above the first dose level. This regimen has therefore not been taken any further, but as a development of this a new study is ongoing, combining 3-weekly epirubicin, weekly docetaxel and capecitabine, days 1-14.

The Human Kinome Targeted by FDA Approved Multi-Target Drugs and Combination Products: A Comparative Study from the Drug-Target Interaction Network Perspective.

PubMed

Li, Ying Hong; Wang, Pan Pan; Li, Xiao Xu; Yu, Chun Yan; Yang, Hong; Zhou, Jin; Xue, Wei Wei; Tan, Jun; Zhu, Feng

2016-01-01

The human kinome is one of the most productive classes of drug target, and there is emerging necessity for treating complex diseases by means of polypharmacology (multi-target drugs and combination products). However, the advantages of the multi-target drugs and the combination products are still under debate. A comparative analysis between FDA approved multi-target drugs and combination products, targeting the human kinome, was conducted by mapping targets onto the phylogenetic tree of the human kinome. The approach of network medicine illustrating the drug-target interactions was applied to identify popular targets of multi-target drugs and combination products. As identified, the multi-target drugs tended to inhibit target pairs in the human kinome, especially the receptor tyrosine kinase family, while the combination products were able to against targets of distant homology relationship. This finding asked for choosing the combination products as a better solution for designing drugs aiming at targets of distant homology relationship. Moreover, sub-networks of drug-target interactions in specific disease were generated, and mechanisms shared by multi-target drugs and combination products were identified. In conclusion, this study performed an analysis between approved multi-target drugs and combination products against the human kinome, which could assist the discovery of next generation polypharmacology.

Private-sector vaccine purchase costs and insurer payments: a disincentive for using combination vaccines?

PubMed

Clark, Sarah J; Cowan, Anne E; Freed, Gary L

2011-04-01

Combination vaccines have been endorsed as a means to decrease the number of injections needed to complete the childhood immunization schedule, yet anecdotal reports suggest that private providers lose money on combination vaccines. The objective of this study was to determine whether practices purchasing combination vaccines had significantly different vaccine costs and reimbursement compared to practices that were not purchasing combination vaccines. Using cross-sectional purchase and insurer payment data collected from a targeted sample of private practices in five US states, we calculated the average total vaccine cost and reimbursement across the childhood immunization schedule. The average vaccine purchase cost across the childhood schedule was significantly higher for practices using a combined vaccine with diphtheria, tetanus, acellular pertussis vaccine, inactivated polio vaccine, and Hepatitis B vaccine (DTaP-IPV-HepB) than for practices using either separate vaccine products or a combined vaccine with Haemophilus influenzae, type b vaccine and Hepatitis B vaccine (Hib-HepB). The average insurer payment for vaccine administration across the childhood schedule was significantly lower for practices using DTaP-IPV-HepB combination vaccine than for practices using separate vaccine products. This study appears to validate anecdotal reports that vaccine purchase costs and insurer payment for combination vaccines can have a negative financial impact for practices that purchase childhood vaccines.

Neurotoxicity induced by methamphetamine-heroin combination in PC12 cells.

PubMed

Tian, Xiang; Ru, Qin; Xiong, Qi; Yue, Kai; Chen, Lin; Ma, Baomiao; Gan, Weimin; Si, Yuanren; Xiao, Huqiao; Li, Chaoying

2017-04-24

Simultaneous administration of psychostimulants and opioids is a major drug abuse problem worldwide. The combination of psychostimulants and opioids produces more serious effects than either drug alone and is responsible for numerous deaths. In recent years, owing to its increased use, methamphetamine (METH), a psychostimulant, has become a popular choice for use in combination with opioids, especially heroin. However, little is known about the neurotoxicity of METH/heroin combination. The aims of this study were to evaluate whether METH/heroin combination was more neurotoxic than either drug alone and analyze the possible neurotoxic mechanisms using rat pheochromocytoma (PC12) cells. Our data showed that METH/heroin combination exhibited a significant decrease in cell viability than either drug alone, and the coefficient of drug interaction (CDI) indicated that the combination appeared to produce synergistic effects. Further studies showed that METH/heroin combination induced apoptosis and decreased the mitochondrial potential significantly, compared to either drug alone. This was demonstrated by a significant decrease in the expression of Bcl-2 and an increase in expression of Bax, accompanied by increase in the activities of caspase-3 and caspase-9. These results suggest that the combination of METH and heroin is more neurotoxic than either drug alone, and it induces apoptosis via the mitochondrial apoptotic pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

Dapsone gel 5% in combination with adapalene gel 0.1%, benzoyl peroxide gel 4% or moisturizer for the treatment of acne vulgaris: a 12-week, randomized, double-blind study.

PubMed

Fleischer, Alan B; Shalita, Alan; Eichenfield, Lawrence F; Abramovits, William; Lucky, Anne; Garrett, Steven

2010-01-01

To evaluate the safety and efficacy of dapsone gel 5% in the treatment of acne when used in combination with adapalene gel 0.1%, benzoyl peroxide gel 4% or moisturizer. This was a twelve-week, randomized, double-blind study. Patients aged 12 years and older (n=301) applied dapsone gel twice daily and were randomly assigned (1:1:1) to one of three additional treatments, applied once daily. By week 12, dapsone gel combined with any of the three additional treatments reduced the mean number of inflammatory lesions. However, the authors did not detect a significant difference in the reduction of inflammatory lesions when dapsone was used in combination with adapalene gel or with benzoyl peroxide gel compared to the dapsone plus moisturizer combination group (P=0.052 for both versus moisturizer combination). Patients treated with dapsone gel combined with adapalene showed a significantly better response in reduction in non-inflammatory and total acne lesion count than those who received the moisturizer combination. Local adverse reactions in all three treatment groups were minimal and generally mild in severity. Dapsone gel in combination with adapalene gel or benzoyl peroxide gel is safe and well tolerated for the treatment of acne vulgaris.

Tramadol and Tramadol+Caffeine Synergism in the Rat Formalin Test Are Mediated by Central Opioid and Serotonergic Mechanisms

PubMed Central

Carrillo-Munguía, Norma; González-Trujano, Ma. Eva; Huerta, Miguel; Trujillo, Xochitl; Díaz-Reval, M. Irene

2015-01-01

Different analgesic combinations with caffeine have shown this drug to be capable of increasing the analgesic effect. Many combinations with nonsteroidal anti-inflammatory drugs (NSAIDs) have been carried out, but, in regard to opioids, only combinations with morphine and tramadol have been reported. The antinociceptive synergism mechanism of these combinations is not well understood. The purpose of the present study was to determine the participation of spinal and supraspinal opioidergic and serotonergic systems in the synergic effect of the tramadol+caffeine combination in the rat formalin test. At the supraspinal level, the opioid antagonist, naloxone, completely reversed the effect of the drug combination, whereas ketanserin, a 5-HT2 receptor antagonist, inhibited the effect by 60%; however, ondansetron, a 5-HT3 receptor antagonist, did not alter the combination effect. When the antagonists were intrathecally administered, there was a significant reduction in all tramadol-caffeine combination effects. With respect to tramadol alone, there was significant participation of the opioid system at the supraspinal level, whereas it was the serotonergic system that participated at the spinal level by means of the two receptors studied. In conclusion, the tramadol+caffeine combination synergically activated the opioid and serotonergic systems at the supraspinal level, as well as at the spinal level, to produce the antinociception. PMID:26146627

Cost-effectiveness analysis of hypertension treatment: controlled release nifedipine and candesartan low-dose combination therapy in patients with essential hypertension--the Nifedipine and Candesartan Combination (NICE-Combi) Study.

PubMed

Fujikawa, Keita; Hasebe, Naoyuki; Kikuchi, Kenjiro

2005-07-01

Societal interest in pharmaco-economic analysis is increasing in Japan. In this study, the cost-effectiveness of low-dose combination therapy with controlled release nifedipine plus candesartan and up-titrated monotherapy with candesartan was estimated, based on the results of the NICE-Combi study. The NICE-Combi study was a double-blind, parallel arm, randomized clinical trial to compare the efficacy of low-dose combination therapy of controlled release nifedipine (20 mg/day) plus candesartan (8 mg/day) vs. up-titrated monotherapy of candesartan (12 mg/day) on blood pressure control in Japanese patients with mild to severe essential hypertension who were not sufficiently controlled by the conventional dose of candesartan (8 mg/ day). The incremental cost effectiveness of each cohort during the 8-week randomization period was compared, from the perspective of a third-party payer (i.e., insurers). The average total cost per patient was 29,943 Japanese yen for the combination therapy group and 33,182 Japanese yen for the candesartan monotherapy group, while the rate of achievement of the target blood pressure was significantly higher in the combination therapy group than in the up-titrated monotherapy group. In the combination therapy group, higher efficacy and lower incremental treatment cost ("Dominance") were observed when compared to the monotherapy group. The sensitivity analyses also supported the results. In conclusion, these results suggest that combination therapy with controlled release nifedipine and low-dose candesartan (8 mg) is "dominant" to up-titrated candesartan monotherapy for the management of essential hypertension. This conclusion was robust to sensitivity analysis.

In Vitro Synergistic Effects of Double and Triple Combinations of β-Lactams, Vancomycin, and Netilmicin against Methicillin-Resistant Staphylococcus aureus Strains

PubMed Central

Rochon-Edouard, Stéphanie; Pestel-Caron, Martine; Lemeland, Jean-François; Caron, François

2000-01-01

Several studies have previously reported synergistic effects between vancomycin and a given β-lactam or a given aminoglycoside against methicillin-resistant Staphylococcus aureus (MRSA) strains. The aim of our study was to exhaustively compare the effects of different combinations of a β-lactam, vancomycin, and/or an aminoglycoside against 32 clinical MRSA strains with different aminoglycoside susceptibility patterns. The effects of 26 different β-lactam–vancomycin and 8 different aminoglycoside-vancomycin combinations were first studied using a disk diffusion screening method. The best interactions with vancomycin were observed with either imipenem, cefazolin, or netilmicin. By checkerboard studies, imipenem-vancomycin and cefazolin-vancomycin each provided a synergistic bacteriostatic effect against 22 strains; the mean fractional inhibitory concentration (FIC) indexes were 0.35 and 0.46 for imipenem-vancomycin and cefazolin-vancomycin, respectively. The vancomycin-netilmicin combination provided an indifferent effect against all of the 32 strains tested; the mean of FIC index was 1.096. The mean concentrations of imipenem, cefazolin, netilmicin, and vancomycin at which FIC indexes were calculated were clinically achievable. Killing experiments were then performed using imipenem, cefazolin, netilmicin, and vancomycin at one-half of the MIC, alone and in different combinations, against 10 strains. The vancomycin-netilmicin regimen was rarely bactericidal, even against strains susceptible to netilmicin. The imipenem-vancomycin and cefazolin-vancomycin combinations were strongly bactericidal against six and five strains, respectively. The addition of netilmicin markedly enhanced the killing activity of the combination of cefazolin or imipenem plus vancomycin, but only for the MRSA strains against which the β-lactam–vancomycin combinations had no bactericidal effect. It is noteworthy that the latter strains were both susceptible to netilmicin and heterogeneously resistant to methicillin. PMID:11036022

Application of Feedback System Control Optimization Technique in Combined Use of Dual Antiplatelet Therapy and Herbal Medicines

PubMed Central

Liu, Wang; Li, Yu-Long; Feng, Mu-Ting; Zhao, Yu-Wei; Ding, Xianting; He, Ben; Liu, Xuan

2018-01-01

Aim: Combined use of herbal medicines in patients underwent dual antiplatelet therapy (DAPT) might cause bleeding or thrombosis because herbal medicines with anti-platelet activities may exhibit interactions with DAPT. In this study, we tried to use a feedback system control (FSC) optimization technique to optimize dose strategy and clarify possible interactions in combined use of DAPT and herbal medicines. Methods: Herbal medicines with reported anti-platelet activities were selected by searching related references in Pubmed. Experimental anti-platelet activities of representative compounds originated from these herbal medicines were investigated using in vitro assay, namely ADP-induced aggregation of rat platelet-rich-plasma. FSC scheme hybridized artificial intelligence calculation and bench experiments to iteratively optimize 4-drug combination and 2-drug combination from these drug candidates. Results: Totally 68 herbal medicines were reported to have anti-platelet activities. In the present study, 7 representative compounds from these herbal medicines were selected to study combinatorial drug optimization together with DAPT, i.e., aspirin and ticagrelor. FSC technique first down-selected 9 drug candidates to the most significant 5 drugs. Then, FSC further secured 4 drugs in the optimal combination, including aspirin, ticagrelor, ferulic acid from DangGui, and forskolin from MaoHouQiaoRuiHua. Finally, FSC quantitatively estimated the possible interactions between aspirin:ticagrelor, aspirin:ferulic acid, ticagrelor:forskolin, and ferulic acid:forskolin. The estimation was further verified by experimentally determined Combination Index (CI) values. Conclusion: Results of the present study suggested that FSC optimization technique could be used in optimization of anti-platelet drug combinations and might be helpful in designing personal anti-platelet therapy strategy. Furthermore, FSC analysis could also identify interactions between different drugs which might provide useful information for research of signal cascades in platelet. PMID:29780330

Combination chemotherapy with Regorafenib in metastatic colorectal cancer treatment: A single center, retrospective study

PubMed Central

Lin, Chun-Yu; Lin, Tseng-Hsi; Chen, Chou-Chen; Chen, Ming-Cheng

2018-01-01

Background Regorafenib has been demonstrated as effective in refractory metastatic colorectal cancer. Combination use with chemotherapy has not been reported. We examined the efficacy and safety of adding chemotherapy to Regorafenib for the treatment of metastatic colorectal cancer(mCRC) patients. Methods We recruited mCRC patients at our institute who received either regorafenib monotherapy or regorafenib in combination with other chemotherapies. All patients had received chemo and target therapies and presented with disease progression before regorafenib treatment. The primary end point was overall survival. Findings Between September1, 2015 and May 31, 2017, 100 mCRC patients at our institute received regorafenib treatment. 39 patients were excluded due to poor performance, lack of timely treatment, or inadequate clinical data. A total of 34 patients received regorafenib combined with other chemotherapies, and 27 patients received regorafenib alone. Median follow up time was 10.4 and 6.1 months, respectively. The primary end point of median OS was higher in the combination group than in the single use group (20.9m vs 10.3m, p = 0.015). The most frequent adverse events were hand-foot skin reactions(16[47.1%]vs 12[44.4%]), fatigue(6[17.6%] vs 7[25.9%]), gastrointestinal discomfort (7[20.6%] vs 6[22.2%]), neutropenia (4[11.8%] vs 1[3.7%]), diarrhea(4[11.8%] vs 1[3.7%]), and mucositis(5[14.7%] vs 1[3.7%]). Conclusion The present study showed the efficacy and side effects of regorafenib combination treatment. Superiority in median OS and median PFS was noted in the combination group. The sampling difference between the study and observation groups effects justifies the comparison. Further clinical evidence of combination therapy efficacy is pending future studies. PMID:29304109

A combination of physical activity and computerized brain training improves verbal memory and increases cerebral glucose metabolism in the elderly.

PubMed

Shah, T; Verdile, G; Sohrabi, H; Campbell, A; Putland, E; Cheetham, C; Dhaliwal, S; Weinborn, M; Maruff, P; Darby, D; Martins, R N

2014-12-02

Physical exercise interventions and cognitive training programs have individually been reported to improve cognition in the healthy elderly population; however, the clinical significance of using a combined approach is currently lacking. This study evaluated whether physical activity (PA), computerized cognitive training and/or a combination of both could improve cognition. In this nonrandomized study, 224 healthy community-dwelling older adults (60-85 years) were assigned to 16 weeks home-based PA (n=64), computerized cognitive stimulation (n=62), a combination of both (combined, n=51) or a control group (n=47). Cognition was assessed using the Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test and the CogState computerized battery at baseline, 8 and 16 weeks post intervention. Physical fitness assessments were performed at all time points. A subset (total n=45) of participants underwent [(18)F] fluorodeoxyglucose positron emission tomography scans at 16 weeks (post-intervention). One hundred and ninety-one participants completed the study and the data of 172 participants were included in the final analysis. Compared with the control group, the combined group showed improved verbal episodic memory and significantly higher brain glucose metabolism in the left sensorimotor cortex after controlling for age, sex, premorbid IQ, apolipoprotein E (APOE) status and history of head injury. The higher cerebral glucose metabolism in this brain region was positively associated with improved verbal memory seen in the combined group only. Our study provides evidence that a specific combination of physical and mental exercises for 16 weeks can improve cognition and increase cerebral glucose metabolism in cognitively intact healthy older adults.

A combination of physical activity and computerized brain training improves verbal memory and increases cerebral glucose metabolism in the elderly

PubMed Central

Shah, T; Verdile, G; Sohrabi, H; Campbell, A; Putland, E; Cheetham, C; Dhaliwal, S; Weinborn, M; Maruff, P; Darby, D; Martins, R N

2014-01-01

Physical exercise interventions and cognitive training programs have individually been reported to improve cognition in the healthy elderly population; however, the clinical significance of using a combined approach is currently lacking. This study evaluated whether physical activity (PA), computerized cognitive training and/or a combination of both could improve cognition. In this nonrandomized study, 224 healthy community-dwelling older adults (60–85 years) were assigned to 16 weeks home-based PA (n=64), computerized cognitive stimulation (n=62), a combination of both (combined, n=51) or a control group (n=47). Cognition was assessed using the Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test and the CogState computerized battery at baseline, 8 and 16 weeks post intervention. Physical fitness assessments were performed at all time points. A subset (total n=45) of participants underwent [18F] fluorodeoxyglucose positron emission tomography scans at 16 weeks (post-intervention). One hundred and ninety-one participants completed the study and the data of 172 participants were included in the final analysis. Compared with the control group, the combined group showed improved verbal episodic memory and significantly higher brain glucose metabolism in the left sensorimotor cortex after controlling for age, sex, premorbid IQ, apolipoprotein E (APOE) status and history of head injury. The higher cerebral glucose metabolism in this brain region was positively associated with improved verbal memory seen in the combined group only. Our study provides evidence that a specific combination of physical and mental exercises for 16 weeks can improve cognition and increase cerebral glucose metabolism in cognitively intact healthy older adults. PMID:25463973

Polymyxin B in Combination with Enrofloxacin Exerts Synergistic Killing against Extensively Drug-Resistant Pseudomonas aeruginosa.

PubMed

Lin, Yu-Wei; Yu, Heidi H; Zhao, Jinxin; Han, Mei-Ling; Zhu, Yan; Akter, Jesmin; Wickremasinghe, Hasini; Walpola, Hasini; Wirth, Veronika; Rao, Gauri G; Forrest, Alan; Velkov, Tony; Li, Jian

2018-06-01

Polymyxins are increasingly used as a last-resort class of antibiotics against extensively drug-resistant (XDR) Gram-negative bacteria. However, resistance to polymyxins can emerge with monotherapy. As nephrotoxicity is the major dose-limiting factor for polymyxin monotherapy, dose escalation to suppress the emergence of polymyxin resistance is not a viable option. Therefore, novel approaches are needed to preserve this last-line class of antibiotics. This study aimed to investigate the antimicrobial synergy of polymyxin B combined with enrofloxacin against Pseudomonas aeruginosa Static time-kill studies were conducted over 24 h with polymyxin B (1 to 4 mg/liter) and enrofloxacin (1 to 4 mg/liter) alone or in combination. Additionally, in vitro one-compartment model (IVM) and hollow-fiber infection model (HFIM) experiments were performed against P. aeruginosa 12196. Polymyxin B and enrofloxacin in monotherapy were ineffective against all of the P. aeruginosa isolates examined, whereas polymyxin B-enrofloxacin in combination was synergistic against P. aeruginosa , with ≥2 to 4 log 10 kill at 24 h in the static time-kill studies. In both IVM and HFIM, the combination was synergistic, and the bacterial counting values were below the limit of quantification on day 5 in the HFIM. A population analysis profile indicated that the combination inhibited the emergence of polymyxin resistance in P. aeruginosa 12196. The mechanism-based modeling suggests that the synergistic killing is a result of the combination of mechanistic and subpopulation synergy. Overall, this is the first preclinical study to demonstrate that the polymyxin-enrofloxacin combination is of considerable utility for the treatment of XDR P. aeruginosa infections and warrants future clinical evaluations. Copyright © 2018 American Society for Microbiology.

Combined hormonal contraceptive (CHC) use among obese women and contraceptive effectiveness: a systematic review.

PubMed

Dragoman, Monica V; Simmons, Katharine B; Paulen, Melissa E; Curtis, Kathryn M

2017-02-01

To evaluate from the literature whether combined hormonal contraception (CHC), including combined oral contraception pills (COCs), transdermal patch, vaginal ring or combined injectables, have different effectiveness or failure rates by body weight or body mass index (BMI). We searched PubMed and the Cochrane Library databases for all articles in all languages published between inception and February 2016, for evidence relevant to body weight or BMI, CHC use and contraceptive effectiveness. The quality of each individual study was assessed using the system for evaluating evidence developed by the United States Preventive Services Task Force. From 2874 articles, we identified 15 reports for inclusion, all of fair to poor quality. Fourteen studies measured the association of obesity status and contraceptive failure among COC users. Three fair quality and one poor quality study reported increased COC failure among a heterogeneous population of overweight and obese women compared with normal weight women, while eight fair quality and two poor quality studies did not find an association. Two fair quality studies reported on contraceptive transdermal patches. One pooled analysis described a higher proportion of pregnancies among women using the patch who weighed ≥90 kg; another secondary analysis suggested BMI>30 was associated with increased failure. No studies directly compared contraceptive effectiveness using the combined vaginal ring or combined injectable. Current available evidence addressing the risk of CHC failure in obese compared to normal weight women is limited to fair and poor quality studies. Studies of COCs show mixed results, though absolute differences in COC failure by body weight and BMI are small. Based on limited evidence, it appears that increasing body weight and BMI may contribute to decreasing contraceptive patch effectiveness. Copyright © 2017. Published by Elsevier Inc.

A double-blind, randomized, comparative study of the use of a combination of uridine triphosphate trisodium, cytidine monophosphate disodium, and hydroxocobalamin, versus isolated treatment with hydroxocobalamin, in patients presenting with compressive neuralgias.

PubMed

Goldberg, Henrique; Mibielli, Marco Antonio; Nunes, Carlos Pereira; Goldberg, Stephanie Wrobel; Buchman, Luiz; Mezitis, Spyros Ge; Rzetelna, Helio; Oliveira, Lisa; Geller, Mauro; Wajnsztajn, Fernanda

2017-01-01

This paper reports on the results of treatment of compressive neuralgia using a combination of nucleotides (uridine triphosphate trisodium [UTP] and cytidine monophosphate disodium [CMP]) and vitamin B 12 . To assess the safety and efficacy of the combination of nucleotides (UTP and CMP) and vitamin B 12 in patients presenting with neuralgia arising from neural compression associated with degenerative orthopedic alterations and trauma, and to compare these effects with isolated administration of vitamin B 12 . A randomized, double-blind, controlled trial, consisting of a 30-day oral treatment period: Group A (n=200) receiving nucleotides + vitamin B 12, and Group B (n=200) receiving vitamin B 12 alone. The primary study endpoint was the percentage of subjects presenting pain visual analog scale (VAS) scores ≤20 at end of study treatment period. Secondary study endpoints included the percentage of subjects presenting improvement ≥5 points on the patient functionality questionnaire (PFQ); percentage of subjects presenting pain reduction (reduction in VAS scores at study end in relation to pretreatment); and number of subjects presenting adverse events. The results of this study showed a more expressive improvement in efficacy evaluations among subjects treated with the combination of nucleotides + vitamin B 12 , with a statistically significant superiority of the combination in pain reduction (evidenced by VAS scores). There were adverse events in both treatment groups, but these were transitory and no severe adverse event was recorded during the study period. Safety parameters were maintained throughout the study in both treatment groups. The combination of uridine, cytidine, and vitamin B 12 was safe and effective in the treatment of neuralgias arising from neural compression associated with degenerative orthopedic alterations and trauma.

Anesthetic efficacy of ketamine–diazepam, ketamine–xylazine, and ketamine–acepromazine in Caspian Pond turtles (Mauremys caspica)

PubMed Central

Adel, Milad; Sadegh, Amin Bigham; Arizza, Vincenzo; Abbasi, Hossein; Inguglia, Luigi; Saravi, Hasan Nasrollahzadeh

2017-01-01

Objectives: The objective of this study was to assess the efficacy of different anesthetic drug combinations on the Caspian Pond turtles (Mauremys caspica). Subjects and Methods: Three groups of the Caspian Pond turtles (n = 6) were anesthetized with three different drug combinations. Initially, a pilot study was conducted to determine the best drug doses for the anesthetization of the turtles, and according to these results, ketamine–diazepam (120 mg/kg ketamine hydrochloride [5%] and 2 mg/kg diazepam [5%]), ketamine–acepromazine (120 mg/kg ketamine hydrochloride [5%] and 1 mg/kg acepromazine [1%]), and ketamine–xylazine (120 mg/kg ketamine hydrochloride [5%] and 1 mg/kg xylazine [2%]) were injected intramuscularly. The onset times of anesthetization and the recovery time were measured. Statistical analysis of the data was performed using one-way analysis of variance followed by t-tests, and P < 0.05 was considered statistically significant. Results: There were statistically significant differences in the mean of the onset times of anesthesia and recovery time among the three drug combinations depending on the treatment used. The onset of anesthesia of the animals treated with the ketamine–diazepam combination was 60% and 42% shorter, for male and female turtles, respectively, compared to that obtained with the ketamine–acepromazine combination and 64% (male turtles) and 50% (female turtles) shorter than that obtained with the ketamine–xylazine combination. Further, the recovery time, in male turtles, was 17% shorter in animals treated with the first drug combination than those treated with the ketamine–acepromazine combination and 37% shorter than those treated with the ketamine–xylazine combination. The recovery time, in female turtles, did not seem to be significantly different among treatments. Conclusions: The study showed that the ketamine–diazepam drug combination is the anesthetic combination with the fastest onset time and shortest recovery time. PMID:28458430

The use of combination therapies in the acute management of migraine.

PubMed

Krymchantowski, Abouch Valenty

2006-09-01

Migraine is a highly prevalent neurological disorder with multiple peripheral and central mechanisms. Targeting a single mechanism for treating individual attacks as well as for performing the prophylaxis has been shown to be only partially effective. Recently, the role of combining agents for acute migraine treatment has gained attention and the combination of a triptan plus a non-steroidal anti-inflammatory drug (NSAID) has demonstrated better efficacy. This review focuses on the fundamentals of treating migraine attacks with two or more agents, and emphasizes the characteristics of the recently approved fixed combination sumatriptan-naproxen. A PubMed search using the terms "migraine", "treatment", "acute", "triptans", "non-steroidal anti-inflammatory drugs", "sumatriptan", "naproxen", and "combination" was used. In addition, abstracts presented in the major meetings of the American Headache and the International Headache Societies along with the American Academy of Neurology were also evaluated. Although most of the few studies encountered were not controlled, there is a clear trend for better efficacy in combining triptans with NSAID. Additionally, the results of two recent large and controlled studies using fixed combinations of sumatriptan (50 mg and 85 mg) with 500 mg naproxen sodium confirm the initial observations of the clear superiority of this combination over the use of each agent alone. The differences in the endpoints 24-hour pain-relief response as well as pain-free and pain-relief parameters at 2-hour time-point are the most noticeable efficacy measures. Tolerability was not different between studied drugs. Combining triptans with NSAID and other agents for the acute treatment of migraine suggests better outcome efficacy measures than the use of single agents. The fixed combination of sumatriptan and naproxen sodium offers improved 2-hour and 24-hour benefits over monotherapy with each one these options. Recently issued FDA approval for marketing the combination (sumatriptan 50 mg-naproxen 500 mg) emphasizes the usefulness and safety of this new treatment for migraine attacks.

Use and Characteristics of Antipsychotic/Methylphenidate Combination Therapy in Children and Adolescents with a Diagnosis of Attention-Deficit/Hyperactivity Disorder.

PubMed

Scholle, Oliver; Banaschewski, Tobias; Enders, Dirk; Garbe, Edeltraut; Riedel, Oliver

2018-05-16

Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) frequently have comorbidities that are potential indications for antipsychotics (APs). Some studies have suggested that the combined use of methylphenidate (MPH) and APs is increasing in this population group. Longitudinal analyses and in-depth investigations on the substance level are lacking. This study aimed to estimate the cumulative proportion of concomitant AP/MPH use in children and adolescents with ADHD over a follow-up of up to 9 years and to describe patient characteristics stratified by specific AP drug. Based on claims data, concomitant AP/MPH use was identified among 67,595 children and adolescents with ADHD starting MPH treatment between 2005 and 2013. Characteristics and diagnoses-including those indicating appropriateness of AP use according to approved indications and/or guidelines-were examined at the time of first AP/MPH combination therapy. In addition, subsequent use of AP/MPH combination therapy was evaluated. The cumulative proportion of individuals with any AP/MPH combination therapy rose to over 6% within 9 years after initiating MPH. The most frequent APs first used in combination with MPH were risperidone (72%), pipamperone (15%), and tiapride (8%). Percentages of psychiatric hospitalization in the year preceding the first combination therapy with MPH were 33%, 43%, and 19%, respectively. The proportion of individuals with potentially appropriate use was high (>72%) in risperidone/MPH and tiapride/MPH and low (15%) in pipamperone/MPH combination users. Conduct disorders and tic disorders were frequent in users who were prescribed MPH with risperidone and tiapride, respectively. One-quarter of patients with AP/MPH combination therapy were one-time-only combination users. Our study suggests that a considerable proportion of children and adolescents with ADHD receive MPH in combination with APs and that this is a factor not only during the first years of MPH treatment. ADHD guidelines should specify algorithms concerning the use of AP medication.

Quantitative Assessment of Combination Antimicrobial Therapy against Multidrug-Resistant Acinetobacter baumannii▿

PubMed Central

Lim, Tze-Peng; Ledesma, Kimberly R.; Chang, Kai-Tai; Hou, Jing-Guo; Kwa, Andrea L.; Nikolaou, Michael; Quinn, John P.; Prince, Randall A.; Tam, Vincent H.

2008-01-01

Treatment of multidrug-resistant bacterial infections poses a therapeutic challenge to clinicians; combination therapy is often the only viable option for multidrug-resistant infections. A quantitative method was developed to assess the combined killing abilities of antimicrobial agents. Time-kill studies (TKS) were performed using a multidrug-resistant clinical isolate of Acinetobacter baumannii with escalating concentrations of cefepime (0 to 512 mg/liter), amikacin (0 to 256 mg/liter), and levofloxacin (0 to 64 mg/liter). The bacterial burden data in single and combined (two of the three agents with clinically achievable concentrations in serum) TKS at 24 h were mathematically modeled to provide an objective basis for comparing various antimicrobial agent combinations. Synergy and antagonism were defined as interaction indices of <1 and >1, respectively. A hollow-fiber infection model (HFIM) simulating various clinical (fluctuating concentrations over time) dosing exposures was used to selectively validate our quantitative assessment of the combined killing effect. Model fits in all single-agent TKS were satisfactory (r2 > 0.97). An enhanced combined overall killing effect was seen in the cefepime-amikacin combination (interactive index, 0.698; 95% confidence interval [CI], 0.675 to 0.722) and the cefepime-levofloxacin combination (interactive index, 0.929; 95% CI, 0.903 to 0.956), but no significant difference in the combined overall killing effect for the levofloxacin-amikacin combination was observed (interactive index, 0.994; 95% CI, 0.982 to 1.005). These assessments were consistent with observations in HFIM validation studies. Our method could be used to objectively rank the combined killing activities of two antimicrobial agents when used together against a multidrug-resistant A. baumannii isolate. It may offer better insights into the effectiveness of various antimicrobial combinations and warrants further investigations. PMID:18505848

An open, comparative study of 10% potassium hydroxide solution versus salicylic and lactic acid combination in the treatment of molluscum contagiosum in children.

PubMed

Köse, Osman; Özmen, İbrahim; Arca, Ercan

2013-08-01

To evaluate and compare the safety and efficacy of 10% potassium hydroxide (KOH) solution and salicylic and lactic acid (SAL + LAC) combination in the treatment of molluscum contagiosum (MC). 26 patients with MC randomized into two treatment groups. 12 patients treated with 10% KOH solution and 14 patients treated with SAL + LAC combination for 6 weeks. Parents of patients were instructed to apply medication once daily only to lesions at study onset. Assessment of response of the treated lesions and side effects was performed at 2, 4 and 6 weeks of the treatment. Newly acquired lesions were not included in the study. At the end of therapy, 83.3% (n = 10) of KOH group demonstrated complete remission and 16.7% (n = 2) of them showed partial remission; four patients (33%) developed new lesions during the study. All the patients in the SAL + LAC combination group (100%) demonstrated complete remission of study entry lesions at the end of 6 weeks with five patients (35%) acquiring new lesions during the study. Minor side effects were observed in two groups. 10% KOH solution and SAL + LAC combination were found to be equally effective in the treatment of MC in children.

Single vs. combination immunotherapeutic strategies for glioma

PubMed Central

Chandran, Mayuri; Candolfi, Marianela; Shah, Diana; Mineharu, Yohei; Yadav, Vivek; Koschmann, Carl; Asad, Antonela S.; Lowenstein, Pedro R.; Castro, Maria G.

2017-01-01

Introduction Malignant gliomas are highly invasive tumors, associated with a dismal survival rate despite standard of care, which includes surgical resection, radiotherapy and chemotherapy with temozolomide (TMZ). Precision immunotherapies or combinations of immunotherapies that target unique tumor-specific featuresmay substantially improve upon existing treatments. Areas covered Clinical trials of single immunotherapies have shown therapeutic potential in high-grade glioma patients, and emerging preclinical studies indicate that combinations of immunotherapies may be more effective than monotherapies. In this review we discuss emerging combinations of immunotherapies and compare efficacy of single vs. combined therapies tested in preclinical brain tumor models. Expert opinion Malignant gliomas are characterized by a number of factors which may limit the success of single immunotherapies including inter-tumor and intra-tumor heterogeneity, intrinsic resistance to traditional therapies, immunosuppression, and immune selection for tumor cells with low antigenicity. Combination of therapies which target multiple aspects of tumor physiology are likely to be more effective than single therapies. While we describe a limited number of combination immunotherapies which are currently being tested in preclinical and clinical studies, the field is expanding at an astounding rate, and endless combinations remain open for exploration. PMID:28286975

The Antioxidative Effect of Chamomile, Anthocyanoside and their Combination on Bleomycin-induced Pulmonary Fibrosis in Rat.

PubMed

Javadi, Iraj; Emami, SeyedAlireza

2015-08-01

Bleomycin is a small peptide with 1500Daltun of molecular weight which has two junction areas in two molecule's opposite sides, one of them to relate to the DNA and the other to relate to the iron. Iron is a crucially important factor in free radical production and cytotoxic activity of bleomycin. The study attempts to study, and compare, the effect of using Chamomile, Anthocyanoside and their combination, as anti-inflammatory agent to ameliorates, to prevent or control the development of fibrosis due to Bleomycin (BLM). to prepare pulmonary fibrosis model, male Wistar rats weighting 180-220g were assigned to specific groups Rats of each group received intratracheally 1U/100 g of BLM. 20 rats were divided to five comparable groups, as(1) BLM group, (2) saline group, (3) Chamomile group, (4) Anthocyanoside group, (5) combination of Anthocyanoside and Chamomile group. Antioxidative combinations were given as pretreatment and treatment after the rats received Bleomycine. After 3 week, Malondialdehyde (MDA)was measured for each rat's lung. After three weeks, MDA was reduced, compared to BLM group, to 44.27%, 37.80% and 46.07% in Anthocyanoside, Chamomiland combination group, respectively. It was concluded from the present study that administration of combination of Chamomile and Anthocyanoside lead to a significant reduction in Bleomycin-induced MDA. The mechanism of the effect of these combinations is possibly the result of phenolic combinations as antioxidant and oxy free radical scavenger and inhibitor of lipid peroxidation.

Inhibitory effects of Silibinin combined with doxorubicin in hepatocellular carcinoma; an in vivo study.

PubMed

Li, Wei-Guo; Wang, He-Qun

2016-01-01

Hepatocellular carcinoma (HCC) is the one of the most common cancers and the third leading cause of cancer related mortality in the world. Unacceptable side effect and development of treatment resistance are the major concerns with the conventional chemotherapeutic agents. Combination therapy using phytotherapeutic agents is attracting the attention of investigators in view of the current needs. In the present study we have evaluated the synergistic effect of silibinin, a nontoxic phytotherapeutic agent in combination with doxorubicin, in advanced HCC using HEPG2 cells and an orthotopic rat model of HCC. The results showed that silibinin strongly synergized with doxorubicin-induced growth inhibition, G2-M arrest, and apoptosis of HEPG2 cells. Silibinin-doxorubicin combination also inhibited cdc2/p34 kinase activity when histone H1 was used as substrate. The combination regimen also moderately increased the expression of cdc25C-cyclin B1-cdc2/p34 associated upstream kinases (Chk1). Simultaneous treatment with silibinin-doxorubicin combination showed a 41% increase in the apoptotic cell death (p=0.01), which was 3-fold higher than what was observed with silibinin or doxorubicin individually. In the orthotopic rat model treatment with silibinin-doxorubicin reduced tumor growth by close to 30% at nearly twice lower dose of individual drugs in the combination group. Our study suggests that combination therapy using silibinin-doxorubicin may show a better therapeutic efficacy in patients with HCC. These findings need to be further validated in human clinical trials.

Contribution of a combined TDEM (Time-Domain electromagnetism) and geoelectrical survey to the investigation of the coastal aquifer of Puerto Morelos, Quintana Roo, Mexico

NASA Astrophysics Data System (ADS)

Rebolledo-Vieyra, M.; Ravelo-Cervantes, J. I.; Lecossec, A.

2007-12-01

This study reports initial results of combined Time Domain Electromagnetic (TDEM) and vertical electrical sounding (VES), geophysical characterization of the Quintana Roo coastal aquifer, with the aim of establishing effective protocols for subsequent surveys in the area, through the association of TDEM and VES. The high resistivity of the carbonate terrain, combined with the very low resistivity range of fresh-water and sea-water, are ideal to use both tools in combination. The results show that both methods used in a combination may provide a useful tool for hydrogeologial studies. In this survey we were able to identifiy a fracture 100 m x 40 m, that was correlated to fresh-water discharges in to the Puerto Morelos Reef lagoon.

Combining Pharmacological Countermeasures to Attenuate the Acute Radiation Syndrome-A Concise Review.

PubMed

Hofer, Michal; Hoferová, Zuzana; Depeš, Daniel; Falk, Martin

2017-05-19

The goal of combined pharmacological approaches in the treatment of the acute radiation syndrome (ARS) is to obtain an effective therapy producing a minimum of undesirable side effects. This review summarizes important data from studies evaluating the efficacy of combining radioprotective agents developed for administration prior to irradiation and therapeutic agents administered in a post-irradiation treatment regimen. Many of the evaluated results show additivity, or even synergism, of the combined treatments in comparison with the effects of the individual component administrations. It can be deduced from these findings that the research in which combined treatments with radioprotectors/radiomitigators are explored, tested, and evaluated is well-founded. The requirement for studies highly emphasizing the need to minimize undesirable side effects of the radioprotective/radiomitigating therapies is stressed.

Biomechanical evaluation of the natural abutment teeth in combined tooth-implant-supported telescopic prostheses: a three-dimensional finite element analysis.

PubMed

Chen, Yu; Wang, Chao; Huang, Yuanding; Feng, Tianming; Zou, Huawei; Fan, Yubo

2017-07-01

Telescopic overdentures supported by the combination of natural teeth and implants have been thought a valuable treatment for the severely compromised partially edentulous patients. But the combination of teeth and implants involves highly complex biomechanical problems. This study is to evaluate biomechanical behaviors of the natural abutment teeth with the treatment of combined tooth-implant supported telescopic crown prostheses in mandible through 3D FEA. According to this study, the prosthetic option supported by a combination of teeth and implants and retained by double crowns could protect teeth and their periodontal support tissues acting as a rigid splint, and may be a valuable treatment option for partially edentulous patients with severely reduced remaining teeth in mandible.

[Study on characteristics of pharmacological effects of traditional Chinese medicines distributing along stomach meridian based on medicinal property combination].

PubMed

Zhang, Bai-Xia; Gu, Hao; Guo, Hong-Ling; Ma, Li; Wang, Yun; Qiao, Yan-Jiang

2014-07-01

At present, studies on traditional Chinese medicine (TCM) properties are mostly restricted to a single or two kinds of medicinal properties, but deviated from the holism of the theoretical system of TCMs. In this paper, the characteristics of pharmacological effects of different property combinations of TCMs distributing in the stomach meridian were take as the study objective. The data of properties of TCMs distributing in the stomach meridian was collected from the Pharmacopoeia of the People's Republic of China (2005). The data of pharmacological effects of TCMs distributing in the stomach meridian was collected from all of literatures recorded in Chinese Journal Full-text Database (CNKI) since 1980, Science of Chinese Materia Medica (Yan Zhenghua, People's Medical Publishing House, 2006) and Clinical Science of Chinese Materia Medica (Gao Xuemin, Zhong Gansheng, Hebei Science and Technology Publishing House, 2005). The corresponding pharmacological effects of property combinations of TCMs distributing in the stomach meridian was mined by the method of association rules. The results of the association rules were consistent with the empirical knowledge, and showed that different medicinal property combinations had respective pharmacological characteristics, including differences and similarities in pharmacological effects of different medicinal property combinations. Medicinal property combinations with identical four properties or five tastes showed similar pharmacological effects; whereas medicinal property combinations with different four properties or five tastes showed differentiated pharmacological effects. However, medicinal property combinations with different four properties or five tastes could also show similar pharmacological effects. In this study, the medicinal property theory and the pharmacological effects of TCMs were combined to reveal the main characteristics and regularity of pharmacological effects of TCMs distributing in the stomach meridian and provide a new way of thinking and method for revealing the mechanism action of TCMs distributing in the stomach meridian and discovering the pharmacological effects of TCMs distributing in the stomach meridian.

Marijuana, alcohol and actual driving performance

DOT National Transportation Integrated Search

1999-07-01

The purpose of this study was to empirically determine the separate and combined effects of Delta-9-tetrahydrocannabinol (THC) and alcohol on actual driving performance. This was the first study ever in which the drugs' combined effects were measured...

[Combined effect of benzylpenicillin, furagin and bile acids on staphylococci].

PubMed

Sytnik, I A; Tkachuk, N I

1982-11-01

The results of the study of the effect of benzylpenicillin or furagin in combination with bile acids, such as cholic, glycocholic and desoxycholic on the collection cultures of staphylococci are presented. The study showed that the subbacteriostatic doses of the bile acids increased the bacteriostatic and bactericidal effects of benzylpenicillin and furagin by tens and hundreds times. The highest potentiation effect was attained with the use of the furagin combination and desoxycholic acid.

Study on the Application Mode and Legal Protection of Green Materials in Medical-Nursing Combined Building

NASA Astrophysics Data System (ADS)

Zhiyong, Xian

2017-09-01

In the context of green development, green materials are the future trend of Medical-Nursing Combined building. This paper summarizes the concept and types of green building materials. Then, on the basis of existing research, it constructs the green material system framework of Medical-Nursing Combined building, puts forward the application mode of green building materials, and studies the policy and legal protection of green material application.

Systematic Review and Meta-Analysis of Randomized Clinical Trials in the Treatment of Human Brucellosis

PubMed Central

Solís García del Pozo, Julián; Solera, Javier

2012-01-01

Background Brucellosis is a persistent health problem in many developing countries throughout the world, and the search for simple and effective treatment continues to be of great importance. Methods and Findings A search was conducted in MEDLINE and in the Cochrane Central Register of Controlled Trials (CENTRAL). Clinical trials published from 1985 to present that assess different antimicrobial regimens in cases of documented acute uncomplicated human brucellosis were included. The primary outcomes were relapse, therapeutic failure, combined variable of relapse and therapeutic failure, and adverse effect rates. A meta-analysis with a fixed effect model was performed and odds ratio with 95% confidence intervals were calculated. A random effect model was used when significant heterogeneity between studies was verified. Comparison of combined doxycycline and rifampicin with a combination of doxycycline and streptomycin favors the latter regimen (OR = 3.17; CI95% = 2.05–4.91). There were no significant differences between combined doxycycline-streptomycin and combined doxycycline-gentamicin (OR = 1.89; CI95% = 0.81–4.39). Treatment with rifampicin and quinolones was similar to combined doxycycline-rifampicin (OR = 1.23; CI95% = 0.63–2.40). Only one study assessed triple therapy with aminoglycoside-doxycycline-rifampicin and only included patients with uncomplicated brucellosis. Thus this approach cannot be considered the therapy of choice until further studies have been performed. Combined doxycycline/co-trimoxazole or doxycycline monotherapy could represent a cost-effective alternative in certain patient groups, and further studies are needed in the future. Conclusions Although the preferred treatment in uncomplicated human brucellosis is doxycycline-aminoglycoside combination, other treatments based on oral regimens or monotherapy should not be rejected until they are better studied. Triple therapy should not be considered the current treatment of choice. PMID:22393379

5-fluorouracil enhances the antitumor effect of sorafenib and sunitinib in a xenograft model of human renal cell carcinoma.

PubMed

Miyake, Makito; Anai, Satoshi; Fujimoto, Kiyohide; Ohnishi, Sayuri; Kuwada, Masaomi; Nakai, Yasushi; Inoue, Takeshi; Tomioka, Atsushi; Tanaka, Nobumichi; Hirao, Yoshihiko

2012-06-01

Sorafenib and sunitinib are multi-kinase inhibitors with antitumor activity in patients with advanced renal cell carcinoma (RCC). Several studies have evaluated the effect of sorafenib/sunitinib in combination with chemotherapeutic agents in different types of tumor. However, few studies have addressed the activity of fluorinated pyrimidine in combination with sorafenib/sunitinib. In this study, we examined the potential of combination therapy with 5FU and sorafenib/sunitinib in human RCC cell lines. Three human RCC cell lines, ACHN, Caki-1 and Caki-2, were used to assess sensitivity to 5-fluorouracil (5FU), sorafenib and sunitinib alone or in combination using an in vitro cell survival assay. Caki-2 cells demonstrated significantly higher resistance to 5FU and sorafenib as compared to ACHN and Caki-1. Additive antitumor effects of the combination therapy were observed in the in vitro study. There was a tendency for a positive correlation between the sensitivity to sunitinib and platelet-derived growth factor β (PDGFR-β) expression levels, which were examined by reverse transcription polymerase chain reaction. Caki-1 xenograft models were prepared by inoculating cells subcutaneously into nude mice, which were divided randomly into six groups: control, 5FU (8 mg/kg/day, intraperitoneally), sorafenib (15 mg/kg/day, orally), sunitinib (20 mg/kg/day, orally), and 5FU with sorafenib or sunitinib. The treatments were administered on 5 days each week, and tumor growth was monitored for 42 days following inoculation of cells. Synergistic antitumor effects of the combination therapy were observed in an in vivo study. The resected tumors were evaluated using the Ki-67 labeling index and microvessel density. Both the Ki-67 labeling index and microvessel density were decreased in tumors treated with the combination therapy compared to those treated with sorafenib/sunitinib alone. These findings suggest that the combination therapy of 5FU with sorafenib/sunitinib may be an effective therapeutic modality for advanced RCC patients.

Calcitriol in Combination Therapy for Prostate Cancer: Pharmacokinetic and Pharmacodynamic Interactions

PubMed Central

Ben-Eltriki, Mohamed; Deb, Subrata; Guns, Emma S. Tomlinson

2016-01-01

Epidemiological studies indicate that vitamin D insufficiency could have an etiological role in prostate cancer. In addition, calcitriol, used in combination with currently available drugs, has the potential to potentiate their anticancer effects or act synergistically by inhibiting distinct mechanisms involved in prostate cancer growth. Clinical data have not yet provided sufficient evidence to demonstrate benefit of vitamin D due to the limited and underpowered studies that have been published to date. Here, we review the preclinical and clinical studies that describe the activity of calcitriol, applied either alone or in combination and assessed the mechanistic basis of pharmacodynamic and pharmacokinetic interactions with calcitriol. Important considerations for calcitriol use in combination therapy with respect to safety and clinical outcomes have been discussed. Many of these combinations have therapeutic potential for the treatment of several cancer types and it is anticipated that future clinical research will put emphasis on well‑designed clinical trials to establish efficacy. PMID:26918053

Antiosteoporotic Effect of Combined Extract of Morus alba and Polygonum odoratum

PubMed Central

Sungkamanee, Sudarat; Thukham-mee, Wipawee

2014-01-01

Due to the limitation of osteoporosis therapy, the alternative therapies from natural sources have been considered. In this study, we aimed to determine the antiosteoporotic effect of the combined extract of Morus alba and Polygonum odoratum leaves. Ovariectomized rats, weighing 200–220 g, were orally given the combined extract at doses of 5, 150, and 300 mg·kg−1 BW for 3 months. At the end of study, blood was collected to determine serum osteocalcin, calcium, and alkaline phosphatase level. In addition, tibia bone was isolated to determine bone oxidative stress markers, cortical bone thickness, and density of osteoblast. The combined extract decreased oxidative stress and osteoclast density but increased osteoblast density and cortical thickness. The elevation of serum calcium, alkaline phosphatase, and osteocalcin was also observed. These results suggested the antiosteoporotic effect of the combined extract via the increased growth formation together with the suppression of bone resorption. However, further studies concerning chronic toxicity and the underlying mechanism are required. PMID:25478061

Combined enteral and parenteral nutrition.

PubMed

Wernerman, Jan

2012-03-01

To review and discuss the evidence and arguments to combine enteral nutrition and parenteral nutrition in the ICU, in particular with reference to the Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) study. The EPaNIC study shows an advantage in terms of discharges alive from the ICU when parenteral nutrition is delayed to day 8 as compared with combining enteral nutrition and parenteral nutrition from day 3 of ICU stay. The difference between the guidelines from the European Society of Enteral and Parenteral Nutrition in Europe and American Society for Parenteral and Enteral Nutrition/Society of Critical Care Medicine in North America concerning the combination of enteral nutrition and parenteral nutrition during the initial week of ICU stay was reviewed. The EPaNIC study clearly demonstrates that early parenteral nutrition in the ICU is not in the best interests of most patients. Exactly at what time point the combination of enteral nutrition and parenteral nutrition should be considered is still an open question.

Bioequivalence and food effect assessment for vildagliptin/metformin fixed-dose combination tablets relative to free combination of vildagliptin and metformin in Japanese healthy subjects.

PubMed

Mita, Sachiko; Chitnis, Shripad D; Kulmatycki, Kenneth; Salunke, Atish; He, Yan-Ling; Zhou, Wei; Suzuki, Hikoe

2016-04-01

To assess the bioequivalence of vildagliptin/metformin fixeddose combination (FDC) tablets (50/250 mg and 50/500 mg) to free combinations of vildagliptin and metformin and the effect of food on the pharmacokinetics (PK) of vildagliptin and metformin following administration of 50/500 mg FDC tablets. Two openlabel, randomized, single-center, singledose, 2-period crossover studies were conducted in Japanese healthy male volunteers. Participants were administered vildagliptin/ metformin FDC tablets (study I: 50/250 mg, study II: 50/500 mg) or their free combinations under fasted condition. Food effect (standard Japanese breakfast: fat, 20 - 30% with ~ 600 kcal in total) was assessed during an additional period in study II (50/500 mg). PK parameters (AUC, C(max), t(max), t(1/2)) were calculated for vildagliptin and metformin. In both studies, vildagliptin/metformin FDC tablets were bioequivalent to their respective free combinations. Administration of FDC tablets after meals had no effect on vildagliptin PK parameters. The rate of absorption of metformin decreased when administered under fed condition, as reflected by a prolonged t(max) (3 hours in fasted state vs. 4 hours in fed state) and decrease in C(max) by 26%, however, the extent of absorption (AUC(last)) was similar to that in the fasted state. Vildagliptin/metformin FDC tablets were bioequivalent to their free combinations. Food decreased the C(max) of metformin by 26%, while AUC(last) was unchanged, consistent with previous reports. No food effect was observed on the C(max) or AUC(last) of vildagliptin. Thus, food had no clinically relevant effects on the PK of metformin or vildagliptin.

Effects on agitation with rivastigmine patch monotherapy and combination therapy with memantine in mild to moderate Alzheimer's disease: a multicenter 24-week prospective randomized open-label study (the Korean EXelon Patch and combination with mEmantine Comparative Trial study).

PubMed

Yoon, Soo J; Choi, Seong H; Na, Hae R; Park, Kyung-Won; Kim, Eun-Joo; Han, Hyun J; Lee, Jae-Hong; Shim, Young S; Na, Duk L

2017-03-01

Memantine is known to be effective in the treatment of the behavioral symptoms of dementia, especially agitation in moderate to severe Alzheimer's disease (AD). However, memantine and rivastigmine patch combination therapy has not been well studied in determining treatment effectiveness with mild to moderate AD patients. This was a multicenter, 24-week, prospective, randomized, open-label study design. A total 147 AD patients with Mini-Mental State Examination scores from 10 to 20 were randomly assigned to rivastigmine patch monotherapy and combination therapy with memantine groups. Agitation symptoms, using the Korean Version of the Cohen Mansfield Agitation Inventory were evaluated at baseline and at study end. Suppression and emergence of agitation symptoms were also evaluated. We carried out factor analyses to evaluate the interrelationship of agitation symptoms and to investigate treatment response in these symptoms. Factor analyses showed two symptom clusters: factor A - aggressive agitated behaviors - versus factor B - non-aggressive agitated behaviors. The rivastigmine patch monotherapy group showed significantly decreased factor B scores and had a tendency of decreased Korean Version of the Cohen Mansfield Agitation Inventory total scores and factor A scores. Conversely, the combination therapy group showed significantly increased Korean Version of the Cohen Mansfield Agitation Inventory total scores and factor B scores. Neither monotherapy nor combination therapy reduced the emergence of new agitation symptoms. In this trial of mild to moderate AD patients, the rivastigmine patch monotherapy group experienced a reduction of non-aggressive agitated behaviors. However, combination therapy with memantine did not show any benefit on the agitation associated with mild to moderate AD. Geriatr Gerontol Int 2017; 17: 494-499. © 2016 Japan Geriatrics Society.

Efficacy and tolerability of brinzolamide/brimonidine suspension and prostaglandin analogs in patients previously treated with dorzolamide/timolol solution and prostaglandin analogs.

PubMed

Lo, Jonathan S; Pang, Pierre M; Lo, Samuel C

2016-01-01

Fixed combination glaucoma medication is increasingly used in glaucoma treatment. There is a lack of comparative study in the literature of non-beta blocker combination agents used adjunctively with a glaucoma agent in a different class. The objective of this study is to evaluate the effect of intraocular pressure (IOP) control and tolerability of non-beta blocker combination suspension with prostaglandin analogs (PGA) in patients with open angle glaucoma who were previously treated with beta blocker combination solution with PGA. Open-label retrospective review of patient records. This study looked at patients with open angle glaucoma taking dorzolamide/timolol solution with PGA that were switched to brinzolamide/brimonidine combination suspension with PGA. This study reviewed the charts of all patients who were at least 21 years old with a clinical diagnosis of open-angle glaucoma or ocular hypertension in at least one eye. Patients needed to have been treated with concomitant use of PGA and dorzolamide/timolol solution for at least one month. Patients using dorzolamide/timolol solution plus PGA with medication related ocular irritation were switched to brinzolamide/brimonidine suspension with the same PGA. Best-corrected visual acuity, ocular hyperemia grading, slit lamp biomicroscopy and Goldmann applanation tonometry measurements, and patient medication preferences were assessed at baseline, 1 month and 3 months. Forty eyes with open angle glaucoma. The mean age of the patients was 68 and 60% were females. The IOP before the switch was 17.2 and 16.5 (P=0.70) following the switch at 3 months. We found a decreasing trend of ocular hyperemia (P=0.064) and strong preference (P=0.011) for non-beta blocker combination suspension but no difference of visual acuity and slit lamp findings. Brinzolamide/brimonidine combination suspension when used adjunctively with PGA is equally effective. Patients in this study reported greatly reduced ocular redness and shorter duration of stinging with non-beta blocker combination suspension. Their preference of it over dorzolamide/timolol combination solution makes it a viable treatment option, particularly for the aging glaucoma patient with comorbidities that restrict the beta blocker use.

Combination inhaled steroid and long-acting beta₂-agonist in addition to tiotropium versus tiotropium or combination alone for chronic obstructive pulmonary disease.

PubMed

Rojas-Reyes, Maria Ximena; García Morales, Olga M; Dennis, Rodolfo J; Karner, Charlotta

2016-06-06

The long-acting bronchodilator tiotropium and single-inhaler combination therapy of inhaled corticosteroids and long-acting beta2-agonists (ICS/LABA) are commonly used for maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Combining these treatments, which have different mechanisms of action, may be more effective than administering the individual components. To assess relative effects of the following treatments on markers of exacerbations, symptoms, quality of life and lung function in patients with COPD.• Tiotropium plus LABA/ICS versus tiotropium.• Tiotropium plus LABA/ICS versus LABA/ICS. We searched the Cochrane Airways Group Specialised Register of Trials (April 2015), ClinicalTrials.gov (www.ClinicalTrials.gov), the World Health Organization (WHO) trials portal and reference lists of relevant articles. We included parallel, randomised controlled trials (RCTs) lasting three months or longer conducted to compare ICS and LABA combination therapy in addition to inhaled tiotropium versus tiotropium alone or combination therapy alone. We independently assessed trials for inclusion, then extracted data on trial quality and outcome results. We contacted study authors to ask for additional information. We collected trial information on adverse effects. Tiotropium plus LABA/ICS versus tiotropiumWe included six studies (1902 participants) with low risk of bias that compared tiotropium in addition to inhaled corticosteroid and long-acting beta2-agonist combination therapy versus tiotropium alone. Investigators found no statistically significant differences in mortality between treatments (odds ratio (OR) 1.80, 95% confidence interval (CI) 0.55 to 5.91; two studies; 961 participants), a reduction in all-cause hospitalisations with the use of combined therapy (tiotropium + LABA/ICS) (OR 0.61, 95% CI 0.40 to 0.92; two studies; 961 participants; number needed to treat for an additional beneficial outcome (NNTB) 19.7, 95% CI 10.75 to 123.41). The effect on exacerbations was heterogeneous among trials and was not meta-analysed. Health-related quality of life measured by St. George's Respiratory Questionnaire (SGRQ) showed a statistically significant improvement in total scores with use of tiotropium + LABA/ICS compared with tiotropium alone (mean difference (MD) -3.46, 95% CI -5.05 to -1.87; four studies; 1446 participants). Lung function was significantly different in the combined therapy (tiotropium + LABA/ICS) group, although average benefit with this therapy was small. None of the included studies included exercise tolerance as an outcome.A pooled estimate of these studies did not show a statistically significant difference in adverse events (OR 1.16, 95% CI 0.92 to 1.47; four studies; 1363 participants), serious adverse events (OR 0.86, 95% CI 0.57 to 1.30; four studies; 1758 participants) and pneumonia (Peto OR 1.62, 95% CI 0.54 to 4.82; four studies; 1758 participants). Tiotropium plus LABA/ICS versus LABA/ICSOne of the six studies (60 participants) also compared combined therapy (tiotropium + LABA/ICS) versus LABA/ICS therapy alone. This study was affected by lack of power; therefore results did not allow us to draw conclusions for this comparison. In this update, we found new moderate-quality evidence that combined tiotropium + LABA/ICS therapy compared with tiotropium plus placebo decreases hospital admission. Low-quality evidence suggests an improvement in disease-specific quality of life with combined therapy. However, evidence is insufficient to support the benefit of tiotropium + LABA/ICS for mortality and exacerbations (moderate- and low-quality evidence, respectively). Of note, not all participants enrolled in the included studies would be candidates for triple therapy according to current international guidance.Compared with the use of tiotropium plus placebo, tiotropium + LABA/ICS-based therapy does not increase undesirable effects such as adverse events or serious non-fatal adverse events.

Improved Design Formulae for Buckling of Orthotropic Plates under Combined Loading

NASA Technical Reports Server (NTRS)

Weaver, Paul M.; Nemeth, Michael P.

2008-01-01

Simple, accurate buckling interaction formulae are presented for long orthotropic plates with either simply supported or clamped longitudinal edges and under combined loading that are suitable for design studies. The loads include 1) combined uniaxial compression (or tension) and shear, 2) combined pure inplane bending and 3) shear and combined uniaxial compression (or tension) and pure inplane bending. The interaction formulae are the results of detailed regression analysis of buckling data obtained from a very accurate Rayleigh-Ritz method.

Chemical combination effects predict connectivity in biological systems

PubMed Central

Lehár, Joseph; Zimmermann, Grant R; Krueger, Andrew S; Molnar, Raymond A; Ledell, Jebediah T; Heilbut, Adrian M; Short, Glenn F; Giusti, Leanne C; Nolan, Garry P; Magid, Omar A; Lee, Margaret S; Borisy, Alexis A; Stockwell, Brent R; Keith, Curtis T

2007-01-01

Efforts to construct therapeutically useful models of biological systems require large and diverse sets of data on functional connections between their components. Here we show that cellular responses to combinations of chemicals reveal how their biological targets are connected. Simulations of pathways with pairs of inhibitors at varying doses predict distinct response surface shapes that are reproduced in a yeast experiment, with further support from a larger screen using human tumour cells. The response morphology yields detailed connectivity constraints between nearby targets, and synergy profiles across many combinations show relatedness between targets in the whole network. Constraints from chemical combinations complement genetic studies, because they probe different cellular components and can be applied to disease models that are not amenable to mutagenesis. Chemical probes also offer increased flexibility, as they can be continuously dosed, temporally controlled, and readily combined. After extending this initial study to cover a wider range of combination effects and pathway topologies, chemical combinations may be used to refine network models or to identify novel targets. This response surface methodology may even apply to non-biological systems where responses to targeted perturbations can be measured. PMID:17332758

Gestrinone combined with ultrasound-guided aspiration and ethanol injection for treatment of chocolate cyst of ovary.

PubMed

Wu, Xiaoyun; Xu, Yun

2015-05-01

The aim of this study was to determine clinical performance of gestrinone combined with ultrasound-guided aspiration and ethanol injection in treating chocolate cyst of ovary. Sixty-eight patients enrolled in this study were randomly divided into two groups: control group and combination treatment group. In the control group, 34 patients were treated with ultrasound-guided aspiration and ethanol injection. In the combination treatment group, 34 patients received gestrinone p.o. following ultrasound-guided aspiration and ethanol injection. The recurrence rate of chocolate cyst was 10-fold lower in the combination treatment group (2.94%, 1/34) than in the control group (29.4%, 10/34) at 12 months. The effective rate for reduction of chocolate cyst was significantly higher in the combination treatment group (94.12%, 32/34) than in the control group (64.71%, 22/34) (P = 0.009). Gestrinone combined with ultrasound-guided aspiration and ethanol injection therapy is an effective treatment for ovarian chocolate cyst with low recurrence rate. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

A quantitative benefit-risk assessment approach to improve decision making in drug development: Application of a multicriteria decision analysis model in the development of combination therapy for overactive bladder.

