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Sample records for treatment resistant major

  1. Treatment-Resistant Major Depression: Rationale for NMDA Receptors as Targets and Nitrous Oxide as Therapy

    Science.gov (United States)

    Zorumski, Charles F.; Nagele, Peter; Mennerick, Steven; Conway, Charles R.

    2015-01-01

    Major depressive disorder (MDD) remains a huge personal and societal encumbrance. Particularly burdensome is a virulent subtype of MDD, treatment resistant major depression (TMRD), which afflicts 15–30% of MDD patients. There has been recent interest in N-methyl-d-aspartate receptors (NMDARs) as targets for treatment of MDD and perhaps TMRD. To date, most pre-clinical and clinical studies have focused on ketamine, although psychotomimetic and other side effects may limit ketamine’s utility. These considerations prompted a recent promising pilot clinical trial of nitrous oxide, an NMDAR antagonist that acts through a mechanism distinct from that of ketamine, in patients with severe TRMD. In this paper, we review the clinical picture of TRMD as a subtype of MDD, the evolution of ketamine as a fast-acting antidepressant, and clinical and basic science studies supporting the possible use of nitrous oxide as a rapid antidepressant. PMID:26696909

  2. A clinical risk stratification tool for predicting treatment resistance in major depressive disorder.

    Science.gov (United States)

    Perlis, Roy H

    2013-07-01

    Early identification of depressed individuals at high risk for treatment resistance could be helpful in selecting optimal setting and intensity of care. At present, validated tools to facilitate this risk stratification are rarely used in psychiatric practice. Data were drawn from the first two treatment levels of a multicenter antidepressant effectiveness study in major depressive disorder, the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) cohort. This cohort was divided into training, testing, and validation subsets. Only clinical or sociodemographic variables available by or readily amenable to self-report were considered. Multivariate models were developed to discriminate individuals reaching remission with a first or second pharmacological treatment trial from those not reaching remission despite two trials. A logistic regression model achieved an area under the receiver operating characteristic curve exceeding .71 in training, testing, and validation cohorts and maintained good calibration across cohorts. Performance of three alternative models with machine learning approaches--a naïve Bayes classifier and a support vector machine, and a random forest model--was less consistent. Similar performance was observed between more and less severe depression, men and women, and primary versus specialty care sites. A web-based calculator was developed that implements this tool and provides graphical estimates of risk. Risk for treatment resistance among outpatients with major depressive disorder can be estimated with a simple model incorporating baseline sociodemographic and clinical features. Future studies should examine the performance of this model in other clinical populations and its utility in treatment selection or clinical trial design. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Carola Rong

    2018-04-01

    Full Text Available Objectives: Extant evidence indicates that ketamine exerts rapid antidepressant effects in treatment-resistant depressive (TRD symptoms as a part of major depressive disorder (MDD and bipolar disorder (BD. The identification of depressed sub-populations that are more likely to benefit from ketamine treatment remains a priority. In keeping with this view, the present narrative review aims to identify the pretreatment predictors of response to ketamine in TRD as part of MDD and BD. Method: Electronic search engines PubMed/MEDLINE, ClinicalTrials.gov, and Scopus were searched for relevant articles from inception to January 2018. The search term ketamine was cross-referenced with the terms depression, major depressive disorder, bipolar disorder, predictors, and response and/or remission. Results: Multiple baseline pretreatment predictors of response were identified, including clinical (i.e., Body Mass Index (BMI, history of suicide, family history of alcohol use disorder, peripheral biochemistry (i.e., adiponectin levels, vitamin B12 levels, polysomnography (abnormalities in delta sleep ratio, neurochemistry (i.e., glutamine/glutamate ratio, neuroimaging (i.e., anterior cingulate cortex activity, genetic variation (i.e., Val66Met BDNF allele, and cognitive functioning (i.e., processing speed. High BMI and a positive family history of alcohol use disorder were the most replicated predictors. Conclusions: A pheno-biotype of depression more, or less likely, to benefit with ketamine treatment is far from complete. Notwithstanding, metabolic-inflammatory alterations are emerging as possible pretreatment response predictors of depressive symptom improvement, most notably being cognitive impairment. Sophisticated data-driven computational methods that are iterative and agnostic are more likely to provide actionable baseline pretreatment predictive information.

  4. Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

    NARCIS (Netherlands)

    Murrough, James W.; Perez, Andrew M.; Pillemer, Sarah; Stern, Jessica; Parides, Michael K.; aan het Rot, Marije; Collins, Katherine A.; Mathew, Sanjay J.; Charney, Dennis S.; Iosifescu, Dan V.

    2013-01-01

    Background: Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine

  5. Nitrous Oxide for Treatment-Resistant Major Depression: A Proof-of-Concept Trial.

    Science.gov (United States)

    Nagele, Peter; Duma, Andreas; Kopec, Michael; Gebara, Marie Anne; Parsoei, Alireza; Walker, Marie; Janski, Alvin; Panagopoulos, Vassilis N; Cristancho, Pilar; Miller, J Philip; Zorumski, Charles F; Conway, Charles R

    2015-07-01

    N-methyl-D-aspartate receptor antagonists, such as ketamine, have rapid antidepressant effects in patients with treatment-resistant depression (TRD). We hypothesized that nitrous oxide, an inhalational general anesthetic and N-methyl-D-aspartate receptor antagonist, may also be a rapidly acting treatment for TRD. In this blinded, placebo-controlled crossover trial, 20 patients with TRD were randomly assigned to 1-hour inhalation of 50% nitrous oxide/50% oxygen or 50% nitrogen/50% oxygen (placebo control). The primary endpoint was the change on the 21-item Hamilton Depression Rating Scale (HDRS-21) 24 hours after treatment. Mean duration of nitrous oxide treatment was 55.6 ± 2.5 (SD) min at a median inspiratory concentration of 44% (interquartile range, 37%-45%). In two patients, nitrous oxide treatment was briefly interrupted, and the treatment was discontinued in three patients. Depressive symptoms improved significantly at 2 hours and 24 hours after receiving nitrous oxide compared with placebo (mean HDRS-21 difference at 2 hours, -4.8 points, 95% confidence interval [CI], -1.8 to -7.8 points, p = .002; at 24 hours, -5.5 points, 95% CI, -2.5 to -8.5 points, p nitrous oxide and placebo, p nitrous oxide compared with one patient (5%) and none after placebo (odds ratio for response, 4.0, 95% CI, .45-35.79; OR for remission, 3.0, 95% CI, .31-28.8). No serious adverse events occurred; all adverse events were brief and of mild to moderate severity. This proof-of-concept trial demonstrated that nitrous oxide has rapid and marked antidepressant effects in patients with TRD. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  6. Beta-amyloid deposition in patients with major depressive disorder with differing levels of treatment resistance: a pilot study.

    Science.gov (United States)

    Li, Peng; Hsiao, Ing-Tsung; Liu, Chia-Yih; Chen, Chia-Hsiang; Huang, She-Yao; Yen, Tzu-Chen; Wu, Kuan-Yi; Lin, Kun-Ju

    2017-12-01

    Lack of treatment response in patients with late-life depression is common. The role of brain beta-amyloid (Aβ) deposition in treatment outcome in subjects with late-life depression remains unclear. The present study aimed to investigate brain Aβ deposition in patients with major depressive disorder (MDD) with differing treatment outcomes in vivo using 18 F-florbetapir imaging. This study included 62 MDD patients and 18 healthy control subjects (HCs).We first employed the Maudsley staging method (MSM) to categorize MDD patients into two groups according to treatment response: mild treatment resistance (n = 29) and moderate-to-severe treatment resistance (n = 33).The standard uptake value ratio (SUVR) of each volume of interest was analysed, and voxel-wise comparisons were made between the MDD patients and HCs. Vascular risk factors, serum homocysteine level, and apolipoprotein E (ApoE) genotype were also determined. The MDD patients with moderate-to-severe treatment resistance had higher 18 F-florbetapir SUVRs than the HCs in the parietal region (P depressive symptoms may represent prodromal manifestations of Alzheimer's disease (AD). Depressive symptomatology in old age, particularly in subjects with a poor treatment response, may underscore early changes of AD-related pathophysiology.

  7. [Clinical and biological predictors of ketamine response in treatment-resistant major depression: Review].

    Science.gov (United States)

    Romeo, B; Choucha, W; Fossati, P; Rotge, J-Y

    2017-08-01

    The aim of this review was to determine the clinical and biological predictors of the ketamine response. A systematic research on PubMed and PsycINFO database was performed without limits on year of publication. The main predictive factors of ketamine response, which were found in different studies, were (i) a family history of alcohol dependence, (ii) unipolar depressive disorder, and (iii) neurocognitive impairments, especially a slower processing speed. Many other predictive factors were identified, but not replicated, such as personal history of alcohol dependence, no antecedent of suicide attempt, anxiety symptoms. Some biological factors were also found such as markers of neural plasticity (slow wave activity, brain-derived neurotrophic factor Val66Met polymorphism, expression of Shank 3 protein), other neurologic factors (anterior cingulate activity, concentration of glutamine/glutamate), inflammatory factors (IL-6 concentration) or metabolic factors (concentration of B12 vitamin, D- and L-serine, alterations in the mitochondrial β-oxidation of fatty acids). This review had several limits: (i) patients had exclusively resistant major depressive episodes which represent a sub-type of depression and not all depression, (ii) response criteria were more frequently assessed than remission criteria, it was therefore difficult to conclude that these predictors were similar, and finally (iii) many studies used a very small number of patients. In conclusion, this review found that some predictors of ketamine response, like basal activity of anterior cingulate or vitamin B12 concentration, were identical to other therapeutics used in major depressive episode. These factors could be more specific to the major depressive episode and not to the ketamine response. Others, like family history of alcohol dependence, body mass index, or D- and L-serine were different from the other therapeutics. Neurocognitive impairments like slower speed processing or alterations in

  8. A Randomized Double-Blind Sham-Controlled Study of Transcranial Direct Current Stimulation for Treatment-Resistant Major Depression

    Directory of Open Access Journals (Sweden)

    Daniel eBlumberger

    2012-08-01

    Full Text Available Objectives: Transcranial direct current stimulation (tDCS has demonstrated some efficacy in treatment-resistant major depression (TRD. The majority of previous controlled studies have used anodal stimulation to the left dorsolateral prefrontal cortex (DLPFC and a control location such as the supraorbital region on for the cathode. Several open label studies have suggested effectiveness from anodal stimulation to the left DLPFC combined with cathodal stimulation to the right DLPFC. Thus, this study evaluated the efficacy of tDCS using anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC compared to sham tDCS. Methods: Subjects between the ages of 18 and 65 were recruited from a tertiary care university hospital. Twenty-four subjects with TRD and a 17-item Hamilton Depression Rating Scale (HDRS greater than 21 were randomized to receive tDCS or sham tDCS. The rates of remission were compared between the two treatment groups.Results: The remission rates did not differ significantly between the two groups using an intention to treat analysis. More subjects in the active tDCS group had failed a course of electroconvulsive therapy in the current depressive episode. Side effects did not differ between the two groups and in general the treatment was very well tolerated. Conclusion: Anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC was not efficacious in TRD. However, a number of methodological limitations warrant caution in generalizing from this study. Ongoing, controlled studies should provide further clarification on the efficacy of this stimulation configuration in TRD.

  9. The Impact of BDNF Polymorphisms on Suicidality in Treatment-Resistant Major Depressive Disorder: A European Multicenter Study.

    Science.gov (United States)

    Schosser, Alexandra; Carlberg, Laura; Calati, Raffaella; Serretti, Alessandro; Massat, Isabel; Spindelegger, Christoph; Linotte, Sylvie; Mendlewicz, Julien; Souery, Daniel; Zohar, Joseph; Montgomery, Stuart; Kasper, Siegfried

    2017-10-01

    Numerous studies have reported associations between the brain-derived neurotrophic factor (BDNF) gene and psychiatric disorders, including suicidal behavior, although with conflicting results. A total of 250 major depressive disorder patients were collected in the context of a European multicenter resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using the Mini International Neuropsychiatric Interview and Hamilton Rating Scale for Depression, and treatment response using the HAM-D. Genotyping was performed for the functional Val66Met polymorphism (rs6265) and 7 additional tagging single nucleotide polymorphisms within the BDNF gene. Neither BDNF single markers nor haplotypes were found to be associated with suicide risk and lifetime history of suicide attempts. Gender-specific analyses revealed nonsignificant single marker (rs908867) and haplotypic association with suicide risk in males after multiple testing correction. Analyzing treatment response phenotypes, the functional Val66Met polymorphism as well as rs10501087 showed significant genotypic and haplotypic association with suicide risk in remitters (n=34, 13.6%). Considering the sample size, the present findings need to be replicated in larger samples to confirm or refute a role of BDNF in the investigated suicidal behavior phenotypes. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  10. Brain microstructural abnormalities revealed by diffusion tensor images in patients with treatment-resistant depression compared with major depressive disorder before treatment

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    Zhou Yan, E-mail: clare1475@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China); Qin Lingdi, E-mail: flyfool318@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China); Chen Jun, E-mail: doctor_cj@msn.com [Shanghai Mental Health Center, Jiao Tong University Medical School, Shanghai, 200030 (China); Qian Lijun, E-mail: dearqlj@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China); Tao Jing, E-mail: jing318@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China); Fang Yiru, E-mail: fangyr@sina.com [Shanghai Mental Health Center, Jiao Tong University Medical School, Shanghai, 200030 (China); Xu Jianrong, E-mail: xujianr@hotmail.com [Department of Radiology, Ren-Ji Hospital, Jiao Tong University Medical School, Shanghai 200127 (China)

    2011-11-15

    Treatment-resistant depression (TRD) is a therapeutic challenge for clinicians. Despite a growing interest in this area, an understanding of the pathophysiology of depression, particularly TRD, remains lacking. This study aims to detect the white matter abnormalities of whole brain fractional anisotropy (FA) in patients with TRD compared with major depressive disorder (MDD) before treatment by voxel-based analysis using diffusion tensor imaging. A total of 100 patients first diagnosed with untreated MDD underwent diffusion tensor imaging scans. 8 weeks after the first treatment, 54 patients showed response to the medication, whereas 46 did not. Finally, 20 patients were diagnosed with TRD after undergoing another treatment. A total of 20 patients with TRD and another 20 with MDD before treatment matched in gender, age, and education was enrolled in the research. For every subject, an FA map was generated and analyzed using SPM5. Subsequently, t-test was conducted to compare the FA values voxel to voxel between the two groups (p < 0.001 [FDR corrected], t > 7.57, voxel size > 30). Voxel-based morphometric (VBM) analysis was performed using T1W images. Significant reductions in FA were found in the white matter located in the bilateral of the hippocampus (left hippocampus: t = 7.63, voxel size = 50; right hippocampus: t = 7.82, voxel size = 48). VBM analysis revealed no morphological abnormalities between the two groups. Investigation of brain anisotropy revealed significantly decreased FA in both sides of the hippocampus. Although preliminary, our findings suggest that microstructural abnormalities in the hippocampus indicate vulnerability to treatment resistance.

  11. Brain microstructural abnormalities revealed by diffusion tensor images in patients with treatment-resistant depression compared with major depressive disorder before treatment

    International Nuclear Information System (INIS)

    Zhou Yan; Qin Lingdi; Chen Jun; Qian Lijun; Tao Jing; Fang Yiru; Xu Jianrong

    2011-01-01

    Treatment-resistant depression (TRD) is a therapeutic challenge for clinicians. Despite a growing interest in this area, an understanding of the pathophysiology of depression, particularly TRD, remains lacking. This study aims to detect the white matter abnormalities of whole brain fractional anisotropy (FA) in patients with TRD compared with major depressive disorder (MDD) before treatment by voxel-based analysis using diffusion tensor imaging. A total of 100 patients first diagnosed with untreated MDD underwent diffusion tensor imaging scans. 8 weeks after the first treatment, 54 patients showed response to the medication, whereas 46 did not. Finally, 20 patients were diagnosed with TRD after undergoing another treatment. A total of 20 patients with TRD and another 20 with MDD before treatment matched in gender, age, and education was enrolled in the research. For every subject, an FA map was generated and analyzed using SPM5. Subsequently, t-test was conducted to compare the FA values voxel to voxel between the two groups (p 7.57, voxel size > 30). Voxel-based morphometric (VBM) analysis was performed using T1W images. Significant reductions in FA were found in the white matter located in the bilateral of the hippocampus (left hippocampus: t = 7.63, voxel size = 50; right hippocampus: t = 7.82, voxel size = 48). VBM analysis revealed no morphological abnormalities between the two groups. Investigation of brain anisotropy revealed significantly decreased FA in both sides of the hippocampus. Although preliminary, our findings suggest that microstructural abnormalities in the hippocampus indicate vulnerability to treatment resistance.

  12. Treatment-Resistant Schizophrenia

    DEFF Research Database (Denmark)

    Howes, Oliver D; McCutcheon, Rob; Agid, Ofer

    2017-01-01

    OBJECTIVE: Research and clinical translation in schizophrenia is limited by inconsistent definitions of treatment resistance and response. To address this issue, the authors evaluated current approaches and then developed consensus criteria and guidelines. METHOD: A systematic review of randomize...

  13. Treatment-Resistant Depression

    Science.gov (United States)

    ... on your own, talk to your doctor or mental health professional. Depression treatment may be unsuccessful until you address your substance use. Manage stress. Relationship issues, financial problems, an unhappy work life and many other issues can all contribute ...

  14. Placebo and antidepressant treatment for major depression

    DEFF Research Database (Denmark)

    Hougaard, Esben

    2010-01-01

    Antidepressant medication is generally considered the primary treatment for major depressive disorders (MDD), but antidepressant treatment has recently approached a crisis with shrinking specific effects and growing placebo responses in current trials. The aim of the paper is to review the placebo...

  15. Resistant and Refractory Hypertension: Antihypertensive Treatment Resistance vs Treatment Failure

    Science.gov (United States)

    Siddiqui, Mohammed; Dudenbostel, Tanja; Calhoun, David A.

    2017-01-01

    Resistant or difficult to treat hypertension is defined as high blood pressure that remains uncontrolled with 3 or more different antihypertensive medications, including a diuretic. Recent definitions also include controlled blood pressure with use of 4 or more medications as also being resistant to treatment. Recently, refractory hypertension, an extreme phenotype of antihypertensive treatment failure has been defined as hypertension uncontrolled with use of 5 or more antihypertensive agents, including a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Patients with resistant vs refractory hypertension share similar characteristics and comorbidities, including obesity, African American race, female sex, diabetes, coronary heart disease, chronic kidney disease, and obstructive sleep apnea. Patients with refractory vs resistant hypertension tend to be younger and are more likely to have been diagnosed with congestive heart failure. Refractory hypertension might also differ from resistant hypertension in terms of underlying cause. Preliminary evidence suggests that refractory hypertension is more likely to be neurogenic in etiology (ie, heightened sympathetic tone), vs a volume-dependent hypertension that is more characteristic of resistant hypertension in general. PMID:26514749

  16. [Major breakthroughs in the medical treatment

    DEFF Research Database (Denmark)

    Kirk, O.; Gerstoft, J.; Lundgren, J.D.

    2009-01-01

    The introduction of antiretroviral combination therapy for patients with HIV infection is described as an example of a breakthrough within the field of medical treatment. The background for the breakthrough and the phases thereof are described and for comparison, the circumstances of major breakt...... breakthroughs within other medical specialities are mentioned Udgivelsesdato: 2009/3/2......The introduction of antiretroviral combination therapy for patients with HIV infection is described as an example of a breakthrough within the field of medical treatment. The background for the breakthrough and the phases thereof are described and for comparison, the circumstances of major...

  17. Major QTL Conferring Resistance to Rice Bacterial Leaf Streak

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Bacterial leaf streak (BLS) is one of the important limiting factors to rice production in southern China and other tropical and sub-tropical areas in Asia. Resistance to BLS was found to be a quantitative trait and no major resistant gene was located in rice until date. In the present study, a new major quantitative trait locus (QTL) conferring resistance to BLS was identified from a highly resistant variety Dular by the employment of Dular/Balilla (DB) and Dular/IR24 (DI) segregation populations and was designated qBLSR-11-1. This QTL was located between the simple sequence repeat (SSR) markers RM120 and RM441 on chromosome 11 and could account for 18.1-21.7% and 36.3% of the variance in DB and DI populations, respectively. The genetic pattern of rice resistance to BLS was discussed.

  18. Evidence-based treatment strategies for treatment-resistant bipolar depression: a systematic review

    NARCIS (Netherlands)

    Sienaert, P.; Lambrichts, L.; Dols, A.; De Fruyt, J.

    2013-01-01

    Objectives: Treatment resistance in bipolar depression is a common clinical problem that constitutes a major challenge for the treating clinician as there is a paucity of treatment options. The objective of this paper was to review the evidence for treatment options in treatment-resistant bipolar

  19. Plasmodium falciparum Resistance to Artemisinin Derivatives and Piperaquine: A Major Challenge for Malaria Elimination in Cambodia

    Science.gov (United States)

    Duru, Valentine; Witkowski, Benoit; Ménard, Didier

    2016-01-01

    Artemisinin-based combination therapies (ACTs) are the cornerstone of current strategies for fighting malaria. Over the last decade, ACTs have played a major role in decreasing malaria burden. However, this progress is being jeopardized by the emergence of artemisinin-resistant Plasmodium falciparum parasites. Artemisinin resistance was first detected in western Cambodia in 2008 and has since been observed in neighboring countries in southeast Asia. The problem of antimalarial drug resistance has recently worsened in Cambodia, with reports of parasites resistant to piperaquine, the latest generation of partner drug used in combination with dihydroartemisinin, leading to worrying rates of clinical treatment failure. The monitoring and the comprehension of both types of resistance are crucial to prevent the spread of multidrug-resistant parasites outside southeast Asia, and particularly to Africa, where the public health consequences would be catastrophic. To this end, new tools are required for studying the biological and molecular mechanisms underlying resistance to antimalarial drugs and for monitoring the geographic distribution of the resistant parasites. In this review, we detail the major advances in our understanding of resistance to artemisinin and piperaquine and define the challenges that the malaria community will have to face in the coming years. PMID:27928074

  20. Carboplatin treatment of antiestrogen-resistant breast cancer cells

    DEFF Research Database (Denmark)

    Larsen, Mathilde S; Yde, Christina Westmose; Christensen, Ib J

    2012-01-01

    Antiestrogen resistance is a major clinical problem in current breast cancer treatment. Therefore, biomarkers and new treatment options for antiestrogen-resistant breast cancer are needed. In this study, we investigated whether antiestrogen‑resistant breast cancer cell lines have increased...... sensitivity to carboplatin, as it was previously shown with cisplatin, and whether low Bcl-2 expression levels have a potential value as marker for increased carboplatin sensitivity. Breast cancer cells resistant to the pure antiestrogen fulvestrant, and two out of four cell lines resistant...... to the antiestrogen tamoxifen, were more sensitive to carboplatin treatment compared to the parental MCF-7 cell line. This indicates that carboplatin may be an advantageous treatment in antiestrogen‑resistant breast cancer; however, a marker for increased sensitivity would be needed. Low Bcl-2 expression...

  1. Transcranial magnetic stimulation for the treatment of major depression

    Directory of Open Access Journals (Sweden)

    Janicak PG

    2015-06-01

    Full Text Available Philip G Janicak, Mehmet E DokucuDepartment of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USAAbstract: Major depression is often difficult to diagnose accurately. Even when the diagnosis is properly made, standard treatment approaches (eg, psychotherapy, medications, or their combination are often inadequate to control acute symptoms or maintain initial benefit. Additional obstacles involve safety and tolerability problems, which frequently preclude an adequate course of treatment. This leaves an important gap in our ability to properly manage major depression in a substantial proportion of patients, leaving them vulnerable to ensuing complications (eg, employment-related disability, increased risk of suicide, comorbid medical disorders, and substance abuse. Thus, there is a need for more effective and better tolerated approaches. Transcranial magnetic stimulation is a neuromodulation technique increasingly used to partly fill this therapeutic void. In the context of treating depression, we critically review the development of transcranial magnetic stimulation, focusing on the results of controlled and pragmatic trials for depression, which consider its efficacy, safety, and tolerability.Keywords: electroconvulsive therapy, treatment-resistant depression, major depression, transcranial magnetic stimulation

  2. Draft Genome Sequences of Six Multidrug-Resistant Clinical Strains of Acinetobacter baumannii, Isolated at Two Major Hospitals in Kuwait.

    Science.gov (United States)

    Nasser, Kother; Mustafa, Abu Salim; Khan, Mohd Wasif; Purohit, Prashant; Al-Obaid, Inaam; Dhar, Rita; Al-Fouzan, Wadha

    2018-04-19

    Acinetobacter baumannii is an important opportunistic pathogen in global health care settings. Its dissemination and multidrug resistance pose an issue with treatment and outbreak control. Here, we present draft genome assemblies of six multidrug-resistant clinical strains of A. baumannii isolated from patients admitted to one of two major hospitals in Kuwait. Copyright © 2018 Nasser et al.

  3. [Interest of scopolamine as a treatment of major depressive disorder].

    Science.gov (United States)

    Rigal, A; Mouchabac, S; Peretti, C S

    2016-12-01

    The number of patients with depression in the world is 350 millions according to estimates. The search for new treatments, particularly in forms of resistant depression, is necessary given the growing number of patients experiencing treatment failure and resistance. Scopolamine, an anticholinergic antimuscarinic molecule, is one of the treatments under evaluation. It falls within the assumptions of cholinergic disruption of the pathophysiology of depression, at different levels (genetic, receptorial [muscarinic and glutamate receptors], hormonal, synaptic…). In 2006, a pilot study made to evaluate the role of the cholinergic system in cognitive symptoms of depression found unexpected results regarding the antidepressant effect of scopolamine in depressive patients. Since that time other studies have been conducted to evaluate the benefits of treatment with intravenous injections of scopolamine. Our main objective was to evaluate the interest of scopolamine as an antidepressant treatment in depressed populations. We conducted a literature review with the aim of assessing the effectiveness of treatment with scopolamine in uni- and bipolar patients with depressive symptoms. The protocol consisted of two injection blocks (each block consisting of three injections spaced fifteen minutes apart within three to five days) of active ingredient or placebo crossover. The selected patients were between 18 and 45years and had the DSM-IV major depressive disorder or bipolar disorder criteria. Regarding the methods of measurement, the primary endpoint was the reduction in scores of the Montgomery Asberg Depression Rating Scale (MADRS) with a total response defined by a decrease of more than 50 % of the score and remission corresponding to a MADRS score<10. Seven sessions of evaluations were performed. The published results are promising in terms of efficiency with rapid antidepressant effect, a total response rate ranging from 59-64% and a remission rate of between 37 and 55

  4. Glucocorticoid resistance as a major drive in sepsis pathology.

    Science.gov (United States)

    Dendoncker, Karen; Libert, Claude

    2017-06-01

    Sepsis is an acute systemic inflammatory disease. Glucocorticoids (GCs), which function by binding to the GC receptor GR have very powerful anti-inflammatory activities, yet they are hardly useful in sepsis. We can thus consider sepsis as a GC resistant disease. We here review the literature which has investigated this GC resistance, and summarize the mechanisms of GC resistance that have been observed in other diseases and in experimental models. We also discuss the importance of GC resistance in sepsis, in terms of the contribution of this phenomenon to the pathogenesis of sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Neuromodulation therapies and treatment-resistant depression

    Directory of Open Access Journals (Sweden)

    Al-Harbi KS

    2012-07-01

    Full Text Available Khalid Saad Al-Harbi,1 Naseem Akhtar Qureshi21National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia; 2General Administration for Research and Studies and Mental Health and Social Services, Riyadh, Saudi ArabiaBackground: Patients with treatment-resistant depression (TRD who showed partial response to pharmacological and psychotherapeutic interventions need a trial of neuromodulation therapies (NTs.Objective: This paper aims to review evidence-based data on the use of NTs in TRD.Method: Using keywords and combined-word strategy, multiple computer searches of PubMed, Google Scholar, Quertle(R, and Medline were conducted for retrieving relevant articles published in English-language peer-reviewed journals (2000–2012. Those papers that addressed NTs in TRD were retained for extensive review.Results: Despite methodological challenges, a range of 30%–93% of TRD patients showed substantial improvement to one of the NTs. One hundred–percent improvement was reported in two single-case studies on deep brain stimulation. Some studies reported no benefits from transcranial direct current stimulation. NTs were reported to have good clinical efficacy, better safety margin, and benign side-effect profile. Data are limited regarding randomized clinical trials, long-term efficacy, and cost-effectiveness of these approaches. Both modified electroconvulsive therapy and magnetic seizure therapy were associated with reversible but disturbing neurocognitive adverse effects. Besides clinical utility, NTs including approaches on the horizon may unlock the biological basis underlying mood disorders including TRD.Conclusion: NTs are promising in patients with TRD, as the majority of them show good clinical response measured by standardized depression scales. NTs need further technological refinements and optimization together with continuing well-designed studies that recruit larger numbers of participants with TRD.Keywords: treatment-resistant

  6. Management of treatment resistant schizophrenia

    African Journals Online (AJOL)

    Adele

    Whilst gains have been made in recent years in the pharmacological treatment of schizophrenia, a number of ... pharmacotherapy to include psychological and occupational ... outcome studies suggesting that only 20-30% of people with.

  7. Test for bacterial resistance build-up against plasma treatment

    International Nuclear Information System (INIS)

    Zimmermann, J L; Shimizu, T; Li, Y-F; Morfill, G E; Schmidt, H-U; Isbary, G

    2012-01-01

    It is well known that the evolution of resistance of microorganisms to a range of different antibiotics presents a major problem in the control of infectious diseases. Accordingly, new bactericidal ‘agents’ are in great demand. Using a cold atmospheric pressure (CAP) plasma dispenser operated with ambient air, a more than five orders of magnitude inactivation or reduction of Methicillin-resistant Staphylococcus aureus (MRSA; resistant against a large number of the tested antibiotics) was obtained in less than 10 s. This makes CAP the most promising candidate for combating nosocomial (hospital-induced) infections. To test for the occurrence and development of bacterial resistance against such plasmas, experiments with Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Enterococcus mundtii) were performed. The aim was to determine quantitative limits for primary (naturally) or secondary (acquired) resistance against the plasma treatment. Our results show that E. coli and E. mundtii possess no primary resistance against the plasma treatment. By generating four generations of bacteria for every strain, where the survivors of the plasma treatment were used for the production of the next generation, a lower limit to secondary resistance was obtained. Our results indicate that CAP technology could contribute to the control of infections in hospitals, in outpatient care and in disaster situations, providing a new, fast and efficient broad-band disinfection technology that is not constrained by bacterial resistance mechanisms. (paper)

  8. Management of treatment resistant schizophrenia | Jones | African ...

    African Journals Online (AJOL)

    Whilst gains have been made in recent years in the pharmacological treatment of schizophrenia, a number of patients still have residual symptoms and disabilities, or simply do not show response to antipsychotic medications. For such 'treatment resistant' patients, there is little by way of randomised controlled data to ...

  9. Mycoplasma genitalium infections: current treatment options and resistance issues

    Directory of Open Access Journals (Sweden)

    Sethi S

    2017-09-01

    Full Text Available Sunil Sethi, Kamran Zaman, Neha Jain Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India Abstract: Mycoplasma genitalium is one of the important causes of non-gonococcal urethritis. Rising incidence and emerging antimicrobial resistance are a major concern these days. The poor clinical outcomes with doxycycline therapy led to the use of azithromycin as the primary drug of choice. Single-dose azithromycin regimen over a period of time was changed to extended regimen following studies showing better clinical cures and less risk of resistance development. However, emerging macrolide resistance, either due to transmission of resistance or drug pressure has further worsened the management of this infection. The issues of drug resistance and treatment failures also exist in cases of M. genitalium infection. At present, the emergence of multidrug-resistant (MDR M. genitalium strains is an alarming sign for its treatment and the associated public health impact due to its complications. However, newer drugs like pristinamycin, solithromycin, sitafloxacin, and others have shown a hope for the clinical cure, but need further clinical trials to optimize the therapeutic dosing schedules and formulate appropriate treatment regimens. Rampant and inappropriate use of these newer drugs will further sabotage future attempts to manage MDR strains. There is currently a need to formulate diagnostic algorithms and etiology-based treatment regimens rather than the syndromic approach, preferably using combination therapy instead of a monotherapy. Awareness about the current guidelines and recommended treatment regimens among clinicians and local practitioners is of utmost importance. Antimicrobial resistance testing and global surveillance are required to assess the efficacy of current treatment regimens and for guiding future research for the early detection and management of MDR M. genitalium infections

  10. Resistant lower rank approximation of matrices by iterative majorization

    NARCIS (Netherlands)

    Verboon, Peter; Heiser, Willem

    2011-01-01

    It is commonly known that many techniques for data analysis based on the least squares criterion are very sensitive to outliers in the data. Gabriel and Odoroff (1984) suggested a resistant approach for lower rank approximation of matrices. In this approach, weights are used to diminish the

  11. IS TREATMENT-RESISTANCE IN PSYCHIATRIC DISORDERS A TRAP FOR POLYPHARMACY?

    OpenAIRE

    Jašović-Gašić, Miroslava

    2015-01-01

    Background: Nowadays, more and more mental health professionals manage patients who fail treatment for major psychiatric disorders. There is not a consensus on how to deal with treatment-resistance patients, but usually psychiatrists result to polypharmacy. Method: In reviewing the evidence based clinical research we will try to answer some questions about treatment-resistant psychiatric disorders. Treatment-resistant symptoms complicate the clinical course of all psychiatric diso...

  12. Enhanced Transmission of Drug-Resistant Parasites to Mosquitoes following Drug Treatment in Rodent Malaria

    OpenAIRE

    Bell, Andrew S.; Huijben, Silvie; Paaijmans, Krijn P.; Sim, Derek G.; Chan, Brian H. K.; Nelson, William A.; Read, Andrew F.

    2012-01-01

    The evolution of drug resistant Plasmodium parasites is a major challenge to effective malaria control. In theory, competitive interactions between sensitive parasites and resistant parasites within infections are a major determinant of the rate at which parasite evolution undermines drug efficacy. Competitive suppression of resistant parasites in untreated hosts slows the spread of resistance; competitive release following treatment enhances it. Here we report that for the murine model Plasm...

  13. Benefits of and Barriers to Pharmacogenomics-Guided Treatment for Major Depressive Disorder.

    Science.gov (United States)

    Ahmed, Ahmed T; Weinshilboum, Richard; Frye, Mark A

    2018-05-01

    Antidepressants have reduced the symptom burden for many Major Depressive Disorder (MDD) patients, but drug-related side effects and treatment resistance continue to present major challenges. Pharmacogenomics represents one approach to enhance antidepressant efficacy and avoid adverse reactions, but concerns remain with regard to the overall "value equation," and several barriers must be overcome to achieve the full potential of MDD pharmacogenomics. © 2018 American Society for Clinical Pharmacology and Therapeutics.

  14. Consistent effects of a major QTL for thermal resistance in field-released Drosophila melanogaster

    DEFF Research Database (Denmark)

    Loeschcke, Volker; Kristensen, Torsten Nygård; Norry, Fabian M

    2011-01-01

    Molecular genetic markers can be used to identify quantitative trait loci (QTL) for thermal resistance and this has allowed characterization of a major QTL for knockdown resistance to high temperature in Drosophila melanogaster. The QTL showed trade-off associations with cold resistance under lab...... of field fitness at different environmental temperatures with genotypic variation in a QTL for thermal tolerance. Graphical abstract...

  15. Plasma treatment of heat-resistant materials

    International Nuclear Information System (INIS)

    Vlasov, V A; Kosmachev, P V; Skripnikova, N K; Bezukhov, K A

    2015-01-01

    Refractory lining of thermal generating units is exposed to chemical, thermal, and mechanical attacks. The degree of fracture of heat-resistant materials depends on the chemical medium composition, the process temperature and the material porosity. As is known, a shortterm exposure of the surface to low-temperature plasma (LTP) makes possible to create specific coatings that can improve the properties of workpieces. The aim of this work is to produce the protective coating on heat-resistant chamotte products using the LTP technique. Experiments have shown that plasma treatment of chamotte products modifies the surface, and a glass-ceramic coating enriched in mullite is formed providing the improvement of heat resistance. For increasing heat resistance of chamotte refractories, pastes comprising mixtures of Bacor, alumina oxide, and chamot were applied to their surfaces in different ratios. It is proved that the appropriate coating cannot be created if only one of heat-resistant components is used. The required coatings that can be used and recommended for practical applications are obtained only with the introduction of powder chamot. The paste composition of 50% chamot, 25% Bacor, and 25% alumina oxide exposed to plasma treatment, has demonstrated the most uniform surface fusion. (paper)

  16. Clinical approach in treatment of resistant hypertension

    Directory of Open Access Journals (Sweden)

    Jennifer Frank

    2009-07-01

    Full Text Available Jennifer Frank, David SommerfeldUniversity of Wisconsin School of Medicine and Public Health, Department of Family Medicine, Appleton, WI, USAAbstract: Resistant hypertension, defined as failure to achieve target blood pressure despite the use of optimal or maximum doses of at least 3 agents, one of which is a diuretic, or requiring 4 or more medications to achieve blood pressure goal, is likely to affect up to 20% of all patients with hypertension. Apparent resistant hypertension may be caused by medication nonadherence, substances that either interfere with antihypertensive mediations or cause blood pressure elevation, and under- or inappropriate medication treatment. Certain patient characteristics are associated with the presence of resistant hypertension and include chronic kidney disease, diabetes, obesity, and presence of end-organ damage (microalbuminuria, retinopathy, left-ventricular hypertrophy. Secondary causes of resistant hypertension are not uncommon and include obstructive sleep apnea, chronic kidney disease, primary aldosteronism, renal artery stenosis, pheochromocytoma, and Cushing’s disease. Initial medication management usually includes adding or increasing the dose of a diuretic, which is effective in lowering the blood pressure of a large number of patients with resistant hypertension. Additional management options include maximizing lifestyle modification, combination therapy of antihypertensive agents depending on individual patient characteristics, adding less-commonly used fourth- or fifth-line antihypertensive agents, and referral to a hypertension specialist.Keywords: resistant hypertension, blood pressure, diuretic

  17. Ketamine for Treatment-Resistant Unipolar Depression

    Science.gov (United States)

    Mathew, Sanjay J.; Shah, Asim; Lapidus, Kyle; Clark, Crystal; Jarun, Noor; Ostermeyer, Britta; Murrough, James W.

    2013-01-01

    Currently available drugs for unipolar major depressive disorder (MDD), which target monoaminergic systems, have a delayed onset of action and significant limitations in efficacy. Antidepressants with primary pharmacological targets outside the monoamine system may offer the potential for more rapid activity with improved therapeutic benefit. The glutamate system has been scrutinized as a target for antidepressant drug discovery. The purpose of this article is to review emerging literature on the potential rapid-onset antidepressant properties of the glutamate NMDA receptor antagonist ketamine, an established anaesthetic agent. The pharmacology of ketamine and its enantiomer S-ketamine is reviewed, followed by examples of its clinical application in chronic, refractory pain conditions, which are commonly co-morbid with depression. The first generation of studies in patients with treatment-resistant depression (TRD) reported the safety and acute efficacy of a single subanaesthetic dose (0.5 mg/kg) of intravenous ketamine. A second generation of ketamine studies is focused on testing alternate routes of drug delivery, identifying methods to prevent relapse following resolution of depressive symptoms and understanding the neural basis for the putative antidepressant actions of ketamine. In addition to traditional depression rating endpoints, ongoing research is examining the impact of ketamine on neurocognition. Although the first clinical report in MDD was published in 2000, there is a paucity of adequately controlled double-blind trials, and limited clinical experience outside of research settings. Given the potential risks of ketamine, safety considerations will ultimately determine whether this old drug is successfully repositioned as a new therapy for TRD. PMID:22303887

  18. Treatment resistance and psychodynamic psychiatry: concepts psychiatry needs from psychoanalysis.

    Science.gov (United States)

    Plakun, Eric

    2012-06-01

    Over the last 30 years psychiatry and psychoanalysis have moved in substantially divergent directions. Psychiatry has become rich in methodology but conceptually limited, with a drift toward biological reductionism. Psychoanalysis has remained relatively limited in methodology, but conceptually rich. The rich methodology of psychiatry has led to major contributions in discovering gene by environment interactions, the importance of early adversity, and to recognition of the serious problem posed by treatment resistance. However, psychiatry's biologically reductionistic conceptual focus interferes with the development of a nuanced clinical perspective based on emerging knowledge that might help more treatment resistant patients become treatment responders. This article argues that recognition of the problem of treatment resistance in psychiatry creates a need for it to reconnect with the conceptual richness of psychoanalysis in order to improve patient care. Psychodynamic psychiatry is defined as the relevant intersection of psychiatry and psychoanalysis where this reconnection can occur. I will suggest selected aspects of psychoanalysis that are especially relevant to psychiatry in improving outcomes in work with treatment resistant patients.

  19. Deep TMS in a resistant major depressive disorder: a brief report.

    Science.gov (United States)

    Rosenberg, O; Shoenfeld, N; Zangen, A; Kotler, M; Dannon, P N

    2010-05-01

    Repetitive transcranial magnetic stimulation (rTMS) has proven effective. Recently, a greater intracranial penetration coil has been developed. We tested the efficacy of the coil in the treatment of resistant major depression. Our sample included seven patients suffering from major depression who were treated using Brainsway's H1-coil connected to a Magstim rapid 2 stimulator. Deep TMS treatment was given to each patient in five sessions per week over a period of 4 weeks. Patients were treated with 120% intensity of the motor threshold and a frequency of 20 HZ with a total of 1,680 pulses per session. Five patients completed 20 sessions: one attained remission (Hamilton Depression Rating Scale (HDRS)=9); three patients reached a reduction of more than 50% in their pre-treatment HDRS; and one patient achieved a partial response (i.e., the HDRS score dropped from 21 to 12). Average HDRS score dropped to 12.6 and average Hamilton Anxiety Rating Scale score dropped to 9.Two patients dropped out: one due to insomnia and the second due to a lack of response. Compared to the pooled response and remission rates when treating major depression with rTMS, deep TMS as used in this study is at least similarly effective. Still, a severe limitation of this study is its small sample size, which makes the comparison of the two methods in terms of their effectiveness or side effects impossible. Greater numbers of subjects should be studied to achieve this aim. An H1 deep TMS coil could be used as an alternative treatment for major depressive disorder.

  20. [A new challenge in clinical practice: resistance to directly acting antivirals in hepatitis C treatment].

    Science.gov (United States)

    Chen, Z W; Hu, P; Ren, H

    2016-03-20

    Directly acting antivirals (DAAs) is a major treatment of hepatitis C virus (HCV) overseas. But DAAs resistance is getting more and more clinicians' attention. DAAs have not been approved in China to date, even though some of them are in clinical trials. However, a good knowledge of DAAs resistance is important on optimizing HCV treatment regimens, increasing sustained virological response (SVR) and decreasing treatment failure in clinical. In this review, DAAs resistance mechanism and virologic barrier to resistance, the prevalence of pre-existing DAAs resistance-associated variants (RAVs), the impact of RAVs on treatment outcome, the options of treatment regimens after resistance and drug resistance testing are discussed, hoping to provide some help for DAAs' standardized treatment in China in the future.

  1. Erosion resistance comparison of alternative surface treatments

    Science.gov (United States)

    Česánek, Z.; Schubert, J.; Houdková, Š.

    2017-05-01

    Erosion is a process characterized by the particle separation and the damage of component functional surfaces. Thermal spraying technology HP/HVOF (High Pressure / High Velocity Oxygen Fuel) is commonly used for protection of component surfaces against erosive wear. Alloy as well as cermet based coatings meet the requirements for high erosion resistance. Wear resistance is in many cases the determining property of required component functioning. The application suitability of coating materials is particularly influenced by different hardness. This paper therefore presents an erosion resistance comparison of alloy and cermet based coatings. The coatings were applied on steel substrates and were subjected to the erosive test using the device for evaluation of material erosion resistance working on the principle of centrifugal erodent flow. Abrasive sand Al2O3 with grain size 212-250 μm was selected as an erosive material. For this purpose, the specimens were prepared by thermal spraying technology HP/HVOF using commercially available powders Stellite 6, NiCrBSi, Cr3C2-25%NiCr, Cr3C2-25%CoNiCrAlY, Hastelloy C-276 and experimental coating TiMoCN-29% Ni. Erosion resistance of evaluated coatings was compared with erosive resistance of 1.4923 high alloyed steel without nitridation and in nitrided state and further with surface treatment using technology PVD. According to the evaluation, the resulting erosive resistance depends not only on the selected erodent and surface protection, but also on the erodent impact angle.

  2. Emerging from Depression: Treatment of Adolescent Depression Using the Major Treatment Models of Adult Depression.

    Science.gov (United States)

    Long, Kathleen M.

    Noting that adolescents who commit suicide are often clinically depressed, this paper examines various approaches in the treatment of depression. Major treatment models of adult depression, which can be directly applied to the treatment of the depressed adolescent, are described. Major treatment models and selected research studies are reviewed in…

  3. Using Electroencephalography for Treatment Guidance in Major Depressive Disorder.

    Science.gov (United States)

    Wade, Elizabeth C; Iosifescu, Dan V

    2016-09-01

    Given the high prevalence of treatment-resistant depression and the long delays in finding effective treatments via trial and error, valid biomarkers of treatment outcome with the ability to guide treatment selection represent one of the most important unmet needs in mood disorders. A large body of research has investigated, for this purpose, biomarkers derived from electroencephalography (EEG), using resting state EEG or evoked potentials. Most studies have focused on specific EEG features (or combinations thereof), whereas more recently machine-learning approaches have been used to define the EEG features with the best predictive abilities without a priori hypotheses. While reviewing these different approaches, we have focused on the predictor characteristics and the quality of the supporting evidence. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  4. Pharmacotherapy for treatment-resistant schizophrenia

    Directory of Open Access Journals (Sweden)

    Meghan E Mcilwain

    2011-03-01

    Full Text Available Meghan E Mcilwain1,2, Jeff Harrison1, Amanda J Wheeler1,3, Bruce R Russell1,21School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; 2Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; 3School of Human Services, Griffith University, Queensland, AustraliaAbstract: Schizophrenia is a disabling mental illness with a lifetime prevalence of 0.7% worldwide and significant, often devastating, consequences on social and occupational functioning. A range of antipsychotic medications are available; however, suboptimal therapeutic response in terms of psychotic symptoms is common and affects up to one-third of people with schizophrenia. Negative symptoms are generally less amenable to treatment. Because of the consequences of inadequate symptom control, effective treatment strategies are required for people with treatment-resistant schizophrenia. Clozapine has been shown to be more effective than other antipsychotics in treatment-resistant populations in several studies; however, the occurrence of adverse effects, some of which are potentially life-threatening, are important limitations. In addition to those who are intolerant to clozapine, only 30% to 50% experience clinically significant symptom improvement. This review describes the recent evidence for treatment strategies for people not responding to nonclozapine antipsychotic agents and people not responding or only partially responding to clozapine.Keywords: antipsychotic, refractory, clozapine

  5. Addressing the Challenges of Hepatitis C Virus Resistance and Treatment Failure

    Directory of Open Access Journals (Sweden)

    Che C. Colpitts

    2016-08-01

    Full Text Available Chronic hepatitis C is a major cause of chronic liver disease, including liver cirrhosis and hepatocellular carcinoma. The development of direct-acting antivirals (DAAs revolutionized hepatitis C virus (HCV treatment by offering genuine prospects for the first comprehensive cure of a chronic viral infection in humans. While antiviral resistance is a significant limitation for interferon-based therapies, resistance and treatment failure still appear to be present in a small fraction of patients even in state-of-the-art DAA combination therapies. Therefore, treatment failure and resistance still remain a clinical challenge for the management of patients not responding to DAAs. In this special issue of Viruses on HCV drug resistance, mechanisms of antiviral resistance for different classes of antiviral drugs are described. Furthermore, the detection and monitoring of resistance in clinical practice, the clinical impact of resistance in different patient groups and strategies to prevent and address resistance and treatment failure using complementary antiviral strategies are reviewed.

  6. Addressing the Challenges of Hepatitis C Virus Resistance and Treatment Failure.

    Science.gov (United States)

    Colpitts, Che C; Baumert, Thomas F

    2016-08-16

    Chronic hepatitis C is a major cause of chronic liver disease, including liver cirrhosis and hepatocellular carcinoma. The development of direct-acting antivirals (DAAs) revolutionized hepatitis C virus (HCV) treatment by offering genuine prospects for the first comprehensive cure of a chronic viral infection in humans. While antiviral resistance is a significant limitation for interferon-based therapies, resistance and treatment failure still appear to be present in a small fraction of patients even in state-of-the-art DAA combination therapies. Therefore, treatment failure and resistance still remain a clinical challenge for the management of patients not responding to DAAs. In this special issue of Viruses on HCV drug resistance, mechanisms of antiviral resistance for different classes of antiviral drugs are described. Furthermore, the detection and monitoring of resistance in clinical practice, the clinical impact of resistance in different patient groups and strategies to prevent and address resistance and treatment failure using complementary antiviral strategies are reviewed.

  7. Impact of drug resistance on the tuberculosis treatment outcome

    Directory of Open Access Journals (Sweden)

    E. Lesnic

    2017-03-01

    Full Text Available Background. The standard treatment of a new case of multidrug-resistant tuberculosis (MDR-TB according to WHO recommendations in the Republic of Moldova is performed since 2005 showing a low treatment succes. Actually the treatment success rate increased due to excluding of MDR-TB patients from the general cohort. The major rate of patients with low outcome is represented by the failed and lost to follow-up cases. The purpose of the study was to assess the impact of multidrug-resiatnce and MDR-TB on the tuberculosis treatment outcome. Materials and methods. A retrospective selective, descriptive study targeting social, demographic, economic and epidemiological peculiarities, case-management, diagnostic radiological aspects and microbiological characteristics of 187 patients with pulmonary tuberculosis registered during 2013–2015 distributed in two groups: 1st group (61 patients with established multidrug-resistant strains using conventional cultural methods and the 2nd group (126 patients with MDR-TB. Results. Multidrug-resistance was established more frequently in new cases and MDR-TB in two thirds of retreated patients. No difference was identified in gender and age distribution, social, economical, educational characteristics; case-management assessment identified a similar proportion of patients revealed by general practitioners and specialists, with low rate of screened high risk groups. All patients from the multidrug-resistant group began the standard treatment for drug-responsiveness tuberculosis before drug susceptibility testing and one third of MDR-TB group was treated from the onset with the DOTS-Plus regimen. Highest success rate was identified in the new-case subgroups of both groups and higher rate of died patients was determined in the retreated subgroups. Such a low rate of patients aggrevates the resistance. Conclusions. Early diagnosis, drug responsiveness testing and raising awareness among about treatment compliance will

  8. Are Sewage Treatment Plants Promoting Antibiotic Resistance?

    Science.gov (United States)

    1. Introduction 1.1. How bacteria exhibit resistance 1.1.1. Resistance to -lactams 1.1.2. Resistance to sulphonamides and trimethoprim 1.1.3. Resistance to macrolides 1.1.4. Resistance to fluoroquinolones 1.1.5. Resistance to tetracyclines 1.1.6. Resistance to nitroimidaz...

  9. Major new developments affecting treatment and prognosis in hypertension.

    Science.gov (United States)

    Gubner, R S

    1990-01-01

    Joint studies of the ALIMDA and Society of Actuaries, notably those of 1935, 1959 and 1979, established that there is a progressive rise in cardiovascular mortality with successive increments in blood pressure. This has provided the basis of underwriting. The converse is not true, or at least has not been true until very recently. Drugs that effectively reduce blood pressure have been available for several decades, but reduction and maintenance of blood pressure is still accomplished in only a minority of hypertensives. Long-term trials employing a combination of drugs, i.e., diuretics, vasodilators and reserpine and subsequently beta-blockers, almost without fail have not shown that treatment with these agents significantly reduces heart disease mortality and sudden death. This has been attributed, perhaps without basis, to an unfavorable countering effect of increased lipid levels, aggravating this risk factor, and other undesirable metabolic effect of diuretics, such as hypokalemia and depletion of body magnesium, increasing the propensity to ventricular arrhythmias, hyperglycemia, worsening diabetes, and hyperuricemia. A survey of 674 persons with hypertension seen personally during the period 1985-89, who were under the care of approximately that many physicians, reveals striking changes in drug prescription and use during this brief period that portend a major change in the outlook of hypertension. Two classes of drugs have increased rapidly in popularity: these are the angiotensin-converting enzyme inhibitors (ACE inhibitors) and the calcium blockers. Both classes of drugs effectively lower blood pressure and have minimal side effects with good compliance. They act not only to reduce peripheral vascular resistance, but also locally in the heart muscle to directly cause left ventricular hypertrophy to regress, an effect of great consequence. The drugs used in former trials such as the vasodilators and diuretics have no effect on left ventricular hypertrophy

  10. Drug-resistant tuberculosis: emerging treatment options

    Directory of Open Access Journals (Sweden)

    Adhvaryu MR

    2011-12-01

    Full Text Available Meghna Adhvaryu1, Bhasker Vakharia21Department of Biotechnology, SRK Institute of Computer Education and Applied Sciences, 2R&D, Bhuma Research in Ayurvedic and Herbal Medicine, Surat, Gujarat, IndiaAbstract: Multidrug-resistant tuberculosis has emerged worldwide, with an increasing incidence due to failure of implementation of apparently effective first-line antituberculous therapy as well as primary infection with drug-resistant strains. Failure of current therapy is attributed to a long duration of treatment leading to nonadherence and irregular therapy, lack of patient education about the disease, poverty, irregular supply by care providers, drug–drug interactions in patients coinfected with human immunodeficiency virus (HIV, inadequate regulations causing market overlap and irresponsible drug usage in the private sector, and lack of research, with no addition of new drugs in the last four decades. Present standards of care for the treatment of drug-susceptible tuberculosis, multidrug-resistant tuberculosis, tuberculosis-HIV coinfection, and latent tuberculosis infection are all unsatisfactory. Since 2000, the World Health Organization (WHO has focused on drug development for tuberculosis, as well as research in all relevant aspects to discover new regimens by 2015 and to eliminate tuberculosis as a public health concern by 2050. As a result, some 20 promising compounds from 14 groups of drugs have been discovered. Twelve candidates from eight classes are currently being evaluated in clinical trials. Ongoing research should prioritize identification of novel targets and newer application of existing drugs, discovery of multitargeted drugs from natural compounds, strengthening host factors by immunopotentiation with herbal immunomodulators, as well as protective vaccines before and after exposure, consideration of surgical measures when indicated, development of tools for rapid diagnosis, early identification of resistant strains, and

  11. Current and emerging somatic treatment strategies in psychotic major depression.

    Science.gov (United States)

    Dannon, Pinhas N; Lowengrub, Katherine; Gonopolski, Yehudit; Kotler, Moshe

    2006-01-01

    Psychotic major depressive disorder (MDD) is a mood disorder characterized by severe affective and neurovegetative symptoms together with the presence of delusions and/or hallucinations. It is a common disorder seen in a quarter of consecutively admitted depressed patients and is often associated with severe symptomatology, increased suicide risk, poor acute response to antidepressants and poor acute and long-term treatment outcome. It is possible that poor response in psychotic depression is caused by the fact that we have yet to identify the most efficacious treatment protocol for psychotic MDD. Multiple studies have shown that modifications in the treatment paradigm may increase treatment efficacy in psychotic MDD. It has been generally accepted that, during the acute treatment phase, antidepressant-antipsychotic drug combination therapy is more effective than either treatment alone, although this strategy has recently been challenged. The question of the optimal duration of pharmacotherapy in order to prevent relapse and improve long-term (i.e., 5-year) outcome is a focus of current investigation. This article will review currently recommended treatment strategies for the acute, continuation and maintenance phases of therapy. In particular, it will address the role of newer-generation antidepressants, the role of second-generation antipsychotics, the use of mood stabilizers and indications for electroconvulsive therapy. Other possible treatment strategies such as transcranial magnetic stimulation, vagus nerve stimulation, deep-brain stimulation and glucocorticoid receptor antagonists will be discussed. Current recommendations for the prevention of relapse and improvement of long-term outcome will be reviewed.

  12. Absence of association between major vault protein (MVP) gene polymorphisms and drug resistance in Chinese Han patients with partial epilepsy.

    Science.gov (United States)

    Zhou, Luo; Zhang, Mengqi; Long, Hongyu; Long, Lili; Xie, Yuanyuan; Liu, Zhaoqian; Kang, Jin; Chen, Qihua; Feng, Li; Xiao, Bo

    2015-11-15

    Drug resistance in epilepsy is common despite many antiepileptic drugs (AEDs) available for treatment. The development of drug resistant epilepsy may be a result of multiple factors. Several previous studies reported that the major vault protein (MVP) was significantly increased in epileptogenic brain tissues resected from patients with partial-onset seizures, indicating the possible involvement of MVP in drug resistance. In this article, we aimed to identify the association between single nucleotide polymorphisms (SNPs) of MVP gene and drug resistance of partial epilepsy in a Chinese Han population. A total of 510 patients with partial-onset seizures and 206 healthy controls were recruited. Among the patients, 222 were drug resistant and 288 were responsive. The selection of tagging SNPs was based on the Hapmap database and Haploview software and the genotyping was conducted on the Sequenom MassARRAY iPLEX platform. For the selected loci rs12149746, rs9938630 and rs4788186 in the MVP gene, there was no significant difference in allele or genotype distribution between the drug resistant and responsive groups, or between all of the patients and healthy controls. Linkage disequilibrium between any two loci was detected but there was no significant difference in haplotype frequency between the drug resistant and responsive groups. Our results suggest that MVP genetic polymorphisms and haplotypes may not be associated with drug resistance of partial epilepsy in the Chinese Han population. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Transcranial magnetic stimulation for the treatment of major depression

    Science.gov (United States)

    Janicak, Philip G; Dokucu, Mehmet E

    2015-01-01

    Major depression is often difficult to diagnose accurately. Even when the diagnosis is properly made, standard treatment approaches (eg, psychotherapy, medications, or their combination) are often inadequate to control acute symptoms or maintain initial benefit. Additional obstacles involve safety and tolerability problems, which frequently preclude an adequate course of treatment. This leaves an important gap in our ability to properly manage major depression in a substantial proportion of patients, leaving them vulnerable to ensuing complications (eg, employment-related disability, increased risk of suicide, comorbid medical disorders, and substance abuse). Thus, there is a need for more effective and better tolerated approaches. Transcranial magnetic stimulation is a neuromodulation technique increasingly used to partly fill this therapeutic void. In the context of treating depression, we critically review the development of transcranial magnetic stimulation, focusing on the results of controlled and pragmatic trials for depression, which consider its efficacy, safety, and tolerability. PMID:26170668

  14. Treatment-resistant depression and suicidality.

    Science.gov (United States)

    Bergfeld, Isidoor O; Mantione, Mariska; Figee, Martijn; Schuurman, P Richard; Lok, Anja; Denys, Damiaan

    2018-08-01

    Thirty percent of patients with treatment-resistant depression (TRD) attempt suicide at least once during their lifetime. However, it is unclear what the attempted and completed suicide incidences are in TRD patients after initiating a treatment, and whether specific treatments increase or decrease these incidences. We searched PubMed systematically for studies of depressed patients who failed at least two antidepressant therapies and were followed for at least three months after initiating a treatment. We estimated attempted and completed suicide incidences using a Poisson meta-analysis. Given the lack of controlled comparisons, we used a meta-regression to estimate whether these incidences differed between treatments. We included 30 studies investigating suicidality in 32 TRD samples, undergoing deep brain stimulation (DBS, n = 9), vagal nerve stimulation (VNS, n = 9), electroconvulsive therapy (ECT, n = 5), treatment-as-usual (n = 3), capsulotomy (n = 2), cognitive behavioral therapy (n = 2), ketamine (n = 1), and epidural cortical stimulation (n = 1). The overall incidence of completed suicides was 0.47 per 100 patient years (95% CI: 0.22-1.00), and of attempted suicides 4.66 per 100 patient years (95% CI: 3.53-6.23). No differences were found in incidences following DBS, VNS or ECT. Suicidality is poorly recorded in many studies limiting the number of studies available. The completed and attempted suicide incidences are high (0.47 and 4.66 per 100 patient years respectively), but these incidences did not differ between three end of the line treatments (DBS, VNS or ECT). Given the high suicide risk in TRD patients, clinical trials should consider suicidality as an explicit outcome measure. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Prevalence of transmitted drug resistance and impact of transmitted resistance on treatment success in the German HIV-1 Seroconverter Cohort.

    Directory of Open Access Journals (Sweden)

    Barbara Bartmeyer

    Full Text Available BACKGROUND: The aim of this study is to analyse the prevalence of transmitted drug resistance, TDR, and the impact of TDR on treatment success in the German HIV-1 Seroconverter Cohort. METHODS: Genotypic resistance analysis was performed in treatment-naïve study patients whose sample was available 1,312/1,564 (83.9% October 2008. A genotypic resistance result was obtained for 1,276/1,312 (97.3%. The resistance associated mutations were identified according to the surveillance drug resistance mutations list recommended for drug-naïve patients. Treatment success was determined as viral suppression below 500 copies/ml. RESULTS: Prevalence of TDR was stable at a high level between 1996 and 2007 in the German HIV-1 Seroconverter Cohort (N = 158/1,276; 12.4%; CI(wilson 10.7-14.3; p(for trend = 0.25. NRTI resistance was predominant (7.5% but decreased significantly over time (CI(Wilson: 6.2-9.1, p(for trend = 0.02. NNRTI resistance tended to increase over time (NNRTI: 3.5%; CI(Wilson: 2.6-4.6; p(for trend= 0.07, whereas PI resistance remained stable (PI: 3.0%; CI(Wilson: 2.1-4.0; p(for trend = 0.24. Resistance to all drug classes was frequently caused by singleton resistance mutations (NRTI 55.6%, PI 68.4%, NNRTI 99.1%. The majority of NRTI-resistant strains (79.8% carried resistance-associated mutations selected by the thymidine analogues zidovudine and stavudine. Preferably 2NRTI/1PIr combinations were prescribed as first line regimen in patients with resistant HIV as well as in patients with susceptible strains (susceptible 45.3%; 173/382 vs. resistant 65.5%; 40/61. The majority of patients in both groups were treated successfully within the first year after ART-initiation (susceptible: 89.9%; 62/69; resistant: 7/9; 77.8%. CONCLUSION: Overall prevalence of TDR remained stable at a high level but trends of resistance against drug classes differed over time. The significant decrease of NRTI-resistance in patients newly infected

  16. Cytokines: abnormalities in major depression and implications for pharmacological treatment.

    LENUS (Irish Health Repository)

    O'Brien, Sinead M

    2012-02-03

    The role of cytokines in depression was first considered when the cytokine interferon resulted in "sickness behaviour", the symptoms of which are similar to those of major depression. The latter is associated with an increase in pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha). These cytokines are potent modulators of corticotropin-releasing hormone (CRH) which produces heightened hypothalamic-pituitary-adrenal axis (HPA) activity characterized by increases in ACTH and cortisol, both of which are reported elevated in major depression. Antidepressant treatment has immunomodulatory effects with increases in the production of IL-10, which is an anti-inflammatory cytokine. This review based on a Medline search from 1980-2003, focuses on the evidence available of cytokine changes in acute stress, chronic stress and major depression. It examines the effects of antidepressant treatment on immune parameters in both animal models and clinical trials. We suggest that future antidepressants may target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.

  17. Genetic mapping of a major dominant gene for resistance to Ralstonia solanacearum in eggplant.

    Science.gov (United States)

    Lebeau, A; Gouy, M; Daunay, M C; Wicker, E; Chiroleu, F; Prior, P; Frary, A; Dintinger, J

    2013-01-01

    Resistance of eggplant against Ralstonia solanacearum phylotype I strains was assessed in a F(6) population of recombinant inbred lines (RILs) derived from a intra-specific cross between S. melongena MM738 (susceptible) and AG91-25 (resistant). Resistance traits were determined as disease score, percentage of wilted plants, and stem-based bacterial colonization index, as assessed in greenhouse experiments conducted in Réunion Island, France. The AG91-25 resistance was highly efficient toward strains CMR134, PSS366 and GMI1000, but only partial toward the highly virulent strain PSS4. The partial resistance found against PSS4 was overcome under high inoculation pressure, with heritability estimates from 0.28 to 0.53, depending on the traits and season. A genetic map was built with 119 AFLP, SSR and SRAP markers positioned on 18 linkage groups (LG), for a total length of 884 cM, and used for quantitative trait loci (QTL) analysis. A major dominant gene, named ERs1, controlled the resistance to strains CMR134, PSS366, and GMI1000. Against strain PSS4, this gene was not detected, but a significant QTL involved in delay of disease progress was detected on another LG. The possible use of the major resistance gene ERs1 in marker-assisted selection and the prospects offered for academic studies of a possible gene for gene system controlling resistance to bacterial wilt in solanaceous plants are discussed.

  18. Importance of proper initial treatment of moderate and major burns

    Directory of Open Access Journals (Sweden)

    Vulović Dejan

    2008-01-01

    Full Text Available Background/Aim. Burns are common injuries with frequency depending on human factors, development of protection, industry and traffic, eventual wars. Organized treatment of major burn injuries has tremendous medical, social and economic importance. The aim of this study was to analyze initial treatment of major and moderate burns, to compare it with the current recommendations and to signify the importance of organized management of burns. Methods. In a prospective study 547 adult patients with major burns were analyzed, covering a period of eight years, with the emphasis on the initial hospital admission and emergency care for burns greater than 10% of total body surface area (TBSA. Results. In the different groups of major burns, the percentage of hospital admission was: 81.5 in burns greater than 10% TBSA, 37.7 in burns of the functional areas, 54.5 in the III degree burns, 81.6 in electrical burns, 55.9 in chemical burns, 61.9 in inhalation injury, 41.0 in burns in patients with the greater risk and 100 in burns with a concomitant trauma. In the group of 145 patients with burns greater than 10% TBSA, intravenous fluids were given in 87 patients, analgesics in 45, corticosteroids in 29, antibiotics in 23 and oxygen administration in 14. In the same group, wound irrigation was done in 14.4%, removing of the clothing and shoes in 29.6%, elevation of the legs in 8.9% and prevention of hypothermia in 7.6% of the victims. There were no initial estimations of burn extent (percentage of a burn, notes about the patient and injury and tetanus immunizations. Conclusion. Based on these findings, it is concluded that there should be much more initial hospital admissions of major burns, and also, necessary steps in the emergency care of burns greater than 10% TBSA should be taken more frequently. On the other side, unnecessary or wrong steps should be avoided in the initial burn treatment.

  19. Effect of different oral oxytetracycline treatment regimes on selection of antimicrobial resistant coliforms in nursery pigs

    DEFF Research Database (Denmark)

    Fresno, Ana Herrero; Zachariasen, Camilla; Norholm, Nanna

    2017-01-01

    A major concern derived from using antimicrobials in pig production is the development of resistance. This study aimed to assess the impact of selected combinations of oral dose and duration of treatment with oxytetracycline (OTC) on selection of tetracycline resistant (TET-R) coliforms recovered...

  20. Depressive personality and treatment outcome in major depressive disorder.

    Science.gov (United States)

    Ryder, Andrew G; Quilty, Lena C; Vachon, David D; Bagby, R Michael

    2010-06-01

    Depressive personality disorder (DPD) is currently included in the DSM-IV Appendix B, Criteria Sets and Axes Provided for Further Study. Evidence of the clinical utility of DPD will likely play an important role in the determination of whether it warrants inclusion in future editions of DSM. The current investigation examines the capacity of DPD traits to predict overall and preferential treatment outcome for patients with Major Depressive Disorder (MDD) (N = 120) using data from a randomized control trial, which included cognitive behavioral therapy (CBT), interpersonal therapy (IPT), and antidepressant medication (ADM) treatment arms. Patients were treated for 16-20 weeks and completed the Structured Clinical Interview for DSM-IV Axis II Personality Disorders Questionnaire (SCID-II/PQ) and the 17-item Hamilton Rating Scale for Depression immediately before and after treatment. Higher scores on a dimensionalized SCID-II/PQ subscale assessing DPD traits were associated with poor outcome for IPT, but not CBT or ADM. This result remained after accounting for variance associated with other personality disorder (PD) traits; none of the other 10 main text PDs predicted treatment outcome.

  1. Neural correlates of treatment outcome in major depression.

    LENUS (Irish Health Repository)

    Lisiecka, Danuta

    2012-02-01

    There is a need to identify clinically useful biomarkers in major depressive disorder (MDD). In this context the functional connectivity of the orbitofrontal cortex (OFC) to other areas of the affect regulation circuit is of interest. The aim of this study was to identify neural changes during antidepressant treatment and correlates associated with the treatment outcome. In an exploratory analysis it was investigated whether functional connectivity measures moderated a response to mirtazapine and venlafaxine. Twenty-three drug-free patients with MDD were recruited from the Department of Psychiatry and Psychotherapy of the Ludwig-Maximilians University in Munich. The patients were subjected to a 4-wk randomized clinical trial with two common antidepressants, venlafaxine or mirtazapine. Functional connectivity of the OFC, derived from functional magnetic resonance imaging with an emotional face-matching task, was measured before and after the trial. Higher OFC connectivity with the left motor areas and the OFC regions prior to the trial characterized responders (p<0.05, false discovery rate). The treatment non-responders were characterized by higher OFC-cerebellum connectivity. The strength of response was positively correlated with functional coupling between left OFC and the caudate nuclei and thalami. Differences in longitudinal changes were detected between venlafaxine and mirtazapine treatment in the motor areas, cerebellum, cingulate gyrus and angular gyrus. These results indicate that OFC functional connectivity might be useful as a marker for therapy response to mirtazapine and venlafaxine and to reconstruct the differences in their mechanism of action.

  2. Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans.

    Science.gov (United States)

    Moyes, Catherine L; Vontas, John; Martins, Ademir J; Ng, Lee Ching; Koou, Sin Ying; Dusfour, Isabelle; Raghavendra, Kamaraju; Pinto, João; Corbel, Vincent; David, Jean-Philippe; Weetman, David

    2017-07-01

    Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus), making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids). Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance.

  3. Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans

    Science.gov (United States)

    Vontas, John; Martins, Ademir J.; Ng, Lee Ching; Koou, Sin Ying; Dusfour, Isabelle; Raghavendra, Kamaraju; Pinto, João; Corbel, Vincent; David, Jean-Philippe; Weetman, David

    2017-01-01

    Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus), making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids). Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance. PMID:28727779

  4. Contemporary status of insecticide resistance in the major Aedes vectors of arboviruses infecting humans.

    Directory of Open Access Journals (Sweden)

    Catherine L Moyes

    2017-07-01

    Full Text Available Both Aedes aegytpi and Ae. albopictus are major vectors of 5 important arboviruses (namely chikungunya virus, dengue virus, Rift Valley fever virus, yellow fever virus, and Zika virus, making these mosquitoes an important factor in the worldwide burden of infectious disease. Vector control using insecticides coupled with larval source reduction is critical to control the transmission of these viruses to humans but is threatened by the emergence of insecticide resistance. Here, we review the available evidence for the geographical distribution of insecticide resistance in these 2 major vectors worldwide and map the data collated for the 4 main classes of neurotoxic insecticide (carbamates, organochlorines, organophosphates, and pyrethroids. Emerging resistance to all 4 of these insecticide classes has been detected in the Americas, Africa, and Asia. Target-site mutations and increased insecticide detoxification have both been linked to resistance in Ae. aegypti and Ae. albopictus but more work is required to further elucidate metabolic mechanisms and develop robust diagnostic assays. Geographical distributions are provided for the mechanisms that have been shown to be important to date. Estimating insecticide resistance in unsampled locations is hampered by a lack of standardisation in the diagnostic tools used and by a lack of data in a number of regions for both resistance phenotypes and genotypes. The need for increased sampling using standard methods is critical to tackle the issue of emerging insecticide resistance threatening human health. Specifically, diagnostic doses and well-characterised susceptible strains are needed for the full range of insecticides used to control Ae. aegypti and Ae. albopictus to standardise measurement of the resistant phenotype, and calibrated diagnostic assays are needed for the major mechanisms of resistance.

  5. A New Prediction Model for Evaluating Treatment-Resistant Depression.

    Science.gov (United States)

    Kautzky, Alexander; Baldinger-Melich, Pia; Kranz, Georg S; Vanicek, Thomas; Souery, Daniel; Montgomery, Stuart; Mendlewicz, Julien; Zohar, Joseph; Serretti, Alessandro; Lanzenberger, Rupert; Kasper, Siegfried

    2017-02-01

    Despite a broad arsenal of antidepressants, about a third of patients suffering from major depressive disorder (MDD) do not respond sufficiently to adequate treatment. Using the data pool of the Group for the Study of Resistant Depression and machine learning, we intended to draw new insights featuring 48 clinical, sociodemographic, and psychosocial predictors for treatment outcome. Patients were enrolled starting from January 2000 and diagnosed according to DSM-IV. Treatment-resistant depression (TRD) was defined by a 17-item Hamilton Depression Rating Scale (HDRS) score ≥ 17 after at least 2 antidepressant trials of adequate dosage and length. Remission was defined by an HDRS score depressive episode, age at first antidepressant treatment, response to first antidepressant treatment, severity, suicidality, melancholia, number of lifetime depressive episodes, patients' admittance type, education, occupation, and comorbid diabetes, panic, and thyroid disorder. While single predictors could not reach a prediction accuracy much different from random guessing, by combining all predictors, we could detect resistance with an accuracy of 0.737 and remission with an accuracy of 0.850. Consequently, 65.5% of predictions for TRD and 77.7% for remission can be expected to be accurate. Using machine learning algorithms, we could demonstrate success rates of 0.737 for predicting TRD and 0.850 for predicting remission, surpassing predictive capabilities of clinicians. Our results strengthen data mining and suggest the benefit of focus on interaction-based statistics. Considering that all predictors can easily be obtained in a clinical setting, we hope that our model can be tested by other research groups. © Copyright 2017 Physicians Postgraduate Press, Inc.

  6. The impact of Cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes on suicide attempt and suicide risk-a European multicentre study on treatment-resistant major depressive disorder.

    Science.gov (United States)

    Höfer, Peter; Schosser, Alexandra; Calati, Raffaella; Serretti, Alessandro; Massat, Isabelle; Kocabas, Neslihan Aygun; Konstantinidis, Anastasios; Linotte, Sylvie; Mendlewicz, Julien; Souery, Daniel; Zohar, Joseph; Juven-Wetzler, Alzbeta; Montgomery, Stuart; Kasper, Siegfried

    2013-08-01

    Recently published data have reported associations between cytochrome P450 metabolizer status and suicidality. The aim of our study was to investigate the role of genetic polymorphisms of the cytochrome P450 genes on suicide risk and/or a personal history of suicide attempts. Two hundred forty-three major depressive disorder patients were collected in the context of a European multicentre resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using the Mini International Neuropsychiatric Interview and the Hamilton Rating Scale for Depression (HAM-D). Treatment response was defined as HAM-D ≤ 17 and remission as HAM-D ≤ 7 after 4 weeks of treatment with antidepressants at adequate dose. Genotyping was performed for all relevant variations of the CYP1A2 gene (*1A, *1F, *1C, *1 J, *1 K), the CYP2C9 gene (*2, *3), the CYP2C19 gene (*2, *17) and the CYP2D6 gene (*3, *4, *5, *6, *9, *19, *XN). No association between both suicide risk and personal history of suicide attempts, and the above mentioned metabolic profiles were found after multiple testing corrections. In conclusion, the investigated cytochrome gene polymorphisms do not seem to be associated with suicide risk and/or a personal history of suicide attempts, though methodological and sample size limitations do not allow definitive conclusions.

  7. Pharmacological Treatment of Major Depressive Disorder in Adolescents

    Directory of Open Access Journals (Sweden)

    Rachel L. Farley

    2005-01-01

    Full Text Available Major depressive disorder (MDD affects a significant number of adolescents today. Its consequences (including social isolation, failure to achieve crucial developmental milestones, and suicide mandate close attention in clinical practice. While tricyclics and monoamine oxidase inhibitors (MAOIs have been used infrequently and with questionable efficacy, selective serotonin reuptake inhibitors (SSRIs, particularly fluoxetine, consistently have been shown to be of benefit in treating outpatient adolescents with MDD. Despite some success with other drugs in its class, fluoxetine remains the only SSRI that is FDA approved for treatment of children and adolescents with depression. A review of recent studies is presented, including the controversy regarding the relationship of antidepressants and suicidal behavior in this patient population.

  8. Desvenlafaxine in the treatment of major depressive disorder

    Directory of Open Access Journals (Sweden)

    Maria Teresa C Lourenco1

    2009-02-01

    Full Text Available Maria Teresa C Lourenco1, Sidney H Kennedy1,21Department of Psychiatry, University Health Network, Toronto; 2Department of Psychiatry, University of Toronto, Toronto, CanadaAbstract: Major depressive disorder (MDD is among the most incapacitating conditions in the world. The emergence of the selective serotonin reuptake inhibitor (SSRI and serotonin norepinephrine reuptake inhibitors (SNRI antidepressants has improved the treatment of MDD. Desvenlafaxine succinate (DVS is the succinate salt of the isolated major active metabolite of venlafaxine, O-desmethylvenlafaxine: it is the third SNRI to become available in the United States, and was approved in 2008 by the US Food and Drug Administration (FDA for the treatment of MDD. Early investigations showed therapeutic efficacy for doses between 50 and 400 mg/day; however in doses above 100 mg/day there were incremental increases in side effects. Nausea was the most frequent adverse effect. Hence the recommended dosing for DVS is in the 50 to 100 mg range. Desvenlafaxine is excreted in urine, it is minimally metabolized via the CYP450 pathway, and is a weak inhibitor of CYP2D6. A reduced risk for pharmacokinetic drug interactions is a potential advantage over other SNRI. Further head-to-head trials involving comparisons of DVS in the 50 to 100 mg dose range with currently available SSRI and SNRI antidepressants are required. Evidence for relapse prevention is available in the 200 to 400 mg dose range, but this needs to be demonstrated in the 50 to 100 mg dose range, as well as health economic measures and quality of life evaluations.Keywords: desvenlafaxine, O-desmethylvenlafaxine, Pristiq®, SNRIs, MDD

  9. Exploring Post-Treatment Reversion of Antimicrobial Resistance in Enteric Bacteria of Food Animals as a Resistance Mitigation Strategy.

    Science.gov (United States)

    Volkova, Victoriya V; KuKanich, Butch; Riviere, Jim E

    2016-11-01

    Antimicrobial drug use in food animals is associated with an elevation in relative abundance of bacteria resistant to the drug among the animal enteric bacteria. Some of these bacteria are potential foodborne pathogens. Evidence suggests that at least in the enteric nontype-specific Escherichia coli, after treatment the resistance abundance reverts to the background pre-treatment levels, without further interventions. We hypothesize that it is possible to define the distribution of the time period after treatment within which resistance to the administered drug, and possibly other drugs in case of coselection, in fecal bacteria of the treated animals returns to the background pre-treatment levels. Furthermore, it is possible that a novel resistance mitigation strategy for microbiological food safety could be developed based on this resistance reversion phenomenon. The strategy would be conceptually similar to existing antimicrobial drug withdrawal periods, which is a well-established and accepted mitigation strategy for avoiding violative drug residues in the edible products from the treated animals. For developing resistance-relevant withdrawals, a mathematical framework can be used to join the necessary pharmacological, microbiological, and animal production components to project the distributions of the post-treatment resistance reversion periods in the production animal populations for major antimicrobial drug classes in use. The framework can also help guide design of empirical studies into the resistance-relevant withdrawal periods and development of mitigation approaches to reduce the treatment-associated elevation of resistance in animal enteric bacteria. We outline this framework, schematically and through exemplar equations, and how its components could be formulated.

  10. Investigation of Rifampicin Resistance Outcome among Tuberculosis Patients Visiting Two Major Health Facilities in Port Harcourt in Niger Delta

    Directory of Open Access Journals (Sweden)

    Wokem Gloria Ngozika

    2018-03-01

    Full Text Available Background: Tuberculosis is caused by Mycobacterium tuberculosis and is spread mainly through contact with air droplets and respiratory fluid from an infected person. Drug of choice for its treatment are rifampicin and isoniazid respectively. However, in recent times, resistance to these drugs as with other antibiotics has been observed across the globe. This study was thus aimed at determining the prevalence of rifampicin resistance strain among TB patients attending two major hospitals (Braithwaite Memorial Hospital and University of Port Harcourt Teaching Hospital in Port Harcourt. Method: Sputum of patients was collected, tested for the presence of TB and rifampicin resistance of the isolates were determined using GeneXpert assay approach. Result: A total of 158 isolates from patients who were TB positive were tested for rifampicin resistance. 13.3% of these were resistant to rifampicin drug. 8.9% was from UPTH while 4.4% was from BMSH. 9.5% were less than age 45 while 3.8% were greater than or equal to age 45 (≥45. Males made up 8.2% of the total prevalence while females made up 5.1% of the total prevalence. Alternative drugs to rifampicin and isoniazid drug should however, be prescribed in confirmed cases of resistance outcome in our health facilities especially in the rural communities. Conclusion: Nonetheless, the use of antibiotics indiscriminately without the effective laboratory assay and physician’s prescription should be discouraged at all levels and patients receiving treatment should be monitored to adhere strictly to the desired dosage as non-adhering to the gold standard option may lead to drug resistance outcome among vulnerable patients who are literally exposed to lack of health education and functional health facilities in the remote communities which are also hard to reach area due to the environmental terrine

  11. Major Gene for Field Stem Rust Resistance Co-Locates with Resistance Gene Sr12 in 'Thatcher' Wheat.

    Science.gov (United States)

    Hiebert, Colin W; Kolmer, James A; McCartney, Curt A; Briggs, Jordan; Fetch, Tom; Bariana, Harbans; Choulet, Frederic; Rouse, Matthew N; Spielmeyer, Wolfgang

    2016-01-01

    Stem rust, caused by Puccinia graminis (Pgt), is a damaging disease of wheat that can be controlled by utilizing effective stem rust resistance genes. 'Thatcher' wheat carries complex resistance to stem rust that is enhanced in the presence of the resistance gene Lr34. The purpose of this study was to examine APR in 'Thatcher' and look for genetic interactions with Lr34. A RIL population was tested for stem rust resistance in field nurseries in Canada, USA, and Kenya. BSA was used to find SNP markers associated with reduced stem rust severity. A major QTL was identified on chromosome 3BL near the centromere in all environments. Seedling testing showed that Sr12 mapped to the same region as the QTL for APR. The SNP markers were physically mapped and the region carrying the resistance was searched for sequences with homology to members of the NB-LRR resistance gene family. SNP marker from one NB-LRR-like sequence, NB-LRR3 co-segregated with Sr12. Two additional populations, including one that lacked Lr34, were tested in field nurseries. NB-LRR3 mapped near the maximum LOD for reduction in stem rust severity in both populations. Lines from a population that segregated for Sr12 and Lr34 were tested for seedling Pgt biomass and infection type, as well as APR to field stem rust which showed an interaction between the genes. We concluded that Sr12, or a gene closely linked to Sr12, was responsible for 'Thatcher'-derived APR in several environments and this resistance was enhanced in the presence of Lr34.

  12. Major Gene for Field Stem Rust Resistance Co-Locates with Resistance Gene Sr12 in ‘Thatcher’ Wheat

    Science.gov (United States)

    Hiebert, Colin W.; Kolmer, James A.; McCartney, Curt A.; Briggs, Jordan; Fetch, Tom; Bariana, Harbans; Choulet, Frederic; Rouse, Matthew N.; Spielmeyer, Wolfgang

    2016-01-01

    Stem rust, caused by Puccinia graminis (Pgt), is a damaging disease of wheat that can be controlled by utilizing effective stem rust resistance genes. ‘Thatcher’ wheat carries complex resistance to stem rust that is enhanced in the presence of the resistance gene Lr34. The purpose of this study was to examine APR in ‘Thatcher’ and look for genetic interactions with Lr34. A RIL population was tested for stem rust resistance in field nurseries in Canada, USA, and Kenya. BSA was used to find SNP markers associated with reduced stem rust severity. A major QTL was identified on chromosome 3BL near the centromere in all environments. Seedling testing showed that Sr12 mapped to the same region as the QTL for APR. The SNP markers were physically mapped and the region carrying the resistance was searched for sequences with homology to members of the NB-LRR resistance gene family. SNP marker from one NB-LRR-like sequence, NB-LRR3 co-segregated with Sr12. Two additional populations, including one that lacked Lr34, were tested in field nurseries. NB-LRR3 mapped near the maximum LOD for reduction in stem rust severity in both populations. Lines from a population that segregated for Sr12 and Lr34 were tested for seedling Pgt biomass and infection type, as well as APR to field stem rust which showed an interaction between the genes. We concluded that Sr12, or a gene closely linked to Sr12, was responsible for ‘Thatcher’-derived APR in several environments and this resistance was enhanced in the presence of Lr34. PMID:27309724

  13. Emergence of nitrosourea resistant sublines of Lewis lung tumour following MeCCNU treatment in vivo.

    Science.gov (United States)

    Stephens, T. C.; Adams, K.; Peacock, J. H.

    1986-01-01

    Several different drug retreatment protocols were employed to examine the emergence of resistance to MeCCNU in Lewis lung tumours. Previous studies suggested that although the majority of cells in untreated Lewis lung tumours were sensitive to MeCCNU, there was a very small proportion of resistant cells (approximately 0.001%) that limited "tumour cure' with that drug. If such cells were inherently drug resistant then it should be possible to derive highly resistant tumours by repeated drug treatment. In the first experiment tumours were treated with a single high dose of MeCCNU (35 or 40 mgkg-1) and on regrowth, transplanted into fresh mice and tested for drug sensitivity. Using both excision cell survival and growth delay endpoints, only approximately 25% of tumours were significantly resistant to the test dose, suggesting that many tumours resist the effects of the drug for reasons other than the presence of inherently drug resistant cells. One of the tumours (R4), that regrew after the initial treatment and appeared to be resistant to the test treatment, was retreated with a further 30 mgkg-1 MeCCNU and became more resistant. This line, designated R4/1, was cross-resistant to the other nitrosoureas, BCNU and CCNU, but not to cyclophosphamide, melphalan, cis-platinum or ionising radiation. The effect of treatment dose on the kinetics of MeCCNU resistance development was also studied in a retreatment regimen where the tumours were allowed to regrow and then transplanted into fresh hosts for the next treatment. Resistance developed more quickly at an intermediate dose of 15 mgkg-1 than at 7.5 mgkg-1 where the selective pressure was lower, or at 30 mgkg-1 where there was probably extinction of partially resistant cells. Resistance to MeCCNU developed even more quickly when tumours were retreated several times in the same host, although in a similar experiment with cyclophosphamide no resistance occurred. PMID:3954945

  14. Utilization of a major brown rust resistance gene in sugarcane breeding

    Science.gov (United States)

    Brown rust, caused by Puccinia melanocephala has had devastating effects on sugarcane (Saccharum spp.) breeding programs and on commercial production. The discovery of Bru1, a major gene conferring resistance to brown rust represented a substantial breakthrough and markers for the detection of Bru1 ...

  15. Treatment of Comorbid Obesity and Major Depressive Disorder: A Prospective Pilot Study for their Combined Treatment

    Directory of Open Access Journals (Sweden)

    Lucy F. Faulconbridge

    2011-01-01

    Full Text Available Background. Obese individuals who suffer from major depressive disorder are routinely screened out of weight loss trials. Treatments targeting obesity and depression concurrently have not been tested. Purpose. To test the short-term efficacy of a treatment that combined behavioral weight management and cognitive behavioral therapy (CBT for obese adults with depression. Methods. Twelve obese females diagnosed with major depressive disorder received weekly group behavioral weight management, combined with CBT for depression, for 16 weeks. Weight, symptoms of depression, and cardiovascular disease (CVD risk factors were measured at baseline and week 16. Results. Participants lost 11.4% of initial weight and achieved significant improvements in symptoms of depression and CVD risk factors. Conclusions. Obese individuals suffering from major depressive disorder can lose weight and achieve improvements in symptoms of depression and CVD risk factors with 16 weeks of combined treatment. A larger randomized controlled trial is needed to establish the efficacy of this treatment.

  16. Bacterial resistance and impetigo treatment trends: a review.

    Science.gov (United States)

    Bangert, Scott; Levy, Moise; Hebert, Adelaide A

    2012-01-01

    Impetigo is a common cutaneous infection that is especially prevalent in children. The prevalence of colonization and infection with resistant strains is continually increasing, forcing clinicians to reevaluate treatment strategies. Newer topical agents are effective in treating infections with resistant strains and may help minimize resistance and adverse effects from systemic agents. Use of topical disinfectants to decrease colonization is an important adjunctive measure. Physicians should be aware of local resistance patterns in impetigo to help guide therapy. © 2012 Wiley Periodicals, Inc.

  17. The use of cognitive behavioral therapy in the treatment of resistant depression in adolescents

    Directory of Open Access Journals (Sweden)

    Prieto-Hicks X

    2012-09-01

    Full Text Available Sarah Hamill-Skoch,1 Paul Hicks,2 Ximena Prieto-Hicks11Department of Psychiatry, 2Department of Family and Community Medicine, University of Arizona, Tuscon, AZ, USAAbstract: Major depressive disorder often begins in adolescence, is chronic and recurrent, and heightens an individual's risk for major depressive disorder in adulthood. Treatment-resistant depression is a problem for a significant minority of adolescents. Few studies have examined treatments for treatment-resistant depression among adolescents, and even fewer have examined the use of cognitive-behavioral therapy as a monotherapy or in combination with pharmacological treatments. Mental health professionals have a strong interest in understanding what treatments are appropriate for adolescents who are treatment resistant. Preliminary evidence from current published trials indicates that the use of cognitive-behavioral therapy in combination with antidepressant medication yields the best outcome for treatment-resistant depression in adolescents. Secondary analyses also suggest that the utility of cognitive behavioral therapy can be increased by ensuring adolescents receive a therapeutic dose of treatment sessions (more than nine sessions and the inclusion of two treatment components: social skills and problem solving training. Guidelines for clinicians as well as areas for future research are discussed.Keywords: cognitive behavior therapy, treatment-resistant depression, adolescent depression

  18. Major Depression and the Degree of Suicidality: Results of the European Group for the Study of Resistant Depression (GSRD).

    Science.gov (United States)

    Dold, Markus; Bartova, Lucie; Fugger, Gernot; Kautzky, Alexander; Souery, Daniel; Mendlewicz, Julien; Papadimitriou, George N; Dikeos, Dimitris; Ferentinos, Panagiotis; Porcelli, Stefano; Serretti, Alessandro; Zohar, Joseph; Montgomery, Stuart; Kasper, Siegfried

    2018-06-01

    This European multicenter study aimed to elucidate suicidality in major depressive disorder. Previous surveys suggest a prevalence of suicidality in major depressive disorder of ≥50%, but little is known about the association of different degrees of suicidality with socio-demographic, psychosocial, and clinical characteristics. We stratified 1410 major depressive disorder patients into 3 categories of suicidality based on the Hamilton Rating Scale for Depression item 3 (suicidality) ratings (0=no suicidality; 1-2=mild/moderate suicidality; 3-4=severe suicidality). Chi-squared tests, analyses of covariance, and Spearman correlation analyses were applied for the data analyses. The prevalence rate of suicidality in major depressive disorder amounted to 46.67% (Hamilton Rating Scale for Depression item 3 score ≥1). 53.33% were allocated into the no, 38.44% into the mild/moderate, and 8.23% into the severe suicidality patient group. Due to the stratification of our major depressive disorder patient sample according to different levels of suicidality, we identified some socio-demographic, psychosocial, and clinical variables differentiating from the patient group without suicidality already in presence of mild/moderate suicidality (depressive symptom severity, treatment resistance, psychotic features, add-on medications in general), whereas others separated only when severe suicidality was manifest (inpatient treatment, augmentation with antipsychotics and benzodiazepines, melancholic features, somatic comorbidities). As even mild/moderate suicidality is associated with a failure of achieving treatment response, adequate recognition of this condition should be ensured in the clinical practice.

  19. Major QTLs Control Resistance to Rice Hoja Blanca Virus and Its Vector Tagosodes orizicolus

    Science.gov (United States)

    Romero, Luz E.; Lozano, Ivan; Garavito, Andrea; Carabali, Silvio J.; Triana, Monica; Villareal, Natalia; Reyes, Luis; Duque, Myriam C.; Martinez, César P.; Calvert, Lee; Lorieux, Mathias

    2013-01-01

    Rice hoja blanca (white leaf) disease can cause severe yield losses in rice in the Americas. The disease is caused by the rice hoja blanca virus (RHBV), which is transmitted by the planthopper vector Tagosodes orizicolus. Because classical breeding schemes for this disease rely on expensive, time-consuming screenings, there is a need for alternatives such as marker-aided selection. The varieties Fedearroz 2000 and Fedearroz 50, which are resistant to RHBV and to the feeding damage caused by T. orizicolus, were crossed with the susceptible line WC366 to produce segregating F2:3 populations. The F3 families were scored for their resistance level to RHBV and T. orizicolus. The F2:3 lines of both crosses were genotyped using microsatellite markers. One major QTL on the short arm of chromosome 4 was identified for resistance to RHBV in the two populations. Two major QTL on chromosomes 5 and 7 were identified for resistance to T. orizicolus in the Fd2000 × WC366 and Fd50 × WC366 crosses, respectively. This comparative study using two distinct rice populations allowed for a better understanding of how the resistance to RHBV and its vector are controlled genetically. Simple marker-aided breeding schemes based on QTL information can be designed to improve rice germplasm to reduce losses caused by this important disease. PMID:24240781

  20. Recombinant Human Erythropoietin for Treating Treatment-Resistant Depression

    DEFF Research Database (Denmark)

    Miskowiak, Kamilla W; Vinberg, Maj; Christensen, Ellen M

    2014-01-01

    improves mood and memory in treatment-resistant depression. Forty treatment-resistant depressed unipolar patients with Hamilton Depression Rating Scale-17 (HDRS-17) score ≥ 17 were randomized to eight weekly EPO (Eprex; 40,000 IU) or saline infusions in a double-blind, placebo-controlled, parallel...

  1. Distribution of triclosan-resistant genes in major pathogenic microorganisms revealed by metagenome and genome-wide analysis

    Science.gov (United States)

    Khan, Raees; Roy, Nazish; Choi, Kihyuck

    2018-01-01

    The substantial use of triclosan (TCS) has been aimed to kill pathogenic bacteria, but TCS resistance seems to be prevalent in microbial species and limited knowledge exists about TCS resistance determinants in a majority of pathogenic bacteria. We aimed to evaluate the distribution of TCS resistance determinants in major pathogenic bacteria (N = 231) and to assess the enrichment of potentially pathogenic genera in TCS contaminated environments. A TCS-resistant gene (TRG) database was constructed and experimentally validated to predict TCS resistance in major pathogenic bacteria. Genome-wide in silico analysis was performed to define the distribution of TCS-resistant determinants in major pathogens. Microbiome analysis of TCS contaminated soil samples was also performed to investigate the abundance of TCS-resistant pathogens. We experimentally confirmed that TCS resistance could be accurately predicted using genome-wide in silico analysis against TRG database. Predicted TCS resistant phenotypes were observed in all of the tested bacterial strains (N = 17), and heterologous expression of selected TCS resistant genes from those strains conferred expected levels of TCS resistance in an alternative host Escherichia coli. Moreover, genome-wide analysis revealed that potential TCS resistance determinants were abundant among the majority of human-associated pathogens (79%) and soil-borne plant pathogenic bacteria (98%). These included a variety of enoyl-acyl carrier protein reductase (ENRs) homologues, AcrB efflux pumps, and ENR substitutions. FabI ENR, which is the only known effective target for TCS, was either co-localized with other TCS resistance determinants or had TCS resistance-associated substitutions. Furthermore, microbiome analysis revealed that pathogenic genera with intrinsic TCS-resistant determinants exist in TCS contaminated environments. We conclude that TCS may not be as effective against the majority of bacterial pathogens as previously presumed

  2. Distribution of triclosan-resistant genes in major pathogenic microorganisms revealed by metagenome and genome-wide analysis.

    Directory of Open Access Journals (Sweden)

    Raees Khan

    Full Text Available The substantial use of triclosan (TCS has been aimed to kill pathogenic bacteria, but TCS resistance seems to be prevalent in microbial species and limited knowledge exists about TCS resistance determinants in a majority of pathogenic bacteria. We aimed to evaluate the distribution of TCS resistance determinants in major pathogenic bacteria (N = 231 and to assess the enrichment of potentially pathogenic genera in TCS contaminated environments. A TCS-resistant gene (TRG database was constructed and experimentally validated to predict TCS resistance in major pathogenic bacteria. Genome-wide in silico analysis was performed to define the distribution of TCS-resistant determinants in major pathogens. Microbiome analysis of TCS contaminated soil samples was also performed to investigate the abundance of TCS-resistant pathogens. We experimentally confirmed that TCS resistance could be accurately predicted using genome-wide in silico analysis against TRG database. Predicted TCS resistant phenotypes were observed in all of the tested bacterial strains (N = 17, and heterologous expression of selected TCS resistant genes from those strains conferred expected levels of TCS resistance in an alternative host Escherichia coli. Moreover, genome-wide analysis revealed that potential TCS resistance determinants were abundant among the majority of human-associated pathogens (79% and soil-borne plant pathogenic bacteria (98%. These included a variety of enoyl-acyl carrier protein reductase (ENRs homologues, AcrB efflux pumps, and ENR substitutions. FabI ENR, which is the only known effective target for TCS, was either co-localized with other TCS resistance determinants or had TCS resistance-associated substitutions. Furthermore, microbiome analysis revealed that pathogenic genera with intrinsic TCS-resistant determinants exist in TCS contaminated environments. We conclude that TCS may not be as effective against the majority of bacterial pathogens as previously

  3. Characterization of putative multidrug resistance transporters of the major facilitator-superfamily expressed in Salmonella Typhi

    DEFF Research Database (Denmark)

    Shaheen, Aqsa; Ismat, Fouzia; Iqbal, Mazhar

    2015-01-01

    Multidrug resistance mediated by efflux pumps is a well-known phenomenon in infectious bacteria. Although much work has been carried out to characterize multidrug efflux pumps in Gram-negative and Gram-positive bacteria, such information is still lacking for many deadly pathogens. The aim...... of this study was to gain insight into the substrate specificity of previously uncharacterized transporters of Salmonella Typhi to identify their role in the development of multidrug resistance. S. Typhi genes encoding putative members of the major facilitator superfamily were cloned and expressed in the drug......-hypersensitive Escherichia coli strain KAM42, and tested for transport of 25 antibacterial compounds, including representative antibiotics of various classes, antiseptics, dyes and detergents. Of the 15 tested putative transporters, STY0901, STY2458 and STY4874 exhibited a drug-resistance phenotype. Among these, STY4874...