PubMed

de Greef-van der Sandt, I; Newgreen, D; Schaddelee, M; Dorrepaal, C; Martina, R; Ridder, A; van Maanen, R

2016-04-01

A multicriteria decision analysis (MCDA) approach was developed and used to estimate the benefit-risk of solifenacin and mirabegron and their combination in the treatment of overactive bladder (OAB). The objectives were 1) to develop an MCDA tool to compare drug effects in OAB quantitatively, 2) to establish transparency in the evaluation of the benefit-risk profile of various dose combinations, and 3) to quantify the added value of combination use compared to monotherapies. The MCDA model was developed using efficacy, safety, and tolerability attributes and the results of a phase II factorial design combination study were evaluated. Combinations of solifenacin 5 mg and mirabegron 25 mg and mirabegron 50 (5+25 and 5+50) scored the highest clinical utility and supported combination therapy development of solifenacin and mirabegron for phase III clinical development at these dose regimens. This case study underlines the benefit of using a quantitative approach in clinical drug development programs. © 2015 The American Society for Clinical Pharmacology and Therapeutics.

The History and Promise of Combined Cycle Engines for Access to Space Applications

NASA Technical Reports Server (NTRS)

Clark, Casie

2010-01-01

For the summer of 2010, I have been working in the Aerodynamics and Propulsion Branch at NASA Dryden Flight Research Center studying combined-cycle engines, a high speed propulsion concept. Combined cycle engines integrate multiple propulsion systems into a single engine capable of running in multiple modes. These different modes allow the engine to be extremely versatile and efficient in varied flight conditions. The two most common types of combined cycle engines are Rocket-Based Combined Cycle (RBCC) and Turbine Based Combined Cycle (TBCC). The RBCC essentially combines a rocket and ramjet engine, while the TBCC integrates a turbojet and ramjet1. These two engines are able to switch between different propulsion modes to achieve maximum performance. Extensive conceptual and ground test studies of RBCC engines have been undertaken; however, an RBCC engine has never, to my knowledge, been demonstrated in flight. RBCC engines are of particular interest because they could potentially power a reusable launch vehicle (RLV) into space. The TBCC has been flight tested and shown to be effective at reaching supersonic speeds, most notably in the SR-71 Blackbird2.

Cumulative Risk and Impact Modeling on Environmental Chemical and Social Stressors.

PubMed

Huang, Hongtai; Wang, Aolin; Morello-Frosch, Rachel; Lam, Juleen; Sirota, Marina; Padula, Amy; Woodruff, Tracey J

2018-03-01

The goal of this review is to identify cumulative modeling methods used to evaluate combined effects of exposures to environmental chemicals and social stressors. The specific review question is: What are the existing quantitative methods used to examine the cumulative impacts of exposures to environmental chemical and social stressors on health? There has been an increase in literature that evaluates combined effects of exposures to environmental chemicals and social stressors on health using regression models; very few studies applied other data mining and machine learning techniques to this problem. The majority of studies we identified used regression models to evaluate combined effects of multiple environmental and social stressors. With proper study design and appropriate modeling assumptions, additional data mining methods may be useful to examine combined effects of environmental and social stressors.

Combined DTP-HBV-HIB vaccine versus separately administered DTP-HBV and HIB vaccines for primary prevention of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae B (HIB).

PubMed

Bar-On, Edna S; Goldberg, Elad; Hellmann, Sarah; Leibovici, Leonard

2012-04-18

Advantages to combining childhood vaccines include reducing the number of visits, injections and patient discomfort, increasing compliance and optimising prevention. The World Health Organization (WHO) recommends that routine infant immunisation programmes include a vaccination against Haemophilus influenzae (H. influenzae) type B (HIB) in the combined diphtheria-tetanus-pertussis (DTP)-hepatitis B virus (HBV) vaccination. The effectiveness and safety of the combined vaccine should be carefully and systematically assessed to ensure its acceptability by the community. To compare the effectiveness of combined DTP-HBV-HIB vaccines versus combined DTP-HBV and separate HIB vaccinations. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (January 1966 to week 1, November 2011), EMBASE (January 1990 to November 2011) and www.clinicaltrials.gov (up to April 2011). Randomised controlled trials (RCTs) or quasi-RCTs comparing vaccination with any combined DTP-HBV-HIB vaccine, with or without three types of inactivated polio virus (IPV) or concomitant oral polio vaccine (OPV) in any dose, preparation or time schedule, compared with separate vaccines or placebo, administered to infants up to two years old. Two review authors independently inspected references identified by the searches and evaluated them against the inclusion criteria, extracted data and assessed the methodological quality of included trials. Data for the primary outcome (prevention of disease) were lacking. We performed a meta-analysis to pool the results of 20 studies with 5874 participants in an immunogenicity analysis and 5232 participants in the reactogenicity analysis. There were no data on clinical outcomes for the primary outcome (prevention of disease) and all studies used immunogenicity and reactogenicity (adverse events). The number of vaccine doses differed significantly between the studies. Heterogeneous interventions, study location, healthcare environment and combining research across disparate geographical locations, may have lead to bias. The risk of bias was unclear across most of the included studies. Comparisons found little heterogeneity. In two immunological responses the combined vaccine achieved lower responses than the separate vaccines for HIB and tetanus. No significant differences in immunogenicity were found for pertussis, diphtheria, polio and hepatitis B. Serious adverse events were comparable with mainly hospitalisation and acute bronchiolitis cases. Minor adverse events such as pain and redness were more common in children given the combined vaccine. Overall, the direction shown by the results is in favour of the DTPw (diptheria-tetanus-whole cell pertussis)-HBV-HIB vaccine rather than the DTPa (diptheria-tetanus-acellular pertussis)-HBV-HIB vaccine when compared to the separate vaccines (size of effect: risk ratio (RR) 1.43; 95% confidence interval (CI) 0.98 to 2.10, for 5269 participants). We could not conclude that the immune responses elicited by the combined vaccine were different from or equivalent to the separate vaccines. There was significantly less immunological response for HIB and tetanus and more local reactions in the combined injections. However, these differences rely mostly on one study each. Studies did not use an intention-to-treat (ITT) analysis and we were uncertain about the risk of bias in many of the studies. These results are therefore inconclusive. Studies addressing clinical end points whenever possible, using correct methodology and a large enough sample size should be conducted.

Cautions on the Use of Investigative Case Studies in Meta-Evaluation.

ERIC Educational Resources Information Center

Smith, Nick L.

1990-01-01

A meta-analysis combining expert evaluation with naturalistic case study methods indicates that such investigations must use special methods to render evaluative judgments of worth. It is demonstrated that descriptive, interpretive, and evaluative aspects of such a study must be combined to yield justifiable conclusions. (TJH)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barker, Christopher A., E-mail: barkerc@mskcc.org; Postow, Michael A.

Radiation therapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiation therapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiation therapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiation therapy. The cytokines interferon-α and interleukin-2 have been combined with radiation therapy in several small studies, with some evidence suggesting increased toxicitymore » and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiation therapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested that radiation therapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiation therapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study.« less

Combinations of Drugs in the Treatment of Obesity

PubMed Central

Halpern, Bruno; Oliveira, Eduardo S. L.; Faria, André M.; Halpern, Alfredo; de Melo, Maria Edna; Cercato, Cintia; Mancini, Marcio C.

2010-01-01

Obesity is a chronic disease associated with excess morbidity and mortality. Clinical treatment, however, currently offers disappointing results, with very high rates of weight loss failure or weight regain cycles, and only two drugs (orlistat and sibutramine) approved for long-term use. Drugs combinations can be an option for its treatment but, although widely used in clinical practice, very few data are available in literature for its validation. Our review focuses on the rationale for their use, with advantages and disadvantages; on combinations often used, with or without studies; and on new perspectives of combinations being studied mainly by the pharmaceutical industry. PMID:27713360

Natural Co-Occurrence of Mycotoxins in Foods and Feeds and Their in vitro Combined Toxicological Effects.

PubMed

Smith, Marie-Caroline; Madec, Stéphanie; Coton, Emmanuel; Hymery, Nolwenn

2016-03-26

Some foods and feeds are often contaminated by numerous mycotoxins, but most studies have focused on the occurrence and toxicology of a single mycotoxin. Regulations throughout the world do not consider the combined effects of mycotoxins. However, several surveys have reported the natural co-occurrence of mycotoxins from all over the world. Most of the published data has concerned the major mycotoxins aflatoxins (AFs), ochratoxin A (OTA), zearalenone (ZEA), fumonisins (FUM) and trichothecenes (TCTs), especially deoxynivalenol (DON). Concerning cereals and derived cereal product samples, among the 127 mycotoxin combinations described in the literature, AFs+FUM, DON+ZEA, AFs+OTA, and FUM+ZEA are the most observed. However, only a few studies specified the number of co-occurring mycotoxins with the percentage of the co-contaminated samples, as well as the main combinations found. Studies of mycotoxin combination toxicity showed antagonist, additive or synergic effects depending on the tested species, cell model or mixture, and were not necessarily time- or dose-dependent. This review summarizes the findings on mycotoxins and their co-occurrence in various foods and feeds from all over the world as well as in vitro experimental data on their combined toxicity.

Natural Co-Occurrence of Mycotoxins in Foods and Feeds and Their in vitro Combined Toxicological Effects

PubMed Central

Smith, Marie-Caroline; Madec, Stéphanie; Coton, Emmanuel; Hymery, Nolwenn

2016-01-01

Some foods and feeds are often contaminated by numerous mycotoxins, but most studies have focused on the occurrence and toxicology of a single mycotoxin. Regulations throughout the world do not consider the combined effects of mycotoxins. However, several surveys have reported the natural co-occurrence of mycotoxins from all over the world. Most of the published data has concerned the major mycotoxins aflatoxins (AFs), ochratoxin A (OTA), zearalenone (ZEA), fumonisins (FUM) and trichothecenes (TCTs), especially deoxynivalenol (DON). Concerning cereals and derived cereal product samples, among the 127 mycotoxin combinations described in the literature, AFs+FUM, DON+ZEA, AFs+OTA, and FUM+ZEA are the most observed. However, only a few studies specified the number of co-occurring mycotoxins with the percentage of the co-contaminated samples, as well as the main combinations found. Studies of mycotoxin combination toxicity showed antagonist, additive or synergic effects depending on the tested species, cell model or mixture, and were not necessarily time- or dose-dependent. This review summarizes the findings on mycotoxins and their co-occurrence in various foods and feeds from all over the world as well as in vitro experimental data on their combined toxicity. PMID:27023609

Biomarker combinations for diagnosis and prognosis in multicenter studies: Principles and methods.

PubMed

Meisner, Allison; Parikh, Chirag R; Kerr, Kathleen F

2017-01-01

Many investigators are interested in combining biomarkers to predict a binary outcome or detect underlying disease. This endeavor is complicated by the fact that many biomarker studies involve data from multiple centers. Depending upon the relationship between center, the biomarkers, and the target of prediction, care must be taken when constructing and evaluating combinations of biomarkers. We introduce a taxonomy to describe the role of center and consider how a biomarker combination should be constructed and evaluated. We show that ignoring center, which is frequently done by clinical researchers, is often not appropriate. The limited statistical literature proposes using random intercept logistic regression models, an approach that we demonstrate is generally inadequate and may be misleading. We instead propose using fixed intercept logistic regression, which appropriately accounts for center without relying on untenable assumptions. After constructing the biomarker combination, we recommend using performance measures that account for the multicenter nature of the data, namely the center-adjusted area under the receiver operating characteristic curve. We apply these methods to data from a multicenter study of acute kidney injury after cardiac surgery. Appropriately accounting for center, both in construction and evaluation, may increase the likelihood of identifying clinically useful biomarker combinations.

49 CFR Schedule E to Subpart B of... - Statement of Changes in Financial Position

Code of Federal Regulations, 2011 CFR

2011-10-01

... over the recent past. Study Carrier Groupings. Schedule E shall be prepared on the following two bases: 1. Greyhound Lines, Inc. 2. Trailways Combined (study carriers, only) 3. All Study Carriers “Funds... combined () All study carriers Line No. and item (a) Source (b) Calendar year 19__ (c) Calendar year 19...

Efficacy and Tolerability of Nilvadipine in Combination with an Angiotensin II Receptor Antagonist in Patients with Essential Hypertension: A Multicenter, Open-Label, Uncontrolled Study

PubMed Central

Noda, Keita; Ideishi, Munehito; Tashiro, Eiichiro; Nakashima, Yoshiyuki; Imamura, Mitsuhide; Seki, Masahiko; Fujino, Masanori; Sou, Toshimitsu; Kohara, Masaki; Kanaya, Hisashi; Saku, Nishiki; Kamei, Ritsu; Yamasaki, Misao; Sakai, Hiroshi; Gondo, Naoki; Saku, Keijiro

2003-01-01

Background: Combination therapy with different classes of antihypertensive drugs often is needed to achieve controlled blood pressure (BP). The combination of an angiotensin II receptor antagonist (AIIA) and a calcium antagonist is a preferred option for reducing uncontrolled BP. Objective: The aim of this study was to assess the clinical efficacy and tolerability of nilvadipine, a dihydropyridine calcium antagonist, in combination with an AIIA. Methods: Patients with essential hypertension whose BP was not controlled by an AIIA alone were eligible for this multicenter, open-label, uncontrolled study. One of 3 AIIAs (candesartan cilexetil, losartan potassium, or valsartan) was given for at least 10 weeks before the addition of nilvadipine (daily dose, 4 or 8 mg orally). This combination therapy was given for 8 weeks. BP and heart rate were measured between 2 and 4 weeks before and 0, 4, and 8 weeks after the start of combination therapy. Adverse events were monitored at each visit. Results: Thirty-one patients (18 women [58.1%], 13 men [41.9%]; mean [SD] age, 58.5 [10.5] years) were enrolled. At weeks 4 and 8 of combination therapy, mean systolic BP (SBP) and diastolic BP (DBP) were significantly decreased (P<0.01) (at week 8, by 22.0 mm Hg and 12.5 mm Hg, respectively). The mean BP-lowering effect did not differ significantly between the 3 AIIAs tested. Pulse pressure also decreased significantly at week 8, by 9.6 mm Hg (P<0.01). The responder rate (ie, the percentage of patients with DBP <90 mm Hg or a decrease in DBP ≥10 mm Hg) was 72.0% at week 8. Three patients experienced a total of 4 adverse events: mild or severe flushing, mild headache, and mild palpitation. All of these symptoms resolved after nilvadipine treatment was discontinued. Conclusions: Nilvadipine in combination with an AIIA showed good antihypertensive efficacy and was well tolerated in the hypertensive patients in this study. This combination also significantly decreased pulse pressure, suggesting that this combination therapy also may have a beneficial effect in elderly patients with isolated systolic hypertension. PMID:25053855

Combinations of long-term care insurance services and associated factors in Japan: a classification tree model.

PubMed

Igarashi, Ayumi; Ishibashi, Tomoaki; Shinozaki, Tomohiro; Yamamoto-Mitani, Noriko

2014-09-10

To develop a quality community-based care management system, it is important to identify the actual use of long-term care insurance (LTCI) services and the most frequent combinations of services. It is also important to determine the factors associated with the use of such combinations. This study was conducted in 10 care management agencies in the urban area around Tokyo, Japan. The assessment and services data of 983 clients using the Minimum Data Set for Home Care were collected from the agencies. We categorized combination patterns of services from descriptive data analysis of service use and conducted chi-squared automatic interaction detection (CHAID) analysis to identify the primary variables determining the combinations of the services used. We identified nine patterns of service use: day care only (16.5%); day care and assistive devices (14.4%); day care, home helper, and assistive devices (13.2%); home helper and assistive devices (11.8%); assistive devices only (10.9%); home helper only (8.7%); day care and home helper (7.7%); home helper, visiting nurse, and assistive devices (5.4%); and others (11.3%). The CHAID dendrogram illustrated the relative importance of significant independent variables in determining combination use; the most important variables in predicting combination use were certified care need level, living arrangements, cognitive function, and need for medical procedures. The characteristics of care managers and agencies were not associated with the combinations. This study clarified patterns of community-based service use in the LTCI system in Japan. The combinations of services were more related to the physical and psychosocial status of older adults than to the characteristics of agencies and care managers. Although we found no association between service use and the characteristics of agencies and care managers, further examination of possible bias in the use of services should be included in future studies. Researchers and policymakers can use these combinations identified in this study to categorize the use of community-based care service and measure the outcomes of care interventions.

[The Morbidity of Students Conditioned by Diet Character in Modern Condition of Education].

PubMed

Novokhatskaya, E A; Yakovleva, T P; Kalitina, M A

2017-09-01

The article considers characteristics of nervous psychic adaptation, morbidity and character of diet of students of the Russian state social university. The main incentives of combination of university studies and work are analyzed. The impact of combining of studies and work, regimen and diet quality on health are investigated. The psychological studies were implemented using computerized techniques of psychological testing and data collection with blank technique. The morbidity of students was discovered using questionnaire. It is established that students combining studies and work, have optimal indices of nervous psychic adaptation. however, level of their morbidity is twice higher than morbidity of students not combining studies and work. The analysis of regimen and diet character of students established deviations in regimen and structure of diet. The ration of proteins, fats and carbohydrates in day ration of students was imbalanced (1.0:1.4:6.1) at the expense of surplus of content of fat and especially carbohydrates that afterwards can results in development of diseases related to irregular diet.

Combination Therapies for Traumatic Brain Injury: Retrospective Considerations

PubMed Central

Anderson, Gail; Atif, Fahim; Badaut, Jerome; Clark, Robert; Empey, Philip; Guseva, Maria; Hoane, Michael; Huh, Jimmy; Pauly, Jim; Raghupathi, Ramesh; Scheff, Stephen; Stein, Donald; Tang, Huiling; Hicks, Mona

2016-01-01

Abstract Patients enrolled in clinical trials for traumatic brain injury (TBI) may present with heterogeneous features over a range of injury severity, such as diffuse axonal injury, ischemia, edema, hemorrhage, oxidative damage, mitochondrial and metabolic dysfunction, excitotoxicity, inflammation, and other pathophysiological processes. To determine whether combination therapies might be more effective than monotherapy at attenuating moderate TBI or promoting recovery, the National Institutes of Health funded six preclinical studies in adult and immature male rats to evaluate promising acute treatments alone and in combination. Each of the studies had a solid rationale for its approach based on previous research, but only one reported significant improvements in long-term outcomes across a battery of behavioral tests. Four studies had equivocal results because of a lack of sensitivity of the outcome assessments. One study demonstrated worse results with the combination in comparison with monotherapies. While specific research findings are reported elsewhere, this article provides an overview of the study designs, insights, and recommendations for future research aimed at therapy development for TBI. PMID:25970337

A retrospective study of treatment persistence and adherence to α-blocker plus antimuscarinic combination therapies, in men with LUTS/BPH in the Netherlands.

PubMed

Drake, Marcus J; Bowditch, Sally; Arbe, Emilio; Hakimi, Zalmai; Guelfucci, Florent; Amri, Ikbel; Nazir, Jameel

2017-05-22

To assess treatment persistence and adherence in men ≥45 years of age with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), using prescription records from the Netherlands IMS Lifelink™ LRx database. In this retrospective, observational cohort study, we identified men who received combination therapy with an α-blocker plus an antimuscarinic (e.g. solifenacin or tolterodine) between 1 November 2013 and 31 October 2014. Treatment could be received as a fixed-dose combination (FDC) tablet or as two drugs administered together (concomitant therapy), if both combination drugs were prescribed within 30 days. The primary objective was to assess treatment persistence, defined as the time from initiation of combination therapy until first discontinuation of the FDC or at least one of the drugs given concomitantly (i.e. ≥30 days without prescription renewal). Subgroup and sensitivity analyses were conducted to assess persistence by antimuscarinic agent, and with different gap lengths used to define discontinuation (45, 60 and 90 days), respectively. A total of 1891 men received an α-blocker plus an antimuscarinic (FDC, N = 665; concomitant therapy, N = 1226). Median time to discontinuation was significantly longer with FDC versus concomitant therapy (414 vs. 112 days; adjusted hazard ratio [HR] 2.04, 95% confidence interval 1.77, 2.35; p < 0.0001). Persistence at 12 months (51.3% vs. 29.9%) was also significantly greater with FDC compared with concomitant therapy. Assessment of antimuscarinic subgroups showed that median time to discontinuation was longest with solifenacin combinations (214 days) compared with other antimuscarinic combinations (range, 47-164 days; adjusted HR range, 1.27-1.77, p = 0.037). No observable impact on treatment persistence was found by adjusting the gaps used to define discontinuation. This study of real-world evidence of men with LUTS/BPH treated with α-blocker plus antimuscarinic combination therapy in the Netherlands showed that treatment persistence was significantly greater in those who received a FDC tablet compared with combination therapy given concomitantly. The study also shows that treatment persistence was extended in men who received combination therapy containing solifenacin compared with other antimuscarinics. Overall, these findings may be useful for prescribers, as improved persistence on-treatment may translate into improved outcomes for men with LUTS/BPH. Further study is warranted to establish the key drivers of persistence in men receiving combination therapy for LUTS/BPH.

Effects of Drugs and Drug Combinations in Pigeons Trained to Discriminate among Pentobarbital, Dizocilpine, a Combination of These Drugs, and Saline

ERIC Educational Resources Information Center

McMillan, D. E.; Wessinger, William D.; Li, Mi

2009-01-01

Drugs with multiple actions can have complex discriminative-stimulus properties. An approach to studying such drugs is to train subjects to discriminate among drug combinations and individual drugs in the combination so that all of the complex discriminative stimuli are present during training. In the current experiments, a four-choice procedure…

Synergistic Antiproliferative Effects of Combined γ-Tocotrienol and PPARγ Antagonist Treatment Are Mediated through PPARγ-Independent Mechanisms in Breast Cancer Cells

PubMed Central

Sylvester, Paul W.

2014-01-01

Previous findings showed that the anticancer effects of combined γ-tocotrienol and peroxisome proliferator activated receptor γ (PPARγ) antagonist treatment caused a large reduction in PPARγ expression. However, other studies suggest that the antiproliferative effects of γ-tocotrienol and/or PPARγ antagonists are mediated, at least in part, through PPARγ-independent mechanism(s). Studies were conducted to characterize the role of PPARγ in mediating the effects of combined treatment of γ-tocotrienol with PPARγ agonists or antagonists on the growth of PPARγ negative +SA mammary cells and PPARγ-positive and PPARγ-silenced MCF-7 and MDA-MB-231 breast cancer cells. Combined treatment of γ-tocotrienol with PPARγ antagonist decreased, while combined treatment of γ-tocotrienol with PPARγ agonist increased, growth of all cancer cells. However, treatment with high doses of 15d-PGJ2, an endogenous natural ligand for PPARγ, had no effect on cancer cell growth. Western blot and qRT-PCR studies showed that the growth inhibitory effects of combined γ-tocotrienol and PPARγ antagonist treatment decreased cyclooxygenase (COX-2), prostaglandin synthase (PGDS), and prostaglandin D2 (PGD2) synthesis. In conclusion, the anticancer effects of combined γ-tocotrienol and PPARγ antagonists treatment in PPARγ negative/silenced breast cancer cells are mediated through PPARγ-independent mechanisms that are associated with a downregulation in COX-2, PGDS, and PGD2 synthesis. PMID:24729783

Cytotoxic Effects of the Therapeutic Radionuclide Rhenium-188 Combined with Taxanes in Human Prostate Carcinoma Cell Lines.

PubMed

Lange, Rogier; ter Heine, Rob; van Wieringen, Wessel N; Tromp, Adrienne M; Paap, Mayke; Bloemendal, Haiko J; de Klerk, John M H; Hendrikse, N Harry; Geldof, Albert A

2017-02-01

Rhenium-188-HEDP is an effective radiopharmaceutical for the treatment of painful bone metastases from prostate cancer. The effectiveness of the β-radiation emitted by 188 Re might be enhanced by combination with chemotherapy, using the radiosensitization concept. Therefore, the authors investigated the combined treatment of the taxanes, docetaxel and cabazitaxel, with 188 Re in prostate carcinoma cell lines. The cytotoxic effects of single and combined treatment with taxanes and 188 Re were investigated in three human prostate carcinoma cell lines (PC-3, DU 145, and LNCaP), using the colony-forming assay. The half maximal effective concentration (EC50) of all individual agents was determined. The combined treatment was studied at 0.25, 0.5, 1, 2, and 4 times the EC50 of each agent. The interaction was investigated with a regression model. The survival curves showed dose-dependent cell growth inhibition for both the taxanes and 188 Re. The regression model showed a good capability of explaining the data. It proved additivity in all combination experiments and confirmed a general trend to a slight subadditive effect. This proof-of-mechanism study exploring radiosensitization by combining 188 Re and taxanes showed no synergism, but significant additivity. This encourages the design of in vivo studies. Future research should explore the potential added value of concomitant treatment of bone metastases with chemotherapy and 188 Re-HEDP.

A study of surface tension driven segregation in monotectic alloy systems

NASA Technical Reports Server (NTRS)

Andrews, J. Barry; Andrews, Rosalia N.; Gowens, Terrell F.

1988-01-01

The compatibilities of various monotectic alloy systems with several different crucible materials were evaluated. The study was carried out using small candidate alloy samples of compositions that produced fifty volume percent of each liquid phase at the monotectic temperature. Compatibility was based on the evaluation of the wetting tendency of the two immiscible phases with the crucible material in a one-g solidified sample. Three types of wetting phenomena were observed during the evaluation. Type 1 indicates an alloy-crucible combination where the L2 phase preferentially wets the crucible material. Since L2 is usually the minority phase in desirable alloys, this material combination would be difficult to process and is therefore considered incompatible. Type 2 behavior indicates an alloy-crucible combination where the L1 phase preferentially wets the crucible material. This type of combination is considered compatible since surface tension effects should aid in processing the alloy to a useful form. Type 3 indicates any combination that leads to major reactions between the alloy and crucible material, gas entrapment, or separation of the metal from the crucible wall. Additional compatibility evaluations would have to be carried out on combinations of this category. The five alloy systems studied included aluminum-bismuth, copper-lead, aluminum-indium, aluminum-lead and cadmium-gallium. The systems were combined with crucibles of alumina, boron nitride, mullite, quartz, silicon carbide and zirconia.

The combination of Hsp90 inhibitor 17AAG and heavy-ion irradiation provides effective tumor control in human lung cancer cells.

PubMed

Hirakawa, Hirokazu; Fujisawa, Hiroshi; Masaoka, Aya; Noguchi, Miho; Hirayama, Ryoichi; Takahashi, Momoko; Fujimori, Akira; Okayasu, Ryuichi

2015-03-01

Hsp90 inhibitors have become well-studied antitumor agents for their selective property against tumors versus normal cells. The combined treatment of Hsp90 inhibitor and conventional photon radiation also showed more effective tumor growth delay than radiation alone. However, little is known regarding the combined treatment of Hsp90 inhibitor and heavy-ion irradiation. In this study, SQ5 human lung tumor cells were used in vitro for clonogenic cell survival and in vivo for tumor growth delay measurement using a mouse xenograft model after 17-allylamino-17-demethoxygeldanamycin (17AAG) pretreatment and carbon ion irradiation. Repair of DNA double strand breaks (DSBs) was also assessed along with expressions of DSB repair-related proteins. Cell cycle analysis after the combined treatment was also performed. The combined treatment of 17AAG and carbon ions revealed a promising treatment option in both in vitro and in vivo studies. One likely cause of this effectiveness was shown to be the inhibition of homologous recombination repair by 17AAG. The more intensified G2 cell cycle delay was also associated with the combined treatment when compared with carbon ion treatment alone. Our findings indicate that the combination of Hsp90 inhibition and heavy-ion irradiation provides a new effective therapeutic alternative for treatment of solid tumors. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Combination of rapamycin and garlic-derived S-allylmercaptocysteine induces colon cancer cell apoptosis and suppresses tumor growth in xenograft nude mice through autophagy/p62/Nrf2 pathway.

PubMed

Li, Siying; Yang, Guang; Zhu, Xiaosong; Cheng, Lin; Sun, Yueyue; Zhao, Zhongxi

2017-09-01

The natural plant-derived product S-allylmercapto-cysteine (SAMC) has been studied in cancer therapy as a single and combination chemotherapeutic agent. The present study was employed to verify the combination use of SAMC and rapamycin that is the mTOR inhibitor with anticancer ability but has limited efficacy due to drug resistance, and to explore the underlying mechanisms. We combined rapamycin and SAMC for colorectal cancer treatment in the HCT‑116 cancer cells and a xenograft murine model. The in vivo study was established by xenografting HCT‑116 cells in BALB/c nude mice. It was found that the combination therapy had enhanced tumor-suppressing ability with the upregulation of the Bax/Bcl-2 ratio as a consequence of activated apoptosis, inhibition of autophagic activity and prevention of Akt phosphorylation. The rapamycin and SAMC combination activated antioxidant transcription expressions of Nrf2 and downstream gene NQO1. Concomitantly, autophagosome cargo p62 was downregulated, indicating that the p62 played a negative-regulatory role between Nrf2 and autophagy. Our results show that the combination of SAMC and rapamycin enhanced the anticancer ability, which could be used for the treatment of colorectal cancer. The underling mechanism of autophagy/p62/Nrf2 pathway discovered may provide a new direction for drug development, especially for traditional Chinese medicines.

The National Football League (NFL) combine: does normalized data better predict performance in the NFL draft?

PubMed

Robbins, Daniel W

2010-11-01

The objective of this study was to investigate the predictive ability of National Football League (NFL) combine physical test data to predict draft order over the years 2005-2009. The NFL combine provides a setting in which NFL personnel can evaluate top draft prospects. The predictive ability of combine data in its raw form and when normalized in both a ratio and allometric manner was examined for 17 positions. Data from 8 combine physical performance tests were correlated with draft order to determine the direction and strength of relationship between the various combine measures and draft order. Players invited to the combine and subsequently drafted in the same year (n = 1,155) were included in the study. The primary finding was that performance in the combine physical test battery, whether normalized or not, has little association with draft success. In terms of predicting draft order from outcomes of the 8 tests making up the combine battery, normalized data provided no advantage over raw data. Of the 8 performance measures investigated, straight sprint time and jumping ability seem to hold the most weight with NFL personnel responsible for draft decisions. The NFL should consider revising the combine test battery to reflect the physical characteristics it deems important. It may be that NFL teams are more interested in attributes other than the purely physical traits reflected in the combine test battery. Players with aspirations of entering the NFL may be well advised to develop mental and technical skills in addition to developing the physical characteristics necessary to optimize performance.

In Vitro Assessment of Combined Polymyxin B and Minocycline Therapy against Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae.

PubMed

Huang, Dennis; Yu, Brenda; Diep, John K; Sharma, Rajnikant; Dudley, Michael; Monteiro, Jussimara; Kaye, Keith S; Pogue, Jason M; Abboud, Cely Saad; Rao, Gauri G

2017-07-01

The multidrug resistance profiles of Klebsiella pneumoniae carbapenemase (KPC) producers have led to increased clinical polymyxin use. Combination therapy with polymyxins may improve treatment outcomes, but it is uncertain which combinations are most effective. Clinical successes with intravenous minocycline-based combination treatments have been reported for infections caused by carbapenemase-producing bacteria. The objective of this study was to evaluate the in vitro activity of polymyxin B and minocycline combination therapy against six KPC-2-producing K. pneumoniae isolates (minocycline MIC range, 2 to 32 mg/liter). Polymyxin B monotherapy (0.5, 1, 2, 4, and 16 mg/liter) resulted in a rapid reduction of up to 6 log in bactericidal activity followed by regrowth by 24 h. Minocycline monotherapy (1, 2, 4, 8, and 16 mg/liter) showed no reduction of activity of >1.34 log against all isolates, although concentrations of 8 and 16 mg/liter prolonged the time to regrowth. When the therapies were used in combination, rapid bactericidal activity was followed by slower regrowth, with synergy (60 of 120 combinations at 24 h, 19 of 120 combinations at 48 h) and additivity (43 of 120 combinations at 24 h, 44 of 120 combinations at 48 h) against all isolates. The extent of killing was greatest against the more susceptible polymyxin B isolates (MICs of ≤0.5 mg/liter) regardless of the minocycline MIC. The pharmacodynamic activity of combined polymyxin B-minocycline therapy against KPC-producing K. pneumoniae is dependent on polymyxin B susceptibility. Further in vitro and animal studies must be performed to fully evaluate the efficacy of this drug combination. Copyright © 2017 American Society for Microbiology.

Efficacy and Safety of Combined Oral Chelation With Deferiprone and Deferasirox in Children With β-Thalassemia Major: An Experience From North India.

PubMed

Parakh, Nupur; Chandra, Jagdish; Sharma, Sunita; Dhingra, Bhavna; Jain, Rajesh; Mahto, DeoNath

2017-04-01

A combination of desferrioxamine with either deferiprone (DFP) or deferasirox (DFX) for patients with β-thalassemia major who do not achieve negative iron balance with monotherapy has been studied widely. However, poor compliance resulting from the need for parentral administration of desferrioxamine and its cost necessicitates combining 2 oral chelators. A prospective study was conducted in patients with transfusion-dependent β-thalassemia major in a tertiary care center over 2 years. Patients on either DFP or DFX who were not improving on monotherapy over a long period and persistently maintaining serum ferritin >2500 µg/L were enrolled. Efficacy was assessed by serum ferritin levels assessed at 12 months and 2 years. Complete blood counts and liver and kidney function tests were monitored to assess the safety of the combination of drugs. In total, 33 patients with a mean age of 12.67 years (7.5 to 17.5 y) and a mean ferritin of 4835.2394±1443.85 µg/L formed the study cohort.In total, 28 patients completed the 1-year study period; and 12 patients completed 2 years. Mean serum ferritin reduction at 1 and 2 years was 34.99%±18.13% (range, -34.36% to 56.17%) and 44.67%±13.78% (range, 22.17% to 62.74%), respectively. The combination therapy was well tolerated. Combined oral chelation with DFP and DFX has better efficacy than either drug used alone. The combination of drugs was well tolerated and no new adverse effects were observed.

Ultrasound-guided Combined Fascial Plane Blocks as an Intervention for Pain Management after Laparoscopic Cholecystectomy: A Randomized Control Study

PubMed Central

Ramkiran, Seshadri; Jacob, Mathews; Honwad, Manish; Vivekanand, Desiraju; Krishnakumar, Mathangi; Patrikar, Seema

2018-01-01

Background: Pain associated with laparoscopic cholecystectomy is most severe during the first 24 h and the port sites are the most painful. Recent multimodal approaches target incisional pain instead of visceral pain which has led to the emergence of abdominal fascial plane blocks. This study embraces a novel combination of two independently effective fascial plane blocks, namely rectus sheath block and subcostal transversus abdominis plane (TAP) block to alleviate postoperative pain. Study Objective: The aim is to evaluate the effectiveness of the combination of rectus sheath block and subcostal TAP block, to compare its efficacy with that of subcostal TAP block alone and with conventional port site infiltration (PSI) in alleviating postoperative pain in patients undergoing laparoscopic cholecystectomy. Methodology: This prospective, randomized control, pilot study included 61 patients scheduled for elective laparoscopic cholecystectomy and distributed among three groups, namely Group 1: Combined subcostal TAP block with rectus sheath block (n = 20); Group 2: Oblique subcostal TAP block alone (n = 21); and Group 3: PSI group as an active control (n = 20). Results: Combined group had significantly lower pain scores, higher satisfaction scores, and reduced rescue analgesia both in early and late postoperative periods than the conventional PSI group. Conclusion: Ultrasound-guided combined fascial plane blocks is a novel intervention in pain management of patients undergoing laparoscopic cholecystectomy and should become the standard of care. PMID:29628547

The effects of combined supplementary cementitious materials on physical properties of Kansas concrete pavements.

DOT National Transportation Integrated Search

2013-12-01

This study evaluated the effects of combining varying proportions of slag cement and Class C fly ash : with Type I/II cement in concrete pavement. Three different ternary cementitious material combinations : containing slag cement and Class C fly ash...

Energy Conversion Alternatives Study (ECAS), Westinghouse phase 1. Volume 5: Combined gas-steam turbine cycles. [energy conversion efficiency in electric power plants

NASA Technical Reports Server (NTRS)

Amos, D. J.; Foster-Pegg, R. W.; Lee, R. M.

1976-01-01

The energy conversion efficiency of gas-steam turbine cycles was investigated for selected combined cycle power plants. Results indicate that it is possible for combined cycle gas-steam turbine power plants to have efficiencies several point higher than conventional steam plants. Induction of low pressure steam into the steam turbine is shown to improve the plant efficiency. Post firing of the boiler of a high temperature combined cycle plant is found to increase net power but to worsen efficiency. A gas turbine pressure ratio of 12 to 1 was found to be close to optimum at all gas turbine inlet temperatures that were studied. The coal using combined cycle plant with an integrated low-Btu gasifier was calculated to have a plant efficiency of 43.6%, a capitalization of $497/kW, and a cost of electricity of 6.75 mills/MJ (24.3 mills/kwh). This combined cycle plant should be considered for base load power generation.

Screening of antibacterial effects of anise essential oil alone and in combination with conventional antibiotics against Streptococcus pneumoniae clinical isolates.

PubMed

Gradinaru, Adina Catinca; Miron, Anca; Trifan, Adriana; Spac, A; Brebu, M; Aprotosoaie, Ana Clara

2014-01-01

This study aimed to investigate the effects of anise essential oil alone and in combination with conventional antibiotics (amoxicillin, ciprofloxacin) against Streptococcus pneumoniae clinical isolates. MATERIAL AND METHODs: Anise essential oil (AEO) was isolated by hydrodistillation from dried powdered fruits. Its chemical composition was investigated by GC-MS and GC-FID. Broth dilution assay was used to evaluate the antibacterial effects of anise essential oil. The interactions with antibiotics were studied by the checkerboard assay. Trans-anethole (90.18%) was identified as major constituent in anise essential oil. Almost all combinations AEO-amoxicillin and AEO-ciprofloxacin showed indifferent interactions (1 < FIC index < or = 2). Positive interactions (addition and weak synergism) were found only for four combinations AEO-amoxicillin (FIC index = 1,0.62, 0.75 and 0.5) and one combination AEO-ciprofloxacin (FIC index = 0.62). Herbal products containing anise essential oil may be used as expectorants in combination with amoxicillin or ciprofloxacin in Streptococcus pneumoniae infections without diminishing antibiotic efficacy.

Randomized controlled trials and real-world observational studies in evaluating cardiovascular safety of inhaled bronchodilator therapy in COPD.

PubMed

Kardos, Peter; Worsley, Sally; Singh, Dave; Román-Rodríguez, Miguel; Newby, David E; Müllerová, Hana

2016-01-01

Long-acting muscarinic antagonist (LAMA) or long-acting β2-agonist (LABA) bronchodilators and their combination are recommended for the maintenance treatment of chronic obstructive pulmonary disease (COPD). Although the efficacy of LAMAs and LABAs has been well established through randomized controlled trials (RCTs), questions remain regarding their cardiovascular (CV) safety. Furthermore, while the safety of LAMA and LABA monotherapy has been extensively studied, data are lacking for LAMA/LABA combination therapy, and the majority of the studies that have reported on the CV safety of LAMA/LABA combination therapy were not specifically designed to assess this. Evaluation of CV safety for COPD treatments is important because many patients with COPD have underlying CV comorbidities. However, severe CV and other comorbidities are often exclusion criteria for RCTs, contributing to a lack in external validity and generalizability. Real-world observational studies are another important tool to evaluate the effectiveness and safety of COPD therapies in a broader population of patients and can improve upon the external validity limitations of RCTs. We examine what is already known regarding the CV and cerebrovascular safety of LAMA/LABA combination therapy from RCTs and real-world observational studies, and explore the advantages and limitations of data derived from each study type. We also describe an ongoing prospective, observational, comparative post-authorization safety study of a LAMA/LABA combination therapy (umeclidinium/vilanterol) and LAMA monotherapy (umeclidinium) versus tiotropium, with a focus on the relative merits of the study design.

Comparison of the activity of three antibiotic regimens in severe Legionnaires' disease.

PubMed

Dournon, E; Mayaud, C; Wolff, M; Schlemmer, B; Samuel, D; Sollet, J P; Levasseur-Rajagopalan, P

1990-10-01

Comparison of the activity of different antibiotic regimens in Legionnaire's disease has never been made because of the rarity of well documented cases of that disease. We have retrospectively compared severe cases of Legionnaires' disease treated with pefloxacin alone or in combination with erythromycin and/or rifampicin using computer-matched cases treated either with erythromycin or with erythromycin in combination with rifampicin. This study suggests that: (1) combined therapy including erythromycin, rifampicin and/or pefloxacin is superior to therapy with erythromycin alone; (2) combinations including pefloxacin may be the most active ones; and (3) pefloxacin alone may be as active as combination therapy. Although these results are in agreement with data obtained in cell and in animal models of legionella infection they need to be further confirmed by the study of larger number of patients.

Synergistic effect of green tea, cinnamon and ginger combination on enhancing postprandial blood glucose.

PubMed

Azzeh, Firas Sultan

2013-01-15

This study was maintained to determine the immediate effect of green tea, cinnamon, ginger and combination of them on postprandial glucose levels. The Glycemic Index (GI) for previous treatments was measured as an indicator for postprandial glucose pattern. Twenty-two healthy volunteers from both genders were enrolled in this study. Mean age was 21.3 years and mean BMI was 24.6 kg m(-2). For each herb and combination treatment, a concentration of 2.5% aqueous tea extract was prepared. The GI of green tea, cinnamon and ginger were 79, 63 and 72 respectively. Herbs combination exerted GI of 60, which was the lowest. Combination of these herbs showed the best lowering effect on postprandial glucose levels as compared with each herb alone. A potential synergism from the active ingredients of blended herbs was determined.

Hemodynamic effects of renin-angiotensin-aldosterone inhibitor and β-blocker combination therapy vs. β-blocker monotherapy for portal hypertension in cirrhosis: A meta-analysis

PubMed Central

Wang, Jianrong; Lu, Wenxia; Li, Jingjing; Zhang, Rong; Zhou, Yuqing; Yin, Qin; Zheng, Yuanyuan; Wang, Fan; Xia, Yujing; Chen, Kan; Li, Sainan; Liu, Tong; Lu, Jie; Zhou, Yingqun; Guo, Chuan-Yong

2017-01-01

β-blockers are commonly used for the treatment of acute variceal bleeding in cirrhosis. Renin-angiotensin-aldosterone antagonists (angiotensin I-converting enzyme inhibitors, angiotensin receptor blockers and aldosterone antagonists) are potential therapies for portal hypertension. Several studies have compared the renin-angiotensin-aldosterone system (RAAS) inhibitor and β-blocker combination therapy vs. β-blocker monotherapy, with inconsistent results. The aim of the present study was to assess the efficacy of the RAAS inhibitor and β-blocker combination therapy vs. β-blocker monotherapy for hepatic vein pressure gradient (HVPG) reduction in cirrhosis. Studies were obtained using PubMed, Embase, Medline and Cochrane library databases up to July 2015, and the weighted mean difference (WMD) in HVPG reduction was used as a measure of treatment efficacy. In total, three studies (91 patients) were included. When compared to the β-blocker monotherapy, the RAAS inhibitor and β-blocker combination therapy resulted in a significant HVPG reduction [WMD 1.70; 95% confidence interval (CI): 0.52–2.88]. However, there was no significant difference in the heart rate reduction between the monotherapy and combination therapy groups (WMD −0.11; 95% CI: −3.51–3.29). In addition, no significant difference in the hemodynamic response was observed between the two groups (WMD 1.46; 95% CI: 0.93–2.30). In conclusion, the RAAS inhibitor and β-blocker combination therapy reduces portal hypertension significantly and to a greater extent than β-blocker monotherapy. Both therapies reduced the heart rate to similar levels; however, the RAAS inhibitor and β-blocker combination therapy reduced the mean arterial pressure to a greater extent. Due to the limited number of studies included, the data available do not allow a satisfactory comparison of adverse events. Moreover, further larger-scale trials are required in order to strengthen the results of the present study. PMID:28565796

The Leadership Practices of the Dean of Combined Arms Academy

ERIC Educational Resources Information Center

Tafere, Matebe

2014-01-01

This study is on the leadership practices of the dean of Combined Army Academy. The research is a qualitative design. The academic staff members were the participants of the study. Formal and informal conversational interview approaches, personal observation and document analysis were the instruments of the study. Thematic analysis was used for…

49 CFR Schedule D to Subpart B of... - Schedule D to Subpart B of Part 1139

Code of Federal Regulations, 2012 CFR

2012-10-01

... [Dollars in thousands] () Greyhound Lines, Inc. () Trailways combined () All study carriers Line No. and... I) Purpose. The purpose of Schedule D (Part I) is to ascertain the financial posture of Greyhound... following two bases: 1. Greyhound Lines, Inc. 2. Trailways Combined (study carriers, only) 3. All Study...

49 CFR Schedule D to Subpart B of... - Schedule D to Subpart B of Part 1139

Code of Federal Regulations, 2011 CFR

2011-10-01

... [Dollars in thousands] () Greyhound Lines, Inc. () Trailways combined () All study carriers Line No. and... I) Purpose. The purpose of Schedule D (Part I) is to ascertain the financial posture of Greyhound... following two bases: 1. Greyhound Lines, Inc. 2. Trailways Combined (study carriers, only) 3. All Study...

49 CFR Schedule D to Subpart B of... - Schedule D to Subpart B of Part 1139

Code of Federal Regulations, 2013 CFR

2013-10-01

... [Dollars in thousands] () Greyhound Lines, Inc. () Trailways combined () All study carriers Line No. and... I) Purpose. The purpose of Schedule D (Part I) is to ascertain the financial posture of Greyhound... following two bases: 1. Greyhound Lines, Inc. 2. Trailways Combined (study carriers, only) 3. All Study...

49 CFR Schedule D to Subpart B of... - Schedule D to Subpart B of Part 1139

Code of Federal Regulations, 2014 CFR

2014-10-01

... [Dollars in thousands] () Greyhound Lines, Inc. () Trailways combined () All study carriers Line No. and... I) Purpose. The purpose of Schedule D (Part I) is to ascertain the financial posture of Greyhound... following two bases: 1. Greyhound Lines, Inc. 2. Trailways Combined (study carriers, only) 3. All Study...

Effects of Problem-Based Learning on Attitude: A Meta-Analysis Study

ERIC Educational Resources Information Center

Demirel, Melek; Dagyar, Miray

2016-01-01

To date, researchers have frequently investigated students' attitudes toward courses supported by problem-based learning. There are several studies with different results in the literature. It is necessary to combine and interpret the findings of these studies through a meta-analysis method. This method aims to combine different results of similar…

Patterns of Student Employment in Russia

ERIC Educational Resources Information Center

Roshchin, Sergey; Rudakov, Victor

2017-01-01

This paper analyses the factors of combining study and work and the factors explaining intensity of work during study in Russia, based on cross-sectional survey data. The issue of how Russian students combine work and study is analysed through the set of financial, academic, social and demographic predictors, quality of university and quality of…

Combined corticosteroid and long-acting beta-agonist in one inhaler versus placebo for chronic obstructive pulmonary disease

PubMed Central

Nannini, Luis Javier; Cates, Christopher J; Lasserson, Toby J; Poole, Phillippa

2014-01-01

Background Long-acting beta-agonists and inhaled corticosteroids have both been recommended in guidelines for the treatment of chronic obstructive pulmonary disease. Their co-administration in a combined inhaler may facilitate adherence to medication regimens, and improve efficacy. Objectives To assess the efficacy of combined inhaled corticosteroid and long-acting beta-agonist preparations, compared to placebo, in the treatment of adults with chronic obstructive pulmonary disease. Search methods We searched the Cochrane Airways Group Specialised Register of trials. The date of the most recent search is April 2007. Selection criteria Studies were included if they were randomised and double-blind. Studies could compare any combined inhaled corticosteroids and long-acting beta-agonist preparation with placebo. Data collection and analysis Two authors independently assessed study risk of bias and extracted data. The primary outcomes were exacerbations, mortality and pneumonia. Health-related quality of life (measured by validated scales), lung function and side-effects were secondary outcomes. Dichotomous data were analysed as fixed effect odds ratios or rate ratios with 95% confidence intervals, and continuous data as mean differences and 95% confidence intervals. Main results Eleven studies met the inclusion criteria (6427 participants randomised). Two different combination preparations (fluticasone/salmeterol and budesonide/formoterol) were used. Study quality was good. Fluticasone/salmeterol and budesonide/formoterol both reduced the rate of exacerbations. Pooled analysis of both combination therapies indicated that exacerbations were less frequent when compared with placebo, Rate Ratio: 0.74 (95% CI 0.7 to 0.8). The clinical impact of this effect depends on the frequency of exacerbations experienced by patients. The patients included in these trials had on average 1-2 exacerbations per year which means that treatment with combination therapy would lead to a reduction of one exacerbation every two to four years in these individuals. There is an overall reduction in mortality, but this outcome is dominated by the results of TORCH and further studies on budesonide/formoterol are required. The three year number needed to treat to prevent one extra death is 36 (95% CI 21 to 258), using a baseline risk of 15.2% from the placebo arm of TORCH. Both treatments led to statistically significant improvement in health status measurements, although the clinical importance of the differences observed is open to interpretation. Symptoms and lung function assessments favoured combination treatments. There was an increase in the risk of pneumonia with combined inhalers. The three year number needed to treat for one extra case of pneumonia is 13, using a baseline risk of 12.3% from the placebo arm of TORCH. Fewer participants withdrew from studies assessing combined inhalers due to adverse events and lack of efficacy. Authors’ conclusions Compared with placebo, combination therapy led to a significant reduction of a quarter in exacerbation rates. There was a significant reduction in all-cause mortality with the addition of data from the TORCH trial. The increased risk of pneumonia is a concern, and better reporting of this outcome in future studies would be helpful. In order to draw firmer conclusions about the effects of combination therapy in a single inhaler more data are necessary, particularly in relation to the profile of adverse events and benefits in relation to different doses of inhaled corticosteroids. PMID:17943798

Overcoming IGF1R/IR Resistance Through Inhibition of MEK Signaling in Colorectal Cancer Models

PubMed Central

Flanigan, Sara A.; Pitts, Todd M.; Newton, Timothy P.; Kulikowski, Gillian N.; Tan, Aik Choon; McManus, Martine C.; Spreafico, Anna; Kachaeva, Maria I.; Selby, Heather M.; Tentler, John J.; Eckhardt, S. Gail; Leong, Stephen

2013-01-01

Purpose Results from clinical trials involving resistance to molecularly targeted therapies have revealed the importance of rational single agent and combination treatment strategies. In this study, we tested the efficacy of a type 1 insulin-like growth factor receptor (IGF1R)/insulin receptor (IR) tyrosine kinase inhibitor (TKI), OSI-906, in combination with a MEK 1/2 inhibitor based on evidence that the MAPK pathway was upregulated in colorectal cancer (CRC) cell lines that were resistant to OSI-906. Experimental Design The antiproliferative effects of OSI-906 and the MEK 1/2 inhibitor U0126, were analyzed both as single agents and in combination in 13 CRC cell lines in vitro. Apoptosis, downstream effector proteins, and cell cycle were also assessed. Additionally, the efficacy of OSI-906 combined with the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886), was evaluated in vivo using human CRC xenograft models. Results The combination of OSI-906 and U0126 resulted in synergistic effects in 11 out of 13 CRC cell lines tested. This synergy was variably associated with apoptosis or cell cycle arrest in addition to molecular effects on pro-survival pathways. The synergy was also reflected in the in vivo xenograft studies following treatment with the combination of OSI-906 and selumetinib. Conclusions Results from this study demonstrate synergistic antiproliferative effects in response to the combination of OSI-906 with a MEK 1/2 inhibitor in CRC cell line models both in vitro and in vivo, which supports the rational combination of OSI-906 with a MEK inhibitor in patients with CRC. PMID:24045180

Combined nattokinase with red yeast rice but not nattokinase alone has potent effects on blood lipids in human subjects with hyperlipidemia.

PubMed

Yang, Nae-Cherng; Chou, Chien-Wen; Chen, Chung-Yin; Hwang, Kai-Lin; Yang, Yi-Chueh

2009-01-01

The purpose of this randomized, double-blind, placebo-controlled, parallel comparison study was to evaluate the lipid-lowering effect of orally administrated nattokinase and nattokinase combined with red yeast rice (RYR) extract on blood lipids in patients with hyperlipidemia. A total of 47 patients with hyperlipidemia were assigned to one of three groups: 1. nattokinase-mono formula (50 mg/capsule), 2. combined formula of nattokinase with RYR (300 mg of extract/capsule) and 3. placebo. Subjects received a twice daily dose of two capsules for six months. The mono formula showed no effects on blood lipids until month six, while the combined formula ameliorated all of measured lipids starting from month one. In the combined group significant decreases were found with regard to: triglycerides (TG) by 15%, total cholesterol (TC) by 25%, low-density lipoprotein cholesterol (LDL-C) by 41%, TC/high-density lipoprotein cholesterol (HDL-C) ratio by 29.5%, and increases in HDL-C by 7.5%. These changes were sustained until the end of study. After controlling for baseline levels, only the combined group, but not mono group, showed a significant difference (p<0.0001) in TC, LDL-C and TC/HDL-C ratio when compared with the placebo group. In summary, this study provides long-term efficacy of nattokinase supplementation and shows that the combined formula has relatively more potent effects than the mono formula on lowering of blood lipids, suggesting that combined nattokinase with RYR will be a better neutraceutical for patients with hyperlipidemia than nattokinase alone.

The objective evaluation of aircrew protective breathing equipment : V., mask/goggles combinations for female crewmembers.

DOT National Transportation Integrated Search

1983-07-01

A study was conducted to determine the degree of respiratory and visual protection given to the female crewmember by various crew oxygen mask/goggle combinations. The acceptance criteria for the mask/goggle combinations were for 10 of 12 test subject...

Inactivation of nuclear factor κB by MIP-based drug combinations augments cell death of breast cancer cells.

PubMed

Subramaniam, Menaga; Liew, Su Ki; In, Lionel LA; Awang, Khalijah; Ahmed, Niyaz; Nagoor, Noor Hasima

2018-01-01

Drug combination therapy to treat cancer is a strategic approach to increase successful treatment rate. Optimizing combination regimens is vital to increase therapeutic efficacy with minimal side effects. In the present study, we evaluated the in vitro cytotoxicity of double and triple combinations consisting of 1'S-1'-acetoxychavicol acetate (ACA), Mycobacterium indicus pranii (MIP) and cisplatin (CDDP) against 14 various human cancer cell lines to address the need for more effective therapy. Our data show synergistic effects in MCF-7 cells treated with MIP:ACA, MIP:CDDP and MIP:ACA:CDDP combinations. The type of interaction between MIP, ACA and CDDP was evaluated based on combination index being <0.8 for synergistic effect. Identifying the mechanism of cell death based on previous studies involved intrinsic apoptosis and nuclear factor kappa B (NF-κB) and tested in Western blot analysis. Inactivation of NF-κB was confirmed by p65 and IκBα, while intrinsic apoptosis pathway activation was confirmed by caspase-9 and Apaf-1 expression. All combinations confirmed intrinsic apoptosis activation and NF-κB inactivation. Double and triple combination regimens that target induction of the same death mechanism with reduced dosage of each drug could potentially be clinically beneficial in reducing dose-related toxicities.

Bone marrow mesenchymal stem cells combined with minocycline improve spinal cord injury in a rat model

PubMed Central

Chen, Dayong; Zeng, Wei; Fu, Yunfeng; Gao, Meng; Lv, Guohua

2015-01-01

The aims of this study were to assess that the effects of bone marrow mesenchymal stem cells (BMSCs) combination with minocycline improve spinal cord injury (SCI) in rat model. In the present study, the Wistar rats were randomly divided into five groups: control group, SCI group, BMSCs group, Minocycline group and BMSCs + minocycline group. Basso, Beattie and Bresnahan (BBB) test and MPO activity were used to assess the effect of combination therapy on locomotion and neutrophil infiltration. Inflammation factors, VEGF and BDNF expression, caspase-3 activation, phosphorylation-p38MAPK, proNGF, p75NTR and RhoA expressions were estimated using commercial kits or western blot, respectively. BBB scores were significantly increased and MPO activity was significantly undermined by combination therapy. In addition, combination therapy significantly decreased inflammation factors in SCI rats. Results from western blot showed that combination therapy significantly up-regulated the protein of VEGF and BDNF expression and down-regulated the protein of phosphorylation-p38MAPK, proNGF, p75NTR and RhoA expressions in SCI rats. Combination therapy stimulation also suppressed the caspase-3 activation in SCI rats. These results demonstrated that the effects of bone marrow mesenchymal stem cells combination with minocycline improve SCI in rat model. PMID:26722382

Synergy of arbekacin-based combinations against vancomycin hetero-intermediate Staphylococcus aureus.

PubMed

Lee, Ji Young; Oh, Won Sup; Ko, Kwan Soo; Heo, Sang Taek; Moon, Chi Sook; Ki, Hyun Kyun; Kiem, Sungmin; Peck, Kyong Ran; Song, Jae Hoon

2006-04-01

This study was undertaken to evaluate the in vitro activities of arbekacin-based combination regimens against vancomycin hetero-intermediate Staphylococcus aureus (hetero-VISA). Combinations of arbekacin with vancomycin, rifampin, ampicillin-sulbactam, teicoplanin, or quinupristin-dalfopristin against seven hetero-VISA strains and two methicillin-resistant S. aureus strains were evaluated by the time-kill assay. The combinations of arbekacin with vancomycin, teicoplanin, or ampicillin-sulbactam showed the synergistic interaction against hetero-VISA strains. Data suggest that these arbekacin-based combination regimens may be useful candidates for treatment options of hetero-VISA infections.

Improved quantitation and reproducibility in multi-PET/CT lung studies by combining CT information.

PubMed

Holman, Beverley F; Cuplov, Vesna; Millner, Lynn; Endozo, Raymond; Maher, Toby M; Groves, Ashley M; Hutton, Brian F; Thielemans, Kris

2018-06-05

Matched attenuation maps are vital for obtaining accurate and reproducible kinetic and static parameter estimates from PET data. With increased interest in PET/CT imaging of diffuse lung diseases for assessing disease progression and treatment effectiveness, understanding the extent of the effect of respiratory motion and establishing methods for correction are becoming more important. In a previous study, we have shown that using the wrong attenuation map leads to large errors due to density mismatches in the lung, especially in dynamic PET scans. Here, we extend this work to the case where the study is sub-divided into several scans, e.g. for patient comfort, each with its own CT (cine-CT and 'snap shot' CT). A method to combine multi-CT information into a combined-CT has then been developed, which averages the CT information from each study section to produce composite CT images with the lung density more representative of that in the PET data. This combined-CT was applied to nine patients with idiopathic pulmonary fibrosis, imaged with dynamic 18 F-FDG PET/CT to determine the improvement in the precision of the parameter estimates. Using XCAT simulations, errors in the influx rate constant were found to be as high as 60% in multi-PET/CT studies. Analysis of patient data identified displacements between study sections in the time activity curves, which led to an average standard error in the estimates of the influx rate constant of 53% with conventional methods. This reduced to within 5% after use of combined-CTs for attenuation correction of the study sections. Use of combined-CTs to reconstruct the sections of a multi-PET/CT study, as opposed to using the individually acquired CTs at each study stage, produces more precise parameter estimates and may improve discrimination between diseased and normal lung.

Addition of citral controls ROS and reduces toxicity in 5-fluorouracil treated Schizosaccharomyces pombe cells.

PubMed

Patel, Pinaki B; Thakkar, Vasudev R

2015-03-01

In systemic therapy, chemotherapeutic drugs, often, cause considerable side effects; and combination of natural compounds lessen the extent of such effects. In the present study, combined effect of citral and 5-fluorouracil was studied in Schizosaccharomyces pombe cells. The antagonistic combination index found was at 0.01 and 0.025 mM of citral with 40 μg or higher concentration of 5-fluorouracil. The combined treatment was so effective that higher number of cells underwent apoptosis compared to individual treatment of 5-fluorouracil. Citral controlled ROS levels and increased survival of normal cells. Several differentially expressed proteins observed in the citral treatment could further help understanding its mechanism of action.

Evaluation of Sub Query Performance in SQL Server

NASA Astrophysics Data System (ADS)

Oktavia, Tanty; Sujarwo, Surya

2014-03-01

The paper explores several sub query methods used in a query and their impact on the query performance. The study uses experimental approach to evaluate the performance of each sub query methods combined with indexing strategy. The sub query methods consist of in, exists, relational operator and relational operator combined with top operator. The experimental shows that using relational operator combined with indexing strategy in sub query has greater performance compared with using same method without indexing strategy and also other methods. In summary, for application that emphasized on the performance of retrieving data from database, it better to use relational operator combined with indexing strategy. This study is done on Microsoft SQL Server 2012.

Drug combination studies of curcumin and genistein against rhodesain of Trypanosoma brucei rhodesiense.

PubMed

Ettari, Roberta; Previti, Santo; Maiorana, Santina; Allegra, Alessandro; Schirmeister, Tanja; Grasso, Silvana; Zappalà, Maria

2018-06-13

Curcumin and genistein are two natural products obtained from Curcuma longa L. and soybeans, endowed with many biological properties. Within the last years they were shown to possess also a promising antitrypanosomal activity. In the present paper, we investigated the activity of both curcumin and genistein against rhodesain, the main cysteine protease of Trypanosoma brucei rhodesiense; drug combination studies, according to Chou and Talalay method, allowed us to demonstrate a potent synergistic effect for the combination curcumin-genistein. As a matter of fact, with our experiments we observed that the combination index of curcumin-genistein is < 1 for the reduction from 10 to 90% of rhodesain activity.

DESIGN NOTE: From nanometre to millimetre: a feasibility study of the combination of scanning probe microscopy and combined optical and x-ray interferometry

NASA Astrophysics Data System (ADS)

Yacoot, Andrew; Koenders, Ludger

2003-09-01

This feasibility study investigates the potential combination of an x-ray interferometer and optical interferometer as a one-dimensional long range high resolution scanning stage for an atomic force microscope (AFM) in order to overcome the problems of non-linearity associated with conventional AFMs and interferometers. Preliminary results of measurements of the uniformity of the period of a grating used as a transfer standards show variations in period at the nanometre level.

Mindfulness-based relapse prevention combined with virtual reality cue exposure for methamphetamine use disorder: Study protocol for a randomized controlled trial.

PubMed

Chen, Xi Jing; Wang, Dong Mei; Zhou, Li Dan; Winkler, Markus; Pauli, Paul; Sui, Nan; Li, Yong Hui

2018-04-19

Mindfulness-based relapse prevention (MBRP) is a method that combines cognitive behavioral relapse prevention with mindfulness practice. Research suggests that MBRP can effectively reduce withdrawal/craving in people with substance use disorder (SUD). An important part of MBRP is to practice mindfulness meditation to cope with high-risk situations for relapse, such as stimuli and situations associated with drug taking. Virtual reality cue exposure (VRCE) may be a complementary approach to MBRP as it allows for controlled and graded presentations of various high-risk situations with distal and proximal drug cues. The aim of the study is to investigate the effects of MBRP combined with VRCE, in comparison to MBRP alone or treatment as usual, on craving and emotional responses in people with methamphetamine use disorders. The study is a parallel randomized controlled study including 180 participants with methamphetamine use disorder. Three parallel groups will receive 8 weeks of MBRP combined with VRCE, MBRP alone, or treatment as usual, respectively. Craving, virtual cue reactivity, anxiety, depression, emotion regulation, mindfulness and drug-related attention bias will be assessed at pre-treatment, post-treatment, and 3 and 6 months of follow-up. This innovative study aims at investigating the effects of MBRP combined with VRCE in people with SUD. The combined intervention may have important clinical implications for relapse prevention due to its ease of application and high cost-effectiveness. This study may also stimulate research on the neuronal and psychological mechanisms of MBRP in substance use disorder. ChiCTR-INR-17013041. Copyright © 2018 Elsevier Inc. All rights reserved.

Mineralocorticoid receptor blockade in addition to angiotensin converting enzyme inhibitor or angiotensin II receptor blocker treatment: an emerging paradigm in diabetic nephropathy: a systematic review.

PubMed

Mavrakanas, Thomas A; Gariani, Karim; Martin, Pierre-Yves

2014-02-01

Blockade of the renin-angiotensin-aldosterone system (RAAS) is a standard therapeutic intervention in diabetic patients with chronic kidney disease (CKD). Concomitant mineralocorticoid receptor blockade has been studied as a novel approach to further slow down CKD progression. We used PubMed and EMBASE databases to search for relevant literature. We included in our review eight studies in patients of at least 18 years of age, with a diagnosis of type 1 or type 2 diabetes mellitus and diabetic nephropathy, under an angiotensin converting enzyme inhibitor (ACEI) and/or an angiotensin II receptor blocker (ARB) as standard treatment. A subset of patients in each study also received a mineralocorticoid receptor blocker (MRB) (either spironolactone or eplerenone) in addition to standard treatment. Combined treatment with a mineralocorticoid receptor blocker further reduced albuminuria by 23 to 61% compared with standard treatment. Estimated glomerular filtration rate values upon study completion slightly decreased under combined treatment. Blood pressure levels upon study completion were significantly lower with combined treatment in three studies. Hyperkalemia prevalence increased in patients under combined treatment raising dropout rate up to 17%. Therefore, combined treatment by an ACEI/ARB and a MRB may further decrease albuminuria in diabetic nephropathy. This effect may be due to the specific properties of the MRB treatment. Clinicians should regularly check potassium levels because of the increased risk of hyperkalemia. Available evidence should be confirmed by an adequately powered comparative trial of the standard treatment (ACEI or ARB) versus combined treatment by an ACEI/ARB and a MRB. Copyright © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Media Combinations and Learning Styles: A Dual Coding Approach.

ERIC Educational Resources Information Center

Beacham, N. A.; Elliott, A. C.; Alty, J. L.; Al-Sharrah, A.

This paper reports initial results from a study which investigated whether different media combinations could be shown to improve students' understanding of computer-based learning materials and to determine whether student learning style affected student understanding for different media combinations. Three groups of participants were given a…

Combined Credential Programs: Pedagogic, Practical, and Ideological Concerns

ERIC Educational Resources Information Center

Young, Kathryn S.

2011-01-01

The number of teacher education programs combining general and special education teacher certification is growing. In spite of this increase, little has been known about how these programs impact preservice teachers' (PSTs) developing professional identities. This article uses a case study of one newly implemented combined credential program at a…

Using Robust Variance Estimation to Combine Multiple Regression Estimates with Meta-Analysis

ERIC Educational Resources Information Center

Williams, Ryan

2013-01-01

The purpose of this study was to explore the use of robust variance estimation for combining commonly specified multiple regression models and for combining sample-dependent focal slope estimates from diversely specified models. The proposed estimator obviates traditionally required information about the covariance structure of the dependent…

Combining large number of weak biomarkers based on AUC.

PubMed

Yan, Li; Tian, Lili; Liu, Song

2015-12-20

Combining multiple biomarkers to improve diagnosis and/or prognosis accuracy is a common practice in clinical medicine. Both parametric and non-parametric methods have been developed for finding the optimal linear combination of biomarkers to maximize the area under the receiver operating characteristic curve (AUC), primarily focusing on the setting with a small number of well-defined biomarkers. This problem becomes more challenging when the number of observations is not order of magnitude greater than the number of variables, especially when the involved biomarkers are relatively weak. Such settings are not uncommon in certain applied fields. The first aim of this paper is to empirically evaluate the performance of existing linear combination methods under such settings. The second aim is to propose a new combination method, namely, the pairwise approach, to maximize AUC. Our simulation studies demonstrated that the performance of several existing methods can become unsatisfactory as the number of markers becomes large, while the newly proposed pairwise method performs reasonably well. Furthermore, we apply all the combination methods to real datasets used for the development and validation of MammaPrint. The implication of our study for the design of optimal linear combination methods is discussed. Copyright © 2015 John Wiley & Sons, Ltd.

Combining large number of weak biomarkers based on AUC

PubMed Central

Yan, Li; Tian, Lili; Liu, Song

2018-01-01

Combining multiple biomarkers to improve diagnosis and/or prognosis accuracy is a common practice in clinical medicine. Both parametric and non-parametric methods have been developed for finding the optimal linear combination of biomarkers to maximize the area under the receiver operating characteristic curve (AUC), primarily focusing on the setting with a small number of well-defined biomarkers. This problem becomes more challenging when the number of observations is not order of magnitude greater than the number of variables, especially when the involved biomarkers are relatively weak. Such settings are not uncommon in certain applied fields. The first aim of this paper is to empirically evaluate the performance of existing linear combination methods under such settings. The second aim is to propose a new combination method, namely, the pairwise approach, to maximize AUC. Our simulation studies demonstrated that the performance of several existing methods can become unsatisfactory as the number of markers becomes large, while the newly proposed pairwise method performs reasonably well. Furthermore, we apply all the combination methods to real datasets used for the development and validation of MammaPrint. The implication of our study for the design of optimal linear combination methods is discussed. PMID:26227901

In-situ Adsorption-Biological Combined Technology Treating Sediment Phosphorus in all Fractions

NASA Astrophysics Data System (ADS)

Zhang, Y.; Wang, C.; He, F.; Liu, B.; Xu, D.; Xia, S.; Zhou, Q.; Wu, Z.

2016-07-01

The removal efficiency of sediment phosphorus (P) in all fractions with in-situ adsorption-biological combined technology was studied in West Lake, Hangzhou, China. The removal amounts of sediment Ca-P, Fe/Al-P, IP, OP and TP by the combined effect of PCFM (Porous ceramic filter media) and V. spiralis was 61 mg/kg, 249 mg/kg, 318 mg/kg, 85 mg/kg and 416 mg/kg, respectively, and the corresponding removing rate reached 10.5%, 44.6%, 27.5%, 30.6% and 29.2%. This study suggested that the combination of PCFM and V. spiralis could achieve a synergetic sediment P removal because the removal rates of the combinations were higher than the sum of that of PCFM and macrophytes used separately. From analysis of sediment microbial community and predicted function, we found that the combined PCFM and V. spiralis enhanced the function of P metabolism by increasing specific genus that belong to phylum Firmicutes and Nitrospirae. Thus it can be seen the in-situ adsorption-biological combined technology could be further applied to treat internal P loading in eutrophic waters.

Benefit of combination therapy in epilepsy: a review of the preclinical evidence with levetiracetam.

PubMed

Kaminski, Rafal M; Matagne, Alain; Patsalos, Philip N; Klitgaard, Henrik

2009-03-01

Levetiracetam (Keppra) is an antiepileptic drug (AED) characterized by a novel mechanism of action, unique profile of activity in seizure models, and broad-spectrum clinical efficacy. The present report critically reviews several preclinical studies focused on combination therapy with levetiracetam and other anticonvulsants in various seizure and epilepsy models. Administration of levetiracetam together with many different clinically used AEDs or other anticonvulsants generally enhances their protective activity and, among existing AEDs, this was particularly prevalent with valproate. The protective activity of other AEDs was also enhanced by levetiracetam, which seems to be a universal finding that is independent of seizure model or drug combination studied. However, particularly strong enhancement was observed when levetiracetam was combined with agents either enhancing GABAergic or reducing glutamatergic neurotransmission. Importantly, these combinations were not associated with exacerbation of side effects or pharmacokinetic interactions. Based on the available preclinical data, it appears that combination treatment with levetiracetam and other anticonvulsants provides additional therapeutic benefit that may be attributed to its novel and distinct mechanism of action. Moreover, combinations of levetiracetam with clinically used AEDs that enhance GABAergic inhibition may be considered for rational polytherapy, which is often necessary in drug-resistant patients.

Evaluation of synergistic antioxidant potential of complex mixtures using oxygen radical absorbance capacity (ORAC) and electron paramagnetic resonance (EPR).

PubMed

Parker, Tory L; Miller, Samantha A; Myers, Lauren E; Miguez, Fernando E; Engeseth, Nicki J

2010-01-13

Previous research has demonstrated that certain combinations of compounds result in a decrease in toxic or pro-oxidative effects, previously noted when compounds were administered singly. Thus, there is a need to study many complex interactions further. Two in vitro techniques [electron paramagnetic resonance (EPR) and oxygen radical absorbance capacity (ORAC) assays] were used in this study to assess pro- and antioxidant capacity and synergistic potential of various compounds. Rutin, p-coumaric acid, abscisic acid, ascorbic acid, and a sugar solution were evaluated individually at various concentrations and in all 26 possible combinations at concentrations found in certain foods (honey or papaya), both before and after simulated digestion. EPR results indicated sugar-containing combinations provided significantly higher antioxidant capacity; those combinations containing sugars and ascorbic acid demonstrated synergistic potential. The ORAC assay suggested additive effects, with some combinations having synergistic potential, although fewer combinations were significantly synergistic after digestion. Finally, ascorbic acid, caffeic acid, quercetin, and urate were evaluated at serum-achievable levels. EPR analysis did not demonstrate additive or synergistic potential, although ORAC analysis did, principally in combinations containing ascorbic acid.

In-situ Adsorption-Biological Combined Technology Treating Sediment Phosphorus in all Fractions

PubMed Central

Zhang, Y.; Wang, C.; He, F.; Liu, B.; Xu, D.; Xia, S.; Zhou, Q.; Wu, Z.

2016-01-01

The removal efficiency of sediment phosphorus (P) in all fractions with in-situ adsorption-biological combined technology was studied in West Lake, Hangzhou, China. The removal amounts of sediment Ca-P, Fe/Al-P, IP, OP and TP by the combined effect of PCFM (Porous ceramic filter media) and V. spiralis was 61 mg/kg, 249 mg/kg, 318 mg/kg, 85 mg/kg and 416 mg/kg, respectively, and the corresponding removing rate reached 10.5%, 44.6%, 27.5%, 30.6% and 29.2%. This study suggested that the combination of PCFM and V. spiralis could achieve a synergetic sediment P removal because the removal rates of the combinations were higher than the sum of that of PCFM and macrophytes used separately. From analysis of sediment microbial community and predicted function, we found that the combined PCFM and V. spiralis enhanced the function of P metabolism by increasing specific genus that belong to phylum Firmicutes and Nitrospirae. Thus it can be seen the in-situ adsorption-biological combined technology could be further applied to treat internal P loading in eutrophic waters. PMID:27418242

Remission of acromegaly after treatment withdrawal in patients controlled by cabergoline alone or in combination with octreotide: results from a multicenter study.

PubMed

Casagrande, A; Bronstein, M D; Jallad, R S; Mota, J I; Tabet, A; Abucham, J

2017-05-01

Remission of acromegaly has been reported after somatostatin analogs withdrawal, but not after withdrawal of combination therapy with cabergoline, and only in case reports of patients controlled by cabergoline alone. To establish the remission rates (normal IGF-1 for age/sex: IGF-1 ≤ 1.00 xULN) after withdrawal of combined treatment with octreotide LAR and cabergoline and of cabergoline alone, we prospectively studied 16 patients with acromegaly controlled by those treatments in the preceding 2 years as part of a larger study on remission of acromegaly after withdrawal of different medical treatments. Among 97 patients with controlled acromegaly included in the entire study, only 16 patients had been on combination therapy (n = 12) or cabergoline alone (n = 4). At 8 weeks after treatment withdrawal, three patients (19%) were in remission (short-term remission). At 60 weeks (long-term remission), IGF-1 levels were still in the normal range in two patients (12.5%) and remained normal up to 108 weeks after treatment withdrawal (last visit). One patient had been treated with cabergoline alone and another one with combination of octreotide and cabergoline before treatment withdrawal. Remission of acromegaly after treatment withdrawal seems to be uncommon in patients controlled by cabergoline, either as monotherapy or in combination with octreotide. In the future, larger studies and/or meta-analysis will be necessary to accurately establish the remission rates of acromegaly after withdrawal of cabergoline with or without somatostatin analogs.

Bone health nutraceuticals alter microarray mRNA gene expression: A randomized, parallel, open-label clinical study.

PubMed

Lin, Yumei; Kazlova, Valentina; Ramakrishnan, Shyam; Murray, Mary A; Fast, David; Chandra, Amitabh; Gellenbeck, Kevin W

2016-01-15

Dietary intake of fruits and vegetables has been suggested to have a role in promoting bone health. More specifically, the polyphenols they contain have been linked to physiological effects related to bone mineral density and bone metabolism. In this research, we use standard microarray analyses of peripheral whole blood from post-menopausal women treated with two fixed combinations of plant extracts standardized to polyphenol content to identify differentially expressed genes relevant to bone health. In this 28-day open-label study, healthy post-menopausal women were randomized into three groups, each receiving one of three investigational fixed combinations of plant extracts: an anti-resorptive (AR) combination of pomegranate fruit (Punica granatum L.) and grape seed (Vitis vinifera L.) extracts; a bone formation (BF) combination of quercetin (Dimorphandra mollis Benth) and licorice (Glycyrrhiza glabra L.) extracts; and a fixed combination of all four plant extracts (AR plus BF). Standard microarray analysis was performed on peripheral whole blood samples taken before and after each treatment. Annotated genes were analyzed for their association to bone health by comparison to a gene library. The AR combination down-regulated a number of genes involved in reduction of bone resorption including cathepsin G (CTSG) and tachykinin receptor 1 (TACR1). The AR combination also up-regulated genes associated with formation of extracellular matrix including heparan sulfate proteoglycan 2 (HSPG2) and hyaluronoglucosaminidase 1 (HYAL1). In contrast, treatment with the BF combination resulted in up-regulation of bone morphogenetic protein 2 (BMP-2) and COL1A1 (collagen type I α1) genes which are linked to bone and collagen formation while down-regulating genes linked to osteoclastogenesis. Treatment with a combination of all four plant extracts had a distinctly different effect on gene expression than the results of the AR and BF combinations individually. These results could be due to multiple feedback systems balancing activities of osteoblasts and osteoclasts. In summary, this ex-vivo microarray study indicated that the pomegranate, grape seed, quercetin and licorice combinations of plant extracts modulated gene expression for both osteoclastic and osteogenic processes. Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.

Chemopreventive effects of combination of honokiol and magnolol with α-santalol on skin cancer developments.

PubMed

Chilampalli, C; Zhang, X; Kaushik, R S; Young, A; Zeman, D; Hildreth, M B; Fahmy, H; Dwivedi, C

2013-06-01

α-Santalol is active component of sandalwood oil and has been shown to have chemopreventive effects against chemically and UVB-induced skin cancer development in mice. α-Santalol is also shown to have skin permeation enhancing effects. Honokiol and magnolol isolated from Magnolia officinalis bark extract have also been shown to have chemopreventive effects against chemically and UVB-induced skin cancer in mice. This study was conducted to investigate the combination effects of α-santalol, honokiol and magnolol to study any additive/synergistic effects to lower the doses required for chemoprevention. Pretreatment of combinations of α-santalol with honokiol and magnolol significantly decreased tumor multiplicity upto 75% than control, α-santalol, honokiol and magnolol alone in SKH-1 mice. Combination of α-santalol with honokiol and magnolol also decreased cell viability, proliferation, and enhanced apotosis in comparison to α-santalol, honokiol and magnolol alone in Human epidrmoid carcinoma A431 cells. Overall, the results of present study indicated combinations of α-santalol with honokiol and magnolol could provide chemoprevention of skin cancer at lower doses than given alone.

Evaluation of various mental task combinations for near-infrared spectroscopy-based brain-computer interfaces

NASA Astrophysics Data System (ADS)

Hwang, Han-Jeong; Lim, Jeong-Hwan; Kim, Do-Won; Im, Chang-Hwan

2014-07-01

A number of recent studies have demonstrated that near-infrared spectroscopy (NIRS) is a promising neuroimaging modality for brain-computer interfaces (BCIs). So far, most NIRS-based BCI studies have focused on enhancing the accuracy of the classification of different mental tasks. In the present study, we evaluated the performances of a variety of mental task combinations in order to determine the mental task pairs that are best suited for customized NIRS-based BCIs. To this end, we recorded event-related hemodynamic responses while seven participants performed eight different mental tasks. Classification accuracies were then estimated for all possible pairs of the eight mental tasks (C=28). Based on this analysis, mental task combinations with relatively high classification accuracies frequently included the following three mental tasks: "mental multiplication," "mental rotation," and "right-hand motor imagery." Specifically, mental task combinations consisting of two of these three mental tasks showed the highest mean classification accuracies. It is expected that our results will be a useful reference to reduce the time needed for preliminary tests when discovering individual-specific mental task combinations.

Ethnic differences in the effectiveness of cognitive behavioral therapy combined with medication: Comparing Asian American and white psychiatric patients.

PubMed

Tang, Jennifer Y; Li, Chieh; Rodgers, Rachel F; Ballou, Mary

2016-12-01

Several meta-analyses have demonstrated the effectiveness of treatment utilizing cognitive behavioral therapy (CBT) combined with medication. There is, however, a paucity of research comparing the effectiveness of this combined treatment with psychiatric patients from different ethnic backgrounds. This study is the first of its kind to compare the effectiveness of CBT combined with medication for Asian American and White patients' psychiatric symptom severity levels of depression, anxiety, psychological well-being, and quality of life. The study examined the effects of CBT combined with medication for 43 Asian American and 43 White Non-Hispanic patients at an acute psychiatric partial hospital. A 2×2 between-within repeated measures analysis of variance was used. Results indicated significant improvement after treatment in all symptom categories assessed for the Asian American and White patients. The findings displayed trends over the course of treatment toward a greater decrease in anxiety symptoms among Asian patients but a larger increase in functioning level among White patients. In conclusion, the findings from this study provide preliminary cross-cultural support for CBT combined with medication as a treatment in partial hospital settings and suggest that the effectiveness of such treatments is similar across cultural groups. Copyright © 2016. Published by Elsevier B.V.

Methodological issues in current practice may lead to bias in the development of biomarker combinations for predicting acute kidney injury.

PubMed

Meisner, Allison; Kerr, Kathleen F; Thiessen-Philbrook, Heather; Coca, Steven G; Parikh, Chirag R

2016-02-01

Individual biomarkers of renal injury are only modestly predictive of acute kidney injury (AKI). Using multiple biomarkers has the potential to improve predictive capacity. In this systematic review, statistical methods of articles developing biomarker combinations to predict AKI were assessed. We identified and described three potential sources of bias (resubstitution bias, model selection bias, and bias due to center differences) that may compromise the development of biomarker combinations. Fifteen studies reported developing kidney injury biomarker combinations for the prediction of AKI after cardiac surgery (8 articles), in the intensive care unit (4 articles), or other settings (3 articles). All studies were susceptible to at least one source of bias and did not account for or acknowledge the bias. Inadequate reporting often hindered our assessment of the articles. We then evaluated, when possible (7 articles), the performance of published biomarker combinations in the TRIBE-AKI cardiac surgery cohort. Predictive performance was markedly attenuated in six out of seven cases. Thus, deficiencies in analysis and reporting are avoidable, and care should be taken to provide accurate estimates of risk prediction model performance. Hence, rigorous design, analysis, and reporting of biomarker combination studies are essential to realizing the promise of biomarkers in clinical practice.

The compatibility and stability of midazolam and dexamethasone in infusion solutions.

PubMed

Good, Phillip D; Schneider, Jennifer J; Ravenscroft, Peter J

2004-05-01

The delivery of subcutaneous medication by continuous infusion is common in palliative medicine. Many centers combine multiple medications, but the analytical confirmation of the compatibility and stability of these combinations has rarely been performed. This study examined the compatibility and stability of midazolam and dexamethasone using high performance liquid chromatography. Nine different solutions were prepared in polypropylene syringes by combining these two drugs with 0.9% sodium chloride. When these two drugs were combined in a syringe, there was significant loss of midazolam over 48 hours, with only 60-80% of the initial concentration remaining in syringes stored at 35-39 degrees C. This study demonstrates that cloudiness of a solution is not the only predictor of drug loss and that drug loss may occur even in solutions that remain clear at time of preparation. The clinical implications of these results are that dexamethasone and midazolam should not be combined in syringe driver solutions.

Beam combining and SBS suppression in white noise and pseudo-random modulated amplifiers

NASA Astrophysics Data System (ADS)

Anderson, Brian; Flores, Angel; Holten, Roger; Ehrenreich, Thomas; Dajani, Iyad

2015-03-01

White noise phase modulation (WNS) and pseudo-random binary sequence phase modulation (PRBS) are effective techniques for mitigation of nonlinear effects such as stimulated Brillouin scattering (SBS); thereby paving the way for higher power narrow linewidth fiber amplifiers. However, detailed studies comparing both coherent beam combination and the SBS suppression of these phase modulation schemes have not been reported. In this study an active fiber cutback experiment is performed comparing the enhancement factor of a PRBS and WNS broadened seed as a function of linewidth and fiber length. Furthermore, two WNS and PRBS modulated fiber lasers are coherently combined to measure and compare the fringe visibility and coherence length as a function of optical path length difference. Notably, the discrete frequency comb of PRBS modulation provides a beam combining re-coherence effect where the lasers periodically come back into phase. Significantly, this may reduce path length matching complexity in coherently combined fiber laser systems.

Combination Immunotherapy in Non-small Cell Lung Cancer.

PubMed

Marmarelis, Melina E; Aggarwal, Charu

2018-05-08

Checkpoint blockade has changed the treatment landscape in non-small cell lung cancer (NSCLC), but single-agent approaches are effective for only a select subset of patients. Here, we will review the evidence for combination immunotherapies in NSCLC and the clinical data evaluating the efficacy of this approach. Clinical trials evaluating combination PD-1 and CTLA-4 blockade as well as PD-1 in combination with agents targeting IDO1, B7-H3, VEGF, and EGFR show promising results. Additional studies targeting other immune pathways like TIGIT, LAG-3, and cellular therapies are ongoing. Combination immunotherapy has the potential to improve outcomes in NSCLC. Data from early clinical trials is promising and reveals that these agents can be administered together safely without a significant increase in toxicity. Further studies are needed to evaluate their long-term safety and efficacy and to determine appropriate patient selection.

Weighted combination of LOD values oa splitted into frequency windows

NASA Astrophysics Data System (ADS)

Fernandez, L. I.; Gambis, D.; Arias, E. F.

In this analysis a one-day combined time series of LOD(length-of-day) estimates is presented. We use individual data series derived by 7 GPS and 3 SLR analysis centers, which routinely contribute to the IERS database over a recent 27-month period (Jul 1996 - Oct 1998). The result is compared to the multi-technique combined series C04 produced by the Central Bureau of the IERS that is commonly used as a reference for the study of the phenomena of Earth rotation variations. The Frequency Windows Combined Series procedure brings out a time series, which is close to C04 but shows an amplitude difference that might explain the evident periodic behavior present in the differences of these two combined series. This method could be useful to generate a new time series to be used as a reference in the high frequency variations of the Earth rotation studies.

[Sensitivity of clinical Proteus strains to antibiotics and their combinations].

PubMed

Sheina, E P; Arutcheva, A A

1978-05-01

In 1976 isolation of Proteus from wounds of patients with various purulent processes amounted to 14.5 per cent. Serotypes 0-10, 0-3 and H-3 predominated among the isolates. Sensitivity of 35 clinical strains of Proteus to 10 antibiotics, furagin and nevigramone was studied by the method of serial dilutions in liquid media. All the isolates were highly resistant to the antibiotics except gentamicin, furagin and nevigramone, the MIC of which for most of the strains was 3.12, 1.6-3.12 and 6.25-12.5 gamma/ml, respectively. The effect of 14 combinations of chemotherapeutics was also studied. The combinations of gentamicin with carbenicillin, gentamicin with ampicillin and monomycin with ampicillin proved to be most effective against the Proteus strains tested. The following combinations may be of practical value: monomycin + carbenicillin, kanamycin + ampicillin, kanamycin + carbenicillin, ampicillin + furagin, gentamicin + nevigramone. The combinations of carbenicillin with furagin and gentamicin with furagin were also rational.

Design of pulse waveform for waveform division multiple access UWB wireless communication system.

PubMed

Yin, Zhendong; Wang, Zhirui; Liu, Xiaohui; Wu, Zhilu

2014-01-01

A new multiple access scheme, Waveform Division Multiple Access (WDMA) based on the orthogonal wavelet function, is presented. After studying the correlation properties of different categories of single wavelet functions, the one with the best correlation property will be chosen as the foundation for combined waveform. In the communication system, each user is assigned to different combined orthogonal waveform. Demonstrated by simulation, combined waveform is more suitable than single wavelet function to be a communication medium in WDMA system. Due to the excellent orthogonality, the bit error rate (BER) of multiuser with combined waveforms is so close to that of single user in a synchronous system. That is to say, the multiple access interference (MAI) is almost eliminated. Furthermore, even in an asynchronous system without multiuser detection after matched filters, the result is still pretty ideal and satisfactory by using the third combination mode that will be mentioned in the study.

Teaching graphic symbol combinations to children with limited speech during shared story reading.

PubMed

Tönsing, Kerstin M; Dada, Shakila; Alant, Erna

2014-12-01

The aim of this study was to determine the effect of an intervention strategy on the production of graphic symbol combinations in children with limited speech. Four children between the ages of 6;5 and 10;8 (years;months) with limited speech participated in the study. A single-subject, multiple probe design across three different types of semantic relations was used. Generalization to untrained exemplars was also monitored. Results were mixed across the four participants: two participants learned to combine symbols across different types of relations, maintained these skills post intervention, and generalized their skills to untrained combinations; and two participants showed less consistent evidence of learning. The effects, as measured during structured probes, were strong for one participant, moderate for another, and inconclusive for the two others. Responses during shared story reading suggested that the measurement probes might have underestimated participants' ability to combine symbols.

A General Model for Estimating and Correcting the Effects of Nonindependence in Meta-Analysis.

ERIC Educational Resources Information Center

Strube, Michael J.

A general model is described which can be used to represent the four common types of meta-analysis: (1) estimation of effect size by combining study outcomes; (2) estimation of effect size by contrasting study outcomes; (3) estimation of statistical significance by combining study outcomes; and (4) estimation of statistical significance by…

"Trying to Keep up": The Experience of Combining Full-Time VET with Work

ERIC Educational Resources Information Center

Morris, Michelle

2013-01-01

Maintaining a healthy work-life relationship is important for the health and wellbeing of individuals and families. This is also true for students studying in vocational education and training (VET) who face increasing pressure to combine study and work. The intersecting commitments of work, life and study create a range of demands for…

A No-Grammar Approach to Sentence Power: John C. Mellon's Sentence-Combining Games.

ERIC Educational Resources Information Center

Cooper, Charles R.

1971-01-01

This study is concerned with increasing the rate at which children progress toward more highly differentiated sentence structure. The study recommends sentence-combining practices that will accelerate this progress. The two main purposes of grammar study have been to prevent errors in writing and to present the full range of sentence structures…

A simulator study of the combined effects of alcohol and marihuana on driving behavior--phase II

DOT National Transportation Integrated Search

1983-02-01

Author's abstract: The study described in this report investigated the effects of alcohol and marihuana, alone and in combination, on driver performance and behavior in a fully interactive driving simulator. The simulator provided the driver a comple...

The combination of scanning electron and scanning probe microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sapozhnikov, I. D.; Gorbenko, O. M., E-mail: gorolga64@gmail.com; Felshtyn, M. L.

2016-06-17

We suggest the SPM module to combine SEM and SPM methods for studying surfaces. The module is based on the original mechanical moving and scanning system. The examples of studies of the steel surface microstructure in both SEM and SPM modes are presented.

Process simulation and economic assessment of hydrothermal pretreatment and enzymatic hydrolysis of multi-feedstock lignocellulose - Separate vs combined processing.

PubMed

Ashraf, Muhammad Tahir; Schmidt, Jens Ejbye

2018-02-01

Biorefinery based on multi-feedstock lignocellulose can be viable where a sustainable supply of a single substrate is limited, for example in arid regions. Processing of mixed feedstocks has been studied in lab scale, however, its economics are less studied. In this study, an economic comparison was made between separate and combined (mixed) processing approaches for multi-feedstock lignocellulose for the production of monomeric sugars. This modular approach of focusing on sugar platform makes the results applicable for many applications using the sugars as feedstock. Feedstock considered in this study were the green and woody lignocellulose residues: Bermuda grass, Jasmine hedges, and date palm fronds. Results showed that, at an identical total feed rate, combined processing was more advantageous as compared to separate processing. A further sensitivity analysis on mixed combined processing showed that the cellulase enzyme price and feed price are the two major factors affecting the production cost. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preclinical activity of combined HDAC and KDM1A inhibition in glioblastoma

PubMed Central

Singh, Melissa M.; Johnson, Blake; Venkatarayan, Avinashnarayan; Flores, Elsa R.; Zhang, Jianping; Su, Xiaoping; Barton, Michelle; Lang, Frederick; Chandra, Joya

2015-01-01

Background Glioblastoma (GBM) is the most common and aggressive form of brain cancer. Our previous studies demonstrated that combined inhibition of HDAC and KDM1A increases apoptotic cell death in vitro. However, whether this combination also increases death of the glioma stem cell (GSC) population or has an effect in vivo is yet to be determined. Therefore, we evaluated the translational potential of combined HDAC and KDM1A inhibition on patient-derived GSCs and xenograft GBM mouse models. We also investigated the changes in transcriptional programing induced by the combination in an effort to understand the induced molecular mechanisms of GBM cell death. Methods Patient-derived GSCs were treated with the combination of vorinostat, a pan-HDAC inhibitor, and tranylcypromine, a KDM1A inhibitor, and viability was measured. To characterize transcriptional profiles associated with cell death, we used RNA-Seq and validated gene changes by RT-qPCR and protein expression via Western blot. Apoptosis was measured using DNA fragmentation assays. Orthotopic xenograft studies were conducted to evaluate the effects of the combination on tumorigenesis and to validate gene changes in vivo. Results The combination of vorinostat and tranylcypromine reduced GSC viability and displayed efficacy in the U87 xenograft model. Additionally, the combination led to changes in apoptosis-related genes, particularly TP53 and TP73 in vitro and in vivo. Conclusions These data support targeting HDACs and KDM1A in combination as a strategy for GBM and identifies TP53 and TP73 as being altered in response to treatment. PMID:25795306

Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia.

PubMed

Ferreira, António Miguel; Marques da Silva, Pedro

2017-06-01

Statin-ezetimibe combinations are a potentially advantageous therapeutic option for high-risk patients who need additional lowering of low-density lipoprotein cholesterol (LDL-C). These combinations may overcome some of the limitations of statin monotherapy by blocking both sources of cholesterol. Recently, a fixed-dose combination with atorvastatin, one of the most extensively studied statins, was approved and launched in several countries, including the USA. Depending on atorvastatin dose, this combination provides LDL-C reductions of 50-60%, triglyceride reductions of 30-40%, and high-density lipoprotein cholesterol (HDL-C) increases of 5-9%. Studies comparing the lipid-lowering efficacy of the atorvastatin-ezetimibe combination with the alternatives of statin dose titration or switching to a more potent statin consistently showed that combination therapy provided greater LDL-C reduction, translating into a greater proportion of patients achieving lipid goals. Simvastatin-ezetimibe combinations have been shown to reduce the incidence of major atherosclerotic events in several clinical settings to a magnitude that seems similar to that observed with statins for the same degree of absolute LDL-C lowering. The atorvastatin-ezetimibe combination has also been shown to induce the regression of coronary atherosclerosis measured by intravascular ultrasound in a significantly greater proportion of patients than atorvastatin alone. Atorvastatin-ezetimibe combinations are generally well tolerated. Previous concerns of a possible increase in the incidence of cancer with ezetimibe were dismissed in large trials with long follow-up periods. In this paper, we examine the rationale for an atorvastatin-ezetimibe combination, review the evidence supporting it, and discuss its potential role in the management of dyslipidemia.

Combined letrozole and clomiphene versus letrozole and clomiphene alone in infertile patients with polycystic ovary syndrome

PubMed Central

Hajishafiha, Masomeh; Dehghan, Meisam; Kiarang, Nazila; Sadegh-Asadi, Nahideh; Shayegh, Seyed Navid; Ghasemi-Rad, Mohammad

2013-01-01

Background Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age (6.8%–18%), is among the most common causes of infertility due to ovulation factors, and accounts for 55%–70% of infertility cases caused by chronic anovulation. In this study, we used a combination of letrozole and clomiphene in patients resistant to both drugs individually, and studied the effects of this combination in ovulation and pregnancy in resistant PCOS patients. Methods The study population included infertile couples diagnosed as PCOS in the wife. The women used clomiphene for at least six cycles in order to ovulate after failure to form the dominant follicle, and were then put on letrozole for four cycles. Patients who were unable to form the dominant follicle were enrolled on letrozole and clomiphene combination therapy. Results One hundred enrolled patients underwent 257 cycles of a combination of letrozole and clomiphene, in which 213 were able to form the dominant follicle (82.9%) and 44 were unable to do so (17.1%). The number of mature follicles was 2.3±1.1. The mean endometrial thickness in patients on the day of human chorionic gonadotropin administration was 8.17±1.3 mm. The pregnancy rate was 42%. Conclusion According to the results of this study, it can be proposed that in PCOS patients resistant to clomiphene and letrozole used as single agents, a combination of the two drugs can be administered before using more aggressive treatment that may have severe complications or surgery. This combination may also be used as a first-line therapy to induce ovulation in severe cases of PCOS in order to save time and expense. PMID:24348019

Combined letrozole and clomiphene versus letrozole and clomiphene alone in infertile patients with polycystic ovary syndrome.

PubMed

Hajishafiha, Masomeh; Dehghan, Meisam; Kiarang, Nazila; Sadegh-Asadi, Nahideh; Shayegh, Seyed Navid; Ghasemi-Rad, Mohammad

2013-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age (6.8%-18%), is among the most common causes of infertility due to ovulation factors, and accounts for 55%-70% of infertility cases caused by chronic anovulation. In this study, we used a combination of letrozole and clomiphene in patients resistant to both drugs individually, and studied the effects of this combination in ovulation and pregnancy in resistant PCOS patients. The study population included infertile couples diagnosed as PCOS in the wife. The women used clomiphene for at least six cycles in order to ovulate after failure to form the dominant follicle, and were then put on letrozole for four cycles. Patients who were unable to form the dominant follicle were enrolled on letrozole and clomiphene combination therapy. One hundred enrolled patients underwent 257 cycles of a combination of letrozole and clomiphene, in which 213 were able to form the dominant follicle (82.9%) and 44 were unable to do so (17.1%). The number of mature follicles was 2.3±1.1. The mean endometrial thickness in patients on the day of human chorionic gonadotropin administration was 8.17±1.3 mm. The pregnancy rate was 42%. According to the results of this study, it can be proposed that in PCOS patients resistant to clomiphene and letrozole used as single agents, a combination of the two drugs can be administered before using more aggressive treatment that may have severe complications or surgery. This combination may also be used as a first-line therapy to induce ovulation in severe cases of PCOS in order to save time and expense.

Mocetinostat combined with gemcitabine for the treatment of leiomyosarcoma: Preclinical correlates

PubMed Central

Braggio, Danielle; Zewdu, Abeba; Casadei, Lucia; Batte, Kara; Bid, Hemant Kumar; Koller, David; Yu, Peter; Iwenofu, Obiajulu Hans; Strohecker, Anne; Choy, Edwin; Lev, Dina; Pollock, Raphael

2017-01-01

Leiomyosarcoma (LMS) is a malignant soft tissue sarcoma (STS) with a dismal prognosis following metastatic disease. Chemotherapeutic intervention has demonstrated to have modest clinical efficacy with no curative potential in LMS patients. Previously, we demonstrated pan-HDAC inhibition to have a superior effect in various complex karyotypic sarcomas. In this study, our goal is to evaluate the therapeutic efficacy of mocetinostat alone and in combination with gemcitabine in LMS. Human leiomyosarcoma (LMS) cell lines were used for in vitro and in vivo studies. Compounds tested included the class I HDAC inhibitor, mocetinostat, and nucleoside analog, gemcitabine. MTS and clonogenic assays were used to evaluate the effect of mocetinostat on LMS cell growth. Cleaved caspase 3/7 analysis was used to determine the effects of mocetinostat on apoptosis. Compusyn software was used to determine in vitro synergy studies for the combination of mocetinostat plus gemcitabine. A LMS xenograft model in SCID mice was used to test the impact of mocetinostat alone, gemcitabine alone and the combination of mocetinostat plus gemcitabine. Mocetinostat abrogated LMS cell growth and clonogenic potential, and enhanced apoptosis in LMS cell lines. The combination of mocetinostat plus gemcitabine exhibited a synergistic effect in LMS cells in vitro. Similarly, mocetinostat combined with gemcitabine resulted in superior anti-LMS effects in vivo. Mocetinostat reduced the expression of gemcitabine-resistance markers RRM1, RRM2, and increased the expression of gemcitabine-sensitivity marker, hENT1, in LMS cells. LMS are aggressive, metastatic tumors with poor prognosis where effective therapeutic interventions are wanting. Our studies demonstrate the potential utility of mocetinostat combined with gemcitabine for the treatment of LMS. PMID:29186204

A numerical study of combined use of two biocontrol agents with different biocontrol mechanisms in controlling foliar pathogens.

PubMed

Xu, X-M; Jeffries, P; Pautasso, M; Jeger, M J

2011-09-01

Effective use of biocontrol agents is an important component of sustainable agriculture. A previous numerical study of a generic model showed that biocontrol efficacy was greatest for a single biocontrol agent (BCA) combining competition with mycoparasitism or antibiosis. This study uses the same mathematical model to investigate whether the biocontrol efficacy of combined use of two BCAs with different biocontrol mechanisms is greater than that of a single BCA with either or both of the two mechanisms, assuming that two BCAs occupy the same host tissue as the pathogen. Within the parameter values considered, a BCA with two biocontrol mechanisms always outperformed the combined use of two BCAs with a single but different biocontrol mechanism. Similarly, combined use of two BCAs with a single but different biocontrol mechanism is shown to be far less effective than that of a single BCA with both mechanisms. Disease suppression from combined use of two BCAs was very similar to that achieved by the more efficacious one. As expected, a higher BCA introduction rate led to increased disease suppression. Incorporation of interactions between two BCAs did not greatly affect the disease dynamics except when a mycoparasitic and, to a lesser extent, an antibiotic-producing BCA was involved. Increasing the competitiveness of a mycoparasitic BCA over a BCA whose biocontrol mechanism is either competition or antibiosis may lead to improved biocontrol initially and reduced fluctuations in disease dynamics. The present study suggests that, under the model assumptions, combined use of two BCAs with different biocontrol mechanisms in most cases only results in control efficacies similar to using the more efficacious one alone. These predictions are consistent with published experimental results, suggesting that combined use of BCAs should not be recommended without clear understanding of their main biocontrol mechanisms and relative competitiveness, and experimental evaluation.

Novel Combination of Prebiotics Galacto-Oligosaccharides and Inulin-Inhibited Aberrant Crypt Foci Formation and Biomarkers of Colon Cancer in Wistar Rats.

PubMed

Qamar, Tahir Rasool; Syed, Fatima; Nasir, Muhammad; Rehman, Habib; Zahid, Muhammad Nauman; Liu, Rui Hai; Iqbal, Sanaullah

2016-08-01

The selectivity and beneficial effects of prebiotics are mainly dependent on composition and glycosidic linkage among monosaccharide units. This is the first study to use prebiotic galacto-oligosaccharides (GOS) that contains β-1,6 and β-1,3 glycosidic linkages and the novel combination of GOS and inulin in cancer prevention. The objective of the present study is to explore the role of novel GOS and inulin against various biomarkers of colorectal cancer (CRC) and the incidence of aberrant crypt foci (ACF) in a 1,2-dimethyl hydrazine dihydrochloride (DMH)-induced rodent model. Prebiotic treatments of combined GOS and inulin (57 mg each), as well as individual doses (GOS: 76-151 mg; inulin 114 mg), were given to DMH-treated animals for 16 weeks. Our data reveal the significant preventive effect of the GOS and inulin combination against the development of CRC. It was observed that inhibition of ACF formation (55.8%) was significantly (p ≤ 0.05) higher using the GOS and inulin combination than GOS (41.4%) and inulin (51.2%) treatments alone. This combination also rendered better results on short-chain fatty acids (SCFA) and bacterial enzymatic activities. Dose-dependent effects of prebiotic treatments were also observed on cecum and fecal bacterial enzymes and on SCFA. Thus, this study demonstrated that novel combination of GOS and inulin exhibited stronger preventive activity than their individual treatments alone, and can be a promising strategy for CRC chemoprevention.

Synergistic effect of fisetin combined with sorafenib in human cervical cancer HeLa cells through activation of death receptor-5 mediated caspase-8/caspase-3 and the mitochondria-dependent apoptotic pathway.

PubMed

Lin, Ming-Te; Lin, Chia-Liang; Lin, Tzu-Yu; Cheng, Chun-Wen; Yang, Shun-Fa; Lin, Chu-Liang; Wu, Chih-Chien; Hsieh, Yi-Hsien; Tsai, Jen-Pi

2016-05-01

Combining antitumor agents with bioactive compounds is a potential strategy for improving the effect of chemotherapy on cancer cells. The goal of this study was to elucidate the antitumor effect of the flavonoid, fisetin, combined with the multikinase inhibitor, sorafenib, against human cervical cancer cells in vitro and in vivo. The combination of fisetin and sorafenib synergistically induced apoptosis in HeLa cells, which is accompanied by a marked increase in loss of mitochondrial membrane potential. Apoptosis induction was achieved by caspase-3 and caspase-8 activation which increased the ratio of Bax/Bcl-2 and caused the subsequent cleavage of PARP level while disrupting the mitochondrial membrane potential in HeLa cells. Decreased Bax/Bcl-2 ratio level and mitochondrial membrane potential were also observed in siDR5-treated HeLa cells. In addition, in vivo studies revealed that the combined fisetin and sorafenib treatment was clearly superior to sorafenib treatment alone using a HeLa xenograft model. Our study showed that the combination of fisetin and sorafenib exerted better synergistic effects in vitro and in vivo than either agent used alone against human cervical cancer, and this synergism was based on apoptotic potential through a mitochondrial- and DR5-dependent caspase-8/caspase-3 signaling pathway. This combined fisetin and sorafenib treatment represents a novel therapeutic strategy for further clinical developments in advanced cervical cancer.

Combination Therapy With Exenatide Plus Pioglitazone Versus Basal/Bolus Insulin in Patients With Poorly Controlled Type 2 Diabetes on Sulfonylurea Plus Metformin: The Qatar Study

PubMed Central

Abdul-Ghani, Muhammad; Migahid, Osama; Megahed, Ayman; Adams, John; Triplitt, Curtis; DeFronzo, Ralph A.; Zirie, Mahmoud; Jayyousi, Amin

2017-01-01

OBJECTIVE The Qatar Study was designed to examine the efficacy of combination therapy with exenatide plus pioglitazone versus basal/bolus insulin in patients with long-standing poorly controlled type 2 diabetes mellitus (T2DM) on metformin plus a sulfonylurea. RESEARCH DESIGN AND METHODS The study randomized 231 patients with poorly controlled (HbA1c >7.5%, 58 mmol/mol) T2DM on a sulfonylurea plus metformin to receive 1) pioglitazone plus weekly exenatide (combination therapy) or 2) basal plus prandial insulin (insulin therapy) to maintain HbA1c <7.0% (53 mmol/mol). RESULTS After a mean follow-up of 12 months, combination therapy caused a robust decrease in HbA1c from 10.0 ± 0.6% (86 ± 5.2 mmol/mol) at baseline to 6.1 ± 0.1% (43 ± 0.7 mmol/mol) compared with 7.1 ± 0.1% (54 ± 0.8 mmol/mol) in subjects receiving insulin therapy. Combination therapy was effective in lowering the HbA1c independent of sex, ethnicity, BMI, or baseline HbA1c. Subjects in the insulin therapy group experienced significantly greater weight gain and a threefold higher rate of hypoglycemia than patients in the combination therapy group. CONCLUSIONS Combination exenatide/pioglitazone therapy is a very effective and safe therapeutic option in patients with long-standing poorly controlled T2DM on metformin plus a sulfonylurea. PMID:28096223

Optimizing neurotrophic factor combinations for neurite outgrowth

NASA Astrophysics Data System (ADS)

Deister, C.; Schmidt, C. E.

2006-06-01

Most neurotrophic factors are members of one of three families: the neurotrophins, the glial cell-line derived neurotrophic factor family ligands (GFLs) and the neuropoietic cytokines. Each family activates distinct but overlapping cellular pathways. Several studies have shown additive or synergistic interactions between neurotrophic factors from different families, though generally only a single combination has been studied. Because of possible interactions between the neurotrophic factors, the optimum concentration of a factor in a mixture may differ from the optimum when applied individually. Additionally, the effect of combinations of neurotrophic factors from each of the three families on neurite extension is unclear. This study examines the effects of several combinations of the neurotrophin nerve growth factor (NGF), the GFL glial cell-line derived neurotrophic factor (GDNF) and the neuropoietic cytokine ciliary neurotrophic factor (CNTF) on neurite outgrowth from young rat dorsal root ganglion (DRG) explants. The combination of 50 ng ml-1 NGF and 10 ng ml-1 of each GDNF and CNTF induced the highest level of neurite outgrowth at a 752 ± 53% increase over untreated DRGs and increased the longest neurite length to 2031 ± 97 µm compared to 916 ± 64 µm for untreated DRGs. The optimum concentrations of the three factors applied in combination corresponded to the optimum concentration of each factor when applied individually. These results indicate that the efficacy of future therapies for nerve repair would be enhanced by the controlled release of a combination of neurotrophins, GFLs and neuropoietic cytokines at higher concentrations than used in previous conduit designs.

Combination of pharmacotherapy and psychotherapy in the treatment of chronic depression: A systematic review and meta-analysis

PubMed Central

2012-01-01

Background Chronic depression represents a substantial portion of depressive disorders and is associated with severe consequences. This review examined whether the combination of pharmacological treatments and psychotherapy is associated with higher effectiveness than pharmacotherapy alone via meta-analysis; and identified possible treatment effect modifiers via meta-regression-analysis. Methods A systematic search was conducted in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ISI Web of Science, BIOSIS, PsycINFO, and CINAHL. Primary efficacy outcome was a response to treatment; primary acceptance outcome was dropping out of the study. Only randomized controlled trials were considered. Results We identified 8 studies with a total of 9 relevant comparisons. Our analysis revealed small, but statistically not significant effects of combined therapies on outcomes directly related to depression (BR = 1.20) with substantial heterogeneity between studies (I² = 67%). Three treatment effect modifiers were identified: target disorders, the type of psychotherapy and the type of pharmacotherapy. Small but statistically significant effects of combined therapies on quality of life (SMD = 0.18) were revealed. No differences in acceptance rates and the long-term effects between combined treatments and pure pharmacological interventions were observed. Conclusions This systematic review could not provide clear evidence for the combination of pharmacotherapy and psychotherapy. However, due to the small amount of primary studies further research is needed for a conclusive decision. PMID:22694751

Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma: North American Brain Tumor Consortium study 05-02

PubMed Central

Lee, Eudocia Q.; Kuhn, John; Lamborn, Kathleen R.; Abrey, Lauren; DeAngelis, Lisa M.; Lieberman, Frank; Robins, H. Ian; Chang, Susan M.; Yung, W. K. Alfred; Drappatz, Jan; Mehta, Minesh P.; Levin, Victor A.; Aldape, Kenneth; Dancey, Janet E.; Wright, John J.; Prados, Michael D.; Cloughesy, Timothy F.; Gilbert, Mark R.; Wen, Patrick Y.

2012-01-01

The activity of single-agent targeted molecular therapies in glioblastoma has been limited to date. The North American Brain Tumor Consortium examined the safety, pharmacokinetics, and efficacy of combination therapy with sorafenib, a small molecule inhibitor of Raf, vascular endothelial growth factor receptor 2, and platelet-derived growth factor receptor–β, and temsirolimus (CCI-779), an inhibitor of mammalian target of rapamycin. This was a phase I/II study. The phase I component used a standard 3 × 3 dose escalation scheme to determine the safety and tolerability of this combination therapy. The phase II component used a 2-stage design; the primary endpoint was 6-month progression-free survival (PFS6) rate. Thirteen patients enrolled in the phase I component. The maximum tolerated dosage (MTD) for combination therapy was sorafenib 800 mg daily and temsirolimus 25 mg once weekly. At the MTD, grade 3 thrombocytopenia was the dose-limiting toxicity. Eighteen patients were treated in the phase II component. At interim analysis, the study was terminated and did not proceed to the second stage. No patients remained progression free at 6 months. Median PFS was 8 weeks. The toxicity of this combination therapy resulted in a maximum tolerated dose of temsirolimus that was only one-tenth of the single-agent dose. Minimal activity in recurrent glioblastoma multiforme was seen at the MTD of the 2 combined agents. PMID:23099651

Safety and maintenance of response for tofacitinib monotherapy and combination therapy in rheumatoid arthritis: an analysis of pooled data from open-label long-term extension studies

PubMed Central

Fleischmann, Roy; Wollenhaupt, Jürgen; Takiya, Liza; Maniccia, Anna; Kwok, Kenneth; Wang, Lisy; van Vollenhoven, Ronald F

2017-01-01

Objective Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. This post hoc analysis evaluated patients receiving tofacitinib monotherapy or combination therapy, as well as those who switched from monotherapy to combination therapy (mono→combo) or vice versa (combo→mono) in long-term extension (LTE) studies. Methods Data were pooled from open-label LTE studies (ORAL Sequel (NCT00413699; ongoing; data collected 14 January 2016) and NCT00661661) involving patients who participated in qualifying index studies. Efficacy outcomes included American College of Rheumatology 20/50/70 rates, change from baseline in Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4(ESR)), Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire-Disability Index and DAS28-4(ESR) and CDAI low disease activity and remission. Safety was evaluated over 96 months. Results Of the 4967 patients treated, 35.4% initiated tofacitinib monotherapy, 64.6% initiated combination therapy, 2.6% were mono→combo switchers and 7.1% were combo→mono switchers. Patients who switched multiple times were excluded. Of those who initiated monotherapy and combination therapy, 87.8% (1543/1757) and 82.0% (2631/3210), respectively, remained on the same regimen throughout the study; efficacy was maintained. Incidence rates (IRs) for serious adverse events with tofacitinib 5 mg and 10 mg twice daily, respectively, were 9.42 and 8.41 with monotherapy and 8.36 and 10.75 with combination therapy; IRs for discontinuations due to AEs were 7.13 and 6.06 with monotherapy and 7.82 and 8.06 with combination therapy (overlapping CIs). For mono→combo and combo→mono switchers, discontinuations due to AEs were experienced by 0.8% and 0.9%, respectively, within 30 days of switching. Conclusion Tofacitinib efficacy as monotherapy or combination therapy was maintained through month 48 and sustained to month 72, with minimal switching of treatment regimens. Safety was consistent over 96 months. Clinical trial registration NCT00413699 (Pre-results) and NCT00661661 (Results). PMID:29435359

ABA is required for the accumulation of APX1 and MBF1c during a combination of water deficit and heat stress

PubMed Central

Zandalinas, Sara I.; Balfagón, Damián; Arbona, Vicent; Gómez-Cadenas, Aurelio; Inupakutika, Madhuri A.; Mittler, Ron

2016-01-01

Abscisic acid (ABA) plays a key role in plant acclimation to abiotic stress. Although recent studies suggested that ABA could also be important for plant acclimation to a combination of abiotic stresses, its role in this response is currently unknown. Here we studied the response of mutants impaired in ABA signalling (abi1-1) and biosynthesis (aba1-1) to a combination of water deficit and heat stress. Both mutants displayed reduced growth, biomass, and survival when subjected to stress combination. Focusing on abi1-1, we found that although its stomata had an impaired response to water deficit, remaining significantly more open than wild type, its stomatal aperture was surprisingly reduced when subjected to the stress combination. Stomatal closure during stress combination in abi1-1 was accompanied by higher levels of H2O2 in leaves, suggesting that H2O2 might play a role in this response. In contrast to the almost wild-type stomatal closure phenotype of abi1-1 during stress combination, the accumulation of ascorbate peroxidase 1 and multiprotein bridging factor 1c proteins, required for acclimation to a combination of water deficit and heat stress, was significantly reduced in abi1-1. Our findings reveal a key function for ABA in regulating the accumulation of essential proteins during a combination of water deficit and heat stress. PMID:27497287

Naltrexone and Bupropion Combination Treatment for Smoking Cessation and Weight Loss in Patients With Schizophrenia.

PubMed

Lyu, Xuechan; Du, Jiang; Zhan, Guilai; Wu, Yujie; Su, Hang; Zhu, Youwei; Jarskog, Fredrik; Zhao, Min; Fan, Xiaoduo

2018-01-01

Objective: The rates of obesity and cigarette smoking are much higher in patients with schizophrenia compared to the general population. This study was to examine whether naltrexone and bupropion combination treatment can help weight loss and smoking cessation in patients with schizophrenia. Methods: Obese male schizophrenia patients with current cigarette smoking were randomized to receive adjunctive naltrexone (25 mg/day) and bupropion (300 mg/day) combination or placebo for 24 weeks. Twenty-two patients were enrolled in the study, and 21 patients completed the study (11 in the treatment group, and 10 in the placebo group). Body weight, body mass index (BMI), fasting lipids, smoking urge, expired carbon monoxide (CO) level and cigarettes smoked per week were measured at baseline and week 24. Results: There was no significant difference between two groups in changes in weight, BMI, fasting lipids, or cigarette smoking measures ( p 's > 0.05) Conclusion: Naltrexone and bupropion combination treatment didn't show weight loss or smoking cessation effect in patients with schizophrenia in this pilot study.Implications for future studies were discussed. ClinicalTrials.gov identifier: NCT02736474.

Naltrexone and Bupropion Combination Treatment for Smoking Cessation and Weight Loss in Patients With Schizophrenia

PubMed Central

Lyu, Xuechan; Du, Jiang; Zhan, Guilai; Wu, Yujie; Su, Hang; Zhu, Youwei; Jarskog, Fredrik; Zhao, Min; Fan, Xiaoduo

2018-01-01

Objective: The rates of obesity and cigarette smoking are much higher in patients with schizophrenia compared to the general population. This study was to examine whether naltrexone and bupropion combination treatment can help weight loss and smoking cessation in patients with schizophrenia. Methods: Obese male schizophrenia patients with current cigarette smoking were randomized to receive adjunctive naltrexone (25 mg/day) and bupropion (300 mg/day) combination or placebo for 24 weeks. Twenty-two patients were enrolled in the study, and 21 patients completed the study (11 in the treatment group, and 10 in the placebo group). Body weight, body mass index (BMI), fasting lipids, smoking urge, expired carbon monoxide (CO) level and cigarettes smoked per week were measured at baseline and week 24. Results: There was no significant difference between two groups in changes in weight, BMI, fasting lipids, or cigarette smoking measures (p's > 0.05) Conclusion: Naltrexone and bupropion combination treatment didn't show weight loss or smoking cessation effect in patients with schizophrenia in this pilot study.Implications for future studies were discussed. ClinicalTrials.gov identifier: NCT02736474. PMID:29563871

Image-Word Pairing-Congruity Effect on Affective Responses

NASA Astrophysics Data System (ADS)

Sanabria Z., Jorge C.; Cho, Youngil; Sambai, Ami; Yamanaka, Toshimasa

The present study explores the effects of familiarity on affective responses (pleasure and arousal) to Japanese ad elements, based on the schema incongruity theory. Print ads showing natural scenes (landscapes) were used to create the stimuli (images and words). An empirical study was conducted to measure subjects' affective responses to image-word combinations that varied in terms of incongruity. The level of incongruity was based on familiarity levels, and was statistically determined by a variable called ‘pairing-congruity status’. The tested hypothesis proposed that even highly familiar image-word combinations, when combined incongruously, would elicit strong affective responses. Subjects assessed the stimuli using bipolar scales. The study was effective in tracing interactions between familiarity, pleasure and arousal, although the incongruous image-word combinations did not elicit the predicted strong effects on pleasure and arousal. The results suggest a need for further research incorporating kansei (i.e., creativity) into the process of stimuli selection.

Combination monoamine oxidase inhibitor and beta-blocker treatment of migraine, with anxiety and depression.

PubMed

Merikangas, K R; Merikangas, J R

1995-11-01

This paper presents the results of a study comparing the effectiveness of a beta-adrenergic blocking agent, atenolol, a monoamine oxidase inhibitor (MAO-I), phenelzine, and the combination in treatment of 61 adults with migraine headache. The goals of the study are (1) to investigate the safety of concomitant treatment of migraine with beta-blockers and phenelzine, (2) to assess whether orthostatic hypertension and other side effects would be relieved, and (3) to compare the results of this open trial of phenelzine to those of a previous study using similar methods. Phenelzine was associated with a large decrease in the frequency and severity of migraine attacks. Anxiety and depression were also reduced by phenelzine both alone, and in combination with a beta-blocker. The results show that the combination of MAO-I's and beta-blockers can be administered safely, and can lead to the reduction in the side effects with either drug alone.

Scaling the spectral beam combining channel by multiple diode laser stacks in an external cavity

NASA Astrophysics Data System (ADS)

Meng, Huicheng; Ruan, Xu; Du, Weichuan; Wang, Zhao; Lei, Fuchuan; Yu, Junhong; Tan, Hao

2017-04-01

Spectral beam combining of a broad area diode laser is a promising technique for direct diode laser applications. We present an experimental study of three mini-bar stacks in an external cavity on spectral beam combining in conjunction with spatial beam combining. At the pump current of 70 A, a CW output power of 579 W, spectral bandwidth of 18.8 nm and electro-optical conversion efficiency of 47% are achieved. The measured M 2 values of spectral beam combining are 18.4 and 14.7 for the fast and the slow axis, respectively. The brightness of the spectral beam combining output is 232 MW · cm-2 · sr-1.

[Combined effect of sulbactam/cefoperazone and other antibiotics against clinical isolates of multi-resistant strains. II. In vitro combined effects of sulbactam/cefoperazone with imipenem/cilastatin, cefuzonam, flomoxef, amikacin or tobramycin].

PubMed

Kouda, M; Kumagai, I; Kobayashi, J; Sugai, R; Matsuzaki, H

1991-02-01

We evaluated combined effects of sulbactam/cefoperazone (SBT/CPZ) with each of imipenem/cilastatin (IPM), cefuzonam, flomoxef, amikacin (AMK) and tobramycin (TOB) against 324 clinical strains. Through this study, we obtained the following results. 1. Against Serratia marcescens and Enterobacter cloacae, good synergism was obtained by combining SBT/CPZ with IPM, AMK, or TOB. 2. Against Pseudomonas aeruginosa, good synergism was obtained by combining SBT/CPZ with AMK or TOB. 3. When SBT/CPZ was used in combination with IPM, antagonism was observed among about 45% of strains of P. aeruginosa.

Estimation of Genetic Relationships Between Individuals Across Cohorts and Platforms: Application to Childhood Height.

PubMed

Fedko, Iryna O; Hottenga, Jouke-Jan; Medina-Gomez, Carolina; Pappa, Irene; van Beijsterveldt, Catharina E M; Ehli, Erik A; Davies, Gareth E; Rivadeneira, Fernando; Tiemeier, Henning; Swertz, Morris A; Middeldorp, Christel M; Bartels, Meike; Boomsma, Dorret I

2015-09-01

Combining genotype data across cohorts increases power to estimate the heritability due to common single nucleotide polymorphisms (SNPs), based on analyzing a Genetic Relationship Matrix (GRM). However, the combination of SNP data across multiple cohorts may lead to stratification, when for example, different genotyping platforms are used. In the current study, we address issues of combining SNP data from different cohorts, the Netherlands Twin Register (NTR) and the Generation R (GENR) study. Both cohorts include children of Northern European Dutch background (N = 3102 + 2826, respectively) who were genotyped on different platforms. We explore imputation and phasing as a tool and compare three GRM-building strategies, when data from two cohorts are (1) just combined, (2) pre-combined and cross-platform imputed and (3) cross-platform imputed and post-combined. We test these three strategies with data on childhood height for unrelated individuals (N = 3124, average age 6.7 years) to explore their effect on SNP-heritability estimates and compare results to those obtained from the independent studies. All combination strategies result in SNP-heritability estimates with a standard error smaller than those of the independent studies. We did not observe significant difference in estimates of SNP-heritability based on various cross-platform imputed GRMs. SNP-heritability of childhood height was on average estimated as 0.50 (SE = 0.10). Introducing cohort as a covariate resulted in ≈2 % drop. Principal components (PCs) adjustment resulted in SNP-heritability estimates of about 0.39 (SE = 0.11). Strikingly, we did not find significant difference between cross-platform imputed and combined GRMs. All estimates were significant regardless the use of PCs adjustment. Based on these analyses we conclude that imputation with a reference set helps to increase power to estimate SNP-heritability by combining cohorts of the same ethnicity genotyped on different platforms. However, important factors should be taken into account such as remaining cohort stratification after imputation and/or phenotypic heterogeneity between and within cohorts. Whether one should use imputation, or just combine the genotype data, depends on the number of overlapping SNPs in relation to the total number of genotyped SNPs for both cohorts, and their ability to tag all the genetic variance related to the specific trait of interest.

Chemotherapy in combination with cytokine-induced killer cell transfusion: An effective therapeutic option for patients with extensive stage small cell lung cancer.