  4. Evidence for Resistance Training as a Treatment Therapy in Obesity

    Directory of Open Access Journals (Sweden)

    Barbara Strasser

    2011-01-01

    Full Text Available Over the last decade, investigators have paid increasing attention to the effects of resistance training (RT on several metabolic syndrome variables. Evidence suggests that skeletal muscle is responsible for up to 40% of individuals' total body weight and may be influential in modifying metabolic risk factors via muscle mass development. Due to the metabolic consequences of reduced muscle mass, it is understood that normal aging and/or decreased physical activity may lead to a higher prevalence of metabolic disorders. The purpose of this review is to (1 evaluate the potential clinical effectiveness and biological mechanisms of RT in the treatment of obesity and (2 provide up-to-date evidence relating to the impact of RT in reducing major cardiovascular disease risk factors (including dyslipidaemia and type 2 diabetes. A further aim of this paper is to provide clinicians with recommendations for facilitating the use of RT as therapy in obesity and obesity-related metabolic disorders.

  5. mtct regimen choice, drug resistance and the treatment of hiv

    African Journals Online (AJOL)

    risk of transmission is highest during labour and delivery, ... will have a major impact on controlling perinatally acquired HIV infection. ... could result in the development of drug resistance with potential .... dosing, pharmacokinetics and safety.

  6. Quantitative disease resistance: to better understand parasite-mediated selection on major histocompatibility complex.

    Science.gov (United States)

    Westerdahl, Helena; Asghar, Muhammad; Hasselquist, Dennis; Bensch, Staffan

    2012-02-07

    We outline a descriptive framework of how candidate alleles of the immune system associate with infectious diseases in natural populations of animals. Three kinds of alleles can be separated when both prevalence of infection and infection intensity are measured--qualitative disease resistance, quantitative disease resistance and susceptibility alleles. Our descriptive framework demonstrates why alleles for quantitative resistance and susceptibility cannot be separated based on prevalence data alone, but are distinguishable on infection intensity. We then present a case study to evaluate a previous finding of a positive association between prevalence of a severe avian malaria infection (GRW2, Plasmodium ashfordi) and a major histocompatibility complex (MHC) class I allele (B4b) in great reed warblers Acrocephalus arundinaceus. Using the same dataset, we find that individuals with allele B4b have lower GRW2 infection intensities than individuals without this allele. Therefore, allele B4b provides quantitative resistance rather than increasing susceptibility to infection. This implies that birds carrying B4b can mount an immune response that suppresses the acute-phase GRW2 infection, while birds without this allele cannot and may die. We argue that it is important to determine whether MHC alleles related to infections are advantageous (quantitative and qualitative resistance) or disadvantageous (susceptibility) to obtain a more complete picture of pathogen-mediated balancing selection.

  7. The improvement of rice varieties for major pest and diseases resistance

    International Nuclear Information System (INIS)

    Sahi, I.; Silitonga, T.S.

    1988-01-01

    Since 1971, the rice breeding program in Indonesia has developed on intensive program to improve varieties for yield potential, resistancy to major pests and diseases, early maturity good grain and eating quality. In recent years, the attacks of insects and diseases are very severe in rice cultivation in Asia. Much of the losses were due to acontinuous planting or certain varieties. Between 1966 and 1973 tungro occured in epidemic proportions on separate occasions in Indonesia, Thailand, Nort East India, Bangladesh, and Philippine. Since 1973, investation of brown planthopper and green leafhopper several damaged rice crop in most parts of Indonesia. Presently, rice improvement are directed to develop high yielding rice varieties that are resistant to brown planthopper, ragged stunt virus, blast, green leafhopper, and gallmidge. Screening for pests and diseases are conducted in the laboratory as well as in the field. The adoption of those improved varieties by farmers has contributed greatly in our efforts to attain self sufficiency in rice production in Indonesia. GH 147 -M-40 krad-Pn-89 (irradiated Barito) showed resistant to brown planthopper biotype 1 and 2 and moderately resistant to biotype 3. Napa 40 krad-St-12 has resistant reaction to blast. (authors). 4 refs, 8 tabs

  8. Expression Analysis of Multiple Genes May Involve in Antimony Resistance among Leishmania major Clinical Isolates from Fars Province, Central Iran

    Directory of Open Access Journals (Sweden)

    Nafiseh GHOBAKHLOO

    2016-10-01

    Full Text Available Background: Treatment of Cutaneous Leishmaniasis (CL is being faced with serious difficulties in Fars Province, due to emerging of resistance against meglumine antimonite (Glucantime®. In this context, determining some biomarkers for drug sensitivity monitoring seems to be highly essential. Different studies have been carried out to decipher the genes might be involved in antimony resistant phenotype in Leishmania spp. Here, we selected three genes: AQP (as drug transporter, TDR-1-1(as drug activator, and γ-GCS (inducing reduction environment for comparative expression analysis on clinical resistant and sensitive isolates of L. major.Methods: The clinical isolates of L. major were collected from CL patients referred to Valfajr Health Center, Shiraz from Oct 2011 to Feb 2012. The susceptibility test was performed to confirm drug sensitivity of strains in vitro as well. Then, the gene expression analysis was performed by quantitative real-time PCR using SYBR® Green.Results: By comparison of expression level between strains, up regulation of γ-GCS gene and down regulation of AQP gene were observed in resistant strains compared to the sensitive isolates; however, down regulation of AQP was not statistically specific. Analysis of TDR-1-1 gene unexpectedly showed a high level of expression in the non-responsive cases.Conclusion: The γ-GCS, at least, can be considered as a suitable molecular marker for screening antimony sensitivity in clinical isolates, although AQP and TDR-1-1gene seem not to be reliable resistant markers. 

  9. Resistant Hypertension : consequences and treatment options

    NARCIS (Netherlands)

    de Beus, E.

    2017-01-01

    Resistant hypertension, uncontrolled blood pressure despite use of ≥3 antihypertensives including a diuretic or use of ≥4 antihypertensives regardless of blood pressure (BP), was studied. In this thesis, 1/3 of patients with chronic kidney disease, including kidney transplant patients, is shown to

  10. Common Secondary Causes of Resistant Hypertension and Rational for Treatment

    OpenAIRE

    Faselis, Charles; Doumas, Michael; Papademetriou, Vasilios

    2011-01-01

    Resistant hypertension is defined as uncontrolled blood pressure despite the use of three antihypertensive drugs, including a diuretic, in optimal doses. Treatment resistance can be attributed to poor adherence to antihypertensive drugs, excessive salt intake, physician inertia, inappropriate or inadequate medication, and secondary hypertension. Drug-induced hypertension, obstructive sleep apnoea, primary aldosteronism, and chronic kidney disease represent the most common secondary causes of ...

  11. Characterization of a Novel Endoplasmic Reticulum Protein Involved in Tubercidin Resistance in Leishmania major.

    Directory of Open Access Journals (Sweden)

    Juliana Ide Aoki

    2016-09-01

    Full Text Available Tubercidin (TUB is a toxic adenosine analog with potential antiparasitic activity against Leishmania, with mechanism of action and resistance that are not completely understood. For understanding the mechanisms of action and identifying the potential metabolic pathways affected by this drug, we employed in this study an overexpression/selection approach using TUB for the identification of potential targets, as well as, drug resistance genes in L. major. Although, TUB is toxic to the mammalian host, these findings can provide evidences for a rational drug design based on purine pathway against leishmaniasis.After transfection of a cosmid genomic library into L. major Friedlin (LmjF parasites and application of the overexpression/selection method, we identified two cosmids (cosTUB1 and cosTU2 containing two different loci capable of conferring significant levels of TUB resistance. In the cosTUB1 contained a gene encoding NUPM1-like protein, which has been previously described as associated with TUB resistance in L. amazonensis. In the cosTUB2 we identified and characterized a gene encoding a 63 kDa protein that we denoted as tubercidin-resistance protein (TRP. Functional analysis revealed that the transfectants were less susceptible to TUB than LmjF parasites or those transfected with the control vector. In addition, the trp mRNA and protein levels in cosTUB2 transfectants were higher than LmjF. TRP immunolocalization revealed that it was co-localized to the endoplasmic reticulum (ER, a cellular compartment with many functions. In silico predictions indicated that TRP contains only a hypothetical transmembrane domain. Thus, it is likely that TRP is a lumen protein involved in multidrug efflux transport that may be involved in the purine metabolic pathway.This study demonstrated for the first time that TRP is associated with TUB resistance in Leishmania. The next challenge is to determine how TRP mediates TUB resistance and whether purine

  12. Characterization of a Novel Endoplasmic Reticulum Protein Involved in Tubercidin Resistance in Leishmania major.

    Science.gov (United States)

    Aoki, Juliana Ide; Coelho, Adriano Cappellazzo; Muxel, Sandra Marcia; Zampieri, Ricardo Andrade; Sanchez, Eduardo Milton Ramos; Nerland, Audun Helge; Floeter-Winter, Lucile Maria; Cotrim, Paulo Cesar

    2016-09-01

    Tubercidin (TUB) is a toxic adenosine analog with potential antiparasitic activity against Leishmania, with mechanism of action and resistance that are not completely understood. For understanding the mechanisms of action and identifying the potential metabolic pathways affected by this drug, we employed in this study an overexpression/selection approach using TUB for the identification of potential targets, as well as, drug resistance genes in L. major. Although, TUB is toxic to the mammalian host, these findings can provide evidences for a rational drug design based on purine pathway against leishmaniasis. After transfection of a cosmid genomic library into L. major Friedlin (LmjF) parasites and application of the overexpression/selection method, we identified two cosmids (cosTUB1 and cosTU2) containing two different loci capable of conferring significant levels of TUB resistance. In the cosTUB1 contained a gene encoding NUPM1-like protein, which has been previously described as associated with TUB resistance in L. amazonensis. In the cosTUB2 we identified and characterized a gene encoding a 63 kDa protein that we denoted as tubercidin-resistance protein (TRP). Functional analysis revealed that the transfectants were less susceptible to TUB than LmjF parasites or those transfected with the control vector. In addition, the trp mRNA and protein levels in cosTUB2 transfectants were higher than LmjF. TRP immunolocalization revealed that it was co-localized to the endoplasmic reticulum (ER), a cellular compartment with many functions. In silico predictions indicated that TRP contains only a hypothetical transmembrane domain. Thus, it is likely that TRP is a lumen protein involved in multidrug efflux transport that may be involved in the purine metabolic pathway. This study demonstrated for the first time that TRP is associated with TUB resistance in Leishmania. The next challenge is to determine how TRP mediates TUB resistance and whether purine metabolism is affected

  13. Considering resistance in systematic reviews of antibiotic treatment.

    Science.gov (United States)

    Leibovici, Leonard; Soares-Weiser, Karla; Paul, Mical; Goldberg, Elad; Herxheimer, Andrew; Garner, Paul

    2003-10-01

    Microorganisms resistant to antibiotic drugs are a threat to the health and chances of survival of patients. Systematic reviews on antibiotic drugs that ignore the topic of resistance present readers with a skewed view, emphasizing short-term efficacy or effectiveness while ignoring long-term consequences. To examine whether systematic reviews of antibiotic treatment consider resistance; if not, to find out whether data on resistance were reported in the original trials; and based on that, to offer a framework for taking resistance into account in systematic reviews. The Cochrane Database of Systematic Reviews (the Cochrane Library, 2001, issue 2); and MEDLINE, 1996-2000. (i) Systematic reviews or meta-analyses of antimicrobial therapy, published during 1996-2000. (ii) Randomized, controlled trials abstracted in systematic reviews that addressed a topic highly relevant to antibiotic resistance. We examined each systematic review, and each article, to see whether the implications of resistance were discussed; and whether data on resistance were collected. Out of 111 systematic reviews, only 44 (40%) discussed resistance. Ten reviews (9%) planned or performed collection of data on the response of patients with susceptible or resistant isolates. In 22 systematic reviews (20%), collection of data on induction of resistance was planned or performed. The topic of 41 reviews was judged highly relevant to resistance, and these reviews extracted data from 337 articles, out of which we retrieved 279 articles (83%). In 201 (72%) articles, resistance was discussed or data pertaining to it were collected. Ninety-seven articles (35%) gave actual data on resistance of pathogens to the study drugs, 71 articles (25%) data on efficacy of antibiotic drugs in patients with susceptible and resistant pathogens, and 55 articles (20%) provided data on infection or colonization with resistant strains during treatment. Most systematic reviews on antibiotic treatment ignored the issue of

  14. The case for SAR as the major component of a hyperthermia treatment unit

    International Nuclear Information System (INIS)

    Scott, R.S.

    1985-01-01

    A major problem facing clinical hyperthermia is the lack of a useful unit of treatment. Most attempts at a treatment unit have utilized some function of temperature and time. Having accepted the validity of such a hypothetical units, one is faced with the formidable problem of obtaining a three dimensional temperature profile so that thermal dose can be determined. A corollary is the desirability of obtaining uniform temperature in the treatment volume. Various studies suggest that a uniform SAR is a more desirable goal when radiotherapy is to be used in combination with hyperthermia. The synergy between radiation and hyperthermia is maximized in low pH regions of tumor which are presumably also hypoxic. These regions are poorly perfused, likely to heat readily, and are resistant to the cytotoxic effects of radiation alone. On the other hand, well perfused regions of tumor are likely sensitive to radiation, and benefit less from the combination treatment. Other studies have definitely shown that tissue temperatures in the range normally associated with desirable hyperthermia treatment result in severe vascular damage. This damage could be expected to unnecessarily compromise the effectiveness of radiotherapy. Models in the literature can be combined to verify these observations

  15. Assessment of clinical guidelines for continuation treatment in major depression.

    Science.gov (United States)

    Nuijten, M J

    2001-01-01

    The primary objective of this study was to assess the appropriateness of the existing Dutch clinical guidelines for the treatment of depression from a health-economic perspective. The existing guidelines recommend continuation treatment for a period up to 9 months. The assessment was based on a Markov model using decision-analytic techniques. For this analysis we defined six mutually exclusive states defined by the existence of depression and type of treatment. The outcomes for the model were defined as: time without depression (TWD), quality-adjusted life years (QALYs), direct medical costs, and cost of lost productivity. The primary perspective of the study was that of the third-party payer, while the secondary perspective was that of the society in 1999. The probabilities of clinical events and therapeutic choices as well as the utilities were based on published literature. The medical resource use related to each state was abstracted from published literature and expert opinion. The associated 1999 unit costs of the used medical resources were derived from official Dutch tariff lists of allowable reimbursements. Indirect costs in this model were based on lost productivity only. The results of the primary analysis showed that the use of the guidelines is not cost-effective. Continuation treatment for a period of 9 months increases the total direct medical costs (NLG 1276 vs. NLG 474), decreases the costs resulting from lost productivity (NLG 304 vs. NLG 909), increases total costs (NLG 1580 vs. NLG 1383) and increases TWD (96.9% vs. 86.4%). However, continuation treatment does not change the utility outcomes (0.60 vs. 0.61 QALYs) for both treatment strategies. Hence continuation treatment is not cost-effective from either a third-party payer perspective or a societal perspective. A scenario analysis showed that an extension of the continuation treatment to maintenance treatment might result in a favorable cost-effectiveness outcome of the treatment guideline. In

  16. Widespread Pyrethroid and DDT Resistance in the Major Malaria Vector Anopheles funestus in East Africa Is Driven by Metabolic Resistance Mechanisms

    Science.gov (United States)

    Mulamba, Charles; Riveron, Jacob M.; Ibrahim, Sulaiman S.; Irving, Helen; Barnes, Kayla G.; Mukwaya, Louis G.; Birungi, Josephine; Wondji, Charles S.

    2014-01-01

    Background Establishing the extent, geographical distribution and mechanisms of insecticide resistance in malaria vectors is a prerequisite for resistance management. Here, we report a widespread distribution of insecticide resistance in the major malaria vector An. funestus across Uganda and western Kenya under the control of metabolic resistance mechanisms. Methodology/Principal Findings Female An. funestus collected throughout Uganda and western Kenya exhibited a Plasmodium infection rate between 4.2 to 10.4%. Widespread resistance against both type I (permethrin) and II (deltamethrin) pyrethroids and DDT was observed across Uganda and western Kenya. All populations remain highly susceptible to carbamate, organophosphate and dieldrin insecticides. Knockdown resistance plays no role in the pyrethroid and DDT resistance as no kdr mutation associated with resistance was detected despite the presence of a F1021C replacement. Additionally, no signature of selection was observed on the sodium channel gene. Synergist assays and qRT-PCR indicated that metabolic resistance plays a major role notably through elevated expression of cytochrome P450s. DDT resistance mechanisms differ from West Africa as the L119F-GSTe2 mutation only explains a small proportion of the genetic variance to DDT resistance. Conclusion The extensive distribution of pyrethroid and DDT resistance in East African An. funestus populations represents a challenge to the control of this vector. However, the observed carbamate and organophosphate susceptibility offers alternative solutions for resistance management. PMID:25333491

  17. Treatment Resistance Mechanisms of Malignant Glioma Tumor Stem Cells

    International Nuclear Information System (INIS)

    Schmalz, Philip G.R.; Shen, Michael J.; Park, John K.

    2011-01-01

    Malignant gliomas are highly lethal because of their resistance to conventional treatments. Recent evidence suggests that a minor subpopulation of cells with stem cell properties reside within these tumors. These tumor stem cells are more resistant to radiation and chemotherapies than their counterpart differentiated tumor cells and may underlie the persistence and recurrence of tumors following treatment. The various mechanisms by which tumor stem cells avoid or repair the damaging effects of cancer therapies are discussed

  18. Transcranial low voltage pulsed electromagnetic fields in patients with treatment-resistant depression

    DEFF Research Database (Denmark)

    Martiny, Klaus Per Juul; Lunde, Marianne; Bech, Per

    2010-01-01

    BACKGROUND: Approximately 30% of patients with depression are resistant to antidepressant drugs. Repetitive transcranial magnetic stimulation (rTMS) has been found effective in combination with antidepressants in this patient group. The aim of this study was to evaluate the antidepressant effect...... of a new principle using low-intensity transcranially applied pulsed electromagnetic fields (T-PEMF) in combination with antidepressants in patients with treatment-resistant depression. METHODS: This was a sham-controlled double-blind study comparing 5 weeks of active or sham T-PEMF in patients...... with treatment-resistant major depression. The antidepressant treatment, to which patients had been resistant, was unchanged 4 weeks before and during the study period. Weekly assessments were performed using both clinician-rated and patient-rated scales. The T-PEMF equipment was designed as a helmet containing...

  19. Identification of Quantitative Trait Loci for Resistance to RSIVD in Red Sea Bream (Pagrus major).

    Science.gov (United States)

    Sawayama, Eitaro; Tanizawa, Shiho; Kitamura, Shin-Ichi; Nakayama, Kei; Ohta, Kohei; Ozaki, Akiyuki; Takagi, Motohiro

    2017-12-01

    Red sea bream iridoviral disease (RSIVD) is a major viral disease in red sea bream farming in Japan. Previously, we identified one candidate male individual of red sea bream that was significantly associated with convalescent individuals after RSIVD. The purpose of this study is to identify the quantitative trait loci (QTL) linked to the RSIVD-resistant trait for future marker-assisted selection (MAS). Two test families were developed using the candidate male in 2014 (Fam-2014) and 2015 (Fam-2015). These test families were challenged with RSIV, and phenotypes were evaluated. Then, de novo genome sequences of red sea bream were obtained through next-generation sequencing, and microsatellite markers were searched and selected for linkage map construction. One immune-related gene, MHC class IIβ, was also used for linkage map construction. Of the microsatellite markers searched, 148 and 197 were mapped on 23 and 27 linkage groups in the female and male linkage maps, respectively, covering approximately 65% of genomes in both sexes. One QTL linked to an RSIVD-resistant trait was found in linkage group 2 of the candidate male in Fam-2014, and the phenotypic variance of the QTL was 31.1%. The QTL was closely linked to MHC class IIβ. Moreover, the QTL observed in Fam-2014 was also significantly linked to an RSIVD-resistant trait in the candidate male of Fam-2015. Our results suggest that the RSIVD-resistant trait in the candidate male was controlled by one major QTL closely linked to the MHC class IIβ gene and could be useful for MAS of red sea bream.

  20. Investigation and Treatment of Fusidic Acid Resistance Among Methicillin-Resistant Staphylococcal Isolates from Egypt.

    Science.gov (United States)

    Abouelfetouh, Alaa; Kassem, Mervat; Naguib, Marwa; El-Nakeeb, Moustafa

    2017-01-01

    Methicillin resistance among staphylococci isolated from patients in northern Egypt has escalated alarmingly in the past decade. Data about the prevalence of fusidic acid (FA) resistance in Egyptian clinical isolates are limited. This work investigates the prevalence and mechanism of FA resistance among 81 methicillin-resistant staphylococcal isolates from major hospitals of Alexandria, Egypt. Some combinations for treating infections due to resistant isolates were studied. Twenty-six isolates (32.1%) were FA resistant (minimum inhibitory concentrations [MICs] = 2-1,024 μg/ml), and fusB and fusC genes coding for FA resistance were detected in 30.77% and 34.62% of the FA-resistant strains, respectively. One highly resistant isolate, S502 (MIC = 1,024 μg/ml), possessed both genes. Plasmid curing resulted in fusB loss and MIC decrease by 16-64 folds. Conjugation caused acquisition of FA resistance among susceptible isolates. Serial passages in subinhibitory FA concentrations produced mutants with increased MIC by 4-32 folds. The combination of FA with rifampin, gentamicin, or ampicillin/sulbactam, in a subinhibitory concentration, was synergistic against the isolates, including serial passage mutants, decreasing number of survivors by an average of 2-4 logs. A relatively moderate rate of FA resistance was detected in Alexandria hospitals. Combination therapy with gentamicin, rifampin, or ampicillin/sulbactam is crucial to preserve the effectiveness of FA.

  1. Patent medicine vendors are major providers antimalaria treatment

    African Journals Online (AJOL)

    management of malaria by this informal sector of healthcare delivery is however ... Methods: Fifty-five patent medicine vendors selected through a multistage sampling ... training of the patent medicine vendors, the overall appropriate treatment ...

  2. Low overlap between carbapenem resistant Pseudomonas aeruginosa genotypes isolated from hospitalized patients and wastewater treatment plants.

    Directory of Open Access Journals (Sweden)

    Andrej Golle

    Full Text Available The variability of carbapenem-resistant Pseudomonas aeruginosa strains (CRPA isolated from urine and respiratory samples in a large microbiological laboratory, serving several health care settings, and from effluents of two wastewater treatment plants (WWTP from the same region was assessed by PFGE typing and by resistance to 10 antibiotics. During the 12-month period altogether 213 carbapenem-resistant P. aeruginosa isolates were cultured and distributed into 65 pulsotypes and ten resistance profiles. For representatives of all 65 pulsotypes 49 different MLSTs were determined. Variability of clinical and environmental strains was comparable, 130 carbapenem-resistant P. aeruginosa obtained from 109 patients were distributed into 38 pulsotypes, while 83 isolates from WWTPs were classified into 31 pulsotypes. Only 9 pulsotypes were shared between two or more settings (hospital or WWTP. Ten MLST were determined for those prevalent pulsotypes, two of them (ST111 and ST235 are among most successful CRPA types worldwide. Clinical and environmental carbapenem-resistant P. aeruginosa strains differed in antibiotic resistance. The highest proportion of clinical isolates was resistant to piperacillin/tazobactam (52.3% and ceftazidime (42.3%. The highest proportion of environmental isolates was resistant to ceftazidime (37.1% and ciprofloxacin (35.5%. The majority of isolates was resistant only to imipenem and/or meropenem. Strains with additional resistances were distributed into nine different patterns. All of them included clinically relevant strains, while environmental strains showed only four additional different patterns.

  3. Psychosocial Treatment Options for Major Depressive Disorder in Older Adults.

    Science.gov (United States)

    Renn, Brenna N; Areán, Patricia A

    2017-03-01

    Late-life depression (LLD) is a public health concern with deleterious effects on overall health, cognition, quality of life, and mortality. Although LLD is relatively common, it is not a normal part of aging and is often under-recognized in older adults. However, psychotherapy is an effective treatment for LLD that aligns with many patients' preferences and can improve health and functioning. This review synthesized the current literature on evidence-based psychotherapies for the treatment of depression in older adults. Findings suggest that active, skills-based psychotherapies (cognitive behavioral therapy [CBT] and problem-solving therapy [PST]) may be more effective for LLD than non-directive, supportive counseling. PST may be particularly relevant for offsetting skill deficit associated with LLD, such as in instances of cognitive impairment (especially executive dysfunction) and disability. Emerging treatments also consider contextual factors to improve treatment delivery, such as personalized care, access, and poverty. Tele-mental health represents one such exciting new way of improving access and uptake of treatment by older adults. Although these strategies hold promise, further investigation via randomized controlled trials and comparative effectiveness are necessary to advance our treatment of LLD. Priority should be given to recruiting and training the geriatric mental health workforce to deliver evidence-based psychosocial interventions for LLD.

  4. Effects of selective serotonin reuptake inhibitor treatment on plasma oxytocin and cortisol in major depressive disorder.

    Science.gov (United States)

    Keating, Charlotte; Dawood, Tye; Barton, David A; Lambert, Gavin W; Tilbrook, Alan J

    2013-04-29

    Oxytocin is known for its capacity to facilitate social bonding, reduce anxiety and for its actions on the stress hypothalamopituitary adrenal (HPA) axis. Since oxytocin can physiologically suppress activity of the HPA axis, clinical applications of this neuropeptide have been proposed in conditions where the function of the HPA axis is dysregulated. One such condition is major depressive disorder (MDD). Dysregulation of the HPA system is the most prominent endocrine change seen with MDD, and normalizing the HPA axis is one of the major targets of recent treatments. The potential clinical application of oxytocin in MDD requires improved understanding of its relationship to the symptoms and underlying pathophysiology of MDD. Previous research has investigated potential correlations between oxytocin and symptoms of MDD, including a link between oxytocin and treatment related symptom reduction. The outcomes of studies investigating whether antidepressive treatment (pharmacological and non-pharmacological) influences oxytocin concentrations in MDD, have produced conflicting outcomes. These outcomes suggest the need for an investigation of the influence of a single treatment class on oxytocin concentrations, to determine whether there is a relationship between oxytocin, the HPA axis (e.g., oxytocin and cortisol) and MDD. Our objective was to measure oxytocin and cortisol in patients with MDD before and following treatment with selective serotonin reuptake inhibitors, SSRI. We sampled blood from arterial plasma. Patients with MDD were studied at the same time twice; pre- and post- 12 weeks treatment, in an unblinded sequential design (clinicaltrials.govNCT00168493). Results did not reveal differences in oxytocin or cortisol concentrations before relative to following SSRI treatment, and there were no significant relationships between oxytocin and cortisol, or these two physiological variables and psychological symptom scores, before or after treatment. These outcomes

  5. Renal sympathetic denervation in the treatment of resistant hypertension.

    Science.gov (United States)

    Sánchez-Álvarez, Catalina; González-Vélez, Miguel; Stilp, Erik; Ward, Charisse; Mena-Hurtado, Carlos

    2014-12-01

    Arterial hypertension (HTN) is a major health problem worldwide. Treatment-resistant hypertension (trHTN) is defined as the failure to achieve target blood pressure despite the concomitant use of maximally tolerated doses of three different antihypertensive medications, including a diuretic. trHTN is associated with considerable morbidity and mortality. Renal sympathetic denervation (RDn) is available and implemented abroad as a strategy for the treatment of trHTN and is currently under clinical investigation in the United States. Selective renal sympathectomy via an endovascular approach effectively decreases renal sympathetic nerve hyperactivity leading to a decrease in blood pressure. The Symplicity catheter, currently under investigation in the United States, is a 6-French compatible system advanced under fluoroscopic guidance via percutaneous access of the common femoral artery to the distal lumen of each of the main renal arteries. Radiofrequency (RF) energy is then applied to the endoluminal surface of the renal arteries via an electrode located at the tip of the catheter. Two clinical trials (Symplicity HTN 1 and Symplicity HTN 2) have shown the efficacy of RDn with a post-procedure decline of 27/17 mmHg at 12 months and 32/12 mmHg at 6 months, respectively, with few minor adverse events. Symplicity HTN-3 study is a, multi-center, prospective, single-blind, randomized, controlled study currently under way and will provide further insights about the safety and efficacy of renal denervation in patients with trHTN.

  6. Reduced dorso-lateral prefrontal cortex in treatment resistant schizophrenia.

    Science.gov (United States)

    Zugman, André; Gadelha, Ary; Assunção, Idaiane; Sato, João; Ota, Vanessa K; Rocha, Deyvis L; Mari, Jair J; Belangero, Sintia I; Bressan, Rodrigo A; Brietzke, Elisa; Jackowski, Andrea P

    2013-08-01

    Treatment resistance affects up to one third of patients with schizophrenia (SCZ). A better understanding of its biological underlying processes could improve treatment. The aim of this study was to compare cortical thickness between non-resistant SCZ (NR-SCZ), treatment-resistant SCZ (TR-SCZ) patients and healthy controls (HC). Structural MRI scans were obtained from 3 groups of individuals: 61 treatment resistant SCZ individuals, 67 non-resistant SCZ and 80 healthy controls. Images were analyzed using cortical surface modelling (implemented in freesurfer package) to identify group differences in cortical thickness. Statistical significant differences were identified using Monte-Carlo simulation method with a corrected p-cluster<0.01. Patients in the TR-SCZ group showed a widespread reduction in cortical thickness in frontal, parietal, temporal and occipital regions bilaterally. NR-SCZ group had reduced cortex in two regions (left superior frontal cortex and left caudal middle frontal cortex). TR-SCZ group also showed decreased thickness in the left dorsolateral prefrontal cortex (DLPFC) when compared with patients from NR-SCZ group. The reduction in cortical thickness in DLPFC indicates a more severe form of the disease or a specific finding for this group. Alterations in this region should be explored as a putative marker for treatment resistance. Prospective studies, with individuals being followed from first episode psychosis until refractoriness is diagnosed, are needed to clarify these hypotheses. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Role of Peripheral Vascular Resistance for the Association Between Major Depression and Cardiovascular Disease

    DEFF Research Database (Denmark)

    Bouzinova, Elena; Wiborg, Ove; Aalkjær, Christian

    2015-01-01

    Major depression and cardiovascular diseases are 2 of the most prevalent health problems in Western society, and an association between them is generally accepted. Although the specific mechanism behind this comorbidity remains to be elucidated, it is clear that it has a complex multifactorial....... The changes in arterial structure, contractile and relaxing functions associated with depression symptoms are discussed, and the role of these abnormalities for the pathology of major depression and cardiovascular diseases are suggested....... character including a number of neuronal, humoral, immune, and circulatory pathways. Depression-associated cardiovascular abnormalities associate with cardiac dysfunctions and with changes in peripheral resistance. Although cardiac dysfunction in association with depression has been studied in detail...

  8. Pharmacodynamic and pharmacokinetic evaluation of buprenorphine + samidorphan for the treatment of major depressive disorder.

    Science.gov (United States)

    Ragguett, Renee-Marie; Rong, Carola; Rosenblat, Joshua D; Ho, Roger C; McIntyre, Roger S

    2018-04-01

    Treatment resistant depression (TRD) represents approximately 20% of all individuals receiving care for major depressive disorder. The opioidergic system is identified as a novel target which hitherto has not been sufficiently investigated in adults with TRD. The combination product buprenorphine + samidorphan is an opioid modulatory agent which has demonstrated replicated evidence of efficacy in TRD without abuse liability. Areas covered: Databases Pubmed, Google Scholar and clinicaltrials.gov were searched from inception through December 2017 for clinical trial information, pharmacokinetics, and pharmacodynamics of buprenorphine + samidorphan. Herein we provide a summary of the available information. Eight clinical trials were identified for inclusion, of the eight trials, five trials had available results and are included in detail in our review. Expert opinion: Buprenorphine + samidorphan has demonstrated efficacy in TRD. Extant evidence surrounding the safety and tolerability profile of buprenorphine + samidorphan does not identify any significant safety concerns. Additional studies are needed in order to assess the long-term safety and efficacy of this product.

  9. Personality, Stressful Life Events, and Treatment Response in Major Depression

    Science.gov (United States)

    Bulmash, Eric; Harkness, Kate L.; Stewart, Jeremy G.; Bagby, R. Michael

    2009-01-01

    The current study examined whether the personality traits of self-criticism or dependency moderated the effect of stressful life events on treatment response. Depressed outpatients (N = 113) were randomized to 16 weeks of cognitive-behavioral therapy, interpersonal psychotherapy, or antidepressant medication (ADM). Stressful life events were…

  10. Antibiotic resistance of Streptococcus pneumoniae in children with acute otitis media treatment failure.

    Science.gov (United States)

    Zielnik-Jurkiewicz, Beata; Bielicka, Anna

    2015-12-01

    The emergence of antibiotic-resistant bacteria is a major cause of treatment failure in children with acute otitis media (AOM). This study aimed to analyze the types of bacterial strains in fluid isolated from the middle ear of children with AOM who did not respond to oral antibiotic treatment. We also determined the antibiotic resistance of the most frequently isolated bacterial strain (Streptococcus pneumoniae) found in these children. This was a prospective study of 157 children with AOM aged from 6 months to 7 years admitted due to unsuccessful oral antibiotic treatment. All children underwent a myringotomy, and samples of the middle ear fluid were collected for bacteriological examination. Positive bacterial cultures were obtained in 104 patients (66.2%), with Streptococcus pneumoniae (39.69%), Haemophilus influenzae (16.03%) Staphylococcus aureus (16.03%), Staphylococcus haemolyticus (6.9%) and Streptococcus pyogenes (5.34%) found most frequently. The majority (65.4%) of S. pneumoniae strains were penicillin-intermediate-resistant or penicillin-resistant, and 67.2% strains of S. pneumoniae were multidrug-resistant. We identified S. pneumoniae as the most frequently isolated pathogen from the middle ear in children with AOM treatment failure and determined that the majority of strains were antibiotic-resistant. We propose that the microbiological identification of bacterial strains and their degree of antibiotic resistance should be performed prior to therapy in order to choose the most appropriate antibiotic therapy for children with AOM treatment failure. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Repetitive transcranial magnetic stimulation for the treatment of major depressive disorder: an evidence-based analysis.

    Science.gov (United States)

    2004-01-01

    This review was conducted to assess the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder (MDD). rTMS is a noninvasive way to stimulate nerve cells in areas of the brain. During rTMS, an electrical current passes through a wire coil placed over the scalp. The current induces a magnetic field that produces an electrical field in the brain that then causes nerve cells to depolarize, resulting in the stimulation or disruption of brain activity. Researchers have investigated rTMS as an option to treat MDD, as an add-on to drug therapy, and, in particular, as an alternative to electroconvulsive therapy (ECT) for patients with treatment-resistant depression. The advantages of rTMS over ECT for patients with severe refractory depression are that general anesthesia is not needed, it is an outpatient procedure, it requires less energy, the simulation is specific and targeted, and convulsion is not required. The advantages of rTMS as an add-on treatment to drug therapy may include hastening of the clinical response when used with antidepressant drugs. The Medical Advisory Secretariat used its standard search strategy to locate international health technology assessments and English-language journal articles published from January 1996 to March 2004. Some early meta-analyses suggested rTMS might be effective for the treatment of MDD (for treatment-resistant MDD and as an add-on treatment to drug therapy for patients not specifically defined as treatment resistant). There were, however, several crucial methodological limitations in the included studies that were not critically assessed. These are discussed below. Recent meta-analyses (including 2 international health technology assessments) have done evidence-based critical analyses of studies that have assessed rTMS for MDD. The 2 most recent health technology assessments (from the Oxford Cochrane Collaboration and the Norwegian Centre for Health Technology

  12. [Improving treatment adherence in kidney transplantation: a major challenge].

    Science.gov (United States)

    Kessler, Michèle

    2014-06-01

    The kidney transplant recipient is faced not only with the perspective of taking immunosuppressive drugs lifelong, but also the possibility of other long-term treatments prescribed for preexisting conditions, complications, or side effects. Proper management, and most importantly patient adherence, can become a complex challenge. Here we recall current definitions and describe methods for measuring treatment adherence, followed by a discussion on the prevalence of non-adherence in kidney transplant recipients, its effect on graft survival, and factors predictive of non-adherence. Ways of improving adherence are examined, leading to the conviction that helping patients take their medications regularly would probably have a greater impact on graft survival than marketing a new immunosuppressive agent. Copyright © 2014 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  13. Treatment of Resistant Idiopathic Hiccups with Pulse Radio ...

    African Journals Online (AJOL)

    2017-09-14

    Sep 14, 2017 ... Our case suggests that administration of gabapentin after pulsed radiofrequency might be effective for the treatment of persistent hiccups. KEYWORDS: Hiccups, persistent, pulse radio frequency. Treatment of Resistant Idiopathic Hiccups with Pulse Radio Frequency on Phrenic Nerve and Gabapentin: A ...

  14. Enhanced transmission of drug-resistant parasites to mosquitoes following drug treatment in rodent malaria.

    Directory of Open Access Journals (Sweden)

    Andrew S Bell

    Full Text Available The evolution of drug resistant Plasmodium parasites is a major challenge to effective malaria control. In theory, competitive interactions between sensitive parasites and resistant parasites within infections are a major determinant of the rate at which parasite evolution undermines drug efficacy. Competitive suppression of resistant parasites in untreated hosts slows the spread of resistance; competitive release following treatment enhances it. Here we report that for the murine model Plasmodium chabaudi, co-infection with drug-sensitive parasites can prevent the transmission of initially rare resistant parasites to mosquitoes. Removal of drug-sensitive parasites following chemotherapy enabled resistant parasites to transmit to mosquitoes as successfully as sensitive parasites in the absence of treatment. We also show that the genetic composition of gametocyte populations in host venous blood accurately reflects the genetic composition of gametocytes taken up by mosquitoes. Our data demonstrate that, at least for this mouse model, aggressive chemotherapy leads to very effective transmission of highly resistant parasites that are present in an infection, the very parasites which undermine the long term efficacy of front-line drugs.

  15. Biologically resistant contaminants, primary treatment with ozone

    Energy Technology Data Exchange (ETDEWEB)

    Echegaray, Diego F. [White Martins Gases Industriais do Nordeste S.A., Salvador, BA (Brazil); Olivieri, Nadja F. [White Martins Gases Industriais S.A., Cordovil, RJ (Brazil)

    1993-12-31

    Organic effluent oxidation tests were conducted in petrochemical companies, in Camacari Petrochemical Complex (Northeast Brazil), to reduce treatment costs and improve the primary treatment efficiency in each industrial process. Ozone achieved 99.96 percent benzene reduction and 100 percent ethyl benzene and toluene reduction. Process efficiency is strongly dependent on the wastewater chemical composition and concentration. For this reason it is necessary to run pilot trials for each specific case. Ozone was obtained feeding commercial oxygen through a corona discharge generator and dissolved in the effluent with a bubble column. Commercial oxygen was used instead of air to increase 250 percent the ozone production, using the same ozone generator. (author). 4 figs., 2 tabs.

  16. Biologically resistant contaminants, primary treatment with ozone

    Energy Technology Data Exchange (ETDEWEB)

    Echegaray, Diego F [White Martins Gases Industriais do Nordeste S.A., Salvador, BA (Brazil); Olivieri, Nadja F [White Martins Gases Industriais S.A., Cordovil, RJ (Brazil)

    1994-12-31

    Organic effluent oxidation tests were conducted in petrochemical companies, in Camacari Petrochemical Complex (Northeast Brazil), to reduce treatment costs and improve the primary treatment efficiency in each industrial process. Ozone achieved 99.96 percent benzene reduction and 100 percent ethyl benzene and toluene reduction. Process efficiency is strongly dependent on the wastewater chemical composition and concentration. For this reason it is necessary to run pilot trials for each specific case. Ozone was obtained feeding commercial oxygen through a corona discharge generator and dissolved in the effluent with a bubble column. Commercial oxygen was used instead of air to increase 250 percent the ozone production, using the same ozone generator. (author). 4 figs., 2 tabs.

  17. Management of treatment-resistant depression.

    Science.gov (United States)

    Keitner, Gabor I; Mansfield, Abigail K

    2012-03-01

    Given the limitations of evidence for treatment options that are consistently effective for TRD and the possibility that TRD is in fact a form of depression that has a low probability of resolving, how can clinicians help patients with TRD? Perhaps the most important conceptual shift that needs to take place before treatment can be helpful is to accept TRD as a chronic illness, an illness similar to many others, one that can be effectively managed but that is not, at our present level of knowledge, likely to be cured. An undue focus on remission or even a 50% diminution of symptoms sets unrealistic goals for both patients and therapists and may lead to overtreatment and demoralization. The focus should be less on eliminating depressive symptoms and more on making sense of and learning to function better in spite of them. It is important to acknowledge the difficult nature of the depressive illness, to remove blame from the patient and clinician for not achieving remission, to set realistic expectations, and to help promote better psychosocial functioning even in the face of persisting symptoms. The critical element when implementing such an approach is a judicious balance between maintaining hope for improvement without setting unrealistic expectations. It is important to reemphasize that following a disease management model with acceptance of the reality of a chronic illness is not nihilistic and does not mean the abandonment of hope for improvement. The first step in treating a patient with TRD is to perform a comprehensive assessment of the patient’s past and current treatment history to ensure that evidence-based treatment trials have in fact been undertaken, and if not, such treatment trials should be implemented. If the patient continues to have significant residual symptoms, it is important to determine the impact is of these symptoms on the patient’s quality of life and ability to function. It is also important to evaluate the factors that may be

  18. Clinical characteristics, drug resistance, and treatment outcomes among tuberculosis patients with diabetes in Peru.

    Science.gov (United States)

    Magee, M J; Bloss, E; Shin, S S; Contreras, C; Huaman, H Arbanil; Ticona, J Calderon; Bayona, J; Bonilla, C; Yagui, M; Jave, O; Cegielski, J P

    2013-06-01

    Diabetes is a risk factor for active tuberculosis (TB). Data are limited regarding the association between diabetes and TB drug resistance and treatment outcomes. We examined characteristics of TB patients with and without diabetes in a Peruvian cohort at high risk for drug-resistant TB. Among TB patients with diabetes (TB-DM), we studied the association between diabetes clinical/management characteristics and TB drug resistance and treatment outcomes. During 2005-2008, adults with suspected TB with respiratory symptoms in Lima, Peru, who received rapid drug susceptibility testing (DST), were prospectively enrolled and followed during treatment. Bivariate and Kaplan-Meier analyses were used to examine the relationships of diabetes characteristics with drug-resistant TB and TB outcomes. Of 1671 adult TB patients enrolled, 186 (11.1%) had diabetes. TB-DM patients were significantly more likely than TB patients without diabetes to be older, have had no previous TB treatment, and to have a body mass index (BMI) >18.5 kg/m(2) (pdiabetes, and 12% and 28%, respectively, among TB-DM patients. Among 149 TB-DM patients with DST results, 104 (69.8%) had drug-susceptible TB and 45 (30.2%) had drug-resistant TB, of whom 29 had multidrug-resistant TB. There was no association between diabetes characteristics and drug-resistant TB. Of 136 TB-DM patients with outcome information, 107 (78.7%) had a favorable TB outcome; active diabetes management was associated with a favorable outcome. Diabetes was common in a cohort of TB patients at high risk for drug-resistant TB. Despite prevalent multidrug-resistant TB among TB-DM patients, the majority had a favorable TB treatment outcome. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  19. Return of the psychedelics: Psilocybin for treatment resistant depression.

    Science.gov (United States)

    Patra, Suravi

    2016-12-01

    Psilocybin, the clinically most researched classic psychedelic has recently been tested for its safety and efficacy in a clinical population of treatment resistant depression. The efficacy of psilocybin in clinical depression previously demonstrated in the elecrophysiologic and neuroimaging findings as also in neuropsychological assessments is further validated by the findings of this rigorously conducted randomized trial. Mechanism of action of psilocybin and efficacy in treatment resistant depression are discussed in this paper. Ethical issues of conducting clinical trials with psychedelics are also discussed with particular emphasis on their relative safety and absence of addiction potential. Implications of these issues for conduct of larger trials for establishing risk benefit ratio in treatment resistant depression are further suggested. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Strategies to Combat Antibiotic Resistance in the Wastewater Treatment Plants

    Directory of Open Access Journals (Sweden)

    Fateme Barancheshme

    2018-01-01

    Full Text Available The main goal of this manuscript is to review different treatment strategies and mechanisms for combating the antibiotic resistant bacteria (ARB and antibiotic resistant genes (ARGs in the wastewater environment. The high amount of antibiotics is released into the wastewater that may promote selection of ARB and ARGs which find their way into natural environments. Emerging microbial pathogens and increasing antibiotic resistance among them is a global public health issue. The propagation and spread of ARB and ARGs in the environment may result in an increase of antibiotic resistant microbial pathogens which is a worldwide environmental and public health concern. A proper treatment of wastewater is essential before its discharge into rivers, lake, or sewage system to prevent the spread of ARB and ARGs into the environment. This review discusses various treatment options applied for combating the spread of ARB and ARGs in wastewater treatment plants (WWTPs. It was reported that low-energy anaerobic–aerobic treatment reactors, constructed wetlands, and disinfection processes have shown good removal efficiencies. Nanomaterials and biochar combined with other treatment methods and coagulation process are very recent strategies regarding ARB and ARGs removal and need more investigation and research. Based on current studies a wide-ranging removal efficiency of ARGs can be achieved depending on the type of genes present and treatment processes used, still, there are gaps that need to be further investigated. In order to find solutions to control dissemination of antibiotic resistance in the environment, it is important to (1 study innovative strategies in large scale and over a long time to reach an actual evaluation, (2 develop risk assessment studies to precisely understand occurrence and abundance of ARB/ARGs so that their potential risks to human health can be determined, and (3 consider operating and environmental factors that affect the

  1. Multistrain models predict sequential multidrug treatment strategies to result in less antimicrobial resistance than combination treatment

    DEFF Research Database (Denmark)

    Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo

    2016-01-01

    generated by a mathematical model of the competitive growth of multiple strains of Escherichia coli.Results: Simulation studies showed that sequential use of tetracycline and ampicillin reduced the level of double resistance, when compared to the combination treatment. The effect of the cycling frequency...... frequency did not play a role in suppressing the growth of resistant strains, but the specific order of the two antimicrobials did. Predictions made from the study could be used to redesign multidrug treatment strategies not only for intramuscular treatment in pigs, but also for other dosing routes.......Background: Combination treatment is increasingly used to fight infections caused by bacteria resistant to two or more antimicrobials. While multiple studies have evaluated treatment strategies to minimize the emergence of resistant strains for single antimicrobial treatment, fewer studies have...

  2. Allelic Variation of Cytochrome P450s Drives Resistance to Bednet Insecticides in a Major Malaria Vector.

    Science.gov (United States)

    Ibrahim, Sulaiman S; Riveron, Jacob M; Bibby, Jaclyn; Irving, Helen; Yunta, Cristina; Paine, Mark J I; Wondji, Charles S

    2015-10-01

    Scale up of Long Lasting Insecticide Nets (LLINs) has massively contributed to reduce malaria mortality across Africa. However, resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness. Deciphering the detailed molecular basis of such resistance and designing diagnostic tools is critical to implement suitable resistance management strategies. Here, we demonstrated that allelic variation in two cytochrome P450 genes is the most important driver of pyrethroid resistance in the major African malaria vector Anopheles funestus and detected key mutations controlling this resistance. An Africa-wide polymorphism analysis of the duplicated genes CYP6P9a and CYP6P9b revealed that both genes are directionally selected with alleles segregating according to resistance phenotypes. Modelling and docking simulations predicted that resistant alleles were better metabolizers of pyrethroids than susceptible alleles. Metabolism assays performed with recombinant enzymes of various alleles confirmed that alleles from resistant mosquitoes had significantly higher activities toward pyrethroids. Additionally, transgenic expression in Drosophila showed that flies expressing resistant alleles of both genes were significantly more resistant to pyrethroids compared with those expressing the susceptible alleles, indicating that allelic variation is the key resistance mechanism. Furthermore, site-directed mutagenesis and functional analyses demonstrated that three amino acid changes (Val109Ile, Asp335Glu and Asn384Ser) from the resistant allele of CYP6P9b were key pyrethroid resistance mutations inducing high metabolic efficiency. The detection of these first DNA markers of metabolic resistance to pyrethroids allows the design of DNA-based diagnostic tools to detect and track resistance associated with bednets scale up, which will improve the design of evidence-based resistance management strategies.

  3. Spread of multidrug-resistant Escherichia coli harboring integron via swine farm waste water treatment plant.

    Science.gov (United States)

    Park, Jin-Hyeong; Kim, Young-Ji; Binn-Kim; Seo, Kun-Ho

    2018-03-01

    Wastewater treatment plants (WWTPs) that release treated wastewater into the environment have emerged as a major threat to public health. In this study, we investigated Escherichia coli load and antibiotic-resistance profiles across different treatment processes at a swine farm WWTP. The frequency of the detection of class 1 and 2 integrons, and their association with antibiotic resistance, were also analyzed. Samples were obtained at each of five sampling sites that represented each processing step within the WWTP. The largest decrease in E. coli load was observed during the anaerobic digestion step (from 4.86 to 2.89log CFU/mL). Isolates resistant to β-lactam antibiotics were efficiently removed after a series of treatment steps, whereas the proportions of isolates resistant to non-β-lactam antibiotics and multidrug-resistant strains were maintained across treatments. The occurrence of integron-positive strains was not significantly different at the various sampling sites (43.4-70%; p>0.05). Of the class 1 integron-positive isolates, 17.9% harbored the integron-associated gene cassettes aadA2, aadA12, aadA22, and dfrA15. To the best of our knowledge, this is the first description of a class 1 integron containing the aadA12 gene cassette from a swine farm and the presence of a class 1 integron containing dfrA15 in E. coli. This suggests that novel antibiotic-resistance gene cassette arrays could be generated in swine farm WWTPs. Moreover, 75% of integron-positive strains were categorized as multidrug resistant, whereas only 15.4% of integron-negative strains were multidrug resistant (pswine farm WWTPs in terms of the spread of antibiotic-resistant bacteria to the aquatic environment. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. A Case of Treatment- resistant Depression and Body Dysmorphic Disorder: The Role of Electroconvulsive Therapy Revisited.