PubMed

Huang, Jianmin; Kan, Quancheng; Lan; Zhao, Xuan; Zhang, Zhen; Yang, Shuangning; Li, Hong; Wang, Liping; Xu, Li; Cheng, Zhe; Zhang, Yi

2017-05-01

In the past decade of clinical studies, the combination of chemotherapy with cytokine induced killer (CIK) cell transfusion has confirmed a promised efficacy in several types of cancer. CIK cells are a mixture of T lymphocytes, generated from peripheral blood mononuclear cells induced by multiple cytokines. This study was aimed to evaluate the clinical efficacy of chemotherapy combined with CIK- cell therapy in patients with extensive stage small cell lung cancer (ES SCLC). Forty four patients with ES SCLC were enrolled in this study. All the patients received treatment from Oct 2010 to Sep 2013 in the First Affiliated Hospital of Zhengzhou University. Included patients were equally divided into 2 groups according to the treatment strategies. Patients in the combined treatment group received chemotherapy combined with CIK-cell transfusion and patients in the control group received chemotherapy alone. The short-term effects, overall survival (OS), progress free survival (PFS) and therapy-related adverse events were analyzed retrospectively. Short-term efficacy evaluation indicated that the total response rates in the combined treatment group and control group were 40.9% (9/22) and 9.1% (2/22), respectively. There was a significant difference between the two groups (p=0.0339). Furthermore, the PFS of the combined treatment group was significantly longer than that of the control group (8 vs. 4months, P=0.005). No severe side effect was observed after transfusion of CIK cells. These results indicated that chemotherapy combined with CIK-cell immunotherapy might provide a safe and effective treatment for patients with ES SCLC. Copyright © 2016. Published by Elsevier B.V.

Combination of Peptide YY3–36 with GLP-17–36 amide Causes an Increase in First-Phase Insulin Secretion after IV Glucose

PubMed Central

Tan, Tricia M.; Salem, Victoria; Troke, Rachel C.; Alsafi, Ali; Field, Benjamin C. T.; De Silva, Akila; Misra, Shivani; Baynes, Kevin C. R.; Donaldson, Mandy; Minnion, James; Ghatei, Mohammad A.; Godsland, Ian F.

2014-01-01

Context: The combination of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) has been proposed as a potential treatment for diabetes and obesity. However, the combined effects of these hormones, PYY3–36 and GLP-17–36 amide, on glucose homeostasis are unknown. Objective: This study sought to investigate the acute effects of PYY3–36 and GLP-17–36 amide, individually and in combination, on insulin secretion and sensitivity. Setting and Design: Using a frequently sampled iv glucose tolerance test (FSIVGTT) and minimal modeling, this study measured the effects of PYY3–36 alone, GLP-17–36 amide alone, and a combination of PYY3–36 and GLP-17–36 amide on acute insulin response to glucose (AIRg) and insulin sensitivity index (SI) in 14 overweight human volunteers, studied in a clinical research facility. Results: PYY3–36 alone caused a small but nonsignificant increase in AIRg. GLP-17–36 amide alone and the combination of PYY3–36 and GLP-17–36 amide did increase AIRg significantly. No significant differences in SI were observed with any intervention. Conclusions: PYY3–36 lacks any significant acute effects on first-phase insulin secretion or SI when tested using an FSIVGTT. Both GLP-17–36 amide alone and the combination of PYY3–36 and GLP-17–36 amide increase first-phase insulin secretion. There does not seem to be any additive or synergistic effect between PYY3–36 and GLP-17–36 amide on first-phase insulin secretion. Neither hormone alone nor the combination had any significant effects on SI. PMID:25144632

Analysis of the combined effects of lanthanum and acid rain, and their mechanisms, on nitrate reductase transcription in plants.

PubMed

Xia, Binxin; Sun, Zhaoguo; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

2017-04-01

Rare earth element (REE) pollution and acid rain are major global environmental concerns, and their spatial distributions overlap. Thus, both forms of pollution combine to act on plants. Nitrogen is important for plant growth, and nitrate reductase (NR) is a key plant enzyme that catalyzes nitrogen assimilation. Studying the combined effects of REEs and acid rain on plant nitrogen-based nutrients has important environmental significance. Here, soybean (Glycine max) plants, commonly used for toxicological studies, were exposed to lanthanum (La), a REE, and acid rain to study the NR activities and NR transcriptional levels in the roots. To explain how the pollution affected the NR transcriptional level, we simultaneously observed the contents of intracellular La and nutrient elements, protoplast morphology, membrane lipid peroxidation and intracellular pH. A combined treatment of 0.08mmol/L La and pH 4.5 acid rain increased the NR activity, decreased the NR transcriptional level, increased the intracellular nutrient elements' contents and caused deformations in membrane structures. Other combined treatments significantly decreased the aforementioned parameters and caused serious damage to the membrane structures. The variation in the amplitudes of combined treatments was greater than those of individual treatments. Compared with the control and individual treatments, combined treatments increased membrane permeability, the malondialdehyde content, and intracellular H + and La contents, and with an increasing La concentration or acid strength, the change in amplitude increased. Thus, the combined effects on NR gene transcription in soybean seedling roots were related to the intracellular nutrient elements' contents, protoplast morphology, membranous lipid peroxidation, intracellular pH and La content. Copyright © 2016 Elsevier Inc. All rights reserved.

Is combined use of intravenous and intraarticular tranexamic acid superior to intravenous or intraarticular tranexamic acid alone in total knee arthroplasty? A meta-analysis of randomized controlled trials.

PubMed

Mi, Bobin; Liu, Guohui; Lv, Huijuan; Liu, Yi; Zha, Kun; Wu, Qipeng; Liu, Jing

2017-04-18

Tranexamic acid (TXA) has been proven to be effective in reducing blood loss and transfusion rate after total knee arthroplasty (TKA) without increasing the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE). Recently, an increasing number of studies have been interested in applying combined intravenous (IV) with intraarticular (IA) tranexamic acid in total knee arthroplasty. The purpose of this meta-analysis was to compare the blood loss and complications of combined TXA with IV TXA or IA TXA on TKA. Systematic search of literatures were conducted to identify related articles that were published in PubMed, MEDLINE, Embase, the Cochrane Library, SpringerLink, ClinicalTrials.gov, and Ovid from their inception to September 2016. All studies that compare blood loss and complications of combined TXA and IV TXA or IA TXA on TKA were included. Main outcomes were collected and analyzed by the Review Manager 5.3. Five studies were included in the present meta-analysis. There was significant difference in total blood loss and blood volume of drainage when compared combined TXA group with IV TXA group or IA TXA group (P < 0.05). There was no difference in transfusion rate and thromboembolic complications when comparing combined TXA with IV TXA or IA TXA alone (P > 0.05). Compared with administration of IA TXA or IV TXA alone on TKA, combined use of TXA has advantages in reducing total blood loss and blood volume of drainage without increasing the incidence of thromboembolic complications. We recommend combined TXA as the preferred option for patients undergoing TKA.

Does tablet formulation alone improve adherence and persistence: a comparison of ezetimibe fixed dose combination versus ezetimibe separate pill combination?

PubMed

Bartlett, Louise E; Pratt, Nicole; Roughead, Elizabeth E

2017-01-01

The aim of this study was to compare adherence and persistence in patients who add ezetimibe to statin therapy as a separate pill combination (SPC) or fixed dose combination (FDC). This is a retrospective cohort study of prescription data conducted in an Australian health dataset. Two cohorts were identified: those dispensed statins and subsequently ezetimibe as either SPC or FDC. We compared adherence to combination therapy using the medication possession ratio (MPR), multivariate linear and logistic regression. Persistence to initial combination medicines and any lipid-lowering therapies were analysed using Kaplan Meyer survival and Cox proportional hazards models. A total of 3651 people initiated ezetimibe SPC and 5740 ezetimibe FDC. There was no significant difference in adherence with mean MPRs: ezetimibe SPC = 0.99 (95% confidence interval 0.98-1.01) and FDC = 0.97 (95% CI 0.95-0.99). One year persistence rates to initial combination medicines were ezetimibe SPC 49.1% vs. FDC 62.4%; hazard ratio (HR) = 1.81 (95% CI 1.76-1.90). However, persistence to any lipid-lowering therapy was higher in those initiating ezetimibe SPC = 84.9% vs. FDC = 76%; HR = 0.62 (95% CI 0.55-0.72). One year persistence rates to any two lipid-lowering medicines were similar: ezetimibe SPC 65.2% and FDC 65%. In this study FDCs have little impact on either adherence or persistence to combination lipid-lowering therapy in people who have been taking statins. The benefit of higher persistence to FDCs in first episode of treatment with initial medicines is debatable as persistence to dual therapy was similar in both cohorts. © 2016 The British Pharmacological Society.

Does tablet formulation alone improve adherence and persistence: a comparison of ezetimibe fixed dose combination versus ezetimibe separate pill combination?

PubMed Central

Pratt, Nicole; Roughead, Elizabeth E.

2016-01-01

Aims The aim of this study was to compare adherence and persistence in patients who add ezetimibe to statin therapy as a separate pill combination (SPC) or fixed dose combination (FDC). Method This is a retrospective cohort study of prescription data conducted in an Australian health dataset. Two cohorts were identified: those dispensed statins and subsequently ezetimibe as either SPC or FDC. We compared adherence to combination therapy using the medication possession ratio (MPR), multivariate linear and logistic regression. Persistence to initial combination medicines and any lipid‐lowering therapies were analysed using Kaplan Meyer survival and Cox proportional hazards models. Results A total of 3651 people initiated ezetimibe SPC and 5740 ezetimibe FDC. There was no significant difference in adherence with mean MPRs: ezetimibe SPC = 0.99 (95% confidence interval 0.98–1.01) and FDC = 0.97 (95% CI 0.95–0.99). One year persistence rates to initial combination medicines were ezetimibe SPC 49.1% vs. FDC 62.4%; hazard ratio (HR) = 1.81 (95% CI 1.76–1.90). However, persistence to any lipid‐lowering therapy was higher in those initiating ezetimibe SPC = 84.9% vs. FDC = 76%; HR = 0.62 (95% CI 0.55–0.72). One year persistence rates to any two lipid‐lowering medicines were similar: ezetimibe SPC 65.2% and FDC 65%. Conclusion In this study FDCs have little impact on either adherence or persistence to combination lipid‐lowering therapy in people who have been taking statins. The benefit of higher persistence to FDCs in first episode of treatment with initial medicines is debatable as persistence to dual therapy was similar in both cohorts. PMID:27517705

A Ka-Band Wide-Bandgap Solid-State Power Amplifier: Architecture Performance Estimates

NASA Technical Reports Server (NTRS)

Epp, L.; Khan, P.; Silva, A.

2005-01-01

Motivated by recent advances in wide-bandgap (WBG) gallium nitride (GaN) semiconductor technology, there is considerable interest in developing efficient solidstate power amplifiers (SSPAs) as an alternative to the traveling-wave tube amplifier (TWTA) for space applications. This article documents the results of a study to investigate power-combining technology and SSPA architectures that can enable a 120-W, 40 percent power-added efficiency (PAE) SSPA. Results of the study indicate that architectures based on at least three power combiner designs are likely to enable the target SSPA. The proposed architectures can power combine 16 to 32 individual monolithic microwave integrated circuits (MMICs) with >80 percent combining efficiency. This corresponds to MMIC requirements of 5- to 10-W output power and >48 percent PAE. For the three proposed architectures [1], detailed analysis and design of the power combiner are presented. The first architecture studied is based on a 16-way septum combiner that offers low loss and high isolation over the design band of 31 to 36 GHz. Analysis of a 2-way prototype septum combiner had an input match >25 dB, output match >30 dB, insertion loss <0.02 dB, and isolation >30 dB over the design band. A 16-way design, based on cascading this combiner in a binary fashion, is documented. The second architecture is based on a 24-way waveguide radial combiner. A prototype 24-way radial base was analyzed to have an input match >30 dB (under equal excitation of all input ports). The match of the mode transducer that forms the output of a radial combiner was found to be >27 dB. The functional bandwidth of the radial base and mode transducer, which together will form a radial combiner/divider, exceeded the design band. The third architecture employs a 32-way, parallel-plate radial combiner. Simulation results indicated an input match >24 dB, output match >22 dB, insertion loss <0.23 dB, and adjacent port isolation >20 dB over the design band. All three architectures utilize a low-loss MMIC amplifier module based on commercial MMIC packaging and a custom microstrip-to-rectangular-waveguide transition. The insertion loss of the module is expected to be 0.45 dB over the design band.

Combining Heterogeneous Correlation Matrices: Simulation Analysis of Fixed-Effects Methods

ERIC Educational Resources Information Center

Hafdahl, Adam R.

2008-01-01

Monte Carlo studies of several fixed-effects methods for combining and comparing correlation matrices have shown that two refinements improve estimation and inference substantially. With rare exception, however, these simulations have involved homogeneous data analyzed using conditional meta-analytic procedures. The present study builds on…

The Establishment of an Inflammatory Breast Cancer Registry and Biospecimen Repository

DTIC Science & Technology

2005-08-01

8217Tamoxifen and Exemestane Triar) study, women will receive an LHRH agonist ( Triptorelin ) immediately after surgery. They will be randomised to...combine Triptorelin with Tamoxifen versus Exemestane. In both the SOFT and the TEXT studies, the new combination of ovarian ablation plus an aromatase

[Meta-analysis on effect of combined supplementation of folic acid, vitamin B12 and B6 on risk of cardio-cerebrovascular diseases in randomized control trials].

PubMed

Lan, X; Dang, S N; Zhao, Y L; Yan, H; Yan, H

2016-07-01

To evaluate the effect of the combined supplementation of folic acid, vitamin B12 and B6 on the risk of cardio-cerebrovascular diseases. The literatures of randomized control trials about the relationship between the combined supplementation of folic acid, vitamin B12 and B6 and risk of cardio-cerebrovascular diseases from 1980 to 2014 were retrieved, and the eligible studies were screened for a Meta-analysis. The study indicators were the incidences of cardiovascular disease events, myocardial infarction and stroke. The cffect indicators were relative risk(RR)and 95% confidence interval(CI). Jadad score was used for the quality evaluation of the trials used in the study. The literatures of 11 randomized control trials, involving 26 395 patients, were used in the Meta-analysis. The combined supplementation of B vitamins had no effect on the incidence of cardiovascular disease events(RR=1.00, 95% CI: 0.94-1.07)based on 8 studies. The combined supplementation of B vitamins had no effect on the incidence of myocardial infarction(RR= 1.03, 95% CI: 0.94-1.13)based on 9 studies. The combined supplementation of B vitamins could reduce the incidence of stroke by 14%(RR=0.86, 95%CI: 0.78-0.95)based on 9 studies. Compared with the control group, Taking folic acid combined with vitamin B12 and B6 could reduce the level of homocysteine by 2.53 μmol/L(95%CI:-3.93--1.12). Subgroup analysis indicated that the follow-up time, the dosage of folic acid and vitamin B12 and B6, the history of diseases had no confounding effect on the incidence of cardio-cerebrovascular disease events. But the subgroup analysis for stroke showed that with the extension of follow-up time, the supplementation of B vitamins could reduce the risk of stroke. The effect of folic acid and B12 in small dosage seemed more significant in the prevention of stroke, while the preventive effect of B6 increased with increasing dosage. The preventive effect of combined supplementation of B vitamins was more significant for the patients with a history of cardio-cerebrovascular diseases. Taking folic acid combined with vitamin B6 and B12 might have no significant effect on the incidences of cardio-cerebrovascular disease events and myocardial infarction, but could lower the risk of stroke and the level of homocysteine.

Individual patient data meta-analysis of combined treatments versus psychotherapy (with or without pill placebo), pharmacotherapy or pill placebo for adult depression: a protocol.

PubMed

Weitz, Erica; Kleiboer, Annet; van Straten, Annemieke; Hollon, Steven D; Cuijpers, Pim

2017-02-13

There are many proven treatments (psychotherapy, pharmacotherapy or their combination) for the treatment of depression. Although there is growing evidence for the effectiveness of combination treatment (psychotherapy + pharmacotherapy) over pharmacotherapy alone, psychotherapy alone or psychotherapy plus pill placebo, for depression, little is known about which specific groups of patients may respond best to combined treatment versus monotherapy. Conventional meta-analyses techniques have limitations when tasked with examining whether specific individual characteristics moderate the effect of treatment on depression. Therefore, this protocol outlines an individual patient data (IPD) meta-analysis to explore which patients, with which clinical characteristics, have better outcomes in combined treatment compared with psychotherapy (alone or with pill placebo), pharmacotherapy and pill placebo. Study searches are completed using an established database of randomised controlled trials (RCTs) on the psychological treatment of adult depression that has previously been reported. Searches were conducted in PubMed, PsycInfo, Embase and the Cochrane Central Register of Controlled Trials. RCTs comparing combination treatment (psychotherapy + pharmacotherapy) with psychotherapy (with or without pill placebo), pharmacotherapy or pill placebo for the treatment of adult depression will be included. Study authors of eligible trials will be contacted and asked to contribute IPD. Conventional meta-analysis techniques will be used to examine differences between studies that have contributed data and those that did not. Then, IPD will be harmonised and analysis using multilevel regression will be conducted to examine effect moderators of treatment outcomes. Study results outlined above will be published in peer-reviewed journals. Study results will contribute to better understanding whether certain patients respond best to combined treatment or other depression treatments and provide new information on moderators of treatment outcome that can be used by patients, clinicians and researchers. CRD42016039028. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Management of cardiovascular risk factors with pioglitazone combination therapies in type 2 diabetes: an observational cohort study

PubMed Central

2011-01-01

Background Type 2 diabetes (T2D) is strongly associated with cardiovascular risk and requires medications that improve glycemic control and other cardiovascular risk factors. The authors aimed to assess the relative effectiveness of pioglitazone (Pio), metformin (Met) and any sulfonylurea (SU) combinations in non-insulin-treated T2D patients who were failing previous hypoglycemic therapy. Methods Over a 1-year period, two multicenter, open-labeled, controlled, 1-year, prospective, observational studies evaluated patients with T2D (n = 4585) from routine clinical practice in Spain and Greece with the same protocol. Patients were eligible if they had been prescribed Pio + SU, Pio + Met or SU + Met serving as a control cohort, once they had failed with previous therapy. Anthropometric measurements, lipid and glycemic profiles, blood pressure, and the proportions of patients at microvascular and macrovascular risk were assessed. Results All study treatment combinations rendered progressive 6-month and 12-month lipid, glycemic, and blood pressure improvements. Pio combinations, especially Pio + Met, were associated with increases in HDL-cholesterol and decreases in triglycerides and in the atherogenic index of plasma. The proportion of patients at high risk decreased after 12 months in all study cohorts. Minor weight changes (gain or loss) and no treatment-related fractures occurred during the study. The safety profile was good and proved similar among treatments, except for more hypoglycemic episodes in patients receiving SU and for the occurrence of edema in patients using Pio combinations. Serious cardiovascular events were rarely reported. Conclusions In patients with T2D failing prior hypoglycemic therapies, Pio combinations with SU or Met (especially Pio + Met) improved blood lipid and glycemic profiles, decreasing the proportion of patients with a high microvascular or macrovascular risk. The combination of Pio with SU or Met may therefore be recommended for T2D second-line therapy in the routine clinical practice, particularly in patients with dyslipidemia. PMID:21314919

Collocational Processing in Light of the Phraseological Continuum Model: Does Semantic Transparency Matter?

ERIC Educational Resources Information Center

Gyllstad, Henrik; Wolter, Brent

2016-01-01

The present study investigates whether two types of word combinations (free combinations and collocations) differ in terms of processing by testing Howarth's Continuum Model based on word combination typologies from a phraseological tradition. A visual semantic judgment task was administered to advanced Swedish learners of English (n = 27) and…

Form and Function in Early Clause-Combining

ERIC Educational Resources Information Center

Lustigman, Lyle; Berman, Ruth A.

2016-01-01

The study characterizes developmental trends in early Hebrew clause-combining (CC) by analyzing the interplay between linguistic form and communicative function in different interactional settings. Analysis applied to all utterances produced by three children aged 2;0-3;0 who combined two or more clauses, either self-initiated or on the basis of…

Examining the Potential of Combining the Methods of Grounded Theory and Narrative Inquiry: A Comparative Analysis

ERIC Educational Resources Information Center

Lal, Shalini; Suto, Melinda; Ungar, Michael

2012-01-01

Increasingly, qualitative researchers are combining methods, processes, and principles from two or more methodologies over the course of a research study. Critics charge that researchers adopting combined approaches place too little attention on the historical, epistemological, and theoretical aspects of the research design. Rather than…

Motor Profile of Children with Attention Deficit Hyperactivity Disorder, Combined Type

ERIC Educational Resources Information Center

Goulardins, Juliana B.; Marques, Juliana C. Bilhar; Casella, Erasmo B.; Nascimento, Roseane O.; Oliveira, Jorge A.

2013-01-01

Objectives: The aim of this study was to assess the motor profile of children with attention deficit hyperactivity disorder (ADHD), combined type. Method: The case group consisted of 34 treatment-naive, male patients, aged 7-11 years, who had been diagnosed with ADHD, combined type, without comorbidities (except oppositional defiant disorder). The…

Evaluation of various combinations of alternative protein feedstuffs to replace soybean meal in diets for pond-raised channel catfish

USDA-ARS?s Scientific Manuscript database

A study was conducted in earthen ponds to evaluate the use of combinations of two or three alternative protein sources to replace soybean meal in diets for Channel Catfish Ictalurus punctatus. Six 28% protein diets containing various combinations of alternative protein feedstuffs including cottonse...

Repeatability and Validity of the Combined Arm-Leg (Cruiser) Ergometer

ERIC Educational Resources Information Center

Simmelink, Elisabeth K.; Wempe, Johan B.; Geertzen, Jan H. B.; Dekker, Rienk

2009-01-01

The measurement of physical fitness of lower limb amputees is difficult, as the commonly used ergometer tests have limitations. A combined arm-leg (Cruiser) ergometer might be valuable. The aim of this study was to establish the repeatability and validity of the combined arm-leg (Cruiser) ergometer. Thirty healthy volunteers carried out three…

Evaluating the Separate and Combined Effects of Positive and Negative Reinforcement on Task Compliance

ERIC Educational Resources Information Center

Bouxsein, Kelly J.; Roane, Henry S.; Harper, Tara

2011-01-01

Positive and negative reinforcement are effective for treating escape-maintained destructive behavior. The current study evaluated the separate and combined effects of these contingencies to increase task compliance. Results showed that a combination of positive and negative reinforcement was most effective for increasing compliance. (Contains 1…

Multi-Model Combination techniques for Hydrological Forecasting: Application to Distributed Model Intercomparison Project Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ajami, N K; Duan, Q; Gao, X

2005-04-11

This paper examines several multi-model combination techniques: the Simple Multi-model Average (SMA), the Multi-Model Super Ensemble (MMSE), Modified Multi-Model Super Ensemble (M3SE) and the Weighted Average Method (WAM). These model combination techniques were evaluated using the results from the Distributed Model Intercomparison Project (DMIP), an international project sponsored by the National Weather Service (NWS) Office of Hydrologic Development (OHD). All of the multi-model combination results were obtained using uncalibrated DMIP model outputs and were compared against the best uncalibrated as well as the best calibrated individual model results. The purpose of this study is to understand how different combination techniquesmore » affect the skill levels of the multi-model predictions. This study revealed that the multi-model predictions obtained from uncalibrated single model predictions are generally better than any single member model predictions, even the best calibrated single model predictions. Furthermore, more sophisticated multi-model combination techniques that incorporated bias correction steps work better than simple multi-model average predictions or multi-model predictions without bias correction.« less

Ambroxol Hydrochloride Combined with Fluconazole Reverses the Resistance of Candida albicans to Fluconazole.

PubMed

Li, Xiuyun; Zhao, Yuanhao; Huang, Xin; Yu, Cuixiang; Yang, Yilei; Sun, Shujuan

2017-01-01

In this study, we found that ambroxol hydrochloride (128 μg/mL) exhibits synergistic antifungal effects in combination with fluconazole (2 μg/mL) against resistant planktonic Candida albicans ( C. albicans ) cells. This combination also exhibited synergistic effects against resistant C. albicans biofilms in different stages (4, 8, and 12 h) according to the microdilution method. In vitro data were further confirmed by the success of this combination in treating Galleria mellonella infected by resistant C. albicans . With respect to the synergistic mechanism, our result revealed that ambroxol hydrochloride has an effect on the drug transporters of resistant C. albicans , increasing the uptake and decreasing the efflux of rhodamine 6G, a fluorescent alternate of fluconazole. This is the first study to investigate the in vitro and in vivo antifungal effects, as well as the possible synergistic mechanism of ambroxol hydrochloride in combination with fluconazole against resistant C. albicans . The results show the potential role for this drug combination as a therapeutic alternative to treat resistant C. albicans and provide insights into the development of antifungal targets and new antifungal agents.

Studies of a new multi-layer compression bandage for the treatment of venous ulceration.

PubMed

Scriven, J M; Bello, M; Taylor, L E; Wood, A J; London, N J

2000-03-01

This study aimed to develop an alternative graduated compression bandage for the treatment of venous leg ulcers. Alternative bandage components were identified and assessed for optimal performance as a graduated multi-layer compression bandage. Subsequently the physical characteristics and clinical efficacy of the optimal bandage combination was prospectively examined. Ten healthy limbs were used to develop the optimal combination and 20 limbs with venous ulceration to compare the physical properties of the two bandage types. Subsequently 42 consecutive ulcerated limbs were prospectively treated to examine the efficacy of the new bandage combination. The new combination produced graduated median (range) sub-bandage pressures (mmHg) as follows: ankle 59 (42-100), calf 36 (27-67) and knee 35 (16-67). Over a seven-day period this combination maintained a comparable level of compression with the Charing Cross system, and achieved an overall healing rate at one year of 88%. The described combination should be brought to the attention of healthcare professionals treating venous ulcers as a possible alternative to other forms of multi-layer graduated compression bandages pending prospective, randomised clinical trials.

Synergy of Arbekacin-based Combinations Against Vancomycin Hetero-intermediate Staphylococcus aureus

PubMed Central

Lee, Ji-Young; Oh, Won Sup; Ko, Kwan Soo; Heo, Sang Taek; Moon, Chi Sook; Ki, Hyun Kyun; Kiem, Sungmin; Peck, Kyong Ran

2006-01-01

This study was undertaken to evaluate the in vitro activities of arbekacin-based combination regimens against vancomycin hetero-intermediate Staphylococcus aureus (hetero-VISA). Combinations of arbekacin with vancomycin, rifampin, ampicillin-sulbactam, teicoplanin, or quinipristin-dalfopristin against seven hetero-VISA strains and two methicillin-resistant S. aureus strains were evaluated by the time-kill assay. The combinations of arbekacin with vancomycin, teicoplanin, or ampicillin-sulbactam showed the synergistic interaction against hetero-VISA strains. Data suggest that these arbekacin-based combination regimens may be useful candidates for treatment options of hetero-VISA infections. PMID:16614499

[Do different interpretative methods used for evaluation of checkerboard synergy test affect the results?].

PubMed

Ozseven, Ayşe Gül; Sesli Çetin, Emel; Ozseven, Levent

2012-07-01

In recent years, owing to the presence of multi-drug resistant nosocomial bacteria, combination therapies are more frequently applied. Thus there is more need to investigate the in vitro activity of drug combinations against multi-drug resistant bacteria. Checkerboard synergy testing is among the most widely used standard technique to determine the activity of antibiotic combinations. It is based on microdilution susceptibility testing of antibiotic combinations. Although this test has a standardised procedure, there are many different methods for interpreting the results. In many previous studies carried out with multi-drug resistant bacteria, different rates of synergy have been reported with various antibiotic combinations using checkerboard technique. These differences might be attributed to the different features of the strains. However, different synergy rates detected by checkerboard method have also been reported in other studies using the same drug combinations and same types of bacteria. It was thought that these differences in synergy rates might be due to the different methods of interpretation of synergy test results. In recent years, multi-drug resistant Acinetobacter baumannii has been the most commonly encountered nosocomial pathogen especially in intensive-care units. For this reason, multidrug resistant A.baumannii has been the subject of a considerable amount of research about antimicrobial combinations. In the present study, the in vitro activities of frequently preferred combinations in A.baumannii infections like imipenem plus ampicillin/sulbactam, and meropenem plus ampicillin/sulbactam were tested by checkerboard synergy method against 34 multi-drug resistant A.baumannii isolates. Minimum inhibitory concentration (MIC) values for imipenem, meropenem and ampicillin/sulbactam were determined by the broth microdilution method. Subsequently the activity of two different combinations were tested in the dilution range of 4 x MIC and 0.03 x MIC in 96-well checkerboard plates. The results were obtained separately using the four different interpretation methods frequently preferred by researchers. Thus, it was aimed to detect to what extent the rates of synergistic, indifferent and antagonistic interactions were affected by different interpretation methods. The differences between the interpretation methods were tested by chi-square analysis for each combination used. Statistically significant differences were detected between the four different interpretation methods for the determination of synergistic and indifferent interactions (p< 0.0001). Highest rates of synergy were observed with both combinations by the method that used the lowest fractional inhibitory concentration index of all the non-turbid wells along the turbidity/non-turbidity interface. There was no statistically significant difference between the four methods for the detection of antagonism (p> 0.05). In conclusion although there is a standard procedure for checkerboard synergy testing it fails to exhibit standard results owing to different methods of interpretation of the results. Thus, there is a need to standardise the interpretation method for checkerboard synergy testing. To determine the most appropriate method of interpretation further studies investigating the clinical benefits of synergic combinations and additionally comparing the consistency of the results obtained from the other standard combination tests like time-kill studies, are required.

The relationship between gene transcription and combinations of histone modifications

NASA Astrophysics Data System (ADS)

Cui, Xiangjun; Li, Hong; Luo, Liaofu

2012-09-01

Histone modification is an important subject of epigenetics which plays an intrinsic role in transcriptional regulation. It is known that multiple histone modifications act in a combinatorial fashion. In this study, we demonstrated that the pathways within constructed Bayesian networks can give an indication for the combinations among 12 histone modifications which have been studied in the TSS+1kb region in S. cerevisiae. After Bayesian networks for the genes with high transcript levels (H-network) and low transcript levels (L-network) were constructed, the combinations of modifications within the two networks were analyzed from the view of transcript level. The results showed that different combinations played dissimilar roles in the regulation of gene transcription when there exist differences for gene expression at transcription level.

Combination of selenium-enriched green tea polysaccharides and Huo-ji polysaccharides synergistically enhances antioxidant and immune activity in mice.

PubMed

Yuan, Chengfu; Li, Zhihong; Peng, Fan; Xiao, Fangxiang; Ren, Dongming; Xue, Hui; Chen, Tao; Mushtaq, Gohar; Kamal, Mohammad Amjad

2015-12-01

The aim of this study was to investigate the influence of a combination of selenium-enriched green tea polysaccharides (Se-GTP) and Huo-ji polysaccharides (HJP) on the immune function and antioxidant activity in mice. The results showed that the indices of spleen and thymus were markedly increased, and the activity of natural killer (NK) cell was promoted in mice treated with the combination of Se-GTP and HJP. The combined treatment of Se-GTP and HJP also reduced the content of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in splenocytes. In addition, the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were remarkably enhanced, and malondialdehyde (MDA) levels were significantly reduced in mice treated with combination of Se-GTP and HJP. Furthermore, the combined treatment of Se-GTP and HJP increased nuclear factor erythroid 2-related factor (Nrf2) expression at mRNA and protein levels in splenocytes. The effects of the combination treatment of Se-GTP and HJP in mice were stronger than with Se-GTP or HJP treatment alone. Our study suggests that the combined administration of Se-GTP and HJP can synergistically improve immune function and decrease the oxidative stress by enhancing the mechanisms involved in the clearance of free radicals. © 2015 Society of Chemical Industry.

Postantifungal effect of the combination of caspofungin with voriconazole and amphotericin B against clinical Candida krusei isolates.

PubMed

Oz, Yasemin; Kiremitci, Abdurrahman; Dag, Ilknur; Metintas, Selma; Kiraz, Nuri

2013-01-01

We evaluated the postantifungal effects (PAFEs) of caspofungin (CAS), voriconazole (VOR), amphotericin B (AmB), and the combinations of CAS + VOR and CAS + AmB against 30 clinical Candida krusei isolates at 0.25, 1 and 4 times the MIC of each individually and in the indicated combinations. Antifungals were removed after 1 hour and colony counts were performed at 0, 2, 6, 24, and 48 h. VOR did not display any measurable PAFE regardless of antifungal concentrations, while AmB and CAS exhibited dose-dependent PAFE. The most effective agent producing a prolonged PAFE in this study was CAS. Although the combination of CAS with VOR generated longer PAFEs at 0.25 and 1 times their respective MICs in comparison with CAS alone, this combination was indifferent rather than synergistic. However, the combination of CAS with AmB at 4 times their MICs exhibited the best performance, reducing the colony counts during the 48 h after removal of drugs and resulted in synergic interaction in respect to 20 (67%) isolates. Consequently, CAS has a prolonged PAFE in vitro against C. krusei isolates, and the combination of AmB + CAS may increase significantly the efficacy of CAS. Our data may be useful in optimizing dosing regimens for these agents and their combinations, although further studies are needed to explore the clinical usefulness of our results.

The combined approach to lysis utilizing eptifibatide and rt-PA in acute ischemic stroke: the CLEAR stroke trial.

PubMed

Pancioli, Arthur M; Broderick, Joseph; Brott, Thomas; Tomsick, Thomas; Khoury, Jane; Bean, Judy; del Zoppo, Gregory; Kleindorfer, Dawn; Woo, Daniel; Khatri, Pooja; Castaldo, John; Frey, James; Gebel, James; Kasner, Scott; Kidwell, Chelsea; Kwiatkowski, Thomas; Libman, Richard; Mackenzie, Richard; Scott, Phillip; Starkman, Sidney; Thurman, R Jason

2008-12-01

Multiple approaches are being studied to enhance the rate of thrombolysis for acute ischemic stroke. Treatment of myocardial infarction with a combination of a reduced-dose fibrinolytic agent and a glycoprotein (GP) IIb/IIIa receptor antagonist has been shown to improve the rate of recanalization versus fibrinolysis alone. The combined approach to lysis utilizing eptifibatide and recombinant tissue-type plasminogen activator (rt-PA) (CLEAR) stroke trial assessed the safety of treating acute ischemic stroke patients within 3 hours of symptom onset with this combination. The CLEAR trial was a National Institutes of Health/National Institute of Neurological Disorders and Stroke-funded multicenter, double-blind, randomized, dose-escalation and safety study. Patients were randomized 3:1 to either low-dose rt-PA (tier 1=0.3 mg/kg, tier 2=0.45 mg/kg) plus eptifibatide (75 microg/kg bolus followed by 0.75 microg/kg per min infusion for 2 hours) or standard-dose rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracerebral hemorrhage within 36 hours. Secondary analyses were performed regarding clinical efficacy. Ninety-four patients (40 in tier 1 and 54 in tier 2) were enrolled. The combination group of the 2 dose tiers (n=69) had a median age of 71 years and a median baseline National Institutes of Health Stroke Scale (NIHSS) score of 14, and the standard-dose rt-PA group (n=25) had a median age of 61 years and a median baseline NIHSS score of 10 (P=0.01 for NIHSS score). Fifty-two (75%) of the combination treatment group and 24 (96%) of the standard treatment group had a baseline modified Rankin scale score of 0 (P=0.04). There was 1 (1.4%; 95% CI, 0% to 4.3%) symptomatic intracranial hemorrhage in the combination group and 2 (8.0%; 95% CI, 0% to 19.2%) in the rt-PA-only arm (P=0.17). During randomization in tier 2, a review by the independent data safety monitoring board demonstrated that the safety profile of combination therapy at the tier 2 doses was such that further enrollment was statistically unlikely to indicate inadequate safety for the combination treatment group, the ultimate outcome of the study. Thus, the study was halted. There was a trend toward increased clinical efficacy of standard-dose rt-PA compared with the combination treatment group. The safety of the combination of reduced-dose rt-PA plus eptifibatide justifies further dose-ranging trials in acute ischemic stroke.

Enhancing the Therapeutic Efficacy of Cancer Treatment With Cannabinoids

PubMed Central

Yasmin-Karim, Sayeda; Moreau, Michele; Mueller, Romy; Sinha, Neeharika; Dabney, Raymond; Herman, Allen; Ngwa, Wilfred

2018-01-01

Over the years, many in vitro and in vivo studies have shown the antineoplastic effects of cannabinoids (CBDs), with reports advocating for investigations of combination therapy approaches that could better leverage these effects in clinical translation. This study explores the potential of combination approaches employing CBDs with radiotherapy (RT) or smart biomaterials toward enhancing therapeutic efficacy during treatment of pancreatic and lung cancers. In in vitro studies, clonogenic assay results showed greater effective tumor cell killing, when combining CBDs and RT. Meanwhile, in vivo study results revealed major increase in survival when employing smart biomaterials for sustained delivery of CBDs to tumor cells. The significance of these findings, considerations for further research, and viable roadmap to clinical translation are discussed. PMID:29740535

In-vitro activity of ciprofloxacin combined with flomoxef against Bacteroides fragilis, compared with that of ciprofloxacin combined with clindamycin.

PubMed

Kato, Komei; Iwai, Shigetomi; Sato, Takeshi; Harada, Tomohide; Nakagawa, Yoshiteru; Iwanaga, Hitomi; Ito, Yumiko; Takayama, Tadatoshi

2002-06-01

Using checkerboard and time-kill assays, the in-vitro activity of ciprofloxacin alone and in combination with flomoxef against clinical Bacteroides fragilis strains was evaluated. In addition, the microbiological efficacy of this combination was compared with that of ciprofloxacin plus clindamycin. In 88% of the 25 strains tested, the combination of ciprofloxacin plus flomoxef exhibited a synergistic or an additive effect, whereas only 56% of the 25 strains ( P< 0.01, chi(2) test) tested with the combination of ciprofloxacin plus clindamycin exhibited similar effects. In a time-kill study using 7 clinical strains, a synergistic or additive effect of the combination of ciprofloxacin plus flomoxef was observed in all 7 strains. In conclusion, the combination of ciprofloxacin plus flomoxef is very active against B. fragilis, suggesting that this combination may be very useful in the treatment of aerobic and B. fragilis mixed infections, because ciprofloxacin has an expanded spectrum against aerobes.

Combining computer and manual overlays—Willamette River Greenway Study

Treesearch

Asa Hanamoto; Lucille Biesbroeck

1979-01-01

We will present a method of combining computer mapping with manual overlays. An example of its use is the Willamette River Greenway Study produced for the State of Oregon Department of Transportation in 1974. This one year planning study included analysis of data relevant to a 286-mile river system. The product is a "wise use" plan which conserves the basic...

Safety of tomatillos and products containing tomatillos canned by the water-bath canning method.

PubMed

McKee, L H; Remmenga, M D; Bock, M A

1998-01-01

Three studies were conducted to evaluate the safety of tomatillos and products containing tomatillos canned by the water-bath processing method. In the first study, plain tomatillos were processed for 25, 37.5, 50 and 62.5 min. In the second study, five tomatillo/onion combinations were prepared while five tomatillo/green chile combinations were prepared in the third study. pH evaluations were conducted to determine safety in all studies using pH 4.2 as the cut-off value. No differences in the pH of plain tomatillos were detected due to processing time. All jars of plain tomatillos had pH values below 4.1. All combinations of tomatillos/onions and tomatillos/green chile containing more than 50% tomatillo had pH values below the 4.2 cut-off value. Results of the three studies indicate (1) acidification of plain tomatillos is probably unnecessary for canning by the water-bath processing method and (2) combinations of acidic tomatillos and low-acid onions or green chile must contain more than 50% tomatillos to have a pH low enough for safe water-bath processing.

Comparative study between atorvastatin and losartan on high fat diet-induced type 2 diabetes mellitus in rats.

PubMed

Mourad, Ahmed A; Heeba, Gehan H; Taye, Ashraf; El-Moselhy, Mohamed A

2013-10-01

Obesity is often associated with chronic inflammatory state which contributes to the development of insulin resistance (IR) and type 2 diabetes mellitus (T2DM). This study investigated the effects of single and combined administration of atorvastatin (ATOR, lipid-lowering drug) and losartan (LOS, angiotensin receptor antagonist) on metabolic disorders and inflammatory status that are implicated in the development of T2DM with the use of pioglitazone (PIO) as a standard antidiabetic drug. T2DM was induced in male rats by high-fat diet (HFD) feeding for 16 weeks. Oral administrations of ATOR (10 mg/kg), LOS (20 mg/kg), PIO (3 mg/kg), their binary combinations, or vehicle were started in the last 4 weeks. Fasting serum glucose, oral glucose tolerance, fasting serum insulin, IR, serum lipid profile, serum TNF-α and body composition index were determined. Results showed that all drugs and their combinations had positive impact effect on all measured parameters, and better results were achieved from binary drug combinations than administration of each drug alone. Combination of PIO with either ATOR or LOS provided better improvements on T2DM-associated metabolic abnormalities and inflammatory status with respect to each drug alone. However, the most pronounced effects of drugs and their combinations regarding the above parameters were attributed to LOS + PIO combination. In conclusion, this study indicates that combination of ATOR + PIO and, in particular, LOS + PIO can be used as promising effective therapies in the management of HFD-induced T2DM. This concept may be attributed to the combined effects of the respective monotherapies to improve lipid profile, insulin sensitivity, and TNF-α level. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

Combination of imatinib and clotrimazole enhances cell growth inhibition in T47D breast cancer cells.

PubMed

Motawi, Tarek M K; Sadik, Nermin A H; Fahim, Sally A; Shouman, Samia A

2015-05-25

Imatinib mesylate (IM), a tyrosine kinase inhibitor, is used as targeted cancer therapy. However, mono-targeting by IM does not always achieve full tumor eradication and thus it is recommended to combine IM with other anticancer agents. Clotrimazole (CLT) is an antifungal azole derivative with promising anticancer effects due to inhibiting the activity of glycolytic enzymes. The present study aimed to evaluate the effect of combining CLT with IM on breast cancer cell line in an attempt to establish effective new combination. T47D human breast cancer cell line was treated with different concentrations of IM and/or CLT for 48 h. IM-CLT interaction was determined by isobologram equation and combination index. Cell viability was confirmed by measuring LDH activity. As indicators of glycolysis inhibition, the expression of hexokinase-2 (HK-2) and 6-phosphofructo-1-kinase (PFK-1) plus the activity of intracellular lactate dehydrogenase (LDH) and pyruvate kinase (PK) were determined. In addition, glucose consumption and adenosine triphosphate (ATP) production were measured. Moreover, nitric oxide (NO), vascular endothelial growth factor (VEGF) and hypoxia inducible factor-α (HIF-α) were also determined as they are modulators for glycolysis. This study demonstrated that IM or CLT synergistically inhibited cell growth in T47D as shown by combination and dose reduction indices. The combination of 15 μM IM and 20 μM CLT significantly decreased glucose consumption, activity of both PK and intracellular LDH, while increased leaked LDH, VEGF and NO in the medium compared to each drug alone. Furthermore the combination decreased gene expression of HK-2, PFK-1 and ATP content compared to the control. In conclusion, the synergistic effect of CLT on IM cytotoxicity in T47D cell line maybe mediated through inhibition of glycolysis and increasing both NO and VEGF. Further studies are required to confirm the efficiency and safety of this combination. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Neutron therapy for salivary and thyroid gland cancer

NASA Astrophysics Data System (ADS)

Gribova, O. V.; Musabaeva, L. I.; Choynzonov, E. L.; Lisin, V. A.; Novikov, V. A.

2016-08-01

The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons for salivary gland cancer and prognostically unfavorable thyroid gland cancer. The study group comprised 127 patients with salivary gland cancer and 46 patients with thyroid gland cancer, who received neutron therapy alone and in combination with surgery. The results obtained demonstrated that the combined modality treatment including fast neutron therapy led to encouraging local control in patients with salivary and thyroid gland cancers.

Neutron therapy for salivary and thyroid gland cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gribova, O. V., E-mail: gribova79@mail.ru; Choynzonov, E. L., E-mail: nii@oncology.tomsk.ru; National Research Tomsk Polytechnic University, Lenina Avenue 30, Tomsk, 634050

The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons for salivary gland cancer and prognostically unfavorable thyroid gland cancer. The study group comprised 127 patients with salivary gland cancer and 46 patients with thyroid gland cancer, who received neutron therapy alone and in combination with surgery. The results obtained demonstrated that the combined modality treatment including fast neutron therapy led to encouraging local control in patients with salivary and thyroid gland cancers.

Amoxicillin-potassium clavulanate: a novel beta-lactamase inhibitor.

PubMed

Smith, B R; LeFrock, J L

1985-06-01

Potassium clavulanate is a novel beta-lactamase inhibitor, which, in combination, expands the spectrum of amoxicillin to include many amoxicillin-resistant organisms. Potassium clavulanate is excreted 30-50 percent unchanged renally and its plasma time-course parallels that of amoxicillin. Several studies suggest that an increased incidence of gastrointestinal side effects may occur with this combination. In the current oral formulation, its greatest utility may be in pediatric infections due to beta-lactamase-producing Haemophilus influenzae and B. cattarhalis. In adults, the combination has not been adequately studied against other effective antibiotics.

[Antihypertensive Efficacy of Fixed Combination Azilsartan Medoxomil / Chlorthalidone in Patients With Uncontrolled Arterial Hypertension].

PubMed

Kobalava, Z D; Villevalde, S V; Kulakov, V V

2017-11-01

To study effects of a fixed azilsartan medoxomil/chlorthalidone combination (Edarbi Clo) on clinical, ambulatory and central blood pressure (BP) in patients with uncontrolled arterial hypertension (AH)). Patients (n=25) with uncontrolled AH were given fixed azilsartan medoxomil/chlorthalidone combination (40 / 12.5 mg / day) for 4 weeks. After 4 weeks, in patients who did not achieve target BP levels the dose was increased up to 40 / 25 mg / day. Duration of the study was 12 weeks. After 12 weeks of treatment 88 % of patients achieved target clinical BP (.

New clinical trial studies drug combination for recurring ovarian cancer | Center for Cancer Research

Cancer.gov

A new clinical trial is studying the effectiveness of an investigational drug combination that looks to see whether reducing the supply of oxygen to the cancer cells can make ovarian cancer shrink or slow its growth in association with an enzyme that repairs DNA damage.

Effects of albendazole combined with TSII-A (a Chinese herb compound) on optic neuritis caused by Angiostrongylus cantonensis in BALB/c mice.

PubMed

Feng, Feng; Feng, Ying; Liu, Zhen; Li, Wei-Hua; Wang, Wen-Cong; Wu, Zhong-Dao; Lv, Zhiyue

2015-11-25

Angiostrongylus cantonensis (A. cantonensis) infection can lead to optic neuritis, retinal inflammation, damage to ganglion cells, demyelination of optic nerve and visual impairment. Combined therapy of albendazole and dexamethasone is a common treatment for the disease in the clinic, but it plays no role in vision recovery. Therefore, it has been necessary to explore alternative therapies to treat this disease. Previous studies reported the neuro-productive effects of two constituents of Danshen (a Chinese herb)-tanshinone II-A (TSII-A) and cryptotanshinone (CPT), and this study aims to evaluate the impacts of TSII-A or CPT combined with albendazole on optic neuritis caused by A. cantonensis infection in a murine model. To assess the effects of TSII-A or CPT combined with albendazole on optic neuritis due to the infection, mice were divided into six groups, including the normal control group, infection group and four treatment groups (albendazole group, albendazole combined with dexamethasone group, albendazole combined with CPT group and albendazole combined with TSII-A group). The infection group and treatment groups were infected with A. cantonensis and the treatment groups received interventions from 14 dpi (days post infection), respectively. At 21 dpi, the visual acuity of mice in each group was examined by visual evoked potential (VEP). The pathologic alteration of the retina and optic nerve were observed by hematoxylin and eosin (H&E) staining and transmission electronic microscopy (TEM). Infection of A. cantonensis caused prolonged VEP latency, obvious inflammatory cell infiltration in the retina, damaged retinal ganglions and retinal swelling, followed by optic nerve fibre demyelination and a decreasing number of axons at 21 dpi. In treatment groups, albendazole could not alleviate the above symptoms; albendazole combined with dexamethasone lessened the inflammation of the retina, but was futile for the other changes; however, albendazole combined with CPT and albendazole combined with TSII-A showed obvious effects on the recovery of prolonged VEP latency, destruction and reduction of ganglion cells, optic nerve demyelination and axon loss. Compared with albendazole-CPT compound, albendazole combined with TSII-A was more effective. The current study demonstrates that albendazole combined with TSII-A plays a more effective role in treating optic neuritis caused by A. cantonensis in mice than with dexamethasone, as applied in conventional treatment, indicating that albendazole combined with TSII-A might be an alternate therapy for this parasitic disease in the clinic.

Cumulative effects of prenatal-exposure to exogenous chemicals and psychosocial stress on fetal growth: Systematic-review of the human and animal evidence

PubMed Central

Morello-Frosch, Rachel; Sen, Saunak; Zeise, Lauren; Woodruff, Tracey J.

2017-01-01

Background Adverse effects of prenatal stress or environmental chemical exposures on fetal growth are well described, yet their combined effect remains unclear. Objectives To conduct a systematic review on the combined impact and interaction of prenatal exposure to stress and chemicals on developmental outcomes. Methods We used the first three steps of the Navigation Guide systematic review. We wrote a protocol, performed a robust literature search to identify relevant animal and human studies and extracted data on developmental outcomes. For the most common outcome (fetal growth), we evaluated risk of bias, calculated effect sizes for main effects of individual and combined exposures, and performed a random effects meta-analysis of those studies reporting on odds of low birthweight (LBW) by smoking and socioeconomic status (SES). Results We identified 17 human- and 22 animal-studies of combined chemical and stress exposures and fetal growth. Human studies tended to have a lower risk of bias across nine domains. Generally, we found stronger effects for chemicals than stress, and these exposures were associated with reduced fetal growth in the low-stress group and the association was often greater in high stress groups, with limited evidence of effect modification. We found smoking associated with significantly increased odds of LBW, with a greater effect for high stress (low SES; OR 4.75 (2.46–9.16)) compared to low stress (high SES; OR 1.95 (95% CI 1.53–2.48)). Animal studies generally had a high risk of bias with no significant combined effect or effect modification. Conclusions We found that despite concern for the combined effects of environmental chemicals and stress, this is still an under-studied topic, though limited available human studies indicate chemical exposures exert stronger effects than stress, and this effect is generally larger in the presence of stress. PMID:28700705

Cumulative effects of prenatal-exposure to exogenous chemicals and psychosocial stress on fetal growth: Systematic-review of the human and animal evidence.

PubMed

Vesterinen, Hanna M; Morello-Frosch, Rachel; Sen, Saunak; Zeise, Lauren; Woodruff, Tracey J

2017-01-01

Adverse effects of prenatal stress or environmental chemical exposures on fetal growth are well described, yet their combined effect remains unclear. To conduct a systematic review on the combined impact and interaction of prenatal exposure to stress and chemicals on developmental outcomes. We used the first three steps of the Navigation Guide systematic review. We wrote a protocol, performed a robust literature search to identify relevant animal and human studies and extracted data on developmental outcomes. For the most common outcome (fetal growth), we evaluated risk of bias, calculated effect sizes for main effects of individual and combined exposures, and performed a random effects meta-analysis of those studies reporting on odds of low birthweight (LBW) by smoking and socioeconomic status (SES). We identified 17 human- and 22 animal-studies of combined chemical and stress exposures and fetal growth. Human studies tended to have a lower risk of bias across nine domains. Generally, we found stronger effects for chemicals than stress, and these exposures were associated with reduced fetal growth in the low-stress group and the association was often greater in high stress groups, with limited evidence of effect modification. We found smoking associated with significantly increased odds of LBW, with a greater effect for high stress (low SES; OR 4.75 (2.46-9.16)) compared to low stress (high SES; OR 1.95 (95% CI 1.53-2.48)). Animal studies generally had a high risk of bias with no significant combined effect or effect modification. We found that despite concern for the combined effects of environmental chemicals and stress, this is still an under-studied topic, though limited available human studies indicate chemical exposures exert stronger effects than stress, and this effect is generally larger in the presence of stress.

Interventions combining motivational interviewing and cognitive behaviour to promote medication adherence: a literature review.

PubMed

Spoelstra, Sandra L; Schueller, Monica; Hilton, Melissa; Ridenour, Kimberly

2015-05-01

This article presents an integrative review of the evidence for combined motivational interviewing and cognitive behavioural interventions that promote medication adherence. We undertook this review to establish a scientific foundation for development of interventions to promote medication adherence and to guide clinical practice. The World Health Organization has designated medication adherence as a global problem. Motivational interviewing and cognitive behaviour interventions have been found to individually promote medication adherence. However, there is a gap in the literature on the effect of combined motivational interviewing and cognitive behavioural approaches to promote medication adherence. Integrative review. COCHRANE, PubMed and CINAHL were searched to access relevant studies between 2004-2014. Inclusion criteria were interventions combining motivational interviewing and cognitive behavioural therapy with medication adherence as the outcome. Articles were assessed for measures of adherence and methodological rigour. Analysis was performed using an integrative review process. Six articles met the inclusion criteria. A randomised controlled trial reported pretreatment missed doses of 5·58 and post-treatment of 0·92 and trended towards significance. Four cohort studies had effect sizes of 0·19-0·35 (p < 0·05). A case study had a pretreatment adherence rate of 25% and post-treatment 77% (p < 0·01). Although there were a limited number of studies on combined motivational interviewing and cognitive behavioural interventions, five out of six were effective at improving medication adherence. Future studies with large rigorous randomised trials are needed. This review provides clinicians with the state of the science in relation to combined motivational interviewing and cognitive behavioural therapy interventions that promote medication adherence. A summary of intervention components and talking points are provided to aid nurses in informing decision-making and translating evidence into practice. © 2014 John Wiley & Sons Ltd.

Evolving methods to combine cognitive and physical training for individuals with mild cognitive impairment: study protocol for a randomized controlled study.

PubMed

Lee, Ya-Yun; Wu, Ching-Yi; Teng, Ching-Hung; Hsu, Wen-Chuin; Chang, Ku-Chou; Chen, Poyu

2016-10-28

Nonpharmacologic interventions, such as cognitive training or physical exercise, are effective in improving cognitive functions for older adults with mild cognitive impairment (MCI). Some researchers have proposed that combining physical exercise with cognitive training may augment the benefits of cognition. However, strong evidence is lacking regarding whether a combined therapy is superior to a single type of training for older adults with MCI. Moreover, which combination approach - combining physical exercise with cognitive training sequentially or simultaneously - is more advantageous for cognitive improvement is not yet clear. This proposed study is designed to clarify these questions. This study is a single-blinded, multicenter, randomized controlled trial. Eighty individuals with MCI will be recruited and randomly assigned to cognitive training (COG), physical exercise training (PE), sequential training (SEQ), and dual-task training (DUAL) groups. The intervention programs will be 90 min/day, 2-3 days/week, for a total of 36 training sessions. The participants in the SEQ group will first perform 45 min of physical exercise followed by 45 min of cognitive training, whereas those in the DUAL group will perform physical exercise and cognitive training simultaneously. Participants will be assessed at baseline, after the intervention, and at 6-month follow-up. The primary cognitive outcome tests will include the Montreal Cognitive Assessment and the color-naming Stroop test. Other outcomes will include assessments that evaluate the cognitive, physical, and daily functions of older adults with MCI. The results of this proposed study will provide important information regarding the feasibility and intervention effects of combining physical exercise and cognitive training for older individuals with MCI. ClinicalTrials.gov Identifier: NCT02512627 , registered on 20 July 2015.

Comparative hygienic assessment of active ingredients content in the air environment after treatment of cereal spiked crops by combined fungicides.

PubMed

Kondratiuk, Mykola; Blagaia, Anna; Pelo, Ihor

2018-01-01

Introduction: The quality of the air environment significantly affects the health of the population. Chemical plant protection products in the spring and summer time may be the main pollutants of the air environment in rural areas. Chemical plant protection products are dangerous substances of anthropogenic origin. If applying pesticides in high concentrations, the risk of poisoning by active ingredients of pesticide preparations in workers directly contacting with it increases. The aim: Comparative hygienic assessment of active ingredients content in the air environment after treatment of cereal spiked crops by combined fungicides was the aim of the work. Materials and methods: Active ingredients of the studied combined fungicides, samples of air, and swabs from workers' skin and stripes from overalls were materials of the research. Methods of full-scale in-field hygienic experiment, gas-liquid chromatography, high-performance liquid chromatography, as well as statistical and bibliographic methods were used in the research. Results and conclusions: Active ingredients of the studied combined fungicides were not detected in the working zone air and atmospheric air at the levels exceeding the limits of its detection by appropriate chromatography methods. Findings confirmed the air environment safety for agricultural workers and rural population if studied combined fungicides are applied following the hygienically approved suggested application rates and in accordance of good agricultural practice rules. However the possible complex risk for workers after certain studied fungicides application may be higher than acceptable due to the elevated values for dermal effects. The complex risk was higher than acceptable in еру case of aerial spraying of both studied fungicides, meanwhile only one combination of active ingredients revealed possible risk for workers applying fungicides by rod method of cereal spiked crops treatment.

Synergistic Killing of Multidrug-Resistant Pseudomonas aeruginosa at Multiple Inocula by Colistin Combined with Doripenem in an In Vitro Pharmacokinetic/Pharmacodynamic Model ▿

PubMed Central

Bergen, Phillip J.; Tsuji, Brian T.; Bulitta, Jurgen B.; Forrest, Alan; Jacob, Jovan; Sidjabat, Hanna E.; Paterson, David L.; Nation, Roger L.; Li, Jian

2011-01-01

Combination therapy may be required for multidrug-resistant (MDR) Pseudomonas aeruginosa. The aim of this study was to systematically investigate bacterial killing and emergence of colistin resistance with colistin and doripenem combinations against MDR P. aeruginosa. Studies were conducted in a one-compartment in vitro pharmacokinetic/pharmacodynamic model for 96 h at two inocula (∼106 and ∼108 CFU/ml) against a colistin-heteroresistant reference strain (ATCC 27853) and a colistin-resistant MDR clinical isolate (19147 n/m). Four combinations utilizing clinically achievable concentrations were investigated. Microbiological response was examined by log changes and population analysis profiles. Colistin (constant concentrations of 0.5 or 2 mg/liter) plus doripenem (peaks of 2.5 or 25 mg/liter every 8 h; half-life, 1.5 h) substantially increased bacterial killing against both strains at the low inoculum, while combinations containing colistin at 2 mg/liter increased activity against ATCC 27853 at the high inoculum; only colistin at 0.5 mg/liter plus doripenem at 2.5 mg/liter failed to improve activity against 19147 n/m at the high inoculum. Combinations were additive or synergistic against ATCC 27853 in 16 and 11 of 20 cases (4 combinations across 5 sample points) at the 106- and 108-CFU/ml inocula, respectively; the corresponding values for 19147 n/m were 16 and 9. Combinations containing doripenem at 25 mg/liter resulted in eradication of 19147 n/m at the low inoculum and substantial reductions in regrowth (including to below the limit of detection at ∼50 h) at the high inoculum. Emergence of colistin-resistant subpopulations of ATCC 27853 was substantially reduced and delayed with combination therapy. This investigation provides important information for optimization of colistin-doripenem combinations. PMID:21911563

Using Active Learning for Speeding up Calibration in Simulation Models.

PubMed

Cevik, Mucahit; Ergun, Mehmet Ali; Stout, Natasha K; Trentham-Dietz, Amy; Craven, Mark; Alagoz, Oguzhan

2016-07-01

Most cancer simulation models include unobservable parameters that determine disease onset and tumor growth. These parameters play an important role in matching key outcomes such as cancer incidence and mortality, and their values are typically estimated via a lengthy calibration procedure, which involves evaluating a large number of combinations of parameter values via simulation. The objective of this study is to demonstrate how machine learning approaches can be used to accelerate the calibration process by reducing the number of parameter combinations that are actually evaluated. Active learning is a popular machine learning method that enables a learning algorithm such as artificial neural networks to interactively choose which parameter combinations to evaluate. We developed an active learning algorithm to expedite the calibration process. Our algorithm determines the parameter combinations that are more likely to produce desired outputs and therefore reduces the number of simulation runs performed during calibration. We demonstrate our method using the previously developed University of Wisconsin breast cancer simulation model (UWBCS). In a recent study, calibration of the UWBCS required the evaluation of 378 000 input parameter combinations to build a race-specific model, and only 69 of these combinations produced results that closely matched observed data. By using the active learning algorithm in conjunction with standard calibration methods, we identify all 69 parameter combinations by evaluating only 5620 of the 378 000 combinations. Machine learning methods hold potential in guiding model developers in the selection of more promising parameter combinations and hence speeding up the calibration process. Applying our machine learning algorithm to one model shows that evaluating only 1.49% of all parameter combinations would be sufficient for the calibration. © The Author(s) 2015.

Anticancer activity of the type I insulin-like growth factor receptor antagonist, ganitumab, in combination with the death receptor 5 agonist, conatumumab.

PubMed

Tabernero, Josep; Chawla, Sant P; Kindler, Hedy; Reckamp, Karen; Chiorean, E Gabriela; Azad, Nilofer S; Lockhart, A Craig; Hsu, Cheng-Pang; Baker, Nigel F; Galimi, Francesco; Beltran, Pedro; Baselga, José

2015-03-01

Agents targeting the insulin-like growth factor receptor type 1 (IGF1R) have shown antitumor activity. Based on the evidence for interaction between the IGF-1 and TRAIL pathways, we hypothesized that the combination of ganitumab (monoclonal antibody to IGF1R) with the pro-apoptotic death receptor 5 agonist, conatumumab, might increase antitumor response. Ganitumab and conatumumab were tested in combination in a Colo-205 xenograft model. Part 1 of the clinical study was a phase Ib program of three doses of conatumumab (1, 3, 15 mg/kg) in combination with 18 mg/kg ganitumab to determine the maximum tolerated dose (MTD) in patients with advanced solid tumors. Part 2 was conducted in six cohorts with advanced non-small cell lung cancer (squamous or non-squamous histology), colorectal cancer, sarcoma, pancreatic cancer, or ovarian cancer, treated at the recommended doses of the combination. The combination was significantly more active in the Colo-205 xenograft model than either single agent alone (p < 0.0015). In part 1 of the clinical study, no dose-limiting toxicities were observed and the MTD of conatumumab was 15 mg/kg in combination with 18 mg/kg ganitumab. In part 2, 78 patients were treated and there were no objective responses but 28 patients (36 %) had stable disease (median 46 days, range 0-261). The combination was well-tolerated with no new toxicities. In conclusion, the combination of ganitumab and conatumumab was well-tolerated but had no objective responses in the population tested. The successful future application of this combination of antitumor mechanisms may rely on the identification of predictive biomarkers.

Efficacy and Safety of Long-term Coadministration of Fenofibrate and Ezetimibe in Patients with Combined Hyperlipidemia: Results of the EFECTL Study

PubMed Central

Yamashita, Shizuya; Nakaya, Noriaki; Sasaki, Jun; Kono, Suminori

2017-01-01

Aim: We investigated the safety and efficacy of a long-term combination therapy with fenofibrate and ezetimibe in Japanese patients with combined hyperlipidemia, in comparison with fenofibrate or ezetimibe alone. Methods: The study was a three-arm parallel-group, open-label randomized trial. Eligible patients were assigned to a combination therapy with fenofibrate (200 mg/day in capsule form or 160 mg/day in tablet form) and ezetimibe (10 mg/day), the fenofibrate monotherapy, or the ezetimibe monotherapy, which lasted for 52 weeks. The changes in serum low-density lipoprotein (LDL) cholesterol and triglycerides were the primary outcomes. Results: A total of 236 patients were assigned to one of the three treatments, and the number of patients included in the final analysis was 107 in the combination therapy, 52 in the fenofibrate monotherapy, and 51 in the ezetimibe monotherapy. Mean ± SD changes in LDL cholesterol were −24.2% ± 14.7% with combination therapy, −16.0% ± 16.0% with fenofibrate alone, and −17.4% ± 10.1% with ezetimibe alone. The combination therapy resulted in a significantly greater reduction in LDL cholesterol as compared with each monotherapy (p < 0.01 for each). The corresponding values for triglycerides were −40.0% ± 29.5%, −40.1% ± 28.7%, and −3.4% ± 32.6%, respectively. Fenofibrate use was associated with some changes in laboratory measurements, but there was no differential adverse effect between the combination therapy and fenofibrate monotherapy. Conclusion: The combination therapy with fenofibrate and ezetimibe substantially reduces concentrations of LDL cholesterol and triglycerides and is safe in a long-term treatment in Japanese patients with combined hyperlipidemia. PMID:27397061

Efficacy and Safety of Long-term Coadministration of Fenofibrate and Ezetimibe in Patients with Combined Hyperlipidemia: Results of the EFECTL Study.

PubMed

Oikawa, Shinichi; Yamashita, Shizuya; Nakaya, Noriaki; Sasaki, Jun; Kono, Suminori

2017-01-01

We investigated the safety and efficacy of a long-term combination therapy with fenofibrate and ezetimibe in Japanese patients with combined hyperlipidemia, in comparison with fenofibrate or ezetimibe alone. The study was a three-arm parallel-group, open-label randomized trial. Eligible patients were assigned to a combination therapy with fenofibrate (200 mg/day in capsule form or 160 mg/day in tablet form) and ezetimibe (10 mg/day), the fenofibrate monotherapy, or the ezetimibe monotherapy, which lasted for 52 weeks. The changes in serum low-density lipoprotein (LDL) cholesterol and triglycerides were the primary outcomes. A total of 236 patients were assigned to one of the three treatments, and the number of patients included in the final analysis was 107 in the combination therapy, 52 in the fenofibrate monotherapy, and 51 in the ezetimibe monotherapy. Mean±SD changes in LDL cholesterol were -24.2%±14.7% with combination therapy, -16.0%±16.0% with fenofibrate alone, and -17.4%± 10.1% with ezetimibe alone. The combination therapy resulted in a significantly greater reduction in LDL cholesterol as compared with each monotherapy (p＜0.01 for each). The corresponding values for triglycerides were -40.0%±29.5%, -40.1%±28.7%, and -3.4%±32.6%, respectively. Fenofibrate use was associated with some changes in laboratory measurements, but there was no differential adverse effect between the combination therapy and fenofibrate monotherapy. The combination therapy with fenofibrate and ezetimibe substantially reduces concentrations of LDL cholesterol and triglycerides and is safe in a long-term treatment in Japanese patients with combined hyperlipidemia.

Using Active Learning for Speeding up Calibration in Simulation Models

PubMed Central

Cevik, Mucahit; Ali Ergun, Mehmet; Stout, Natasha K.; Trentham-Dietz, Amy; Craven, Mark; Alagoz, Oguzhan

2015-01-01

Background Most cancer simulation models include unobservable parameters that determine the disease onset and tumor growth. These parameters play an important role in matching key outcomes such as cancer incidence and mortality and their values are typically estimated via lengthy calibration procedure, which involves evaluating large number of combinations of parameter values via simulation. The objective of this study is to demonstrate how machine learning approaches can be used to accelerate the calibration process by reducing the number of parameter combinations that are actually evaluated. Methods Active learning is a popular machine learning method that enables a learning algorithm such as artificial neural networks to interactively choose which parameter combinations to evaluate. We develop an active learning algorithm to expedite the calibration process. Our algorithm determines the parameter combinations that are more likely to produce desired outputs, therefore reduces the number of simulation runs performed during calibration. We demonstrate our method using previously developed University of Wisconsin Breast Cancer Simulation Model (UWBCS). Results In a recent study, calibration of the UWBCS required the evaluation of 378,000 input parameter combinations to build a race-specific model and only 69 of these combinations produced results that closely matched observed data. By using the active learning algorithm in conjunction with standard calibration methods, we identify all 69 parameter combinations by evaluating only 5620 of the 378,000 combinations. Conclusion Machine learning methods hold potential in guiding model developers in the selection of more promising parameter combinations and hence speeding up the calibration process. Applying our machine learning algorithm to one model shows that evaluating only 1.49% of all parameter combinations would be sufficient for the calibration. PMID:26471190

Application of combined treatment for control of Botrytis cinerea in phytosanitary irradiation processing

NASA Astrophysics Data System (ADS)

Jung, Koo; Yoon, Minchul; Park, Hae-Jun; Youll Lee, Kwang; Jeong, Rae-Dong; Song, Beom-Seok; Lee, Ju-Woon

2014-06-01

Phytosanitary treatments are required to disinfest quarantine pests and pathogens in agricultural commodities. Gray mold in fruit is caused by Botrytis cinerea, which is one of the major postharvest pathogen of apple and pear. Irradiation treatment is a viable alternative for phytosanitary purposes and a useful nonchemical method for controlling pests and postharvest pathogens. An irradiation dose of over 0.4 kGy is used for the control of insects and fungal disease in fresh fruit, but a loss of firmness occurs. Combined treatments are needed to reduce the irradiation dose in phytosanitary irradiation processing. This study focuses on the application of combined treatments to reduce the loss of fruit quality when fresh fruit is irradiated for phytosanitary purposes. Comparing the antifungal activity against B. cinerea, while gamma irradiation showed no antifungal activity at a dose of 1.0 kGy, combined treatments (nano Ag particle, nano-sized silica silver) at a dose of 1.0 kGy showed the strongest antifungal activity. This study demonstrates the synergistic impacts of combined treatments in phytosanitary irradiation processing. Taken together, the combined treatments may affect reduction of fruit injury that occurred with irradiation only, meaning that the use of combined treatments with gamma irradiation is significantly effective for the preservation of fruit quality.

[Changes of twenty-four-hour profile blood pressure and its correction of patients with arterial hypertension on the background of combined antihypertensive therapy application].

PubMed

Solomennchuk, T M; Slaba, N A; Prots'ko, V V; Bedzaĭ, A O

2014-01-01

The aim of this research was the study of efficiency and endurance antihypertensive therapy on the basis of fixed combination of enalapril and hydrochlorothiazide (HCTZ) and enalapril and HCTZ in combination with amlodipine according to the twenty-four-hour (? day-and-night) monitoring of blood pressure (? 24H BPM) of patients with arterial hypertension (AH) 2-3 severity. The study included 33 patients with 2-3 grade of hypertension (average age--54,40 ± 3.45 years). All patients performed ? 24H BPM before treatment and after 12 weeks of therapy. The combination of enalapril and HCTZ allowed to achieve target levels of blood pressure in 79% of patients, amlodipine additional purpose--in 86% of patients. We found that this therapy has a corrective effect on daily blood pressure profile, significantly reducing the load pressure and blood pressure variability. During treatment with the combination of enalapril and HCTZ combination of enalapril, HCTZ with amlodipine optimal daily profile of blood pressure after 12 weeks of reaching respectively 63.1% and 71.4% of patients. The treatment with combination of enalapril and HCTZ and adding of amlodipine is characterized by good endurance and high adherence to treatment.

Desloratadine and pseudoephedrine combination therapy as a comprehensive treatment for allergic rhinitis and nasal congestion.

PubMed

Anolik, Robert

2009-06-01

Allergic rhinitis (AR) is rapidly increasing in global prevalence. Symptoms of AR, particularly nasal congestion, can cause quality of life (QoL) impairment. Second-generation antihistamines are a recommended first-line therapy for AR but are not viewed as very effective for the treatment of congestion. Therefore, an antihistamine plus a decongestant, such as the combination of desloratadine and pseudoephedrine, is a convenient and efficacious treatment. To review the clinical evidence on the efficacy and safety of combination desloratadine/pseudoephedrine for the treatment of AR symptoms, particularly nasal congestion. Four large studies found that improvement in nasal congestion is enhanced when patients are treated with combination desloratadine/pseudoephedrine. The combination drug significantly improved mean reflective nasal congestion scores in these studies compared with either component as monotherapy (p

A special terpene combination (Rowatinex®) improves stone clearance after extracorporeal shockwave lithotripsy in urolithiasis patients: results of a placebo-controlled randomised controlled trial.

PubMed

Romics, Imre; Siller, György; Kohnen, Ralf; Mavrogenis, Stelios; Varga, József; Holman, Endre

2011-01-01

To investigate the safety and efficacy of a special terpene combination in the treatment of patients with urolithiasis after extracorporeal shockwave lithotripsy (ESWL). 222 patients with clinically stable kidney or ureter stones of 0.3-2.0 cm undergoing complication-free ESWL were randomised to receive a special terpene combination (Rowatinex®; 3 × 2 capsules/day) or placebo. The study consisted of a 12-week active treatment phase and a 2-week follow-up phase. All patients had a physical examination, and diagnosis of kidney stones was made by X-ray, intravenous pyelogram or ultrasound at weeks 1, 4, 8 and 12 as well as after 2 weeks of follow-up. Stone-free status was defined as obviously successful expulsion of calculi/fragments, being without any stone. In all, when compared to placebo, significantly more patients receiving the terpene combination treatment in the intent-to-treat (ITT) group [72 (67.9%) vs. 49 (50.0%); p = 0.0009] and the per-protocol (PP) group [69 (78.4%) vs. 48 (52.2%); p = 0.0004] were stone-free at the end of the study. Treatment with the terpene combination was also more effective when analysed with respect to the size of the treated stone. In addition, treatment with the terpene combination significantly reduced the median time to stone-free status from 85.0 to 56.0 days (p = 0.0061) and from 85.0 to 49.5 days (p = 0.0028) in the ITT and PP populations, respectively. Nine mild-to-moderate adverse events (AE; terpene combination group: 7 AE in 4 patients; placebo group: 2 AE in 2 patients) were assessed as drug-related. Treatment with the terpene combination is well tolerated and safe. The terpene combination was found to be an efficacious treatment in eliminating calculi fragments generated by ESWL as compared to placebo. The pharmacodynamic properties of the terpene combination (antilithogenic, antibacterial, antiinflammatory, spasmolytic and analgesic effects), which have been also confirmed in preclinical studies, represent a valuable alternative to the different drugs used in the treatment of urolithiasis. Copyright © 2010 S. Karger AG, Basel.

Identification and replication of the interplay of four genetic high-risk variants for urinary bladder cancer

PubMed Central

Selinski, Silvia; Blaszkewicz, Meinolf; Ickstadt, Katja; Gerullis, Holger; Otto, Thomas; Roth, Emanuel; Volkert, Frank; Ovsiannikov, Daniel; Moormann, Oliver; Banfi, Gergely; Nyirady, Peter; Vermeulen, Sita H; Garcia-Closas, Montserrat; Figueroa, Jonine D; Johnson, Alison; Karagas, Margaret R; Kogevinas, Manolis; Malats, Nuria; Schwenn, Molly; Silverman, Debra T; Koutros, Stella; Rothman, Nathaniel; Kiemeney, Lambertus A; Hengstler, Jan G; Golka, Klaus

2017-01-01

Abstract Little is known whether genetic variants identified in genome-wide association studies interact to increase bladder cancer risk. Recently, we identified two- and three-variant combinations associated with a particular increase of bladder cancer risk in a urinary bladder cancer case–control series (Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), 1501 cases, 1565 controls). In an independent case–control series (Nijmegen Bladder Cancer Study, NBCS, 1468 cases, 1720 controls) we confirmed these two- and three-variant combinations. Pooled analysis of the two studies as discovery group (IfADo-NBCS) resulted in sufficient statistical power to test up to four-variant combinations by a logistic regression approach. The New England and Spanish Bladder Cancer Studies (2080 cases and 2167 controls) were used as a replication series. Twelve previously identified risk variants were considered. The strongest four-variant combination was obtained in never smokers. The combination of rs1014971[AA] near apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A) and chromobox homolog 6 (CBX6), solute carrier family 1s4 (urea transporter), member 1 (Kidd blood group) (SLC14A1) exon single nucleotide polymorphism (SNP) rs1058396[AG, GG], UDP glucuronosyltransferase 1 family, polypeptide A complex locus (UGT1A) intron SNP rs11892031[AA] and rs8102137[CC, CT] near cyclin E1 (CCNE1) resulted in an unadjusted odds ratio (OR) of 2.59 (95% CI = 1.93–3.47; P = 1.87 × 10−10), while the individual variant ORs ranged only between 1.11 and 1.30. The combination replicated in the New England and Spanish Bladder Cancer Studies (ORunadjusted = 1.60, 95% CI = 1.10–2.33; P = 0.013). The four-variant combination is relatively frequent, with 25% in never smoking cases and 11% in never smoking controls (total study group: 19% cases, 14% controls). In conclusion, we show that four high-risk variants can statistically interact to confer increased bladder cancer risk particularly in never smokers. PMID:29028944

A phase I dose-escalation study of selumetinib in combination with docetaxel or dacarbazine in patients with advanced solid tumors.

PubMed

LoRusso, Patricia M; Infante, Jeffrey R; Kim, Kevin B; Burris, Howard A; Curt, Gregory; Emeribe, Ugochi; Clemett, Delyth; Tomkinson, Helen K; Cohen, Roger B

2017-03-06

The RAS/RAF/MEK/ERK pathway is constitutively activated in many cancers. Selumetinib (AZD6244, ARRY-142886) is an oral, potent and highly selective, allosteric MEK1/2 inhibitor with a short half-life that has shown clinical activity as monotherapy in phase I and II studies of advanced cancer. Preclinical data suggest that selumetinib may enhance the activity of chemotherapeutic agents. We assessed the safety, tolerability, and pharmacokinetics (PK) of selumetinib (AZD6244, ARRY-142886) in combination with docetaxel or dacarbazine in patients with advanced solid tumors. This study was a phase I, open-label, multicenter study in patients aged ≥18 years with advanced solid tumors who were candidates for docetaxel or dacarbazine treatment. Part A of the study (dose escalation) evaluated safety, tolerability, PK, and maximum tolerated dose (MTD) of selumetinib twice daily (BID) with docetaxel 75 mg/m 2 or dacarbazine 1000 mg/m 2 administered every 21 days. Patients receiving docetaxel could be administered primary prophylactic granulocyte-colony stimulating factor according to standard guidelines. Part B of the study (dose expansion) further evaluated safety, tolerability, and PK in 12 additional patients at the MTD combinations determined in part A. A total of 35 patients received selumetinib plus docetaxel, and 25 received selumetinib plus dacarbazine. The MTD of selumetinib was 75 mg BID in combination with either docetaxel (two dose-limiting toxicity [DLT] events: neutropenia with fever, and thrombocytopenia) or dacarbazine (one DLT event: thrombocytopenia). Common adverse events occurring with each treatment combination were diarrhea, peripheral/periorbital edema, fatigue, and nausea. PK parameters for selumetinib and docetaxel or dacarbazine were similar when administered alone or in combination. Partial responses were reported in 6/35 patients receiving selumetinib plus docetaxel and 4/25 patients receiving selumetinib plus dacarbazine. The combinations of selumetinib plus docetaxel and selumetinib plus dacarbazine demonstrated manageable safety and tolerability profiles and preliminary signs of clinical activity in patients with advanced solid tumors. ClinicalTrials.gov NCT00600496; registered 8 July 2009.

A retrospective claims analysis of combination therapy in the treatment of adult attention-deficit/hyperactivity disorder (ADHD).

PubMed

Pohl, Gerhardt M; Van Brunt, David L; Ye, Wenyu; Stoops, William W; Johnston, Joseph A

2009-06-08

Combination therapy in managing psychiatric disorders is not uncommon. While combination therapy has been documented for depression and schizophrenia, little is known about combination therapy practices in managing attention-deficit/hyperactivity disorder (ADHD). This study seeks to quantify the combination use of ADHD medications and to understand predictors of combination therapy. Prescription dispensing events were drawn from a U.S. national claims database including over 80 managed-care plans. Patients studied were age 18 or over with at least 1 medical claim with a diagnosis of ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 314.0), a pharmacy claim for ADHD medication during the study period July 2003 to June 2004, and continuous enrollment 6 months prior to and throughout the study period. Dispensing events were grouped into 6 categories: atomoxetine (ATX), long-acting stimulants (LAS), intermediate-acting stimulants (IAS), short-acting stimulants (SAS), bupropion (BUP), and Alpha-2 Adrenergic Agonists (A2A). Events were assigned to calendar months, and months with combined use from multiple categories within patient were identified. Predictors of combination therapy for LAS and for ATX were modeled for patients covered by commercial plans using logistic regression in a generalized estimating equations framework to adjust for within-patient correlation between months of observation. Factors included age, gender, presence of the hyperactive component of ADHD, prior diagnoses for psychiatric disorders, claims history of recent psychiatric visit, insurance plan type, and geographic region. There were 18,609 patients identified representing a total of 11,886 months of therapy with ATX; 40,949 months with LAS; 13,622 months with IAS; 38,141 months with SAS; 22,087 months with BUP; and 1,916 months with A2A. Combination therapy was present in 19.7% of continuing months (months after the first month of therapy) for ATX, 21.0% for LAS, 27.4% for IAS, 23.1% for SAS, 36.9% for BUP, and 53.0% for A2A.For patients receiving LAS, being age 25-44 or age 45 and older versus being 18-24 years old, seeing a psychiatrist, having comorbid depression, or having point-of-service coverage versus a Health Maintenance Organization (HMO) resulted in odds ratios significantly greater than 1, representing increased likelihood for combination therapy in managing adult ADHD.For patients receiving ATX, being age 25-44 or age 45 and older versus being 18-24 years old, seeing a psychiatrist, having a hyperactive component to ADHD, or having comorbid depression resulted in odds ratios significantly greater than 1, representing increased likelihood for combination therapy in managing adult ADHD. ATX and LAS are the most likely drugs to be used as monotherapy. Factors predicting combination use were similar for months in which ATX was used and for months in which LAS was used except that a hyperactive component to ADHD predicted increased combination use for ATX but not for LAS.

Opportunistic Beamforming with Wireless Powered 1-bit Feedback Through Rectenna Array

NASA Astrophysics Data System (ADS)

Krikidis, Ioannis

2015-11-01

This letter deals with the opportunistic beamforming (OBF) scheme for multi-antenna downlink with spatial randomness. In contrast to conventional OBF, the terminals return only 1-bit feedback, which is powered by wireless power transfer through a rectenna array. We study two fundamental topologies for the combination of the rectenna elements; the direct-current combiner and the radio-frequency combiner. The beam outage probability is derived in closed form for both combination schemes, by using high order statistics and stochastic geometry.

[The application of combined physiotherapeutic methods for the complex treatment of patients with dyscirculatory encephalopathy].

PubMed

Shiman, A G; Klocheva, E G; Kaiumov, S F; Shoferova, S D; Zhukova, M V

2012-01-01

This article reports the results of applying basic pharmacotherapy (enalapril, cytoflavin) and its combination with physical factors (transcranial electrostimulation, combined application oftranscranial electrostimulation and low-frequency magnetic therapy) in the complex treatment of patients with stage I-II dyscirculatory encephalopathy. The study has demonstrated that the combined treatment with cytoflavin, enalapril, transcranial electrostimulation and low-frequency magnetic therapy produced the most pronounced therapeutic effect (82.5%), as confirmed by positive dynamics of clinical and functional parameters.

NLLSS: Predicting Synergistic Drug Combinations Based on Semi-supervised Learning

PubMed Central

Chen, Ming; Wang, Quanxin; Zhang, Lixin; Yan, Guiying

2016-01-01

Fungal infection has become one of the leading causes of hospital-acquired infections with high mortality rates. Furthermore, drug resistance is common for fungus-causing diseases. Synergistic drug combinations could provide an effective strategy to overcome drug resistance. Meanwhile, synergistic drug combinations can increase treatment efficacy and decrease drug dosage to avoid toxicity. Therefore, computational prediction of synergistic drug combinations for fungus-causing diseases becomes attractive. In this study, we proposed similar nature of drug combinations: principal drugs which obtain synergistic effect with similar adjuvant drugs are often similar and vice versa. Furthermore, we developed a novel algorithm termed Network-based Laplacian regularized Least Square Synergistic drug combination prediction (NLLSS) to predict potential synergistic drug combinations by integrating different kinds of information such as known synergistic drug combinations, drug-target interactions, and drug chemical structures. We applied NLLSS to predict antifungal synergistic drug combinations and showed that it achieved excellent performance both in terms of cross validation and independent prediction. Finally, we performed biological experiments for fungal pathogen Candida albicans to confirm 7 out of 13 predicted antifungal synergistic drug combinations. NLLSS provides an efficient strategy to identify potential synergistic antifungal combinations. PMID:27415801

Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study.

PubMed

Sitbon, Olivier; Jaïs, Xavier; Savale, Laurent; Cottin, Vincent; Bergot, Emmanuel; Macari, Elise Artaud; Bouvaist, Hélène; Dauphin, Claire; Picard, François; Bulifon, Sophie; Montani, David; Humbert, Marc; Simonneau, Gérald

2014-06-01

Patients with severe pulmonary arterial hypertension (PAH) in New York Heart Association (NYHA) functional class (FC) III/IV have a poor prognosis, despite survival benefits being demonstrated with intravenous epoprostenol. In this pilot study, the efficacy and safety of a triple combination therapy regimen in patients with severe PAH was investigated. Data from newly diagnosed NYHA FC III/IV PAH patients (n=19) initiated on upfront triple combination therapy (intravenous epoprostenol, bosentan and sildenafil) were collected retrospectively from a prospective registry. Significant improvements in 6-min walk distance and haemodynamics were observed after 4 months' triple combination therapy in 18 patients (p<0.01); 17 patients had improved to NYHA FC I or II. One patient was not included in the month 4 assessment (due to an emergency lung transplant in month 3). At the final evaluation (mean ± sd 32 ± 19 months), all 18 patients had sustained clinical and haemodynamic improvement. Overall survival estimates for the triple combination cohort were 100% at 1, 2 and 3 years. Expected survival calculated from the French equation was 75% (95% CI 68-82%), 60% (95% CI 50-70%) and 49% (95% CI 38-60%) at 1, 2 and 3 years, respectively. This pilot study provides preliminary evidence of the long-term benefits of upfront triple combination therapy in patients with severe PAH. ©ERS 2014.

Interactions between imidazoline I2 receptor ligands and acetaminophen in adult male rats: antinociception and schedule-controlled responding

PubMed Central

Siemian, Justin N.; Li, Jiuzhou; Zhang, Yanan; Li, Jun-Xu

2015-01-01

Rationale Recent evidence suggests that imidazoline I2 receptor ligands are suitable for combination therapy with opioids. Quantitative analysis of I2 receptor ligands combined with non-opioid drugs is necessary for justification of alternative pain therapies. Objective This study systematically examined the anti-hyperalgesic and response rate-suppressing effects of selective I2 receptor ligands (2-BFI and phenyzoline) alone and in combination with acetaminophen. Methods Von Frey and Hargreaves tests were used to examine the anti-hyperalgesic effects of drugs in complete Freund’s adjuvant (CFA)-induced inflammatory pain in rats. Food-reinforced schedule-controlled responding was used to assess the rate-suppressing effects of study drugs. Dose-addition and isobolographic analyses were used to assess drug-drug interactions for all assays. Results 2-BFI (3.2–17.8 mg/kg, i.p.), phenyzoline (17.8–100 mg/kg, i.p.), and acetaminophen (56–178 mg/kg, i.p.) all dose-dependently produced significant antinociceptive effects. When studied as combinations, 2-BFI and acetaminophen produced infra-additive to additive interactions while phenyzoline and acetaminophen produced additive to supra-additive interactions. The same drug combinations suppressed response rate in a supra-additive manner. Conclusions Quantitative analysis of the anti-hyperalgesic and response rate-suppressing effects suggests that I2 receptor ligands are not well suited to combination therapy with acetaminophen. PMID:26613734

Anti-tumorigenic activity of five culinary and medicinal herbs grown under greenhouse conditions and their combination effects.

PubMed

Yi, Weiguang; Wetzstein, Hazel Y

2011-08-15

Herbs and spices have been used as food preservatives, flavorings, and in traditional medicines for thousands of years. More and more scientific evidence supports the medicinal properties of culinary herbs. Colon cancer is the third leading cause of cancer death in the USA, and the fourth most common form of cancer worldwide. The objectives of this study were to evaluate the antitumor activity of five selected herbs grown under greenhouse conditions, and to study the potential synergistic effects among different herbal extract combinations. Thyme, rosemary, sage, spearmint, and peppermint extracts significantly inhibited SW-480 colon cancer cell growth, with sage extracts exhibiting the highest bioactivity, with 50% inhibition at 35.9 µg mL⁻¹, which was equivalent to 93.9 µg dried leaves mL⁻¹ of culture medium. Some mixtures of different herbal extracts had combination effects on cancer cell growth. The inhibitory effects of peppermint + sage combinations at a 1:1 ratio were significantly higher than rosemary + sage combinations at 1:1 ratio, although peppermint extracts showed lower inhibition than rosemary extracts. Extracts from herb species (thyme, rosemary, sage, spearmint and peppermint) can significantly inhibit the growth of human colon cancer cells. Mixtures of herb extracts can have combination effects on cancer cell growth. The study suggests that these five herbs may have potential health benefits to suppress colon cancer. Copyright © 2011 Society of Chemical Industry.

Pre-clinical toxicity of a combination of berberine and 5-aminosalicylic acid in mice.

PubMed

Li, Yan-Hong; Zhang, Man; Fu, Hai-Bo; Xiao, Hai-Tao; Bian, Zhao-Xiang

2016-11-01

Our previous study demonstrated that a combination of alternative medicine berberine and conventional 5-aminosalicylic acid (5-ASA) showed promise to be a novel therapeutic strategy for ulcerative colitis (UC). This present study aims to sketch the pre-clinical toxicity profile of this combination (1:10 dose ratio) on mice. In acute toxicity test, the determined median lethal dose (LD 50 ) was 278.7 mg/kg berberine plus 2787 mg/kg 5-ASA. The results from subacute toxicity test demonstrated that no toxic signs of clinical symptoms, no significant changes in hematological or biochemical parameters were detected in mice treated with 14 + 140, 28 + 280 or 56 + 560 mg/kg of berberine plus 5-ASA treatment. Histological examinations revealed that accompanied with an increase in spleen weight, frequently recorded enlargement and white pulp hyperplasia of spleen were detected in mice when exposed to three doses of combination treatments. Further in vitro assessment suggested that the spleen toxicity was originated from berberine by its inhibition in cell viability and cell proliferation of lymphocytes. The results of this study indicate that the combination of berberine and 5-ASA shows a slight toxic effect on spleen, suggesting that this combination should be used with caution for patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of lightweight outdoor clothing on the prevention of hypothermia during low-intensity exercise in the cold.

PubMed

Burtscher, Martin; Kofler, Philipp; Gatterer, Hannes; Faulhaber, Martin; Philippe, Marc; Fischer, Kathrin; Walther, Rebekka; Herten, Anne

2012-11-01

To study protective effects of windbreaker jacket and pants during exercise in the cold. Randomized pilot study. Climate chamber. Nine well-trained (V[Combining Dot Above]O2max 61.7 ± 6.6 mL/min/kg) sport students (6 male and 3 female participants). Subjects started walking for 1 hour in a climate chamber (0°C ambient temperature and wind speed of 10 km/h) at 70% V[Combining Dot Above]O2max wearing gloves, a T-shirt, and shorts. Then, the walking speed was reduced to 30% V[Combining Dot Above]O2max for an additional 60 minutes or until core temperature dropped below 35.5°C. Subsequently, 3 groups of 3 participants continued walking without change of clothing or obtaining additionally a cap and a windbreaker jacket or windbreaker jacket and pants. Core and skin temperature, thermal comfort. The main findings of this study were that exercising at 70% V[Combining Dot Above]O2max in the cold was sufficient to prevent hypothermia and that during low-intensity exercise (30% V[Combining Dot Above]O2max), the combined use of a polyester cap, lightweight windbreaker jacket, and pants was necessary to increase a prehypothermic core temperature. We strongly recommend taking a cap, windbreaker jacket, and pants for the prevention of hypothermia during exhaustive walking or running in cold weather conditions.

A phase III, open-label, multicenter study to evaluate the safety and efficacy of long-term triple combination therapy with azilsartan, amlodipine, and hydrochlorothiazide in patients with essential hypertension.

PubMed

Rakugi, Hiromi; Shimizu, Kohei; Nishiyama, Yuya; Sano, Yuhei; Umeda, Yuusuke

2018-06-01

Patients with essential hypertension who are receiving treatment with an angiotensin II receptor blocker and a calcium channel blocker often develop inadequate blood pressure (BP) control and require the addition of a diuretic. This study aimed to evaluate the long-term safety and efficacy of a triple combination therapy with 20 mg azilsartan (AZL), 5 mg amlodipine (AML) and 12.5 mg hydrochlorothiazide (HCTZ). The phase III, open-label, multicenter study (NCT02277691) comprised a 4-week run-in period and 52-week treatment period. Patients with inadequate BP control despite AZL/AML therapy (n = 341) received 4 weeks' treatment with AZL/AML (combination tablet) + HCTZ (tablet) and 4 weeks' treatment with AZL/AML/HCTZ (combination tablet) in a crossover manner, followed by AZL/AML/HCTZ (combination tablet) from Week 8 of the treatment period up to Week 52. The primary and secondary endpoints were long-term safety and BP (office and home), respectively. Most adverse events (AEs) were mild or moderate in intensity, and no deaths or treatment-related serious AEs were reported. The triple therapy provided consistent BP-lowering effects in both office and home measurements. The triple combination therapy with AZL/AML/HCTZ was well tolerated and effective for 52 weeks in Japanese patients with essential hypertension.

Dihydroartemisinin sensitizes Lewis lung carcinoma cells to carboplatin therapy via p38 mitogen-activated protein kinase activation

PubMed Central

Zhang, Bicheng; Zhang, Zhimin; Wang, Jun; Yang, Bo; Zhao, Yong; Rao, Zhiguo; Gao, Jianfei

2018-01-01

Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin isolated from the traditional Chinese herb Artemisia annua, is an effective novel antimalarial agent. Studies have suggested that it also exhibits anticancer effects when administered alone or in combination with conventional chemotherapeutic agents. The present study investigated the therapeutic effect of DHA combined with carboplatin (CBP) on Lewis lung carcinoma (LLC) cells and the possible underlying molecular mechanisms. MTT and clonogenic assays demonstrated that the proliferation activity of LLC cells was inhibited in a dose-dependent manner by DHA combined with CBP. In addition, flow cytometry analysis revealed that cell cycle arrest was induced at the G0/G1 phase and apoptosis was induced following treatment with the combination. When administered in combination with CBP, DHA exhibited more effective anticancer activity compared with DHA or CBP used alone, via increased apoptosis. Following treatment with DHA with or without CBP, the expression of phosphorylated-p38 mitogen-activated protein kinase (MAPK), which can be inhibited with the selective inhibitor SB202190, was detected by western blotting. To summarize, the results of the present study indicated that DHA may sensitize LLC cells to CBP therapy via the activation of p38MAPK, which suggests that a combined treatment of DHA and CBP may be a potential novel therapeutic schedule for lung adenocarcinoma. PMID:29740482

The Impact of Web Page Text-Background Colour Combinations on Readability, Retention, Aesthetics and Behavioural Intention

ERIC Educational Resources Information Center

Hall, Richard H.; Hanna, Patrick

2004-01-01

The purpose of this experiment was to examine the effect of web page text/background colour combination on readability, retention, aesthetics, and behavioural intention. One hundred and thirty-six participants studied two Web pages, one with educational content and one with commercial content, in one of four colour-combination conditions. Major…

Combinations of Epoch Durations and Cut-Points to Estimate Sedentary Time and Physical Activity among Adolescents

ERIC Educational Resources Information Center

Fröberg, Andreas; Berg, Christina; Larsson, Christel; Boldemann, Cecilia; Raustorp, Anders

2017-01-01

The purpose of the current study was to investigate how combinations of different epoch durations and cut-points affect the estimations of sedentary time and physical activity in adolescents. Accelerometer data from 101 adolescents were derived and 30 combinations were used to estimate sedentary time, light, moderate, vigorous, and combined…

Recurrent Word Combinations in EAP Test-Taker Writing: Differences between High- and Low-Proficiency Levels

ERIC Educational Resources Information Center

Appel, Randy; Wood, David

2016-01-01

The correct use of frequently occurring word combinations represents an important part of language proficiency in spoken and written discourse. This study investigates the use of English-language recurrent word combinations in low-level and high-level L2 English academic essays sourced from the Canadian Academic English Language (CAEL) assessment.…

Activity of Picolinic Acid in Combination with the Antiprotozoal Drug Quinacrine against Mycobacterium avium Complex

PubMed Central

Shimizu, Toshiaki; Tomioka, Haruaki

2006-01-01

We studied the in vitro and in vivo antimicrobial activities of picolinic acid (PA) in combination with the antiprotozoal drug quinacrine against intramacrophage Mycobacterium avium complex (MAC). Quinacrine significantly potentiated the anti-MAC activity of PA, suggesting the usefulness of this combination in the clinical control of MAC infection. PMID:16940126

Using Robust Standard Errors to Combine Multiple Regression Estimates with Meta-Analysis

ERIC Educational Resources Information Center

Williams, Ryan T.

2012-01-01

Combining multiple regression estimates with meta-analysis has continued to be a difficult task. A variety of methods have been proposed and used to combine multiple regression slope estimates with meta-analysis, however, most of these methods have serious methodological and practical limitations. The purpose of this study was to explore the use…

The Cost-Effectiveness and Return-On-Investment of a Combined Social and Physical Environmental Intervention in Office Employees

ERIC Educational Resources Information Center

van Dongen, J. M.; Coffeng, J. K.; van Wier, M. F.; Boot, C. R. L.; Hendriksen, I. J. M.; van Mechelen, W.; Bongers, P. M.; van der Beek, A. J.; Bosmans, J. E.; van Tulder, M. W.

2017-01-01

This study explored the cost-effectiveness and return-on-investment of a combined social and physical environmental worksite health promotion program compared with usual practice, and of both intervention conditions separately. Participants were randomized to the combined intervention (n = 92), social environmental intervention (n = 118), physical…

Efficacy of antibiotic treatment of implant-associated Staphylococcus aureus infections with moxifloxacin, flucloxacillin, rifampin, and combination therapy: an animal study.

PubMed

Greimel, Felix; Scheuerer, Christine; Gessner, Andre; Simon, Michaela; Kalteis, Thomas; Grifka, Joachim; Benditz, Achim; Springorum, Hans-Robert; Schaumburger, Jens

2017-01-01

The efficacy of antibiotic monotherapy and combination therapy in the treatment of implant-associated infection by Staphylococcus aureus was evaluated in an animal study. The femoral medullary cavity of 66 male Wistar rats was contaminated with S. aureus (ATCC 29213) and a metal device was implanted, of which 61 could be evaluated. Six treatment groups were studied: flucloxacillin, flucloxacillin in combination with rifampin, moxifloxacin, moxifloxacin in combination with rifampin, rifampin, and a control group with aqua. The treatment was applied for 14 days. After euthanasia, the bacterial counts in the periprosthetic bone, the soft tissue, and the implant-associated biofilm were measured. Both antibiotic combination treatments (moxifloxacin plus rifampin and flucloxacillin plus rifampin) achieved a highly significant decrease in microbial counts in the bone and soft tissue and in the biofilm. Mono-antibiotic treatments with either moxifloxacin or flucloxacillin were unable to achieve a significant decrease in microbial counts in bone and soft tissue or the biofilm, whilst rifampin was able to reduce the counts significantly only in the biofilm. Antibiotic resistance was measured in 1/3 of the cases in the rifampin group, whereas no resistance was measured in all other groups. The results show that combinations of both moxifloxacin and flucloxacillin plus rifampin are adequate for the treatment of periprosthetic infections due to infections with S. aureus , whereas monotherapies are not effective or not applicable due to the rapid development of antibiotic resistance. Therefore, moxifloxacin is an effective alternative in combination with rifampin for the treatment of implant-associated infections.

Multiple morbidity combinations impact on medical expenditures among older adults.

PubMed

Chi, Mei-ju; Lee, Cheng-yi; Wu, Shwu-chong

2011-01-01

This study aims to explore the medical needs of patients who have different combinations of multiple chronic diseases in order to improve care strategy for chronic patients. This study was based on a national probability proportional to size (PPS) sampling to older adults over 50 years old. We collaborated the files of the 2000-2001 health insurance claims and selected 8 types of common chronic diseases among seniors, for the discussion of multiple combinations of chronic diseases, including hypertension, diabetes, heart disease, stroke, dementia, cancer, arthritis and chronic obstructive pulmonary disease. Among the NHI users, there are 50.6% of the cases suffering from at least one chronic disease, 27.3% suffering from two types of chronic diseases and above. From possible combinations of eight common chronic diseases, it is found hypertension has the highest prevalence rate (7.5%); arthritis ranks the next (6.2%); the combination of hypertension and heart disease ranks the third (3.4%). In the 22 types of major chronic disease clusters, the average total medical expense for people who have five or more chronic diseases ranks the highest, USD 4465; the combination of hypertension, diabetes, heart disease, and arthritis ranks the next, USD 2703; the combination of hypertension, diabetes, and heart disease ranks the third, USD 2550; cancer only ranks the fourth, USD 2487. Our study may provide statistical data concerning co-morbidity among older adults and their medical needs. Through our analysis, the major population that exhausts the medical resources may be discovered. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Relationship of carbohydrate molecular spectroscopic features in combined feeds to carbohydrate utilization and availability in ruminants

NASA Astrophysics Data System (ADS)

Zhang, Xuewei; Yu, Peiqiang

To date, there is no study on the relationship between carbohydrate (CHO) molecular structures and nutrient availability of combined feeds in ruminants. The objective of this study was to use molecular spectroscopy to reveal the relationship between CHO molecular spectral profiles (in terms of functional groups (biomolecular, biopolymer) spectral peak area and height intensity) and CHO chemical profiles, CHO subfractions, energy values, and CHO rumen degradation kinetics of combined feeds of hulless barley with pure wheat dried distillers grains with solubles (DDGS) at five different combination ratios (hulless barley to pure wheat DDGS: 100:0, 75:25, 50:50, 25:75, 0:100). The molecular spectroscopic parameters assessed included: lignin biopolymer molecular spectra profile (peak area and height, region and baseline: ca. 1539-1504 cm-1); structural carbohydrate (STCHO, peaks area region and baseline: ca. 1485-1186 cm-1) mainly associated with hemi- and cellulosic compounds; cellulosic materials peak area (centered at ca. 1240 cm-1 with region and baseline: ca. 1272-1186 cm-1); total carbohydrate (CHO, peaks area region and baseline: ca. 1186-946 cm-1). The results showed that the functional groups (biomolecular, biopolymer) in the combined feeds are sensitive to the changes of carbohydrate chemical and nutrient profiles. The changes of the CHO molecular spectroscopic features in the combined feeds were highly correlated with CHO chemical profiles, CHO subfractions, in situ CHO rumen degradation kinetics and fermentable organic matter supply. Further study is needed to investigate possibility of using CHO molecular spectral features as a predictor to estimate nutrient availability in combined feeds for animals and quantify their relationship.

Evaluation of efficacy of combinations of five endodontic sealers with five antibiotics against Enterococcus Faecalis – An in-vitro study

PubMed Central

Sharma, Deepak; Grover, Rohit; Pinnameneni, Prasanth Sai; Dey, Subhra; Raju, P Ramakrishnam

2014-01-01

Background: To evaluate and compare in vitro the antibacterial efficacy of five antibiotics when added individually to five endodontic sealers against Enterococcus faecalis (EF). Materials & Methods: This controlled trial with systematic allocation method was carried out to detect the combined antibacterial activity of five endodontic sealers (Kerr sealer EWT, Endomethasone, AH26, AH Plus, Roekoseal) with five antibiotics regularly used (Amoxicillin, metronidazole, azithromyacin, gatifloxacin, doxycycline) on EF. For each sealerantibiotic combinations, thirty BHI agar plates (15 aerobic and 15 anaerobic) were inoculated with EF, containing five sterile paper discs- three of various sealer- antibiotic combinations, one of sealer alone (positive control) & plain disc as negative control were incubated at 370C for 48 hrs and the zone of inhibition was measured. Data analysis was done by ANOVA and Tukey’s post- hoc test using SPSS( version 17). Results: The findings of this study revealed that sealer-antibiotic combination containing amoxicillin had the significant difference (p<0.001) in the mean zone of inhibition compared to other combinations. Metronidazole showed the minimum zone of inhibition among used antibiotics. The sealers in the decreasing order according to their effectiveness on EF were Kerr sealer endomethasone, AH26, Rockseal, AH plus. Conclusion: Addition of antibiotics to endodontic sealers enhances their antibacterial activity against Enterococcus faecalis. How to cite the article: Sharma D, Grover R, Pinnameneni PS, Dey S, Raju PR. Evaluation of efficacy of combinations of five endodontic sealers with five antibiotics against Enterococcus Faecalis – An in-vitro study. J Int Oral Health 2014;6(2):90-5. PMID:24876708

In vitro reactivity of allospecific cytotoxic T lymphocytes does not explain the taboo phenomenon.

PubMed

Stobbe, I; van der Meer-Prins, E; Smits, J M; Doxiadis, I I; Claas, F H

1999-12-01

Matching for human leucocyte antigens (HLA) is important for graft survival in kidney transplantation. Nevertheless, most patients receive a kidney graft with multiple HLA mismatches. Some of these mismatches seem to be more harmful than others. By studying the effect of single HLA mismatches in the context of the patients' own HLA, we have previously identified donor/recipient combinations with a significantly higher incidence of early graft failure, the so-called taboo combinations. In the present study we investigated whether a higher cytotoxic T lymphocyte (CTL) response towards taboo mismatches may be involved in this phenomenon. CTL reactivity was determined both in taboo and control combinations by in vitro CTL precursor assays, using peripheral blood mononuclear cells and proximal tubular epithelial cells as target cells. Inhibition studies with CD8-antibody as well as Cyclosporin A were performed to identify high avidity and primed CTLs. Furthermore, in committed CTLp assays indirect recognition of the taboo mismatch was tested using synthetic peptides. The CTL precursor frequencies in taboo combinations were always lower than the CTL precursor frequencies in control combinations. No difference in avidity and activation status of the CTLs could be detected when taboo combinations were compared with the controls. In the committed CTLp assays no reactivity towards any of the synthetic peptides was observed. The significantly poorer graft survival of taboo combinations cannot be explained by a higher number of donor-specific CTLs. Furthermore, the avidity or activation status of these CTLs does not provide a clue to the taboo phenomenon.

Enhanced efficacy of synergistic combinations of antimicrobial peptides with caspofungin versus Candida albicans in insect and murine models of systemic infection.

PubMed

MacCallum, D M; Desbois, A P; Coote, P J

2013-08-01

The objective of this study was to determine whether combinations of antimicrobial peptides (AMPs) with caspofungin display enhanced antifungal activity versus Candida albicans in vitro and in vivo. Three conventional AMPs that satisfied criteria favouring their potential development as novel antifungals were selected for investigation. Colistin sulphate was also included as a cyclic peptide antibiotic used in the clinic. Minimum inhibitory concentrations (MICs) were determined for each antifungal agent and checkerboard assays were used to determine fractional inhibitory concentration index (FICI) values for dual combinations of AMPs or colistin with caspofungin. Viability assays were performed for the same combinations in order to investigate fungicidal interactions. Synergistic antifungal combinations were then tested for efficacy in vivo and compared to monotherapies in wax moth larva and murine models of systemic C. albicans infection. In combination with caspofungin, each of the AMPs [hMUC7-12, DsS3(1-16), hLF(1-11)] and colistin were synergistic and candidacidal in vitro. The treatment of infected wax moth larvae with combinations of caspofungin with hMUC7-12, DsS3(1-16) or colistin resulted in significant enhancements in survival compared to treatment with monotherapies. Notably, the treatment of C. albicans-infected mice with a combination of caspofungin and DsS3(1-16) resulted in the enhancement of survival compared to groups treated with just the individual agents. This study demonstrates that combination therapies containing caspofungin and AMPs or colistin merit further development as potential novel treatments for C. albicans infections.

Myricetin and methyl eugenol combination enhances the anticancer activity, cell cycle arrest and apoptosis induction of cis-platin against HeLa cervical cancer cell lines

PubMed Central

Yi, Jin-Ling; Shi, Song; Shen, Yan-Li; Wang, Ling; Chen, Hai-Yan; Zhu, Jun; Ding, Yan

2015-01-01

Drug combination therapies are common practice in the treatment of cancer. In this study, we evaluated the anticancer effects of myricetin (MYR), methyl eugenol (MEG) and cisplatin (CP) both separately as well as in combination against cervical cancer (HeLa) cells. To demonstrate whether MYR and MEG enhance the anticancer activity of CP against cervical cancer cells, we treated HeLa cells with MYR and MEG alone or in combination with cisplatin and evaluated cell growth and apoptosis using MTT (3 (4, 5 dimethyl thiazol 2yl) 2, 5 diphenyltetrazolium bromide) assay, LDH release assay, flow cytometry and fluorescence microscopy. The results revealed that, as compared to single drug treatment, the combination of MYR or MEG with CP resulted in greater effect in inhibiting cancer cell growth and inducing apoptosis. Cell apoptosis induction, Caspase-3 activity, cell cycle arrest and mitochondrial membrane potential loss were systematically studied to reveal the mechanisms of synergy between MYR, MEG and CP. Combination of MYR or MEG with CP resulted in more potent apoptosis induction as revealed by fluorescence microscopy using Hoechst 33258 and AO-ETBR staining. The combination treatment also increased the number of cells in G0/G1 phase dramatically as compared to single drug treatment. Mitochondrial membrane potential loss (ΛΨm) as well as Caspase-3 activity was much higher in combination treatment as compared to single drug treatment. Findings of this investigation suggest that MYR and MEG combined with cisplatin is a potential clinical chemotherapeutic approach in human cervical cancer. PMID:25972998

The role of combination medical therapy in the treatment of acromegaly.

PubMed

Lim, Dawn Shao Ting; Fleseriu, Maria

2017-02-01

Uncontrolled acromegaly results in approximately 2-fold excess mortality. Pituitary surgery is first-line therapy, and medical treatment is indicated for persistent disease. While cabergoline and pegvisomant are used in select patients, somatostatin receptor ligands (SRLs) remain the cornerstone of medical treatment. Management of patients poorly responsive to SRLs is therefore, challenging. The purpose of this review is to highlight the options for combination medical therapy in the treatment of acromegaly, with an emphasis on efficacy and safety. All original articles/abstracts detailing combination medical therapy in acromegaly were identified from a PubMed search. Studies reviewed included retrospective and open-label prospective studies. While the combination of SRL and cabergoline was generally well tolerated, a lower baseline insulin-like growth factor-1 (IGF-1) level was the best predictor of efficacy; this combination may be most effective in patients with mildly elevated IGF-1. SRL-pegvisomant combination normalized IGF-1 in the majority of patients; continued efficacy despite individual drug dosing reduction was also reported. The risk of significant liver enzyme elevation was, however, higher than that reported with SRL monotherapy; close monitoring is recommended. Data on pegvisomant-cabergoline combination is limited, but this may be an option in the setting of SRL intolerance. Reports on temozolomide used in combination with other medical therapies in patients with aggressive GH-secreting tumors are also summarized. While more prospective, randomized controlled trials on long-term efficacy and safety are needed, combination medical therapy remains a treatment strategy that should be considered for acromegaly patients poorly responsive to SRLs.

Flow cytometric detection of micronuclei by combined staining of DNA and membranes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wessels, J.M.; Nuesse, M.

1995-03-01

A new staining method is presented for flow cytometric measurement of micronuclei (MN) in cell cultures and human lymphocytes using membrane-specific fluorescent dyes in addition to DNA staining. Several combinations of fluorescent membrane and DNA dyes were studied for a better discrimination of MN from debris in a suspension of nuclei and micronuclei. For staining of membranes, the lipophilic dyes 2-hydroxyethyl-7,12,17-tris(methoxyethyl)porphycene (HEPn) and 1,6-diphenyl-1,3,5-hexatriene (DPH) were used in combination with ethidium bromide (EB), proflavine (PF), and Hoechst 33258 (HO). Due to their spectral properties, HO or EB combined with HEPn were not as suitable for the discrimination of MN frommore » debris as was HEPn in combination with PF. With HEPn in combination with PF, however, additional noise was found at low fluorescence intensities, probably due to free fluorescent dye molecules in the solution. The optimal simultaneous staining of membranes and DNA was obtained using a combination of DPH and EB. The induction of MN in Chinese hamster and mouse NIH-3T3 cells by UV-B illumination was studied with this new staining technique. UV-B illumination (280-360 nm) induced MN in both cell lines. Chinese hamster cells were found to be more sensitive to these wavelengths. Illumination with wavelengths above 360 nm did not induce MN in either cell line. The results obtained from human lymphocytes using the combination of EB or DPH were comparable to the results obtained with the combination of EB and HO. 23 refs., 7 figs.« less

Meta-analysis: the efficacy and safety of combined treatment with ARB and ACEI on diabetic nephropathy.

PubMed

Ren, Feifeng; Tang, Lin; Cai, Yin; Yuan, Xin; Huang, Wenhan; Luo, Lei; Zhou, Jun; Zheng, Yaning

2015-05-01

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reduce proteinuria in diabetic nephropathy (DN). Some studies have suggested that dual blockade of the renin-angiotensin system provides additive benefits in DN but others showed increased adverse events. We performed a meta-analysis to evaluate the efficacy and safety of combination therapy for DN. Studies were identified by searching MEDLINE, EMBASE, PubMed, and CNKI. All trials involved ACEI + ARB (combination therapy), and ACEI or ARB alone (monotherapy) for DN. The outcomes measured were urinary total proteinuria (UTP), urinary albumin excretion rate (UAER), serum creatinine, glomerular filtration rate (GFR), end-stage renal disease (ESRD), hyperkalemia, hypotension, and acute kidney injury (AKI). In the 32 included trials, 2596 patients received combination therapy and 3947 received monotherapy. UTP and UAER were significantly reduced by combined treatment compared with monotherapy. It was notable that low doses of combination therapy reduced UTP more than high doses. Serum creatinine, GFR, and ESRD were not significantly different between the two groups. In severe DN, the occurrence of hyperkalemia and AKI were higher with combination therapy. However, in mild DN, the prevalence of hyperkalemia and AKI were the same in both the groups. In mild DN, the occurrence of hypotension was higher with combination therapy; however, in severe DN, it was not different between the two groups. Our meta-analysis suggests that combination therapy can be used on DN with proteinuria, but should be used with caution in those with decreased renal function, especially with severe renal failure.

Combined treatment with Dendrobium candidum and black tea extract promotes osteoprotective activity in ovariectomized estrogen deficient rats and osteoclast formation.

PubMed

Wang, Ming-Yue; Shen, Chang; An, Meng-Fei; Xie, Chuan-Qi; Wu, Xin; Zhu, Qiang-Qiang; Sun, Bin; Huang, Yan-Ping; Zhao, Yun-Li; Wang, Xuan-Jun; Sheng, Jun

2018-05-01

Dendrobium candidum (DC) and black tea, are traditional chinese drinks, which contain multiple active ingredients. However, whether or not the combination of these two ingredients can improve osteoporosis remains unknown. This study therefore aimed to examine the effects of the combination of DC and black tea extract (BTE) on osteoporosis. Ovariectomy (OVX)-induced osteoporosis in vivo as well as receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in vitro was selected. Results showed that OVX rats that were treated orally with a DC and BTE combination for 12 weeks maintained their calcium (Ca) and phosphorus (P) homeostasis and exhibited significantly enhanced estradiol (E 2 ) and OPG levels. This combination treatment also simultaneously reduced levels of interleukin (IL)-1β, IL-6 and improved the organ coefficients of the uterus and femur as well as BMD and BMC in OVX rats. In addition, this DC and BTE combination suppressed osteoclast differentiation in the RANKL-stimulated osteoclastogenesis of RAW 264.7 cells and effectively inhibited the expression of osteoclast-associated genes and proteins. The results of this study further highlight the fact that a combination of DC and BTE improved ovariectomy-induced osteoporosis in rats and suppressed RANKL-stimulated osteoclastogenesis in RAW 264.7 cells. This combination also significantly alleviated osteoporosis when compared to the alternative sole treatments above, due to synergistic effects among components. One partial mechanism of this combination might be the inhibition of osteoclast proliferation and the regulation of NFATC1/c-Fos expression. Copyright © 2018 Elsevier Inc. All rights reserved.

A study of health beliefs and practices of the Yoruba.

PubMed

Adepoju, Joseph A

2012-01-01

The issue of how immigrant populations combine traditional and Western health beliefs and practices has not been given due attention. Hence, this qualitative research study of Yoruba immigrants, an ethnic group from south-western Nigeria, living in the mid-Atlantic region of the United States, sheds some light on the question of how best to provide culturally appropriate health care to Yoruba immigrant groups with differences in health beliefs and practices. The study found that there are three types of Yoruba immigrant groups: (1) those who use only Western medicine (though mostly for pragmatic reason); (2) those who combine traditional Yoruba and Western beliefs; and (3) those who combine Western medicine and Christian beliefs.

Revisiting the Quantitative-Qualitative Debate: Implications for Mixed-Methods Research

PubMed Central

SALE, JOANNA E. M.; LOHFELD, LYNNE H.; BRAZIL, KEVIN

2015-01-01

Health care research includes many studies that combine quantitative and qualitative methods. In this paper, we revisit the quantitative-qualitative debate and review the arguments for and against using mixed-methods. In addition, we discuss the implications stemming from our view, that the paradigms upon which the methods are based have a different view of reality and therefore a different view of the phenomenon under study. Because the two paradigms do not study the same phenomena, quantitative and qualitative methods cannot be combined for cross-validation or triangulation purposes. However, they can be combined for complementary purposes. Future standards for mixed-methods research should clearly reflect this recommendation. PMID:26523073

A Comparative Theoretical and Computational Study on Robust Counterpart Optimization: I. Robust Linear Optimization and Robust Mixed Integer Linear Optimization

PubMed Central

Li, Zukui; Ding, Ran; Floudas, Christodoulos A.

2011-01-01

Robust counterpart optimization techniques for linear optimization and mixed integer linear optimization problems are studied in this paper. Different uncertainty sets, including those studied in literature (i.e., interval set; combined interval and ellipsoidal set; combined interval and polyhedral set) and new ones (i.e., adjustable box; pure ellipsoidal; pure polyhedral; combined interval, ellipsoidal, and polyhedral set) are studied in this work and their geometric relationship is discussed. For uncertainty in the left hand side, right hand side, and objective function of the optimization problems, robust counterpart optimization formulations induced by those different uncertainty sets are derived. Numerical studies are performed to compare the solutions of the robust counterpart optimization models and applications in refinery production planning and batch process scheduling problem are presented. PMID:21935263

Commercial Essential Oils as Potential Antimicrobials to Treat Skin Diseases

PubMed Central

Orchard, Ané

2017-01-01

Essential oils are one of the most notorious natural products used for medical purposes. Combined with their popular use in dermatology, their availability, and the development of antimicrobial resistance, commercial essential oils are often an option for therapy. At least 90 essential oils can be identified as being recommended for dermatological use, with at least 1500 combinations. This review explores the fundamental knowledge available on the antimicrobial properties against pathogens responsible for dermatological infections and compares the scientific evidence to what is recommended for use in common layman's literature. Also included is a review of combinations with other essential oils and antimicrobials. The minimum inhibitory concentration dilution method is the preferred means of determining antimicrobial activity. While dermatological skin pathogens such as Staphylococcus aureus have been well studied, other pathogens such as Streptococcus pyogenes, Propionibacterium acnes, Haemophilus influenzae, and Brevibacterium species have been sorely neglected. Combination studies incorporating oil blends, as well as interactions with conventional antimicrobials, have shown that mostly synergy is reported. Very few viral studies of relevance to the skin have been made. Encouragement is made for further research into essential oil combinations with other essential oils, antimicrobials, and carrier oils. PMID:28546822

Combining fluorescent in situ hybridization data with ISS staging improves risk assessment in myeloma: an International Myeloma Working Group collaborative project.

PubMed

Avet-Loiseau, H; Durie, B G M; Cavo, M; Attal, M; Gutierrez, N; Haessler, J; Goldschmidt, H; Hajek, R; Lee, J H; Sezer, O; Barlogie, B; Crowley, J; Fonseca, R; Testoni, N; Ross, F; Rajkumar, S V; Sonneveld, P; Lahuerta, J; Moreau, P; Morgan, G

2013-03-01

The combination of serum β2-microglobulin and albumin levels has been shown to be highly prognostic in myeloma as the International Staging System (ISS). The aim of this study was to assess the independent contributions of ISS stage and cytogenetic abnormalities in predicting outcomes. A retrospective analysis of international studies looking at both ISS and cytogenetic abnormalities was performed in order to assess the potential role of combining ISS stage and cytogenetics to predict survival. This international effort used the International Myeloma Working Group database of 12 137 patients treated worldwide for myeloma at diagnosis, of whom 2309 had cytogenetic studies and 5387 had analyses by fluorescent in situ hybridization (iFISH). Comprehensive analyses used 2642 patients with sufficient iFISH data available. Using the comprehensive iFISH data, combining both t(4;14) and deletion (17p), along with ISS stage, significantly improved the prognostic assessment in terms of progression-free survival and overall survival. The additional impact of patient age and use of high-dose therapy was also demonstrated. In conclusion, the combination of iFISH data with ISS staging significantly improves risk assessment in myeloma.

Smart watch-based coaching with tiotropium and olodaterol ameliorates physical activity in patients with chronic obstructive pulmonary disease

PubMed Central

Hataji, Osamu; Nishii, Yoichi; Ito, Kentaro; Sakaguchi, Tadashi; Saiki, Haruko; Suzuki, Yuta; D'Alessandro-Gabazza, Corina; Fujimoto, Hajime; Kobayashi, Tetsu; Gabazza, Esteban C.; Taguchi, Osamu

2017-01-01

Combined therapy with tiotropium and olodaterol notably improves parameters of lung function and quality of life in patients with chronic obstructive pulmonary disease (COPD) compared to mono-components; however, its effect on physical activity is unknown. The present study evaluated whether combination therapy affects daily physical performance in patients with COPD under a smart watch-based encouragement program. This was a non-blinded clinical trial with no randomization or placebo control. A total of 20 patients with COPD were enrolled in the present study. The patients carried an accelerometer for 4 weeks; they received no therapy during the first 2 weeks but they were treated with combined tiotropium and olodaterol under a smart watch-based encouragement program for the last 2 weeks. The pulmonary function test, COPD assessment test, 6-min walk distance and parameters of physical activity were significantly improved (P<0.05) by combination therapy under smart watch-based coaching compared with values prior to treatment. To the best of our knowledge, the present study for the first time provides evidence that smart watch-based coaching in combination with tiotropium and olodaterol may improve daily physical activity in chronic obstructive pulmonary disease. PMID:29104624

Smart watch-based coaching with tiotropium and olodaterol ameliorates physical activity in patients with chronic obstructive pulmonary disease.

PubMed

Hataji, Osamu; Nishii, Yoichi; Ito, Kentaro; Sakaguchi, Tadashi; Saiki, Haruko; Suzuki, Yuta; D'Alessandro-Gabazza, Corina; Fujimoto, Hajime; Kobayashi, Tetsu; Gabazza, Esteban C; Taguchi, Osamu

2017-11-01

Combined therapy with tiotropium and olodaterol notably improves parameters of lung function and quality of life in patients with chronic obstructive pulmonary disease (COPD) compared to mono-components; however, its effect on physical activity is unknown. The present study evaluated whether combination therapy affects daily physical performance in patients with COPD under a smart watch-based encouragement program. This was a non-blinded clinical trial with no randomization or placebo control. A total of 20 patients with COPD were enrolled in the present study. The patients carried an accelerometer for 4 weeks; they received no therapy during the first 2 weeks but they were treated with combined tiotropium and olodaterol under a smart watch-based encouragement program for the last 2 weeks. The pulmonary function test, COPD assessment test, 6-min walk distance and parameters of physical activity were significantly improved (P<0.05) by combination therapy under smart watch-based coaching compared with values prior to treatment. To the best of our knowledge, the present study for the first time provides evidence that smart watch-based coaching in combination with tiotropium and olodaterol may improve daily physical activity in chronic obstructive pulmonary disease.

Role of rifampin-based combination therapy for severe community-acquired Legionella pneumophila pneumonia.

PubMed

Varner, Terra R; Bookstaver, P Brandon; Rudisill, Celeste N; Albrecht, Helmut

2011-07-01

To review the literature concerning the role of rifampin in the combination treatment of Legionella pneumophila pneumonia. A search of MEDLINE and Ovid databases was conducted (January 1970-May 2011) using the search terms Legionella pneumophila, pneumonia, Legionnaires' disease, rifampin or rifampicin, macrolide, fluoroquinolone, erythromycin, clarithromycin, levofloxacin, ciprofloxacin, and moxifloxacin In vivo studies published in English that compared antimicrobial therapies including rifampin for the treatment of Legionella pneumonia, as well as in vitro studies including an assessment of rifampin bioactivity, were included. Macrolides and fluoroquinolones have been effective as monotherapy in the treatment of L. pneumophila pneumonia. This review includes evidence summaries from 4 bioactivity evaluations, 6 clinical studies, and 6 reported cases of combination rifampin use. Combined with supporting evidence, the role of combination rifampin therapy is further delineated. Interpretation of the data is limited by the potential for selection bias and lack of consistent comparators. Rifampin therapy should be considered only for patients with severe disease or significant comorbid conditions (eg, uncontrolled diabetes, smoking, or obstructive lung disease) including immunocompromised hosts and those refractory to conventional monotherapy regimens. Caution for significant adverse drug events and drug-drug interactions should be taken with the addition of rifampin.

Combined Efficacy of Gallic Acid and MiADMSA with Limited Beneficial Effects Over MiADMSA Against Arsenic-induced Oxidative Stress in Mouse

PubMed Central

Pachauri, Vidhu; Flora, SJS

2015-01-01

Gallic acid is an organic acid known for its antioxidant and anticancer properties. The present study is focused on evaluating the role of gallic acid in providing better therapeutic outcomes against arsenic-induced toxicity. Animals pre-exposed to arsenic were treated with monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), a new chelating drug, alone and in combination with gallic acid, consecutively for 10 days. The study suggests that (1) gallic acid in presence of MiADMSA is only moderately beneficial against arsenic, (2) monotherapy with gallic acid is more effective than in combination with MiADMSA after arsenic exposure in reducing oxidative injury, and (3) MiADMSA monotherapy as reported previously provides significant therapeutic efficacy against arsenic. Thus, based on the present results, we conclude that gallic acid is effective against arsenic-induced oxidative stress but provides limited additional beneficial effects when administered in combination with MiADMSA. We still recommend that lower doses of gallic acid be evaluated both individually and in combination with MiADMSA, as it might not exhibit the shortcomings we observed with higher doses in this study. PMID:26339189

Combined Efficacy of Gallic Acid and MiADMSA with Limited Beneficial Effects Over MiADMSA Against Arsenic-induced Oxidative Stress in Mouse.