    Science.gov (United States)

    Mahato, Ram S; San Gabriel, Maria Chona P; Longshore, Carrol T; Schnur, David B

    2016-01-01

    Body dysmorphic disorder is a common, often disabling condition, and is frequently comorbid with major depressive disorder. Selective serotonin reuptake inhibitors constitute first line set of somatic interventions but the management of refractory patients remains challenging. Electroconvulsive therapy, an often highly beneficial treatment for medication resistant-depression, is not considered an effective therapeutic alternative for treatment refractory body dysmorphic disorder. Here we present a 50-year-old woman with body dysmorphic disorder and comorbid major depressive disorder who remained incapacitated and suicidal despite several trials with selective serotonin reuptake inhibitors and antipsychotic medication. Depressive and dysmorphic symptoms appeared to resolve with electroconvulsive therapy, and remission was sustained for two months. Electroconvulsive therapy has an important place in the management of treatment- resistant depression associated with body dysmorphic disorder, and, in select cases, may be effective for dysmorphic symptoms as well.

  5. Prevalence, predictors, and outcomes in treatment-resistant hypertension in patients with coronary disease.

    Science.gov (United States)

    Bangalore, Sripal; Fayyad, Rana; Laskey, Rachel; Demicco, David A; Deedwania, Prakash; Kostis, John B; Messerli, Franz H

    2014-01-01

    Increasingly, apparent treatment-resistant hypertension has been recognized. However, much of the prevalence, predictors, and outcomes are largely unknown, especially in patients with coronary artery disease. We evaluated 10,001 patients with coronary artery disease who were enrolled in the Treating to New Targets trial. Apparent treatment-resistant hypertension was defined as blood pressure ≥ 140 mm Hg despite 3 antihypertensive agents or hypertension. In a multivariable model adjusting for baseline differences, the treatment-resistant hypertension group had a 64% increase in primary outcome (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.39-1.94; P hypertension group. In addition, patients with apparent treatment-resistant hypertension had a 71% increase in major coronary event (P hypertension group. Results were largely similar whether the definition of apparent treatment-resistant hypertension was based on a blood pressure ≥ 140 mm Hg despite 3 agents or a blood pressure hypertension is associated with a marked increase in the risk of cardiovascular morbidity and mortality, including an increase in all-cause death. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Refining a major QTL controlling spotted wilt disease resistance in cultivated peanut (Arachis hypogaea L.)and evaluating its contribution to the resistance variations in peanut germplasm

    Science.gov (United States)

    Spotted wilt, caused by tomato spotted wilt virus (TSWV), has been one of major diseases in cultivated peanut grown in the southeastern United States (US) since 1990. Previously a major quantitative trait locus (QTL) controlling spotted wilt disease resistance was mapped to an interval of 2.55 cent...

  7. Mechanisms Underlying the Antidepressant Response and Treatment Resistance

    Directory of Open Access Journals (Sweden)

    Marjorie Rose Levinstein

    2014-06-01

    Full Text Available Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance.

  8. Treatment resistance in urothelial carcinoma: an evolutionary perspective.

    Science.gov (United States)

    Vlachostergios, Panagiotis J; Faltas, Bishoy M

    2018-05-02

    The emergence of treatment-resistant clones is a critical barrier to cure in patients with urothelial carcinoma. Setting the stage for the evolution of resistance, urothelial carcinoma is characterized by extensive mutational heterogeneity, which is detectable even in patients with early stage disease. Chemotherapy and immunotherapy both act as selective pressures that shape the evolutionary trajectory of urothelial carcinoma throughout the course of the disease. A detailed understanding of the dynamics of evolutionary drivers is required for the rational development of curative therapies. Herein, we describe the molecular basis of the clonal evolution of urothelial carcinomas and the use of genomic approaches to predict treatment responses. We discuss various mechanisms of resistance to chemotherapy with a focus on the mutagenic effects of the DNA dC->dU-editing enzymes APOBEC3 family of proteins. We also review the evolutionary mechanisms underlying resistance to immunotherapy, such as the loss of clonal tumour neoantigens. By dissecting treatment resistance through an evolutionary lens, the field will advance towards true precision medicine for urothelial carcinoma.

  9. IGF-1 and Insulin Resistance Are Major Determinants of Common Carotid Artery Thickness in Morbidly Obese Young Patients.

    Science.gov (United States)

    Sirbu, Anca; Nicolae, Horia; Martin, Sorina; Barbu, Carmen; Copaescu, Catalin; Florea, Suzana; Panea, Cristina; Fica, Simona

    2016-03-01

    We assessed the relationship between insulin resistance, serum insulin-like growth factor 1 (IGF-1) levels, and common carotid intima-media thickness (CC-IMT) in morbidly obese young patients. A total of 249 patients (aged 37.9 ± 9.8 years, body mass index [BMI] 45.6 ± 8.3 kg/m(2)) were evaluated (metabolic tests, serum IGF-1 measurements, homeostasis model assessment-insulin resistance [HOMA-IR], and ultrasonographically assessed CC-IMT) in a research program for bariatric surgery candidates. After adjusting for age, gender, BMI, systolic blood pressure, uric acid, antihypertensive and lipid-lowering treatment, metabolic syndrome, and metabolic class, both HOMA-IR and IGF-1 z-score were significantly associated with CC-IMT. These results were confirmed in logistic regression analysis, in which age (β = 1.11, P = .001), gender (β = 3.19, P = .001), HOMA-IR (β = 1.221, P = .005), and IGF-1 z-score (β = 1.734, P = .009) were the only independent determinants of abnormal CC-IMT, presumably modulating the effect of the other risk factors included in the regression. Area under the receiver-operating characteristic curve for the model was 0.841 (confidence interval: 0.776-0.907; P IGF-1 z-score are significantly associated with CC-IMT, independent of other major cardiovascular risk factors. © The Author(s) 2015.

  10. Triiodothyronine addition to paroxetine in the treatment of major depressive disorder

    NARCIS (Netherlands)

    Appelhof, Bente C.; Brouwer, Jantien P.; van Dyck, Richard; Fliers, Eric; Hoogendijk, Witte J. G.; Huyser, Jochanan; Schene, Aart H.; Tijssen, Jan G. P.; Wiersinga, Wilmar M.

    2004-01-01

    There is evidence that thyroid hormone T-3 increases serotonergic neurotransmission. Therefore, T-3 addition to antidepressants may improve treatment response in major depression. In nonrefractory depression, T-3 addition to tricyclic antidepressants indeed accelerates treatment response. Current

  11. Pharmacological Approaches for Treatment-resistant Bipolar Disorder

    Science.gov (United States)

    Poon, Shi Hui; Sim, Kang; Baldessarini, Ross J.

    2015-01-01

    Bipolar disorder is prevalent, with high risks of disability, substance abuse and premature mortality. Treatment responses typically are incomplete, especially for depressive components, so that many cases can be considered “treatment resistant.” We reviewed reports on experimental treatments for such patients: there is a striking paucity of such research, mainly involving small incompletely controlled trials of add-on treatment, and findings remain preliminary. Encouraging results have been reported by adding aripiprazole, bupropion, clozapine, ketamine, memantine, pramipexole, pregabalin, and perhaps tri-iodothyronine in resistant manic or depressive phases. The urgency of incomplete responses in such a severe illness underscores the need for more systematic, simpler, and better controlled studies in more homogeneous samples of patients. PMID:26467409

  12. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up.

    Science.gov (United States)

    Carhart-Harris, R L; Bolstridge, M; Day, C M J; Rucker, J; Watts, R; Erritzoe, D E; Kaelen, M; Giribaldi, B; Bloomfield, M; Pilling, S; Rickard, J A; Forbes, B; Feilding, A; Taylor, D; Curran, H V; Nutt, D J

    2018-02-01

    Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy. Here, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression. Twenty patients (six females) with (mostly) severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart) in a supportive setting. Depressive symptoms were assessed from 1 week to 6 months post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure. Treatment was generally well tolerated. Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen's d = 2.2 at week 1 and 2.3 at week 5, both p psilocybin. Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience. Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort. Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind randomised control trials.

  13. Repetitive Transcranial Magnetic Stimulation for the Treatment of Major Depressive Disorder

    Science.gov (United States)

    2004-01-01

    Executive Summary Objective This review was conducted to assess the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder (MDD). The Technology rTMS is a noninvasive way to stimulate nerve cells in areas of the brain. During rTMS, an electrical current passes through a wire coil placed over the scalp. The current induces a magnetic field that produces an electrical field in the brain that then causes nerve cells to depolarize, resulting in the stimulation or disruption of brain activity. Researchers have investigated rTMS as an option to treat MDD, as an add-on to drug therapy, and, in particular, as an alternative to electroconvulsive therapy (ECT) for patients with treatment-resistant depression. The advantages of rTMS over ECT for patients with severe refractory depression are that general anesthesia is not needed, it is an outpatient procedure, it requires less energy, the simulation is specific and targeted, and convulsion is not required. The advantages of rTMS as an add-on treatment to drug therapy may include hastening of the clinical response when used with antidepressant drugs. Review Strategy The Medical Advisory Secretariat used its standard search strategy to locate international health technology assessments and English-language journal articles published from January 1996 to March 2004. Summary of Findings Some early meta-analyses suggested rTMS might be effective for the treatment of MDD (for treatment-resistant MDD and as an add-on treatment to drug therapy for patients not specifically defined as treatment resistant). There were, however, several crucial methodological limitations in the included studies that were not critically assessed. These are discussed below. Recent meta-analyses (including 2 international health technology assessments) have done evidence-based critical analyses of studies that have assessed rTMS for MDD. The 2 most recent health technology assessments (from the

  14. Increasing trend of metronidazole resistance in the treatment of ...

    African Journals Online (AJOL)

    Helicobacter pylori are gram negative spiral bacteria that colonize the human stomach. Infection with H. pylori is associated with chronic gastritis, peptic ulcer, gastric adenocarcinoma and gastric mucosaassociated lymphoid tissue (MALT) lymphoma. Antibiotic resistance is an ever increasing problem with the treatment of ...

  15. Sofa dermatitis presenting as a chronic treatment resistant dermatitis.

    LENUS (Irish Health Repository)

    Lynch, M

    2010-04-01

    There is now a well publicised increase in cases of sofa dermatitis since 2007. These have been linked to allergic contact sensitization to dimethlylfumarate, a novel contact allergen. We report on a case associated with a two year history of a treatment resistant dermatitis.

  16. Bedaquiline in the multidrug-resistant tuberculosis treatment: Belarus experience

    Directory of Open Access Journals (Sweden)

    Alena Skrahina

    2016-01-01

    Conclusion: Our interim results on safety and effectiveness of bedaquiline-containing regimens in multidrug and extensively drug-resistant tuberculosis (M/XDR-TB patients are encouraging. They will add value to understanding role and place of this new anti-TB drug in M/XDR-TB treatment.

  17. Efflux Pumps Might Not Be the Major Drivers of QAC Resistance in Methicillin-Resistant Staphylococcus aureus.

    Science.gov (United States)

    Jennings, Megan C; Forman, Megan E; Duggan, Stephanie M; Minbiole, Kevin P C; Wuest, William M

    2017-08-17

    Quaternary ammonium compounds (QACs) are commonly used antiseptics that are now known to be subject to bacterial resistance. The prevalence and mechanisms of such resistance, however, remain underexplored. We investigated a variety of QACs, including those with multicationic structures (multiQACs), and the resistance displayed by a variety of Staphylococcus aureus strains with and without genes encoding efflux pumps, the purported main driver of bacterial resistance in MRSA. Through minimum inhibitory concentration (MIC)-, kinetic-, and efflux-based assays, we found that neither the qacR/qacA system present in S. aureus nor another efflux pump system is the main reason for bacterial resistance to QACs. Our findings suggest that membrane composition could be the predominant driver that allows CA-MRSA to withstand the assault of conventional QAC antiseptics. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Phosphine resistance does not confer cross-resistance to sulfuryl fluoride in four major stored grain insect pests.

    Science.gov (United States)

    Jagadeesan, Rajeswaran; Nayak, Manoj K

    2017-07-01

    Susceptibility to phosphine (PH 3 ) and sulfuryl fluoride (SF) and cross-resistance to SF were evaluated in two life stages (eggs and adults) of key grain insect pests, Rhyzopertha dominca (F.), Sitophilus oryzae (L.), Cryptolestes ferrugineus (Stephens), and Tribolium castaneum (Herbst). This study was performed with an aim to integrate SF into phosphine resistance management programmes in Australia. Characterisation of susceptibility and resistance to phosphine in eggs and adults showed that C. ferrugineus was the most tolerant as well as resistant species. Mortality responses of eggs and adults to SF at 25 °C revealed T. castaneum to be the most tolerant species followed by S. oryzae, C. ferrugineus and R. dominica. A high dose range of SF, 50.8-62.2 mg L -1 over 48 h, representing c (concentration) × t (time) products of 2438-2985 gh m -3 , was required for complete control of eggs of T. castaneum, whereas eggs of the least tolerant R. dominca required only 630 gh m -3 for 48 h (13.13 mg L -1 ). Mortality response of eggs and adults of phosphine-resistant strains to SF in all four species confirmed the lack of cross-resistance to SF. Our research concludes that phosphine resistance does not confer cross-resistance to SF in grain insect pests irrespective of the variation in levels of tolerance to SF itself or resistance to phosphine in their egg and adult stages. While our study confirms that SF has potential as a 'phosphine resistance breaker', the observed higher tolerance in eggs stresses the importance of developing SF fumigation protocols with longer exposure periods. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  19. Methotrexate resistance in relation to treatment outcome in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Wojtuszkiewicz, Anna; Peters, Godefridus J; van Woerden, Nicole L

    2015-01-01

    BACKGROUND: Methotrexate (MTX) eradicates leukemic cells by disrupting de novo nucleotide biosynthesis and DNA replication, resulting in cell death. Since its introduction in 1947, MTX-containing chemotherapeutic regimens have proven instrumental in achieving curative effects in acute lymphoblast...... resistant to MTX at diagnosis may allow for tailoring novel treatment strategies to individual leukemia patients....... leukemia (ALL). However, drug resistance phenomena pose major obstacles to efficacious ALL chemotherapy. Moreover, clinically relevant molecular mechanisms underlying chemoresistance remain largely obscure. Several alterations in MTX metabolism, leading to impaired accumulation of this cytotoxic agent...... in tumor cells, have been classified as determinants of MTX resistance. However, the relation between MTX resistance and long-term clinical outcome of ALL has not been shown previously. METHODS: We have collected clinical data for 235 childhood ALL patients, for whom samples taken at the time of diagnosis...

  20. Treatment Options for Carbapenem-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Infections

    Science.gov (United States)

    Viehman, J. Alexander; Nguyen, Minh-Hong; Doi, Yohei

    2014-01-01

    Acinetobacter baumannii is a leading cause of healthcare-associated infections worldwide. Due to various intrinsic and acquired mechanisms of resistance, most β-lactam agents are not effective against many strains, and carbapenems have played an important role in therapy. Recent trends show many infections are caused by carbapenem-resistant, or even extensively drug-resistant (XDR) strains, for which effective therapy is not well established. Evidence to date suggests that colistin constitutes the backbone of therapy, but the unique pharmacokinetic properties of colistin have led many to suggest the use of combination antimicrobial therapy. However, the combination of agents and dosing regimens that delivers the best clinical efficacy while minimizing toxicity is yet to be defined. Carbapenems, sulbactam, rifampin and tigecycline have been the most studied in the context of combination therapy. Most data regarding therapy for invasive, resistant A. baumannii infections come from uncontrolled case series and retrospective analyses, though some clinical trials have been completed and others are underway. Early institution of appropriate antimicrobial therapy is shown to consistently improve survival of patients with carbapenem-resistant and XDR A. baumannii infection, but the choice of empiric therapy in these infections remains an open question. This review summarizes the most current knowledge regarding the epidemiology, mechanisms of resistance, and treatment considerations of carbapenem-resistant and XDR A. baumannii. PMID:25091170

  1. Herpesvirus infections in immunocompromised patients : treatment, treatment failure and antiviral resistance

    NARCIS (Netherlands)

    Beek, Martha Trijntje van der

    2012-01-01

    The research described in this thesis aims to study determinants of the course and outcome of treatment of herpesvirus infections in immunocompromised patients. Both viral factors, such as antiviral resistance, and patient factors, including immunological parameters, were investigated. Techniques to

  2. Multistrain models predict sequential multidrug treatment strategies to result in less antimicrobial resistance than combination treatment

    DEFF Research Database (Denmark)

    Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo

    2016-01-01

    Background: Combination treatment is increasingly used to fight infections caused by bacteria resistant to two or more antimicrobials. While multiple studies have evaluated treatment strategies to minimize the emergence of resistant strains for single antimicrobial treatment, fewer studies have...... the sensitive fraction of the commensal flora.Growth parameters for competing bacterial strains were estimated from the combined in vitro pharmacodynamic effect of two antimicrobials using the relationship between concentration and net bacterial growth rate. Predictions of in vivo bacterial growth were...... (how frequently antibiotics are alternated in a sequential treatment) of the two drugs was dependent upon the order in which the two drugs were used.Conclusion: Sequential treatment was more effective in preventing the growth of resistant strains when compared to the combination treatment. The cycling...

  3. HIV-1 integrase resistance among antiretroviral treatment naive and experienced patients from Northwestern Poland

    Directory of Open Access Journals (Sweden)

    Parczewski Miłosz

    2012-12-01

    Full Text Available Abstract Background HIV integrase inhibitor use is limited by low genetic barrier to resistance and possible cross-resistance among representatives of this class of antiretrovirals. The aim of this study was to analyse integrase sequence variability among antiretroviral treatment naive and experienced patients with no prior integrase inhibitor (InI exposure and investigate development of the InI drug resistance mutations following the virologic failure of the raltegravir containing regimen. Methods Sequencing of HIV-1 integrase region from plasma samples of 80 integrase treatment naive patients and serial samples from 12 patients with observed virologic failure on raltegravir containing treatment whenever plasma vireamia exceeded >50 copies/ml was performed. Drug resistance mutations were called with Stanford DB database and grouped into major and minor variants. For subtyping bootstrapped phylogenetic analysis was used; Bayesian Monte Carlo Marcov Chain (MCMC model was implemented to infer on the phylogenetic relationships between the serial sequences from patients failing on raltegravir. Results Majority of the integrase region sequences were classified as subtype B; the remaining ones being subtype D, C, G, as well as CRF01_AE , CRF02_AG and CRF13_cpx recombinants. No major integrase drug resistance mutations have been observed in InI-treatment naive patients. In 30 (38.5% cases polymorphic variation with predominance of the E157Q mutation was observed. This mutation was more common among subtype B (26 cases, 54.2% than non-B sequences (5 cases, 16.7%, p=0.00099, OR: 5.91 (95% CI:1.77-22.63]. Other variants included L68V, L74IL, T97A, E138D, V151I, R263K. Among 12 (26.1% raltegravir treated patients treatment failure was observed; major InI drug resistance mutations (G140S, Q148H and N155H, V151I, E92EQ, V151I, G163R were noted in four of these cases (8.3% of the total InI-treated patients. Time to the development of drug resistance ranged

  4. Genetic mapping of a major dominant gene for resistance to Ralstonia solanacearum in eggplant

    OpenAIRE

    Lebeau, A.; Gouy, M.; Daunay, Marie Christine; Wicker, E.; Chiroleu, F.; Prior, P.; Frary, Anne; Dintinger, J.

    2013-01-01

    Resistance of eggplant against Ralstonia solanacearum phylotype I strains was assessed in a F6 population of recombinant inbred lines (RILs) derived from a intra-specific cross between S. melongena MM738 (susceptible) and AG91-25 (resistant). Resistance traits were determined as disease score, percentage of wilted plants, and stem-based bacterial colonization index, as assessed in greenhouse experiments conducted in Réunion Island, France. The AG91-25 resistance was highly efficient toward st...

  5. Antibiotic Resistant Bacteria And Their Associated Resistance Genes in a Conventional Municipal Wastewater Treatment Plant

    KAUST Repository

    Aljassim, Nada I.

    2013-12-01

    With water scarcity as a pressing issue in Saudi Arabia and other Middle Eastern countries, the treatment and reuse of municipal wastewater is increasingly being used as an alternative water source to supplement country water needs. Standards are in place to ensure a safe treated wastewater quality, however they do not regulate pathogenic bacteria and emerging contaminants. Information is lacking on the levels of risk to public health associated with these factors, the efficiency of conventional treatment strategies in removing them, and on wastewater treatment in Saudi Arabia in general. In this study, a municipal wastewater treatment plant in Saudi Arabia is investigated to assess the efficiency of conventional treatment in meeting regulations and removing pathogens and emerging contaminants. The study found pathogenic bacterial genera, antibiotic resistance genes and antibiotic resistant bacteria, many of which were multi-resistant in plant discharges. It was found that although the treatments are able to meet traditional quality guidelines, there remains a risk from the discussed contaminants with wastewater reuse. A deeper understanding of this risk, and suggestions for more thorough guidelines and monitoring are needed.

  6. INFORMATION MODEL OF MAJOR DEPRESSION TREATMENT COST - RELEVANCE OF QUALITY MANAGEMENT OF HEALTH SYSTEM

    Directory of Open Access Journals (Sweden)

    Danijela Tadić

    2010-09-01

    Full Text Available This paper develops multirelational data base for major depression costs. It lists how data are collected and stored into the fact base and dimension base. Uncertain data is described linguistically and modelled by fuzzy sets. Linguistic expressions are stored in dimension base. Models of major depression treatment costs are developed for each patient and all population. On the basis of this model and multirelational data base MD-OLAP a model for major depression treatment costs is developed.

  7. Fasting: a major limitation for resistance exercise training effects in rodents.

    Science.gov (United States)

    das Neves, W; de Oliveira, L F; da Silva, R P; Alves, C R R; Lancha, A H

    2017-11-17

    Protocols that mimic resistance exercise training (RET) in rodents present several limitations, one of them being the electrical stimulus, which is beyond the physiological context observed in humans. Recently, our group developed a conditioning system device that does not use electric shock to stimulate rats, but includes fasting periods before each RET session. The current study was designed to test whether cumulative fasting periods have some influence on skeletal muscle mass and function. Three sets of male Wistar rats were used in the current study. The first set of rats was submitted to a RET protocol without food restriction. However, rats were not able to perform exercise properly. The second and third sets were then randomly assigned into three experimental groups: 1) untrained control rats, 2) untrained rats submitted to fasting periods, and 3) rats submitted to RET including fasting periods before each RET session. While the second set of rats performed a short RET protocol (i.e., an adaptation protocol for 3 weeks), the third set of rats performed a longer RET protocol including overload (i.e., 8 weeks). After the short-term protocol, cumulative fasting periods promoted loss of weight (P0.05 for all). Despite no effects on EDL mass, soleus muscle displayed significant atrophy in the fasting experimental groups (Pfasting is a major limitation for RET in rats.

  8. Fasting: a major limitation for resistance exercise training effects in rodents

    Directory of Open Access Journals (Sweden)

    W. das Neves

    2017-11-01

    Full Text Available Protocols that mimic resistance exercise training (RET in rodents present several limitations, one of them being the electrical stimulus, which is beyond the physiological context observed in humans. Recently, our group developed a conditioning system device that does not use electric shock to stimulate rats, but includes fasting periods before each RET session. The current study was designed to test whether cumulative fasting periods have some influence on skeletal muscle mass and function. Three sets of male Wistar rats were used in the current study. The first set of rats was submitted to a RET protocol without food restriction. However, rats were not able to perform exercise properly. The second and third sets were then randomly assigned into three experimental groups: 1 untrained control rats, 2 untrained rats submitted to fasting periods, and 3 rats submitted to RET including fasting periods before each RET session. While the second set of rats performed a short RET protocol (i.e., an adaptation protocol for 3 weeks, the third set of rats performed a longer RET protocol including overload (i.e., 8 weeks. After the short-term protocol, cumulative fasting periods promoted loss of weight (P0.05 for all. Despite no effects on EDL mass, soleus muscle displayed significant atrophy in the fasting experimental groups (P<0.01. Altogether, these data indicate that fasting is a major limitation for RET in rats.

  9. Renal denervation in moderate treatment-resistant hypertension.

    Science.gov (United States)

    Ott, Christian; Mahfoud, Felix; Schmid, Axel; Ditting, Tilmann; Sobotka, Paul A; Veelken, Roland; Spies, Aline; Ukena, Christian; Laufs, Ulrich; Uder, Michael; Böhm, Michael; Schmieder, Roland E

    2013-11-12

    This study sought to investigate the effect of renal denervation (RDN) in patients with treatment-resistant hypertension according to the established definition (Joint National Committee VII and European Society of Hypertension/European Society of Cardiology guidelines), that is, office blood pressure (BP) ≥140/90 mm Hg (with at least three antihypertensive drugs, including a diuretic, in adequate doses) and confirmed by 24-h ambulatory BP monitoring (ABPM). RDN emerged as an innovative interventional antihypertensive therapy. However, so far, only patients with severe hypertension (systolic BP ≥160 mm Hg or ≥150 mm Hg for patients with type 2 diabetes) have been investigated. In this study, there were 54 patients with moderate treatment-resistant hypertension (office BP ≥140/90 mm Hg and who underwent catheter-based RDN using the Symplicity catheter (Medtronic Inc., Mountain View, California). Patients were treated with 5.1 ± 1.4 antihypertensive drugs on average. Office BP was significantly reduced by 13/7 mm Hg 6 months after RDN (systolic: 151 ± 6 mm Hg vs. 138 ± 21 mm Hg, p who underwent ABPM 6 months after treatment, there was a reduction in average 24-h ABPM by 14/7 mm Hg (systolic: 150 ± 16 mm Hg vs. 136 ± 16 mm Hg, p hypertension. (Renal Denervation in Treatment Resistant Hypertension; NCT01687725). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  10. Treatment resistance in potentially malignant disorders-'Nature' or 'Nurture'…?

    Science.gov (United States)

    Thomson, P J; Goodson, M L; Smith, D R

    2017-11-01

    Contemporary potentially malignant disorder management is based upon provisional histological diagnosis followed by interventional surgery to excise or ablate 'high-risk' mucosal lesions. Although the majority of patients achieve disease-free status post-treatment, others develop further or persistent disease unresponsive to intervention. A detailed, retrospective clinico-pathological review of treatment resistant potentially malignant lesions, from a 590 patient cohort treated by CO 2 laser surgery and followed for a mean of 7.3 years, was undertaken. Clinical outcome was determined at study census date (31 December 2014). A total of 87 patients (15%) exhibited PMD disease resistant to treatment: 34 (6%) became disease free following further treatment, whilst 53 (9%) had persistent disease despite intervention. Disease-free patients were younger, changed lesion appearance from erythroleukoplakia to leukoplakia (P = .004), developed further lesions at new sites, demonstrated reduction in dysplasia severity with time and required multiple treatments to achieve disease-free status (P = .0005). In contrast, persistent disease patients were older, male, often presented with proliferative verrucous leukoplakia (PVL) on gingival and alveolar sites, displayed less severe dysplasia initially and underwent laser ablation rather than excision (P = .027). Despite clinico-pathological profiling of treatment resistant patients, the precise inter-relationship between the inherent nature of potentially malignant disease and the external influence of treatment intervention remains obscure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Short communication: high prevalence of drug-resistant human immunodeficiency virus type 1 in treatment-naive patients in Greenland

    DEFF Research Database (Denmark)

    Madsen, T.V.; Lohse, N.; Jensen, E.S.

    2008-01-01

    was transmitted. Resistance mutations detected in untreated patients were backed up by the treatment history of index patients in the possible transmission chains and indicated that these drug-resistant variants were in fact transmitted and had not emerged due to unregistered drug intake Udgivelsesdato: 2008/8......A molecular epidemiologic study of HIV-1 in Greenland showed distinct transmission clusters correlated with demographic and behavioral data. Resistance mutations were found in a majority of the pol sequences. The objective of the present study was to estimate prevalence of drug resistance...... in Greenland and identify transmission chains by comparing resistance data with phylogeny and treatment history. Of 60 untreated patients, 15 (25%) had primary resistance mutations. The most prevalent mutations were T69D/N (15%), K70R (15%), and M184V (10%). Four possible transmission chains were identified...

  12. Yeasts acquire resistance secondary to antifungal drug treatment by adaptive mutagenesis.

    Directory of Open Access Journals (Sweden)

    David Quinto-Alemany

    Full Text Available Acquisition of resistance secondary to treatment both by microorganisms and by tumor cells is a major public health concern. Several species of bacteria acquire resistance to various antibiotics through stress-induced responses that have an adaptive mutagenesis effect. So far, adaptive mutagenesis in yeast has only been described when the stress is nutrient deprivation. Here, we hypothesized that adaptive mutagenesis in yeast (Saccharomyces cerevisiae and Candida albicans as model organisms would also take place in response to antifungal agents (5-fluorocytosine or flucytosine, 5-FC, and caspofungin, CSP, giving rise to resistance secondary to treatment with these agents. We have developed a clinically relevant model where both yeasts acquire resistance when exposed to these agents. Stressful lifestyle associated mutation (SLAM experiments show that the adaptive mutation frequencies are 20 (S. cerevisiae -5-FC, 600 (C. albicans -5-FC or 1000 (S. cerevisiae--CSP fold higher than the spontaneous mutation frequency, the experimental data for C. albicans -5-FC being in agreement with the clinical data of acquisition of resistance secondary to treatment. The spectrum of mutations in the S. cerevisiae -5-FC model differs between spontaneous and acquired, indicating that the molecular mechanisms that generate them are different. Remarkably, in the acquired mutations, an ectopic intrachromosomal recombination with an 87% homologous gene takes place with a high frequency. In conclusion, we present here a clinically relevant adaptive mutation model that fulfils the conditions reported previously.

  13. Antimicrobial Resistance Expressed by Neisseria gonorrhoeae: A Major Global Public Health Problem in the 21st Century.

    Science.gov (United States)

    Unemo, Magnus; Del Rio, Carlos; Shafer, William M

    2016-06-01

    Neisseria gonorrhoeae is a strictly human pathogen that is typically transmitted by sexual contact. The associated disease gonorrhea has plagued humankind for thousands of years, with a current estimated incidence of 78 million cases per year. Advances in antimicrobial discovery in the 1920s and 1930s leading to the discovery of sulfonamides and penicillin begun the era of effective antimicrobial treatment of gonorrhea. Unfortunately, the gonococcus developed decreased susceptibility or even resistance to these initially employed antibiotics, a trend that continued over subsequent decades with each new antibiotic that was brought into clinical practice. As this pattern of resistance has continued into the 21st century, there is now reason for great concern, especially in an era when few new antibiotics have prospects for use as treatment of gonorrhea. Here, we review the history of gonorrhea treatment regimens and gonococcal resistance to antibiotics, the mechanisms of resistance, resistance monitoring schemes that exist in different international settings, global responses to the challenge of resistance, and prospects for future treatment regimens in the 21st century.

  14. Mass transfer resistance in ASFF reactors for waste water treatment.

    Science.gov (United States)

    Ettouney, H M; Al-Haddad, A A; Abu-Irhayem, T M

    1996-01-01

    Analysis of mass transfer resistances was performed for an aerated submerged fixed-film reactor (ASFF) for the treatment of waste water containing a mixture of sucrose and ammonia. Both external and internal mass transfer resistances were considered in the analysis, and characterized as a function of feed flow-rate and concentration. Results show that, over a certain operating regime, external mass transfer resistance in the system was greater for sucrose removal than ammonia. This is because the reaction rates for carbon removal were much larger than those of nitrogen. As a result, existence of any form of mass transfer resistance caused by inadequate mixing or diffusion limitations, strongly affects the overall removal rates of carbon more than nitrogen. Effects of the internal måss transfer resistance were virtually non-existent for ammonia removal. This behaviour was found over two orders of magnitude range for the effective diffusivity for ammonia, and one order of magnitude for the film specific surface area. However, over the same parameters' range, it is found that sucrose removal was strongly affected upon lowering its effective diffusivity and increasing the film specific surface area.

  15. Treatment of methicillin-resistant Staphylococcus aureus in Latin America

    Directory of Open Access Journals (Sweden)

    Carlos M Luna

    Full Text Available The global spread of methicillin-resistant Staphylococcus aureus (MRSA means it is now a pathogen of worldwide public health concern. Within Latin America, MRSA is highly prevalent, with the proportion of S. aureus isolates that are methicillin-resistant on the rise, yet resources for managing the infection are limited. While several guidelines exist for the treatment of MRSA infections, many are written for the North American or European setting and need adaptation for use in Latin America. In this article, we aim to emphasize the importance of appropriate treatment of MRSA in the healthcare and community settings of Latin America. We present a summary of the available guidelines and antibiotics, and discuss particular considerations for clinicians treating MRSA in Latin America

  16. Functional Recovery in Major Depressive Disorder: Providing Early Optimal Treatment for the Individual Patient

    Science.gov (United States)

    Katzman, Martin A; Habert, Jeffrey; McIntosh, Diane; MacQueen, Glenda M; Milev, Roumen V; McIntyre, Roger S; Blier, Pierre

    2018-01-01

    Abstract Major depressive disorder is an often chronic and recurring illness. Left untreated, major depressive disorder may result in progressive alterations in brain morphometry and circuit function. Recent findings, however, suggest that pharmacotherapy may halt and possibly reverse those effects. These findings, together with evidence that a delay in treatment is associated with poorer clinical outcomes, underscore the urgency of rapidly treating depression to full recovery. Early optimized treatment, using measurement-based care and customizing treatment to the individual patient, may afford the best possible outcomes for each patient. The aim of this article is to present recommendations for using a patient-centered approach to rapidly provide optimal pharmacological treatment to patients with major depressive disorder. Offering major depressive disorder treatment determined by individual patient characteristics (e.g., predominant symptoms, medical history, comorbidities), patient preferences and expectations, and, critically, their own definition of wellness provides the best opportunity for full functional recovery. PMID:29024974

  17. Anhedonia Predicts Poorer Recovery among Youth with Selective Serotonin Reuptake Inhibitor Treatment-Resistant Depression

    Science.gov (United States)

    McMakin, Dana L.; Olino, Thomas M.; Porta, Giovanna; Dietz, Laura J.; Emslie, Graham; Clarke, Gregory; Wagner, Karen Dineen; Asarnow, Joan R.; Ryan, Neal D.; Birmaher, Boris; Shamseddeen, Wael; Mayes, Taryn; Kennard, Betsy; Spirito, Anthony; Keller, Martin; Lynch, Frances L.; Dickerson, John F.; Brent, David A.

    2012-01-01

    Objective: To identify symptom dimensions of depression that predict recovery among selective serotonin reuptake inhibitor (SSRI) treatment-resistant adolescents undergoing second-step treatment. Method: The Treatment of Resistant Depression in Adolescents (TORDIA) trial included 334 SSRI treatment-resistant youth randomized to a medication…

  18. pH and Heat Resistance of the Major Celery Allergen Api g 1.

    Science.gov (United States)

    Rib-Schmidt, Carina; Riedl, Philipp; Meisinger, Veronika; Schwaben, Luisa; Schulenborg, Thomas; Reuter, Andreas; Schiller, Dirk; Seutter von Loetzen, Christian; Rösch, Paul

    2018-05-25

    The major celery allergen Api g 1 is a member of the pathogenesis-related 10 class protein family. Here we aimed to investigate the impact of heat and pH on the native protein conformation required for Immunoglobulin E (IgE) recognition. Spectroscopic methods, MS and IgE binding analyses were used to study the effects of pH and thermal treatment on Api g 1.0101. Heat processing results in a loss of the native protein fold via denaturation, oligomerisation and precipitation along with a subsequent reduction of IgE recognition. The induced effects and timescales are strongly pH depended. While Api g 1 refolds partially into an IgE-binding conformation at physiological pH, acidic pH treatment leads to the formation of structurally heat resistant, IgE-reactive oligomers. Thermal processing in the presence of a celery matrix or at pH conditions close to the isoelectric point (pI = 4.63) of Api g 1.0101 results in almost instant precipitation. Our data demonstrate that Api g 1.0101 is not intrinsically susceptible to heat treatment in vitro. However, the pH and the celery matrix strongly influence the stability of Api g 1.0101 and might be the main reasons for the observed temperature lability of this important food allergen. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. Major vault protein (MVP) gene polymorphisms and drug resistance in mesial temporal lobe epilepsy with hippocampal sclerosis.

    Science.gov (United States)

    Balan, Shabeesh; Radhab, Saradalekshmi Koramannil; Radha, Koramannil; Sathyan, Sanish; Vijai, Joseph; Banerjee, Moinak; Radhakrishnan, Kurupath

    2013-09-10

    The human major vault protein (MVP) has been implicated in the development of drug resistance in cancer cells. Over expression of MVP has also been reported in brain tissue samples from antiepileptic drug (AED)-resistant human focal epilepsies. To investigate the relationship between single nucleotide polymorphisms (SNPs) involving the MVP gene and AED-resistance, we compared the distribution of three SNPs in the MVP gene, rs4788187, rs3815824 and rs3815823, among 220 patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) (prototype of AED-resistant epilepsy syndrome), 201 patients with juvenile myoclonic epilepsy (JME) (prototype of AED-responsive epilepsy syndrome) and 213 ethnically matched non-epilepsy controls. All the patients and controls were residents of the South Indian state of Kerala for more than three generations. We did not find any significant difference in allele and genotypic frequencies of the studied SNPs between AED-resistant and AED-responsive cohorts, and between AED-resistant and AED-responsive cohorts independently and pooled together when compared with the controls. We conclude that rs4788187, rs3815824, rs3815823 variants of the MVP gene are associated neither with predisposition for epilepsy nor with AED-resistance in the population that we have studied. Our results suggest the need for further research into the link between MVP and AED-resistance. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Prevalence of drug resistance and importance of viral load measurements in Honduran HIV-infected patients failing antiretroviral treatment.

    Science.gov (United States)

    Murillo, Wendy; de Rivera, I L; Parham, L; Jovel, E; Palou, E; Karlsson, A C; Albert, J

    2010-02-01

    The Honduran HIV/AIDS Program began to scale up access to HIV therapy in 2002. Up to May 2008, more than 6000 patients received combination antiretroviral therapy (cART). As HIV drug resistance is the major obstacle for effective treatment, the purpose of this study was to assess the prevalence of antiretroviral drug resistance in Honduran HIV-1-infected individuals. We collected samples from 138 individuals (97 adults and 41 children) on cART with virological, immunological or clinical signs of treatment failure. HIV-1 pol sequences were obtained using an in-house method. Resistance mutations were identified according to the 2007 International AIDS Society (IAS)-USA list and predicted susceptibility to cART was scored using the ANRS algorithm. Resistance mutations were detected in 112 patients (81%), 74% in adults and 98% in children. Triple-, dual- and single-class drug resistance was documented in 27%, 43% and 11% of the study subjects, respectively. Multiple logistic regression showed that resistance was independently associated with type of treatment failure [virological failure (odds ratio (OR) = 1) vs. immunological failure (OR = 0.11; 95% confidence interval (CI) 0.030-0.43) vs. clinical failure (OR = 0.037; 95% CI 0.0063-0.22)], route of transmission (OR = 42.8; 95% CI 3.73-491), and years on therapy (OR = 1.81; 95% CI 1.11-2.93). The prevalence of antiretroviral resistance was high in Honduran HIV-infected patients with signs of treatment failure. A majority of study subjects showed dual- or triple-class resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Virologically defined treatment failure was a strong predictor of resistance, indicating that viral load testing is needed to correctly identify patients with treatment failure attributable to resistance.

  1. Antimicrobial resistance: the major contribution of poor governance and corruption to this growing problem.

    Science.gov (United States)

    Collignon, Peter; Athukorala, Prema-Chandra; Senanayake, Sanjaya; Khan, Fahad

    2015-01-01

    To determine how important governmental, social, and economic factors are in driving antibiotic resistance compared to the factors usually considered the main driving factors-antibiotic usage and levels of economic development. A retrospective multivariate analysis of the variation of antibiotic resistance in Europe in terms of human antibiotic usage, private health care expenditure, tertiary education, the level of economic advancement (per capita GDP), and quality of governance (corruption). The model was estimated using a panel data set involving 7 common human bloodstream isolates and covering 28 European countries for the period 1998-2010. Only 28% of the total variation in antibiotic resistance among countries is attributable to variation in antibiotic usage. If time effects are included the explanatory power increases to 33%. However when the control of corruption indicator is included as an additional variable, 63% of the total variation in antibiotic resistance is now explained by the regression. The complete multivariate regression only accomplishes an additional 7% in terms of goodness of fit, indicating that corruption is the main socioeconomic factor that explains antibiotic resistance. The income level of a country appeared to have no effect on resistance rates in the multivariate analysis. The estimated impact of corruption was statistically significant (pcorruption indicator is associated with a reduction in antibiotic resistance by approximately 0.7 units. The estimated coefficient of private health expenditure showed that one unit reduction is associated with a 0.2 unit decrease in antibiotic resistance. These findings support the hypothesis that poor governance and corruption contributes to levels of antibiotic resistance and correlate better than antibiotic usage volumes with resistance rates. We conclude that addressing corruption and improving governance will lead to a reduction in antibiotic resistance.

  2. Antimicrobial resistance: the major contribution of poor governance and corruption to this growing problem.

    Directory of Open Access Journals (Sweden)

    Peter Collignon

    Full Text Available To determine how important governmental, social, and economic factors are in driving antibiotic resistance compared to the factors usually considered the main driving factors-antibiotic usage and levels of economic development.A retrospective multivariate analysis of the variation of antibiotic resistance in Europe in terms of human antibiotic usage, private health care expenditure, tertiary education, the level of economic advancement (per capita GDP, and quality of governance (corruption. The model was estimated using a panel data set involving 7 common human bloodstream isolates and covering 28 European countries for the period 1998-2010.Only 28% of the total variation in antibiotic resistance among countries is attributable to variation in antibiotic usage. If time effects are included the explanatory power increases to 33%. However when the control of corruption indicator is included as an additional variable, 63% of the total variation in antibiotic resistance is now explained by the regression. The complete multivariate regression only accomplishes an additional 7% in terms of goodness of fit, indicating that corruption is the main socioeconomic factor that explains antibiotic resistance. The income level of a country appeared to have no effect on resistance rates in the multivariate analysis. The estimated impact of corruption was statistically significant (p< 0.01. The coefficient indicates that an improvement of one unit in the corruption indicator is associated with a reduction in antibiotic resistance by approximately 0.7 units. The estimated coefficient of private health expenditure showed that one unit reduction is associated with a 0.2 unit decrease in antibiotic resistance.These findings support the hypothesis that poor governance and corruption contributes to levels of antibiotic resistance and correlate better than antibiotic usage volumes with resistance rates. We conclude that addressing corruption and improving governance

  3. Overview of treatment of castration-resistant prostate cancer

    International Nuclear Information System (INIS)

    Obertova, J.

    2012-01-01

    Prostatic cancer is a very heterogenic disease. Initial treatment of metastatic disease is androgen deprivation therapy, however upon the time eventually all cases develop castrate resistant disease (CRCP). In CRPC the combination of docetaxel with prednisone is considered to be the gold standard first line therapy with prolongation of overall survival. Until recently there was not standardly defined second line treatment. According to the international guidelines of today cabazitaxel and abirateron is recommended as second line therapy. The objective of this article is to present a review of the therapy of CRPC upon results from randomised phase III clinical trials. (author)

  4. Phenotypic evidence suggests a possible major-gene element to weevil resistance in Sitka spruce

    Science.gov (United States)

    John N. King; René I. Alfaro; Peter Ott; Lara vanAkker

    2012-01-01

    The weevil resistance breeding program against the white pine weevil, Pissodes strobi Peck (Coleoptera: Curculionidae), particularly for Sitka spruce (Picea sitchensis (Bong.) Carr), is arguably one of the most successful pest resistance breeding programs for plantation forest species, and it has done a lot to rehabilitate...

  5. Cuticle thickening associated with pyrethroid resistance in the major malaria vector Anopheles funestus

    Directory of Open Access Journals (Sweden)

    Coetzee M

    2010-08-01

    Full Text Available Abstract Background Malaria in South Africa is primarily transmitted by Anopheles funestus Giles. Resistance to pyrethroid insecticides in An. funestus in northern Kwazulu/Natal, South Africa, and in neighbouring areas of southern Mozambique enabled populations of this species to increase their ranges into areas where pyrethroids were being exclusively used for malaria control. Pyrethroid resistance in southern African An. funestus is primarily conferred by monooxygenase enzyme metabolism. However, selection for this resistance mechanism is likely to have occurred in conjunction with other factors that improve production of the resistance phenotype. A strong candidate is cuticle thickening. This is because thicker cuticles lead to slower rates of insecticide absorption, which is likely to increase the efficiency of metabolic detoxification. Results Measures of mean cuticle thickness in laboratory samples of female An. funestus were obtained using scanning electron microscopy (SEM. These females were drawn from a laboratory colony carrying the pyrethroid resistance phenotype at a stable rate, but not fixed. Prior to cuticle thickness measurements, these samples were characterised as either more or less tolerant to permethrin exposure in one experiment, and either permethrin resistant or susceptible in another experiment. There was a significant and positive correlation between mean cuticle thickness and time to knock down during exposure to permethrin. Mean cuticle thickness was significantly greater in those samples characterised either as more tolerant or resistant to permethrin exposure compared to those characterised as either less tolerant or permethrin susceptible. Further, insecticide susceptible female An. funestus have thicker cuticles than their male counterparts. Conclusion Pyrethroid tolerant or resistant An. funestus females are likely to have thicker cuticles than less tolerant or susceptible females, and females generally have

  6. The effect of multiple blood-feeding on the longevity and insecticide resistant phenotype in the major malaria vector Anopheles arabiensis (Diptera: Culicidae).

    Science.gov (United States)

    Oliver, Shüné V; Brooke, Basil D

    2014-08-23

    Anopheles arabiensis is a major malaria vector in Africa. Adult females are likely to imbibe multiple blood meals during their lifetime. This results in regular exposure to potential toxins and blood-meal induced oxidative stress. Defence responses to these stressors may affect other factors of epidemiological significance, such as insecticide resistance and longevity. The aims of this study were to examine the effect of multiple blood-feeding on insecticide tolerance/resistance with increasing age, to assess the underlying biochemical mechanisms for the responses recorded, and to assess the effect of multiple blood-feeding on the life histories of adult females drawn from insecticide resistant and susceptible laboratory reared An. arabiensis. Laboratory reared An. arabiensis females from an insecticide resistant and an insecticide susceptible colony were offered either a single blood meal or multiple blood meals at 3-day intervals. Their tolerance or resistance to insecticide was then monitored by WHO bioassay four hours post blood-feeding. The biochemical basis of the phenotypic response was assessed by examining the effect of blood on detoxification enzyme activity and the effect of blood-meals on detoxification enzyme activity in ageing mosquitoes. Control cohorts that were not offered any blood meals showed steadily decreasing levels of insecticide tolerance/resistance with age, whereas a single blood meal significantly increased tolerance/resistance primarily at the age of three days. The expression of resistance/tolerance in those cohorts fed multiple blood meals generally showed the least variation with age. These results were consistent following exposure to DDT and pyrethroids but not to malathion. Multiple blood-meals also maintained the DDT and permethrin resistant phenotype, even after treatment females had stopped taking blood-meals. Biochemical analysis suggests that this phenotypic effect in resistant females may be mediated by the maintenance of

  7. Resistance to treatment in gastrointestinal stromal tumours: What radiologists should know

    International Nuclear Information System (INIS)

    Tirumani, S.H.; Jagannathan, J.P.; Hornick, J.L.; Ramaiya, N.H.

    2013-01-01

    Gastrointestinal stromal tumour resistance to treatment with imatinib occurs due to pre-existing or acquired mutations. Computed tomography and positron-emission tomography play an essential role in prompt recognition of resistance to treatment. Primary resistance to treatment, which is encountered in the first 6 months of treatment, is associated with specific mutations. Imaging of these tumours shows no anatomical or metabolic response to treatment. Secondary resistance to treatment, which develops after an initial response, is associated with a variety of mutations acquired after the start of treatment. Imaging findings of secondary resistance are of disease progression

  8. Annotating MYC Status in Treatment-Resistant Metastatic Castration-Resistant Prostate Cancer With Gallium-68 Citrate PET

    Science.gov (United States)

    2017-09-01

    which avidly binds to circulating transferrin) labeled transferrin (Tf) can detect MYC-positive prostate cancer tumors, since the transferrin receptor ...Castration-Resistant Prostate Cancer with Androgen Receptor - Axis Imaging. Journal of nuclear medicine : official publication, Society of Nuclear...AWARD NUMBER: W81XWH-16-1-0469 TITLE: Annotating MYC Status in Treatment-Resistant Metastatic Castration- Resistant Prostate Cancer With

  9. World Health Organization treatment guidelines for drug-resistant tuberculosis, 2016 update.

    Science.gov (United States)

    Falzon, Dennis; Schünemann, Holger J; Harausz, Elizabeth; González-Angulo, Licé; Lienhardt, Christian; Jaramillo, Ernesto; Weyer, Karin

    2017-03-01

    Antimicrobial resistance is a major global concern. Tuberculosis (TB) strains resistant to rifampicin and other TB medicines challenge patient survival and public health. The World Health Organization (WHO) has published treatment guidelines for drug-resistant TB since 1997 and last updated them in 2016 based on reviews of aggregated and individual patient data from published and unpublished studies. An international expert panel formulated recommendations following the GRADE approach. The new WHO guidelines recommend a standardised 9-12 months shorter treatment regimen as first choice in patients with multidrug- or rifampicin-resistant TB (MDR/RR-TB) strains not resistant to fluoroquinolones or second-line injectable agents; resistance to these two classes of core second-line medicines is rapidly detectable with molecular diagnostics also approved by WHO in 2016. The composition of longer regimens for patients ineligible for the shorter regimen was modified. A first-ever meta-analysis of individual paediatric patient data allowed treatment recommendations for childhood MDR/RR-TB to be made. Delamanid is now also recommended in patients aged 6-17 years. Partial lung resection is a recommended option in MDR/RR-TB care. The 2016 revision highlighted the continued shortage of high-quality evidence and implementation research, and reiterated the need for clinical trials and best-practice studies to improve MDR/RR-TB patient treatment outcomes and strengthen policy. The content of this work is copyright of the authors or their employers. Design and branding are copyright ©ERS 2017.

  10. A radioattenuated Leishmania major vaccine markedly increases the resistance of CBA mice to subsequent infection with Leishmania mexicana mexicana

    International Nuclear Information System (INIS)

    Alexander, J.

    1982-01-01

    Vaccinating CBA mice with radioattenuated Leishmania major amastigotes but not with radioattenuated L. mexicana amastigotes rendered them highly resistant to subsequent infection with L. m. mexicana. Unvaccinated CBA mice were highly susceptible to infection with L. m. mexicana producing rapidly growing non-ulcerating cutaneous lesions. Two manifestations of resistance were induced in vaccinated animals depending on the timing of the challenge infection: no lesions appeared at the site of subcutaneous challenge in animals vaccinated four or more weeks previously, while lesions grew rapidly but ulcerated and healed in animals vaccinated less than 3 weeks beforehand. L. major amastigotes were found to be markedly more resistant to γ irradiation than L. m.mexicana amastigotes both as measured by their ability to infect susceptible strains of mice and to transform and multiply as promastigotes in NNN medium. (author)

  11. Distribution and frequency of Bru1, a major brown rust resistance gene, in the sugarcane world collection

    Science.gov (United States)

    Brown rust, caused by Puccinia melanocephala, is an important disease of sugarcane worldwide. Molecular markers for a major brown rust resistance gene, Bru1, were used to screen a total of 1,282 clones in the World Collection of Sugarcane and Related Grasses (WCSRG) to determine the distribution and...

  12. Review of a major epidemic of methicillin-resistant Staphylococcus aureus: The costs of screening and consequences of outbreak management

    NARCIS (Netherlands)

    A. van der Zee (Anneke); W. Hendriks; L.D. Roorda (Lieuwe); J.M. Ossewaarde (Jacobus); J. Buitenwerf (Johannes)

    2013-01-01

    textabstractBackground: A major outbreak of methicillin-resistant Staphylococcus aureus (MRSA) occurred in locations C and Z of our hospital and lasted for several years. It affected 1,230 patients and 153 personnel. Methods: Outbreak management was installed according to the Dutch "search and

  13. Natural variation in partial resistance to Pseudomonas syringae is controlled by two major QTLs in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Laure Perchepied

    Full Text Available BACKGROUND: Low-level, partial resistance is pre-eminent in natural populations, however, the mechanisms underlying this form of resistance are still poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we used the model pathosystem Pseudomonas syringae pv. tomato DC3000 (Pst - Arabidopsis thaliana to study the genetic basis of this form of resistance. Phenotypic analysis of a set of Arabidopsis accessions, based on evaluation of in planta pathogen growth revealed extensive quantitative variation for partial resistance to Pst. It allowed choosing a recombinant inbred line (RIL population derived from a cross between the accessions Bayreuth and Shahdara for quantitative genetic analysis. Experiments performed under two different environmental conditions led to the detection of two major and two minor quantitative trait loci (QTLs governing partial resistance to Pst and called PRP-Ps1 to PRP-Ps4. The two major QTLs, PRP-Ps1 and PRP-Ps2, were confirmed in near isogenic lines (NILs, following the heterogeneous inbred families (HIFs strategy. Analysis of marker gene expression using these HIFs indicated a negative correlation between the induced amount of transcripts of SA-dependent genes PR1, ICS and PR5, and the in planta bacterial growth in the HIF segregating at PRP-Ps2 locus, suggesting an implication of PRP-Ps2 in the activation of SA dependent responses. CONCLUSIONS/SIGNIFICANCE: These results show that variation in partial resistance to Pst in Arabidopsis is governed by relatively few loci, and the validation of two major loci opens the way for their fine mapping and their cloning, which will improve our understanding of the molecular mechanisms underlying partial resistance.

  14. Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections.

    Science.gov (United States)

    Thangamani, Shankar; Younis, Waleed; Seleem, Mohamed N

    2015-06-26

    Novel antimicrobials and new approaches to developing them are urgently needed. Repurposing already-approved drugs with well-characterized toxicology and pharmacology is a novel way to reduce the time, cost, and risk associated with antibiotic innovation. Ebselen, an organoselenium compound, is known to be clinically safe and has a well-known pharmacology profile. It has shown potent bactericidal activity against multidrug-resistant clinical isolates of staphylococcus aureus, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA). We demonstrated that ebselen acts through inhibition of protein synthesis and subsequently inhibited toxin production in MRSA. Additionally, ebselen was remarkably active and significantly reduced established staphylococcal biofilms. The therapeutic efficacy of ebselen was evaluated in a mouse model of staphylococcal skin infections. Ebselen 1% and 2% significantly reduced the bacterial load and the levels of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and monocyte chemo attractant protein-1 (MCP-1) in MRSA USA300 skin lesions. Furthermore, it acts synergistically with traditional antimicrobials. This study provides evidence that ebselen has great potential for topical treatment of MRSA skin infections and lays the foundation for further analysis and development of ebselen as a potential treatment for multidrug-resistant staphylococcal infections.

  15. [Renal denervation a treatment for resistant hypertension: a French experience].

    Science.gov (United States)

    Benamer, H; Mylotte, D; Garcia-Alonso, C; Unterseeh, T; Garot, P; Louvard, Y; Lefevre, T; Morice, M-C

    2013-12-01

    Arterial hypertension is the largest single contributor to global mortality, and is poorly controlled in approximately 50% of patients despite lifestyle and pharmacologic interventions. Randomized clinical trials have demonstrated that catheter-based renal sympathetic denervation reduces blood pressure (BP) in patients with resistant hypertension. We sought to evaluate the efficacy of this novel therapy in "Real World" clinical practice. Consecutive patients with treatment-resistant primary hypertension, as defined as home BP>160 mmHg despite treatment with ≥3 antihypertensive drugs, were selected for denervation following renal artery screening. Ambulatory and home BP monitoring was performed in all patients prior to and following percutaneous renal sympathetic denervation. In total, 35 patients were selected for catheter-based renal sympathetic denervation. The mean age was 63.6 ± 11.7 years, 37.1% were women, 37.1% were diabetic, and 11.4% had renal impairment (GFRdenervation was performed in 33/35 patients (1 renal artery stenosis on angiography [not ablated], 1 patient with renal artery spasm [unilateral denervation]), with an average 5.9 ± 1.6 ablations per renal artery. No procedural complications occurred. At 6 months, blood pressure was 15.5 ± 22.37/87.76 ± 13.97 mmHg (Prenal function was observed. Catheter-based renal denervation is safe and efficacious treatment, which results in significant reductions in blood pressure in patients with treatment-resistant hypertension, stable at 2 years follow-up. These results are applicable to real-world patient populations. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  16. Substance Use and the Treatment of Resistant Depression in Adolescents

    Science.gov (United States)

    Goldstein, Benjamin I.; Shamseddeen, Wael; Spirito, Anthony; Emslie, Graham; Clarke, Greg; Wagner, Karen Dineen; Asarnow, Joan Rosenbaum; Vitiello, Benedetto; Ryan, Neal; Birmaher, Boris; Mayes, Taryn; Onorato, Matthew; Zelazny, Jamie; Brent, David A.

    2009-01-01

    Objective: Despite the known association between substance use disorders and major depressive disorder (MDD) among adolescents, little is known regarding substance use among adolescents with MDD. Method: Youths with MDD who had not improved after an adequate selective serotonin reuptake inhibitor trial (N = 334) were enrolled in the Treatment of…

  17. Antibiotic resistance and trend of urinary pathogens in general outpatients from a major urban city

    Directory of Open Access Journals (Sweden)

    Carlos R. Kiffer

    2007-02-01

    Full Text Available OBJECTIVE: We assessed the antimicrobial resistance patterns of pathogens responsible for urinary tract infections (UTI in outpatients in São Paulo, Brazil, as well as the Escherichia coli antimicrobial resistance trend. MATERIALS AND METHODS: Outpatients urine cultures were collected from January 2000 to December 2003. Statistical analysis considered positive results for one bacterial species with colony count > 100,000 CFU/mL. Stratification was done on age group and gender. Statistical tests used included chi-square and the chi-square test for trend to evaluate differences between susceptibility rates among age groups and ordering in the E. coli resistance rates per year, respectively. RESULTS: There were 37,261 positive results with Enterobacteriaceae isolated in 32,530 (87.3% and Gram-positive cocci in 2,570 (6.9% cultures. E. coli had the highest prevalence (71.6%. Susceptibility tests were performed in 31,716 cultures. E. coli had elevated resistance rates (> 30% to ampicillin, trimethoprim-sulfamethoxazole, and tetracycline. Significant differences between age groups and ordering among years were observed. CONCLUSIONS: The use of trimethoprim-sulfamethoxazole is precluded in the population studied due to elevated resistance rates (> 30% among most prevalent pathogens. Significant resistance rate differences among age groups and years were observed, particularly for fluoroquinolones. Fluoroquinolones should be used with caution. Nitrofurantoin should be used as empirical therapy for primary, non-complicated urinary tract infections.

  18. Influence of heat treatment on corrosive resistance of concrete steels

    International Nuclear Information System (INIS)

    Woldan, A.; Suliga, I.; Kusinski, J.; Jazowy, R.

    1998-01-01

    The reinforcing bars are essential elements of ferro-concrete structures. During the building structure service the reinforcing bars should co-operate with surrounding concrete. Any bonding defects as well as corrosion induced strength reduction may result in construction failure. The reinforcing steel working environment is determined by concrete chemical and phase composition and surrounding environmental properties. The aggressive corrosive activity of the letter implies necessity of effective ways development to protect elements against corrosion. The effect of heat treatment, increased Si content in steel on corrosion resistance of reinforcing steel in concrete was studied in the current work. Corrosion tests and metallographic examinations proved a positive influence of hardening and Si enrichment on corrosion resistance of reinforcing bars in ferro-concrete structures. (author)

  19. Lodging resistant pea line derived after mutagenic treatment

    International Nuclear Information System (INIS)

    Naidenova, N.; Vassilevska-Ivanova, R.

    2006-01-01

    Line 1/502 is a new lodging resistant pea ( Pisum sativum L.) developed for the Bulgarian field pea industry. This line is a direct chlorophyll mutant, which originates after treatment of the initial line, cultivar Auralia, with 150 Gy 60 Co γ - radiation. In regional evaluation trials conducted in Sofia over seven successive seasons 1/502 has revealed improved standing ability that most probably is a result from modification of the architecture of the plants appearing in reduction of plant height. The agronomic and morphological characteristics of the mutant line were reported. The upright plant habit and resistance to lodging is especially beneficial for production of high quality peas because pods are held above the soil surface during crop development and during maturity which aids in keeping the peas clean and free of pathogens that can cause discoloration and rotting. (authors)

  20. Antimicrobial resistance of Escherichia coli isolated in newly-hatched chickens and effect of amoxicillin treatment during their growth.

    Science.gov (United States)

    Jiménez-Belenguer, Ana; Doménech, Eva; Villagrá, Arantxa; Fenollar, Alejandro; Ferrús, Maria Antonia

    2016-08-01

    The use of antimicrobials in food animals is the major determinant for the propagation of resistant bacteria in the animal reservoir. However, other factors may also play a part, and in particular vertical spread between the generations has been suggested to be an important transmission pathway. The objective of this paper was to determine the resistance patterns of Escherichia coli isolated from newly-hatched chickens as well as to study the antibiotic pressure effect when amoxicillin was administered during their growing period. With this aim, meconium from 22 one-day-old Ross chickens was analysed. In addition, during their growth period, amoxicillin treatments at days 7, 21 and 35 were carried out. Results showed a high number of E. coli-resistant strains were isolated from the treated one-day-old chickens, and were the highest for β-lactams group, followed by quinolone and tetracyclines. After treatment with amoxicillin, the highest percentage of resistances were detected for this antibiotic compared to the others analysed, with significant differences in resistance percentages between control and treated broilers detected in relation to ampicillin, cephalothin, streptomycin, kanamycin, gentamicin, chloramphenicol and tetracycline. Differences in resistances to ciprofloxacin and nalidixic acid between control and treated animals were not observed and there was lack of resistance for amikacin and ceftriaxone. These results suggest the possibility of vertical transmission of resistant strains to newly-hatched chicks from parent flocks, and seem to indicate that the treatment with amoxicillin increased the resistance of E. coli to other antibiotics.

  1. Mismatch repair and treatment resistance in ovarian cancer

    International Nuclear Information System (INIS)

    Helleman, Jozien; Staveren, Iris L van; Dinjens, Winand NM; Kuijk, Patricia F van; Ritstier, Kirsten; Ewing, Patricia C; Burg, Maria EL van der; Stoter, Gerrit; Berns, Els MJJ

    2006-01-01

    The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR) inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. We determined, microsatellite instability (MSI) as a marker for MMR inactivation (analysis of BAT25 and BAT26), MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA) and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR) in 75 ovarian carcinomas and eight ovarian cancer cell lines MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation), SKOV3 (no MLH1 mRNA expression) and 2774 (no altered expression of MMR genes). Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response). The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation

  2. Mismatch repair and treatment resistance in ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Helleman, Jozien; Staveren, Iris L van [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Dinjens, Winand NM [Department of Pathology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Kuijk, Patricia F van; Ritstier, Kirsten [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Ewing, Patricia C [Department of Pathology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Burg, Maria EL van der; Stoter, Gerrit [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Berns, Els MJJ [Department of Medical Oncology, Erasmus MC/Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Erasmus MC, Department of Medical Oncology, Josephine Nefkens Institute, Room Be424, P.O. Box 1738, 3000 DR (Netherlands)

    2006-07-31

    The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR) inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. We determined, microsatellite instability (MSI) as a marker for MMR inactivation (analysis of BAT25 and BAT26), MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA) and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR) in 75 ovarian carcinomas and eight ovarian cancer cell lines MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation), SKOV3 (no MLH1 mRNA expression) and 2774 (no altered expression of MMR genes). Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response). The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation.

  3. Mismatch repair and treatment resistance in ovarian cancer

    Directory of Open Access Journals (Sweden)

    van der Burg Maria EL

    2006-07-01

    Full Text Available Abstract Background The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy. Methods We determined, microsatellite instability (MSI as a marker for MMR inactivation (analysis of BAT25 and BAT26, MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR in 75 ovarian carcinomas and eight ovarian cancer cell lines Results MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation, SKOV3 (no MLH1 mRNA expression and 2774 (no altered expression of MMR genes. Overall, there was no association between cisplatin response and MMR status in these eight cell lines. Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response. The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation. Conclusion No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation.

  4. The potential of transcranial photobiomodulation therapy for treatment of major depressive disorder.

    Science.gov (United States)

    Salehpour, Farzad; Rasta, Seyed Hossein

    2017-05-24

    Major depressive disorder is a common debilitating mood disorder that affects quality of life. Prefrontal cortex abnormalities, an imbalance in neurotransmitters, neuroinflammation, and mitochondrial dysfunction are the major factors in the etiology of major depressive disorder. Despite the efficacy of pharmacotherapy in the treatment of major depressive disorder, 30%-40% of patients do not respond to antidepressants. Given this, exploring the alternative therapies for treatment or prevention of major depressive disorder has aroused interest among scientists. Transcranial photobiomodulation therapy is the use of low-power lasers and light-emitting diodes in the far-red to near-infrared optical region for stimulation of neuronal activities. This non-invasive modality improves the metabolic capacity of neurons due to more oxygen consumption and ATP production. Beneficial effects of transcranial photobiomodulation therapy in the wide range of neurological and psychological disorders have been already shown. In this review, we focus on some issue relating to the application of photobiomodulation therapy for major depressive disorder. There is some evidence that transcranial photobiomodulation therapy using near-infrared light on 10-Hz pulsed mode appears to be a hopeful technique for treatment of major depressive disorder. However, further studies are necessary to find the safety of this method and to determine its effective treatment protocol.

  5. Study of Insulin Resistance in Patients With β Thalassemia Major and Validity of Triglyceride Glucose (TYG) Index.

    Science.gov (United States)

    Ansari, Arif M; Bhat, Kamalakshi G; Dsa, Smitha S; Mahalingam, Soundarya; Joseph, Nitin

    2018-03-01

    Complications like impaired glucose tolerance and diabetes mellitus due to iron overload need early identification in thalassemia. We studied the proportion of insulin resistance in thalassemia major patients on chronic transfusion, identified insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride glucose (TYG) index, compared them and validated TYG index. In total, 73 thalassemia patients on regular transfusion for 3 years with serum ferritin >1500 ng/mL were studied. Serum ferritin, fasting blood glucose, triglycerides, and insulin levels were measured, HOMA-IR, and TYG index calculated and analyzed. Mean fasting glucose, triglyceride, and serum insulin values were 104 mg/dL, 164.18 mg/dL, and 19.6 m IU/mL, respectively. Mean serum ferritin was 5156 ng/mL. Insulin resistance was prevalent in one third of thalassemia patients and showed increase with age and serum ferritin. Insulin resistance by HOMA-IR was 32% as against 16% by TYG index with a cut-off value of 4.3. Using receiver operating charecteristic curve analysis, it was found that, by lowering the value of TYG index to 4.0215, sensitivity improved to 78.3% (from 39.13%) with specificity of 70%. Hence, we recommend a newer lower cut-off value of 4.0215 for TYG index for better sensitivity and specificity in identifying insulin resistance.

  6. Review of major sweetpotato pests in Japan, with information on resistance breeding programs.

    Science.gov (United States)

    Okada, Yoshihiro; Kobayashi, Akira; Tabuchi, Hiroaki; Kuranouchi, Toshikazu

    2017-01-01

    Sweetpotato ( Ipomoeae batatas (L.) Lam.) is an important food crop affected by several pests throughout the world, especially in tropical, subtropical, and temperate regions. Although Japan is relatively free from many serious sweetpotato pests, some pests, especially soil-borne pathogens, viruses, and insects such as plant-parasitic nematodes and weevils, cause severe damage in Japan. In this review, we describe the current status and management options for sweetpotato pests and diseases in Japan and review research related to sweetpotato breeding that can promote resistance to these problems. Furthermore, we describe methods to evaluate resistance to pests and disease used in sweetpotato breeding at the National Agriculture and Food Research Organization (NARO).

  7. Immobilisation increases yeast cells' resistance to dehydration-rehydration treatment.

    Science.gov (United States)

    Borovikova, Diana; Rozenfelde, Linda; Pavlovska, Ilona; Rapoport, Alexander

    2014-08-20

    This study was performed with the goal of revealing if the dehydration procedure used in our new immobilisation method noticeably decreases the viability of yeast cells in immobilised preparations. Various yeasts were used in this research: Saccharomyces cerevisiae cells that were rather sensitive to dehydration and had been aerobically grown in an ethanol-containing medium, a recombinant strain of S. cerevisiae grown in aerobic conditions which were completely non-resistant to dehydration and an anaerobically grown bakers' yeast strain S. cerevisiae, as well as a fairly resistant Pichia pastoris strain. Experiments performed showed that immobilisation of all these strains essentially increased their resistance to a dehydration-rehydration treatment. The increase of cells' viability (compared with control cells dehydrated in similar conditions) was from 30 to 60%. It is concluded that a new immobilisation method, which includes a dehydration stage, does not lead to an essential loss of yeast cell viability. Correspondingly, there is no risk of losing the biotechnological activities of immobilised preparations. The possibility of producing dry, active yeast preparations is shown, for those strains that are very sensitive to dehydration and which can be used in biotechnology in an immobilised form. Finally, the immobilisation approach can be used for the development of efficient methods for the storage of recombinant yeast strains. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Is placebo useful in the treatment of major depression in clinical practice?

    Directory of Open Access Journals (Sweden)

    Marchesi C

    2013-06-01

    Full Text Available Carlo Marchesi, Chiara De Panfilis, Matteo Tonna, Paolo Ossola University of Parma, Department of Neuroscience, Psychiatric Unit, Parma, Italy Background: For many years, placebo has been defined by its inert content and use in clinical trials. In recent years, several studies have demonstrated its effect in the treatment of major depression. The aim of this paper is to present the conclusions of recent meta-analyses of the placebo effect in major depression, to explain the mechanism by which placebo exerts its effect, and to discuss whether placebo can be used in the treatment of patients with major depression in clinical practice. Recent meta-analyses have demonstrated that the placebo effect is estimated to account for 67% of the treatment effect in patients receiving antidepressants, and furthermore that placebo is as effective as antidepressants in patients with mild to moderate major depression (reporting a Hamilton Depression Rating Scale score lower than 25, whereas placebo is less effective than antidepressants in severely depressed patients. However, several limitations make the translation of these conclusions into clinical practice impracticable. Clinicians should learn from the "placebo lesson" to maximize the nonspecific effects of treatment when they prescribe an antidepressant, particularly in less severely depressed patients, who show a higher placebo response in randomized controlled trials. This strategy can increase the antidepressant effect and may reduce nonadherence with treatment. Keywords: placebo effect, major depressive disorder, subthreshold depressive disorder, antidepressants

  9. Effect of different oral oxytetracycline treatment regimes on selection of antimicrobial resistant coliforms in nursery pigs.

    Science.gov (United States)

    Herrero-Fresno, Ana; Zachariasen, Camilla; Nørholm, Nanna; Holm, Anders; Christiansen, Lasse Engbo; Olsen, John Elmerdahl

    2017-09-01

    A major concern derived from using antimicrobials in pig production is the development of resistance. This study aimed to assess the impact of selected combinations of oral dose and duration of treatment with oxytetracycline (OTC) on selection of tetracycline resistant (TET-R) coliforms recovered from swine feces. The work encompassed two studies: 1) OTC 5mg/kg and 20mg/kg were administered to nursery pigs for 3 and 10days, respectively, under controlled experimental conditions, and 2) 10mg/kg, 20mg/kg and 30mg/kg OTC were given to a higher number of pigs for 6, 3 and 2days, respectively, under field conditions. Statistical modeling was applied to analyze trends in the proportion of TET-R coliforms. In the experimental study, no statistical difference in proportion of TET-R coliforms was observed between treatments at the end of the trial (day 18) and compared to day 0. In the field study, treatment had a significant effect on the proportion of TET-R bacteria two days after the end of treatment (2dAT) with the regimes "low dose-six days" and "medium dose-three days" yielding the highest and lowest proportions of TET-R strains, respectively. No indication of co-selection for ampicillin- and sulphonamide -R bacteria was observed for any treatment at 2dAT. By the end of the nursery period, the proportion of TET-R bacteria was not significantly different between treatments and compared to day 0. Our results suggest that similar resistance levels might be obtained by using different treatment regimes regardless of the combinations of oral dose-duration of treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. White pine blister rust resistance in limber pine: Evidence for a major gene

    Science.gov (United States)

    A. W. Schoettle; R. A. Sniezko; A. Kegley; K. S. Burns

    2014-01-01

    Limber pine (Pinus flexilis) is being threatened by the lethal disease white pine blister rust caused by the non-native pathogen Cronartium ribicola. The types and frequencies of genetic resistance to the rust will likely determine the potential success of restoration or proactive measures. These first extensive inoculation trials using individual tree seed collections...

  11. Risk Factors for Acquisition of Drug Resistance during Multidrug-Resistant Tuberculosis Treatment, Arkhangelsk Oblast, Russia, 2005–2010

    Science.gov (United States)

    Ershova, Julia; Vlasova, Natalia; Nikishova, Elena; Tarasova, Irina; Eliseev, Platon; Maryandyshev, Andrey O.; Shemyakin, Igor G.; Kurbatova, Ekaterina; Cegielski, J. Peter

    2015-01-01

    Acquired resistance to antituberculosis drugs decreases effective treatment options and the likelihood of treatment success. We identified risk factors for acquisition of drug resistance during treatment for multidrug-resistant tuberculosis (MDR TB) and evaluated the effect on treatment outcomes. Data were collected prospectively from adults from Arkhangelsk Oblast, Russia, who had pulmonary MDR TB during 2005–2008. Acquisition of resistance to capreomycin and of extensively drug-resistant TB were more likely among patients who received 3 effective drugs (9.4% vs. 0% and 8.6% vs. 0.8%, respectively). Poor outcomes were more likely among patients with acquired capreomycin resistance (100% vs. 25.9%), acquired ofloxacin resistance (83.6% vs. 22.7%), or acquired extensive drug resistance (100% vs. 24.4%). To prevent acquired drug resistance and poor outcomes, baseline susceptibility to first- and second-line drugs should be determined quickly, and treatment should be adjusted to contain >3 effective drugs. PMID:25988954

  12. Psychosocial aspects of resistance in complex treatment of depressive disorder.

    Science.gov (United States)

    Sedlackova, Zuzana; Prasko, Jan; Latalova, Klara; Kamaradova, Dana; Ociskova, Marie; Grambal, Ales; Sigmundova, Zuzana; Kasalova, Petra; Cakirpaloglu, Snezana

    2015-01-01

    Treatment of major depressive disorder can be affected by a broad range of factors. In our study, we focused on the relationships of demographic, psychological, clinical and social factors to the course of treatment of depression. The study included 151 patients (finally 140 patients were evaluated) hospitalized for major depressive disorder. They were assessed for demographic characteristics, the rates of depression and anxiety, quality of life, the rates of dissociation and insomnia, and subjective and objective disease severity at different times during treatment. Patients were treated with standard doses of antidepressants or other psychiatric medication. They also completed a 6-week long daily cognitive-behavioural therapy. Data were statistically analyzed. There were significant decreases in the overall severity of the disorder, anxiety level and depression rate during treatment. Improvement measured by objective Clinical Global Impression (oCGI-I) at the end of treatment was not significantly correlated with any of the measured parameters (age of patient, onset of illness, duration of disease, doses of medication etc.). It only significantly positively correlated with the initial evaluation of the patient by oCGI. However, the improvement in subjective assessment (using sCGI-I) correlated with many parameters (increased age, later onset of the disease, greater disease severity at baseline in both overall and subjective evaluation of the severity, anxiety and depressive symptomatology). Furthermore, it was negatively correlated with most quality of life parameters, such as H (Home), F (Feelings), L (Leisure), Sr (Social relations) and G (General). The results suggest that individual variables, such as the degree of psychopathology, particularly depression and anxiety, most quality of life parameters, higher patient age and age of disorder onset may be associated with poorer subjective response to complex treatment of patients with major depressive disorder.

  13. Reasons for entering treatment reported by initially treatment-resistant patients with substance use disorders

    NARCIS (Netherlands)

    Meyers, Robert J.; Roozen, Hendrik G.; Smith, Jane Ellen; Evans, Brittany E.

    2014-01-01

    Many individuals with substance use disorders are resistant to entering formal treatment, despite the negative consequences that plague their own lives and the lives of concerned significant others (CSOs). Community Reinforcement and Family Training (CRAFT) has been developed as an effective

  14. THE IMPACT OF FERTILIZATION AND FOLIAR STIMULATION PRODUCTS BOTH ON INCREASING THE RESISTANCE TO MAJOR PHYTOPATHOGENS ATTACKS, AND ON INCREASING THE QUANTITY AND QUALITY OF WINE GRAPES HARVEST

    Directory of Open Access Journals (Sweden)

    Cristina BUNESCU

    2014-12-01

    Full Text Available The paper aimed to demonstrate the impact of fertilization and foliar stimulation products both on increasing the resistance to major phytopathogens attacks, and on increasing the quantity and quality of wine grapes harvest. Applying the foliar fertilizer products Plonvit Kali (c1, Tytanit (c2 and Optysil (c3 to vines, for a period of three years (2011/2013, in phenophases of intensive growth of shoots and grapes at approved dosages, simultaneously with pesticide treatment, not only a reduction of pathogenic fungi attack was obtained, but also and an increase of harvest without diminishing the quality of the grapes.

  15. Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression : a pilot randomized, placebo-controlled continuation trial

    NARCIS (Netherlands)

    Mathew, S.J.; Murrough, J.W.; Aan het Rot, M.; Collins, K.A.; Reich, D.L.; Charney, D.S.

    2010-01-01

    The N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine may have rapid, albeit transient, antidepressant properties. This study in patients with treatment-resistant major depression (TRD) aimed to (1) replicate the acute efficacy of single-close intravenous (i.v.) ketamine; (2) test

  16. Enhancing motivation for change in treatment-resistant eating disorders.

    Science.gov (United States)

    Vitousek, K; Watson, S; Wilson, G T

    1998-06-01

    Denial and resistance to change are prominent features in most patients with anorexia nervosa. The egosyntonic quality of symptoms can contribute to inaccuracy in self-report, avoidance of treatment, difficulties in establishing a therapeutic relationship, and high rates of attrition and relapse. Individuals with bulimia nervosa are typically more motivated to recover, but often ambivalent about forfeiting the ideal of slenderness and the protective functions of binge-purge behavior. Few attempts have been made to assess denial and resistance in the eating disorders, or to examine alternative strategies for enhancing motivation to change. Review of the clinical literature indicates a striking convergence of recommendations across conceptually distinct treatment approaches. Clinicians are encouraged to acquire a frame of reference that can help them understand the private experience of individuals with eating disorders, empathize with their distress at the prospect of weight gain, and acknowledge the difficulty of change. The Socratic method seems particularly well-suited to work with this population because of its emphasis on collaboration, openness, curiosity, patience, focused and systematic inquiry, and individual discovery. Four themes are crucial in engaging reluctant eating-disordered clients in therapy: the provision of psychoeducational material, an examination of the advantages and disadvantages of symptoms, the explicit use of experimental strategies, and an exploration of personal values.

  17. Spironolactone and doxazosin treatment in patients with resistant hypertension.

    Science.gov (United States)

    Rodilla, Enrique; Costa, José A; Pérez-Lahiguera, Francisco; Baldó, Emilio; González, Carmen; Pascual, José M

    2009-02-01

    The aim of this study was to evaluate the use of spironolactone and doxazosin as treatment for patients with resistant hypertension. This retrospective study involved 181 outpatients with resistant hypertension (defined as a failure of blood pressure [BP] control despite treatment with three drugs, one of which was a diuretic) who received additional spironolactone (n=88) or doxazosin (n=93). Mean systolic BP in the spironolactone group fell by 28 mmHg (95% confidence interval [CI], 24-32 mmHg; P< .001) and mean diastolic BP fell by 12 mmHg (95% CI, 9-14 mmHg; P< .001). The corresponding falls in the doxazosin group were 16 mmHg (95% CI, 13-20 mmHg; P< .001) and 7 mmHg (95% CI, 5-9 mmHg; P< .001), respectively. The decrease was significantly greater with spironolactone for both systolic (P< .001) and diastolic (P=.003) pressures. At the end of follow-up, 30% of all patients had achieved BP control, with control being more frequent with spironolactone (39%) than doxazosin (23%; P=.02). Multivariate logistic regression analysis showed that the only factors that significantly influenced the achievement of BP control were diabetes (odds ratio=0.17; 95% CI, 0.08-0.39; P< .001) and baseline systolic BP <165 mmHg (odds ratio=2.56; 95% CI, 1.11-5.90; P=.03). In patients with resistant hypertension, the addition of either spironolactone or doxazosin resulted in a significant decrease in BP, though the decrease appeared to be greater with spironolactone. The presence of diabetes complicated BP control.

  18. Effect of Heat treatment on Hardness and Corrosion Resistance of Super Cast Iron

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Roun; Kim, Young Sik [Andong National University, Andong (Korea, Republic of)

    2014-07-15

    In fossil-fuel-fired power plants, a variety of pollutants are produced from the combustion of conventional fuels such as coal, oil and gas. Major component of such pollution are ash and corrosive chemicals, which also destroy pumps and piping; by causing erosion/corrosion, pitting, and wear. In order to over come such damage, materials with high hardness and high corrosion resistance are needed. In this work, we melted super-cast-iron with excellent corrosion resistance and high hardness. To elucidate the effect of heat treatment, microstructural analysis, hardness measurement, and corrosion tests were performed. Test results revealed that the super-cast-iron had several tens better corrosion resistance than 316 L stainless steel, and it also had a high surface hardness (> HRC45). High hardness, in spite of its low carbon content (0.74%C), could resulted from a hardening heat treatment to precipitate sufficient Cr{sub 7}C{sub 3} and Cr{sub 2}3C{sub 6}. Also, it was concluded that the excellent corrosion resistance of the super-cast-iron was due to the increase of the relative chromium content by minimizing the carbon content, and by the enhancement of passive film by the addition of Cr, Mo, Cu, and W.

  19. Cultivar-Based Introgression Mapping Reveals Wild Species-Derived Pm-0, the Major Powdery Mildew Resistance Locus in Squash

    Science.gov (United States)

    Holdsworth, William L.; LaPlant, Kyle E.; Bell, Duane C.; Jahn, Molly M.; Mazourek, Michael

    2016-01-01

    Powdery mildew is a major fungal disease on squash and pumpkin (Cucurbita spp.) in the US and throughout the world. Genetic resistance to the disease is not known to occur naturally within Cucurbita pepo and only infrequently in Cucurbita moschata, but has been achieved in both species through the introgression of a major resistance gene from the wild species Cucurbita okeechobeensis subsp. martinezii. At present, this gene, Pm-0, is used extensively in breeding, and is found in nearly all powdery mildew-resistant C. pepo and C. moschata commercial cultivars. In this study, we mapped C. okeechobeensis subsp. martinezii-derived single nucleotide polymorphism (SNP) alleles in a set of taxonomically and morphologically diverse and resistant C. pepo and C. moschata cultivars bred at Cornell University that, by common possession of Pm-0, form a shared-trait introgression panel. High marker density was achieved using genotyping-by-sequencing, which yielded over 50,000 de novo SNP markers in each of the three Cucurbita species genotyped. A single 516.4 kb wild-derived introgression was present in all of the resistant cultivars and absent in a diverse set of heirlooms that predated the Pm-0 introgression. The contribution of this interval to powdery mildew resistance was confirmed by association mapping in a C. pepo cultivar panel that included the Cornell lines, heirlooms, and 68 additional C. pepo cultivars and with an independent F2 population derived from C. okeechobeensis subsp. martinezii x C. moschata. The interval was refined to a final candidate interval of 76.4 kb and CAPS markers were developed inside this interval to facilitate marker-assisted selection. PMID:27936008

  20. Cultivar-Based Introgression Mapping Reveals Wild Species-Derived Pm-0, the Major Powdery Mildew Resistance Locus in Squash.

    Science.gov (United States)

    Holdsworth, William L; LaPlant, Kyle E; Bell, Duane C; Jahn, Molly M; Mazourek, Michael

    2016-01-01

    Powdery mildew is a major fungal disease on squash and pumpkin (Cucurbita spp.) in the US and throughout the world. Genetic resistance to the disease is not known to occur naturally within Cucurbita pepo and only infrequently in Cucurbita moschata, but has been achieved in both species through the introgression of a major resistance gene from the wild species Cucurbita okeechobeensis subsp. martinezii. At present, this gene, Pm-0, is used extensively in breeding, and is found in nearly all powdery mildew-resistant C. pepo and C. moschata commercial cultivars. In this study, we mapped C. okeechobeensis subsp. martinezii-derived single nucleotide polymorphism (SNP) alleles in a set of taxonomically and morphologically diverse and resistant C. pepo and C. moschata cultivars bred at Cornell University that, by common possession of Pm-0, form a shared-trait introgression panel. High marker density was achieved using genotyping-by-sequencing, which yielded over 50,000 de novo SNP markers in each of the three Cucurbita species genotyped. A single 516.4 kb wild-derived introgression was present in all of the resistant cultivars and absent in a diverse set of heirlooms that predated the Pm-0 introgression. The contribution of this interval to powdery mildew resistance was confirmed by association mapping in a C. pepo cultivar panel that included the Cornell lines, heirlooms, and 68 additional C. pepo cultivars and with an independent F2 population derived from C. okeechobeensis subsp. martinezii x C. moschata. The interval was refined to a final candidate interval of 76.4 kb and CAPS markers were developed inside this interval to facilitate marker-assisted selection.

  1. Predictors of response to combined wake and light therapy in treatment-resistant inpatients with depression

    DEFF Research Database (Denmark)

    Kragh, Mette; Roj Larsen, Erik; Martiny, Klaus

    2018-01-01

    There is growing evidence for combined chronotherapeutic interventions as adjunctive treatments for major depression. However, as the treatments can be demanding, we need to identify predictors of response. This study aimed to describe predictors of response, remission and deterioration in the sh......There is growing evidence for combined chronotherapeutic interventions as adjunctive treatments for major depression. However, as the treatments can be demanding, we need to identify predictors of response. This study aimed to describe predictors of response, remission and deterioration...... in the short-term phase, as well as predictors of long-term response. The predictors investigated were gender, type of depression, severity of depression, treatment resistance, quetiapine use, general self-efficacy, educational level and positive diurnal variation. Follow-up data from 27 inpatients...... with moderate-to-severe depression participating in a chronotherapeutic intervention were analysed. As a supplement to standard treatment, they completed 3 wake therapy sessions in the first week, 30 min daily light treatment and sleep-time stabilisation in the entire 9-week study period. Patients had...

  2. The effects of cognitive therapy versus 'treatment as usual' in patients with major depressive disorder

    DEFF Research Database (Denmark)

    Jakobsen, Janus Christian; Lindschou Hansen, Jane; Storebø, Ole Jakob

    2011-01-01

    BACKGROUND: Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Cognitive therapy may be an effective treatment option for major depressive disorder, but the effects have only had limited assessment in systematic reviews....... METHODS/PRINCIPAL FINDINGS: Cochrane systematic review methodology, with meta-analyses and trial sequential analyses of randomized trials, are comparing the effects of cognitive therapy versus 'treatment as usual' for major depressive disorder. To be included the participants had to be older than 17 years....... Meta-analysis on the data from the Hamilton Rating Scale for Depression showed that cognitive therapy compared with 'treatment as usual' significantly reduced depressive symptoms (mean difference -2.15 (95% confidence interval -3.70 to -0.60; P

  3. Differential in vivo gene expression of major Leptospira proteins in resistant or susceptible animal models.

    Science.gov (United States)

    Matsui, Mariko; Soupé, Marie-Estelle; Becam, Jérôme; Goarant, Cyrille

    2012-09-01

    Transcripts of Leptospira 16S rRNA, FlaB, LigB, LipL21, LipL32, LipL36, LipL41, and OmpL37 were quantified in the blood of susceptible (hamsters) and resistant (mice) animal models of leptospirosis. We first validated adequate reference genes and then evaluated expression patterns in vivo compared to in vitro cultures. LipL32 expression was downregulated in vivo and differentially regulated in resistant and susceptible animals. FlaB expression was also repressed in mice but not in hamsters. In contrast, LigB and OmpL37 were upregulated in vivo. Thus, we demonstrated that a virulent strain of Leptospira differentially adapts its gene expression in the blood of infected animals.

  4. Emerging (val)ganciclovir resistance during treatment of congenital CMV infection: a case report and review of the literature.

    Science.gov (United States)

    Morillo-Gutierrez, Beatriz; Waugh, Sheila; Pickering, Ailsa; Flood, Terence; Emonts, Marieke

    2017-08-22

    Congenital cytomegalovirus (cCMV) infection is an important illness that is a common cause of hearing loss in newborn infants and a major cause of disability in children. For that reason, treatment of symptomatic patients with either ganciclovir or its pro-drug valganciclovir is recommended. Treatment duration of 6 months has been shown to be more beneficial than shorter courses; however, there is uncertainty regarding emergence of resistance strains, secondary effects and long term sequelae. Here we present a female infant with symptomatic cCMV who was treated from day 5 of life with oral valganciclovir. In spite of close monitoring of her drug levels and increments of her treatment dose according to weight gain, she developed ganciclovir resistance after 4 months of treatment, with increasing viraemia and petechiae. Adherence to treatment was assessed and felt to be good. Clinically, although she had marked developmental delay, she was making steady progress. In view of the development of resistance treatment was stopped at 5 months of age. No secondary effects of ganciclovir were noted during the whole course. There were few cases in the literature reporting resistance to ganciclovir for cCMV before the new recommendations for a 6 months treatment course for this infection were published. As demonstrated in our patient, surveillance with periodic viral loads and drug monitoring are vital to identify emerging resistance and optimise antiviral dosing according to weight gain.

  5. Management of patients with resistant hypertension: current treatment options

    Directory of Open Access Journals (Sweden)

    Kumar N

    2013-10-01

    Full Text Available Nilay Kumar,1 David A Calhoun,2 Tanja Dudenbostel21Department of Medicine, 2Division of Cardiovascular Disease, Hypertension and Vascular Biology Program, University of Alabama at Birmingham, Birmingham, AL, USAAbstract: Resistant hypertension (RHTN is an increasingly common clinical problem that is often heterogeneous in etiology, risk factors, and comorbidities. It is defined as uncontrolled blood pressure on optimal doses of three antihypertensive agents, ideally one being a diuretic. The definition also includes controlled hypertension with use of four or more antihypertensive agents. Recent observational studies have advanced the characterization of patients with RHTN. Patients with RHTN have higher rates of cardiovascular events and mortality compared with patients with more easily controlled hypertension. Secondary causes of hypertension, including obstructive sleep apnea, primary aldosteronism, renovascular disease, are common in patients with RHTN and often coexist in the same patient. In addition, RHTN is often complicated by metabolic abnormalities. Patients with RHTN require a thorough evaluation to confirm the diagnosis and optimize treatment, which typically includes a combination of lifestyle adjustments, and pharmacologic and interventional treatment. Combination therapy including a diuretic, a long-acting calcium channel blocker, an angiotensin-converting enzyme inhibitor, a beta blocker, and a mineralocorticoid receptor antagonist where warranted is the classic regimen for patients with treatment-resistant hypertension. Mineralocorticoid receptor antagonists like spironolactone or eplerenone have been shown to be efficacious in patients with RHTN, heart failure, chronic kidney disease, and primary aldosteronism. Novel interventional therapies, including baroreflex activation and renal denervation, have shown that both of these methods may be used to lower blood pressure safely, thereby providing exciting and promising new

  6. Single-session treatment of a major complication of dens invaginatus: a case report.

    Science.gov (United States)

    Caldari, Mauro; Monaco, Carlo; Ciocca, Leonardo; Scotti, Roberto

    2006-05-01

    Dens invaginatus is a dental malformation that may give rise to several complications. Caries of the invagination can severely weaken the whole tooth, making it susceptible to fracture. Subgingival fractures are major complications threatening tooth survival and usually require periodontal/orthodontic/prosthetic treatment if long-term viability is to be ensured. This article describes a case of single-session restoration of a fractured invaginated tooth by means of endodontic treatment followed by fragment reattachment.

  7. Modulating affect, cognition and behavior – prospects of deep brain stimulation for treatment resistant psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Thomas E. Schlaepfer

    2011-06-01

    Full Text Available Most patients suffering from psychiatric disorders respond to combina-tions of psycho- and psychopharmacotherapy, however there are patients who profit little if anything even after many years of treatment. Since about a decade different modalities of targeted neuromodulation – among them most prominently – Deep Brain Stimulation (DBS - are being actively researched as putative approaches to very treatment resistant forms of those disorders. Recently, promising pilot data have been re-ported both for Major Depression (MD and Obsessive-Compulsive Disor-der (OCD. Given the fact that patients studied had been treated unsuc-cessfully for many years renders these findings remarkable. Remarkable is the fact, that in case of the long-term studies underway for MD, patients show a stable response. This gives hope to a substantial percentage of therapy-resistant psychiatric patients requiring new therapy approaches. There are no fundamental ethic objections to its use in psychiatric disor-ders, but until substantial clinical data is available, mandatory standards are needed. DBS is a unique and very promising method for the treat-ment of therapy-resistant psychiatric patients. The method allows ma-nipulating pathological neuronal networks in a very precise way.

  8. Second Generation Antipsychotics in the Treatment of Major Depressive Disorder: An Update

    Science.gov (United States)

    Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Jun, Tae-Youn; Patkar, Ashwin A; Masand, Prakash S

    2016-01-01

    Less than one third of patients who suffer from major depressive disorder (MDD) report remission following antidepressant treatments requiring more diverse treatment approaches. Augmentation of second generation antipsychotics (SGAs) has been increasingly recognized as an important treatment option. The authors have previously provided a comprehensive review of SGAs for the treatment of MDD in 2013. Since then, numerous additional clinical trials have been conducted to investigate diverse issues regarding the utility of SGAs in MDD. Moreover, a new SGA, brexpiprazole, was recently approved by the Food and Drug Administration in July 2015 for the treatment of MDD as an augmentation agent to antidepressants. Thus, the aim of this study was to provide a concise update of all the available SGAs for the treatment of MDD, in particular on the additional clinical trials which have been published since 2013. PMID:27689026

  9. Interpersonal impacts mediate the association between personality and treatment response in major depression.

    Science.gov (United States)

    Dermody, Sarah S; Quilty, Lena C; Bagby, R Michael

    2016-07-01

    Personality, as characterized by the Five-Factor Model, predicts response to psychotherapy for depression. To explain how personality impacts treatment response, the present study investigated patient and therapist interpersonal processes in treatment sessions as an explanatory pathway. A clinical trial was conducted in which 103 outpatients (mean age: 41.17 years, 65% female) with primary major depressive disorder completed 16-20 weeks of cognitive-behavioral or interpersonal therapy. Before treatment, patients completed the Revised NEO Personality Inventory to assess personality domains (neuroticism, extraversion, openness-to-experience, agreeableness, and conscientiousness). After 3 and 13 weeks, patient interpersonal behavior was rated by the therapist and vice versa to determine levels of patient and therapist communal and agentic behaviors. Depression levels were measured before and after treatment. Structural equation modeling supported that patients' interpersonal behavior during therapy mediated the associations between pretreatment personality and depression treatment outcome. Specifically, extraversion, conscientiousness, and neuroticism (inverse) predicted higher levels of patient communion throughout treatment, which was in turn associated with improved treatment outcomes. Furthermore, patient agreeableness was inversely associated with agency throughout treatment, which was linked to poorer treatment response. Therapist interpersonal behavior was not a significant mediator. Results suggest that patient interpersonal behavior during treatment may be one way that patient personality impacts clinical outcomes in depression. Results underscore the clinical utility of Five-Factor Model domains in treatment process and outcome. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  10. Utility of lytic bacteriophage in the treatment of multidrug-resistant Pseudomonas aeruginosa septicemia in mice

    Directory of Open Access Journals (Sweden)

    Vinodkumar C

    2008-07-01

    Full Text Available Drug resistance is the major cause of increase in morbidity and mortality in neonates. One thousand six hundred forty-seven suspected septicemic neonates were subjected for microbiological analysis over a period of 5 years. Forty-two P. aeruginosa were isolated and the antibiogram revealed that 28 P. aeruginosa were resistant to almost all the common drugs used (multidrug-resistant. The emergence of antibiotic-resistant bacterial strains is one of the most critical problems of modern medicine. As a result, a novel and most effective approaches for treating infection caused by multidrug-resistant bacteria are urgently required. In this context, one intriguing approach is to use bacteriophages (viruses that kill bacteria in the treatment of infection caused by drug-resistant bacteria. In the present study, the utility of lytic bacteriophages to rescue septicemic mice with multidrug-resistant (MDR P. aeruginosa infection was evaluated. MDR P. aeruginosa was used to induce septicemia in mice by intraperitoneal (i.p. injection of 10 7 CFU. The resulting bacteremia was fatal within 48 hrs. The phage strain used in this study had lytic activity against a wide range of clinical isolates of MDR P. aeruginosa. A single i.p. injection of 3 x 10 9 PFU of the phage strain, administered 45 min after the bacterial challenge, was sufficient to rescue 100% of the animals. Even when treatment was delayed to the point where all animals were moribund, approximately 50% of them were rescued by a single injection of this phage preparation. The ability of this phage to rescue septicemic mice was demonstrated to be due to the functional capabilities of the phage and not to a nonspecific immune effect. The rescue of septicemic mice could be affected only by phage strains able to grow in vitro on the bacterial host used to infect the animals and when such strains are heat-inactivated, they lose their ability to rescue the infected mice. Multidrug-resistant bacteria have

  11. Cortisol Modulation by Ayahuasca in Patients With Treatment Resistant Depression and Healthy Controls

    Directory of Open Access Journals (Sweden)

    Ana C. de Menezes Galvão

    2018-05-01

    Full Text Available Major depression is a highly prevalent mood disorder, affecting about 350 million people, and around 30% of the patients are resistant to currently available antidepressant medications. Recent evidence from a randomized controlled trial (RCT supports the rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression. The aim of this study was to explore the effect of ayahuasca on plasma cortisol and awakening salivary cortisol response, in the same group of treatment-resistant patients (MD and in healthy volunteers (C. Subjects received a single dose of ayahuasca or placebo (dosing session, and both plasma and awakening salivary cortisol response were measured at baseline (before dosing session and 48 h after the dosing session. Baseline assessment (D0 showed blunted awakening salivary cortisol response and hypocortisolemia in patients, with respect to healthy controls. Salivary cortisol was also measured during dosing session, and we observed higher increases for both C and MD that ingested ayahuasca than placebo. After 48 h from the dosing session with ayahuasca, patients' awakening salivary cortisol response is similar to the ones detected in controls. No significant changes in plasma cortisol levels were observed 48 h after the sessions. Therefore, these findings point to new evidence on the modulation of salivary cortisol levels as a result of an ayahuasca session, both in healthy and depressive volunteers. Considering that cortisol acts in regulation of distinct physiological pathways, emotional and cognitive processes, it is assumed to be critically involved to the etiology of depression and its regulation seems to be important for the treatment and remission of major depression, ayahuasca use as antidepressant should be further investigated. Moreover, this study highlights the importance of psychedelics in the treatment of human mental disorders.