PubMed

Pachauri, Vidhu; Flora, Sjs

2015-01-01

Gallic acid is an organic acid known for its antioxidant and anticancer properties. The present study is focused on evaluating the role of gallic acid in providing better therapeutic outcomes against arsenic-induced toxicity. Animals pre-exposed to arsenic were treated with monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), a new chelating drug, alone and in combination with gallic acid, consecutively for 10 days. The study suggests that (1) gallic acid in presence of MiADMSA is only moderately beneficial against arsenic, (2) monotherapy with gallic acid is more effective than in combination with MiADMSA after arsenic exposure in reducing oxidative injury, and (3) MiADMSA monotherapy as reported previously provides significant therapeutic efficacy against arsenic. Thus, based on the present results, we conclude that gallic acid is effective against arsenic-induced oxidative stress but provides limited additional beneficial effects when administered in combination with MiADMSA. We still recommend that lower doses of gallic acid be evaluated both individually and in combination with MiADMSA, as it might not exhibit the shortcomings we observed with higher doses in this study.

The Strength and Number of Visual Mediators in Learning Letter-Sound Associations in Reading: A Film Study.

ERIC Educational Resources Information Center

Ackerman, Jerrold

The role of visual imagery in the learning of letter-sound combinations was investigated using such mediating images as two scoops of ice cream for the letter "m." In a preliminary study, high-, medium-, and low-strength mediating images were determined for each letter-sound combination. The 216 kindergarten subjects in the main study were…

When Worlds Collide--Examining the Challenges Faced by Teacher Education Programmes Combining Professional Vocational Competence with Academic Study, Lessons from Further Education to Higher Education

ERIC Educational Resources Information Center

Shaw, Angela

2016-01-01

This paper examines the challenges faced by higher education institutions in designing, teaching and quality assuring programmes of study which, of necessity, must combine the gaining of professional vocational competence with academic study. The paper gives recognition to the policy framework in which these programmes fit--with particular…

An Evaluation of a Progressive High-Probability Instructional Sequence Combined with Low-Probability Demand Fading in the Treatment of Food Selectivity

ERIC Educational Resources Information Center

Penrod, Becky; Gardella, Laura; Fernand, Jonathan

2012-01-01

Few studies have examined the effects of the high-probability instructional sequence in the treatment of food selectivity, and results of these studies have been mixed (e.g., Dawson et al., 2003; Patel et al., 2007). The present study extended previous research on the high-probability instructional sequence by combining this procedure with…

Introduction to Film and Video--An Integrative Approach.

ERIC Educational Resources Information Center

Lev, Peter; Moore, Barry

1986-01-01

Outlines an introductory course that combines filmmaking experience with theoretical and critical film studies. Approach combines traditional aesthetic emphasis with practical understanding of how films are made. (MS)

Combined fractional resurfacing (10600 nm/1540 nm): Tridimensional imaging evaluation of a new device for skin rejuvenation.

PubMed

Mezzana, Paolo; Valeriani, Maurizio; Valeriani, Roberto

2016-11-01

In this study were described the results, by tridimensional imaging evaluation, of the new "Combined Fractional Resurfacing" technique with the first fractional laser that overtakes the limits of traditional ablative, nonablative fractional resurfacing by combining CO 2 ablative and GaAs nonablative lasers. These two wavelengths can work separately or in a mixed modality to give the best treatment choice to all the patients. In this study, it is demonstrated that the simultaneous combination of the CO 2 wavelength (10600 nm) and GaAs wavelength (1540 nm) reduced the downtime, reduced pain during the treatment, and produced better results on fine wrinkles reduction and almost the same results on pigmentation as seen with 3D analysis by Antera (Miravex).

Are Chinese Correlative Conjunctions Psychologically Real? An Investigation of the Combination Frequency Effect.

PubMed

Kong, Lingyue; Zhang, John X; Zhang, Yongwei

2016-08-01

The present study used an online grammaticality judgment task to examine whether Chinese discontinuous correlative conjunctions are psychologically real in mental lexicon. High- and low-frequency discontinuous correlative conjunctions were compared with random combinations differing in combination frequencies but matched for constituent word frequency. Forty graduate students participated in the study. Results showed that responses were faster and more accurate for high-frequency correlative conjunctions than low-frequency ones, but the effects were absent for random combinations. The results indicate that Chinese discontinuous correlative conjunctions have psychological reality in mental lexicon in addition to the representation of their constituent words, and that grammatical functions of correlative conjunctions may be a critical factor for the formation of such holistic representations. © The Author(s) 2016.

[Comparative study of combined local treatment (sulfadimidine, metronidazole and nystatin) and the standard monotherapy in uncomplicated bacterial vaginosis].

PubMed

Milánkovits, Márton; Baksay, László; Plachy, János

2002-12-22

Comparative, in vivo, human, prospective, single blind, clinical and microbiological diagnoses based and randomised study of the treatment of uncomplicated bacterial vaginosis with two forms of combined (metronidazole + nystatin + sulfadimidin) vaginal suppositories (laminated and mixed containing the same ingredients) and the standard preparations available in the Hungarian market (Dalacin vaginal cream and Klion vaginal suppository). The examinations involved 60 volunteers and were performed in the Gynecological Outpatient Clinic of the Council of Erd, the microbiological samples were examined at Saint Rókus Hospital in Budapest. The combined treatment was better tolerated and resulted in normal vaginal pH significantly more often at the same rate of recovery. The combined treatment is simultaneously effective in cases of the most prevalent coinfections too.

On the displacement of leisure items by food during multiple-stimulus preference assessments.

PubMed Central

Bojak, S L; Carr, J E

1999-01-01

Previous studies have demonstrated that when food and leisure stimuli are combined in multiple-stimulus preference assessments, individuals typically select food more often, although the leisure stimuli also have known reinforcing properties. The purpose of the current study was to replicate this effect and determine its durability by examining the effect after mealtimes. Four adults who had been diagnosed with severe mental retardation were given three initial multiple-stimulus (without replacement) preference assessments (i.e., food, leisure stimuli, and combined). All participants selected food items as the most preferred stimuli in the combined assessments. Combined assessments were then administered immediately before and after the evening meal for each participant for 1 week. The results showed similar data both before and after mealtimes. PMID:10641304

High power (2+1) ×1 taper-fused all-fiber side-pumped combiner

NASA Astrophysics Data System (ADS)

Wu, Juan; Ma, Yi; Yan, Hong

2018-03-01

A novel design and fabrication method of a (2+1) ×1 taper-fused all-fiber side-pumped combiner is reported. The pump coupling efficiency of this pump combiner was studied theoretically and experimentally. The measurement results indicated that the coupling efficiency of the pump light is 96.5%, the signal-to-pump isolation reaches 31dB, and the signal loss of the combiner is 0.19dB. A backward-pumped fiber laser system was established by using this (2+1) ×1 side-pumped combiner directly, achieving a signal laser output of 1007W with M2=1.33.

The effects of luminance contrast, colour combinations, font, and search time on brand icon legibility.

PubMed

Ko, Ya-Hsien

2017-11-01

This study explored and identified the effects of luminance contrast, colour combinations, font, and search time on brand icon legibility. A total of 108 participants took part in the experiment. As designed, legibility was measured as a function of the following independent variables: four levels of luminance contrast, sixteen target/background colour combinations, two fonts, and three search times. The results showed that a luminance contrast of 18:1 provided readers with the best legibility. Yellow on black, yellow on blue, and white on blue were the three most legible colour combinations. One of this study's unique findings was that colour combinations may play an even more important role than luminance contrast in the overall legibility of brand icon design. The 12-s search time corresponded with the highest legibility. Arial font was more legible than Times New Roman. These results provide some guidance for brand icon and product advertisement design. Copyright © 2017 Elsevier Ltd. All rights reserved.

Low-temperature, ultrahigh-vacuum tip-enhanced Raman spectroscopy combined with molecular beam epitaxy for in situ two-dimensional materials' studies

NASA Astrophysics Data System (ADS)

Sheng, Shaoxiang; Li, Wenbin; Gou, Jian; Cheng, Peng; Chen, Lan; Wu, Kehui

2018-05-01

Tip-enhanced Raman spectroscopy (TERS), which combines scanning probe microscopy with the Raman spectroscopy, is capable to access the local structure and chemical information simultaneously. However, the application of ambient TERS is limited by the unstable and poorly controllable experimental conditions. Here, we designed a high performance TERS system based on a low-temperature ultrahigh-vacuum scanning tunneling microscope (LT-UHV-STM) and combined with a molecular beam epitaxy (MBE) system. It can be used for growing two-dimensional (2D) materials and for in situ STM and TERS characterization. Using a 2D silicene sheet on the Ag(111) surface as a model system, we achieved an unprecedented 109 Raman single enhancement factor in combination with a TERS spatial resolution down to 0.5 nm. The results show that TERS combined with a MBE system can be a powerful tool to study low dimensional materials and surface science.

Treatment of selective mutism based on cognitive behavioural therapy, psychopharmacology and combination therapy - a systematic review.

PubMed

Østergaard, Kasper Rud

2018-05-01

Selective mutism (SM) is a debilitating childhood anxiety disorder characterized by a persistent lack of speech in certain social settings and is considered hard to treat. Cognitive behavioral therapy (CBT) and pharmacological treatments are the best described treatments in the literature. To test whether there is evidence on treatment based on CBT, medication or a combination of these. Systematic and critical review of the literature on CBT and/or pharmacological treatments of SM. Literature was sought on PubMed, Embase and Psycinfo in March 2017. Of the included studies, six examined CBT, seven pharmacologic treatment and two a combination of these. Using CBT 53/60 children improved symptomatically whilst respectively 55/67 and 6/7 improved using pharmacologic- and combination-treatment. Pharmacologic treatment and especially CBT showed promising results supported by some degree of evidence, which combination treatment lacks. Yet small numbers, few RCTs, heterogeneous study designs, lack of consistent measures, short treatment and follow-up periods, generally limits the evidence. This needs focus in future research.

Combined treatment with oral finasteride and topical minoxidil in male androgenetic alopecia: a randomized and comparative study in Chinese patients.

PubMed

Hu, Ruiming; Xu, Feng; Sheng, Youyu; Qi, Sisi; Han, Yumei; Miao, Ying; Rui, Wenlong; Yang, Qinping

2015-01-01

Finasteride at 1 mg/day and 5% topical minoxidil are effective in male androgenetic alopecia (MAGA). However, studies describing their effects in Chinese individuals are scarce. 450 Chinese MAGA patients were randomly assigned to receive finasteride (n = 160), minoxidil (n = 130) and combined medication (n = 160) for 12 months. The patients returned to the clinic every 3 months for efficacy evaluation. And efficacy was evaluated in 428 men at treatment end, including 154, 122, and 152 in the finasteride, 5% minoxidil, and combination groups, respectively. All groups showed similar baseline characteristics, including age at enrollment, and duration and severity of alopecia (p > 0.05). At 12 months, 80.5, 59, and 94.1% men treated with finasteride, 5% minoxidil and the combination therapy showed improvement, respectively. Adverse reactions were rare (finasteride, 1.8%; minoxidil, 6.1%), and disappeared right after drug withdrawal. In conclusion, finasteride is superior to 5% minoxidil, while the combined medication showed the best efficacy. © 2015 Wiley Periodicals, Inc.

Metformin and propranolol combination prevents cancer progression and metastasis in different breast cancer models

PubMed Central

Bondarenko, Maryna; Laluce, Nahuel Cesatti; Rozados, Viviana; Nicolas, André; Carré, Manon; Scharovsky, O. Graciela; Márquez, Mauricio Menacho

2017-01-01

Discovery of new drugs for cancer treatment is an expensive and time-consuming process and the percentage of drugs reaching the clinic remains quite low. Drug repositioning refers to the identification and development of new uses for existing drugs and represents an alternative drug development strategy. In this work, we evaluated the antitumor effect of metronomic treatment with a combination of two repositioned drugs, metformin and propranolol, in triple negative breast cancer models. By in vitro studies with five different breast cancer derived cells, we observed that combined treatment decreased proliferation (P < 0.001), mitochondrial activity (P < 0.001), migration (P < 0.001) and invasion (P < 0.001). In vivo studies in immunocompetent mice confirmed the potential of this combination in reducing tumor growth (P < 0.001) and preventing metastasis (P < 0.05). Taken together our results suggest that metformin plus propranolol combined treatment might be beneficial for triple negative breast cancer control, with no symptoms of toxicity. PMID:27926515

Clinical experience with trimegestone as a new progestin in HRT.

PubMed

Grubb, Gary; Spielmann, Daniele; Pickar, James; Constantine, Ginger

2003-11-01

Trimegestone (TMG) is a novel, 19-norpregnane progestin, which demonstrates endometrial selectivity with a reduced progestin-related side effect profile when compared to several other currently marketed progestins. TMG has been studied in combination with 17beta-estradiol (17beta-E2) and conjugated equine estrogens (CEE). TMG-containing HRT agents were effective in relieving vasomotor symptoms and providing protection from endometrial hyperplasia with < or =1% hyperplasia. In clinical trials with sequential regimens, TMG provided predictable withdrawal bleeding associated with a low incidence of irregular and prolonged bleeding. Clinical studies of continuous combined regimens of estrogen/TMG combinations demonstrated high levels of amenorrhea. Both 17beta-E2 and CEE/TMG combinations have shown improved bone mineral density and quality-of-life assessments. Both continuous combined and sequential regimens of 17beta-E2/TMG and CEE/TMG have a favorable clinical profile. TMG provides an important new option for the treatment of postmenopausal symptoms and the prevention of osteoporosis.

Pharmacological aspects of the combined use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and gamma-hydroxybutyric acid (GHB): a review of the literature.

PubMed

Uys, Joachim D K; Niesink, Raymond J M

2005-07-01

Epidemiological studies show that the use of club drugs is on the rise. Furthermore, the last few decades have seen a rise in patterns of polydrug use. One of the combinations frequently used is ecstasy (MDMA) with gammahydroxybutyrate (GHB). For effective prevention it is important to be aware of this phenomenon and of the pharmacology of these drugs. The effects of the combination extend to different neurotransmitter systems, including serotonin, dopamine and noradrenaline. Studies investigating the effects of combinations of psychoactive substances are limited. In this review we describe the subjective effects of the MDMA/GHB combination. Furthermore, we review the individual actions of MDMA on serotonin, dopamine and noradrenaline systems. In addition, actions of GHB on these systems are discussed as a possible pharmacological basis for the interaction of both drugs. It is postulated that GHB attenuates the unpleasant or dysphoric effects of MDMA by its effect on the central dopaminergic system.

Predictors of transitions from single to multiple job holding: Results of a longitudinal study among employees aged 45-64 in the Netherlands.

PubMed

Bouwhuis, Stef; Geuskens, Goedele A; Boot, Cécile R L; Bongers, Paulien M; van der Beek, Allard J

2017-08-01

To construct prediction models for transitions to combination multiple job holding (MJH) (multiple jobs as an employee) and hybrid MJH (being an employee and self-employed), among employees aged 45-64. A total of 5187 employees in the Netherlands completed online questionnaires annually between 2010 and 2013. We applied logistic regression analyses with a backward elimination strategy to construct prediction models. Transitions to combination MJH and hybrid MJH were best predicted by a combination of factors including: demographics, health and mastery, work characteristics, work history, skills and knowledge, social factors, and financial factors. Not having a permanent contract and a poor household financial situation predicted both transitions. Some predictors only predicted combination MJH, e.g., working part-time, or hybrid MJH, e.g., work-home interference. A wide variety of factors predict combination MJH and/or hybrid MJH. The prediction model approach allowed for the identification of predictors that have not been previously studied. © 2017 Wiley Periodicals, Inc.

Effects of etoposide alone and in combination with piroxicam on canine osteosarcoma cell lines.

PubMed

Ong, S M; Saeki, K; Tanaka, Y; Nishimura, R; Nakagawa, T

2016-12-01

Osteosarcoma (OSA) is the most common primary bone tumour in dogs. The poor survival rate in dogs with OSA highlights the need for new therapeutic approaches. This study evaluated the cytotoxic effects of etoposide, alone and in combination with piroxicam, on canine OSA cell cultures. Etoposide alone significantly suppressed cell growth and viability, whereas etoposide in combination with piroxicam exhibited concentration dependent cytotoxicity. The anti-proliferative effect was a result of inactivity of the Cdc2-cyclin B1 complex, which correlated with an increase in the G 2 /M fraction. This subsequently activated the apoptosis cascade, as indicated by elevated apoptosis levels and up-regulation of poly (ADP-ribose) polymerase proteolytic cleavage. Down-regulation of survivin expression induced by the combination treatment may have contributed to the enhanced cytotoxicity. The results of this study suggest that further investigation of etoposide and piroxicam as a therapeutic combination for canine OSA is warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

Social Competence Intervention in Autistic Spectrum Disorders (ASDS) - A Case Study

ERIC Educational Resources Information Center

Amin, Noor A.; Oweini, Ahmad

2013-01-01

The purpose of this case study was to determine the effectiveness of a combined intervention in remediating the social skills in a first-grader with a disorder from the autism spectrum disorders (ASDs). The researcher also aimed to identify the changes observed during the intervention period. The combined intervention consisted of reading…

Guide for Teaching Chemistry-Physics Combined 1-2, 3-4 (PSSC - CHEMS).

ERIC Educational Resources Information Center

Millstone, H. George

This guide is written for a combined physics-chemistry course taught over a two-year period. The subject matter contains the major ideas in Chemical Education Materials Study (CHEMS) Chemistry and Physical Science Study Committee (PSSC) Physics. The guide includes discussion of text references, laboratory experiments, films, testing and evaluation…

Students' Thinking Process in Solving Combination Problems Considered from Assimilation and Accommodation Framework

ERIC Educational Resources Information Center

Jalan, Sukoriyanto; Nusantara, Toto; Subanji, Subanji; Chandra, Tjang Daniel

2016-01-01

This study aims to explain the thinking process of students in solving combination problems considered from assimilation and accommodation frameworks. This research used a case study approach by classifying students into three categories of capabilities namely high, medium and low capabilities. From each of the ability categories, one student was…

Patterns of Adolescents' Participation in Organized Activities: Are Sports Best when Combined with Other Activities?

ERIC Educational Resources Information Center

Linver, Miriam R.; Roth, Jodie L.; Brooks-Gunn, Jeanne

2009-01-01

Although many adolescents participate in sports and other types of organized activities, little extant research explores how youth development outcomes may vary for youth involved in different combinations of activities. The present study uses the Child Development Supplement of the Panel Study of Income Dynamics, a large, nationally…

Expanding Simulations as a Means of Tactical Training with Multinational Partners

DTIC Science & Technology

2017-06-09

gap through DOTMLPF in combination with an assessment of two case studies involving higher echelon use of simulations. Through this methodology , the...DOTMLPF in combination with an assessment of two case studies involving higher echelon use of simulations. Through this methodology , the findings...CHAPTER 3 RESEARCH METHODOLOGY .................................................................26 CHAPTER 4 ANALYSIS

Considering the Impact of Racial Stigmas and Science Identity: Persistence among Biomedical and Behavioral Science Aspirants

ERIC Educational Resources Information Center

Chang, Mitchell J.; Eagan, M. Kevin; Lin, Monica H.; Hurtado, Sylvia

2011-01-01

This longitudinal study examined whether the combination of having negative racial interactions and identifying with one's domain of study affects underrepresented racial minority freshmen. In line with stereotype threat theory, students reporting higher levels of this combination of experiences and attributes were significantly less likely to…

34 CFR 656.10 - What combined application may an institution submit?

Code of Federal Regulations, 2010 CFR

2010-07-01

... LANGUAGE AND AREA STUDIES OR FOREIGN LANGUAGE AND INTERNATIONAL STUDIES How Does One Apply for a Grant... 34 Education 3 2010-07-01 2010-07-01 false What combined application may an institution submit? 656.10 Section 656.10 Education Regulations of the Offices of the Department of Education (Continued...

E-Learning Education of Educational Technologies in Full-Time and Combined Studies

ERIC Educational Resources Information Center

Nagyová, Ingrid

2010-01-01

The article focuses on research in the area of Educational Technologies, mainly on the comparison of ways, methods and processes of education in full-time and combined studies. The work was undertaken in the Pedagogical Faculty, Ostrava University, Ostrava, Czech Republic. The fundamental presumptions and hypotheses that the work intended to…

Everything Old Is New Again: Using Nelfinavir to Radiosensitize Rectal Cancer

PubMed Central

Meyn, Raymond E.; Krishnan, Sunil; Skinner, Heath D.

2016-01-01

Summary Repurposing agents approved for other indications to radiosensitize tumors may be advantageous. The study by Hill and colleagues utilizes Nelfinavir, an HIV protease inhibitor, in combination with radiotherapy in rectal cancer in a prospective study. This combination may improve tumor perfusion and regression compared to radiotherapy alone. PMID:26920893

Combining Mass Spectrometry and Toxicology for a Multi-Country European Epidemiologic Study on Drinking Water Disinfection By-Products.

EPA Science Inventory

The HiWATE (Health Impacts of long-term exposure to disinfection by-products in drinking WATEr) project is the first systematic analysis that combines the epidemiology on adverse pregnancy outcomes with analytical chemistry and analytical biology in the European Union. This study...

Combining Mass Spectrometry and Toxicology for a Multi-Country European Epidemiologic Study on Drinking Water Disinfection By-Products

EPA Science Inventory

The HiWATE (Health Impacts of long-term exposure to disinfection by-products in drinking WATEr) project is the first systematic analysis that combines the epidemiology on adverse pregnancy outcomes with analytical chemistry and analytical biology in the European Union. This study...

School Enterprises: Combining Vocational Learning with Production. International Project on Technical and Vocational Education (UNEVOC).

ERIC Educational Resources Information Center

Singh, Madhu

Trends in combining learning and production were examined through case studies of school enterprises in 11 countries: China, India, Indonesia, Papua New Guinea, Germany, Botswana, Kenya, Ghana, Algeria, Cuba, and Costa Rica. The study focused on the following: types and structures of school enterprises; organization of learning; competency…

Better Cognitive Performance in Elderly Taking Antioxidant Vitamins E and C Supplements in Combination with NSAIDs: The Cache County Study

PubMed Central

Fotuhi, Majid; Zandi, Peter P.; Hayden, Kathleen M.; Khachaturian, Ara S.; Szekely, Christine A.; Wengreen, Heidi; Munger, Ronald G.; Norton, Maria C.; Tschanz, JoAnn T.; Lyketsos, Constantine G.; Breitner, John C.S.; Welsh-Bohmer, Kathleen A.

2009-01-01

Studies have shown less cognitive decline and lower risk of Alzheimer's disease in elderly individuals consuming either antioxidant vitamins or non-steroidal anti-inflammatory drugs (NSAIDs). The potential of added benefit from their combined use has not been studied. We therefore analyzed data from 3,376 elderly participants of the Cache County Study who were given the Modified Mini-Mental State (3MS) examination up to three times over eight years. Those who used a combination of Vitamins E and C supplements and NSAIDs at baseline declined by an average 0.96 fewer points every 3 years than non-users (p<0.05). This apparent effect was attributable entirely to participants with the APOE ε4 allele, whose users declined by 2.25 fewer points than non-users every 3 years (p<0.05). These results suggest that among elderly individuals with an APOE ε4 allele, there is an association between using antioxidant supplements in combination with NSAIDs and less cognitive decline over time. PMID:18631971

Effects of combining vertical and horizontal information into a primary flight display

NASA Technical Reports Server (NTRS)

Abbott, Terence S.; Nataupsky, Mark; Steinmetz, George G.

1987-01-01

A ground-based aircraft simulation study was conducted to determine the effects of combining vertical and horizontal flight information into a single display. Two display configurations were used in this study. The first configuration consisted of a Primary Flight Display (PFD) format and a Horizontal Situation Display (HSD) with the PFD displayed conventionally above the HSD. For the second display configuration, the HSD format was combined with the PFD format. Four subjects participated in this study. Data were collected on performance parameters, pilot-control inputs, auditory evoked response parameters (AEP), oculometer measurements (eye-scan), and heart rate. Subjective pilot opinion was gathered through questionnaire data and scorings for both the Subjective Workload Assessment Technique (SWAT) and the NASA Task Load Index (NASA-TLX). The results of this study showed that, from a performance and subjective standpoint, the combined configuration was better than the separate configuration. Additionally, both the eye-transition and eye-dwell times for the separate HSD were notably higher than expected, with a 46% increase in available visual time when going from double to single display configuration.

Meta-analyses and adaptive group sequential designs in the clinical development process.

PubMed

Jennison, Christopher; Turnbull, Bruce W

2005-01-01

The clinical development process can be viewed as a succession of trials, possibly overlapping in calendar time. The design of each trial may be influenced by results from previous studies and other currently proceeding trials, as well as by external information. Results from all of these trials must be considered together in order to assess the efficacy and safety of the proposed new treatment. Meta-analysis techniques provide a formal way of combining the information. We examine how such methods can be used in combining results from: (1) a collection of separate studies, (2) a sequence of studies in an organized development program, and (3) stages within a single study using a (possibly adaptive) group sequential design. We present two examples. The first example concerns the combining of results from a Phase IIb trial using several dose levels or treatment arms with those of the Phase III trial comparing the treatment selected in Phase IIb against a control This enables a "seamless transition" from Phase IIb to Phase III. The second example examines the use of combination tests to analyze data from an adaptive group sequential trial.

Combination could be another tool for bowel preparation?

PubMed Central

Soh, Jae Seung; Kim, Kyung-Jo

2016-01-01

Optimal bowel preparation increases the cecal intubation rate and detection of neoplastic lesions while decreasing the procedural time and procedural-related complications. Although high-volume polyethylene glycol (PEG) solution is the most frequently used preparation for bowel cleansing, patients are often unwilling to take PEG solution due to its large volume, poor palatability, and high incidence of adverse events, such as abdominal bloating and nausea. Other purgatives include osmotic agents (e.g., sodium phosphate, magnesium citrate, and sodium sulfate), stimulant agents (e.g., senna, bisacodyl, and sodium picosulfate), and prokinetic agents (e.g., cisapride, mosapride, and itopride). A combination of PEG with an osmotic, stimulant, or prokinetic agent could effectively reduce the PEG solution volume and increase patients’ adherence. Some such solutions have been found in several published studies to not be inferior to PEG alone in terms of bowel cleansing quality. Although combination methods showed similar efficacy and safety, the value of these studies is limited by shortcomings in study design. New effective and well-tolerated combination preparations are required, in addition to rigorous new validated studies. PMID:26973388

Effectiveness of Manual Therapy Combined With Physical Therapy in Treatment of Patellofemoral Pain Syndrome: Systematic Review.

PubMed

Espí-López, Gemma Victoria; Arnal-Gómez, Anna; Balasch-Bernat, Mercè; Inglés, Marta

2017-06-01

The purpose of this study was to conduct a review of randomized controlled trials (RCTs) to determine the treatment effectiveness of the combination of manual therapy (MT) with other physical therapy techniques. Systematic searches of scientific literature were undertaken on PubMed and the Cochrane Library (2004-2014). The following terms were used: "patellofemoral pain syndrome," "physical therapy," "manual therapy," and "manipulation." RCTs that studied adults diagnosed with patellofemoral pain syndrome (PFPS) treated by MT and physical therapy approaches were included. The quality of the studies was assessed by the Jadad Scale. Five RCTs with an acceptable methodological quality (Jadad ≥ 3) were selected. The studies indicated that MT combined with physical therapy has some effect on reducing pain and improving function in PFPS, especially when applied on the full kinetic chain and when strengthening hip and knee muscles. The different combinations of MT and physical therapy programs analyzed in this review suggest that giving more emphasis to proximal stabilization and full kinetic chain treatments in PFPS will help better alleviation of symptoms.

Better cognitive performance in elderly taking antioxidant vitamins E and C supplements in combination with nonsteroidal anti-inflammatory drugs: the Cache County Study.

PubMed

Fotuhi, Majid; Zandi, Peter P; Hayden, Kathleen M; Khachaturian, Ara S; Szekely, Christine A; Wengreen, Heidi; Munger, Ronald G; Norton, Maria C; Tschanz, Joann T; Lyketsos, Constantine G; Breitner, John C S; Welsh-Bohmer, Kathleen

2008-05-01

Studies have shown less cognitive decline and lower risk of Alzheimer's disease in elderly individuals consuming either antioxidant vitamins or nonsteroidal anti-inflammatory drugs (NSAIDs). The potential of added benefit from their combined use has not been studied. We therefore analyzed data from 3,376 elderly participants of the Cache County Study who were given the Modified Mini-Mental State examination up to three times during a period of 8 years. Those who used a combination of vitamins E and C supplements and NSAIDs at baseline declined by an average 0.96 fewer points every 3 years than nonusers (P < .05). This apparent effect was attributable entirely to participants with the APOE epsilon4 allele, whose users declined by 2.25 fewer points than nonusers every 3 years (P < .05). These results suggest that among elderly individuals with an APOE epsilon4 allele, there is an association between using antioxidant supplements in combination with NSAIDs and less cognitive decline over time.

Upper Limb Outcome Measures Used in Stroke Rehabilitation Studies: A Systematic Literature Review

PubMed Central

Santisteban, Leire; Térémetz, Maxime; Bleton, Jean-Pierre; Baron, Jean-Claude; Maier, Marc A.; Lindberg, Påvel G.

2016-01-01

Background Establishing which upper limb outcome measures are most commonly used in stroke studies may help in improving consensus among scientists and clinicians. Objective In this study we aimed to identify the most commonly used upper limb outcome measures in intervention studies after stroke and to describe domains covered according to ICF, how measures are combined, and how their use varies geographically and over time. Methods Pubmed, CinHAL, and PeDRO databases were searched for upper limb intervention studies in stroke according to PRISMA guidelines and477 studies were included. Results In studies 48different outcome measures were found. Only 15 of these outcome measures were used in more than 5% of the studies. The Fugl-Meyer Test (FMT)was the most commonly used measure (in 36% of studies). Commonly used measures covered ICF domains of body function and activity to varying extents. Most studies (72%) combined multiple outcome measures: the FMT was often combined with the Motor Activity Log (MAL), the Wolf Motor Function Test and the Action Research Arm Test, but infrequently combined with the Motor Assessment Scale or the Nine Hole Peg Test. Key components of manual dexterity such as selective finger movements were rarely measured. Frequency of use increased over a twelve-year period for the FMT and for assessments of kinematics, whereas other measures, such as the MAL and the Jebsen Taylor Hand Test showed decreased use over time. Use varied largely between countries showing low international consensus. Conclusions The results showed a large diversity of outcome measures used across studies. However, a growing number of studies used the FMT, a neurological test with good psychometric properties. For thorough assessment the FMT needs to be combined with functional measures. These findings illustrate the need for strategies to build international consensus on appropriate outcome measures for upper limb function after stroke. PMID:27152853

Combined BTK and PI3Kδ Inhibition with Acalabrutinib and ACP-319 Improves Survival and Tumor Control in CLL Mouse Model.

PubMed

Niemann, Carsten U; Mora-Jensen, Helena I; Dadashian, Eman L; Krantz, Fanny; Covey, Todd; Chen, Shih-Shih; Chiorazzi, Nicholas; Izumi, Raquel; Ulrich, Roger; Lannutti, Brian J; Wiestner, Adrian; Herman, Sarah E M

2017-10-01

Purpose: Targeting the B-cell receptor (BCR) pathway with inhibitors of Bruton tyrosine kinase (BTK) and PI3Kδ is highly effective for the treatment of chronic lymphocytic leukemia (CLL). However, deep remissions are uncommon, and drug resistance with single-agent therapy can occur. In vitro studies support the effectiveness of combing PI3Kδ and BTK inhibitors. Experimental Design: As CLL proliferation and survival depends on the microenvironment, we used murine models to assess the efficacy of the BTK inhibitor acalabrutinib combined with the PI3Kδ inhibitor ACP-319 in vivo We compared single-agent with combination therapy in TCL1-192 cell-injected mice, a model of aggressive CLL. Results: We found significantly larger reductions in tumor burden in the peripheral blood and spleen of combination-treated mice. Although single-agent therapy improved survival compared with control mice by a few days, combination therapy extended survival by over 2 weeks compared with either single agent. The combination reduced tumor proliferation, NF-κB signaling, and expression of BCL-xL and MCL-1 more potently than single-agent therapy. Conclusions: The combination of acalabrutinib and ACP-319 was superior to single-agent treatment in a murine CLL model, warranting further investigation of this combination in clinical studies. Clin Cancer Res; 23(19); 5814-23. ©2017 AACR . ©2017 American Association for Cancer Research.

Combination Therapy Strategies Against Multiple-Resistant Streptococcus Suis.

PubMed

Yu, Yang; Fang, Jin-Tao; Zheng, Mei; Zhang, Qing; Walsh, Timothy R; Liao, Xiao-Ping; Sun, Jian; Liu, Ya-Hong

2018-01-01

Streptococcus suis is a major swine pathogen, an emerging zoonotic agent responsible for meningitis, endocarditis and septicaemia followed by deafness in humans. The development of antimicrobial resistance in S. suis increases the risk for therapeutic failure in both animals and humans. In this study, we report the synergism of combination therapy against multi-resistant S. suis isolates from swine. Twelve antibiotic profiles were determined against 11 S. suis strains. To investigate their synergistic/antagonistic activity, checkerboard assay was performed for all the possible combinations. In-vitro killing curves and in-vivo treatment trials were used to confirm the synergistic activity of special combinations against S. suis dominant clones. In this study, 11 S. suis isolates were highly resistant to erythromycin, clindamycin, trimethoprim/sulfamethoxazole, and tetracycline with ratios of 80-100%, and the resistance percentages to enrofloxacin, florfenicol, and spectinomycin were ~50%. The checkerboard data identified two combination regimens, ampicillin plus apramycin and tiamulin plus spectinomycin which gave the greatest level of synergism against the S. suis strains. In-vitro kill-curves showed a bacterial reduction of over 3-logCFU with the use of combination treatments, whilst the application of mono-therapies achieve less than a 2-logCFU cell killing. In-vivo models confirm that administration of these two combinations significantly reduced the number of bacterial cells after 24 h of treatment. In conclusions, the combinations of ampicillin plus apramycin and tiamulin plus spectinomycin showed the greatest synergism and may be potential strategies for treatment of multi-resistant S. suis in animal.

Combining Biomarkers Linearly and Nonlinearly for Classification Using the Area Under the ROC Curve

PubMed Central

Fong, Youyi; Yin, Shuxin; Huang, Ying

2016-01-01

In biomedical studies, it is often of interest to classify/predict a subject’s disease status based on a variety of biomarker measurements. A commonly used classification criterion is based on AUC - Area under the Receiver Operating Characteristic Curve. Many methods have been proposed to optimize approximated empirical AUC criteria, but there are two limitations to the existing methods. First, most methods are only designed to find the best linear combination of biomarkers, which may not perform well when there is strong nonlinearity in the data. Second, many existing linear combination methods use gradient-based algorithms to find the best marker combination, which often result in sub-optimal local solutions. In this paper, we address these two problems by proposing a new kernel-based AUC optimization method called Ramp AUC (RAUC). This method approximates the empirical AUC loss function with a ramp function, and finds the best combination by a difference of convex functions algorithm. We show that as a linear combination method, RAUC leads to a consistent and asymptotically normal estimator of the linear marker combination when the data is generated from a semiparametric generalized linear model, just as the Smoothed AUC method (SAUC). Through simulation studies and real data examples, we demonstrate that RAUC out-performs SAUC in finding the best linear marker combinations, and can successfully capture nonlinear pattern in the data to achieve better classification performance. We illustrate our method with a dataset from a recent HIV vaccine trial. PMID:27058981

Additional increased effects of mannitol-temozolomide combined treatment on blood-brain barrier permeability.

PubMed

Choi, Chunggab; Kim, Hye Min; Shon, Jeeheun; Park, Jiae; Kim, Hyeong-Taek; Oh, Seung-Hun; Kim, Nam Keun; Kim, Ok Joon

2018-03-04

The blood-brain barrier (BBB) is major obstacle in drug or stem cell treatment in chronic stroke. We hypothesized that adding mannitol to temozolomide (TMZ) is a practically applicable method for resolving the low efficacy of intravenous mannitol therapy. In this study, we investigated whether BBB permeability could be increased by this combined treatment. First, we established a chronic ischemic stroke rat model and examined changes in leakage of Evans blue dye within a lesion site, and in expression of tight junction proteins (TJPs), by this combined treatment. Additionally, in an in vitro BBB model using trans-wells, we analyzed changes in diffusion of a fluorescent tracer and in expression of TJPs. Mannitol-TMZ combined treatment not only increased the amount of Evans blue dye within the stroke lesion site, but also reduced occludin expression in rat brain microvessels. The in vitro study also showed that combined treatment increased the permeability for two different-sized fluorescent tracers, especially large size, and decreased expression of TJPs, such as occludin and ZO-1. Increased BBB permeability effects were more prominent with combined than with single treatments. Mannitol-TMZ combined treatment induced a decrease of TJPs with a consequent increase in BBB permeability. This combined treatment is clinically useful and might provide new therapeutic options by enabling efficient intracerebral delivery of various drugs that could not otherwise be used to treat many CNS diseases due to their inability to penetrate the BBB. Copyright © 2018 Elsevier Inc. All rights reserved.

The allele combinations of three loci based on, liver, stomach cancers, hematencephalon, COPD and normal population: A preliminary study.

PubMed

Gai, Liping; Liu, Hui; Cui, Jing-Hui; Yu, Weijian; Ding, Xiao-Dong

2017-03-20

The purpose of this study was to examine the specific allele combinations of three loci connected with the liver cancers, stomach cancers, hematencephalon and patients with chronic obstructive pulmonary disease (COPD) and to explore the feasibility of the research methods. We explored different mathematical methods for statistical analyses to assess the association between the genotype and phenotype. At the same time we still analyses the statistical results of allele combinations of three loci by difference value method and ratio method. All the DNA blood samples were collected from patients with 50 liver cancers, 75 stomach cancers, 50 hematencephalon, 72 COPD and 200 normal populations. All the samples were from Chinese. Alleles from short tandem repeat (STR) loci were determined using the STR Profiler plus PCR amplification kit (15 STR loci). Previous research was based on combinations of single-locus alleles, and combinations of cross-loci (two loci) alleles. Allele combinations of three loci were obtained by computer counting and stronger genetic signal was obtained. The methods of allele combinations of three loci can help to identify the statistically significant differences of allele combinations between liver cancers, stomach cancers, patients with hematencephalon, COPD and the normal population. The probability of illness followed different rules and had apparent specificity. This method can be extended to other diseases and provide reference for early clinical diagnosis. Copyright © 2016. Published by Elsevier B.V.

Transgender women of color: discrimination and depression symptoms

PubMed Central

Jefferson, Kevin; Neilands, Torsten B.; Sevelius, Jae

2014-01-01

Purpose Trans women of color contend with multiple marginalizations; the purpose of this study is to examine associations between experiencing discriminatory (racist/transphobic) events and depression symptoms. It uses a categorical measure of combined discrimination, and examines a protective association of transgender identity on depression symptoms. Design/methodology/approach Data from a subset of trans women of color participants in the Sheroes study were analyzed with linear and logistic regression. Associations of depression symptoms with racist and transphobic events, combined discrimination, coping self-efficacy, and transgender identity were assessed with odds ratios. Findings Exposure to discriminatory events and combined discrimination positively associated with depression symptom odds. Increased transgender identity associated with increased coping self-efficacy, which negatively associated with depression symptom odds. Research limitations/implications Cross-sectional study data prohibits inferring causality; results support conducting longitudinal research on discrimination’s health effects, and research on transgender identity. Results also support operationalizing intersectionality in health research. The study’s categorical approach to combined discrimination may be replicable in studies with hard to reach populations and small sample sizes. Practical implications Health programs could pursue psychosocial interventions and anti-discrimination campaigns. Interventions might advocate increasing participants’ coping self-efficacy while providing space to explore and develop social identity. Social implications There is a need for policy and health programs to center trans women of color concerns. Originality/value This study examines combined discrimination and identity in relation to depression symptoms among trans women of color, an underserved population. Paper type Research paper PMID:25346778

Combined Functional Voice Therapy in Singers With Muscle Tension Dysphonia in Singing.

PubMed

Sielska-Badurek, Ewelina; Osuch-Wójcikiewicz, Ewa; Sobol, Maria; Kazanecka, Ewa; Rzepakowska, Anna; Niemczyk, Kazimierz

2017-07-01

The purpose of this study was to evaluate vocal tract function and the voice quality in singers with muscle tension dysphonia (MTD) after undergoing combined functional voice therapy of the singing voice. This is a prospective, randomized study. Forty singers (29 females and 11 males, mean age: 24.6 ± 8.8 years) with MTD were enrolled in the study. The study group consisted of 20 singers who underwent combined functional voice therapy (10-15 individual sessions, 30-40 minutes each). Singers who did not opt for vocal rehabilitation consisted of the control group. Effects of rehabilitation were assessed with videolaryngostroboscopy, palpation of the vocal tract structures, flexible fiberoptic evaluation of the pharynx and the larynx, perceptual speaking and singing voice assessment, acoustic analysis, maximal phonation time, and the Voice Handicap Index. After combined functional voice therapy in the study group, great improvement was noticed in palpation of the vocal tract structures (P < 0.001), perceptual voice assessment (P < 0.001), phonetograms (P = 0.002), and singing range obtained from acoustic analysis of glissando (P < 0.001). In the control group, no statistically significant differences were found between the first and the second assessments. Combined functional voice therapy proved to be an efficacious treatment method in singers with MTD in singing. Development of palpation and perceptual singing voice examination protocols enables one to compare results before and after rehabilitation in clinics. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Losartan/hydrochlorothiazide combination is safe and effective for morning hypertension in Very-Elderly patients.

PubMed

Uchiwa, Hiroki; Kai, Hisashi; Iwamoto, Yoshiko; Anegawa, Takahiro; Kajimoto, Hidemi; Fukuda, Kenji; Imaizumi, Tsutomu; Fukumoto, Yoshihiro

2018-01-01

Morning hypertension is an independent risk for cerebrovascular and cardiovascular events. Although the prevalence of morning hypertension increases with age, treatment of morning hypertension has not been established, particularly in Very-Elderly patients. We compared the safety and efficacy of a losartan/hydrochlorothiazide (HCTZ) combination in controlling morning hypertension between Very-Elderly (≥75 years) and Young/Elderly patients (<75 years). This study was a subanalysis of the Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy study, in which patients with morning hypertension (≥135/85 mmHg) received a 50-mg losartan/12.5-mg HCTZ combination tablet (combination therapy) or 100-mg losartan (high-dose therapy) for 3 months. High adherence rates and few adverse effects were observed in Very-Elderly patients receiving combination (n = 32) and high-dose (n = 34) therapies and in Young/Elderly patients receiving combination (n = 69) and high-dose (n = 66) therapies. Baseline morning systolic BP (SBP) was similar in both age groups receiving either therapy. Morning SBP was reduced by 20.2 and 18.1 mmHg with combination therapy and by 7.1 and 9.1 mmHg with high-dose therapy in the Very-Elderly and Young/Elderly patients, respectively. Morning BP target (<135/85 mmHg) was achieved in 40.6% and 55.1% by combination therapy and in 14.7% and 24.2% by high-dose therapy in the Very-Elderly and Young/Elderly patients, respectively. Neither therapy changed renal function and serum potassium in Very-Elderly patients. In conclusion, the losartan/HCTZ combination was safe and effective in controlling morning hypertension in Very-Elderly as well as Young/Elderly patients. In addition, combination therapy was also superior to high-dose therapy for lowering morning SBP in Very-Elderly patients.

Slip Rates of Main Active Fault Zones Through Turkey Inferred From GPS Observations

NASA Astrophysics Data System (ADS)

Ozener, H.; Aktug, B.; Dogru, A.; Tasci, L.; Acar, M.; Emre, O.; Yilmaz, O.; Turgut, B.; Halicioglu, K.; Sabuncu, A.; Bal, O.; Eraslan, A.

2015-12-01

Active Fault Map of Turkey was revised and published by General Directorate of Mineral Research and Exploration in 2012. This map reveals that there are about 500 faults can generate earthquakes.In order to understand the earthquake potential of these faults, it is needed to determine the slip rates. Although many regional and local studies were performed in the past, the slip rates of the active faults in Turkey have not been determined. In this study, the block modelling, which is the most common method to produce slip rates, will be done. GPS velocities required for block modeling is being compiled from the published studies and the raw data provided then velocity field is combined. To form a homogeneous velocity field, different stochastic models will be used and the optimal velocity field will be achieved. In literature, GPS site velocities, which are computed for different purposes and published, are combined globally and this combined velocity field are used in the analysis of strain accumulation. It is also aimed to develop optimal stochastic models to combine the velocity data. Real time, survey mode and published GPS observations is being combined in this study. We also perform new GPS observations. Furthermore, micro blocks and main fault zones from Active Fault Map Turkey will be determined and homogeneous velocity field will be used to infer slip rates of these active faults. Here, we present the result of first year of the study. This study is being supported by THE SCIENTIFIC AND TECHNOLOGICAL RESEARCH COUNCIL OF TURKEY (TUBITAK)-CAYDAG with grant no. 113Y430.

Efficacy and tolerability of rasagiline in daily clinical use--a post-marketing observational study in patients with Parkinson's disease.

PubMed

Reichmann, H; Jost, W H

2010-09-01

The MAO-B inhibitor rasagiline is indicated for the treatment of idiopathic Parkinson's disease (PD), and its use is supported by evidence from large-scale, controlled clinical studies. The post-marketing observational study presented here investigated the efficacy and tolerability of rasagiline treatment (monotherapy or combination therapy) in daily clinical practice. The study included patients with idiopathic PD who received rasagiline (recommended dose 1 mg, once daily) as monotherapy or combination therapy. The treatment and observation period was approximately 4 months. Outcome measures included the change from baseline in the Columbia University Rating Scale (CURS), the Unified PD Rating Scale fluctuation subscale, daily OFF time (patient home diaries) and the PD Questionnaire-39. Adverse drug reactions/adverse events (ADRs/AEs) and the physician's global judgement of tolerability and efficacy were also examined. Overall, 754 patients received rasagiline during the study. Patients treated with rasagiline (monotherapy or combination therapy) showed significant improvements from baseline in symptom severity (including classical motor and non-classical motor/non-motor symptoms) and quality of life (QoL). Patients receiving combination therapy also experienced significant reductions in daily OFF time. Tolerability was rated as good/very good in over 90% of patients. In daily clinical practice, monotherapy or combination therapy with rasagiline is able to improve PD symptoms, reduce OFF time, and improve QoL, whilst demonstrating favourable tolerability. In addition, rasagiline has a simple dosing schedule of one tablet, once daily, with no titration. These results are consistent with the pivotal rasagiline clinical studies (TEMPO, LARGO and PRESTO).

Shared and unique responses of plants to multiple individual stresses and stress combinations: physiological and molecular mechanisms

PubMed Central

Pandey, Prachi; Ramegowda, Venkategowda; Senthil-Kumar, Muthappa

2015-01-01

In field conditions, plants are often simultaneously exposed to multiple biotic and abiotic stresses resulting in substantial yield loss. Plants have evolved various physiological and molecular adaptations to protect themselves under stress combinations. Emerging evidences suggest that plant responses to a combination of stresses are unique from individual stress responses. In addition, plants exhibit shared responses which are common to individual stresses and stress combination. In this review, we provide an update on the current understanding of both unique and shared responses. Specific focus of this review is on heat–drought stress as a major abiotic stress combination and, drought–pathogen and heat–pathogen as examples of abiotic–biotic stress combinations. We also comprehend the current understanding of molecular mechanisms of cross talk in relation to shared and unique molecular responses for plant survival under stress combinations. Thus, the knowledge of shared responses of plants from individual stress studies and stress combinations can be utilized to develop varieties with broad spectrum stress tolerance. PMID:26442037

Concomitant use of the matrix strategy and the mand-model procedure in teaching graphic symbol combinations.

PubMed

Nigam, Ravi; Schlosser, Ralf W; Lloyd, Lyle L

2006-09-01

Matrix strategies employing parts of speech arranged in systematic language matrices and milieu language teaching strategies have been successfully used to teach word combining skills to children who have cognitive disabilities and some functional speech. The present study investigated the acquisition and generalized production of two-term semantic relationships in a new population using new types of symbols. Three children with cognitive disabilities and little or no functional speech were taught to combine graphic symbols. The matrix strategy and the mand-model procedure were used concomitantly as intervention procedures. A multiple probe design across sets of action-object combinations with generalization probes of untrained combinations was used to teach the production of graphic symbol combinations. Results indicated that two of the three children learned the early syntactic-semantic rule of combining action-object symbols and demonstrated generalization to untrained action-object combinations and generalization across trainers. The results and future directions for research are discussed.

A Cochrane review of combined chiropractic interventions for low-back pain.

PubMed

Walker, Bruce F; French, Simon D; Grant, William; Green, Sally

2011-02-01

Cochrane systematic review of randomized controlled trials. To determine the effects of combined chiropractic interventions on pain, disability, back-related function, overall improvement, and patient satisfaction in adults with low-back pain (LBP). Chiropractors commonly use a combination of interventions to treat people with LBP, but little is known about the effects of this care. We used a comprehensive search strategy. All randomized trials comparing combined chiropractic interventions (rather than spinal manipulation alone) with no treatment or other therapies were included. At least two authors selected studies, assessed bias risk, and extracted data. Descriptive synthesis and meta-analyses were performed. We included 12 studies involving 2887 LBP participants. Three studies had low risk of bias. Included studies evaluated a range of chiropractic procedures in a variety of subpopulations with LBP. For acute and subacute LBP, chiropractic interventions improved short- and medium-term pain (standardized mean difference [SMD] -0.25 [95% CI: -0.46 to -0.04] and MD -0.89 [95%CI: -1.60 to -0.18]) compared with other treatments, but there was no significant difference in long-term pain (MD -0.46 [95% CI -1.18 to 0.26]). Short-term improvement in disability was greater in the chiropractic group compared to other therapies (SMD -0.36 [95% CI: -0.70 to -0.02]). However, the effect was small and studies contributing to these results had high risk of bias. There was no difference in medium- and long-term disability. No difference was demonstrated for combined chiropractic interventions for chronic LBP and studies that had a mixed population of LBP. Combined chiropractic interventions slightly improved pain and disability in the short term and pain in the medium term for acute/subacute LBP. However, there is currently no evidence that supports or refutes that these interventions provide a clinically meaningful difference for pain or disability in people with LBP when compared to other interventions.

Practical Applications for Single Pill Combinations in the Cardiovascular Continuum

PubMed Central

Iellamo, Ferdinando; Werdan, Karl; Narkiewicz, Krzysztof; Rosano, Giuseppe

2017-01-01

Despite the availability of new drugs and devices, the treatment of cardiovascular disease remains suboptimal. Single-pill combination therapy offers a number of potential advantages. It can combine different classes of drugs to increase efficacy while mitigating the risks of treatment-related adverse events, reduce pill burden, lower medical cost, and improve patient adherence. Furthermore, in hypertension, single pill combinations include standard to lower doses of each drug than would be necessary to achieve goals with monotherapy, which may explain their better tolerability compared with higher dose monotherapy. Combination therapy is now established in the treatment of hypertension. In ischaemic heart disease, the concept of a preventative polypill has been studied, but its benefits have not been established conclusively. However, the combination of ivabradine and beta-blockers has proven efficacy in patients with stable angina pectoris. This combination has also demonstrated benefits in patients with chronic heart failure. PMID:28785474

Strategy combination during execution of memory strategies in young and older adults.

PubMed

Hinault, Thomas; Lemaire, Patrick; Touron, Dayna

2017-05-01

The present study investigated whether people can combine two memory strategies to encode pairs of words more efficiently than with a single strategy, and age-related differences in such strategy combination. Young and older adults were asked to encode pairs of words (e.g., satellite-tunnel). For each item, participants were told to use either the interactive-imagery strategy (e.g., mentally visualising the two words and making them interact), the sentence-generation strategy (i.e., generate a sentence linking the two words), or with strategy combination (i.e., generating a sentence while mentally visualising it). Participants obtained better recall performance on items encoded with strategy combination than on items encoded with interactive-imagery or sentence-generation strategies. Moreover, we found age-related decline in such strategy combination. These findings have important implications to further our understanding of execution of memory strategies, and suggest that strategy combination occurs in a variety of cognitive domains.

The Single and Combined Effects of Multiple Intensities of Behavior Modification and Methylphenidate for Children with Attention Deficit Hyperactivity Disorder in a Classroom Setting

ERIC Educational Resources Information Center

Fabiano, Gregory A.; Pelham, William E., Jr.; Gnagy, Elizabeth M.; Burrows-MacLean, Lisa; Coles, Erika K.; Chacko, Anil; Wymbs, Brian T.; Walker, Kathryn S.; Arnold, Fran; Garefino, Allison; Keenan, Jenna K.; Onyango, Adia N.; Hoffman, Martin T.; Massetti, Greta M.; Robb, Jessica A.

2007-01-01

Currently behavior modification, stimulant medication, and combined treatments are supported as evidence-based interventions for attention deficit hyperactivity disorder in classroom settings. However, there has been little study of the relative effects of these two modalities and their combination in classrooms. Using a within-subject design, the…

The Combined Effect of Instruction and Monitor in Improving Pronunciation of Potential English Teachers

ERIC Educational Resources Information Center

Liu, Qian; Fu, Zunwei

2011-01-01

The role that instruction and monitor can play in improvement of pronunciation has long been a focus of argument among linguists and researchers. It is assumed that their combination will result in positive effect. An empirical study is carried out and it is confirmed that their combination contributes greatly to the improvement of pronunciation…

Mount Rogers Combined School: The Experiences and Perspectives of Students and Staff When a Community School Closed

ERIC Educational Resources Information Center

Delp, Cynthia D.

2015-01-01

The purpose of the study was to document and examine the experiences and perspectives of students and staff who were affected by the closure of Mount Rogers Combined School in 2010. Mount Rogers Combined School was established in Grayson County, Virginia, by the concerted efforts of volunteers and community members who valued education and…

An Experimental Study on Micro Clinching of Metal Foils with Cutting by Laser Shock Forming.

PubMed

Wang, Xiao; Li, Cong; Ma, Youjuan; Shen, Zongbao; Sun, Xianqing; Sha, Chaofei; Gao, Shuai; Li, Liyin; Liu, Huixia

2016-07-13

This paper describes a novel technique for joining similar and dissimilar metal foils, namely micro clinching with cutting by laser shock forming. A series of experiments were conducted to study the deformation behavior of single layer material, during which many important process parameters were determined. The process window of the 1060 pure aluminum foils and annealed copper foils produced by micro clinching with cutting was analyzed. Moreover, similar material combination (annealed copper foils) and dissimilar material combination (1060 pure aluminum foils and 304 stainless steel foils) were successfully achieved. The effect of laser energy on the interlock and minimum thickness of upper foils was investigated. In addition, the mechanical strength of different material combinations joined by micro clinching with cutting was measured in single lap shearing tests. According to the achieved results, this novel technique is more suitable for material combinations where the upper foil is thicker than lower foil. With the increase of laser energy, the interlock increased while the minimum thickness of upper foil decreased gradually. The shear strength of 1060 pure aluminum foils and 304 stainless steel foils combination was three times as large as that of 1060 pure aluminum foils and annealed copper foils combination.

Effect of Cordyceps sinensis and taurine either alone or in combination on streptozotocin induced diabetes.

PubMed

El Zahraa Z El Ashry, Fatma; Mahmoud, Mona F; El Maraghy, Nabila N; Ahmed, Ahmed F

2012-03-01

The present study aimed to investigate the antidiabetic effects of Cordyceps sinensis, taurine and their combination in comparison with glibenclamide both in vivo and in vitro using streptozotocin rat model. The diabetic rats were orally given glibenclamide, C. sinensis, taurine or Cordyceps and taurine combination for 21 days. Their effects were studied both in vivo and in vitro. Oral administration of Cordyceps, taurine and their combination decreased serum glucose, fructosamine, total cholesterol, triglycerides levels, insulin resistance index and pancreatic malondialdehyde content. Cordyceps significantly increased serum insulin, HDL-cholesterol, total antioxidant capacity levels, β cell function percent, and pancreatic reduced glutathione (GSH) content. However, taurine was unable to elevate pancreatic GSH level to a significant level. These natural products and their combinations were more effective than glibenclamide in reducing insulin resistance index and they had stronger antioxidant properties. Cordyceps and taurine significantly enhanced glucose uptake by diaphragms of normal and diabetic rats in absence and presence of insulin. In conclusion, Cordyceps and taurine either alone or in combination have less potent hypoglycemic effects than glibenclamide; however, they have more ability to reduce insulin resistance and stronger antioxidant properties. Copyright © 2011 Elsevier Ltd. All rights reserved.

Combined intranasal nerve growth factor and ventricle neural stem cell grafts prolong survival and improve disease outcome in amyotrophic lateral sclerosis transgenic mice.

PubMed

Zhong, Shi-Jiang; Gong, Yan-Hua; Lin, Yan-Chen

2017-08-24

Amyotrophic lateral sclerosis (ALS) is a fatal disease that selectively involves motor neurons. Neurotrophic factor supplementation and neural stem cell (NSC) alternative therapy have been used to treat ALS. The two approaches can affect each other in their pathways of action, and there is a possibility for synergism. However, to date, there have been no studies demonstrating the effects of combined therapy in the treatment of ALS. In this study, for the first time, we adopted a method involving the intranasal administration of nerve growth factor combined with lateral ventricle NSC transplantation using G93A-SOD1 transgenic mice as experimental subjects to explore the treatment effect of this combined therapy in ALS. We discover that the combined therapy increase the quantity of TrkA receptors, broaden the migration of exogenous NSCs, further promote active proliferation in neurogenic regions of the brain and enhance the preservation of motor neurons in the spinal cord. Regarding physical activity, the combined therapy improved motor functions, further postponed ALS onset and extended the survival time of the mice. Copyright © 2017 Elsevier B.V. All rights reserved.

Combination of mild hypothermia with neuroprotectants has greater neuroprotective effects during oxygen-glucose deprivation and reoxygenation-mediated neuronal injury

PubMed Central

Gao, Xiao-Ya; Huang, Jian-Ou; Hu, Ya-Fang; Gu, Yong; Zhu, Shu-Zhen; Huang, Kai-Bin; Chen, Jin-Yu; Pan, Su-Yue

2014-01-01

Co-treatment of neuroprotective reagents may improve the therapeutic efficacy of hypothermia in protecting neurons during ischemic stroke. This study aimed to find promising drugs that enhance the neuroprotective effect of mild hypothermia (MH). 26 candidate drugs were selected based on different targets. Primary cultured cortical neurons were exposed to oxygen-glucose deprivation and reoxygenation (OGD/R) to induce neuronal damage, followed by either single treatment (a drug or MH) or a combination of a drug and MH. Results showed that, compared with single treatment, combination of MH with brain derived neurotrophic factor, glibenclamide, dizocilpine, human urinary kallidinogenase or neuroglobin displayed higher proportion of neuronal cell viability. The latter three drugs also caused less apoptosis rate in combined treatment. Furthermore, co-treatment of those three drugs and MH decreased the level of reactive oxygen species (ROS) and intracellular calcium accumulation, as well as stabilized mitochondrial membrane potential (MMP), indicating the combined neuroprotective effects are probably via inhibiting mitochondrial apoptosis pathway. Taken together, the study suggests that combined treatment with hypothermia and certain neuroprotective reagents provide a better protection against OGD/R-induced neuronal injury. PMID:25404538

Combined chloroquine, sulfadoxine/pyrimethamine and primaquine against Plasmodium falciparum in Central Java, Indonesia

PubMed Central

Lederman, Edith R; Maguire, Jason D; Sumawinata, Iwa W; Chand, Krisin; Elyazar, Iqbal; Estiana, Lusi; Sismadi, Priyanto; Bangs, Michael J; Baird, J Kevin

2006-01-01

Background Chloroquine (CQ) or sulfadoxine-pyrimethamine (SP) monotherapy for Plasmodium falciparum often leads to therapeutic failure in Indonesia. Combining CQ with other drugs, like SP, may provide an affordable, available and effective option where artemisinin-combined therapies (ACT) are not licensed or are unavailable. Methods This study compared CQ (n = 29 subjects) versus CQ + SP (with or without primaquine; n = 88) for clinical and parasitological cure of uncomplicated falciparum malaria in the Menoreh Hills region of southern Central Java, Indonesia. Gametocyte clearance rates were measured with (n = 56 subjects) and without (n = 61) a single 45 mg dose of primaquine (PQ). Results After 28 days, 58% of subjects receiving CQ had cleared parasitaemia and remained aparasitaemic, compared to 94% receiving CQ combined with SP (p < 0.001). Msp-2 genotyping permitted reinfection-adjusted cure rates for CQ and CQ combined with SP, 70% and 99%, respectively (p = 0.0006). Conclusion Primaquine exerted no apparent affect on cure of asexual stage parasitaemia, but clearly accelerated clearance of gametocytes. CQ combined with SP was safe and well-tolerated with superior efficacy over CQ for P. falciparum parasitaemia in this study. PMID:17105658

Combined oral contraceptives: venous thrombosis.

PubMed

de Bastos, Marcos; Stegeman, Bernardine H; Rosendaal, Frits R; Van Hylckama Vlieg, Astrid; Helmerhorst, Frans M; Stijnen, Theo; Dekkers, Olaf M

2014-03-03

Combined oral contraceptive (COC) use has been associated with venous thrombosis (VT) (i.e., deep venous thrombosis and pulmonary embolism). The VT risk has been evaluated for many estrogen doses and progestagen types contained in COC but no comprehensive comparison involving commonly used COC is available. To provide a comprehensive overview of the risk of venous thrombosis in women using different combined oral contraceptives. Electronic databases (Pubmed, Embase, Web of Science, Cochrane, CINAHL, Academic Search Premier and ScienceDirect) were searched in 22 April 2013 for eligible studies, without language restrictions. We selected studies including healthy women taking COC with VT as outcome. The primary outcome of interest was a fatal or non-fatal first event of venous thrombosis with the main focus on deep venous thrombosis or pulmonary embolism. Publications with at least 10 events in total were eligible. The network meta-analysis was performed using an extension of frequentist random effects models for mixed multiple treatment comparisons. Unadjusted relative risks with 95% confidence intervals were reported.Two independent reviewers extracted data from selected studies. 3110 publications were retrieved through a search strategy; 25 publications reporting on 26 studies were included. Incidence of venous thrombosis in non-users from two included cohorts was 0.19 and 0.37 per 1 000 person years, in line with previously reported incidences of 0,16 per 1 000 person years. Use of combined oral contraceptives increased the risk of venous thrombosis compared with non-use (relative risk 3.5, 95% confidence interval 2.9 to 4.3). The relative risk of venous thrombosis for combined oral contraceptives with 30-35 μg ethinylestradiol and gestodene, desogestrel, cyproterone acetate, or drospirenone were similar and about 50-80% higher than for combined oral contraceptives with levonorgestrel. A dose related effect of ethinylestradiol was observed for gestodene, desogestrel, and levonorgestrel, with higher doses being associated with higher thrombosis risk. All combined oral contraceptives investigated in this analysis were associated with an increased risk of venous thrombosis. The effect size depended both on the progestogen used and the dose of ethinylestradiol. Risk of venous thrombosis for combined oral contraceptives with 30-35 μg ethinylestradiol and gestodene, desogestrel, cyproterone acetate and drospirenone were similar, and about 50-80% higher than with levonorgestrel. The combined oral contraceptive with the lowest possible dose of ethinylestradiol and good compliance should be prescribed-that is, 30 μg ethinylestradiol with levonorgestrel.