  12. Development of transgenic cotton lines expressing Allium sativum agglutinin (ASAL) for enhanced resistance against major sap-sucking pests.

    Science.gov (United States)

    Vajhala, Chakravarthy S K; Sadumpati, Vijaya Kumar; Nunna, Hariprasad Rao; Puligundla, Sateesh Kumar; Vudem, Dashavantha Reddy; Khareedu, Venkateswara Rao

    2013-01-01

    Mannose-specific Allium sativum leaf agglutinin encoding gene (ASAL) and herbicide tolerance gene (BAR) were introduced into an elite cotton inbred line (NC-601) employing Agrobacterium-mediated genetic transformation. Cotton transformants were produced from the phosphinothricin (PPT)-resistant shoots obtained after co-cultivation of mature embryos with the Agrobacterium strain EHA105 harbouring recombinant binary vector pCAMBIA3300-ASAL-BAR. PCR and Southern blot analysis confirmed the presence and stable integration of ASAL and BAR genes in various transformants of cotton. Basta leaf-dip assay, northern blot, western blot and ELISA analyses disclosed variable expression of BAR and ASAL transgenes in different transformants. Transgenes, ASAL and BAR, were stably inherited and showed co-segregation in T1 generation in a Mendelian fashion for both PPT tolerance and insect resistance. In planta insect bioassays on T2 and T3 homozygous ASAL-transgenic lines revealed potent entomotoxic effects of ASAL on jassid and whitefly insects, as evidenced by significant decreases in the survival, development and fecundity of the insects when compared to the untransformed controls. Furthermore, the transgenic cotton lines conferred higher levels of resistance (1-2 score) with minimal plant damage against these major sucking pests when bioassays were carried out employing standard screening techniques. The developed transgenics could serve as a potential genetic resource in recombination breeding aimed at improving the pest resistance of cotton. This study represents the first report of its kind dealing with the development of transgenic cotton resistant to two major sap-sucking insects.

  13. Collateral Resistance and Sensitivity Modulate Evolution of High-Level Resistance to Drug Combination Treatment in Staphylococcus aureus

    DEFF Research Database (Denmark)

    de Evgrafov, Mari Cristina Rodriguez; Gumpert, Heidi; Munck, Christian

    2015-01-01

    As drug-resistant pathogens continue to emerge, combination therapy will increasingly be relied upon to treat infections and to help combat further development of multidrug resistance. At present a dichotomy exists between clinical practice, which favors therapeutically synergistic combinations......, to reflect drug concentrations more likely to be encountered during treatment. We performed a series of adaptive evolution experiments using Staphylococcus aureus. Interestingly, no relationship between drug interaction type and resistance evolution was found as resistance increased significantly beyond wild......-type levels. All drug combinations, irrespective of interaction types, effectively limited resistance evolution compared with monotreatment. Cross-resistance and collateral sensitivity were found to be important factors in the extent of resistance evolution toward a combination. Comparative genomic analyses...

  14. Treatment of amiodarone-induced thyrotoxicosis resistant to conventional therapy

    Directory of Open Access Journals (Sweden)

    Nišić Tanja

    2017-01-01

    Full Text Available Introduction: Amiodarone as an antiarrhythmic medication is necessary in the prevention and treatment of malignant ventricular arrhythmias, however, it can induce thyroid dysfunction. Thyroid dysfunction may be either hypothyroidism or thyrotoxicosis, however, 50% of patients who have used amiodarone are euthyroid. Case report: A 27-year-old female patient, hospitalized at the Clinic for Endocrinology due to type 2 amiodarone-induced thyrotoxicosis. The patient had previously received amiodarone for two years. At age 25, the patient was diagnosed with dilated cardiomyopathy (EF 25%, EDD/ESD 56-57/47 mm with mild Ebstein’s anomaly, WPW Sy and recorded episodes of non-sustained VT. In order to reduce the risk of sudden death and prevent malignant ventricular arrhythmias, ICD-VR was implanted and amiodarone was prescribed. Treatment with propylthiouracil (PTU and dexamethasone was initiated after thyrotoxicosis was diagnosed. Three weeks after the introduction of PTU, hepatotoxicity was registered, thus the medication was discontinued. Thyrozol, which regulates the hepatotoxicity parameters, was introduced. Sodium perchlorate and glucocorticoid (per os, IV and intrathyroidal therapy was introduced. The treatment had lasted for fifty days and laboratory signs of thyrotoxicosis were still present, which is why a total of eight plasmapheresis sessions were performed. Each plasmapheresis resulted in a significant decrease in FT4 and a slight decrease in FT3. After seventy two days of treatment, an optimal hormonal status of the thyroid gland was established and total thyroidectomy was performed. Conclusion: Patient was treated for amiodarone-induced thyrotoxicosis (AIT type 2, which was resistant to conventional therapy for a long period of time. Successful treatment was achieved by applying plasmapheresis although the effect of perchlorate and glucocorticoids application cannot be disregarded.

  15. [Economic evaluation of desvenlafaxine in the treatment of major depressive disorder in Spain].

    Science.gov (United States)

    Rejas Gutiérrez, Javier; Blanca Tamayo, Milagrosa; Gascón Barrachina, Josep; Armada Peláez, Beatriz

    2016-01-01

    The objective of this analysis was to evaluate the clinical and economic value of the use of 50mg-desvenlafaxine compared to the usual care (mix of duloxetine and venlafaxine) in the outpatient treatment of major depressive disorder after first line treatment failure (relapse) in Spain. A Markov model was used to follow up a cohort of major depressive disorder patients for one year after failure of first-line treatment with a serotonin-specific reuptake inhibitor and estimate outcome measures (percentage remission and depression-free days) and accrued and direct costs incurred during outpatient treatment of major depressive disorder. In order to obtain the efficacy data related to the treatment alternatives, a literature review of clinical trials was performed. A panel of clinical experts validated the use of clinical resources employed in the estimation of economic outcomes together with model assumptions. The analysis was performed in 2014 from the perspective of the National Health System. Due to fewer discontinuations, initiating second line treatment with desvenlafaxine was associated with more depression-free days and a higher percentage of patients in remission versus usual care: 1.7 days and 0.5%, respectively. This was translated into lower drug and events management costs, and an overall cost reduction of €108 for the National Health System. In patients who have not responded to a first-line serotonin-specific reuptake inhibitor therapy, desvenlafaxine-50mg was clinically similar in effectiveness, but a less costly option, compared with a weighted average of duloxetine and venlafaxine for the second-line treatment of major depressive disorder patients from a payer (National Health System) perspective in Spain. Copyright © 2015 SEP y SEPB. Published by Elsevier España. All rights reserved.

  16. Hypnosis in the Treatment of Major Depression: An Analysis of Heart Rate Variability.

    Science.gov (United States)

    Chen, Xiuwen; Yang, Rongqian; Ge, Lulu; Luo, Jie; Lv, Ruixue

    2017-01-01

    Hypnosis is an adjuvant treatment of major depression (MD). Heart rate variability (HRV) can assess the autonomic nervous system, which is associated with MD, and HRV is decreased in MD patients. There is a lack of research on HRV changes before, during, and after the use of hypnosis in MD patients. A total of 21 MD patients participated in this study, and 5-minute electrocardiograms were recorded before, during, and after hypnosis. Compared with the prehypnotic condition, HRV parameters significantly (p hypnosis treatment should bring some functional improvement to the autonomic nervous system. HRV is potentially a useful tool that quantifies the physiological impact of hypnosis treatment in MD patients.

  17. Using the Story of Cinderella To Teach the Major Approaches to Treatment and Therapy.

    Science.gov (United States)

    Kaminski, Patricia L.; Haynes, Sandra D.

    2000-01-01

    Describes a classroom activity to enhance understanding of how major theorists differ in their conceptualization and treatment of a client's problems. Participants either watched a dramatized play in which prominent clinicians discuss a case, or attended a comparable lecture. Results of a quiz indicate that students who watched the play…

  18. Behavioral Activation in the Treatment of Comorbid Posttraumatic Stress Disorder and Major Depressive Disorder

    Science.gov (United States)

    Mulick, Patrick S.; Naugle, Amy E.

    2009-01-01

    This study investigated the efficacy of 10-weeks of Behavioral Activation (BA) in the treatment of comorbid Post-traumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD) in four adults using a nonconcurrent multiple baseline across participants design. All participants met full "DSM-IV" criteria for both MDD and PTSD at the…

  19. Psychosocial Treatments for Major Depression and Dysthymia in Older Adults: A Review of the Research Literature

    Science.gov (United States)

    Zalaquett, Carlos P.; Stens, Andrea N.

    2006-01-01

    Older adults represent a growing segment of the population with the highest suicide rate and an increasing need of counseling services for major depression and dysthymia. The present study examined the literature with the purpose of identifying research addressing psychosocial treatments of depression in later life. A summary of treatments…

  20. Cast Steels for Creep-Resistant Parts Used in Heat Treatment Plants

    Directory of Open Access Journals (Sweden)

    Drotlew A.

    2012-12-01

    Full Text Available Creep-resistant parts of heat treatment furnaces are in most cases made from high-alloyed chromium-nickel and nickel-chromium iron alloys, both cast and wrought. This paper presents the types of casting alloys used for this particular purpose, since the majority of furnace components are made by the casting process. Standards were cited which give symbols of alloy grades used in technical specifications by the domestic industry. It has been indicated that castings made currently are based on a wider spectrum of the creep-resistant alloy grades than the number of alloys covered by the standards. Alloy grades recommended by the technical literature for individual parts of the furnace equipment were given. The recommendations reflect both the type of the technological process used and the technical tasks performed by individual parts of the furnace equipment. Comments were also made on the role of individual alloying elements in shaping the performance properties of castings.

  1. Cast Steels for Creep-resistant Parts Used in Heat Treatment Plants

    Directory of Open Access Journals (Sweden)

    A. Drotlew

    2012-12-01

    Full Text Available Creep-resistant parts of heat treatment furnaces are in most cases made from high-alloyed chromium-nickel and nickel-chromium ironalloys, both cast and wrought. This paper presents the types of casting alloys used for this particular purpose, since the majority of furnace components are made by the casting process. Standards were cited which give symbols of alloy grades used in technical specifications by the domestic industry. It has been indicated that castings made currently are based on a wider spectrum of the creep-resistant alloy grades than the number of alloys covered by the standards. Alloy grades recommended by the technical literature for individual parts of the furnace equipment were given. The recommendations reflect both the type of the technological process used and the technical tasks performed by individual parts of the furnace equipment. Comments were also made on the role of individual alloying elements in shaping the performance properties of castings.

  2. Non-specific activities of the major herbicide-resistance gene BAR.

    Science.gov (United States)

    Christ, Bastien; Hochstrasser, Ramon; Guyer, Luzia; Francisco, Rita; Aubry, Sylvain; Hörtensteiner, Stefan; Weng, Jing-Ke

    2017-12-01

    Bialaphos resistance (BAR) and phosphinothricin acetyltransferase (PAT) genes, which convey resistance to the broad-spectrum herbicide phosphinothricin (also known as glufosinate) via N-acetylation, have been globally used in basic plant research and genetically engineered crops 1-4 . Although early in vitro enzyme assays showed that recombinant BAR and PAT exhibit substrate preference toward phosphinothricin over the 20 proteinogenic amino acids 1 , indirect effects of BAR-containing transgenes in planta, including modified amino acid levels, have been seen but without the identification of their direct causes 5,6 . Combining metabolomics, plant genetics and biochemical approaches, we show that transgenic BAR indeed converts two plant endogenous amino acids, aminoadipate and tryptophan, to their respective N-acetylated products in several plant species. We report the crystal structures of BAR, and further delineate structural basis for its substrate selectivity and catalytic mechanism. Through structure-guided protein engineering, we generated several BAR variants that display significantly reduced non-specific activities compared with its wild-type counterpart in vivo. The transgenic expression of enzymes can result in unintended off-target metabolism arising from enzyme promiscuity. Understanding such phenomena at the mechanistic level can facilitate the design of maximally insulated systems featuring heterologously expressed enzymes.

  3. Nucleotide diversity analysis of three major bacterial blight resistance genes in rice.

    Directory of Open Access Journals (Sweden)

    Waikhom Bimolata

    Full Text Available Nucleotide sequence polymorphisms among R gene alleles influence the process of co-evolutionary interaction between host and pathogen by shaping the response of host plants towards invading pathogens. Here, we present the DNA sequence polymorphisms and diversities present among natural alleles of three rice bacterial blight resistance genes, Xa21, Xa26 and xa5. The diversity was examined across different wild relatives and cultivars of Oryza species. Functional significance of selected alleles was evaluated through semi-quantitative reverse transcription polymerase chain reaction and real time PCR. The greatest nucleotide diversity and singleton variable sites (SVS were present in Xa26 (π = 0.01958; SVS = 182 followed by xa5 and Xa21 alleles. The highest frequency of single nucleotide polymorphisms were observed in Xa21 alleles and least in xa5. Transition bias was observed in all the genes and 'G' to 'A' transitions were more favored than other form of transitions. Neutrality tests failed to show the presence of selection at these loci, though negative Tajima's D values indicate the presence of a rare form of polymorphisms. At the interspecies level, O. nivara exhibited more diversity than O. sativa. We have also identified two nearly identical resistant alleles of xa5 and two sequentially identical alleles of Xa21. The alleles of xa5 showed basal levels of expression while Xa21 alleles were functionally not expressed.

  4. Predictors of treatment resistance in patients with schizophrenia

    DEFF Research Database (Denmark)

    Wimberley, Theresa; Støvring, Henrik; Sørensen, Holger J

    2016-01-01

    ·13-1·37]), comorbid personality disorder (1·24 [1·11-1·39]), psychotropic drug use (antipsychotics 1·51 [1·35-1·69], antidepressants 1·15 [1·03-1·29], and benzodiazepines 1·22 [1·10-1·37]), and previous suicide attempt (1·21 [1·07-1·39]) were all significantly associated with treatment-resistant schizophrenia...... (provincial 1·38 [1·23-1·56], rural 1·44 [1·25-1·65]), primary education level (0·88 [0·79-0·98]), more than 30 bed-days in psychiatric hospital in the year before first schizophrenia diagnosis (1·54 [1·35-1·75]), inpatient at first schizophrenia diagnosis (2·07 [1·87-2·29]), paranoid subtype (1·24 [1...

  5. A kinase inhibitor screen identifies Mcl-1 and Aurora kinase A as novel treatment targets in antiestrogen-resistant breast cancer cells

    DEFF Research Database (Denmark)

    Thrane, S; Pedersen, A M; Thomsen, M B H

    2015-01-01

    Antiestrogen resistance is a major problem in breast cancer treatment. Therefore, the search for new therapeutic targets and biomarkers for antiestrogen resistance is crucial. In this study, we performed a kinase inhibitor screen on antiestrogen responsive MCF-7 cells and a panel of MCF-7-derived...

  6. Renal sympathetic denervation for treatment of resistant hypertension: Egyptian experience.

    Science.gov (United States)

    Hamza, Mohamed; Khamis, Hazem

    2014-08-01

    Among the Egyptian population with essential hypertension, a minority are under control (systolic pressure renal artery radiofrequency (RF) ablation. To evaluate the feasibility, efficacy, and safety of catheter-based radiofrequency renal sympathetic denervation for treatment of resistant hypertension in Egyptian patients. Patients with essential hypertension unresponsive to at least 3 types of antihypertensive medical therapy (baseline office systolic blood pressure ≥160 mmHg) (n = 55) were enrolled between February 2012 and June 2013 and received percutaneous RF ablation. Patients were followed up for 6 months after treatment to detect any change in office-based measurement of blood pressure. Urine and blood samples were taken to evaluate the effects on renal function. A reduction of mean office blood pressure was seen from 174/103 ± 9/5 mmHg at baseline to 150/91 ± 8/5 mmHg at 6 months follow-up (P = 0.001). Also, we noted a significant decrease in plasma renin activity (3.66 ± 0.64 vs. 3.37 ± 0.47 ng/mL per hour; P = 0.003), and there were no periprocedural complications, no adverse events, and no change in renal function during the follow-up period. Also, no change was noted in the number of medications after 6 months (3.95 ± 1.64 vs. 3.67 ± 0.72; P = 0.27). In this observational study, catheter-based renal denervation causes sustained blood pressure reduction in patients with resistant hypertension, without serious adverse events. © 2014, Wiley Periodicals, Inc.

  7. Treatment strategy for a multidrug-resistant Klebsiella UTI.

    Science.gov (United States)

    Fleming, Erin; Heil, Emily L; Hynicka, Lauren M

    2014-01-01

    To describe the management strategy for a multidrug-resistant (MDR) Klebsiella urinary tract infection (UTI). A 69-year-old Caucasian woman with a past medical history of recurrent UTIs and a right-lung transplant presented with fever to 101.4°F, chills, malaise, and cloudy, foul-smelling urine for approximately 1 week. She was found to have a MDR Klebsiella UTI that was sensitive to tigecycline and cefepime. To further evaluate the degree of resistance Etest minimum inhibitory concentrations were requested for cefepime, amikacin, meropenem, and ertapenem. The patient received a 14-day course of amikacin, which resulted in resolution of her symptoms. One month later, the patient's UTI symptoms returned. The urine culture again grew MDR Klebsiella, sensitive only to tigecycline. Fosfomycin was initiated and resulted in limited resolution of her symptoms. Colistin was started, however, therapy was discontinued on day 5 secondary to the development of acute kidney injury. Despite the short course of therapy, the patient's symptoms resolved. The case presented lends itself well to numerous discussion items that are important to consider when determining optimal treatment for MDR Gram-negative bacilli (GNBs). Susceptibility testing is an important tool for optimizing antibiotic therapy, however, automated systems may overestimate the susceptibility profile for a MDR GNB. Treatment strategies evaluated to treat MDR GNB, include combination therapy with a carbepenem and synergy using polymyxin. We have described the management strategy for a MDR Klebsiella UTI, the consequences of the initial management strategy, and potential strategies to manage these types of infections in future patients.

  8. The timing and targeting of treatment in influenza pandemics influences the emergence of resistance in structured populations.

    Science.gov (United States)

    Althouse, Benjamin M; Patterson-Lomba, Oscar; Goerg, Georg M; Hébert-Dufresne, Laurent

    2013-01-01

    Antiviral resistance in influenza is rampant and has the possibility of causing major morbidity and mortality. Previous models have identified treatment regimes to minimize total infections and keep resistance low. However, the bulk of these studies have ignored stochasticity and heterogeneous contact structures. Here we develop a network model of influenza transmission with treatment and resistance, and present both standard mean-field approximations as well as simulated dynamics. We find differences in the final epidemic sizes for identical transmission parameters (bistability) leading to different optimal treatment timing depending on the number initially infected. We also find, contrary to previous results, that treatment targeted by number of contacts per individual (node degree) gives rise to more resistance at lower levels of treatment than non-targeted treatment. Finally we highlight important differences between the two methods of analysis (mean-field versus stochastic simulations), and show where traditional mean-field approximations fail. Our results have important implications not only for the timing and distribution of influenza chemotherapy, but also for mathematical epidemiological modeling in general. Antiviral resistance in influenza may carry large consequences for pandemic mitigation efforts, and models ignoring contact heterogeneity and stochasticity may provide misleading policy recommendations.

  9. Adjunctive minocycline treatment for major depressive disorder: A proof of concept trial.

    Science.gov (United States)

    Dean, Olivia M; Kanchanatawan, Buranee; Ashton, Melanie; Mohebbi, Mohammadreza; Ng, Chee Hong; Maes, Michael; Berk, Lesley; Sughondhabirom, Atapol; Tangwongchai, Sookjaroen; Singh, Ajeet B; McKenzie, Helen; Smith, Deidre J; Malhi, Gin S; Dowling, Nathan; Berk, Michael

    2017-08-01

    Conventional antidepressant treatments result in symptom remission in 30% of those treated for major depressive disorder, raising the need for effective adjunctive therapies. Inflammation has an established role in the pathophysiology of major depressive disorder, and minocycline has been shown to modify the immune-inflammatory processes and also reduce oxidative stress and promote neuronal growth. This double-blind, randomised, placebo-controlled trial examined adjunctive minocycline (200 mg/day, in addition to treatment as usual) for major depressive disorder. This double-blind, randomised, placebo-controlled trial investigated 200 mg/day adjunctive minocycline (in addition to treatment as usual) for major depressive disorder. A total of 71 adults with major depressive disorder ( Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition) were randomised to this 12-week trial. Outcome measures included the Montgomery-Asberg Depression Rating Scale (primary outcome), Clinical Global Impression-Improvement and Clinical Global Impression-Severity, Hamilton Anxiety Rating Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool. The study was registered on the Australian and New Zealand Clinical Trials Register: www.anzctr.org.au , #ACTRN12612000283875. Based on mixed-methods repeated measures analysis of variance at week 12, there was no significant difference in Montgomery-Asberg Depression Rating Scale scores between groups. However, there were significant differences, favouring the minocycline group at week 12 for Clinical Global Impression-Improvement score - effect size (95% confidence interval) = -0.62 [-1.8, -0.3], p = 0.02; Quality of Life Enjoyment and Satisfaction Questionnaire score - effect size (confidence interval) = -0.12 [0.0, 0.2], p minocycline may be a useful adjunct to improve global experience, functioning and quality of life in people with

  10. Continuation treatment of major depressive disorder: is there a case for duloxetine?

    Directory of Open Access Journals (Sweden)

    Trevor R Norman

    2010-02-01

    Full Text Available Trevor R Norman, James S OlverDepartment of Psychiatry, University of Melbourne, Austin Hospital, Heidelberg, Victoria, AustraliaAbstract: Duloxetine is a serotonin–noradrenaline reuptake inhibitor with established efficacy for the short-term treatment of major depressive disorder. Efficacy in continuation treatment (greater than six months of continuous treatment has been established from both open and placebocontrolled relapse prevention and comparative studies. Seven published studies were available for review and showed that in both younger and older populations (aged more than 65 years the acute efficacy of duloxetine was maintained for up to one year. Response to treatment was based on accepted criteria for remission of depression and in continuation studies remission rates were greater than 70%. Comparative studies showed that duloxetine was superior to placebo and comparable to paroxetine and escitalopram in relapse prevention. Importantly a study of duloxetine in patients prone to relapse of major depressive disorder showed that the medication was more effective than placebo in this difficult to treat population. Side effects of duloxetine during continuation treatment were predictable on the basis of the known pharmacology of the drug. In particular there were no significant life-threatening events which emerged with continued use of the medication. On the other hand vigilance is required since the data base on which to judge very rare events is limited by the relatively low exposure to the drug. Duloxetine has established both efficacy and safety for continuation treatment but its place as a first-line treatment of relapse prevention requires further experience. In particular further comparative studies against established agents would be useful in deciding the place of duloxetine in therapy.Keywords: major depression, duloxetine, continuation treatment, placebo studies, relapse prevention, clinical trials

  11. Rapid molecular detection of rifampicin resistance facilitates early diagnosis and treatment of multi-drug resistant tuberculosis: case control study.

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    Philly O'Riordan

    2008-09-01

    Full Text Available Multi-drug resistant tuberculosis (MDR-TB is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months. Rapid diagnostic molecular techniques have the potential to shorten the time to commencing appropriate therapy, but have not been put to the test under field conditions.This retrospective case-control study aimed to identify risk factors for MDR-TB, and analyse the impact of testing for rifampicin resistance using RNA polymerase B (rpoB mutations as a surrogate for MDR-TB. Forty two MDR-TB cases and 84 fully sensitive TB controls were matched by date of diagnosis; and factors including demographics, clinical presentation, microbiology findings, management and outcome were analysed using their medical records. Conventionally recognised risk factors for MDR-TB were absent in almost half (43% of the cases, and 15% of cases were asymptomatic. A significant number of MDR-TB cases were identified in new entrants to the country. Using rpoB mutation testing, the time to diagnosis of MDR-TB was dramatically shortened by a median of 6 weeks, allowing patients to be commenced on appropriate therapy a median of 51days earlier than those diagnosed by conventional culture and sensitivity testing.MDR-TB is frequently an unexpected finding, may be asymptomatic, and is particularly prevalent among TB infected new entrants to the country. Molecular resistance testing of all acid fast bacilli positive specimens has the potential to rapidly identify MDR-TB patients and commence them on appropriate therapy significantly earlier than by conventional methods.

  12. Mapping of a Leishmania major gene/locus that confers pentamidine resistance by deletion and insertion of transposable element

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    Coelho Adriano C.

    2004-01-01

    Full Text Available Pentamidine (PEN is an alternative compound to treat antimony-resistant leishmaniasis patients, which cellular target remains unclear. One approach to the identification of prospective targets is to identify genes able to mediate PEN resistance following overexpression. Starting from a genomic library of transfected parasites bearing a multicopy episomal cosmid vector containing wild-type Leishmania major DNA, we isolated one locus capable to render PEN resistance to wild type cells after DNA transfection. In order to map this Leishmania locus, cosmid insert was deleted by two successive sets of partial digestion with restriction enzymes, followed by transfection into wild type cells, overexpression, induction and functional tests in the presence of PEN. To determine the Leishmania gene related to PEN resistance, nucleotide sequencing experiments were done through insertion of the transposon Mariner element of Drosophila melanogaster (mosK into the deleted insert to work as primer island. Using general molecular techniques, we described here this method that permits a quickly identification of a functional gene facilitating nucleotide sequence experiments from large DNA fragments. Followed experiments revealed the presence of a P-Glycoprotein gene in this locus which role in Leishmania metabolism has now been analyzed.

  13. Diversity of multi-drug resistant Acinetobacter baumannii population in a major hospital in Kuwait

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    Leila eVali

    2015-07-01

    Full Text Available Acinetobacter baumannii is one of the most important opportunistic pathogens that causes serious health care associated complications in critically ill patients. In the current study we report on the diversity of the clinical multi-drug resistant A. baumannii in Kuwait by molecular characterization. One hundred A. baumannii were isolated from one of the largest governmental hospitals in Kuwait. Following the identification of the isolates by molecular methods, the amplified blaOXA-51-like gene product of one isolate (KO-12 recovered from blood showed the insertion of the ISAba19 at position 379 in blaOXA-78. Of the 33 multi-drug resistant isolates, 28 (85% contained blaOXA-23, 2 (6% blaOXA-24 and 6 (18% blaPER-1 gene. We did not detect blaOXA-58, blaVIM, blaIMP, blaGES, blaVEB and blaNDM genes in any of the tested isolates. In 3 blaPER-1 positive isolates the genetic environment of blaPER-1 consisted of two copies of ISPa12 (tnpiA1 surrounding the blaPER-1 gene on a highly stable plasmid of ca. 140-kb. MLST analysis of the 33 A. baumannii isolates identified 20 different STs, of which 6 (ST-607, ST-608, ST-609, ST-610, ST-611 and ST-612 were novel. Emerging STs such as ST15 (identified for the first time in the Middle East, ST78 and ST25 were also detected. The predominant clonal complex was CC2. PFGE and MLST defined the MDR isolates as multi-clonal with diverse lineages. Our results lead us to believe that A. baumannii is diverse in clonal origins and / or is undergoing clonal expansion continuously while multiple lineages of MDR A. baumannii circulate in hospital wards simultaneously.

  14. Recent advances in novel heterocyclic scaffolds for the treatment of drug-resistant malaria.

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    Kumar, Sahil; Singh, Rajesh K; Patial, Babita; Goyal, Sachin; Bhardwaj, T R

    2016-01-01

    Malaria is a major public health problem all over the world, particularly in tropical and subtropical countries due to the development of resistance and most deadly infection is caused by Plasmodium falciparum. There is a direct need for the discovery of new drugs with unique structures and mechanism of action to treat sensitive and drug-resistant strains of various plasmodia for radical cure of this disease. Traditional compounds such as quinine and related derivatives represent a major source for the development of new drugs. This review presents recent modifications of 4-aminoquinoline and 8-aminoquinolone rings as leads to novel active molecules which are under clinical trials. The review also encompasses the other heterocyclic compounds emerged as potential antimalarial agents with promising results such as acridinediones and acridinone analogues, pyridines and quinolones as antimalarials. Miscellaneous heterocyclics such as tetroxane derivatives, indole derivatives, imidazolopiperazine derivatives, biscationic choline-based compounds and polymer-linked combined antimalarial drugs are also discussed. At last brief introduction to heterocyclics in natural products is also reviewed. Most of them have been under clinical trials and found to be promising in the treatment of drug-resistant strains of Plasmodium and others can be explored for the same purpose.

  15. Treatment-resistant depression in adolescents: is the addition of cognitive behavioral therapy of benefit?

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    Hetrick SE

    2011-08-01

    Full Text Available Sarah E Hetrick1, Georgina R Cox1, Sally N Merry21Orygen Youth Health Research Centre, Centre for Youth Mental Health, Melbourne, Parkville, Victoria, Australia; 2Werry Centre for Child and Adolescent Mental Health, Department of Psychological Medicine, The University of Auckland, Auckland, New ZealandBackground: Many young people with major depression fail first-line treatments. Treatment resistant depression has various definitions in the literature but typically assumes nonresponse to medication. In young people, cognitive behavioral therapy (CBT is the recommended firstline intervention, thus the definition of treatment resistance should be expanded. Therefore, our aim was to synthesize the existing evidence of any interventions for treatment-resistant depression, broadly defined, in children and adolescents and to investigate the effectiveness of CBT in this context. Methods: We used Cochrane Collaboration methodology, with electronic searches of Medline, PsycINFO, Embase, and the Cochrane Depression Anxiety and Neurosis Group trials registers. Only randomized controlled trials were included, and were assessed for risk of bias. Meta-analysis was undertaken where possible and appropriate.Results: Of 953 articles retrieved, four trials were eligible for inclusion. For one study, only the trial registration document was available, because the study was never completed. All other studies were well conducted with a low risk of bias, although one study had a high dropout rate. Two studies assessed the effect of adding CBT to medication. While an assertive trial of antidepressants does appear to lead to benefit, when compared with placebo, there was no significant advantage, in either study, or in a meta-analysis of data from these trials, that clearly demonstrated an additional benefit of CBT. The third trial showed little advantage of a tricyclic antidepressant over placebo in the context of an inpatient admission. Conclusion: Few randomized

  16. HIV diversity and drug resistance from plasma and non-plasma analytes in a large treatment programme in western Kenya.

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    Kantor, Rami; DeLong, Allison; Balamane, Maya; Schreier, Leeann; Lloyd, Robert M; Injera, Wilfred; Kamle, Lydia; Mambo, Fidelis; Muyonga, Sarah; Katzenstein, David; Hogan, Joseph; Buziba, Nathan; Diero, Lameck

    2014-01-01

    Antiretroviral resistance leads to treatment failure and resistance transmission. Resistance data in western Kenya are limited. Collection of non-plasma analytes may provide additional resistance information. We assessed HIV diversity using the REGA tool, transmitted resistance by the WHO mutation list and acquired resistance upon first-line failure by the IAS-USA mutation list, at the Academic Model Providing Access to Healthcare (AMPATH), a major treatment programme in western Kenya. Plasma and four non-plasma analytes, dried blood-spots (DBS), dried plasma-spots (DPS), ViveST(TM)-plasma (STP) and ViveST-blood (STB), were compared to identify diversity and evaluate sequence concordance. Among 122 patients, 62 were treatment-naïve and 60 treatment-experienced; 61% were female, median age 35 years, median CD4 182 cells/µL, median viral-load 4.6 log10 copies/mL. One hundred and ninety-six sequences were available for 107/122 (88%) patients, 58/62 (94%) treatment-naïve and 49/60 (82%) treated; 100/122 (82%) plasma, 37/78 (47%) attempted DBS, 16/45 (36%) attempted DPS, 14/44 (32%) attempted STP from fresh plasma and 23/34 (68%) from frozen plasma, and 5/42 (12%) attempted STB. Plasma and DBS genotyping success increased at higher VL and shorter shipment-to-genotyping time. Main subtypes were A (62%), D (15%) and C (6%). Transmitted resistance was found in 1.8% of plasma sequences, and 7% combining analytes. Plasma resistance mutations were identified in 91% of treated patients, 76% NRTI, 91% NNRTI; 76% dual-class; 60% with intermediate-high predicted resistance to future treatment options; with novel mutation co-occurrence patterns. Nearly 88% of plasma mutations were identified in DBS, 89% in DPS and 94% in STP. Of 23 discordant mutations, 92% in plasma and 60% in non-plasma analytes were mixtures. Mean whole-sequence discordance from frozen plasma reference was 1.1% for plasma-DBS, 1.2% plasma-DPS, 2.0% plasma-STP and 2.3% plasma-STB. Of 23 plasma

  17. Risperidone, quetiapine, and olanzapine adjunctive treatments in major depression with psychotic features: a comparative study

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    Gabriel A

    2013-04-01

    Full Text Available A Gabriel Departments of Psychiatry and Community Health Sciences, University of Calgary, Calgary, AB, Canada Objectives: The purpose of this study was to compare the effectiveness of novel antipsychotics in the treatment of psychotic depression. Method: Consecutive patients who were admitted (n = 51 with a confirmed diagnosis of major depression with psychotic features (delusions or hallucinations or both participated in this open-label, naturalistic study. All patients were treated with selective serotonin reuptake inhibitors (SSRIs and serotonin–norepinephrine reuptake inhibitors (SNRIs (citalopram or venlafaxine extended release [XR], and atypical antipsychotic agents were added, as tolerated, during the first week of initiating the citalopram or venlafaxine. There were patients (n = 16 who received risperidone, who received quetiapine (n = 20, and who received olanzapine (n = 15, as an adjunctive treatment to either citalopram or venlafaxine for at least 8 weeks. Outcome measures included the Clinical Global Impression-Severity subscale (CGI-S, as the primary outcome measure, as well as the Hamilton Rating Scale for Depression-21 item (HAM-D21 and the Brief Psychiatric Rating Scale (BPRS. Tolerance to treatments and weight changes were monitored over the period of the trial. Results: All patients completed the trial with no drop outs. At 8 weeks, there was a statistically significant (P 0.01 in the olanzapine group. Conclusion: Quetiapine, risperidone, and olanzapine, given as adjunctive treatment with SSRIS or SNRIs can significantly and equally improve depressive and psychotic symptoms, in the short-term treatment of major depression with psychotic features. The author recommends that large controlled trials be conducted to examine the differences in long-term efficacy and tolerance between the atypical antipsychotic agents, in the treatment of major depression with or without psychotic features. Keywords: depression, novels

  18. Depression and Suicidal Ideation During Two Psychosocial Treatments in Older Adults with Major Depression and Dementia.

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    Kiosses, Dimitris N; Rosenberg, Paul B; McGovern, Amanda; Fonzetti, Pasquale; Zaydens, Hana; Alexopoulos, George S

    2015-01-01

    Depression is prevalent in dementia and contributes to poor outcomes for patients and their families. Antidepressants have limited efficacy in older adults with major depression and dementia, and psychosocial interventions are under-investigated. To examine the course, predictors and moderators of depression and suicidal ideation during 12 weeks of home-delivered Problem Adaptation Therapy (PATH) versus Supportive Therapy for Cognitively Impaired Older Adults (ST-CI) in 39 older adults with major depression and dementia. Thirty-nine older adults with major depression, mild or moderate dementia, and disability participated in a randomized controlled trial that compared the efficacy of PATH versus ST-CI. Depression and suicidal ideation were assessed with Cornell Scale for Depression in Dementia Total Score and Suicide Item. PATH participants had significantly greater reduction in depression than ST-CI participants over 12 weeks of treatment. PATH participants with high social support had the greatest reduction in depression. Both treatments had comparable reduction in suicidal ideation. PATH is more effective in reducing depression in older adults with major depression and dementia compared to ST-CI. These results are clinically significant as antidepressants have limited efficacy in this population. Home-delivered psychosocial treatments may reduce suicidal ideation in this population.

  19. Tertiary work-up of apparent treatment-resistant hypertension.

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    Heimark, Sondre; Eskås, Per Anders; Mariampillai, Julian Eek; Larstorp, Anne Cecilie K; Høieggen, Aud; Fadl Elmula, Fadl Elmula M

    2016-10-01

    Treatment-resistant hypertension (TRH) has regained attention with development of new methods for treatment. However, the prevalence of TRH varies considerably from primary to secondary and tertiary care. We aimed to assess the prevalence of true TRH in a population of patients with apparent TRH in a university hospital setting of tertiary work-up and also investigate reasons for poor BP control and evaluate how work-up can be performed in general practice and secondary care. In this cohort study, we characterize a study population from Oslo Renal Denervation (RDN) Study. Patients (n = 83) were referred for RDN from secondary care. All patients underwent thorough medical investigation and 24-h ambulatory blood pressure measurements (24ABPM) after directly observed therapy (DOT). We then assessed reasons for lack of BP control. Fifty-three of 83 patients did not have true TRH. Main reasons for non-TRH were poor drug adherence (32%), secondary hypertension (30%) and white coat hypertension (15%). Forty-seven percent achieved blood pressure control after DOT with subsequent 24ABPM. There were otherwise no statistically significant differences in patient characteristics between the true TRH and the non-TRH group. Despite being a highly selected cohort referred for tertiary work-up of apparent TRH, BP control was achieved or secondary causes were identified in almost two thirds of the patients. Thorough investigation according to guidelines and DOT with subsequent 24ABPM is needed in work-up of apparent TRH.

  20. High vitamin B12 level and good treatment outcome may be associated in major depressive disorder

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    Tanskanen Antti

    2003-12-01

    Full Text Available Abstract Background Despite of an increasing body of research the associations between vitamin B12 and folate levels and the treatment outcome in depressive disorders are still unsolved. We therefore conducted this naturalistic prospective follow-up study. Our aim was to determine whether there were any associations between the vitamin B12 and folate level and the six-month treatment outcome in patients with major depressive disorder. Because vitamin B12 and folate deficiency may result in changes in haematological indices, including mean corpuscular volume, red blood cell count and hematocrit, we also examined whether these indices were associated with the treatment outcome. Methods Haematological indices, erythrocyte folate and serum vitamin B12 levels were determined in 115 outpatients with DSM-III-R major depressive disorder at baseline and serum vitamin B12 level again on six-month follow-up. The 17-item Hamilton Depression Rating Scale was also compiled, respectively. In the statistical analysis we used chi-squared test, Pearson's correlation coefficient, the Student's t-test, analysis of variance (ANOVA, and univariate and multivariate linear regression analysis. Results Higher vitamin B12 levels significantly associated with a better outcome. The association between the folate level and treatment outcome was weak and probably not independent. No relationship was found between haematological indices and the six-month outcome. Conclusion The vitamin B12 level and the probability of recovery from major depression may be positively associated. Nevertheless, further studies are suggested to confirm this finding.

  1. [Physician knowledge and attitudes on the clinical evaluation and treatment of resistant hypertension: The RESIST study].

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    Coca, A

    Resistant hypertension (RH) is associated with a high risk of cardiovascular and renal complications. The purpose of this study was to assess the knowledge and attitudes of Primary Care physicians, general medicine doctors, and clinical cardiologists on the management of this condition. A multicentre, descriptive, observational study based on an ad hoc questionnaire distributed to Primary Care physicians (n=1017) and general medicine physicians/clinical cardiologists (n=457). To establish the diagnosis of resistant hypertension, 69.1% of physicians confirm that systolic/diastolic blood pressure is above 140/90 mmHg, despite treatment. Furthermore, 64.9% only consider this diagnosis if the patient is treated with at least 3 medications, and 50.3% also requires that one of them is a thiazide diuretic (56.7% among specialists, P=.0004). To establish a definite diagnosis of true RH, 89.6% perform 24-h ambulatory blood pressure monitoring (93.3% of specialists, P=.0017), looking specifically for «white-coat» effect in 70.2% of cases. In addition, 79.3% verify that adherence to treatment is adequate. Between 87 and 95% of physicians indicate examinations to exclude causes of secondary hypertension. Up to 54.3% of physicians (71.3% specialists, P<.0001) consider adding a fourth drug and insisting on lifestyle interventions as a priority therapeutic measure. These data show that physician knowledge regarding the management of patients with RH is good. Interestingly, this knowledge is somewhat higher among specialists than among Primary Care physicians. Copyright © 2016 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Mental health treatment after major surgery among Vietnam-era Veterans with posttraumatic stress disorder.

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    Tsan, Jack Y; Stock, Eileen M; Greenawalt, David S; Zeber, John E; Copeland, Laurel A

    2016-07-01

    The purpose of this study was to examine mental health treatment use among Vietnam Veterans with posttraumatic stress disorder and determine whether undergoing major surgery interrupted mental health treatment or increased the risk of psychiatric hospitalization. Using retrospective data from Veterans Health Administration's electronic medical record system, a total of 3320 Vietnam-era surgery patients with preoperative posttraumatic stress disorder were identified and matched 1:4 with non-surgical patients with posttraumatic stress disorder. The receipt of surgery was associated with a decline in overall mental health treatment and posttraumatic stress disorder-specific treatment 1 month following surgery but not during any subsequent month thereafter. Additionally, surgery was not associated with psychiatric admission. © The Author(s) 2014.

  3. Low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use.

    Science.gov (United States)

    Le, Thuy; Chiarella, Jennifer; Simen, Birgitte B; Hanczaruk, Bozena; Egholm, Michael; Landry, Marie L; Dieckhaus, Kevin; Rosen, Marc I; Kozal, Michael J

    2009-06-29

    It is largely unknown how frequently low-abundance HIV drug-resistant variants at levels under limit of detection of conventional genotyping (<20% of quasi-species) are present in antiretroviral-experienced persons experiencing virologic failure. Further, the clinical implications of low-abundance drug-resistant variants at time of virologic failure are unknown. Plasma samples from 22 antiretroviral-experienced subjects collected at time of virologic failure (viral load 1380 to 304,000 copies/mL) were obtained from a specimen bank (from 2004-2007). The prevalence and profile of drug-resistant mutations were determined using Sanger sequencing and ultra-deep pyrosequencing. Genotypes were interpreted using Stanford HIV database algorithm. Antiretroviral treatment histories were obtained by chart review and correlated with drug-resistant mutations. Low-abundance drug-resistant mutations were detected in all 22 subjects by deep sequencing and only in 3 subjects by Sanger sequencing. In total they accounted for 90 of 247 mutations (36%) detected by deep sequencing; the majority of these (95%) were not detected by standard genotyping. A mean of 4 additional mutations per subject were detected by deep sequencing (p<0.0001, 95%CI: 2.85-5.53). The additional low-abundance drug-resistant mutations increased a subject's genotypic resistance to one or more antiretrovirals in 17 of 22 subjects (77%). When correlated with subjects' antiretroviral treatment histories, the additional low-abundance drug-resistant mutations correlated with the failing antiretroviral drugs in 21% subjects and correlated with historical antiretroviral use in 79% subjects (OR, 13.73; 95% CI, 2.5-74.3, p = 0.0016). Low-abundance HIV drug-resistant mutations in antiretroviral-experienced subjects at time of virologic failure can increase a subject's overall burden of resistance, yet commonly go unrecognized by conventional genotyping. The majority of unrecognized resistant mutations correlate with

  4. Low-abundance HIV drug-resistant viral variants in treatment-experienced persons correlate with historical antiretroviral use.

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    Thuy Le

    Full Text Available BACKGROUND: It is largely unknown how frequently low-abundance HIV drug-resistant variants at levels under limit of detection of conventional genotyping (<20% of quasi-species are present in antiretroviral-experienced persons experiencing virologic failure. Further, the clinical implications of low-abundance drug-resistant variants at time of virologic failure are unknown. METHODOLOGY/PRINCIPAL FINDINGS: Plasma samples from 22 antiretroviral-experienced subjects collected at time of virologic failure (viral load 1380 to 304,000 copies/mL were obtained from a specimen bank (from 2004-2007. The prevalence and profile of drug-resistant mutations were determined using Sanger sequencing and ultra-deep pyrosequencing. Genotypes were interpreted using Stanford HIV database algorithm. Antiretroviral treatment histories were obtained by chart review and correlated with drug-resistant mutations. Low-abundance drug-resistant mutations were detected in all 22 subjects by deep sequencing and only in 3 subjects by Sanger sequencing. In total they accounted for 90 of 247 mutations (36% detected by deep sequencing; the majority of these (95% were not detected by standard genotyping. A mean of 4 additional mutations per subject were detected by deep sequencing (p<0.0001, 95%CI: 2.85-5.53. The additional low-abundance drug-resistant mutations increased a subject's genotypic resistance to one or more antiretrovirals in 17 of 22 subjects (77%. When correlated with subjects' antiretroviral treatment histories, the additional low-abundance drug-resistant mutations correlated with the failing antiretroviral drugs in 21% subjects and correlated with historical antiretroviral use in 79% subjects (OR, 13.73; 95% CI, 2.5-74.3, p = 0.0016. CONCLUSIONS/SIGNIFICANCE: Low-abundance HIV drug-resistant mutations in antiretroviral-experienced subjects at time of virologic failure can increase a subject's overall burden of resistance, yet commonly go unrecognized by conventional

  5. Predictors, moderators, and mediators (correlates) of treatment outcome in major depressive disorder.

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    Papakostas, George I; Fava, Maurizio

    2008-01-01

    Major Depressive Disorder (MDD) is a prevalent illness that is frequently associated with significant disability, morbidity and mortality Despite the development and availability of numerous treatment options for MDD, studies have shown that antidepressant monotherapy yields only modest rates of response and remission. Clearly, there is an urgent need to develop more effective treatment strategies for patients with MDD. One possible approach towards the development of novel pharmacotherapeutic strategies for MDD involves identifying subpopulations of depressed patients who are more likely to experience the benefits of a given (existing) treatment versus placebo, or versus a second treatment. Attempts have been made to identify such "subpopulations", specifically by testing whether a given biological or clinical marker also serves as a moderator, mediator (correlate), or predictor of clinical improvement following the treatment of MDD with standard, first-line antidepressants. In the following article, we will attempt to summarize the literature focusing on several major areas ("leads") where preliminary evidence exists regarding clinical and biologic moderators, mediators, and predictors of symptom improvement in MDD. Such clinical leads will include the presence of hopelessness, anxious symptoms, or medical comorbidity. Biologic leads will include gene polymorphisms, brain metabolism, quantitative electroencephalography, loudness dependence of auditory evoked potentials, and functional brain asymmetry.

  6. Primary Sjogren’s Syndrome Associated With Treatment-Resistant Obsessive–Compulsive Disorder

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    Lawrence T. C. Ong

    2017-07-01

    Full Text Available There is an increasing awareness that autoimmune diseases can present with neuropsychiatric manifestations. We present the case of a 17-year-old female requiring psychiatric hospitalization for obsessive–compulsive disorder and major depressive disorder with mixed affective features, who was subsequently diagnosed with primary Sjogren’s syndrome. Treatment with potent immunosuppression resulted in remission of psychiatric illness. Due to a lack of awareness and/or the lack of specific biomarkers, clinicians may not associate psychiatric symptoms with autoimmune disease, including primary Sjogren’s syndrome. This case demonstrates that Sjogren’s syndrome may be a causative or aggravating factor in mental disorders and that autoimmune diseases should be carefully considered in the differential diagnosis of psychiatric illness especially in cases of concurrent physical symptomatology and severity or treatment resistance of psychiatric disease.

  7. Biofilm is a Major Virulence Determinant in Bacterial Colonization of Chronic Skin Ulcers Independently from the Multidrug Resistant Phenotype

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    Enea Gino Di Domenico

    2017-05-01

    Full Text Available Bacterial biofilm is a major factor in delayed wound healing and high levels of biofilm production have been repeatedly described in multidrug resistant organisms (MDROs. Nevertheless, a quantitative correlation between biofilm production and the profile of antimicrobial drug resistance in delayed wound healing remains to be determined. Microbial identification, antibiotic susceptibility and biofilm production were assessed in 135 clinical isolates from 87 patients. Gram-negative bacteria were the most represented microorganisms (60.8% with MDROs accounting for 31.8% of the total isolates. Assessment of biofilm production revealed that 80% of the strains were able to form biofilm. A comparable level of biofilm production was found with both MDRO and not-MDRO with no significant differences between groups. All the methicillin-resistant Staphylococcus aureus (MRSA and 80% of Pseudomonas aeruginosa MDR strains were found as moderate/high biofilm producers. Conversely, less than 17% of Klebsiella pneumoniae extended-spectrum beta-lactamase (ESBL, Escherichia coli-ESBL and Acinetobacter baumannii were moderate/high biofilm producers. Notably, those strains classified as non-biofilm producers, were always associated with biofilm producer bacteria in polymicrobial colonization. This study shows that biofilm producers were present in all chronic skin ulcers, suggesting that biofilm represents a key virulence determinant in promoting bacterial persistence and chronicity of ulcerative lesions independently from the MDRO phenotype.