Abdominal Obesity and Risk of Hip Fracture: A Systematic Review and Meta-Analysis of Prospective Studies.

PubMed

Sadeghi, Omid; Saneei, Parvaneh; Nasiri, Morteza; Larijani, Bagher; Esmaillzadeh, Ahmad

2017-09-01

Data on the association between general obesity and hip fracture were summarized in a 2013 meta-analysis; however, to our knowledge, no study has examined the association between abdominal obesity and the risk of hip fracture. The present systematic review and meta-analysis of prospective studies was undertaken to summarize the association between abdominal obesity and the risk of hip fracture. We searched online databases for relevant publications up to February 2017, using relevant keywords. In total, 14 studies were included in the systematic review and 9 studies, with a total sample size of 295,674 individuals (129,964 men and 165,703 women), were included in the meta-analysis. Participants were apparently healthy and aged ≥40 y. We found that abdominal obesity (defined by various waist-hip ratios) was positively associated with the risk of hip fracture (combined RR: 1.24, 95% CI: 1.05, 1.46, P = 0.01). Combining 8 effect sizes from 6 studies, we noted a marginally significant positive association between abdominal obesity (defined by various waist circumferences) and the risk of hip fracture (combined RR: 1.36; 95% CI: 0.97, 1.89, P = 0.07). This association became significant in a fixed-effects model (combined effect size: 1.40, 95% CI: 1.25, 1.58, P < 0.001). Based on 5 effect sizes, we found that a 0.1-U increase in the waist-hip ratio was associated with a 16% increase in the risk of hip fracture (combined RR: 1.16, 95% CI: 1.04, 1.29, P = 0.007), whereas a 10-cm increase in waist circumference was not significantly associated with a higher risk of hip fracture (combined RR: 1.13, 95% CI: 0.94, 1.36, P = 0.19). This association became significant, however, when we applied a fixed-effects model (combined effect size: 1.21, 95% CI: 1.15, 1.27, P < 0.001). We found that abdominal obesity was associated with a higher risk of hip fracture in 295,674 individuals. Further studies are needed to test whether there are associations between abdominal obesity and fractures at other bone sites. © 2017 American Society for Nutrition.

[The combined action of drinking mineral water and low-intensity electromagnetic radiation under the immobilization stress conditions (an experimental study)].

PubMed

Korolev, Yu N; Bobrovnitsky, I P; Geniatulina, M S; Mikhailik, L V; Nikulina, L A; Bobkova, A S; Yakovlev, M Yu

2015-01-01

The present study carried out on white male rats in experiments with the use of biochemical, radioimmunological, and electron- microscopic methods. It was shown that the combined treatment with potable mineral water (MV) and low-intensity electromagnetic radiation (LIEMR) of ultrahigh frequency (power density less than 1 pW/cm2, the frequency about 1000 MHz) facilitated the activation of metabolic and intracellular regenerative processes in the liver and testes. One of the advantages of the combined application of MV and LIEMR over the single-factor treatment manifested itself as the weakening of stress reactions, the increase in the frequency of the plastic processes, and the more harmonious development of different forms of intracellular regeneration. The results of the study provide a deeper insight ino the mechanisms underlying the combined actions of drinking mineral water and low-intensity electromagnetic radiation; also, they justify the application of these factors for the protection of the reproductive system and the entire body from stress-induced disorders.

Susceptibility testing of terbinafine alone and in combination with amphotericin B, itraconazole, or voriconazole against conidia and hyphae of dematiaceous molds.

PubMed

Biancalana, Fernanda Simas Corrêa; Lyra, Luzia; Moretti, Maria Luiza; Schreiber, Angélica Zaninelli

2011-12-01

Studies have demonstrated excellent in vivo efficacy of terbinafine combined with other antifungal agents against dematiaceous molds; however, there is a lack of in vitro studies. Most studies evaluated conidia inocula, but susceptibility testing of hyphae could mimic the fungal status in infected tissues and might reflect the therapeutic potential of the agent. We investigated the in vitro susceptibility of terbinafine alone and in combination with amphotericin B, itraconazole, or voriconazole against conidia by microdilution and dynamic measurement of hyphae growth of dematiaceous molds. The MIC values for hyphae were, until 3 dilutions, below the MIC obtained for conidia. The results indicated 100% synergistic interactions between terbinafine and azoles or amphotericin B in all tests, but lower MICs for hyphae. In conclusion, our findings allow us to say that the hyphal form of tested dematiaceous molds showed high susceptibility to all antifungal agents evaluated, alone and in combination with terbinafine. Copyright © 2011 Elsevier Inc. All rights reserved.

Implementing Community Engagement for Combination Prevention: Lessons Learnt From the First Year of the HPTN 071 (PopART) Community-Randomized Study.

PubMed

Simwinga, Musonda; Bond, Virginia; Makola, Nozizwe; Hoddinott, Graeme; Belemu, Steve; White, Rhonda; Shanaube, Kwame; Seeley, Janet; Moore, Ayana

2016-08-01

Key to the success of a HIV combination prevention strategy, including galvanizing the current push to roll out universal test and treat (UTT), is the involvement and buy-in of the populations that the strategy aims to reach. Drawing on the experiences of engaging with 21 communities in Zambia and South Africa in the design and implementation of a community-randomized study of combination HIV prevention including UTT, this paper reflects on the commitment to, approaches for and benefits of involving communities. Key lessons learnt include that all communities require continuous community engagement (CE) and engagement needs to be adapted to diverse local contexts. Intrinsic goals of CE, such as building trusting relationships between study stakeholders, are necessary precursors to instrumental goals which strengthen the research quality. Engaging the community for combination prevention requires that CE successfully bridges science and real life, paying attention to influences in the wider social landscape.

Femara® and the future: tailoring treatment and combination therapies with Femara

PubMed Central

Ma, Cynthia

2007-01-01

Long-term estrogen deprivation treatment for breast cancer can, in some patients, lead to the activation of alternate cellular pathways, resulting in the re-emergence of the disease. This is a distressing scenario for oncologists and patients, but recent intensive molecular and biochemical studies are beginning to unravel these pathways, revealing opportunities for new targeted treatments. Far from making present therapies redundant, these new discoveries open the door to novel combination therapies that promise to provide enhanced efficacy or overcome treatment resistance. Letrozole, one of the most potent aromatase inhibitors, is the ideal candidate for combination therapy; indeed, it is one of the most intensively studied aromatase inhibitors in the evolving combinatorial setting. Complementary to the use of combination therapy is the development of molecular tools to identify patients who will benefit the most from these new treatments. Microarray gene profiling studies, designed to detect letrozole-responsive targets, are currently under way to understand how the use of the drug can be tailored more efficiently to specific patient needs. PMID:17912640

Study of New Method Combined Ultra-High Frequency (UHF) Method and Ultrasonic Method on PD Detection for GIS

NASA Astrophysics Data System (ADS)

Li, Yanran; Chen, Duo; Zhang, Jiwei; Chen, Ning; Li, Xiaoqi; Gong, Xiaojing

2017-09-01

GIS (gas insulated switchgear), is an important equipment in power system. Partial discharge plays an important role in detecting the insulation performance of GIS. UHF method and ultrasonic method frequently used in partial discharge (PD) detection for GIS. It is necessary to investigate UHF method and ultrasonic method for partial discharge in GIS. However, very few studies have been conducted on the method combined this two methods. From the view point of safety, a new method based on UHF method and ultrasonic method of PD detection for GIS is proposed in order to greatly enhance the ability of anti-interference of signal detection and the accuracy of fault localization. This paper presents study aimed at clarifying the effect of the new method combined UHF method and ultrasonic method. Partial discharge tests were performed in laboratory simulated environment. Obtained results show the ability of anti-interference of signal detection and the accuracy of fault localization for this new method combined UHF method and ultrasonic method.

Mechanical bowel preparation and oral antibiotic prophylaxis in colorectal surgery: Analysis of evidence and narrative review.

PubMed

Badia, Josep M; Arroyo-García, Nares

2018-05-14

The role of oral antibiotic prophylaxis and mechanical bowel preparation in colorectal surgery remains controversial. The lack of efficacy of mechanical preparation to improve infection rates, its adverse effects, and multimodal rehabilitation programs have led to a decline in its use. This review aims to evaluate current evidence on antegrade colonic cleansing combined with oral antibiotics for the prevention of surgical site infections. In experimental studies, oral antibiotics decrease the bacterial inoculum, both in the bowel lumen and surgical field. Clinical studies have shown a reduction in infection rates when oral antibiotic prophylaxis is combined with mechanical preparation. Oral antibiotics alone seem to be effective in reducing infection in observational studies, but their effect is inferior to the combined preparation. In conclusion, the combination of oral antibiotics and mechanical preparation should be considered the gold standard for the prophylaxis of postoperative infections in colorectal surgery. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

On applying cognitive psychology.

PubMed

Baddeley, Alan

2013-11-01

Recent attempts to assess the practical impact of scientific research prompted my own reflections on over 40 years worth of combining basic and applied cognitive psychology. Examples are drawn principally from the study of memory disorders, but also include applications to the assessment of attention, reading, and intelligence. The most striking conclusion concerns the many years it typically takes to go from an initial study, to the final practical outcome. Although the complexity and sheer timescale involved make external evaluation problematic, the combination of practical satisfaction and theoretical stimulation make the attempt to combine basic and applied research very rewarding. © 2013 The British Psychological Society.

Combined Quitline Counseling and Text Messaging for Smoking Cessation: A Quasi-Experimental Evaluation.

PubMed

Boal, Ashley L; Abroms, Lorien C; Simmens, Samuel; Graham, Amanda L; Carpenter, Kelly M

2016-05-01

This study seeks to determine whether comprehensive quitline services combined with text messaging improve smoking cessation rates beyond those achieved by offering comprehensive quitline services alone. The study sample consisted of callers to the Alere Wellbeing, Inc, commercial quitline in 2012. A quasi-experimental design was implemented using propensity score matching to create the intervention and control groups. The intervention group consisted of those who were offered and accepted a text message intervention in addition to usual quitline services, while the control group consisted of those who were not offered the text message intervention. Analyses utilized baseline data collected at intake, program use data (eg, call history and text message use), and reports of smoking behaviors and program satisfaction collected 6 months after intake. Similar rates of 7-day abstinence were reported regardless of whether participants received combined multi-call quitline services plus text messaging (25.3%) or multi-call quitline services in isolation (25.5%), though those who received combined services reported higher treatment satisfaction (P < .05). Among those who received combined services, the number of text messages sent to the text message program predicted 7-day abstinence such that those who sent more text messages were less likely to report 7-day abstinence. Text messaging may not confer additional benefits over and above those received through multi-modal, multi-call quitline programs. Future research should investigate whether text messaging programs improve quit rates when combined with less intensive services such as single-call phone counseling. While the impact of quitline and text messaging services for smoking cessation have been examined in isolation, no study has explored the impact of combined services on smoking outcomes. This study examines the role of text messaging in combination with comprehensive quitline services including multi-call phone counseling, access to an interactive website and nicotine replacement therapy. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Diagnosis of tuberculous pleurisy with combination of adenosine deaminase and interferon-γ immunospot assay in a tuberculosis-endemic population: A prospective cohort study.

PubMed

Xu, Han-Yan; Li, Cheng-Ye; Su, Shan-Shan; Yang, Li; Ye, Min; Ye, Jun-Ru; Ke, Pei-Pei; Chen, Cheng-Shui; Xie, Yu-Peng; Li, Yu-Ping

2017-11-01

The aim of this study was to identify the optimal cut-off value of T cell enzyme-linked immunospot assay for tuberculosis (T-SPOT.TB) and evaluate its diagnostic performance alone (in the peripheral blood) or in combination with the adenosine deaminase (ADA) activity test (in peripheral blood and the pleural fluid) in patients with tuberculous pleurisy.Adult patients presenting with pleural effusion were included in this prospective cohort study. Tuberculous pleurisy was diagnosed by T-SPOT.TB in peripheral blood and a combination of T-SPOT.TB and ADA activity test in pleural fluid and peripheral blood. Receiver operating characteristic (ROC) curve in combination with multivariate logistic regression was used to evaluate the diagnostic performance of the assays.Among a total of 189 patients with suspected tuberculous pleurisy who were prospectively enrolled in this study, 177 patients were validated for inclusion in the final analysis. ROC analysis revealed that the area under the ROC curve (AUC) for T-SPOT.TB in pleural fluid and peripheral blood was 0.918 and 0.881, respectively, and for the ADA activity test in pleural fluid was 0.944. In addition, 95.5 spot-forming cells (SFCs)/2.5 × 10 cells were determined as the optimal cut-off value for T-SPOT.TB in pleural fluid. Parallel combination of T-SPOT.TB and ADA activity test in pleural fluid showed increased sensitivity (96.9%) and specificity (87.5%), whereas serial combination showed increased specificity (97.5%). The combination of 3 assays had the highest sensitivity at 97.9%, with an AUC value of 0.964.T-SPOT.TB in pleural fluid performed better than that in peripheral blood and the ADA activity test in pleural fluid for tuberculous pleurisy diagnosis. The optimal cut-off value of T-SPOT.TB in pleural fluid was 95.5 SFCs/2.5 × 10 cells. Combination of 3 assays might be a promising approach for tuberculous pleurisy diagnosis. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

New developments in chemotherapy of advanced breast cancer.

PubMed

Lebwohl, D E; Canetta, R

1999-01-01

Anthracyclines and taxanes are the two most active classes of chemotherapy for the treatment of advanced breast cancer. Recent studies have investigated combination therapy including doxorubicin (Dox) and paclitaxel. The efficacy of this combination has been established in a phase III study conducted by ECOG, comparing Dox/paclitaxel versus Dox versus paclitaxel. The combination is superior to Dox or paclitaxel with respect to response rate and time to disease progression, indicating that the combination provides a new standard for the first line treatment of metastatic breast cancer [1]. Phase II studies using higher doses of Dox and using shorter infusions of paclitaxel have suggested the combination can be further optimized; Gianni reported a 94% objective response rate using Dox 60 mg/m2 followed by paclitaxel 175 mg/m2 given over three hours [2]. The more active regimens are associated with enhanced cardiotoxicity; this toxicity can be avoided, however, by limiting the exposure to doxorubicin. The newer regimens have now been moved into phase III studies. Future progress for this disease will depend on the introduction of new agents. Two novel drugs are currently being investigated in randomised phase III trials as potentiators of Dox and/or paclitaxel. One is a monoclonal antibody from Genentech (Herceptin, trastuzumab) directed at the HER-2/neu oncogene, which is overexpressed in > 25% of breast cancers [3]. Recent results indicate that Herceptin in combination with paclitaxel (or with a Dox plus cyclophosphamide regimen) induces a higher response rate (RR) and prolongs the time to disease progression when compared to chemotherapy alone. The second agent N,N-diethyl-2[4-(phenylmethyl)-phenoxy] ethanamine.HCl (DPPE, BMS-217380-01), when combined with Dox, was associated with a higher RR than previously observed with Dox alone [4]. A randomized trial of Dox versus Dox plus DPPE is ongoing. The possible mechanisms underlying chemo-potentiation by these agents are discussed. As new anthracycline/taxane combinations establish themselves in earlier stages of the disease, the need for effective, non-cross resistant salvage regimens will emerge.

An isobolographic analysis of the antinociceptive effect of xylopic acid in combination with morphine or diclofenac

PubMed Central

Woode, Eric; Ameyaw, Elvis Ofori; Abotsi, Wonder Kofi Mensah; Boakye-Gyasi, Eric

2015-01-01

Background: A common practice of managing pain globally is the combination of analgesics and this is aimed at facilitating patient compliance, simplifying prescription, and improving efficacy without increasing adverse effects. Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders and xylopic acid (XA) present in the fruit extract have been shown to possess analgesic properties in animals. There is the likelihood of concomitant use of XA and the commonly used analgesics in traditional settings. This study, therefore, evaluated the pharmacologic interaction between XA/morphine and xylopic/diclofenac combinations. Methods: The formalin test and acetic acid writhing test were used to study the antinociceptive activity of XA, morphine, and diclofenac. The isobolographic analysis was used to study the antinociceptive interactions between XA co-administered with morphine or diclofenac. Results: Results obtained revealed that XA (10–100 mg/kg), morphine (1–10 mg/kg), and diclofenac (1–10 mg/kg) produced dose-related antinociception with different potencies in the formalin and acetic acid writhing tests. Isobolographic analysis of XA/morphine and XA/diclofenac combinations revealed potentiation of their antinociceptive effects. The degree of potentiation calculated as interaction index showed synergism for both combinations in all the nociceptive tests. Conclusion: In conclusion, the present study demonstrated synergism for the co-administration of XA with morphine or diclofenac. PMID:26692735

Systematic review of the relationships between combinations of movement behaviours and health indicators in the early years (0-4 years).

PubMed

Kuzik, Nicholas; Poitras, Veronica J; Tremblay, Mark S; Lee, Eun-Young; Hunter, Stephen; Carson, Valerie

2017-11-20

A recent review highlighted important relationships between combinations of movement behaviours (i.e., sleep, sedentary behaviour, and physical activity) and health indicators among school-aged children and youth (aged 5-17 years). It is unclear whether similar relationships exist in younger children. Therefore, this review sought to examine the relationships between combinations of movement behaviours and health indicators in the early years (1.00 month to 4.99 years). Medline, EMBASE, PsycINFO, and SportDiscus were searched for relevant studies up to November 2016, with no date or study design limits. Included studies met the a priori-determined population (apparently healthy children aged 1.00 month to 4.99 years), intervention (combination of ≥2 movement behaviours [i.e., sleep and sedentary behaviour; sleep and physical activity; sedentary behaviour and physical activity; and sleep, sedentary behaviour, and physical activity]), comparator (various levels and combinations of movement behaviours), and health outcome/indicator (Critical: adiposity, motor development, psychosocial health/emotional regulation, cognitive development, fitness, and growth; Important: bone and skeletal health, cardiometabolic health, and risks). For each health indicator, quality of evidence was assessed by study design using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Ten articles (n = 7436 participants; n = 5 countries) were included. Across observational and experimental study designs, the most ideal combinations of sedentary behaviour and physical activity were: favourably associated with motor development and fitness among preschool-aged children (3.00 to 4.99 years); both favourably and not associated with adiposity among toddlers (1.10 to 2.99 years) and preschool-aged children; and not associated with growth among toddlers and preschool-aged children. The most ideal combinations of sleep and sedentary behaviour were favourably associated with adiposity among infants (1.00 month to 1.00 years) and toddlers. Quality of evidence ranged from "very low" to "moderate". The most ideal combinations of movement behaviours (e.g., high sleep, low sedentary behaviour, high physical activity) may be important for optimal health in the early years. Findings can help inform movement behaviour guidelines for the early years. Given the limited evidence, future research is needed to determine the ideal distribution of daily movement behaviours for optimal health throughout the early years.

The message of the survival curves: I. Composite analysis of long-term treatment studies in bipolar disorder.

PubMed

Frecska, Ede; Kovacs, Attila Istvan; Balla, Petra; Falussy, Linda; Ferencz, Akos; Varga, Zsofia

2012-09-01

There is a shortage of studies analyzing the time course of recurrent episodes and comparing effectiveness of long-term treatments in bipolar disorder. 'Number needed to treat' (NNT) analyses have been proven to be useful for clinically meaningful comparisons, but results vary considerably among studies. The survival curves of different trials also show a great variability preventing reliable conclusions on the time course of maintenance therapies. The variance of survival analyses on long-term medication management can be reduced with increasing the statistical power by combining the life-tables of individual studies. In this study the survival tables of 28 studies on maintenance treatment of bipolar disorder were reconstructed from the published diagrams, and the numbers of relapsed patients in the original studies were estimated for plotting composite survival curves of an inactive, mono- and combination therapy arm. The review was finally based on 5231 subjects. The resulting composite diagrams indicate that within the first year 48% of patients on monotherapy, and 35% on combination therapy experienced recurrence of any affective episode ('early relapsers'). The rest of the patient population was affected by recurrences in a smaller rate over a more extended period of time ('late relapsers'). For a favorable outcome at 40 months of episode prevention in bipolar disorder the NNT was 6 for mono- and 3 for combination therapy. Log-rank analyses of the composite data supported the effectiveness of both medication protocols over placebo, and the superiority of drug combination over monotherapy; though there were some indications of decreased efficacy in the two treatment arms after extended maintenance. Composite analysis offers increased statistical power for studying the time course of survival data. Mood episodes in bipolar disorder are likely to recur early on and relapses in "real-life" can be more frequent than the rates published here. Our results favor combination therapy for the long-term management of bipolar disorder. Concerns are expressed that NNT analyses have significant limitations when applied to recurring events with cumulative deterioration instead of cases where cumulative improvement is expected over time.

Preclinical systemic toxicity evaluation of chitosan-solid lipid nanoparticle-encapsulated aspirin and curcumin in combination with free sulforaphane in BALB/c mice

PubMed Central

Thakkar, Arvind; Chenreddy, Sushma; Thio, Astrid; Khamas, Wael; Wang, Jeffrey; Prabhu, Sunil

2016-01-01

Our previous studies have established the efficacy of chemopreventive regimens of aspirin and curcumin (CUR) encapsulated within solid lipid nanoparticles (SLNs) in combination with free sulforaphane (ACS combination) to prevent or delay the initiation and progression of pancreatic cancer, classified as one of the deadliest diseases with very low chances of survival upon diagnosis. Although toxicity of individual drugs and SLN has been studied previously, there are no studies in current literature that evaluate the potential toxicity of a combined regimen of ACS, especially when encapsulated within chitosan-SLNs (c-SLNs). Hence, objective of the current study was to investigate the potential toxic effects of ACS c-SLN combined chemopreventive regimens following acute (3 days), subacute (28 days), and subchronic (90 days) administrations by oral gavage in BALB/c mice. Mice were administered the following regimens: saline, blank c-SLN, low-dose ACS c-SLN (2+4.5+0.16 mg/kg), medium-dose ACS c-SLN (20+45+1.6 mg/kg), and high-dose ACS c-SLN (60+135+4.8 mg/kg). The potential toxicity was evaluated based on animal survival, body weight, hematology, blood chemistry, and organ histopathology. During 3-day, 28-day, and 90-day study periods, no animal deaths were observed. Treatment with ACS c-SLNs did not cause alteration in complete blood counts and blood chemistry data. Histopathological examination of various organ sections (pancreas, heart, liver, kidney, and brain) appeared normal. Based on the results of this study, no signs of toxicity in acute, subacute, and subchronic studies following oral administration of ACS c-SLNs were found indicating that the oral dosing regimens were safe at the levels tested for long-term administration to prevent the onset of pancreatic cancer. PMID:27499621

Molecular characterization and combined genotype association study of bovine cluster of differentiation 14 gene with clinical mastitis in crossbred dairy cattle

PubMed Central

Selvan, A. Sakthivel; Gupta, I. D.; Verma, A.; Chaudhari, M. V.; Magotra, A.

2016-01-01

Aim: The present study was undertaken with the objectives to characterize and to analyze combined genotypes of cluster of differentiation 14 (CD14) gene to explore its association with clinical mastitis in Karan Fries (KF) cows maintained in the National Dairy Research Institute herd, Karnal. Materials and Methods: Genomic DNA was extracted using blood of randomly selected 94 KF lactating cattle by phenol-chloroform method. After checking its quality and quantity, polymerase chain reaction (PCR) was carried out using six sets of reported gene-specific primers to amplify complete KF CD14 gene. The forward and reverse sequences for each PCR fragments were assembled to form complete sequence for the respective region of KF CD14 gene. The multiple sequence alignments of the edited sequence with the corresponding reference with reported Bos taurus sequence (EU148610.1) were performed with ClustalW software to identify single nucleotide polymorphisms (SNPs). Basic Local Alignment Search Tool analysis was performed to compare the sequence identity of KF CD14 gene with other species. The restriction fragment length polymorphism (RFLP) analysis was carried out in all KF cows using Helicobacter pylori 188I (Hpy188I) (contig 2) and Haemophilus influenzae I (HinfI) (contig 4) restriction enzyme (RE). Cows were assigned genotypes obtained by PCR-RFLP analysis, and association study was done using Chi-square (χ2) test. The genotypes of both contigs (loci) number 2 and 4 were combined with respect to each animal to construct combined genotype patterns. Results: Two types of sequences of KF were obtained: One with 2630 bp having one insertion at 616 nucleotide (nt) position and one deletion at 1117 nt position, and the another sequence was of 2629 bp having only one deletion at 615 nt position. ClustalW, multiple alignments of KF CD14 gene sequence with B. taurus cattle sequence (EU148610.1), revealed 24 nt changes (SNPs). Cows were also screened using PCR-RFLP with Hpy188I (contig 2) and HinfI (contig 4) RE, which revealed three genotypes each that differed significantly regarding mastitis incidence. The maximum possible combination of these two loci shown nine combined genotype patterns and it was observed only eight combined genotypes out of nine: AACC, AACD, AADD, ABCD, ABDD, BBCC, BBCD, and BBDD. The combined genotype ABCC was not observed in the studied population of KF cows. Out of 94 animals, AACD combined genotype animals (10.63%) were found to be not affected with mastitis, and ABDD combined genotyped animals was observed having the highest mastitis incidence of 15.96%. Conclusion: AACD typed cows were found to be least susceptible to mastitis incidence as compared to other combined genotypes. PMID:27536026

Molecular characterization and combined genotype association study of bovine cluster of differentiation 14 gene with clinical mastitis in crossbred dairy cattle.

PubMed

Selvan, A Sakthivel; Gupta, I D; Verma, A; Chaudhari, M V; Magotra, A

2016-07-01

The present study was undertaken with the objectives to characterize and to analyze combined genotypes of cluster of differentiation 14 (CD14) gene to explore its association with clinical mastitis in Karan Fries (KF) cows maintained in the National Dairy Research Institute herd, Karnal. Genomic DNA was extracted using blood of randomly selected 94 KF lactating cattle by phenol-chloroform method. After checking its quality and quantity, polymerase chain reaction (PCR) was carried out using six sets of reported gene-specific primers to amplify complete KF CD14 gene. The forward and reverse sequences for each PCR fragments were assembled to form complete sequence for the respective region of KF CD14 gene. The multiple sequence alignments of the edited sequence with the corresponding reference with reported Bos taurus sequence (EU148610.1) were performed with ClustalW software to identify single nucleotide polymorphisms (SNPs). Basic Local Alignment Search Tool analysis was performed to compare the sequence identity of KF CD14 gene with other species. The restriction fragment length polymorphism (RFLP) analysis was carried out in all KF cows using Helicobacter pylori 188I (Hpy188I) (contig 2) and Haemophilus influenzae I (HinfI) (contig 4) restriction enzyme (RE). Cows were assigned genotypes obtained by PCR-RFLP analysis, and association study was done using Chi-square (χ (2)) test. The genotypes of both contigs (loci) number 2 and 4 were combined with respect to each animal to construct combined genotype patterns. Two types of sequences of KF were obtained: One with 2630 bp having one insertion at 616 nucleotide (nt) position and one deletion at 1117 nt position, and the another sequence was of 2629 bp having only one deletion at 615 nt position. ClustalW, multiple alignments of KF CD14 gene sequence with B. taurus cattle sequence (EU148610.1), revealed 24 nt changes (SNPs). Cows were also screened using PCR-RFLP with Hpy188I (contig 2) and HinfI (contig 4) RE, which revealed three genotypes each that differed significantly regarding mastitis incidence. The maximum possible combination of these two loci shown nine combined genotype patterns and it was observed only eight combined genotypes out of nine: AACC, AACD, AADD, ABCD, ABDD, BBCC, BBCD, and BBDD. The combined genotype ABCC was not observed in the studied population of KF cows. Out of 94 animals, AACD combined genotype animals (10.63%) were found to be not affected with mastitis, and ABDD combined genotyped animals was observed having the highest mastitis incidence of 15.96%. AACD typed cows were found to be least susceptible to mastitis incidence as compared to other combined genotypes.

CROPPER: a metagene creator resource for cross-platform and cross-species compendium studies.

PubMed

Paananen, Jussi; Storvik, Markus; Wong, Garry

2006-09-22

Current genomic research methods provide researchers with enormous amounts of data. Combining data from different high-throughput research technologies commonly available in biological databases can lead to novel findings and increase research efficiency. However, combining data from different heterogeneous sources is often a very arduous task. These sources can be different microarray technology platforms, genomic databases, or experiments performed on various species. Our aim was to develop a software program that could facilitate the combining of data from heterogeneous sources, and thus allow researchers to perform genomic cross-platform/cross-species studies and to use existing experimental data for compendium studies. We have developed a web-based software resource, called CROPPER that uses the latest genomic information concerning different data identifiers and orthologous genes from the Ensembl database. CROPPER can be used to combine genomic data from different heterogeneous sources, allowing researchers to perform cross-platform/cross-species compendium studies without the need for complex computational tools or the requirement of setting up one's own in-house database. We also present an example of a simple cross-platform/cross-species compendium study based on publicly available Parkinson's disease data derived from different sources. CROPPER is a user-friendly and freely available web-based software resource that can be successfully used for cross-species/cross-platform compendium studies.

The effect of tuning ankle foot orthoses-footwear combination on the gait parameters of children with cerebral palsy.

PubMed

Eddison, Nicola; Chockalingam, Nachiappan

2013-04-01

There are a wide variety of ankle foot orthoses used in clinical practice which are characterised by their design, the material used and the stiffness of that material. Changing any of these three components will alter the effect of the ankle foot orthosis on gait. The purpose of this article is to provide an overview on the available research on ankle foot orthosis-footwear combination tuning on the gait characteristics of children with cerebral palsy through a structured review. Literature review. A thorough search of previous studies published in English was conducted within all major databases using relevant phrases without any limits for the dates. These searches were then supplemented by tracking all key references from the appropriate articles identified including hand searching of published books where relevant. To date, there are 947 papers in the literature pertaining to the study of ankle foot orthosis. Of these, 153 investigated the use of ankle foot orthosis for children with cerebral palsy. All the studies included in this review were of a within-subjects design and the evidence levels were generally low. The overall results suggested that ankle foot orthosis-footwear combination tuning has the potential to improve the kinematics and kinetics of gait in children with cerebral palsy. However, the review highlights a lack of well-designed and adequately powered studies. Clinical relevance While the research described in this article indicates an improvement in the gait of children with cerebral palsy following tuning of their ankle foot orthosis-footwear combination, there is still a paucity of research with quantitative data on the effects of kinematics and kinetics of ankle foot orthosis-footwear combination tuning, comparing untuned ankle foot orthosis-footwear combinations with tuned ankle foot orthosis-footwear combination. Furthermore, current research does not identify the effect of tuning on energy efficiency.

Single-pill combination therapy for type 2 diabetes mellitus: linagliptin plus empagliflozin.

PubMed

Aronson, Ronnie

2015-05-01

Treatment of type 2 diabetes mellitus invariably requires the use of multiple daily medications which can impact negatively on patient adherence. As a result, there is growing interest in the use of single-pill combinations that can reduce the pill burden. Many such formulations incorporate metformin, although this agent is not suitable for all patients. The single-pill combination of the dipeptidyl peptidase-4 inhibitor linagliptin with the sodium glucose co-transporter 2 inhibitor empagliflozin offers a new and attractive option, given their complementary mechanisms of action. Publications with titles containing the keywords 'linagliptin' or 'empagliflozin' were identified from a non-systematic search of PubMed without date restrictions, together with abstracts presented at the annual meetings of the American Diabetes Association and the European Association for the Study of Diabetes 2012-2014. ClinicalTrials.gov was searched for entries containing these two keywords. Additional references known to the author were included. The efficacy and safety of linagliptin and empagliflozin as monotherapy or in combination with other oral antidiabetic drugs has been established through extensive clinical trial programs. Studies specifically evaluating the efficacy/safety of a dipeptidyl peptidase-4 inhibitor/sodium glucose co-transporter 2 inhibitor in combination are limited, but do include two studies of linagliptin/empagliflozin of up to 52 weeks in duration. These studies show that the single-pill combination of linagliptin and empagliflozin produced clinical improvements in glycemic control that were generally superior to the improvements seen with linagliptin and empagliflozin alone, but with a safety profile comparable to that of the individual constituents. The single-pill combination of linagliptin and empagliflozin, with their complementary mechanisms of action, is a promising treatment option for patients with type 2 diabetes mellitus. It would reduce the daily pill burden in this population, potentially improving adherence to, and optimizing the benefits of, treatment of diabetes mellitus.

Cutting needle biopsy combined with immunohistochemical study of myeloperoxidase for the diagnosis of histiocytic necrotizing lymphadenitis.

PubMed

Hanakawa, Hiroyuki; Orita, Yorihisa; Sato, Yasuharu; Takeuchi, Mai; Ohno, Kyotaro; Iwaki, Noriko; Ito, Toshihiro; Nishizaki, Kazunori; Yoshino, Tadashi

2013-12-01

Cutting needle biopsy (CNB) combined with immunohistochemical study of myeloperoxidase (MPO) is a useful minimally invasive diagnostic procedure for histiocytic necrotizing lymphadenitis (HNL). HNL is mainly diagnosed by pathological findings of open surgical biopsy (OSB) specimens. Recently the appearance of anti-MPO positive histiocytes has been reported as a highly specific pathological diagnosis for HNL. Considering the cosmetic impact and burden on the patients, we performed CNB combined with immunohistochemical study of MPO for the diagnosis of HNL. Few studies have reported the utility of this method in the diagnosis of HNL. A retrospective study was conducted using clinical data from 20 HNL patients. CNB was performed in 8 patients and OSB in 13 (OSB after CNB in 1). MPO-positive histiocytes were observed in all of the 20 cases. The accuracy of the diagnoses was finally confirmed by the clinical courses in all cases.

Data analysis using a combination of independent component analysis and empirical mode decomposition

NASA Astrophysics Data System (ADS)

Lin, Shih-Lin; Tung, Pi-Cheng; Huang, Norden E.

2009-06-01

A combination of independent component analysis and empirical mode decomposition (ICA-EMD) is proposed in this paper to analyze low signal-to-noise ratio data. The advantages of ICA-EMD combination are these: ICA needs few sensory clues to separate the original source from unwanted noise and EMD can effectively separate the data into its constituting parts. The case studies reported here involve original sources contaminated by white Gaussian noise. The simulation results show that the ICA-EMD combination is an effective data analysis tool.

Phase I study of neratinib in combination with temsirolimus in patients with human epidermal growth factor receptor 2-dependent and other solid tumors.

PubMed

Gandhi, Leena; Bahleda, Rastislav; Tolaney, Sara M; Kwak, Eunice L; Cleary, James M; Pandya, Shuchi S; Hollebecque, Antoine; Abbas, Richat; Ananthakrishnan, Revathi; Berkenblit, Anna; Krygowski, Mizue; Liang, Yali; Turnbull, Kathleen W; Shapiro, Geoffrey I; Soria, Jean-Charles

2014-01-10

Human epidermal growth factor (HER) -mediated signaling is critical in many cancers, including subsets of breast and lung cancer. HER family members signal via the phosphatidylinositide 3-kinase (PI3K) -AKT/protein kinase B-mammalian target of rapamycin (mTOR) cascade; mTOR activation is critical for the expression of multiple contributors to tumor growth and invasion. On the basis of preclinical data suggesting synergy of HER2 inhibition and mTOR inhibition in breast and lung cancer models, we conducted a phase I combination study of neratinib, a small-molecule irreversible pan-HER tyrosine kinase inhibitor, and temsirolimus, an mTOR inhibitor, in patients with advanced solid tumors. This study enrolled patients to dosing combinations of neratinib and temsirolimus. The primary objective was to estimate the toxicity contour of the combination and establish recommended phase II doses. Sixty patients were treated on 12 of 16 possible dosing combinations. Diarrhea was the most common drug-related (93%) and dose-limiting toxicity (DLT), constituting four of 10 DLTs. Dose-limiting grade 3 metabolic abnormalities were also observed. Other frequent drug-related toxicities included nausea, stomatitis (both 53%), and anemia (48%). Two maximum-tolerated dose combinations were identified: 200 mg of neratinib/25 mg of temsirolimus and 160 mg of neratinib/50 mg of temsirolimus. Responses were noted in patients with HER2-amplified breast cancer resistant to trastuzumab, HER2-mutant non-small-cell lung cancer, and tumor types without identified mutations in the HER-PI3K-mTOR pathway. The combination of neratinib and temsirolimus was tolerable and demonstrated antitumor activity in multiple tumor types, warranting further evaluation.

Citrus limonoids and curcumin additively inhibit human colon cancer cells.

PubMed

Chidambara Murthy, Kotamballi N; Jayaprakasha, G K; Patil, Bhimanagouda S

2013-04-30

In the current study, we examined the ability of limonoids, including limonin, limonin glucoside (LG) and curcumin, to inhibit proliferation of human colon cancer (SW480) cells. Additionally, we studied the effect of combining these two classes of natural compounds on inhibition of proliferation and the possible mode of cytotoxicity. The SW480 cells were treated with compounds individually and in combination to understand the effect on cell death, DNA fragmentation, caspase-3 activity and the expression of Bax, Bcl-2 and caspase-3 proteins. Results of cell proliferation assays suggest that combinations of limonoids with curcumin at three different ratios (1 : 3, 1 : 1 and 3 : 1) to a final concentration of 50 ppm demonstrated up to 96% inhibition of cell proliferation. The MTT assay results were also confirmed by counting viable cells. Further, incubation of cells with combinations of limonoids and curcumin resulted in elevation of total cellular caspase-3 activity by 3.5-4.0 fold along with a 2- to 4-fold increase in the Bax/Bcl-2 ratio. The expression of pro-caspase-3 and its cleaved products in cells treated with curcumin (individually or combination) indicates higher potency of the combination to induce apoptosis. For the first time, this study provides compelling evidence of the pharmacodynamic additive effect of limonoids and curcumin in inhibiting human colon cancer cells. The above results were also confirmed by fluorescence microscopy of SW480 cells treated with limonoids, curcumin and combination, after tagging with fluorescent probes. These results suggest that consumption of curcumin and limonoids together may offer greater protection against colon cancer.

Tolerance to Stress Combination in Tomato Plants: New Insights in the Protective Role of Melatonin.

PubMed

Martinez, Vicente; Nieves-Cordones, Manuel; Lopez-Delacalle, Maria; Rodenas, Reyes; Mestre, Teresa C; Garcia-Sanchez, Francisco; Rubio, Francisco; Nortes, Pedro A; Mittler, Ron; Rivero, Rosa M

2018-02-28

Abiotic stresses such as drought, heat or salinity are major causes of yield loss worldwide. Recent studies have revealed that the acclimation of plants to a combination of different environmental stresses is unique and therefore cannot be directly deduced from studying the response of plants to each of the different stresses applied individually. The efficient detoxification of reactive oxygen species (ROS) is thought to play a key role in enhancing the tolerance of plants to abiotic stresses. Here, we report on the role of melatonin in the protection of the photosynthetic apparatus through the increase in ROS detoxification in tomato plants grown under the combination of salinity and heat, two of the most common abiotic stresses known to act jointly. Plants treated with exogenous melatonin showed a different modulation in the expression on some antioxidant-related genes and their related enzymes. More specifically, ascorbate peroxidase, glutathione reductase, glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase (APX, GR, GPX and Ph-GPX, resepctively) showed an antagonistic regulation as compared to plants that did not receive melatonin. This translated into a better antioxidant capacity and to a lesser ROS accumulation under stress combination. The performance of the photosynthesis parameters and the photosystems was also increased in plants treated with exogenous melatonin under the combination of salinity and heat. In accordance with these findings, tomato plants treated with melatonin were found to grow better under stress combination that the non-treated ones. Our study highlights the important role that exogenous melatonin plays in the acclimation of plants to a combination of two different abiotic stresses, and how this compound can specifically regulate oxidative stress-related genes and enzymes to increase plant tolerance.

Combined Effects of Simultaneous Exposure to Caffeine and Cocaine in the Mouse Striatum.

PubMed

Muñiz, Javier A; Gomez, Gimena; González, Betina; Rivero-Echeto, María Celeste; Cadet, Jean Lud; García-Rill, Edgar; Urbano, Francisco J; Bisagno, Veronica

2016-05-01

Caffeine is the world's most popular psychoactive drug and is also an active adulterant found in many drugs of abuse, including seized cocaine samples. Despite several studies which examine the effects of caffeine or cocaine administered as single agents, little data are available for these agents when given in combination. The purpose of the present study was to determine if combined intake of both psychostimulants can lead to maladaptive changes in striatal function. Mice were injected with a binge regimen (intermittent treatment for 13 days) of caffeine (3 × 5 mg/kg), cocaine (3 × 10 mg/kg), or combined administration. We found that chronic caffeine potentiated locomotion induced by cocaine and that both caffeine-treated groups showed sensitization. Striatal tissue was obtained 24 h and 7 days after last injection (withdrawal) for immunohistochemistry and mRNA expression. Our results show that combined intake of both psychostimulants can increase GFAP immunoreactivity in the striatum at both times post treatment. Gene expression analysis, targeted at dopamine, adenosine, and glutamate receptor subunit genes, revealed significant transcript down-regulation in the dorsal striatum of AMPA, NMDA, D1 and D2 receptor subunit mRNA expression in the group that received combined treatment, but not after individual administration. At withdrawal, we found increased D1 receptor mRNA expression along with increased A1, AMPA, NMDA, and metabotropic subunit expression. A2A mRNA showed decreased expression after both times in all experimental groups. Our study provides evidence that there are striatal alterations mediated by combined caffeine and cocaine administration, and highlights negative outcomes of chronic intake of both psychostimulants.

Factors that lead to the use of crack cocaine in combination with marijuana in Brazil: a qualitative study.

PubMed

Gonçalves, Janaina R; Nappo, Solange A

2015-07-25

In Brazil, crack cocaine use remains a healthcare challenge due to the rapid onset of its pleasurable effects, its ability to induce craving and addiction, and the fact that it is easily accessible. Delayed action on the part of the Brazilian Government in addressing the drug problem has led users to develop their own strategies for surviving the effects of crack cocaine use, particularly the drug craving and psychosis. In this context, users have sought the benefits of combining crack cocaine with marijuana. Our aim was to identify the reasons why users combine crack cocaine with marijuana and the health implications of doing so. The present study is a qualitative study, using in-depth interviews and criteria-based sampling, following 27 crack cocaine users who combined its use with marijuana. Participants were recruited using the snowball sampling technique, and the point of theoretical saturation was used to define the sample size. Data were analyzed using the content analysis technique. The interviewees reported that the combination of crack cocaine use with marijuana provided "protection" (reduced undesirable effects, improved sleep and appetite, reduced craving for crack cocaine, and allowed the patients to recover some quality of life). Combined use of cannabis as a strategy to reduce the effects of crack exhibited several significant advantages, particularly an improved quality of life, which "protected" users from the violence typical of the crack culture. Crack use is considered a serious public health problem in Brazil, and there are few solution strategies. Within that limited context, the combination of cannabis and crack deserves more thorough clinical investigation to assess its potential use as a strategy to reduce the damage associated with crack use.

Intense pulsed light, near infrared pulsed light, and fractional laser combination therapy for skin rejuvenation in Asian subjects: a prospective multi-center study in China.

PubMed

Tao, Li; Wu, Jiaqiang; Qian, Hui; Lu, Zhong; Li, Yuanhong; Wang, Weizhen; Zhao, Xiaozhong; Tu, Ping; Yin, Rui; Xiang, Leihong

2015-09-01

Ablative skin rejuvenation therapies have limitations for Asian people, including post-inflammatory hyperpigmentation and long down time. Non-ablative lasers are safer but have limited efficacy. This study is to investigate the safety and efficacy of a combination therapy consisting of intense pulsed light (IPL), near infrared (NIR) light, and fractional erbium YAG (Er:YAG) laser for skin rejuvenation in Asian people. This study recruited 113 subjects from six sites in China. Subjects were randomly assigned to a full-face group, who received combination therapy, and split-face groups, in which one half of the face received combination therapy and the other half received IPL monotherapy. Each subject received five treatment sessions during a period of 90 days. Subjects were followed up at 1 and 3 months post last treatment. Three months after last treatment, the full-face group (n = 57) had a global improvement rate of 29 % and 29 % for wrinkles, 32 % for skin texture, 33 % for pigment spots, 28 % for pore size, respectively. For patients in the split-face groups (n = 54), monotherapy side had a global improvement rate of 23 % and 20 % for wrinkles, 27 % for skin texture, 25 % for pigment spots, 25 % for pore size, respectively. Both combination therapy and monotherapy resulted in significant improvements at the follow-up visits compared to baseline (P < 0.001). Combination therapy showed significantly greater improvements compared to monotherapy at two follow-up visits (P < 0.05). Combination therapy is a safe and more effective strategy than IPL monotherapy for skin rejuvenation in Asian people.

Supra-additive effects of tramadol and acetaminophen in a human pain model.

PubMed

Filitz, Jörg; Ihmsen, Harald; Günther, Werner; Tröster, Andreas; Schwilden, Helmut; Schüttler, Jürgen; Koppert, Wolfgang

2008-06-01

The combination of analgesic drugs with different pharmacological properties may show better efficacy with less side effects. Aim of this study was to examine the analgesic and antihyperalgesic properties of the weak opioid tramadol and the non-opioid acetaminophen, alone as well as in combination, in an experimental pain model in humans. After approval of the local Ethics Committee, 17 healthy volunteers were enrolled in this double-blind and placebo-controlled study in a cross-over design. Transcutaneous electrical stimulation at high current densities (29.6+/-16.2 mA) induced spontaneous acute pain (NRS=6 of 10) and distinct areas of hyperalgesia for painful mechanical stimuli (pinprick-hyperalgesia). Pain intensities as well as the extent of the areas of hyperalgesia were assessed before, during and 150 min after a 15 min lasting intravenous infusion of acetaminophen (650 mg), tramadol (75 mg), a combination of both (325 mg acetaminophen and 37.5mg tramadol), or saline 0.9%. Tramadol led to a maximum pain reduction of 11.7+/-4.2% with negligible antihyperalgesic properties. In contrast, acetaminophen led to a similar pain reduction (9.8+/-4.4%), but a sustained antihyperalgesic effect (34.5+/-14.0% reduction of hyperalgesic area). The combination of both analgesics at half doses led to a supra-additive pain reduction of 15.2+/-5.7% and an enhanced antihyperalgesic effect (41.1+/-14.3% reduction of hyperalgesic areas) as compared to single administration of acetaminophen. Our study provides first results on interactions of tramadol and acetaminophen on experimental pain and hyperalgesia in humans. Pharmacodynamic modeling combined with the isobolographic technique showed supra-additive effects of the combination of acetaminophen and tramadol concerning both, analgesia and antihyperalgesia. The results might act as a rationale for combining both analgesics.

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: subgroup analysis of the DISTINCT randomised trial.

PubMed

Mancia, G; Cha, G; Gil-Extremera, B; Harvey, P; Lewin, A J; Villa, G; Kjeldsen, S E

2017-03-01

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS-Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min -1 , n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy.

Combined MTOR and autophagy inhibition

PubMed Central

Rangwala, Reshma; Chang, Yunyoung C; Hu, Janice; Algazy, Kenneth M; Evans, Tracey L; Fecher, Leslie A; Schuchter, Lynn M; Torigian, Drew A; Panosian, Jeffrey T; Troxel, Andrea B; Tan, Kay-See; Heitjan, Daniel F; DeMichele, Angela M; Vaughn, David J; Redlinger, Maryann; Alavi, Abass; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; O’Dwyer, Peter J; Amaravadi, Ravi K

2014-01-01

The combination of temsirolimus (TEM), an MTOR inhibitor, and hydroxychloroquine (HCQ), an autophagy inhibitor, augments cell death in preclinical models. This phase 1 dose-escalation study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with TEM in cancer patients. In the dose escalation portion, 27 patients with advanced solid malignancies were enrolled, followed by a cohort expansion at the top dose level in 12 patients with metastatic melanoma. The combination of HCQ and TEM was well tolerated, and grade 3 or 4 toxicity was limited to anorexia (7%), fatigue (7%), and nausea (7%). An MTD was not reached for HCQ, and the recommended phase II dose was HCQ 600 mg twice daily in combination with TEM 25 mg weekly. Other common grade 1 or 2 toxicities included fatigue, anorexia, nausea, stomatitis, rash, and weight loss. No responses were observed; however, 14/21 (67%) patients in the dose escalation and 14/19 (74%) patients with melanoma achieved stable disease. The median progression-free survival in 13 melanoma patients treated with HCQ 1200mg/d in combination with TEM was 3.5 mo. Novel 18-fluorodeoxyglucose positron emission tomography (FDG-PET) measurements predicted clinical outcome and provided further evidence that the addition of HCQ to TEM produced metabolic stress on tumors in patients that experienced clinical benefit. Pharmacodynamic evidence of autophagy inhibition was evident in serial PBMC and tumor biopsies only in patients treated with 1200 mg daily HCQ. This study indicates that TEM and HCQ is safe and tolerable, modulates autophagy in patients, and has significant antitumor activity. Further studies combining MTOR and autophagy inhibitors in cancer patients are warranted. PMID:24991838

Combined MTOR and autophagy inhibition: phase I trial of hydroxychloroquine and temsirolimus in patients with advanced solid tumors and melanoma.

PubMed

Rangwala, Reshma; Chang, Yunyoung C; Hu, Janice; Algazy, Kenneth M; Evans, Tracey L; Fecher, Leslie A; Schuchter, Lynn M; Torigian, Drew A; Panosian, Jeffrey T; Troxel, Andrea B; Tan, Kay-See; Heitjan, Daniel F; DeMichele, Angela M; Vaughn, David J; Redlinger, Maryann; Alavi, Abass; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; O'Dwyer, Peter J; Amaravadi, Ravi K

2014-08-01

The combination of temsirolimus (TEM), an MTOR inhibitor, and hydroxychloroquine (HCQ), an autophagy inhibitor, augments cell death in preclinical models. This phase 1 dose-escalation study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with TEM in cancer patients. In the dose escalation portion, 27 patients with advanced solid malignancies were enrolled, followed by a cohort expansion at the top dose level in 12 patients with metastatic melanoma. The combination of HCQ and TEM was well tolerated, and grade 3 or 4 toxicity was limited to anorexia (7%), fatigue (7%), and nausea (7%). An MTD was not reached for HCQ, and the recommended phase II dose was HCQ 600 mg twice daily in combination with TEM 25 mg weekly. Other common grade 1 or 2 toxicities included fatigue, anorexia, nausea, stomatitis, rash, and weight loss. No responses were observed; however, 14/21 (67%) patients in the dose escalation and 14/19 (74%) patients with melanoma achieved stable disease. The median progression-free survival in 13 melanoma patients treated with HCQ 1200mg/d in combination with TEM was 3.5 mo. Novel 18-fluorodeoxyglucose positron emission tomography (FDG-PET) measurements predicted clinical outcome and provided further evidence that the addition of HCQ to TEM produced metabolic stress on tumors in patients that experienced clinical benefit. Pharmacodynamic evidence of autophagy inhibition was evident in serial PBMC and tumor biopsies only in patients treated with 1200 mg daily HCQ. This study indicates that TEM and HCQ is safe and tolerable, modulates autophagy in patients, and has significant antitumor activity. Further studies combining MTOR and autophagy inhibitors in cancer patients are warranted.

Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma.

PubMed

Rangwala, Reshma; Leone, Robert; Chang, Yunyoung C; Fecher, Leslie A; Schuchter, Lynn M; Kramer, Amy; Tan, Kay-See; Heitjan, Daniel F; Rodgers, Glenda; Gallagher, Maryann; Piao, Shengfu; Troxel, Andrea B; Evans, Tracey L; DeMichele, Angela M; Nathanson, Katherine L; O'Dwyer, Peter J; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; Amaravadi, Ravi K

2014-08-01

Blocking autophagy with hydroxychloroquine (HCQ) augments cell death associated with alkylating chemotherapy in preclinical models. This phase I study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with dose-intense temozolomide (TMZ) in patients with advanced solid malignancies. Forty patients (73% metastatic melanoma) were treated with oral HCQ 200 to 1200 mg daily with dose-intense oral TMZ 150 mg/m (2) daily for 7/14 d. This combination was well tolerated with no recurrent dose-limiting toxicities observed. An MTD was not reached for HCQ and the recommended phase II dose was HCQ 600 mg twice daily combined with dose-intense TMZ. Common toxicities included grade 2 fatigue (55%), anorexia (28%), nausea (48%), constipation (20%), and diarrhea (20%). Partial responses and stable disease were observed in 3/22 (14%) and 6/22 (27%) patients with metastatic melanoma. In the final dose cohort 2/6 patients with refractory BRAF wild-type melanoma had a near complete response, and prolonged stable disease, respectively. A significant accumulation in autophagic vacuoles (AV) in peripheral blood mononuclear cells was observed in response to combined therapy. Population pharmacokinetics (PK) modeling, individual PK simulations, and PK-pharmacodynamics (PD) analysis identified a threshold HCQ peak concentration that predicts therapy-associated AV accumulation. This study indicates that the combination of high-dose HCQ and dose-intense TMZ is safe and tolerable, and is associated with autophagy modulation in patients. Prolonged stable disease and responses suggest antitumor activity in melanoma patients, warranting further studies of this combination, or combinations of more potent autophagy inhibitors and chemotherapy in melanoma.

Immunotoxicity of ochratoxin A and aflatoxin B1 in combination is associated with the nuclear factor kappa B signaling pathway in 3D4/21 cells.

PubMed

Hou, Lili; Gan, Fang; Zhou, Xuan; Zhou, Yajiao; Qian, Gang; Liu, Zixuan; Huang, Kehe

2018-05-01

The co-contamination of cereals, grains, crops, and animal feeds by mycotoxins is a universal problem. Humans and animals are exposed to several mycotoxins simultaneously as evidenced by extensive studies on this topic. Yet, most studies have addressed the effects of mycotoxins individually. Aflatoxin B1 and ochratoxin A can induce immunotoxicity. However, it remains unclear whether a combination of these mycotoxins aggravates immunotoxicity and the potential mechanism underlying this effect. In this study, we used the cell line 3D4/21, swine alveolus macrophages and innate immune cell. The results showed that the percentage of cell inhibition, annexin V/PI-positive rates, and the expression of pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-6) significantly increased and the release of lactate dehydrogenase and phagocytotic index were significantly decreased at different concentrations of aflatoxin B1 and ochratoxin A combination when compared with control. The combination of aflatoxin B1 and ochratoxin A significantly decreased the production of GSH and increased reactive oxygen species level. However, N-acetylcysteine suppressed the oxidative stress and alleviated the immunotoxicity induced by the combination. The combination of aflatoxin B1 and ochratoxin A markedly enhanced the degradation of IκBa, the phosphorylation of nuclear factor kappa B (p65), and the translocation of activated nuclear factor kappa B (NF-κB) into the nuclei as demonstrated by western blotting and confocal laser scanning microscopy. These effects could be reversed by BAY 11-7082, a specific inhibitor of NF-κB. Taken together, a combination of aflatoxin B1 and ochratoxin A could aggravate immunotoxicity by activating the NF-κB signaling pathway. Copyright © 2018 Elsevier Ltd. All rights reserved.

Combination therapy of chitosan, gynostemma, and motherwort alleviates the progression of experimental rat chronic renal failure by inhibiting STAT1 activation

PubMed Central

Bai, Wenxia; Wang, Shudong; An, Shanshan; Guo, Mengjie; Gong, Guangming; Liu, Wenya; Ma, Shaoxin; Li, Xin; Fu, Jihua; Yao, Wenbing

2018-01-01

This study aimed to investigate the effect of single and combination therapy using chitosan (K), gynostemma (J), and motherwort (Y) on an experimental rat model of chronic renal failure (CRF) induced by adenine and the underlying mechanisms. CRF rats were treated with individual or combinational therapy with two or three of these agents. Biochemical indicators showed that the levels of blood urea nitrogen, creatinine and uric acid decreased and the levels of albumin and hemoglobin increased by single or combination therapy of these drugs. Drug treatment also decreased oxidative stress damage of renal tissues in CRF rats. Histopathological lesions were attenuated in each drug treatment group by various degrees. Additionally, drug treatment affected the expression of extracellular matrix (ECM) proteins including plasminogen activator inhibitor 1, collagen I, matrix metalloprotease-1, and tissue inhibitor of metalloproteinases 1. In particular, the combination therapy of K, J, and Y was superior to the respective monotherapy, which supported the prescription of KJY combination. We further studied the inhibitory effect of KJY on LPS-induced inflammation in RAW264.7 macrophages. The results showed that KJY inhibited LPS-induced secretion of inflammatory cytokines (Interferon-gamma, Interleukin-1 Beta, chemokine (C-X-C motif) ligand 10, cyclooxygenase-2 and Tumor necrosis factor-α in RAW264.7 macrophages. Combination therapy of KJY suppressed the protein expression of Cyclooxygenase-2 and inducible nitric oxide synthase in vivo and in vitro. Further study indicated that KJY inhibited STAT1 activation by down regulating p-STAT1 to exert anti-inflammatory effect and improve renal function in rats with chronic renal failure. PMID:29643988

Chemoprevention of Head and Neck Cancer by Simultaneous Blocking of Epidermal Growth Factor Receptor and Cyclooxygenase-2 Signaling Pathways: Preclinical and Clinical Studies

PubMed Central

Shin, Dong M.; Zhang, Hongzheng; Saba, Nabil; Chen, Amy; Nannapaneni, Sreenivas; Amin, A.R.M. Ruhul; Müller, Susan; Lewis, Melinda; Sica, Gabriel; Kono, Scott; Brandes, Johann C.; Grist, William; Moreno-Williams, Rachel; Beitler, Jonathan J.; Thomas, Sufi M.; Chen, Zhengjia; Shin, Hyung Ju C.; Grandis, Jennifer R.; Khuri, Fadlo R.; Chen, Zhuo Georgia

2013-01-01

Purpose We investigated the efficacy and underlying molecular mechanism of a novel chemopreventive strategy combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with cyclooxygenase-2 inhibitor (COX-2I). Experimental Design We examined the inhibition of tumor cell growth by combined EGFR-TKI (erlotinib) and COX-2I (celecoxib) treatment using head and neck cancer (HNC) cell lines and a preventive xenograft model. We studied the antiangiogenic activity of these agents and examined the affected signaling pathways by immunoblotting analysis in tumor cell lysates and immunohistochemistry (IHC) and enzyme immunoassay (EIA) analyses on the mouse xenograft tissues and blood, respectively. Biomarkers in these signaling pathways were studied by IHC, EIA, and an antibody array analysis in samples collected from participants in a phase I chemoprevention trial of erlotinib and celecoxib. Results The combined treatment inhibited HNC cell growth significantly more potently than either single agent alone in cell line and xenograft models, and resulted in greater inhibition of cell cycle progression at G1 phase than either single drug. The combined treatment modulated the EGFR and mTOR signaling pathways. A phase I chemoprevention trial of combined erlotinib and celecoxib revealed an overall pathologic response rate of 71% at time of data analysis. Analysis of tissue samples from participants consistently showed downregulation of EGFR, pERK and pS6 levels after treatment, which correlated with clinical response. Conclusion Treatment with erlotinib combined with celecoxib offers an effective chemopreventive approach through inhibition of EGFR and mTOR pathways, which may serve as potential biomarkers to monitor the intervention of this combination in the clinic. PMID:23422093

Ablative fractional carbon dioxide laser combined with intense pulsed light for the treatment of photoaging skin in Chinese population: A split-face study.

PubMed

Mei, Xue-Ling; Wang, Li

2018-01-01

Intense pulsed light (IPL) is effective for the treatment of lentigines, telangiectasia, and generalized erythema, but is less effective in the removal of skin wrinkles. Fractional laser is effective on skin wrinkles and textural irregularities, but can induce postinflammatory hyperpigmentation (PIH), especially in Asians. This study evaluated the safety and efficacy of ablative fractional laser (AFL) in combination with IPL in the treatment of photoaging skin in Asians.This study included 28 Chinese women with Fitzpatrick skin type III and IV. The side of the face to be treated with IPL alone (3 times) or AFL in combination with IPL (2 IPL treatments and 1 AFL treatment) was randomly selected. Skin conditions including hydration, transepidermal water loss, elasticity, spots, ultraviolet spots, brown spots, wrinkle, texture, pore size and red areas, as well as adverse effects were evaluated before the treatment and at 30 days after the treatment.Compared with IPL treatment alone, AFL in combination with IPL significantly increased elasticity, decreased pore size, reduced skin wrinkles, and improved skin texture (P = .004, P = .039, P = .015, and P = .035, respectively). Both treatment protocols produced similar effects in relation to the improvement of photoaging-induced pigmentation. The combined therapy did not impair epidermal barrier function. No postoperative infection, hypopigmentation, or scarring occurred after IPL and AFL treatments. PIH occurred at 1 month after AFL treatment and disappeared at 30 days after completion of the combined therapy.AFL in combination with IPL is safe and effective for photoaging skin in Asians. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

The combination of plyometric and balance training improves sprint and shuttle run performances more often than plyometric-only training with children.

PubMed

Chaouachi, Anis; Othman, Aymen Ben; Hammami, Raouf; Drinkwater, Eric J; Behm, David G

2014-02-01

Because balance is not fully developed in children and studies have shown functional improvements with balance only training studies, a combination of plyometric and balance activities might enhance static balance, dynamic balance, and power. The objective of this study was to compare the effectiveness of plyometric only (PLYO) with balance and plyometric (COMBINED) training on balance and power measures in children. Before and after an 8-week training period, testing assessed lower-body strength (1 repetition maximum leg press), power (horizontal and vertical jumps, triple hop for distance, reactive strength, and leg stiffness), running speed (10-m and 30-m sprint), static and dynamic balance (Standing Stork Test and Star Excursion Balance Test), and agility (shuttle run). Subjects were randomly divided into 2 training groups (PLYO [n = 14] and COMBINED [n = 14]) and a control group (n = 12). Results based on magnitude-based inferences and precision of estimation indicated that the COMBINED training group was considered likely to be superior to the PLYO group in leg stiffness (d = 0.69, 91% likely), 10-m sprint (d = 0.57, 84% likely), and shuttle run (d = 0.52, 80% likely). The difference between the groups was unclear in 8 of the 11 dependent variables. COMBINED training enhanced activities such as 10-m sprints and shuttle runs to a greater degree. COMBINED training could be an important consideration for reducing the high velocity impacts of PLYO training. This reduction in stretch-shortening cycle stress on neuromuscular system with the replacement of balance and landing exercises might help to alleviate the overtraining effects of excessive repetitive high load activities.