  8. Antidepressant efficacy of sertraline and imipramine for the treatment of major depression in elderly outpatients

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    Orestes Vicente Forlenza

    2000-07-01

    Full Text Available CONTEXT: Most double-blind studies of efficacy and tolerability of sertraline as compared to tricyclics in the treatment of late-life major depression have used amitriptyline as a standard, leading to the inevitable conclusion that the former drug is better tolerated than the latter, with both being equally efficacious. OBJECTIVE: To compare the antidepressant efficacy and tolerability of sertraline (50 mg/day and imipramine (150 mg/day in the first 6 weeks of the treatment of major depression in the elderly. DESIGN: A randomized double-blind parallel study with 6 weeks of follow-up. SETTING: The psychogeriatric clinic at the Institute of Psychiatry, Hospital das Clínicas, Faculty of Medicine of the University of São Paulo. PARTICIPANTS: 55 severe and moderately depressed non-demented outpatients aged 60 years or more. INTERVENTION: Patients were assigned to sertraline 50 mg/day or imipramine 150 mg/day. MAIN MEASUREMENTS: CAMDEX interview. Psychiatric diagnosis followed the guidelines for "Major Depressive Episode" according to DSM-IV criteria. Severity of symptoms was evaluated using the "CGI" and "MADRS" scales. Cognitive state was assessed using the Mini-Mental State Examination. Side effects were assessed using the "Safetee-Up" schedule. RESULTS: Both groups had a significant decrease in depressive symptoms according to the MADRS scores after 6 weeks of treatment (P = 0.01. No significant differences between groups were detected regarding treatment outcome (t = 0.4; P = 0.7. Although the dropout rate was greater in the imipramine group, the overall tolerability among patients who completed the 6-week trial was similar in both test groups. CONCLUSIONS: Both sertraline and imipramine exhibited good efficacy and an acceptable side-effect profile for elderly depressed patients after 6 weeks of antidepressant treatment.

  9. Monitoring of drug resistance amplification and attenuation with the use of tetracycline-resistant bacteria during wastewater treatment

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    Harnisz, Monika; Korzeniewska, Ewa; Niestępski, Sebastian; Osińska, Adriana; Nalepa, Beata

    2017-11-01

    The objective of this study was to monitor changes (amplification or attenuation) in antibiotic resistance during wastewater treatment based on the ecology of tetracycline-resistant bacteria. The untreated and treated wastewater were collected in four seasons. Number of tetracycline-(TETR) and oxytetracycline-resistant (OTCR) bacteria, their qualitative composition, minimum inhibitory concentrations (MICs), sensitivity to other antibiotics, and the presence of tet (A, B, C, D, E) resistance genes were determined. TETR and OTCR counts in untreated wastewater were 100 to 1000 higher than in treated effluent. OTCR bacterial counts were higher than TETR populations in both untreated and treated wastewater. TETR isolates were not dominated by a single bacterial genus or species, whereas Aeromonas hydrophila and Aeromonas sobria were the most common in OTCR isolates. The treatment process attenuated the drug resistance of TETR bacteria and amplified the resistance of OTCR bacteria. In both microbial groups, the frequency of tet(A) gene increased in effluent in comparison with untreated wastewater. Our results also indicate that treated wastewater is a reservoir of multiple drug-resistant bacteria as well as resistance determinants which may pose a health hazard for humans and animals when released to the natural environment.

  10. Effect of Omega-3 Fatty Acids Treatment on Insulin Resistance

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    Mogoş Tiberius

    2014-12-01

    Full Text Available Background and aims: Insulin resistance (IR is a common pathogenic factor of several diseases: diabetes mellitus, the metabolic syndrome, arterial hypertension, atherosclerosis, dyslipidemia, etc. There are many therapeutic factors involved in decreasing IR. Among them we mention metformin, pioglitazone, physical activity, weight loss, diet, etc. In the last decade, there are more observations of the influence of polyunsaturated fatty acids on IR. The most powerful seem to be omega-3 fatty acids. In our study, we wanted to asses if the administration of omega-3 fatty acids is involved in modifying IR. Materials and methods: We evaluated 126 diabetic patients with IR from January 2011 until July 2014. The study was open-label and non-randomized. For the determination of IR we used the HOMA-IR method. Results: For both males and females there was a regression of HOMA-IR during the 4 weeks of treatment with omega-3 and also after 2 weeks after stopping the administration of these fatty acids. The decrease of HOMA-IR was statistically significant (p<0.05. The statistic result observed in the next 2 weeks after stopping administration of omega-3 was also significant (p<0.05.

  11. Renal denervation for treatment of drug-resistant hypertension.

    Science.gov (United States)

    Esler, Murray

    2015-02-01

    At the seven-year anniversary of the first catheter-based renal denervation procedure for resistant hypertension, it is timely to reflect on the past, present, and future of the development and clinical application of this treatment. Unresolved procedural and technical questions are central: How much renal denervation is optimal? How can this level of denervation be achieved? What test for denervation can be applied in renal denervation trials? Will renal denervation show a "class effect," with the different energy forms now used for renal nerve ablation producing equivalent blood pressure lowering? When I have assessed renal denervation efficacy, using measurements of the spillover of norepinephrine from the renal sympathetic nerves to plasma, the only test validated to this point, denervation was found to be incomplete and non-uniform between patients. It is probable that the degree of denervation has commonly been suboptimal in renal denervation trials; this criticism applying with special force to the Symplicity HTN-3 trial, where the proceduralists, although expert interventional cardiologists, had no prior experience with the renal denervation technique. Recently presented results from the Symplicity HTN-3 trial confirm that renal denervation was not achieved effectively or consistently. Given this, and other difficulties in the execution of the trial relating to drug adherence, an idea mooted is that the US pivotal trial of the future may be in younger, untreated patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Targeted therapy and personalized medicine in hepatocellular carcinoma: drug resistance, mechanisms, and treatment strategies

    Directory of Open Access Journals (Sweden)

    Galun D

    2017-07-01

    Full Text Available Danijel Galun,1,2 Tatjana Srdic-Rajic,3 Aleksandar Bogdanovic,1 Zlatibor Loncar,2,4 Marinko Zuvela1,2 1Hepato-Pancreato-Biliary Unit, University Clinic for Digestive Surgery, Clinical Center of Serbia, 2Medical School, University of Belgrade, 3Institute for Oncology and Radiology of Serbia/Unit for Experimental Oncology, 4Emergency Center, Clinical Center of Serbia, Belgrade, Serbia Abstract: Hepatocellular carcinoma (HCC is characterized by a growing number of new cases diagnosed each year that is nearly equal to the number of deaths from this cancer. In a majority of the cases, HCC is associated with the underlying chronic liver disease, and it is diagnosed in advanced stage of disease when curative treatment options are not applicable. Sorafenib is a treatment of choice for patients with performance status 1 or 2 and/or macrovascular invasion or extrahepatic spread, and regorafenib is the only systemic treatment found to provide survival benefit in HCC patients progressing on sorafenib treatment. Other drugs tested in different trials failed to demonstrate any benefit. Disappointing results of numerous trials testing the efficacy of various drugs indicate that HCC has low sensitivity to chemotherapy that is in great part caused by multidrug resistance. Immunotherapy for HCC is a new challenging treatment option and involves immune checkpoint inhibitors/antibody-based therapy and peptide-based vaccines. Another challenging approach is microRNA-based therapy that involves two strategies. The first aims to inhibit oncogenic miRNAs by using miRNA antagonists and the second strategy is miRNA replacement, which involves the reintroduction of a tumor-suppressor miRNA mimetic to restore a loss of function. Keywords: hepatocellular carcinoma, drug resistance, multimodal treatment, chemotherapy 

  13. Childhood maltreatment and differential treatment response and recurrence in adult major depressive disorder.

    Science.gov (United States)

    Harkness, Kate L; Bagby, R Michael; Kennedy, Sidney H

    2012-06-01

    A substantial number of patients with major depressive disorder (MDD) do not respond to treatment, and recurrence rates remain high. The purpose of this study was to examine a history of severe childhood abuse as a moderator of response following a 16-week acute treatment trial, and of recurrence over a 12-month follow-up. Participants included 203 adult outpatients with MDD (129 women; age 18-60). The design was a 16-week single-center randomized, open label trial of interpersonal psychotherapy, cognitive-behavioral therapy, or antidepressant medication, with a 12-month naturalistic follow-up, conducted at a university psychiatry center in Canada. The main outcome measure was Hamilton Depression Rating Scale scores at treatment end point. Childhood maltreatment was assessed at the completion of treatment using an interview-based contextual measure of childhood physical, sexual, and emotional abuse. Multiple imputation was adopted to estimate missing values. Patients with severe maltreatment were significantly less likely to respond to interpersonal psychotherapy than to cognitive-behavioral therapy or medication (OR = 3.61), whereas no differences among treatments were found in those with no history of maltreatment (ORs therapy than from interpersonal psychotherapy. However, these patients remain vulnerable to recurrence regardless of treatment modality.

  14. Bupropion in the treatment of problematic online game play in patients with major depressive disorder.

    Science.gov (United States)

    Han, Doug Hyun; Renshaw, Perry F

    2012-05-01

    As one of the problematic behaviors in patients with major depressive disorder (MDD), excessive online game play (EOP) has been reported in a number of recent studies. Bupropion has been evaluated as a potential treatment for MDD and substance dependence. We hypothesized that bupropion treatment would reduce the severity of EOP as well as depressive symptoms. Fifty male subjects with comorbid EOP and MDD were randomly assigned to bupropion + education for internet use (EDU) or placebo + EDU groups. The current study consisted in a 12-week, prospective, randomized, double-blind clinical trial, including an eight-week active treatment phase and a four-week post treatment follow-up period. During the active treatment period, Young Internet Addiction Scale (YIAS) scores and the mean time of online game playing in the bupropion group were greatly reduced compared with those of the placebo group. The Beck Depression Inventory (BDI) scores in the bupropion group were also greatly reduced compared with those of the placebo group. During the four-week post-treatment follow-up period, bupropion-associated reductions in online game play persisted, while depressive symptoms recurred. Conclusively, bupropion may improve depressive mood as well as reduce the severity of EOP in patients with comorbid MDD and online game addiction.

  15. Bupropion in the treatment of problematic online game play in patients with major depressive disorder

    Science.gov (United States)

    Han, Doug Hyun; Renshaw, Perry F

    2015-01-01

    As one of the problematic behaviors in patients with major depressive disorder (MDD), excessive online game play (EOP) has been reported in a number of recent studies. Bupropion has been evaluated as a potential treatment for MDD and substance dependence. We hypothesized that bupropion treatment would reduce the severity of EOP as well as depressive symptoms. Fifty male subjects with comorbid EOP and MDD were randomly assigned to bupropion + education for internet use (EDU) or placebo + EDU groups. The current study consisted in a 12-week, prospective, randomized, double-blind clinical trial, including an eight-week active treatment phase and a four-week post treatment follow-up period. During the active treatment period, Young Internet Addiction Scale (YIAS) scores and the mean time of online game playing in the bupropion group were greatly reduced compared with those of the placebo group. The Beck Depression Inventory (BDI) scores in the bupropion group were also greatly reduced compared with those of the placebo group. During the four-week post-treatment follow-up period, bupropion-associated reductions in online game play persisted, while depressive symptoms recurred. Conclusively, bupropion may improve depressive mood as well as reduce the severity of EOP in patients with comorbid MDD and online game addiction. PMID:21447539

  16. Developing Community Reinforcement and Family Training (CRAFT) for Parents of Treatment-Resistant Adolescents

    Science.gov (United States)

    Kirby, Kimberly C.; Versek, Brian; Kerwin, MaryLouise E.; Meyers, Kathleen; Benishek, Lois A.; Bresani, Elena; Washio, Yukiko; Arria, Amelia; Meyers, Robert J.

    2015-01-01

    We describe a project focused on training parents to facilitate their treatment-resistant adolescent's treatment entry and to manage their child after entry into community-based treatment. Controlled studies show that Community Reinforcement and Family Training (CRAFT) is a unilateral treatment that fosters treatment entry of adults; however,…

  17. Deletion of IL-4Ralpha on CD4 T cells renders BALB/c mice resistant to Leishmania major infection.

    Directory of Open Access Journals (Sweden)

    Magdalena Radwanska

    2007-05-01

    Full Text Available Effector responses induced by polarized CD4+ T helper 2 (Th2 cells drive nonhealing responses in BALB/c mice infected with Leishmania major. Th2 cytokines IL-4 and IL-13 are known susceptibility factors for L. major infection in BALB/c mice and induce their biological functions through a common receptor, the IL-4 receptor alpha chain (IL-4Ralpha. IL-4Ralpha-deficient BALB/c mice, however, remain susceptible to L. major infection, indicating that IL-4/IL-13 may induce protective responses. Therefore, the roles of polarized Th2 CD4+ T cells and IL-4/IL-13 responsiveness of non-CD4+ T cells in inducing non-healer or healer responses have yet to be elucidated. CD4+ T cell-specific IL-4Ralpha (Lck(creIL-4Ralpha(-/lox deficient BALB/c mice were generated and characterized to elucidate the importance of IL-4Ralpha signaling during cutaneous leishmaniasis in the absence of IL-4-responsive CD4+ T cells. Efficient deletion was confirmed by loss of IL-4Ralpha expression on CD4+ T cells and impaired IL-4-induced CD4+ T cell proliferation and Th2 differentiation. CD8+, gammadelta+, and NK-T cells expressed residual IL-4Ralpha, and representative non-T cell populations maintained IL-4/IL-13 responsiveness. In contrast to IL-4Ralpha(-/lox BALB/c mice, which developed ulcerating lesions following infection with L. major, Lck(creIL-4Ralpha(-/lox mice were resistant and showed protection to rechallenge, similar to healer C57BL/6 mice. Resistance to L. major in Lck(creIL-4Ralpha(-/lox mice correlated with reduced numbers of IL-10-secreting cells and early IL-12p35 mRNA induction, leading to increased delayed type hypersensitivity responses, interferon-gamma production, and elevated ratios of inducible nitric oxide synthase mRNA/parasite, similar to C57BL/6 mice. These data demonstrate that abrogation of IL-4 signaling in CD4+ T cells is required to transform non-healer BALB/c mice to a healer phenotype. Furthermore, a beneficial role for IL-4Ralpha signaling in L

  18. Resistance to valproic acid as predictor of treatment resistance in genetic generalized epilepsies

    DEFF Research Database (Denmark)

    Gesche, Joanna; Khanevski, Marina; Solberg, Carl

    2017-01-01

    for refractory seizures. Resistance to valproic acid had a specificity of 100% to identify patients with drug resistance and correlated strongly with bad social outcome and seizure burden. Conversely, 21.2% of all patients with refractory seizures according to the ILAE definition later became seizure free...... (mainly with valproic acid). Our data suggest that "drug resistant GGE" must not be declared unless patients were adequately treated with valproic acid, and advocate resistance to valproic acid as a new clinical biomarker for drug-resistant GGE. A PowerPoint slide summarizing this article is available...

  19. Multidrug-Resistant Candida: Epidemiology, Molecular Mechanisms, and Treatment.

    Science.gov (United States)

    Arendrup, Maiken Cavling; Patterson, Thomas F

    2017-08-15

    Invasive Candida infections remain an important cause of morbidity and mortality, especially in hospitalized and immunocompromised or critically ill patients. A limited number of antifungal agents from only a few drug classes are available to treat patients with these serious infections. Resistance can be either intrinsic or acquired. Resistance mechanisms are not exchanged between Candida; thus, acquired resistance either emerges in response to an antifungal selection pressure in the individual patient or, more rarely, occur due to horizontal transmission of resistant strains between patients. Although multidrug resistance is uncommon, increasing reports of multidrug resistance to the azoles, echinocandins, and polyenes have occurred in several Candida species, most notably Candida glabrata and more recently Candida auris. Drivers are overall antifungal use, subtherapeutic drug levels at sites of infection/colonization, drug sequestration in the biofilm matrix, and, in the setting of outbreaks, suboptimal infection control. Moreover, recent research suggests that DNA mismatch repair gene mutations may facilitate acquisition of resistance mutations in C. glabrata specifically. Diagnosis of antifungal-resistant Candida infections is critical to the successful management of patients with these infections. Reduction of unnecessary use of antifungals via antifungal stewardship is critical to limit multidrug resistance emergence. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  20. Presence of Methicillin Resistant Staphylococcus aureus (MRSA) in sewage treatment plant.

    Science.gov (United States)

    Boopathy, Raj

    2017-09-01

    The presence of antibiotic resistant bacteria and antibiotic resistance genes in rural sewage treatment plants are not well reported in the literature. The aim of the present study was to study the frequency occurrence of Methicillin Resistant Staphylococcus aureus (MRSA) in a rural sewage treatment plant. This study was conducted using raw sewage as well as treated sewage from a small town sewage treatment plant in rural southeast Louisiana of USA. Results showed the presence of MRSA consistently in both raw and treated sewage. The presence of mecA gene responsible for methicillin resistance was confirmed in the raw and treated sewage water samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. [What are Considerations for Clinical Investigation of New Drugs and Treatment Techniques for Major Depressive Disorders?].

    Science.gov (United States)

    Nakabayashi, Tetsuo

    2015-01-01

    Major depressive disorder treatments remain unsatisfactory, and the development of novel antidepressants is continuing. Therefore, not only the establishment of therapeutic strategies to accumulate evidence on existing therapies, but also the development of novel therapies is required in order to improve the medical standards. In principle, parallel, double-blind, randomized, placebo-controlled trials are necessary to assess new compounds for the treatment of major depressive disorders from a scientific perspective. To provide unambiguous evidence of antidepressant activity, well-controlled studies with adequate designs must show efficacy with a statistically significant effect on a clinically meaningful endpoint. For this purpose, it is important to examine all aspects of factors that adversely affect the efficacy and safety assessment in the planning stage of clinical trials and reduce these factors. There are several specific characteristics of clinical trials for neuropsychiatric disorders. Some typical features are as follows: 1) a high and variable response, 2) impact on the effect of the baseline severity of disorders, 3) high dropout rates, 4) biases related to subjective measures of clinical symptoms. In this paper, considerations for the planning and performing of clinical trials for major depressive disorders will be discussed based on these features.

  2. Catheter based radiofrequency ablation of renal nerves for the treatment of resistant hypertension

    Directory of Open Access Journals (Sweden)

    Markus P. Schlaich

    2013-03-01

    Full Text Available Introduction Resistant hypertension is a common and growing clinical problem characterized by the failure to attain target blood pressure levels despite adequate use of at least three antihypertensive agents. Objectives The aim of this article is to emphasize the role of novel approaches to treat resistant hypertension. Materials and methods After an excursus on the physiological role of renal nerves on kidney function, volume homeostasis and blood pressure control, this article describes the radiofrequency ablation technology to obtain kidneys denervation. Results Activation of the sympathetic nervous system plays a prominent role as a major regulator of circulatory and metabolic control. The kidneys have a particularly dense afferent sensory and efferent sympathetic innervation and are thereby strategically positioned to be origin as well as target of sympathetic activation. In this context, recent evidence suggests that a novel catheter-based approach to functionally denervate the human kidneys using radiofrequency ablation technology may provide a safe and effective treatment alternative for resistant hypertension and its adverse consequences. Conclusions Despite the availability of numerous safe and effective pharmacological therapies to treat elevated blood pressure, novel therapeutic approaches are warranted to improve the management and prognosis of patients with refractory hypertension. Several clinical trials are currently conducted and planned to further substantiate the blood pressure lowering efficacy of this novel renal denervation procedure.

  3. Repetitive transcranial magnetic stimulation for treatment of major depressive disorder with comorbid generalized anxiety disorder.

    Science.gov (United States)

    White, Daniela; Tavakoli, Sason

    2015-08-01

    Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in treating individuals with behavioral disorders such as major depressive disorder (MDD), posttraumatic stress disorder, obsessive-compulsive disorder, and social anxiety disorder. A number of applications of rTMS to different regions of the left and right prefrontal cortex have been used to treat these disorders, but no study of treatment for MDD with generalized anxiety disorder (GAD) has been conducted with application of rTMS to both the left and right prefrontal cortex. We hypothesized that applying low-frequency rTMS to the right dorsolateral prefrontal cortex (DLPFC) before applying it to the left DLPFC for the treatment of depression would be anxiolytic in patients with MDD with GAD. Thirteen adult patients with comorbid MDD and GAD received treatment with rTMS in an outpatient setting. The number of treatments ranged from 24 to 36 over 5 to 6 weeks. Response was defined as a ≥ 50% reduction in symptoms from baseline, and remission was defined as a score of anxiety symptoms on the 7-item Generalized Anxiety Disorder (GAD-7) scale and depressive symptoms on the 21-item Hamilton Rating Scale for Depression (HAM-D-21). At the end of the treatment period, for the GAD-7 scale, 11 out of 13 (84.6%) patients' anxiety symptoms were in remission, achieving a score of depressive symptoms. In this small pilot study of 13 patients with comorbid MDD and GAD, significant improvement in anxiety symptoms along with depressive symptoms was achieved in a majority of patients after bilateral rTMS application.

  4. Hypothalamus-Anchored Resting Brain Network Changes before and after Sertraline Treatment in Major Depression

    Directory of Open Access Journals (Sweden)

    Rui Yang

    2014-01-01

    Full Text Available Sertraline, one of the oldest antidepressants, remains to be the most efficacious treatment for depression. However, major depression disorder (MDD is characterized by altered emotion processing and deficits in cognitive control. In cognitive interference tasks, patients with MDD have shown excessive hypothalamus activity. The purpose of this study was to examine the effects of antidepressant treatment (sertraline on hypothalamus-anchored resting brain circuitry. Functional magnetic resonance imaging was conducted on depressed patients (n=12 both before and after antidepressant treatment. After eight weeks of antidepressant treatment, patients with depression showed significantly increased connectivity between the hypothalamus and dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, insula, putamen, caudate, and claustrum. By contrast, decreased connectivity of the hypothalamus-related areas was primarily located in the inferior frontal gyrus, medial frontal gyrus, cingulated gyrus, precuneus, thalamus, and cerebellum. After eight weeks of antidepressant therapy, 8 out of the 12 depressed subjects achieved 70% reduction or better in depressive symptoms, as measured on the Hamilton depression rating scale. Our findings may infer that antidepressant treatment can alter the functional connectivity of the hypothalamus resting brain to achieve its therapeutic effect.

  5. Quality of life and functioning of Hispanic patients with Major Depressive Disorder before and after treatment.

    Science.gov (United States)

    López, Enrique; Steiner, Alexander J; Manier, Karra; Shapiro, Bryan B; Vanle, Brigitte; Parisi, Thomas; Dang, Jonathan; Chang, Tiffany; Ganjian, Shaina; Mirocha, James; Danovitch, Itai; IsHak, Waguih William

    2018-01-01

    Similar rates of remission from Major Depressive Disorder (MDD) have been documented between ethnic groups in response to antidepressant treatment. However, ethnic differences in functional outcomes, including patient-reported quality of life (QOL) and functioning, have not been well-characterized. We compared symptomatic and functional outcomes of antidepressant treatment in Hispanic and non-Hispanic patients with MDD. We analyzed 2280 nonpsychotic treatment-seeking adults with MDD who received citalopram monotherapy in Level 1 of the Sequenced Treatment Alternatives to Relieve Depression study. All subjects (239 Hispanic, 2041 non-Hispanic) completed QOL, functioning, and depressive symptom severity measures at entry and exit. Hispanic participants had significantly worse QOL scores at entry and exit (p depressive symptom severity or functioning. Both groups had significant improvements in depressive symptom severity, QOL, and functioning from entry to exit (all p values depressive symptom severity, greater QOL, and better functioning at exit compared to patients without private insurance. This study was a retrospective data analysis, and the Hispanic group was relatively small compared to the non-Hispanic group. Hispanic and non-Hispanic participants with MDD had similar responses to antidepressant treatment as measured by depressive symptom severity scores, quality of life, and functioning. Nevertheless, Hispanic patients reported significantly worse quality of life at entry. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Testing the predictive value of peripheral gene expression for nonremission following citalopram treatment for major depression.

    Science.gov (United States)

    Guilloux, Jean-Philippe; Bassi, Sabrina; Ding, Ying; Walsh, Chris; Turecki, Gustavo; Tseng, George; Cyranowski, Jill M; Sibille, Etienne

    2015-02-01

    Major depressive disorder (MDD) in general, and anxious-depression in particular, are characterized by poor rates of remission with first-line treatments, contributing to the chronic illness burden suffered by many patients. Prospective research is needed to identify the biomarkers predicting nonremission prior to treatment initiation. We collected blood samples from a discovery cohort of 34 adult MDD patients with co-occurring anxiety and 33 matched, nondepressed controls at baseline and after 12 weeks (of citalopram plus psychotherapy treatment for the depressed cohort). Samples were processed on gene arrays and group differences in gene expression were investigated. Exploratory analyses suggest that at pretreatment baseline, nonremitting patients differ from controls with gene function and transcription factor analyses potentially related to elevated inflammation and immune activation. In a second phase, we applied an unbiased machine learning prediction model and corrected for model-selection bias. Results show that baseline gene expression predicted nonremission with 79.4% corrected accuracy with a 13-gene model. The same gene-only model predicted nonremission after 8 weeks of citalopram treatment with 76% corrected accuracy in an independent validation cohort of 63 MDD patients treated with citalopram at another institution. Together, these results demonstrate the potential, but also the limitations, of baseline peripheral blood-based gene expression to predict nonremission after citalopram treatment. These results not only support their use in future prediction tools but also suggest that increased accuracy may be obtained with the inclusion of additional predictors (eg, genetics and clinical scales).

  7. Pharmacokinetic evaluation of vortioxetine for the treatment of major depressive disorder.

    Science.gov (United States)

    Dubovsky, Steven L

    2014-05-01

    Major depressive disorder (MDD), one of the most common disorders in medical practice and one of the leading causes of disability worldwide, is frequently comorbid with anxiety disorders. Vortioxetine (Lu AA21004) is a new antidepressant that combines a number of neurotransmitter reuptake and receptor effects that have been thought to predict efficacy as a treatment for depressive and anxiety disorders. This review summarizes the pharmacology and neurobiology of vortioxetine. Studies of its efficacy and tolerability in major depression and generalized anxiety disorder are critically reviewed. Despite the fact that industry-sponsored studies are more likely than other clinical trials to support efficacy of the experimental drug, results have been mixed. Some studies supported that vortioxetine is superior to placebo in the treatment of MDD and some do not. Two studies supported the efficacy of vortioxetine in the treatment of generalized anxiety disorder and two do not. The incidence of sexual dysfunction has varied considerably in different studies, but cardiac effects and psychomotor impairment seem to be minimal. Advantages of vortioxetine over existing antidepressants are not yet clear.

  8. Personality modulates the efficacy of treatment in patients with major depressive disorder.

    Science.gov (United States)

    Wardenaar, Klaas J; Conradi, Henk Jan; Bos, Elisabeth H; de Jonge, Peter

    2014-09-01

    Effects of depression treatment are obscured by heterogeneity among patients. Personality types could be one source of heterogeneity that explains variability in treatment response. Clinically meaningful variations in personality patterns could be captured with data-driven subgroups. The aim of this study was to identify such personality types and to explore their predictive value for treatment efficacy. Participants (N = 146) in the current exploratory study came from a randomized controlled trial in primary care depressed patients, conducted between January 1998 and June 2003, comparing different treatments. All participants were diagnosed with a major depressive disorder (MDD) according to the DSM-IV. Primary (care as usual [CAU] or CAU plus a psychoeducational prevention program [PEP]) and specialized (CAU + PEP + psychiatric consultation or cognitive-behavioral therapy) treatment were compared. Personality was assessed with the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI). Personality classes were identified with latent profile analysis (LPA). During 1 year, weekly depression ratings were obtained by trimonthly assessment with the Composite International Diagnostic Interview. Mixed models were used to analyze the effects of personality on treatment efficacy. A 2-class LPA solution fit best to the NEO-FFI data: Class 1 (vulnerable, n = 94) was characterized by high neuroticism, low extraversion, and low conscientiousness, and Class 2 (resilient, n = 52) by medium neuroticism and extraversion and higher agreeableness and conscientiousness. Recovery was quicker in the resilient class (class × time: P Personality profile may predict whether specialized clinical efforts have added value, showing potential implications for planning of treatments. © Copyright 2014 Physicians Postgraduate Press, Inc.

  9. Brain activation predicts treatment improvement in patients with major depressive disorder.

    LENUS (Irish Health Repository)

    Samson, Andrea C

    2012-02-01

    Major depressive disorder (MDD) is associated with alterations in brain function that might be useful for therapy evaluation. The current study aimed to identify predictors for therapy improvement and to track functional brain changes during therapy. Twenty-one drug-free patients with MDD underwent functional MRI twice during performance of an emotional perception task: once before and once after 4 weeks of antidepressant treatment (mirtazapine or venlafaxine). Twelve healthy controls were investigated once with the same methods. A significant difference between groups was a relative greater activation of the right dorsolateral prefrontal cortex (dlPFC) in the patients vs. controls. Before treatment, patients responding better to pharmacological treatment showed greater activation in the dorsomedial PFC (dmPFC), posterior cingulate cortex (pCC) and superior frontal gyrus (SFG) when viewing of negative emotional pictures was compared with the resting condition. Activations in the caudate nucleus and insula contrasted for emotional compared to neutral stimuli were also associated with successful treatment. Responders had also significantly higher levels of activation, compared to non-responders, in a range of other brain regions. Brain activation related to treatment success might be related to altered self-referential processes and a differential response to external emotional stimuli, suggesting differences in the processing of emotionally salient stimuli between those who are likely to respond to pharmacological treatment and those who will not. The present investigation suggests the pCC, dmPFC, SFG, caudate nucleus and insula may have a key role as a biological marker for treatment response and predictor for therapeutic success.

  10. Prediction of treatment outcomes to exercise in patients with nonremitted major depressive disorder.

    Science.gov (United States)

    Rethorst, Chad D; South, Charles C; Rush, A John; Greer, Tracy L; Trivedi, Madhukar H

    2017-12-01

    Only one-third of patients with major depressive disorder (MDD) achieve remission with initial treatment. Consequently, current clinical practice relies on a "trial-and-error" approach to identify an effective treatment for each patient. The purpose of this report was to determine whether we could identify a set of clinical and biological parameters with potential clinical utility for prescription of exercise for treatment of MDD in a secondary analysis of the Treatment with Exercise Augmentation in Depression (TREAD) trial. Participants with nonremitted MDD were randomized to one of two exercise doses for 12 weeks. Participants were categorized as "remitters" (≤12 on the IDS-C), nonresponders (drop in IDS-C), or neither. The least absolute shrinkage and selection operator (LASSO) and random forests were used to evaluate 30 variables as predictors of both remission and nonresponse. Predictors were used to model treatment outcomes using logistic regression. Of the 122 participants, 36 were categorized as remitters (29.5%), 56 as nonresponders (45.9%), and 30 as neither (24.6%). Predictors of remission were higher levels of brain-derived neurotrophic factor (BDNF) and IL-1B, greater depressive symptom severity, and higher postexercise positive affect. Predictors of treatment nonresponse were low cardiorespiratory fitness, lower levels of IL-6 and BDNF, and lower postexercise positive affect. Models including these predictors resulted in predictive values greater than 70% (true predicted remitters/all predicted remitters) with specificities greater than 25% (true predicted remitters/all remitters). Results indicate feasibility in identifying patients who will either remit or not respond to exercise as a treatment for MDD utilizing a clinical decision model that incorporates multiple patient characteristics. © 2017 Wiley Periodicals, Inc.

  11. Predicting tDCS treatment outcomes of patients with major depressive disorder using automated EEG classification.

    Science.gov (United States)

    Al-Kaysi, Alaa M; Al-Ani, Ahmed; Loo, Colleen K; Powell, Tamara Y; Martin, Donel M; Breakspear, Michael; Boonstra, Tjeerd W

    2017-01-15

    Transcranial direct current stimulation (tDCS) is a promising treatment for major depressive disorder (MDD). Standard tDCS treatment involves numerous sessions running over a few weeks. However, not all participants respond to this type of treatment. This study aims to investigate the feasibility of identifying MDD patients that respond to tDCS treatment based on resting-state electroencephalography (EEG) recorded prior to treatment commencing. We used machine learning to predict improvement in mood and cognition during tDCS treatment from baseline EEG power spectra. Ten participants with a current diagnosis of MDD were included. Power spectral density was assessed in five frequency bands: delta (0.5-4Hz), theta (4-8Hz), alpha (8-12Hz), beta (13-30Hz) and gamma (30-100Hz). Improvements in mood and cognition were assessed using the Montgomery-Åsberg Depression Rating Scale and Symbol Digit Modalities Test, respectively. We trained the classifiers using three algorithms (support vector machine, extreme learning machine and linear discriminant analysis) and a leave-one-out cross-validation approach. Mood labels were accurately predicted in 8 out of 10 participants using EEG channels FC4-AF8 (accuracy=76%, p=0.034). Cognition labels were accurately predicted in 10 out of 10 participants using channels pair CPz-CP2 (accuracy=92%, p=0.004). Due to the limited number of participants (n=10), the presented results mainly aim to serve as a proof of concept. These finding demonstrate the feasibility of using machine learning to identify patients that will respond to tDCS treatment. These promising results warrant a larger study to determine the clinical utility of this approach. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Major Pathophysiology in Prediabetes and Type 2 Diabetes: Decreased Insulin in Lean and Insulin Resistance in Obese.

    Science.gov (United States)

    Kabadi, Udaya M

    2017-06-01

    Lowering of body mass index (BMI) to ≥25 kg/m 2 as obesity by ADA suggests insulin resistance as a major mechanism of impaired glucose metabolism (IGM) in Asians. However, glimepiride, an insulin secretagogue, delayed onset of type 2 diabetes (DM2) from prediabetes (PreDM), indicating decreased insulin secretion (IS) as a major factor in lean (L; BMI DM2. Seventy-five men and 45 women ages 36 to 75 years were divided into six groups: LN, LPreDM, LDM2, ObN, ObPreDM, and ObDM2. Determination of IS by insulinogenic indices (I/G) at fasting (FI/FG), first phase (∆I/∆G), and cumulative responses over 2 hours of OGTT (CRI/CRG), and IR by FIXFG, ∆IX∆G, and CRIXCRG. Changes in IS and IR for PreDM and DM2 were calculated as % fall and % rise, respectively, from levels in N. All indices of IS and IR were lower ( P DM2 ( P < 0.05) in both groups. However, the declines in IS were greater ( P < 0.05) than rises in IR in LPreDM and LDM2. Whereas, the rises in IR were higher ( P < 0.05) than declines in IS in ObPreDM and ObDM2. In L, major mechanism of IGM is declining IS and not rising IR documented among Ob.

  13. Emerging drug -resistance and guidelines for treatment of malaria

    International Nuclear Information System (INIS)

    Khan, M.A.; Smego Jr, R.A.; Razi, S.T.; Beg, M.A.

    2004-01-01

    The increasing prevalence of multi-resistant Plasmodium falciparum malaria worldwide is a serious public health threat to the global control of malaria, especially in poor countries like Pakistan. In many countries chloroquine-resistance is a huge problem, accounting for more than 90% of malaria cases. In Pakistan, resistance to chloroquine is on the rise and reported in up to 16- 62% of Plasmodium falciparum. Four to 25% of Plasmodium falciparum also reported to be resistant to sulfadoxine-pyrimethamine and several cases of delayed parasite clearance have been observed in patients with Plasmodium falciparum malaria treated with quinine. In this article we have introduced the concept of artemisinin- based combination therapy (ACT) and emphasize the use of empiric combination therapy for all patients with Plasmodium falciparum malaria to prevent development of drug resistance and to obtain additive and synergistic killing of parasite. (author)

  14. Symptom predictors of response to electroconvulsive therapy in older patients with treatment-resistant depression

    Directory of Open Access Journals (Sweden)

    Tominaga K

    2011-07-01

    Full Text Available Keiichiro Tominaga¹, Mioto Okazaki¹, Hisashi Higuchi¹, Itaru Utagawa¹, Etsuko Nakamura², Noboru Yamaguchi¹¹Department of Neuropsychiatry, St Marianna University School of Medicine, Miyamae-ku, Kawasaki City, Kanagawa, ²Tsurukawa Sanatorium Hospital, Machida City, Tokyo, JapanBackground: Electroconvulsive therapy (ECT has been used for treatment-resistant depression. However, predictors of response to ECT have not been adequately studied using the Montgomery and Åsberg Depression Rating Scale, especially in older patients with treatment-resistant depression.Methods: This study included 18 Japanese patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision criteria for a diagnosis of major depressive disorder or bipolar disorder with a current major depressive episode, and met the definition of treatment-resistant depression outlined by Thase and Rush, scoring ≥21 on the Montgomery and Åsberg Depression Rating Scale. The three-factor model of the Montgomery and Åsberg Depression Rating Scale was used for analysis. Factor 1 was defined by three items, factor 2 by four items, and factor 3 by three items, representing dysphoria, retardation, and vegetative symptoms, respectively. ECT was performed twice a week for a total of six sessions using a Thymatron System IV device with the brief pulse technique. Clinical responses were defined on the basis of a ≥50% decrease in total pretreatment Montgomery and Åsberg Depression Rating Scale scores.Results: The mean pretreatment factor 2 score for responders (n = 7 was significantly lower than that for nonresponders (n = 11. Furthermore, a significant difference in mean factor 3 score between responders and nonresponders was observed one week after six sessions of ECT, indicating a time lag of response. No significant differences were observed for age, number of previous episodes, and duration of the current episode between responders and

  15. Using SNP markers to dissect linkage disequilibrium at a major quantitative trait locus for resistance to the potato cyst nematode Globodera pallida on potato chromosome V

    NARCIS (Netherlands)

    Achenbach, U.; Caldas Paulo, M.J.; Ilarionova, E.; Lübeck, J.; Strahwald, J.; Tacke, E.; Hofferbert, H.R.

    2009-01-01

    The damage caused by the parasitic root cyst nematode Globodera pallida is a major yield-limiting factor in potato cultivation . Breeding for resistance is facilitated by the PCR-based marker 'HC', which is diagnostic for an allele conferring high resistance against G. pallida pathotype Pa2/3 that

  16. S-adenosylmethionine blood levels in major depression: changes with drug treatment.

    Science.gov (United States)

    Bell, K M; Potkin, S G; Carreon, D; Plon, L

    1994-01-01

    The relationship between plasma levels of S-adenosylmethionine (SAMe), an endogenous methyl donor, and clinical response were studied in patients with a DSM-III-R diagnosis of major depression. A double-blind randomized protocol comparing oral SAMe with oral desipramine, involving a total of 26 patients, was employed. At the end of the 4-week trial, 62% of the patients treated with SAMe and 50% of the patients treated with desipramine had significantly improved. Regardless of the type of treatment, patients with a 50% decrease in their Hamilton Depression Scale (HAM-D) score showed a significant increase in plasma SAMe concentration. The significant correlation between plasma SAMe levels and the degree of clinical improvement in depressed patients regardless of the type of treatment suggests that SAMe may play an important role in regulating mood.

  17. Efficacy of escitalopram monotherapy in the treatment of major depressive disorder

    Science.gov (United States)

    Li, Guanjun; Shen, Yifeng; Luo, Jianfeng; Li, Huafang

    2017-01-01

    Abstract This study aimed to evaluate the efficacy of escitalopram monotherapy in the treatment of major depressive disorder (MDD) on the basis of pooled data analysis of 4 Chinese clinical trials. A total of 649 outpatients with MDD score of ≥18 at the 17-item Hamilton Depression Rating Scale (HAMD17) were included across 4 eligible studies. Patients were treated with 10 mg/day escitalopram for 2 weeks, and then 20 mg/day escitalopram was administered if the clinical response was poor. The change in total HAMD17 score was significantly greater in moderate MDD group than in other subgroups (P Escitalopram monotherapy is effective and safe in the treatment of MDD in Chinese patients, and therapeutic efficacy is dependent on the severity of MDD. Further study is needed to identify better predictors of therapeutic responses. PMID:28953649

  18. Third-wave cognitive therapy versus mentalisation-based treatment for major depressive disorder

    DEFF Research Database (Denmark)

    Jakobsen, Janus Christian; Gluud, Christian; Kongerslev, Mickey

    2014-01-01

    OBJECTIVE: To compare the benefits and harms of third-wave cognitive therapy versus mentalisation-based therapy in a small sample of depressed participants. SETTING: The trial was conducted at an outpatient psychiatric clinic for non-psychotic patients in Roskilde, Denmark. PARTICIPANTS: 44...... consecutive adult participants diagnosed with major depressive disorder. INTERVENTIONS: 18 weeks of third-wave cognitive therapy (n=22) versus 18 weeks of mentalisation-based treatment (n=22). OUTCOMES: The primary outcome was the Hamilton Rating Scale for Depression (HDRS) at end of treatment (18 weeks...... for baseline HDRS score, the difference was favouring third-wave cognitive therapy (p=0.039). At 18 weeks, five of the third-wave participants (22.7%) were in remission versus none of the mentalisation-based participants (p=0.049). We recorded no suicide attempts or suicides during the intervention period...

  19. Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression

    Directory of Open Access Journals (Sweden)

    Alik S. Widge

    2018-03-01

    Full Text Available Major depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial “failures” are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this “valley of disillusionment,” DBS may be nearing a “slope of enlightenment.” Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI, the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care.

  20. Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression

    Science.gov (United States)

    Widge, Alik S.; Malone, Donald A.; Dougherty, Darin D.

    2018-01-01

    Major depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS) in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial “failures” are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this “valley of disillusionment,” DBS may be nearing a “slope of enlightenment.” Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI), the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care. PMID:29618967

  1. Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression.

    Science.gov (United States)

    Widge, Alik S; Malone, Donald A; Dougherty, Darin D

    2018-01-01

    Major depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS) in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial "failures" are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this "valley of disillusionment," DBS may be nearing a "slope of enlightenment." Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI), the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care.

  2. Oral ketamine for the treatment of pain and treatment-resistant depression†.

    Science.gov (United States)

    Schoevers, Robert A; Chaves, Tharcila V; Balukova, Sonya M; Rot, Marije Aan Het; Kortekaas, Rudie

    2016-02-01

    Recent studies with intravenous (i.v.) application of ketamine show remarkable but short-term success in patients with MDD. Studies in patients with chronic pain have used different ketamine applications for longer time periods. This experience may be relevant for psychiatric indications. To review the literature about the dosing regimen, duration, effects and side-effects of oral, intravenous, intranasal and subcutaneous routes of administration of ketamine for treatment-resistant depression and pain. Searches in PubMed with the terms 'oral ketamine', 'depression', 'chronic pain', 'neuropathic pain', 'intravenous ketamine', 'intranasal ketamine' and 'subcutaneous ketamine' yielded 88 articles. We reviewed all papers for information about dosing regimen, number of individuals who received ketamine, number of ketamine days per study, results and side-effects, as well as study quality. Overall, the methodological strength of studies investigating the antidepressant effects of ketamine was considered low, regardless of the route of administration. The doses for depression were in the lower range compared with studies that investigated analgesic use. Studies on pain suggested that oral ketamine may be acceptable for treatment-resistant depression in terms of tolerability and side-effects. Oral ketamine, given for longer time periods in the described doses, appears to be well tolerated, but few studies have systematically examined the longer-term negative consequences. The short- and longer-term depression outcomes as well as side-effects need to be studied with rigorous randomised controlled trials. © The Royal College of Psychiatrists 2016.

  3. Role of major histocompatibility complex class II in resistance of mice to naturally acquired infection with Syphacia obvelata

    Science.gov (United States)

    Stewart, Patricia W.; Chapes, Stephen K.

    2003-01-01

    Genetics plays a substantial role in host resistance in many host-parasite interactions. We examined the prevalence of naturally acquired infection with Syphacia obvelata in a number of mouse strains housed in a non-barrier facility. These mice, which included cross-bred and congenic, inbred strains on various genetic backgrounds, differ in the loci for the immune function genes--major histocompatibility complex class II (MHCII), toll-like receptor 4 (Tlr4), and solute carrier family 11, member 1 (Slc11a1)--which allowed comparisons of the impact of these genes on resistance to pinworm infection. Male and female mice of various ages were sampled over an 18-month period; infection was determined by use of the cellophane tape test. Results indicated that mice that were MHCII+/+ had a significantly lower prevalence of infection than did mice that were MHCII-/-. Differences were not seen between male and female mice. Although MHCII+/+ mice had an age-associated decrease in infection prevalence, such decrease was not seen in MHCII-/- mice. In contrast, infection prevalence in mice with the normal Tlr4 gene (Tlr4(LPS-n/LPS-n)) gene did not differ significantly compared with that in mice that were homozygous for either the point mutation (Tlr4(LPS-d/LPS-d)) or deletion (Tlr4(LPS-del/LPS-del)) of that gene. Likewise, the presence (Sle11a1r/r) or absence (Slc11a1s/s) of functional alleles for Slc11a1 had no effect on the prevalence of infection with S. obvelata. In conclusion, presence of MHCII, but not Tlr4 or Slc11a1 significantly influences prevalence of naturally acquired infection with S. obvelata. These data justify further comprehensive analyses of the immune components that are involved in pinworm resistance.

  4. Thioridazine Induces Major Changes in Global Gene Expression and Cell Wall Composition in Methicillin-Resistant Staphylococcus aureus USA300

    DEFF Research Database (Denmark)

    Thorsing, Mette; Klitgaard, Janne Kudsk; Atilano, Magda L.

    2013-01-01

    and the transcriptomic response of S. aureus to known inhibitors of cell wall synthesis suggests that TDZ disturbs PGN biosynthesis at a stage that precedes transpeptidation by penicillin-binding proteins (PBPs). In support of this notion, dramatic changes in the muropeptide profile of USA300 were observed following....... In the present study, we have examined the effect of a subinhibitory concentration of TDZ on antimicrobial resistance, the global transcriptome, and the cell wall composition of MRSA USA300. We show that TDZ is able to sensitize the bacteria to several classes of antimicrobials targeting the late stages...... a major impact on the cell wall biosynthesis pathway in S. aureus and provides new insights into how MRSA may be sensitized towards β-lactam antibiotics....

  5. Major vault protein/lung resistance-related protein (MVP/LRP) expression in nervous system tumors.

    Science.gov (United States)

    Sasaki, Tsutomu; Hankins, Gerald R; Helm, Gregory A

    2002-01-01

    Lung resistance-related protein (LRP) was identified as the major vault protein (MVP), the main component of multimeric vault particles. It functions as a transport-associated protein that can be associated with multidrug resistance. In previous studies, expression of MVP/LRP has been documented in tumors of various types. In general, good correlations have been reported for expression of MVP/LRP and decreased sensitivity to chemotherapy and poor prognosis. MVP/LRP expression has been documented in glioblastomas, but its expression in nervous system tumors in general has not been well characterized. Immunohistochemistry using anti-human MVP/LRP antibody (LRP-56) was performed on formalin-fixed, paraffin-embedded archival tissue from 69 primary central nervous system tumors. Expression of MVP/LRP was observed in 81.2% (56/69) of primary nervous system tumors, including astrocytomas (11/13), oligodendrogliomas (1/2), oligoastrocytomas (5/5), ependymoma (1/1), meningiomas (35/45), schwannomas (2/2), and neurofibroma (1/1). Various degrees and distributions of immunoreactivity to MVP/ LRP were observed. Neither the presence nor the degree of immunoreactivity to MVP/LRP showed any correlation with either tumor grade or the presence of brain invasion.

  6. Growth hormone (GH) and atherosclerosis: changes in morphology and function of major arteries during GH treatment.

    Science.gov (United States)

    Pfeifer, M; Verhovec, R; Zizek, B

    1999-04-01

    Patients with hypopituitarism have increased carotid artery intima-media thickness and reduced arterial distensibility. The effect of 2 years of growth hormone (GH) replacement therapy on these parameters was studied in 11 GH-deficient men (age range, 24-49 years) with hypopituitarism and compared with 12 healthy, age-matched men with no evidence of pituitary or vascular disease. Before treatment the intima-media of the common carotid arteries and the carotid bifurcations were significantly thicker in patients (P < 0.001) than in the control group. Treatment with GH normalized the intima-media thickness of the common carotid artery within 6 months and of the carotid bifurcation within 3 months. The changes in intima-media thickness of the carotid artery were negatively correlated with changes in serum levels of insulin-like growth factor I during treatment. There was a significant improvement in flow-mediated, endothelium-dependent dilation of the brachial artery at 3 months, which was sustained at 6, 18 and 24 months of GH treatment (P < 0.05). Thus, GH replacement therapy in GH-deficient men reverses early morphological and functional atherosclerotic changes in major arteries, and may reduce rates of vascular morbidity and mortality.

  7. Pattern of intensive phase treatment outcomes of multi-drug resistant ...

    African Journals Online (AJOL)

    Pattern of intensive phase treatment outcomes of multi-drug resistant tuberculosis in University of Port Harcourt Treatment Centre: a review of records from ... Data on patients' age, sex, HIV status, treatment outcomes were extracted from the hospital book records into a computer data sheet at the UPTH treatment centre.