Biomechanical analysis of combining head-down tilt traction with vibration for different grades of degeneration of the lumbar spine.

PubMed

Wang, Sicong; Wang, Lizhen; Wang, Yawei; Du, Chengfei; Zhang, Ming; Fan, Yubo

2017-01-01

In recent years, a combination of traction and vibration therapy is usually used to alleviate low back pain (LBP) in clinical settings. Combining head-down tilt (HDT) traction with vibration was demonstrated to be efficacious for LBP patients in our previous study. However, the biomechanics of the lumbar spine during this combined treatment is not well known and need quantitative analysis. In addition, LBP patients have different grades of degeneration of the lumbar spinal structure, which are often age related. Selecting a suitable rehabilitation therapy for different age groups of patients has been challenging. Therefore, a finite element (FE) model of the L1-L5 lumbar spine and a vibration dynamic model are developed in this study in order to investigate the biomechanical effects of the combination of HDT traction and vibration therapy on the age-related degeneration of the lumbar spine. The decrease of intradiscal pressure is more effective when vibration is combined with traction therapy. Moreover, the stresses on the discs are lower in the "traction+vibration" mode than the "traction-only" mode. The stress concentration at the posterior part of nucleus is mitigated after the vibration is combined. The disc deformations especially posterior disc radial retraction is improved in the "traction+vibration" mode. These beneficial effects of this therapy could help decompress the discs and spinal nerves and therefore relieve LBP. Simultaneously, patients with grade 1 degeneration (approximately 41-50 years old) are able to achieve better results compared with other age groups. This study could be used to provide a more effective LBP rehabilitation therapy. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) for the prevention of surgical site infection in elective colorectal surgery: study protocol for a multicentre, double-blind, randomised controlled clinical trial

PubMed Central

Vignaud, Marie; Paugam-Burtz, Catherine; Garot, Matthias; Jaber, Samir; Slim, Karem; Panis, Yves; Lucet, Jean-Christophe; Bourdier, Justine; Morand, Dominique; Pereira, Bruno; Futier, Emmanuel

2018-01-01

Introduction Surgical site infections (SSIs) account for 30% of all healthcare-associated infections, with reported rates ranging from 8% and 30% after colorectal surgery and are associated with increased morbidity and mortality rates, length of hospital stay and costs in healthcare. Administration of systemic antimicrobial prophylaxis before surgery is recommended to reduce the risk of SSI, but the optimal regimen remains unclear. We aim to evaluate whether a combined oral and intravenous antimicrobial prophylaxis could be more effective to reduce the incidence of SSI after colorectal surgery, as compared with the standard practice of intravenous antimicrobial prophylaxis alone. Methods and analysis Comparison of intravenous versus combined oral and intravenous antimicrobial prophylaxis (COMBINE) trial is a randomised, placebo-controlled, parallel, double-blind, multicentre study of 960 patients undergoing elective colorectal surgery. Patients will be randomly allocated in a 1:1 ratio to receive either combined oral and intravenous antimicrobial prophylaxis or intravenous antibiotic prophylaxis alone, stratified by centre, the surgical procedure (laparoscopic or open surgery) and according to the surgical skin antisepsis (chlorexidine–alcohol or povidione-iodine alcoholic solution). The primary endpoint is the rate of SSI by day 30 following surgery, with SSI defined by the criteria developed by the Centers for Disease Control and Prevention. Data will be analysed on the intention-to-treat principle and a per-protocol basis. Ethics and dissemination COMBINE trial has been approved by an independent ethics committee for all study centres. Participant recruitment began in May 2016. Results will be published in international peer-reviewed medical journals. Trial registration number EudraCT 2015-002559-84; NCT02618720. PMID:29654027

Barley responses to combined waterlogging and salinity stress: separating effects of oxygen deprivation and elemental toxicity

PubMed Central

Zeng, Fanrong; Shabala, Lana; Zhou, Meixue; Zhang, Guoping; Shabala, Sergey

2013-01-01

Salinity and waterlogging are two major factors affecting crop production around the world and often occur together (e.g., salt brought to the surface by rising water tables). While the physiological and molecular mechanisms of plant responses to each of these environmental constraints are studied in detail, the mechanisms underlying plant tolerance to their combined stress are much less understood. In this study, whole-plant physiological responses to individual/combined salinity and waterlogging stresses were studied using two barley varieties grown in either vermiculite (semi-hydroponics) or sandy loam. Two weeks of combined salinity and waterlogging treatment significantly decreased plant biomass, chlorophyll content, maximal quantum efficiency of PSII and water content (WC) in both varieties, while the percentage of chlorotic and necrotic leaves and leaf sap osmolality increased. The adverse effects of the combined stresses were much stronger in the waterlogging-sensitive variety Naso Nijo. Compared with salinity stress alone, the combined stress resulted in a 2-fold increase in leaf Na+, but a 40% decrease in leaf K+ content. Importantly, the effects of the combined stress were more pronounced in sandy loam compared with vermiculite and correlated with changes in the soil redox potential and accumulation of Mn and Fe in the waterlogged soils. It is concluded that hypoxia alone is not a major factor determining differential plant growth under adverse stress conditions, and that elemental toxicities resulting from changes in soil redox potential have a major impact on genotypic differences in plant physiological and agronomical responses. These results are further discussed in the context of plant breeding for waterlogging stress tolerance. PMID:23967003

Health-related quality of life impact in a randomised phase III study of the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600 metastatic melanoma.

PubMed

Schadendorf, Dirk; Amonkar, Mayur M; Stroyakovskiy, Daniil; Levchenko, Evgeny; Gogas, Helen; de Braud, Filippo; Grob, Jean-Jacques; Bondarenko, Igor; Garbe, Claus; Lebbe, Celeste; Larkin, James; Chiarion-Sileni, Vanna; Millward, Michael; Arance, Ana; Mandalà, Mario; Flaherty, Keith T; Nathan, Paul; Ribas, Antoni; Robert, Caroline; Casey, Michelle; DeMarini, Douglas J; Irani, Jhangir G; Aktan, Gursel; Long, Georgina V

2015-05-01

To present the impact of treatments on health-related quality of life (HRQoL) from the double-blind, randomised phase III COMBI-d study that investigated the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600E/K-mutant metastatic melanoma. COMBI-d showed significantly prolonged progression-free survival for the combination. HRQoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, a generic cancer questionnaire (completed at baseline, during study treatment, at progression and post progression) assessing various dimensions (global health/QoL, functional status, and symptom impact). A mixed-model, repeated-measures analyses of covariance evaluated differences between arms. Questionnaire completion rates were >95% at baseline, >85% to week 40 and >70% at disease progression. Baseline scores across both arms were comparable for all dimensions. Global health dimension scores were significantly better at weeks 8, 16 and 24 for patients receiving the combination during treatment and at progression. The majority of functional dimension scores (physical, social, role, emotional and cognitive functioning) trended in favour of the combination. Pain scores were significantly improved and clinically meaningful (6-13 point difference) for patients receiving the combination for all follow-up assessments versus those receiving dabrafenib monotherapy. For other symptom dimensions (nausea and vomiting, diarrhoea, dyspnoea, and constipation), scores trended in favour of dabrafenib monotherapy. This analysis demonstrates that the combination of dabrafenib and trametinib provides better preservation of HRQoL and pain improvements versus dabrafenib monotherapy while also delaying progression. (Clinicaltrials.gov registration number: NCT01584648). Copyright © 2015 Elsevier Ltd. All rights reserved.

Pupil dilation dynamics with an intracameral fixed combination of mydriatics and anesthetic during cataract surgery.

PubMed

Chiambaretta, Frederic; Pleyer, Uwe; Behndig, Anders; Pisella, Pierre-Jean; Mertens, Erik; Limao, Antonio; Fasce, Francesco; Fernandez, Joaquin; Benmoussa, Salah-Eddine; Labetoulle, Marc; Cochener, Beatrice

2018-03-01

To compare the pupil dynamics of an intracameral combination of 2 mydriatics and 1 anesthetic (Mydrane) to a standard topical regimen for cataract surgery. Sixty-two centers in Europe and 6 centers in Algeria. Prospective case series. Pupil size measurements were performed in 2 randomized studies (phase 2 and phase 3) under masked conditions (recorded videography, masked reading center). The outcomes in the phase 2 study supported evaluation of the timeframe to obtain pupil dilation and the phase 3 study provided results on mydriasis stability. Phase 2 and phase 3 comprised 139 patients and 591 patients, respectively. After intracameral combination administration, 95% of the pupil dilation was achieved within a mean of 28.6 seconds ± 4.6 (SD). At the beginning of capsulorhexis creation, the mean pupil diameter was larger than 7.0 mm in both groups. The intraoperative pupil diameter remained stable in the intracameral combination group and decreased in the topical group. The mean change in pupil size just before capsulorhexis to the end of surgery (just before cefuroxime injection) was -0.22 ± 0.72 mm and -1.67 ± 0.98 mm, respectively. No clinically significant change in pupil diameter (change <1.0 mm) occurred in the majority of the intracameral combination group (89.3%) compared with the topical group (26.8%). Intracameral combination of 2 mydriatics and 1 anesthetic is an alternative to topical mydriatics for cataract surgery. The prompt onset of pupil dilation and the stable mydriasis induced by this drug combination improved the intraoperative conditions during crucial steps, such as intraocular lens implantation. Copyright © 2018. Published by Elsevier Inc.

TRANSFORMATIONAL SENTENCE-COMBINING, A METHOD FOR ENHANCING THE DEVELOPMENT OF SYNTACTIC FLUENCY IN ENGLISH COMPOSITION. FINAL REPORT.

ERIC Educational Resources Information Center

MELLON, JOHN C.

THIS STUDY REPORTS AN EXPERIMENT ON THE HYPOTHESIS THAT GRAMMAR-RELATED SENTENCE-COMBINING PRACTICE WILL MEANINGFULLY ENHANCE THE NORMAL GROWTH OF SYNTACTIC FLUENCY. TRADITIONAL STUDIES ON ERROR THERAPY AND SENTENCE STRUCTURE ARE REVIEWED, AND DESIGN AND RATIONALE ARE INFERRED FROM THE RESEARCH OF BATEMAN AND ZIDONIS. RULE LEARNING, PATTERN…

Assessment by Time-Kill Methodology of the Synergistic Effects of Oritavancin in Combination with Other Antimicrobial Agents against Staphylococcus aureus▿

PubMed Central

Belley, Adam; Neesham-Grenon, Eve; Arhin, Francis F.; McKay, Geoffrey A.; Parr, Thomas R.; Moeck, Gregory

2008-01-01

Oritavancin is a semisynthetic lipoglycopeptide in clinical development for serious gram-positive infections. This study describes the synergistic activity of oritavancin in combination with gentamicin, linezolid, moxifloxacin, or rifampin in time-kill studies against methicillin-susceptible, vancomycin-intermediate, and vancomycin-resistant Staphylococcus aureus. PMID:18644953

Problem-Based Learning--Buginese Cultural Knowledge Model--Case Study: Teaching Mathematics at Junior High School

ERIC Educational Resources Information Center

Cheriani, Cheriani; Mahmud, Alimuddin; Tahmir, Suradi; Manda, Darman; Dirawan, Gufran Darma

2015-01-01

This study aims to determine the differences in learning output by using Problem Based Model combines with the "Buginese" Local Cultural Knowledge (PBL-Culture). It is also explores the students activities in learning mathematics subject by using PBL-Culture Models. This research is using Mixed Methods approach that combined quantitative…

Combined Application of Study Design and Case-Based Learning Comprehensive Model in Epidemiology Teaching

ERIC Educational Resources Information Center

Shi, Xiuquan; Zhou, Yanna; Wang, Haiyan; Wang, Tao; Nie, Chan; Shi, Shangpeng

2017-01-01

This paper aims to conduct the SD-CBL (study design with the case based learning, SD-CBL) in Epidemiology teaching and evaluate its effect. Students from five classes were recruited, and a combined comprehensive teaching model of SD-CBL was used in the "Injury Epidemiology" chapter, while other chapters in "Epidemiology"…

The Isolated and Combined Effects of Intervention Components on Mathematic Fluency

ERIC Educational Resources Information Center

Hastings, Kimberly A.

2010-01-01

Scope and Method of Study: The scope of the study was to compare empirically supported math fluency interventions to a control group as well as each other. The intervention components were isolated to investigate their initial strength as well as adding them together to investigate if the combined intervention was actually stronger or more…

The Statistical Power of the Cluster Randomized Block Design with Matched Pairs--A Simulation Study

ERIC Educational Resources Information Center

Dong, Nianbo; Lipsey, Mark

2010-01-01

This study uses simulation techniques to examine the statistical power of the group- randomized design and the matched-pair (MP) randomized block design under various parameter combinations. Both nearest neighbor matching and random matching are used for the MP design. The power of each design for any parameter combination was calculated from…

Laparoscopic Surgical Treatment of Severe Obesity Combined with Gastroesophageal Reflux Disease: A Pilot Randomized Two-Arm Controlled Clinical Study

ERIC Educational Resources Information Center

Ospanov, Oral B.; Orekeshova, Akzhunis M.; Fursov, Roman A.; Yelemesov, Aset A.

2016-01-01

Obesity and gastroesophageal reflux disease (GERD) are serious medical, social, and economic problems of modern society. A pilot randomized two-arm controlled clinical study was conducted to compare laparoscopic plication of the greater gastric curvature combined with Nissen fundoplication (LFN+LGP) versus only Nissen fundoplication (LFN). The…

What We Gain by Combining Variationist and Concept-Oriented Approaches: The Case of Acquiring Spanish Future-Time Expression

ERIC Educational Resources Information Center

Kanwit, Matthew

2017-01-01

This study aimed to advance research on first and second language future-time expression in Spanish and to demonstrate the strengths of combining functionalist, concept-oriented approaches (e.g., Andersen, 1984; Bardovi-Harlig, 2000; Shirai, 1995; von Stutterheim & Klein, 1987) with variationist approaches. The study targeted 140 participants…

The Shifting Subtypes of ADHD: Classification Depends on How Symptom Reports Are Combined

ERIC Educational Resources Information Center

Rowland, Andrew S.; Skipper, Betty; Rabiner, David L.; Umbach, David M.; Stallone, Lil; Campbell, Richard A.; Hough, Richard L.; Naftel, A. J.; Sandler, Dale P.

2008-01-01

Research on the correlates of ADHD subtypes has yielded inconsistent findings, perhaps because the procedures used to define subtypes vary across studies. We examined this possibility by investigating whether the ADHD subtype distribution in a community sample was sensitive to different methods for combining informant data. We conducted a study to…

Combined treatments of enterocin AS-48 with biocides to improve the inactivation of methicillin-sensitive and methicillin-resistant Staphylococcus aureus planktonic and sessile cells.

PubMed

Caballero Gómez, Natacha; Abriouel, Hikmate; Grande, M José; Pérez Pulido, Rubén; Gálvez, Antonio

2013-05-15

Control of staphylococci during cleaning and disinfection is important to the food industry. Broad-spectrum bacteriocins with proved anti-staphylococcal activity, such as enterocin AS-48, could open new possibilities for disinfection in combination with biocides. In the present study, enterocin AS-48 was tested singly or in combination with biocides against a cocktail of six Staphylococcus aureus strains (including three methicillin-resistant strains) in planktonic state as well as in biofilms formed on polystyrene microtiter plates. Cells were challenged with enterocin, biocides or enterocin/biocide combinations. Inactivation of planktonic cells increased significantly (p<0.05) when enterocin AS-48 (25mg/l) was tested in combination with benzalkonium chloride (BC), cetrimide (CT) and hexadecylpyridinium chloride (HDP), and non-significantly in combination with didecyldimethylammonium bromide (AB), triclosan (TC), hexachlorophene (CF), polyhexamethylen guanidinium chloride (PHMG), chlorhexidine (CH) or P3-oxonia (OX). In the sessile state (24h biofilms), staphylococci required higher biocide concentrations in most cases, except for OX. Inactivation of sessile staphylococci increased remarkably when biocides were applied in combination with enterocin AS-48, especially when the bacteriocin was added at 50mg/l. During storage, the concentrations of sessile as well as planktonic cells in the treated samples decreased remarkably for BC, TC and PHMG, but OX failed to inhibit proliferation of the treated biofilms as well as growth of planktonic cells. The observed inhibitory effects during storage were potentiated when the biocides were combined with 50 mg/l enterocin AS-48. Results from this study suggest that selected combinations of enterocin AS-48 and biocides offer potential use against planktonic and sessile, methicillin-sensitive and methicillin-resistant S. aureus. Copyright © 2013 Elsevier B.V. All rights reserved.

Acetaminophen and non-steroidal anti-inflammatory drugs interact with morphine and tramadol analgesia for the treatment of neuropathic pain in rats.

PubMed

Shinozaki, Tomonari; Yamada, Toshihiko; Nonaka, Takahiro; Yamamoto, Tatsuo

2015-06-01

Although non-steroidal anti-inflammatory drugs and acetaminophen have no proven efficacy against neuropathic pain, they are frequently prescribed for neuropathic pain patients. We examined whether the combination of opioids (tramadol and morphine) with indomethacin or acetaminophen produce favorable effects on neuropathic pain and compared the efficacy for neuropathic pain with that for inflammatory pain. The carrageenan model was used as the inflammatory pain model while the tibial neuroma transposition (TNT) model was used as the neuropathic pain model. The tibial nerve is transected in the TNT model, with the tibial nerve stump then transpositioned to the lateral aspect of the hindlimb. Neuropathic pain (mechanical allodynia and neuroma pain) is observed after TNT injury. Drugs were administered orally. In the carrageenan model, all drugs produced anti-allodynic effects and all drug combinations, but not tramadol + indomethacin combination, produced synergistic anti-allodynic effects. In the TNT model, tramadol and morphine, but not acetaminophen and indomethacin, produced anti-neuropathic pain effects. In the combination, with the exception of morphine + acetaminophen combination, both acetaminophen and indomethacin reduced the 50% effective dose (ED50) of tramadol and morphine as compared with the ED50s for the single drug study in the TNT model. The ED50s of tramadol and morphine in the carrageenan combination test were not statistically significantly different from the ED50s in the TNT model combination study. The combination of opioids with indomethacin or acetaminophen produced a synergistic analgesic effect both in inflammatory and neuropathic pain with some exceptions. The efficacy of these combinations for neuropathic pain was not different from that for inflammatory pain.

Non-lipid effects of rosuvastatin-fenofibrate combination therapy in high-risk Asian patients with mixed hyperlipidemia.

PubMed

Lee, Sang-Hak; Cho, Kyoung-Im; Kim, Jang-Young; Ahn, Young Keun; Rha, Seung-Woon; Kim, Yong-Jin; Choi, Yun-Seok; Choi, Si Wan; Jeon, Dong Woon; Min, Pil-Ki; Choi, Dong-Ju; Baek, Sang Hong; Kim, Kwon Sam; Byun, Young Sup; Jang, Yangsoo

2012-03-01

The aim of this study is to compare the non-lipid effects of rosuvastatin-fenofibrate combination therapy with rosuvastatin monotherapy in high-risk Asian patients with mixed hyperlipidemia. A total of 236 patients were initially screened. After six weeks of diet and life style changes, 180 of these patients were randomly assigned to receive one of two regimens: rosuvastatin 10 mg plus fenofibrate 160 mg or rosuvastatin 10 mg. The primary outcome variables were the incidences of muscle or liver enzyme elevation. The patients were followed for 24 weeks during drug treatment and for an additional four weeks after drug discontinuation. The rates of the primary outcome variables were similar between the two groups (2.8% and 3.9% in the combination and the rosuvastatin groups, respectively, p=1.00). The combination group had more, but not significantly, common treatment-related adverse events (AEs) (13.3% and 5.6%, respectively) and drug discontinuation due to AEs (10.0% and 3.3%, respectively) than the rosouvastatin group. Combination therapy was associated with higher elevations in homocysteine, blood urea nitrogen, and serum creatinine, whereas elevation in alanine aminotransferase was greater in the rosuvastatin group. Leukocyte count and hemoglobin level decreased to a greater extent in the combination group. The combination group showed greater reductions in TG and elevation in HDL-cholesterol. In our study population, the rosuvastatin-fenofibrate combination resulted in comparable incidences of myo- or hepatotoxicity as rosuvastatin monotherapy. However, this combination may need to be used with caution in individuals with underlying pathologies such as renal dysfunction (NCT01414803). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Capacities of metabotropic glutamate modulators in counteracting soman-induced seizures in rats.

PubMed

Myhrer, Trond; Mariussen, Espen; Enger, Siri; Aas, Pål

2013-10-15

Current treatment of nerve agent poisoning with ionotropic drugs proves inadequate, and alternative treatment strategies are searched for. Based on positive findings with metabotropic glutamate modulators in microinfusion studies, the present study was initiated to examine anticonvulsant effects of MPEP (2-Methyl-6-(phenylethynyl)pyridine hydrochloride), a metabotropic glutamate receptor 5 antagonist, and DCG-IV ((2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine), a metabotropic glutamate receptor 2/3 agonist, when administered systemically in combinations with HI-6 (1-[([4-(aminocarbonyl)pyridino]methoxy)methyl]-2-[(hydroxyimino)methyl]pyridinium) and procyclidine or HI-6 and levetiracetam relative to the combination of HI-6, procyclidine, and levetiracetam. The results showed that MPEP or DCG-IV combined with HI-6 and procyclidine resulted in substantial antidotal efficacy when administered 20 min after onset of seizures elicited by soman. MPEP or DCG-IV combined with HI-6 and levetiracetam did not terminate seizures and preserve lives. When given 20 min before challenge with soman, DCG-IV in combination with HI-6 and procyclidine provided protection, whereas MPEP combined with HI-6 and procyclidine did not. Combinations with metabotropic glutamate receptor modulators did not achieve the same high level of antidotal efficacy as the combination of HI-6, procyclidine, and levetiracetam. MPEP alone inhibited pseudocholinesterase activity in the brain markedly. A positive correlation was found between latency to seizure onset or full protection and level of pseudocholinesterase activity in brain. MPEP and DCG-IV can serve as effective anticonvulsants against nerve agent poisoning when combined with HI-6 and procyclidine. Metabotropic glutamate receptor modulators may represent an alternative or supplement to treatment with ionotropic drugs. © 2013 Elsevier B.V. All rights reserved.

Combination Therapy of Etanercept and Fumarates versus Etanercept Monotherapy in Psoriasis: A Randomized Exploratory Study

PubMed Central

van Bezooijen, Ji Sun; Balak, Deepak M.W.; van Doorn, Martijn B.A.; Looman, Caspar W.N.; Schreurs, Marco W.J.; Koch, Birgit C.P.; van Gelder, Teun; Prens, Errol P.

2016-01-01

Background Biologics are a safe and efficacious therapy for psoriasis. The drug survival of biologics may be disappointing, primarily due to loss of efficacy. Therefore, safe combination treatments are sought to improve their clinical response. Objective To assess the efficacy, safety and tolerability of the combination therapy of etanercept with fumarates versus etanercept monotherapy. Methods Thirty-three patients with psoriasis were randomized 1:1 to receive etanercept combined with fumarates or etanercept monotherapy. The primary outcome measure was the difference in PASI-75 response after 24 weeks; additionally, a longitudinal analysis was performed. An important secondary outcome measure was the proportion of patients with a Physician Global Assessment (PGA) of clear or almost clear. Adverse events were collected throughout the study. Results In the combination therapy group, 78% (14 out of 18 patients) reached PASI-75 at week 24 versus 57% (8 out of 14 patients) in the monotherapy group (p = 0.27). The longitudinal analysis showed a PASI reduction of 5.97% per week for the combination therapy group and of 4.76% for the monotherapy group (p = 0.11). In the combination therapy group, 94% (17 out of 18 patients) of patients had a PGA of clear/almost clear versus 64% (9 out of 14 patients) in the monotherapy group (p = 0.064). The incidence of mild gastrointestinal complaints was higher in the combination group than in the monotherapy group. Conclusion Using the PGA, combination therapy showed a trend towards faster improvement in the first 24 weeks. The difference in the PASI score between the two groups was not statistically significant. Addition of fumarates to etanercept for 48 weeks appeared safe with an acceptable tolerability. PMID:27576483

Inappropriate combination of warfarin and aspirin.

PubMed

Turan, Burak; Demir, Hakan; Mutlu, Ayhan; Daşlı, Tolga; Erkol, Ayhan; Erden, İsmail

2016-03-01

A combination of warfarin and aspirin is associated with increased bleeding compared with warfarin monotherapy. The aim of the study was to investigate the incidence and appropriateness of the combination of warfarin and aspirin in patients with atrial fibrillation (AF) or mechanical heart valve (MHV). This cross-sectional study included consecutive patients with AF or MHV on chronic warfarin therapy (>3 months) without acute coronary syndrome or have not undergone a revascularization procedure in the preceding year. Medical history, concomitant diseases, and treatment data were acquired through patient interviews and from hospital records. Three hundred and sixty patients (213 with AF, 147 with MHV) were included. In those with AF, a significantly higher warfarin-aspirin combination was observed with concomitant vascular disease (38.8% vs. 14.6%), diabetes (36.6% vs. 16.3%), statin therapy (40% vs. 16.9%), left ventricular systolic dysfunction (33.3% vs. 17.5%) (p<0.05 for all). The use of combination therapy was similar between different CHADS-VASc scores. In patients with MHV, higher combination therapy was observed in males (41% vs. 26.7% in females; p=0.070), concomitant vascular disease (47.8% vs. 29.8%; p=0.091), and AF (56.3% vs. 29.8%; p=0.033). Independent predictors of warfarin-aspirin combination were concomitant vascular disease, diabetes, and (younger) age in patients with AF and were concomitant AF and male sex in patients with MHV. Interestingly, the incidence of combination therapy was found to increase with a higher HAS-BLED score in both patients with AF and MHV (p<0.001). The combination of warfarin and aspirin was found to be prescribed to patients with AF mainly for the prevention of cardiovascular events, for which warfarin monotherapy usually suffices. On the other hand, co-treatment with aspirin appeared to be underused in patients with MHV.

Systematic study of probable projectile-target combinations for the synthesis of the superheavy nucleus 302120

NASA Astrophysics Data System (ADS)

Santhosh, K. P.; Safoora, V.

2016-08-01

Probable projectile-target combinations for the synthesis of the superheavy element 302120 have been studied taking the Coulomb and proximity potential as the interaction barrier. The probabilities of the compound nucleus formation PCN for the projectile-target combinations found in the cold reaction valley of 302120 are estimated. At energies near and above the Coulomb barrier, we have calculated the capture, fusion, and evaporation residue cross sections for the reactions of all probable projectile-target combinations so as to predict the most promising projectile-target combinations for the synthesis of the superheavy element 302120 in heavy-ion fusion reactions. The calculated fusion and evaporation cross sections for the more asymmetric ("hotter") projectile-target combination is found to be higher than the less asymmetric ("colder") combination. It can be seen from the nature of the quasifission barrier height, mass asymmetry, the probability of compound nucleus formation, survival probability, and excitation energy, the systems 44Ar+258No , 46Ar+256No , 48Ca+254Fm , 50Ca+252Fm , 54Ti+248Cf , and 58Cr+244Cm in deep region I of the cold reaction valley and the systems 62Fe+240Pu , 64Fe+238Pu , 68Ni+234U , 70Ni+232U , 72Ni+230U , and 74Zn+228Th in the other cold valleys are identified as the better projectile-target combinations for the synthesis of 302120. Our predictions on the synthesis of 302120 superheavy nuclei using the combinations 54Cr+248Cm , 58Fe+244Pu , 64Ni+238U , and 50Ti+249Cf are compared with available experimental data and other theoretical predictions.

Efficacy of combined orthodontic-periodontic treatment for patients with periodontitis and its effect on inflammatory cytokines: A comparative study.

PubMed

Zhang, Jin; Zhang, Ai-Min; Zhang, Zong-Mei; Jia, Jin-Lin; Sui, Xin-Xin; Yu, Lu-Rui; Liu, Hai-Tao

2017-10-01

In this study, we aimed to investigate the efficacy of combined orthodontic-periodontic treatment in the treatment of patients with periodontitis and its effects on the levels of inflammatory cytokines. A total of 117 patients with periodontitis were randomly assigned to the basic group (receiving basic periodontic treatment, n = 58) and the combined group (receiving combined orthodontic-periodontic treatment, n = 59). In addition, 52 healthy people without periodontal disease were selected as the normal group. Probing depth, tooth mobility, plaque index, clinical attachment level, and sulcus bleeding index were recorded. ELISA was applied to detect gingival crevicular fluid (GCF) and serum levels of inflammatory cytokines. A 2-year clinical follow-up was conducted. Before treatment, the periodontal parameters (probing depth, tooth mobility, plaque index, clinical attachement level, and sulcus bleeding index) and GCF and serum levels of inflammatory cytokines (high-sensitivity C-reactive protein, interleukin-1β, interleukin-5, interleukin-6, interleukin-8, tumor necrosis factor-α, and prostaglandin E2) in the combined and basic groups were higher than those in the normal group. After 6 and 18 months of treatment, the periodontal parameters and GCF and serum levels of inflammatory cytokines decreased in the combined and basic groups. The periodontal parameters and the GCF and serum levels of inflammatory cytokines in the combined group were significantly lower than those in the basic group after 18 months of treatment. The combined group had a lower recurrence rate compared with the basic group. Combined orthodontic-periodontic treatment had good clinical efficacy in the treatment of periodontitis and could effectively decrease the levels of inflammatory cytokines. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Combined treatment technology based on synergism between hydrodynamic cavitation and advanced oxidation processes.

PubMed

Gogate, Parag R; Patil, Pankaj N

2015-07-01

The present work highlights the novel approach of combination of hydrodynamic cavitation and advanced oxidation processes for wastewater treatment. The initial part of the work concentrates on the critical analysis of the literature related to the combined approaches based on hydrodynamic cavitation followed by a case study of triazophos degradation using different approaches. The analysis of different combinations based on hydrodynamic cavitation with the Fenton chemistry, advanced Fenton chemistry, ozonation, photocatalytic oxidation, and use of hydrogen peroxide has been highlighted with recommendations for important design parameters. Subsequently degradation of triazophos pesticide in aqueous solution (20 ppm solution of commercially available triazophos pesticide) has been investigated using hydrodynamic cavitation and ozonation operated individually and in combination for the first time. Effect of different operating parameters like inlet pressure (1-8 bar) and initial pH (2.5-8) have been investigated initially. The effect of addition of Fenton's reagent at different loadings on the extent of degradation has also been investigated. The combined method of hydrodynamic cavitation and ozone has been studied using two approaches of injecting ozone in the solution tank and at the orifice (at the flow rate of 0.576 g/h and 1.95 g/h). About 50% degradation of triazophos was achieved by hydrodynamic cavitation alone under optimized operating parameters. About 80% degradation of triazophos was achieved by combination of hydrodynamic cavitation and Fenton's reagent whereas complete degradation was achieved using combination of hydrodynamic cavitation and ozonation. TOC removal of 96% was also obtained for the combination of ozone and hydrodynamic cavitation making it the best treatment strategy for removal of triazophos. Copyright © 2014 Elsevier B.V. All rights reserved.

Neutron therapy of resistant thyroid gland cancer

NASA Astrophysics Data System (ADS)

Choynzonov, E. L.; Gribova, O. V.; Startseva, Zh. A.; Lisin, V. A.; Novikov, V. A.; Musabaeva, L. I.

2017-09-01

The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons c. The study included 45 patients with thyroid gland cancers who received the combined modality treatment and radiation therapy alone with the use of 6.3 MeV fast neutrons generated within U-120 cyclotron. The clinical trial of neutron-photon therapy used alone and in combination with the surgery for the patients with aggressive forms of thyroid cancer showed feasibility of increasing the effectiveness of treatment due to the reduction in the incidence of local recurrences. In addition, satisfactory treatment tolerance and absence of severe specific complications dictate the necessity of prospective studies to improve treatment outcomes.

Ventricular fractional shortening in 108 dogs with malignant lymphoma undergoing chemotherapy with a cyclic combination protocol including doxorubicin.

PubMed

Tater, G; Eberle, N; Hungerbuehler, S; Joetzke, A; Nolte, I; Wess, G; Betz, D

2012-01-01

The aim of this study was to evaluate whether changes in the left ventricular fractional shortening (LVFS) can be detected in dogs with malignant lymphoma undergoing a cyclic combination chemotherapy protocol including doxorubicin. Left ventricular fractional shortening as a stand-alone measurement will not show a significant change during the cyclic combination protocol. In this retrospective study, the records of dogs with malignant lymphoma treated between April 2001 and October 2010 were reviewed. Inclusion criteria comprised: a diagnosis of malignant lymphoma, a cyclic combination chemotherapy (including L-asparaginase, vincristine, cyclophosphamide, doxorubicin and prednisolone), and an echocardiographic examination by an experienced examiner before treatment and after each doxorubicin administration. One hundred and eight dogs were included and a total of 446 LVFS measurements had been performed. Patients were divided into four groups according to the number of doxorubicin administrations. Median LVFS did not change significantly during the cyclic combination protocol in all groups. All median LVFS values remained above the lower reference value of 25%. The measurement of LVFS did not show a significant change during the cyclic combination protocol treatment including doxorubicin in this population of dogs. Therefore either this cyclic combination protocol does not cause a systolic dysfunction or LVFS is not sensitive enough to detect early changes. Newer methods that are more sensitive then LVFS might be necessary to detect such changes.

Combination therapy using intratumoral bacillus Calmette-Guerin (BCG) and vincristine in dogs with transmissible venereal tumours: therapeutic efficacy and histological changes.

PubMed

Mukaratirwa, S; Chitanga, S; Chimatira, T; Makuleke, C; Sayi, S T; Bhebhe, E

2009-06-01

Therapeutic efficacy and histological changes after bacillus Calmette-Guerin (BCG), vincristine and BCG/vincristine combination therapy of canine transmissible venereal tumours (CTVT) were studied. Twenty dogs with naturally occurring CTVT in the progression stage were divided into 4 groups and treated with intratumoral BCG, vincristine, BCG/vincristine combination therapy or intratumoral buffered saline (control group). Tumour sizes were determined weekly and tumour response to therapy was assessed. Tumour biopsies were taken weekly to evaluate histological changes. Complete tumour regression was observed in all the dogs treated with BCG, vincristine and BCG/vincristine combination therapy. BCG/vincristine combination therapy had a statistically significantly shorter regression time than BCG or vincristine therapy. No tumour regression was observed in the control group. Intratumoral BCG treatment resulted in the appearance of macrophages and increased numbers of tumour infiltrating lymphocytes (TILs) followed by tumour cell apoptosis and necrosis. Treatment with vincristine resulted in increased tumour cell apoptosis, reduction in the mitotic index and a decrease in the number of TILs. Tumours from dogs on BCG/vincristine combination were characterised by reduction in the mitotic index, and appearance of numerous TILs and macrophages followed by marked tumour cell apoptosis and necrosis. This study indicates that combined BCG and vincristine therapy is more effective than vincristine in treating CTVT, suggesting that the clinical course of this disease may be altered by immunochemotherapy.

Evaluating Temporal Factors in Combined Interventions of Workforce Shift and School Closure for Mitigating the Spread of Influenza

PubMed Central

Zhang, Tianyou; Fu, Xiuju; Ma, Stefan; Xiao, Gaoxi; Wong, Limsoon; Kwoh, Chee Keong; Lees, Michael; Lee, Gary Kee Khoon; Hung, Terence

2012-01-01

Background It is believed that combined interventions may be more effective than individual interventions in mitigating epidemic. However there is a lack of quantitative studies on performance of the combination of individual interventions under different temporal settings. Methodology/Principal Findings To better understand the problem, we develop an individual-based simulation model running on top of contact networks based on real-life contact data in Singapore. We model and evaluate the spread of influenza epidemic with intervention strategies of workforce shift and its combination with school closure, and examine the impacts of temporal factors, namely the trigger threshold and the duration of an intervention. By comparing simulation results for intervention scenarios with different temporal factors, we find that combined interventions do not always outperform individual interventions and are more effective only when the duration is longer than 6 weeks or school closure is triggered at the 5% threshold; combined interventions may be more effective if school closure starts first when the duration is less than 4 weeks or workforce shift starts first when the duration is longer than 4 weeks. Conclusions/Significance We therefore conclude that identifying the appropriate timing configuration is crucial for achieving optimal or near optimal performance in mitigating the spread of influenza epidemic. The results of this study are useful to policy makers in deliberating and planning individual and combined interventions. PMID:22403634

A combination of resveratrol and 3,3'-diindolylmethane, a potent radioprotector.

PubMed

Thekkekkara, Dithu; Basavan, Duraiswamy; Chandna, Sudhir; Nanjan, Moola Joghee

2018-06-01

Exposure to ionizing radiation causes damage to the genomic integrity and stability of the cell. Though a large number of molecules have been studied for their radioprotective capability, no single agent is available today that meets all the requirements of a good radiprotector. In this study, we have investigated a combination of Resveratrol (RSV) and 3,3'-Diindolyl methane (DIM) for its efficacy for radioprotection. It is our hypothesis that this combination that possesses less toxicity than synthetic compounds, free radical scavenging potential, and the capacity to interfere with the several of the signaling cascades that trigger damage to cell by ionizing radiation may possess good radioprotective capability. Mice were pre-treated with a combination of RSV and DIM and the 30-day mortality assay, endogenous antioxidant levels in intestinal mucosa, metaphase chromosomal aberrations, and micronuclei formation were assessed after exposed to ionizing radiation. The dose modifying factor (DRF) obtained for RSV, DIM, and the combination is 1.15, 1.17, and 1.3, respectively. Pre-treatment of mice with the combination results in significant (***p = .001) protection of the endogenous antioxidant levels, chromosomal aberrations, micronuclei formation, after exposure to ionizing radiation. Our findings suggest that pre-treatment with the combination of RSV and DIM protects effectively from the ionizing radiation-induced damage at the molecular, cellular, and tissue levels by counteracting both the direct and indirect effects.

In vitro cytogenetic evaluation of the particular combination of flurbiprofen and roxithromycin.

PubMed

Timocin, Taygun; Husunet, Mehmet Tahir; Valipour, Ebrahim; Norizadeh Tazehkand, Mostafa; Celik, Rima; Topaktas, Mehmet; Ila, Hasan B

2017-07-01

Flurbiprofen (FLB) (anti-inflammatory and analgesic drug) and roxithromycin (RXM) (antibiotic) were widely used in world wide. This study deals with investigation of genotoxicity, cytotoxicity, and oxidative stress effects of a particular combination of these drugs in human cultured lymphocytes. Also, DNA damaging-protective effects of combination of these drugs were analyzed on plasmid DNA. Human lymphocytes were treated with different concentrations (FLB + RXM; 10 μg/mL + 25 μg/mL, 15 μg/mL + 50 μg/mL, and 20 μg/mL + 100 μg/mL) of the drugs following by study of their genotoxic and cytotoxic effects by analysis of cytokinesis-block micronucleus test and nuclear division index, respectively. The effect of the combination in aspect of anti-oxidative and DNA damaging activity was evaluated on Pet-22b plasmid. According to our results, the combination of FLB and RXM did not show a notable genotoxic effect on cells. Although each of the substances had been shown as a cytotoxic agent by previous researchers, in this research, the combination of these drugs did not exhibit any adverse effect on cell division. FLB had DNA protection effect against H 2 O 2 while in combination with RXM had not the same effect on the plasmid.

Combined chiropractic interventions for low-back pain.

PubMed

Walker, Bruce F; French, Simon D; Grant, William; Green, Sally

2010-04-14

Chiropractors commonly use a combination of interventions to treat people with low-back pain (LBP). To determine the effects of combined chiropractic interventions (that is, a combination of therapies, other than spinal manipulation alone) on pain, disability, back-related function, overall improvement, and patient satisfaction in adults with LBP, aged 18 and older. We searched: The Cochrane Back Review Group Trials Register (May 2009), CENTRAL (The Cochrane Library 2009, Issue 2), and MEDLINE (from January 1966), EMBASE (from January 1980), CINAHL (from January 1982), MANTIS (from Inception) and the Index to Chiropractic Literature (from Inception) to May 2009. We also screened references of identified articles and contacted chiropractic researchers. All randomised trials comparing the use of combined chiropractic interventions (rather than spinal manipulation alone) with no treatment or other therapies. At least two review authors selected studies, assessed the risk of bias, and extracted the data using standardised forms. Both descriptive synthesis and meta-analyses were performed. We included 12 studies involving 2887 participants with LBP. Three studies had low risk of bias. Included studies evaluated a range of chiropractic procedures in a variety of sub-populations of people with LBP.No trials were located of combined chiropractic interventions compared to no treatment. For acute and subacute LBP, chiropractic interventions improved short- and medium-term pain (SMD -0.25 (95% CI -0.46 to -0.04) and MD -0.89 (95%CI -1.60 to -0.18)) compared to other treatments, but there was no significant difference in long-term pain (MD -0.46 (95% CI -1.18 to 0.26)). Short-term improvement in disability was greater in the chiropractic group compared to other therapies (SMD -0.36 (95% CI -0.70 to -0.02)). However, the effect was small and all studies contributing to these results had high risk of bias. There was no difference in medium- and long-term disability. No difference was demonstrated for combined chiropractic interventions for chronic LBP and for studies that had a mixed population of LBP. Combined chiropractic interventions slightly improved pain and disability in the short-term and pain in the medium-term for acute and subacute LBP. However, there is currently no evidence that supports or refutes that these interventions provide a clinically meaningful difference for pain or disability in people with LBP when compared to other interventions. Future research is very likely to change the estimate of effect and our confidence in the results.

Differences in Mortality among Heroin, Cocaine, and Methamphetamine Users: A Hierarchical Bayesian Approach

PubMed Central

Liang, Li-Jung; Huang, David; Brecht, Mary-Lynn; Hser, Yih-ing

2010-01-01

Studies examining differences in mortality among long-term drug users have been limited. In this paper, we introduce a Bayesian framework that jointly models survival data using a Weibull proportional hazard model with frailty, and substance and alcohol data using mixed-effects models, to examine differences in mortality among heroin, cocaine, and methamphetamine users from five long-term follow-up studies. The traditional approach to analyzing combined survival data from numerous studies assumes that the studies are homogeneous, thus the estimates may be biased due to unobserved heterogeneity among studies. Our approach allows us to structurally combine the data from different studies while accounting for correlation among subjects within each study. Markov chain Monte Carlo facilitates the implementation of Bayesian analyses. Despite the complexity of the model, our approach is relatively straightforward to implement using WinBUGS. We demonstrate our joint modeling approach to the combined data and discuss the results from both approaches. PMID:21052518

Iodine Clock Reaction.

ERIC Educational Resources Information Center

Mitchell, Richard S.

1996-01-01

Describes a combination of solutions that can be used in the study of kinetics using the iodine clock reaction. The combination slows down degradation of the prepared solutions and can be used successfully for several weeks. (JRH)

Black and white teas as potential agents to combine with amphotericin B and protect red blood cells from amphotericin B-mediated toxicity.

PubMed

Oliveira, V M; Khalil, N M; Carraro, E

2018-02-01

Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with black tea or white tea and protective of citotoxic effect. The present study shows that white and black teas have additive effects with amphotericin B against some species Candida. In addition, the combination of white and black tea with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that white and black tea is a potential agent to combine with amphotericin for antifungal efficacy and to reduce the amphotericin dose to lessen side effects.

[Efficiency of combined methods of hemorroid treatment using hal-rar and laser destruction].

PubMed

Rodoman, G V; Kornev, L V; Shalaeva, T I; Malushenko, R N

2017-01-01

To develop the combined method of treatment of hemorrhoids with arterial ligation under Doppler control and laser destruction of internal and external hemorrhoids. The study included 100 patients with chronic hemorrhoids stage II and III. Combined method of HAL-laser was used in study group, HAL RAR-technique in control group 1 and closed hemorrhoidectomy with linear stapler in control group 2. Сomparative evaluation of results in both groups was performed. Combined method overcomes the drawbacks of traditional surgical treatment and limitations in external components elimination which are inherent for HAL-RAR. Moreover, it has a higher efficiency in treating of hemorrhoids stage II-III compared with HAL-RAR and is equally safe and well tolerable for patients. This method does not increase the risk of recurrence, reduces incidence of complications and time of disability.

Combination of platelet-rich plasma with degradable bioactive borate glass for segmental bone defect repair.

PubMed

Zhang, Ya-Dong; Wang, Gang; Sun, Yan; Zhang, Chang-Qing

2011-02-01

Porous scaffold biomaterials may offer a clinical alternative to bone grafts; however, scaffolds alone are typically insufficient to heal large bone defects. Numerous studies have demonstrated that osteoinductive growth factor significantly improves bone repair. In this study, a strategy combining degradable bioactive borate glass (BG) scaffolds with platelet-rich plasma (PRP) was tested. The bone defect was filled with BG alone, BG combined with autologous PRP or left empty. Bone formation was analyzed at 4, 8 and 12 weeks using both histology and radiology. The PRP treated group yielded better bone formation than the pure BG scaffold as determined by both histology and microcomputer tomography after 12 weeks. In conclusion, PRP improved bone healing in a diaphyseal rabbit model on BG. The combination of PRP and BG may be an effective approach to repair critical defects.

Effects of dietary mixture of garlic (Allium sativum), coriander (Coriandrum sativum) and probiotics on immune responses and caecal counts in young laying hens.

PubMed

Lee, J S; Kim, M J; Park, S H; Lee, S B; Wang, T; Jung, U S; Im, J; Kim, E J; Lee, K W; Lee, H G

2017-10-01

This study was conducted to evaluate the effects of a combined mixture of phytogenic extracts (garlic and coriander) and probiotics on growth performance and immune responses in laying hens based on the results of in vitro studies to screen for immunomodulatory potency of each ingredient. Several parameters of immunomodulatory potency were estimated using lamina propria leucocytes (LPLs) isolated from rat intestinal mucosa tissue. Results show that the combined mixture enhanced LPLs proliferation, increased LPL-mediated cytotoxicity against YAC-1 tumour cells, and decreased lipopolysaccharide (LPS)-induced cytokine production including tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in LPLs. For in vivo study, laying hens (n = 50/each diet group) were fed with control diet, a diet containing antibiotics (0.01% per kg feed) or the combined mixture (0.02% per kg feed) for 21 days. The dietary combined mixture improved egg production (p < 0.05) but not growth performance and carcass traits. Interestingly, the patterns of suppressing plasma IFN-γ productions during inflammation by LPS injection and decreasing caecal E. coli counts in the combined mixture group were comparable to those in the antibiotics group. Taken together, our results suggested that the 0.02% of combined mixture of phytogenic extracts and probiotics as ingredients has potential immunomodulatory effects in laying hens. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Combination therapies for neurobehavioral and cognitive recovery after experimental traumatic brain injury: is more better?

PubMed Central

Kline, Anthony E.; Leary, Jacob B.; Radabaugh, Hannah L.; Cheng, Jeffrey P.; Bondi, Corina O.

2016-01-01

Traumatic brain injury (TBI) is a significant health care crisis that affects two million individuals in the United Sates alone and over ten million worldwide each year. While numerous monotherapies have been evaluated and shown to be beneficial at the bench, similar results have not translated to the clinic. One reason for the lack of successful translation may be due to the fact that TBI is a heterogeneous disease that affects multiple mechanisms, thus requiring a therapeutic approach that can act on complementary, rather than single, targets. Hence, the use of combination therapies (i.e., polytherapy) has emerged as a viable approach. Stringent criteria, such as verification of each individual treatment plus the combination, a focus on behavioral outcome, and post-injury vs. pre-injury treatments, were employed to determine which studies were appropriate for review. The selection process resulted in 37 papers that fit the specifications. The review, which is the first to comprehensively assess the effects of combination therapies on behavioral outcomes after TBI, encompasses five broad categories (inflammation, oxidative stress, neurotransmitter dysregulation, neurotrophins, and stem cells, with and without rehabilitative therapies). Overall, the findings suggest that combination therapies can be more beneficial than monotherapies as indicated by 46% of the studies exhibiting an additive or synergistic positive effect versus on 19% reporting a negative interaction. These encouraging findings serve as an impetus for continued combination studies after TBI and ultimately for the development of successful clinically relevant therapies. PMID:27166858

Beneficial effects of warmed humidified oxygen combined with nebulized albuterol and ipratropium in pediatric patients with acute exacerbation of asthma in winter months.

PubMed

Nibhanipudi, Kumara; Hassen, Getaw Worku; Smith, Arthur

2009-11-01

The objective of this study was to determine whether a combination of nebulized albuterol and ipratropium with warmed humidified oxygen would be more beneficial when compared to the same combination with humidified oxygen at room temperature. Albuterol alone was tested in the same settings. All patients between 6 and 17 years of age who presented to a pediatric emergency department in the winter months with acute exacerbation of bronchial asthma were given a combination of nebulized albuterol and ipratropium with warmed or room temperature humidified oxygen. Peak flow was measured before and after the treatment. Sixty patients were enrolled in the study, with 15 subjects in each group. The mean increase in peak flow in the albuterol-ipratropium with warm humidified oxygen group was 52.6, and in the albuterol-ipratropium with humidified oxygen at room temperature group, it was 26.2. The results of the albuterol with warmed humidified oxygen and with humidified oxygen at room temperature groups were 20.6 and 34.3, respectively. The differences between the groups were statistically significant. Our study shows that warmed humidified oxygen given along with the combination of nebulized albuterol and ipratropium is more beneficial for pediatric patients having an acute exacerbation of bronchial asthma in the winter months when compared to nebulized albuterol alone with warmed humidified oxygen, nebulized albuterol alone with room temperature humidified oxygen, or a combination of nebulized albuterol and ipratropium with room temperature humidified oxygen.

Microneedling combined with platelet-rich plasma or trichloroacetic acid peeling for management of acne scarring: A split-face clinical and histologic comparison.

PubMed

El-Domyati, Moetaz; Abdel-Wahab, Hossam; Hossam, Aliaa

2018-02-01

Minimally invasive procedures provide effective, safe, relatively long-lasting, and natural results without large damage to the skin. A combination treatment is considered an approach that includes at least 2 different and unrelated modalities. This study aims to evaluate the use and effectiveness of some combined minimally invasive procedures for management of acne scarring. Twenty-four volunteers with postacne atrophic scars were randomly divided into 3 equal groups according to performed procedure on each side of the face (microneedling by dermaroller alone or combined with platelet-rich plasma [PRP] or trichloroacetic acid [TCA] 15% peeling) and received 6 bi-weekly sessions of treatment. Photography and punch biopsies were taken before and after 3 months of treatment for clinical, histological, and histometrical evaluation. Combined treatment of dermaroller and PRP or dermaroller and TCA 15% showed significant improvement when compared with dermaroller alone (P = .015 and .011 respectively). Epidermal thickness showed statistically significant increase in studied groups, mainly after dermaroller and TCA 15%. Moreover, the 3 studied groups showed more organized collagen bundles and newly formed collagen formation and markedly decreased abnormal elastic fibers. Based on the clinical, histometrical, and histochemical assessment, inspite that most volunteers showed significant improvement after treatment, however, the combined use of dermaroller and TCA 15% was more effective in postacne atrophic scars than the use of dermaroller and PRP or dermaroller only. © 2017 Wiley Periodicals, Inc.

Is there a decline in cognitive functions after combined electroconvulsive therapy and antipsychotic therapy in treatment-refractory schizophrenia?

PubMed

Pawełczyk, Agnieszka; Kołodziej-Kowalska, Emilia; Pawełczyk, Tomasz; Rabe-Jabłońska, Jolanta

2015-03-01

An analysis of literature shows that there is still little evidence concerning the efficacy of electroconvulsive therapy (ECT) combined with antipsychotic therapy in a group of treatment-resistant schizophrenia patients. More precisely, its influence on cognitive functions is still equivocal. The aim of this study was to assess the influence of ECT combined with antipsychotic therapy on working memory, attention, and executive functions in a group of treatment-refractory schizophrenia patients. Twenty-seven patients completed the study: 14 men and 13 women, aged 21 to 55 years (mean age, 32.8 years), diagnosed with treatment-resistant schizophrenia. Each patient underwent a course of ECT sessions and was treated with antipsychotic medications. Before the ECT and within 3 days after the last ECT session, the participants were assessed with the following neuropsychological tests: Trail Making Test (TMT) and Wisconsin Cart Sorting Test (WCST). There were no significant differences in the TMT and WCST results after combined ECT and antipsychotic therapy in treatment-refractory schizophrenia patients. According to the results of the neuropsychological tests, there was no decline in attention, executive functions, or working memory. The current study shows no significant difference in attention, working memory, or executive functions after treatment with a combination of electroconvulsive and antipsychotic therapy. This suggests that combined electroconvulsive therapy may not have a negative influence on the neuropsychological functioning of patients with treatment resistant schizophrenia.

Safety of the electroconvulsive therapy and amisulpride combination.

PubMed

Takács, Rozália; Iványi, Zsolt; Ungvari, Gabor S; Gazdag, Gábor

2013-03-01

Electroconvulsive therapy is frequently considered when pharmacotherapy is ineffective. In such cases the combination of the two treatment modalities are commonly used. Amisulpiride, a second generation antipsychotic drug is used in the treatment of schizophrenia and psychotic depression. When amisulpiride is ineffective as a monotherapy, combination with ECT could be an option to enhance its efficacy. To the best of our knowledge, to date there have been no data about the safety of this combination. Medical notes of all patients who were given ECT while on amisulpiride were selected from the archives of the Department of Psychiatry, Semmelweis University Medical School, Budapest, covering a 10-year period. A randomly selected matched control group was formed from patients who underwent ECT but were not taking amisulpiride. Patients in both groups also received a variety of psychotropic drugs other than amisulpide. Side effects were compared between the two groups of patients. Twenty patients received amisulpride with ECT. The most common side effects were headache, hypertension, tachycardia, nausea, dizziness, confusion, psychomotor agitation, sialorrhea, and prolonged seizure activity. All adverse effects resolved within 24 hours. No side effects of any kind were observed in 7 and 8 cases in the study and control groups, respectively. This was the first study that examined the safety of amisulpride-ECT combination in schizophrenia. Comparing the side-effects between the study and control groups, no significant differences were detected in terms of their types or frequency. The amisulpiride-ECT combination appears to be a safe treatment option.

Effects of combined physical and cognitive training on fitness and neuropsychological outcomes in healthy older adults

PubMed Central

Desjardins-Crépeau, Laurence; Berryman, Nicolas; Fraser, Sarah A; Vu, Thien Tuong Minh; Kergoat, Marie-Jeanne; Li, Karen ZH; Bosquet, Laurent; Bherer, Louis

2016-01-01

Purpose Physical exercise and cognitive training have been shown to enhance cognition among older adults. However, few studies have looked at the potential synergetic effects of combining physical and cognitive training in a single study. Prior trials on combined training have led to interesting yet equivocal results. The aim of this study was to examine the effects of combined physical and cognitive interventions on physical fitness and neuropsychological performance in healthy older adults. Methods Seventy-six participants were randomly assigned to one of four training combinations using a 2×2 factorial design. The physical intervention was a mixed aerobic and resistance training program, and the cognitive intervention was a dual-task (DT) training program. Stretching and toning exercises and computer lessons were used as active control conditions. Physical and cognitive measures were collected pre- and postintervention. Results All groups showed equivalent improvements in measures of functional mobility. The aerobic–strength condition led to larger effect size in lower body strength, independently of cognitive training. All groups showed improved speed of processing and inhibition abilities, but only participants who took part in the DT training, independently of physical training, showed increased task-switching abilities. The level of functional mobility after intervention was significantly associated with task-switching abilities. Conclusion Combined training did not yield synergetic effects. However, DT training did lead to transfer effects on executive performance in neuropsychological tests. Both aerobic-resistance training and stretching-toning exercises can improve functional mobility in older adults. PMID:27698558

Effects of Different Modes of Exercise Training on Body Composition and Risk Factors for Cardiovascular Disease in Middle-aged Men

PubMed Central

Mohammadi, Hamid Reza; Khoshnam, Mohammad Sadegh; Khoshnam, Ebrahim

2018-01-01

Background: Previous studies have indicated that exercise training improves body composition and cardiovascular disease risk factors. The aim of the present study was to investigate the effect of 12 weeks of aerobic, strength and combined training on body composition, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and C-reactive protein (CRP) in sedentary middle-aged men. Methods: Forty-seven male aged 40–60 years voluntarily participated in this study and were divided in four groups: aerobic (n = 12), strength (n = 12), combined (n = 11), and control (n = 12) groups randomly. Body composition, ICAM-1, VCAM-1, and CRP were measured before and after 12 weeks. Data were analyzed using paired t-test and analysis of variance statistical methods. Results: There were significant differences in body weight between aerobic and strength training (P = 0.004) and aerobic and control groups (P = 0.018), body mass index between combined and strength training (P = 0.004) and combined and control groups (P = 0.001), fat percentage between aerobic training and control group (P = 0.017) and combined training and control groups (P = 0.004), and finally, fat-free mass between aerobic and strength training (P = 0.024), aerobic and combined training (P = 0.0001), strength and control groups (P = 0.035), and combined and control groups (P = 0.0001). Conclusions: The results indicated that 12-week workout, 20–60 min/session, 3 days a week of moderate intensity exercise improved body composition, ICAM-1, VCAM-1, and CRP compared to those who did not participate in any training. However, all three types of exercises had small benefits on body composition, ICAM-1, VCAM-1, and CRP in sedentary middle-aged men, and the importance of combined training required further investigations. PMID:29441186

Anti-tumor effects on the combination of photodynamic therapy with arsenic compound in TC-1 cells implanted C57BL/6 mice

NASA Astrophysics Data System (ADS)

Lee, Kyu Wan; Wen, Lan Ying; Bae, Su Mi; Park, Choong Hak; Jeon, Woo Kyu; Lee, Doo Yun; Ahn, Woong Shick

2009-06-01

The effects of As4O6 were studied as adjuvant on photodynamic therapy. As4O6 is considered to have anticancer activity via several biological actions such as free radical producing and inhibition of VEGF expression. In vitro experiments, cell proliferation and morphology were determined by MTT assay. Also, quantitative PCR array was performed to study the synergetic mechanism. Additionally, this study was supported by the finding that combination of photodynamic therapy and As4O6 shows an inhibition effect of tumor growth in C57BL/6 mice with TC-1 cells xenographs in vivo. Radachlorin and As4O6 significantly inhibited TC-1 cell proliferation in a dose-dependent manner (P < 0.05). Antiproliferative effect of combination treatment was significantly higher than those of TC-1 cells treated with either photodynamic therapy or As4O6 (62.4 and 52.5% decrease, respectively, compared to photodynamic therapy or As4O6 alone, P < 0.05). In addition, cell proliferation in combination of photodynamic therapy and As4O6 treatment significantly decreased by 77.4% compared to vehicle-only treated TC-1 cells (P < 0.05). Cell survival pathway (Naip1, Tert and Aip1) and p53-dependent pathway (Bax, p21Cip1, Fas, Gadd45, IGFBP-3 and Mdm-2) were markedly increased by combination treatment of photodynamic therapy and As4O6. Besides, the immunology response NEAT pathway (Ly- 12, CD178 and IL-2) also modulated after combination treatment of photodynamic therapy and As4O6. This combination effect apparently shows a same pattern in vivo model. These findings suggest the benefit of the combination treatment of photodynamic therapy and As4O6 for the inhibition of cervical cancer growth.

Risk assessments using the Strain Index and the TLV for HAL, Part II: Multi-task jobs and prevalence of CTS.

PubMed

Kapellusch, Jay M; Silverstein, Barbara A; Bao, Stephen S; Thiese, Mathew S; Merryweather, Andrew S; Hegmann, Kurt T; Garg, Arun

2018-02-01

The Strain Index (SI) and the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value for hand activity level (TLV for HAL) have been shown to be associated with prevalence of distal upper-limb musculoskeletal disorders such as carpal tunnel syndrome (CTS). The SI and TLV for HAL disagree on more than half of task exposure classifications. Similarly, time-weighted average (TWA), peak, and typical exposure techniques used to quantity physical exposure from multi-task jobs have shown between-technique agreement ranging from 61% to 93%, depending upon whether the SI or TLV for HAL model was used. This study compared exposure-response relationships between each model-technique combination and prevalence of CTS. Physical exposure data from 1,834 workers (710 with multi-task jobs) were analyzed using the SI and TLV for HAL and the TWA, typical, and peak multi-task job exposure techniques. Additionally, exposure classifications from the SI and TLV for HAL were combined into a single measure and evaluated. Prevalent CTS cases were identified using symptoms and nerve-conduction studies. Mixed effects logistic regression was used to quantify exposure-response relationships between categorized (i.e., low, medium, and high) physical exposure and CTS prevalence for all model-technique combinations, and for multi-task workers, mono-task workers, and all workers combined. Except for TWA TLV for HAL, all model-technique combinations showed monotonic increases in risk of CTS with increased physical exposure. The combined-models approach showed stronger association than the SI or TLV for HAL for multi-task workers. Despite differences in exposure classifications, nearly all model-technique combinations showed exposure-response relationships with prevalence of CTS for the combined sample of mono-task and multi-task workers. Both the TLV for HAL and the SI, with the TWA or typical techniques, appear useful for epidemiological studies and surveillance. However, the utility of TWA, typical, and peak techniques for job design and intervention is dubious.

Does the combination of 3% mepivacaine plain plus 2% lidocaine with epinephrine improve anesthesia and reduce the pain of anesthetic injection for the inferior alveolar nerve block? A prospective, randomized, double-blind study.

PubMed

Lammers, Emily; Nusstein, John; Reader, Al; Drum, Melissa; Beck, Mike; Fowler, Sara

2014-09-01

In theory, using 3% mepivacaine initially for an inferior alveolar nerve (IAN) block would decrease the pain of injection, provide faster onset, and increase anesthetic success. The purpose of this prospective, randomized, double-blind study was to compare the degree of pulpal anesthesia obtained with a combination of 3% mepivacaine/2% lidocaine (1:100,000 epinephrine) versus a combination of 2% lidocaine (1:100,000 epinephrine)/2% lidocaine (1:100,000 epinephrine) in IAN blocks. Injection pain was also studied. One hundred asymptomatic subjects were randomly given a combination of a 1-cartridge volume of 3% mepivacaine plus a 1-cartridge volume of 2% lidocaine with 1:100,000 epinephrine and a combination of a 1-cartridge volume of 2% lidocaine with 1:100,000 epinephrine plus a 1-cartridge volume of 2% lidocaine with 1:100,000 epinephrine for the IAN block at 2 separate appointments. Subjects rated the pain of injection. The molars, premolars, and incisors were tested with an electric pulp tester in 4-minute cycles for 60 minutes. Anesthetic success was defined as the subject achieving 2 consecutive 80 readings within 15 minutes after completion of the IAN blocks and sustaining the 80 reading for 60 minutes. Success was not significantly different (P > .05) between the 2 combinations. No statistical differences in injection pain or onset times were found. The combination of 3% mepivacaine plus 2% lidocaine with 1:100,000 epinephrine was equivalent to the combination of 2 cartridges of 2% lidocaine with 1:100,000 epinephrine in terms of injection pain, onset time, and pulpal anesthetic success for the IAN block. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.