  8. Treatment resistant adolescent depression with upper airway resistance syndrome treated with rapid palatal expansion: a case report

    Directory of Open Access Journals (Sweden)

    Miller Paul

    2012-12-01

    Full Text Available Abstract Introduction To the best of our knowledge, this is the first report of a case of treatment-resistant depression in which the patient was evaluated for sleep disordered breathing as the cause and in which rapid palatal expansion to permanently treat the sleep disordered breathing produced a prolonged symptom-free period off medication. Case presentation An 18-year-old Caucasian man presented to our sleep disorders center with chronic severe depression that was no longer responsive to medication but that had recently responded to electroconvulsive therapy. Ancillary, persistent symptoms included mild insomnia, moderate to severe fatigue, mild sleepiness and severe anxiety treated with medication. Our patient had no history of snoring or witnessed apnea, but polysomnography was consistent with upper airway resistance syndrome. Although our patient did not have an orthodontic indication for rapid palatal expansion, rapid palatal expansion was performed as a treatment of his upper airway resistance syndrome. Following rapid palatal expansion, our patient experienced a marked improvement of his sleep quality, anxiety, fatigue and sleepiness. His improvement has been maintained off all psychotropic medication and his depression has remained in remission for approximately two years following his electroconvulsive therapy. Conclusions This case report introduces the possibility that unrecognized sleep disordered breathing may play a role in adolescent treatment-resistant depression. The symptoms of upper airway resistance syndrome are non-specific enough that every adolescent with depression, even those responding to medication, may have underlying sleep disordered breathing. In such patients, rapid palatal expansion, by widening the upper airway and improving airflow during sleep, may produce a prolonged improvement of symptoms and a tapering of medication. Psychiatrists treating adolescents may benefit from having another treatment option for

  9. Release of Antibiotic Resistant Bacteria by a Waste Treatment Plant from Romania.

    Science.gov (United States)

    Lupan, Iulia; Carpa, Rahela; Oltean, Andreea; Kelemen, Beatrice Simona; Popescu, Octavian

    2017-09-27

    The occurrence and spread of bacterial antibiotic resistance are subjects of great interest, and the role of wastewater treatment plants has been attracting particular interest. These stations are a reservoir of bacteria, have a large range of organic and inorganic substances, and the amount of bacteria released into the environment is very high. The main purpose of the present study was to assess the removal degree of bacteria with resistance to antibiotics and identify the contribution of a wastewater treatment plant to the microbiota of Someşul Mic river water in Cluj county. The resistance to sulfamethoxazole and tetracycline and some of their representative resistance genes: sul1, tet(O), and tet(W) were assessed in this study. The results obtained showed that bacteria resistant to sulphonamides were more abundant than those resistant to tetracycline. The concentration of bacteria with antibiotic resistance changed after the treatment, namely, bacteria resistant to sulfamethoxazole. The removal of all bacteria and antibiotic-resistant bacteria was 98-99% and the degree of removal of bacteria resistant to tetracycline was higher than the bacteria resistant to sulfamethoxazole compared to total bacteria. The wastewater treatment plant not only contributed to elevating ARG concentrations, it also enhanced the possibility of horizontal gene transfer (HGT) by increasing the abundance of the intI1 gene. Even though the treatment process reduced the concentration of bacteria by two orders of magnitude, the wastewater treatment plant in Cluj-Napoca contributed to an increase in antibiotic-resistant bacteria concentrations up to 10 km downstream of its discharge in Someşul Mic river.

  10. Resource competition may lead to effective treatment of antibiotic resistant infections.

    Directory of Open Access Journals (Sweden)

    Antonio L C Gomes

    Full Text Available Drug resistance is a common problem in the fight against infectious diseases. Recent studies have shown conditions (which we call antiR that select against resistant strains. However, no specific drug administration strategies based on this property exist yet. Here, we mathematically compare growth of resistant versus sensitive strains under different treatments (no drugs, antibiotic, and antiR, and show how a precisely timed combination of treatments may help defeat resistant strains. Our analysis is based on a previously developed model of infection and immunity in which a costly plasmid confers antibiotic resistance. As expected, antibiotic treatment increases the frequency of the resistant strain, while the plasmid cost causes a reduction of resistance in the absence of antibiotic selection. Our analysis suggests that this reduction occurs under competition for limited resources. Based on this model, we estimate treatment schedules that would lead to a complete elimination of both sensitive and resistant strains. In particular, we derive an analytical expression for the rate of resistance loss, and hence for the time necessary to turn a resistant infection into sensitive (tclear. This time depends on the experimentally measurable rates of pathogen division, growth and plasmid loss. Finally, we estimated tclear for a specific case, using available empirical data, and found that resistance may be lost up to 15 times faster under antiR treatment when compared to a no treatment regime. This strategy may be particularly suitable to treat chronic infection. Finally, our analysis suggests that accounting explicitly for a resistance-decaying rate may drastically change predicted outcomes in host-population models.

  11. Resource competition may lead to effective treatment of antibiotic resistant infections.

    Science.gov (United States)

    Gomes, Antonio L C; Galagan, James E; Segrè, Daniel

    2013-01-01

    Drug resistance is a common problem in the fight against infectious diseases. Recent studies have shown conditions (which we call antiR) that select against resistant strains. However, no specific drug administration strategies based on this property exist yet. Here, we mathematically compare growth of resistant versus sensitive strains under different treatments (no drugs, antibiotic, and antiR), and show how a precisely timed combination of treatments may help defeat resistant strains. Our analysis is based on a previously developed model of infection and immunity in which a costly plasmid confers antibiotic resistance. As expected, antibiotic treatment increases the frequency of the resistant strain, while the plasmid cost causes a reduction of resistance in the absence of antibiotic selection. Our analysis suggests that this reduction occurs under competition for limited resources. Based on this model, we estimate treatment schedules that would lead to a complete elimination of both sensitive and resistant strains. In particular, we derive an analytical expression for the rate of resistance loss, and hence for the time necessary to turn a resistant infection into sensitive (tclear). This time depends on the experimentally measurable rates of pathogen division, growth and plasmid loss. Finally, we estimated tclear for a specific case, using available empirical data, and found that resistance may be lost up to 15 times faster under antiR treatment when compared to a no treatment regime. This strategy may be particularly suitable to treat chronic infection. Finally, our analysis suggests that accounting explicitly for a resistance-decaying rate may drastically change predicted outcomes in host-population models.

  12. Novel melatonin-based therapies: potential advances in the treatment of major depression.

    Science.gov (United States)

    Hickie, Ian B; Rogers, Naomi L

    2011-08-13

    Major depression is one of the leading causes of premature death and disability. Although available drugs are effective, they also have substantial limitations. Recent advances in our understanding of the fundamental links between chronobiology and major mood disorders, as well as the development of new drugs that target the circadian system, have led to a renewed focus on this area. In this review, we summarise the associations between disrupted chronobiology and major depression and outline new antidepressant treatment strategies that target the circadian system. In particular, we highlight agomelatine, a melatonin-receptor agonist and selective serotonergic receptor subtype (ie, 5-HT(2C)) antagonist that has chronobiotic, antidepressant, and anxiolytic effects. In the short-term, agomelatine has similar antidepressant efficacy to venlafaxine, fluoxetine, and sertraline and, in the longer term, fewer patients on agomelatine relapse (23·9%) than do those receiving placebo (50·0%). Patients with depression treated with agomelatine report improved sleep quality and reduced waking after sleep onset. As agomelatine does not raise serotonin levels, it has less potential for the common gastrointestinal, sexual, or metabolic side-effects that characterise many other antidepressant compounds. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. UV-Surface Treatment of Fungal Resistant Polyether Polyurethane Film-Induced Growth of Entomopathogenic Fungi.

    Science.gov (United States)

    Lando, Gabriela Albara; Marconatto, Letícia; Kessler, Felipe; Lopes, William; Schrank, Augusto; Vainstein, Marilene Henning; Weibel, Daniel Eduardo

    2017-07-18

    Synthetic polymers are the cause of some major environmental impacts due to their low degradation rates. Polyurethanes (PU) are widely used synthetic polymers, and their growing use in industry has produced an increase in plastic waste. A commercial polyether-based thermoplastic PU with hydrolytic stability and fungus resistance was only attacked by an entomopathogenic fungus, Metarhiziumanisopliae , when the films were pre-treated with Ultraviolet (UV) irradiation in the presence of reactive atmospheres. Water contact angle, Fourier transform infrared spectroscopy in attenuated total reflection mode (FTIR-ATR), scanning electron microscopy (SEM), and profilometer measurements were mainly used for analysis. Permanent hydrophilic PU films were produced by the UV-assisted treatments. Pristine polyether PU films incubated for 10, 30, and 60 days did not show any indication of fungal growth. On the contrary, when using oxygen in the UV pre-treatment a layer of fungi spores covered the sample, indicating a great adherence of the microorganisms to the polymer. However, if acrylic acid vapors were used during the UV pre-treatment, a visible attack by the entomopathogenic fungi was observed. SEM and FTIR-ATR data showed clear evidence of fungal development: growth and ramifications of hyphae on the polymer surface with the increase in UV pre-treatment time and fungus incubation time. The results indicated that the simple UV surface activation process has proven to be a promising alternative for polyether PU waste management.

  14. UV-Surface Treatment of Fungal Resistant Polyether Polyurethane Film-Induced Growth of Entomopathogenic Fungi

    Directory of Open Access Journals (Sweden)

    Gabriela Albara Lando

    2017-07-01

    Full Text Available Synthetic polymers are the cause of some major environmental impacts due to their low degradation rates. Polyurethanes (PU are widely used synthetic polymers, and their growing use in industry has produced an increase in plastic waste. A commercial polyether-based thermoplastic PU with hydrolytic stability and fungus resistance was only attacked by an entomopathogenic fungus, Metarhiziumanisopliae, when the films were pre-treated with Ultraviolet (UV irradiation in the presence of reactive atmospheres. Water contact angle, Fourier transform infrared spectroscopy in attenuated total reflection mode (FTIR-ATR, scanning electron microscopy (SEM, and profilometer measurements were mainly used for analysis. Permanent hydrophilic PU films were produced by the UV-assisted treatments. Pristine polyether PU films incubated for 10, 30, and 60 days did not show any indication of fungal growth. On the contrary, when using oxygen in the UV pre-treatment a layer of fungi spores covered the sample, indicating a great adherence of the microorganisms to the polymer. However, if acrylic acid vapors were used during the UV pre-treatment, a visible attack by the entomopathogenic fungi was observed. SEM and FTIR-ATR data showed clear evidence of fungal development: growth and ramifications of hyphae on the polymer surface with the increase in UV pre-treatment time and fungus incubation time. The results indicated that the simple UV surface activation process has proven to be a promising alternative for polyether PU waste management.

  15. Novel Approaches for the Treatment of the Patient with Resistant Hypertension: Renal Nerve Ablation

    Science.gov (United States)

    Gulati, Vinay; White, William B.

    2013-01-01

    Sympathetic innervation of the kidneys plays a major role in the pathogenesis of hypertension through modulation of renin secretion, glomerular filtration rate and renal absorption of sodium. Targeted interventions for renal nerve ablation are being developed for treatment of drug resistant hypertension in the USA and rest of the world. Early studies with the use of radiofrequency based renal denervation systems have shown encouraging results with significant reduction of blood pressure in patients inadequately controlled despite nearly maximal drug therapy regimens. Thus far, the renal denervation procedure has been associated with minimal side effects. Long term efficacy and safety beyond 3 years needs to be determined for renal nerve ablation. This review focuses on the physiology of the renal sympathetic system, the rationale for renal nerve ablation and current evidence in support of the available therapeutic renal denervation systems. PMID:24244757

  16. A systematic review and meta-analysis of the effect of prophylactic tranexamic acid treatment in major benign uterine surgery

    DEFF Research Database (Denmark)

    Topsoee, Märta F; Settnes, Annette; Ottesen, Bent

    2017-01-01

    BACKGROUND: The value of tranexamic acid (TA) treatment as bleeding prophylaxis in major uterine surgery is unclear. OBJECTIVES: To evaluate the antihemorrhagic effect of prophylactic TA treatment in major benign uterine surgery. SEARCH STRATEGY: PubMed, Embase, Cochrane Library, and Web of Science...

  17. Isoniazid-resistant tuberculosis in Denmark: mutations, transmission and treatment outcome

    DEFF Research Database (Denmark)

    Bang, Didi; Andersen, Peter Henrik; Andersen, Ase Bengaard

    2010-01-01

    A retrospective study on isoniazid-resistant tuberculosis (TB) was conducted in the low-burden country, Denmark (DK). The aim was to describe treatment outcome and transmission and to evaluate a mutation analysis for high- and low-level isoniazid resistance detection.......A retrospective study on isoniazid-resistant tuberculosis (TB) was conducted in the low-burden country, Denmark (DK). The aim was to describe treatment outcome and transmission and to evaluate a mutation analysis for high- and low-level isoniazid resistance detection....

  18. Comparison of escitalopram versus citalopram for the treatment of major depressive disorder in a geriatric population.

    Science.gov (United States)

    Wu, Eric; Greenberg, Paul E; Yang, Elaine; Yu, Andrew; Erder, M Haim

    2008-09-01

    To compare escitalopram versus citalopram for the treatment of major depressive disorder (MDD) in geriatric patients. Administrative claims data (2003-2005) were analyzed for patients aged > or =65 years with at least one inpatient claim or two independent medical claims associated with MDD diagnosis. Patients were continuously enrolled for at least 12 months, filled at least one prescription for citalopram or escitalopram and had no second generation antidepressant use during the 6-month pre-index date. Contingency table analysis and survival analysis were used to compare outcomes between the two treatment groups. Treatment persistence, hospitalization utilization, and prescription drug, medical, and total healthcare costs were analyzed. Outcomes were compared between patients initiated on escitalopram and those initiated on citalopram both descriptively and using multivariate analysis adjusting for baseline characteristics. Among 691 geriatric patients, escitalopram-treated patients (n=459) were less likely to discontinue treatment (hazard ratio [HR]=0.83, p=0.049) or switch to another second generation antidepressant (HR=0.62, p=0.001) compared to patients treated with citalopram (n=232). Patients treated with escitalopram had a significantly lower hospitalization rate (31.2% vs. 38.8%, p=0.045) and 66% fewer hospitalization days based on negative binomial regression (pescitalopram patients had comparable prescription drug costs, they had lower total medical service costs (regression: $9748 vs. $19,208, pescitalopram had better treatment persistence, fewer hospitalizations, and lower medical and total healthcare costs than patients treated with citalopram. Most of the cost reduction was attributable to significantly lower hospitalizations and total medical costs.

  19. Characteristics of patients who suffer major osteoporotic fractures despite adhering to alendronate treatment

    DEFF Research Database (Denmark)

    Abrahamsen, B; Rubin, K H; Eiken, Pia Agnete

    2013-01-01

    .03-1.06, for each drug). Dementia (HR 1.81, 95 % CI 1.18-2.78), prior fracture (one: HR 1.17, 95 % CI 1.02-1.34; multiple: HR 1.34, 95 % CI 1.08-1.67), and ulcer disease (HR 1.45, 95 % CI 1.04-2.03) also increased the risk. Diabetes did not influence fracture risk, nor did rheumatic disorders. The risk was lower...... and associations may not be causal, it may be prudent to include dementia, ulcer disease, and Parkinson's disease to capture the risk of fractures on treatment. Lower risk in patients treated with glucocorticoids and in men probably reflects a lower treatment threshold related to guidelines.......Antiresorptive treatment reduces the risk of fractures, but most patients remain at elevated risk. We used health registers to identify predictors of new major osteoporotic fractures in patients adhering to alendronate. Risk factors showed a different pattern than in the general population...

  20. Increased Treatment Complexity for Major Depressive Disorder for Inpatients With Comorbid Personality Disorder.

    Science.gov (United States)

    Wiegand, Hauke F; Godemann, Frank

    2017-05-01

    The study examined inpatient treatment for major depressive disorder (MDD) when it is complicated by comorbid personality disorder. In this descriptive analysis of a large data sample from 2013 (German VIPP data set) of 58,913 cases from 75 hospitals, three groups were compared: patients with MDD, patients with MDD and a comorbid personality disorder, and patients with a main diagnosis of personality disorder. Compared with MDD patients, those with comorbid personality disorder had higher rates of recurrent depression and nearly twice as many readmissions within one year, despite longer mean length of stay. Records of patients with comorbidities more often indicated accounting codes for "complex diagnostic procedures," "crisis intervention," and "constant observation." Patients with comorbid disorders differed from patients with a main diagnosis of personality disorder in treatment indicator characteristics and distribution of personality disorder diagnoses. Personality disorder comorbidity made MDD treatment more complex, and recurrence of MDD episodes and hospital readmission occurred more often than if patients had a sole MDD diagnosis.

  1. Cognitive-behavioral group therapy is an effective treatment for major depression in hemodialysis patients.

    Science.gov (United States)

    Duarte, Priscila Silveira; Miyazaki, Maria Cristina; Blay, Sergio Luís; Sesso, Ricardo

    2009-08-01

    Depression is an important target of psychological assessment in patients with end-stage renal disease because it predicts their morbidity, mortality, and quality of life. We assessed the effectiveness of cognitive-behavioral therapy in chronic hemodialysis patients diagnosed with major depression by the Mini International Neuropsychiatric Interview (MINI). In a randomized trial conducted in Brazil, an intervention group of 41 patients was given 12 weekly sessions of cognitive-behavioral group therapy led by a trained psychologist over 3 months while a control group of 44 patients received the usual treatment offered in the dialysis unit. In both groups, the Beck Depression Inventory, the MINI, and the Kidney Disease and Quality of Life-Short Form questionnaires were administered at baseline, after 3 months of intervention or usual treatment, and after 9 months of follow-up. The intervention group had significant improvements, compared to the control group, in the average scores of the Beck Depression Inventory overall scale, MINI scores, and in quality-of-life dimensions that included the burden of renal disease, sleep, quality of social interaction, overall health, and the mental component summary. We conclude that cognitive-behavioral group therapy is an effective treatment of depression in chronic hemodialysis patients.

  2. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.

    Science.gov (United States)

    Carhart-Harris, Robin L; Bolstridge, Mark; Rucker, James; Day, Camilla M J; Erritzoe, David; Kaelen, Mendel; Bloomfield, Michael; Rickard, James A; Forbes, Ben; Feilding, Amanda; Taylor, David; Pilling, Steve; Curran, Valerie H; Nutt, David J

    2016-07-01

    Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression. In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of psilocybin's effects. Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up. Depressive symptoms were assessed with standard assessments from 1 week to 3 months after treatment, with the 16-item Quick Inventory of Depressive Symptoms (QIDS) serving as the primary efficacy outcome. This trial is registered with ISRCTN, number ISRCTN14426797. Psilocybin's acute psychedelic effects typically became detectable 30-60 min after dosing, peaked 2-3 h after dosing, and subsided to negligible levels at least 6 h after dosing. Mean self-rated intensity (on a 0-1 scale) was 0·51 (SD 0·36) for the low-dose session and 0·75 (SD 0·27) for the high-dose session. Psilocybin was well tolerated by all of the patients, and no serious or unexpected adverse events occurred. The adverse reactions we noted were transient anxiety during drug onset (all patients), transient confusion or thought disorder (nine patients), mild and transient nausea (four patients), and transient headache (four patients). Relative to baseline, depressive symptoms were markedly reduced 1

  3. Impact of treatment and re-treatment with artemether-lumefantrine and artesunate-amodiaquine on selection of Plasmodium falciparum multidrug resistance gene-1 polymorphisms in the Democratic Republic of Congo and Uganda

    DEFF Research Database (Denmark)

    Baraka, Vito; Mavoko, Hypolite Muhindo; Nabasumba, Carolyn

    2018-01-01

    fragment length polymorphism (RFLP) assays. RESULTS: The pre-treatment prevalence of Pfmdr1 N86 and D1246Y varied significantly between the sites, (p>0.001) and (p = 0.013), respectively. There was borderline significant directional selection for Pfmdr1 184F in recurrent malaria infections after treatment...... with AL in Uganda site (p = 0.05). Pfmdr1 NFD haplotype did not significantly change in post-treatment infections after re-treatment with either AL or ASAQ. Comparison between pre-treatment and post-treatment recurrences did not indicate directional selection of Pfmdr1 N86, D1246 alleles in the pre......BACKGROUND: The emergence of resistance against artemisinin combination treatment is a major concern for malaria control. ACTs are recommended as the rescue treatment, however, there is limited evidence as to whether treatment and re-treatment with ACTs select for drug-resistant P. falciparum...

  4. TREATMENT OF RESISTANT DEPRESSIONS AND CASE OF SUCCESSFUL USE OF DONEPEZIL HCl IN THEIR THERAPY

    Directory of Open Access Journals (Sweden)

    Dragan Terzič

    2001-07-01

    Full Text Available Background. In this article some approaches how to treat a stadium of resistant depression are described. There is also a description of the successful use of inhibitors acetylholinesterase donepezil hydrochloride (Aricept in treatment of this kind of depression. Taking into account a great number of depressive patients who are resistant to usual antidepressivs these new approaches to treatment are of a great importance due to the fact that in many cases previous treatments of a depressive patients proved to be unsuccessful. This article is considered to be one of the first description in respect of the use of inhibitors of acetylcholinesterase in treatment of resistant depressions.Conclusions. In case of resistant depressions, one of the possibilities of its treatment is the use of inhibitors of acetylcholinesterase (and may be others in combination with antidepressants.

  5. Treatment of Multidrug-Resistant Leukemia Cells by Novel Artemisinin-, Egonol-, and Thymoquinone-Derived Hybrid Compounds

    Directory of Open Access Journals (Sweden)

    Lisa Gruber

    2018-04-01

    Full Text Available Two major obstacles for successful cancer treatment are the toxicity of cytostatics and the development of drug resistance in cancer cells during chemotherapy. Acquired or intrinsic drug resistance is responsible for almost 90% of treatment failure. For this reason, there is an urgent need for new anticancer drugs with improved efficacy against cancer cells, and with less toxicity on normal cells. There are impressive examples demonstrating the success of natural plant compounds to fight cancer, such as Vinca alkaloids, taxanes, and anthracyclines. Artesunic acid (ARTA, a drug for malaria treatment, also exerts cytotoxic activity towards cancer cells. Multidrug resistance often results from drug efflux pumps (ABC-transporters that reduce intracellular drug levels. Hence, it would be interesting to know, whether ARTA could overcome drug resistance of tumor cells, and in what way ABC-transporters are involved. Different derivatives showing improved features concerning cytotoxicity and pharmacokinetic behavior have been developed. Considering both drug sensitivity and resistance, we chose a sensitive and a doxorubicin-resistant leukemia cell line and determined the killing effect of ARTA on these cells. Molecular docking and doxorubicin efflux assays were performed to investigate the interaction of the derivatives with P-glycoprotein. Using single-cell gel electrophoresis (alkaline comet assay, we showed that the derivatives of ARTA induce DNA breakage and accordingly programmed cell death, which represents a promising strategy in cancer treatment. ARTA activated apoptosis in cancer cells by the iron-mediated generation of reactive oxygen species (ROS. In conclusion, ARTA derivatives may bear the potential to be further developed as anticancer drugs.

  6. A wavelet-based technique to predict treatment outcome for Major Depressive Disorder

    Science.gov (United States)

    Xia, Likun; Mohd Yasin, Mohd Azhar; Azhar Ali, Syed Saad

    2017-01-01

    Treatment management for Major Depressive Disorder (MDD) has been challenging. However, electroencephalogram (EEG)-based predictions of antidepressant’s treatment outcome may help during antidepressant’s selection and ultimately improve the quality of life for MDD patients. In this study, a machine learning (ML) method involving pretreatment EEG data was proposed to perform such predictions for Selective Serotonin Reuptake Inhibitor (SSRIs). For this purpose, the acquisition of experimental data involved 34 MDD patients and 30 healthy controls. Consequently, a feature matrix was constructed involving time-frequency decomposition of EEG data based on wavelet transform (WT) analysis, termed as EEG data matrix. However, the resultant EEG data matrix had high dimensionality. Therefore, dimension reduction was performed based on a rank-based feature selection method according to a criterion, i.e., receiver operating characteristic (ROC). As a result, the most significant features were identified and further be utilized during the training and testing of a classification model, i.e., the logistic regression (LR) classifier. Finally, the LR model was validated with 100 iterations of 10-fold cross-validation (10-CV). The classification results were compared with short-time Fourier transform (STFT) analysis, and empirical mode decompositions (EMD). The wavelet features extracted from frontal and temporal EEG data were found statistically significant. In comparison with other time-frequency approaches such as the STFT and EMD, the WT analysis has shown highest classification accuracy, i.e., accuracy = 87.5%, sensitivity = 95%, and specificity = 80%. In conclusion, significant wavelet coefficients extracted from frontal and temporal pre-treatment EEG data involving delta and theta frequency bands may predict antidepressant’s treatment outcome for the MDD patients. PMID:28152063

  7. A wavelet-based technique to predict treatment outcome for Major Depressive Disorder.

    Science.gov (United States)

    Mumtaz, Wajid; Xia, Likun; Mohd Yasin, Mohd Azhar; Azhar Ali, Syed Saad; Malik, Aamir Saeed

    2017-01-01

    Treatment management for Major Depressive Disorder (MDD) has been challenging. However, electroencephalogram (EEG)-based predictions of antidepressant's treatment outcome may help during antidepressant's selection and ultimately improve the quality of life for MDD patients. In this study, a machine learning (ML) method involving pretreatment EEG data was proposed to perform such predictions for Selective Serotonin Reuptake Inhibitor (SSRIs). For this purpose, the acquisition of experimental data involved 34 MDD patients and 30 healthy controls. Consequently, a feature matrix was constructed involving time-frequency decomposition of EEG data based on wavelet transform (WT) analysis, termed as EEG data matrix. However, the resultant EEG data matrix had high dimensionality. Therefore, dimension reduction was performed based on a rank-based feature selection method according to a criterion, i.e., receiver operating characteristic (ROC). As a result, the most significant features were identified and further be utilized during the training and testing of a classification model, i.e., the logistic regression (LR) classifier. Finally, the LR model was validated with 100 iterations of 10-fold cross-validation (10-CV). The classification results were compared with short-time Fourier transform (STFT) analysis, and empirical mode decompositions (EMD). The wavelet features extracted from frontal and temporal EEG data were found statistically significant. In comparison with other time-frequency approaches such as the STFT and EMD, the WT analysis has shown highest classification accuracy, i.e., accuracy = 87.5%, sensitivity = 95%, and specificity = 80%. In conclusion, significant wavelet coefficients extracted from frontal and temporal pre-treatment EEG data involving delta and theta frequency bands may predict antidepressant's treatment outcome for the MDD patients.

  8. Investigation of Biofield Treatment on Antimicrobial Susceptibility, Biochemical Reaction Pattern and Biotyping of Enteropathogenic Multidrug-Resistant Escherichia coli Isolates

    OpenAIRE

    Trivedi, Dahryn; Trivedi, Mahendra Kumar; Branton, Alice; Nayak, Gopal; Shettigar, Harish; Gangwar, Mayank; Jana, Snehasis

    2015-01-01

    Study background: Multidrug resistant Escherichia coli (MDR E. coli) has become a major health concern, and failure of treatment leads to huge health burden. Aim of the present study was to determine the impact of Mr. Trivedi’s biofield treatment on E. coli. Methods: Four MDR clinical lab isolates (LSs) of E. coli (LS 8, LS 9, LS 10, and LS 11) were taken and divided into two groups i.e. control and biofield treated. Control and treated samples were identified with respect to its antimicr...

  9. A randomized controlled comparison of electroconvulsive therapy and repetitive transcranial magnetic stimulation in severe and resistant nonpsychotic major depression.

    Science.gov (United States)

    Grunhaus, Leon; Schreiber, Shaul; Dolberg, Ornah T; Polak, Dana; Dannon, Pinhas N

    2003-02-15

    Studies published over the past few years suggest that transcranial magnetic stimulation (TMS) may have significant antidepressant actions. In a previous report, we compared electroconvulsive therapy (ECT) and repetitive TMS (rTMS) and found ECT to be superior for psychotic major depression (MD); however, ECT and rTMS had similar results in nonpsychotic MD. We now report on a controlled randomized comparison of ECT and rTMS in patients with nonpsychotic MD. Forty patients with nonpsychotic MD referred for ECT were included. Electroconvulsive therapy was performed according to established protocols. Repetitive TMS was performed over the left dorsolateral prefrontal cortex at 90% motor threshold. Patients were treated with 20 sessions (five times per week for 4 weeks) of 10-Hz treatments (1200 pulses per treatment-day) at 90% motor threshold. Response to treatment was defined as a decrease of at least 50% in the Hamilton Rating Scale for Depression (HRSD) score, with a final HRSD equal or less than 10 points and a final Global Assessment of Function Scale rating of 60 or more points. The overall response rate was 58% (23 out of 40 patients responded to treatment). In the ECT group, 12 responded and eight did not; in the rTMS group, 11 responded and nine did not (chi2 =.10, ns). Thus, patients responded as well to either ECT or rTMS. This study adds to the growing literature supporting an antidepressant effect for rTMS. This study is particularly relevant because it suggests that rTMS and ECT reach similar results in nonpsychotic major depressive disorder.

  10. Efficacy and safety profile of linezolid in the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis: a systematic review and meta-analysis.

    Science.gov (United States)

    Agyeman, Akosua Adom; Ofori-Asenso, Richard

    2016-06-22

    Treatment options for drug-resistant tuberculosis are still limited. Linezolid has been recommended for treatment of patients with multidrug-resistant (MDR) or extensively-drug-resistant (XDR) tuberculosis, although uncertainties remain regarding its safety and tolerability in these circumstances. To systematically evaluate the existing evidence regarding the efficacy and tolerability of linezolid in the treatment of MDR or XDR tuberculosis. We conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines. Searches were conducted in PubMed, Web of Science and EMBASE followed by direct search of abstracts in the International Journal of Tuberculosis and Lung Disease to retrieve primary studies published between January 2000 and January 2016 assessing linezolid efficacy and safety in the treatment of drug-resistant TB. We evaluated the occurrence of outcomes including culture conversion, treatment success and incidence of adverse events such as myelosuppression and neuropathy. Twenty-three (23) studies conducted in fourteen (14) countries and involving 507 patients were retrieved. Only 1 randomized controlled trial was identified and none of the identified studies involved participants from Africa. The pooled proportion for treatment success was 77.36 % (95 % CI = 71.38-82.83 %, I(2) = 37.6 %) with culture conversion rate determined as 88.45 % (95 % CI = 83.82-92.38 %, I(2) = 45.4 %). There was no strong evidence for both culture conversion (p = 0.0948) and treatment success (p = 0.0695) between linezolid daily doses ≤ 600 and > 600 mg. Only myelosuppression showed a strong statistical significance (p linezolid also showed no significance upon dose comparisons (p = 0.3213, p = 0.9050 respectively). Available evidence presents Linezolid as a viable option in the treatment of MDR/XDR TB although patients ought to be monitored closely for the incidence of major adverse events such as myelosuppression and

  11. Low-dose ketamine for treatment resistant depression in an academic clinical practice setting.

    Science.gov (United States)

    Feifel, David; Malcolm, Benjamin; Boggie, Danielle; Lee, Kelly

    2017-10-15

    Recent studies demonstrating a rapid, robust improvement in treatment resistant depression (TRD) following a single sub-anesthetic infusion of ketamine have generated much excitement. However, these studies are limited in their generalizability to the broader TRD population due to their subject exclusion criteria which typically limit psychiatric comorbidity, concurrent medication, and level of suicide risk. This paper describes the safety and efficacy of sub-anesthetic ketamine infusions in a naturalistic TRD patient sample participating in a real-world TRD treatment program within a major university health system. The effects of a sub-anesthetic dose (0.5mg/kg) of ketamine infused IV over forty minutes on TRD patients participating in a treatment program at the University of California, San Diego was investigated by retrospectively analyzing the medical charts of 41 adult TRD patients with a diagnosis of Major Depressive Disorder (MDD) or Bipolar Disorder (BD). Subjects were aged 48.6, 78% white, 36.6% female, and 82.9% had MDD. Significant psychiatric comorbidity existed in 73%. Average pre-infusion BDI score was 32.6 ± 8.4 (S.D) and dropped to 16.8 ± 3.1 at 24-h post-infusion (p Ketamine infusions were well tolerated with occasional nausea or anxiety and mild hemodynamic effects during the infusion. Retrospective nature of this study, lack of control group and use of self-report depression ratings scales. This is the first published study of sub-anesthetic ketamine infusions in a real-world TRD population. The results suggest that this treatment is effective and well tolerated in this population. Copyright © 2017. Published by Elsevier B.V.

  12. Failure of hippocampal deactivation during loss events in treatment-resistant depression.

    Science.gov (United States)

    Johnston, Blair A; Tolomeo, Serenella; Gradin, Victoria; Christmas, David; Matthews, Keith; Steele, J Douglas

    2015-09-01

    Major depressive disorder is characterized by anhedonia, cognitive biases, ruminations, hopelessness and increased anxiety. Blunted responses to rewards have been reported in a number of recent neuroimaging and behavioural studies of major depressive disorder. In contrast, neural responses to aversive events remain an under-studied area. While selective serotonergic reuptake inhibitors are often effective in treating major depressive disorder, their mechanism of action remains unclear. Following a series of animal model investigations of depressive illness and serotonergic function, Deakin and Graeff predicted that brain activity in patients with major depressive disorder is associated with an overactive dorsal raphe nucleus with overactive projections to the amygdala, periaqueductal grey and striatum, and an underactive median raphe nucleus with underactive projections to the hippocampus. Here we describe an instrumental loss-avoidance and win-gain reinforcement learning functional magnetic resonance imaging study with 40 patients with highly treatment-resistant major depressive disorder and never-depressed controls. The dorsal raphe nucleus/ periaqueductal grey region of the midbrain and hippocampus were found to be overactive in major depressive disorder during unsuccessful loss-avoidance although the median raphe nucleus was not found to be underactive. Hippocampal overactivity was due to a failure to deactivate during loss events in comparison to controls, and hippocampal over-activity correlated with depression severity, self-report 'hopelessness' and anxiety. Deakin and Graeff argued that the median raphe nucleus normally acts to inhibit consolidation of aversive memories via the hippocampus and this system is underactive in major depressive disorder, facilitating the development of ruminations, while the dorsal raphe nucleus system is engaged by distal cues predictive of threats and is overactive in major depressive disorder. During win events the striatum

  13. Transcranial Direct Current Stimulation (tDCS): A Promising Treatment for Major Depressive Disorder?

    Science.gov (United States)

    Bennabi, Djamila; Haffen, Emmanuel

    2018-01-01

    Background: Transcranial direct current stimulation (tDCS) opens new perspectives in the treatment of major depressive disorder (MDD), because of its ability to modulate cortical excitability and induce long-lasting effects. The aim of this review is to summarize the current status of knowledge regarding tDCS application in MDD. Methods: In this review, we searched for articles published in PubMed/MEDLINE from the earliest available date to February 2018 that explored clinical and cognitive effects of tDCS in MDD. Results: Despite differences in design and stimulation parameters, the examined studies indicated beneficial effects of tDCS for MDD. These preliminary results, the non-invasiveness of tDCS, and its good tolerability support the need for further research on this technique. Conclusions: tDCS constitutes a promising therapeutic alternative for patients with MDD, but its place in the therapeutic armamentarium remains to be determined. PMID:29734768

  14. Recombinant factor VIIa treatment for asymptomatic factor VII deficient patients going through major surgery.

    Science.gov (United States)

    Livnat, Tami; Shenkman, Boris; Spectre, Galia; Tamarin, Ilia; Dardik, Rima; Israeli, Amnon; Rivkind, Avraham; Shabtai, Moshe; Marinowitz, Uri; Salomon, Ophira

    2012-07-01

    Factor VII deficiency is the most common among the rare autosomal recessive coagulation disorders worldwide. In factor VII deficient patients, the severity and clinical manifestations cannot be reliably determined by factor VII levels. Severe bleeding tends to occur in individuals with factor VII activity levels of 2% or less of normal. Patients with 2-10% factor VII vary between asymptomatic to severe life threatening haemorrhages behaviour. Recombinant factor VIIa (rFVIIa) is the most common replacement therapy for congenital factor VII deficiency. However, unlike haemophilia patients for whom treatment protocols are straight forward, in asymptomatic factor VII deficiency patients it is still debatable. In this study, we demonstrate that a single and very low dose of recombinant factor VIIa enabled asymptomatic patients with factor VII deficiency to go through major surgery safely. This suggestion was also supported by thrombin generation, as well as by thromboelastometry.

  15. Vortioxetine: A new alternative for the treatment of major depressive disorder.

    Science.gov (United States)

    Salagre, Estela; Grande, Iria; Solé, Brisa; Sanchez-Moreno, Jose; Vieta, Eduard

    Major Depressive Disorder (MDD) is a serious psychiatric condition. Its treatment remains a challenge nowadays. Vortioxetine is a novel antidepressant with a unique profile, as it acts as a multimodal serotoninergic agent. Its efficacy in MDD has been established in many short- and long-term studies, with 7 positive, 4 negative and 1 failed randomized controlled trials. Moreover, its ability to modulate a wide range of neurotransmitters (serotonin, dopamine, norepinephrine, histamine, glutamate or GABA) confers vortioxetine pro-cognitive effects. Side effects are also different from conventional antidepressants, according to its low incidence of sexual dysfunction, weight gain or cardiovascular alterations. The aim of this systematic review is to describe the pharmacology, clinical efficacy and safety profile of vortioxetine, as well as its potential effectiveness in improving cognitive symptoms. Copyright © 2017 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Acute and long-term treatment of late-life major depressive disorder: duloxetine versus placebo.

    Science.gov (United States)

    Robinson, Michael; Oakes, Tina Myers; Raskin, Joel; Liu, Peng; Shoemaker, Scarlett; Nelson, J Craig

    2014-01-01

    To compare the efficacy of duloxetine with placebo on depression in elderly patients with major depressive disorder. Multicenter, 24-week (12-week short-term and 12-week continuation), randomized, placebo-controlled, double-blind trial. United States, France, Mexico, Puerto Rico. Age 65 years or more with major depressive disorder diagnosis (one or more previous episode); Mini-Mental State Examination score ≥20; Montgomery-Asberg Depression Rating Scale total score ≥20. Duloxetine 60 or 120 mg/day or placebo; placebo rescue possible. Primary-Maier subscale of the 17-item Hamilton Depression Rating Scale (HAMD-17) at week 12. Secondary-Geriatric Depression Scale, HAMD-17 total score, cognitive measures, Brief Pain Inventory (BPI), Numeric Rating Scales (NRS) for pain, Clinical Global Impression-Severity scale, Patient Global Impression of Improvement in acute phase and acute plus continuation phase of treatment. Compared with placebo, duloxetine did not show significantly greater improvement from baseline on Maier subscale at 12 weeks, but did show significantly greater improvement at weeks 4, 8, 16, and 20. Similar patterns for Geriatric Depression Scale and Clinical Global Impression-Severity scale emerged, with significance also seen at week 24. There was a significant treatment effect for all BPI items and 4 of 6 NRS pain measures in the acute phase, most BPI items and half of the NRS measures in the continuation phase. More duloxetine-treated patients completed the study (63% versus 55%). A significantly higher percentage of duloxetine-treated patients versus placebo discontinued due to adverse event (15.3% versus 5.8%). Although the antidepressant efficacy of duloxetine was not confirmed by the primary outcome, several secondary measures at multiple time points suggested efficacy. Duloxetine had significant and meaningful beneficial effects on pain. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights

  17. Symmetrical treatment of "Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition", for major depressive disorders.

    Science.gov (United States)

    Sawamura, Jitsuki; Morishita, Shigeru; Ishigooka, Jun

    2016-01-01

    We previously presented a group theoretical model that describes psychiatric patient states or clinical data in a graded vector-like format based on modulo groups. Meanwhile, the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5, the current version), is frequently used for diagnosis in daily psychiatric treatments and biological research. The diagnostic criteria of DSM-5 contain simple binominal items relating to the presence or absence of specific symptoms. In spite of its simple form, the practical structure of the DSM-5 system is not sufficiently systemized for data to be treated in a more rationally sophisticated way. To view the disease states in terms of symmetry in the manner of abstract algebra is considered important for the future systematization of clinical medicine. We provide a simple idea for the practical treatment of the psychiatric diagnosis/score of DSM-5 using depressive symptoms in line with our previously proposed method. An expression is given employing modulo-2 and -7 arithmetic (in particular, additive group theory) for Criterion A of a 'major depressive episode' that must be met for the diagnosis of 'major depressive disorder' in DSM-5. For this purpose, the novel concept of an imaginary value 0 that can be recognized as an explicit 0 or implicit 0 was introduced to compose the model. The zeros allow the incorporation or deletion of an item between any other symptoms if they are ordered appropriately. Optionally, a vector-like expression can be used to rate/select only specific items when modifying the criterion/scale. Simple examples are illustrated concretely. Further development of the proposed method for the criteria/scale of a disease is expected to raise the level of formalism of clinical medicine to that of other fields of natural science.

  18. Neurofeedback as a treatment for major depressive disorder--a pilot study.

    Science.gov (United States)

    Peeters, Frenk; Oehlen, Mare; Ronner, Jacco; van Os, Jim; Lousberg, Richel

    2014-01-01

    There is growing interest in neurofeedback as a treatment for major depressive disorder. Reduction of asymmetry of alpha-activity between left and right prefrontal areas with neurofeedback has been postulated as effective in earlier studies. Unfortunately, methodological shortcomings limit conclusions that can be drawn from these studies. In a pilot-study, we investigated the effectiveness of reduction of asymmetry of alpha-activity with neurofeedback in depressed participants with the use of a stringent methodological approach. Nine participants meeting DSM-IV criteria for major depressive disorder were treated with a maximum of 30 neurofeedback-sessions, aimed at reducing asymmetry of alpha-activity, over a 10-week period. No changes in the use of antidepressants were allowed 6 weeks before and during the intervention. Changes in depressive symptomatology were assessed with the Quick Inventory of Depressive Symptoms, self-report version. We observed response in 1 and remission in 4 out of a total of 9 participants. The effectiveness appeared largest in female participants. The mean asymmetry of alpha-activity decreased significantly over sessions in a quadratic fashion. This decrease was associated with clinical response. This pilot study suggests that neurofeedback aimed at a reduction of frontal asymmetry of alpha-activity may be effective as a treatment for depression. However, this was an open label pilot study. Non-specific effects of the procedure and/or a beneficial natural course may have confounded the results. Randomized controlled trials will have to establish the efficacy of neurofeedback for depression. Nederlands Trial Register NTR1629.

  19. LIGHT Is critical for IL-12 production by dendritic cells, optimal CD4+ Th1 cell response, and resistance to Leishmania major.

    Science.gov (United States)

    Xu, Guilian; Liu, Dong; Okwor, Ifeoma; Wang, Yang; Korner, Heinrich; Kung, Sam K P; Fu, Yang-Xin; Uzonna, Jude E

    2007-11-15

    Although studies indicate LIGHT (lymphotoxin (LT)-like, exhibits inducible expression and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes) enhances inflammation and T cell-mediated immunity, the mechanisms involved in this process remain obscure. In this study, we assessed the role of LIGHT in IL-12 production and development of CD4(+) Th cells type one (Th1) in vivo. Bone marrow-derived dendritic cells from LIGHT(-/-) mice were severely impaired in IL-12p40 production following IFN-gamma and LPS stimulation in vitro. Furthermore, blockade of LIGHT in vitro and in vivo with HVEM-Ig and LT beta receptor (LTbetaR)-Ig leads to impaired IL-12 production and defective polyclonal and Ag-specific IFN-gamma production in vivo. In an infection model, injection of HVEM-Ig or LTbetaR-Ig into the usually resistant C57BL/6 mice results in defective IL-12 and IFN-gamma production and severe susceptibility to Leishmania major that was reversed by rIL-12 treatment. This striking susceptibility to L. major in mice injected with HVEM-Ig or LTbetaR-Ig was also reproduced in LIGHT(-/-) --> RAG1(-/-) chimeric mice. In contrast, L. major-infected LTbeta(-/-) mice do not develop acute disease, suggesting that the effect of LTbetaR-Ig is not due to blockade of membrane LT (LTalpha1beta2) signaling. Collectively, our data show that LIGHT plays a critical role for optimal IL-12 production by DC and the development of IFN-gamma-producing CD4(+) Th1 cells and its blockade results in severe susceptibility to Leishmania major.

  20. Fate of antibiotic resistance genes within the microbial communities of three waste water treatment plants

    OpenAIRE

    Di Cesare, Andrea; Eckert, Ester; D'Urso, Silvia; Doppelbauer, Julia; Corno, Gianluca

    2016-01-01

    Although Waste Water Treatment Plant (WWTP) are designed to reduce the biological pollution of urban waters, they lack a specific action against antibiotic resistance bacteria (ARB) or antibiotic resistance genes (ARGs). Nowadays, it is well documented that WWTPs constitute a reservoir of antibiotic resistances and, in some cases, they can be a favorable environment for the selection of ARB. This represent a serious concern for the public health, because the effluents of the WWTPs can be reus...

  1. Brain functional changes in facial expression recognition in patients with major depressive disorder before and after antidepressant treatment

    OpenAIRE

    Jiang, Wenyan; Yin, Zhongmin; Pang, Yixin; Wu, Feng; Kong, Lingtao; Xu, Ke

    2012-01-01

    Functional magnetic resonance imaging was used during emotion recognition to identify changes in functional brain activation in 21 first-episode, treatment-naive major depressive disorder patients before and after antidepressant treatment. Following escitalopram oxalate treatment, patients exhibited decreased activation in bilateral precentral gyrus, bilateral middle frontal gyrus, left middle temporal gyrus, bilateral postcentral gyrus, left cingulate and right parahippocampal gyrus, and inc...

  2. Host range of antibiotic resistance genes in wastewater treatment plant influent and effluent.

    Science.gov (United States)

    Hultman, Jenni; Tamminen, Manu; Pärnänen, Katariina; Cairns, Johannes; Karkman, Antti; Virta, Marko

    2018-04-01

    Wastewater treatment plants (WWTPs) collect wastewater from various sources for a multi-step treatment process. By mixing a large variety of bacteria and promoting their proximity, WWTPs constitute potential hotspots for the emergence of antibiotic resistant bacteria. Concerns have been expressed regarding the potential of WWTPs to spread antibiotic resistance genes (ARGs) from environmental reservoirs to human pathogens. We utilized epicPCR (Emulsion, Paired Isolation and Concatenation PCR) to detect the bacterial hosts of ARGs in two WWTPs. We identified the host distribution of four resistance-associated genes (tetM, int1, qacEΔ1and blaOXA-58) in influent and effluent. The bacterial hosts of these resistance genes varied between the WWTP influent and effluent, with a generally decreasing host range in the effluent. Through 16S rRNA gene sequencing, it was determined that the resistance gene carrying bacteria include both abundant and rare taxa. Our results suggest that the studied WWTPs mostly succeed in decreasing the host range of the resistance genes during the treatment process. Still, there were instances where effluent contained resistance genes in bacterial groups not carrying these genes in the influent. By permitting exhaustive profiling of resistance-associated gene hosts in WWTP bacterial communities, the application of epicPCR provides a new level of precision to our resistance gene risk estimates.

  3. Post-treatment resistance analysis of hepatitis C virus from phase II and III clinical trials of ledipasvir/sofosbuvir.

    Science.gov (United States)

    Wyles, David; Dvory-Sobol, Hadas; Svarovskaia, Evguenia S; Doehle, Brian P; Martin, Ross; Afdhal, Nezam H; Kowdley, Kris V; Lawitz, Eric; Brainard, Diana M; Miller, Michael D; Mo, Hongmei; Gane, Edward J

    2017-04-01

    Ledipasvir/sofosbuvir combination treatment in phase III clinical trials resulted in sustained viral suppression in 94-99% of patients. This study characterized drug resistance in treatment failures, which may help to inform retreatment options. We performed NS5A and NS5B deep sequencing of hepatitis C virus (HCV) from patients infected with genotype (GT) 1 who participated in ledipasvir/sofosbuvir phase II and III clinical trials. Fifty-one of 2144 (2.4%) (42 GT1a and 9 GT1b) treated patients met the criteria for resistance analysis due to virologic failure following the end of treatment. The majority of patients with virologic failure (38 of 51; 74.5%) had detectable ledipasvir-specific resistance-associated substitutions (RASs) at the time of virologic failure (1% deep sequencing cut-off). The percent of patients with NS5A RASs at virologic failure were 37.5%, 66.7%, 94.7% and 100% in patients treated for 6, 8, 12 and 24weeks, respectively. The common substitutions detected at failure were Q30R/H, and/or Y93H/N in GT1a and Y93H in GT1b. At failure, 35.3% (18/51) of virologic failure patients' viruses had two or more NS5A RASs and the majority of patients harbored NS5A RASs conferring a 100-1000-fold (n=10) or >1000-fold (n=23) reduced susceptibility to ledipasvir. One patient in a phase II study with a known ledipasvir RAS at baseline (L31M) developed the S282T sofosbuvir (NS5B) RAS at failure. In GT1 HCV-infected patients treated with ledipasvir/sofosbuvir±ribavirin, virologic failure was rare. Ledipasvir resistance in NS5A was selected or enhanced in most patients with virologic failure, one of whom also developed resistance to sofosbuvir. Clinical studies have shown that combination treatment with ledipasvir/sofosbuvir efficiently cures most patients with genotype 1 hepatitis C infection. For the few patients failing treatment, we show that resistance to ledipasvir was observed in most patients, whereas resistance to sofosbuvir was less common. This has

  4. Cognitive remission: a novel objective for the treatment of major depression?

    Science.gov (United States)

    Bortolato, Beatrice; Miskowiak, Kamilla W; Köhler, Cristiano A; Maes, Michael; Fernandes, Brisa S; Berk, Michael; Carvalho, André F

    2016-01-22

    Cognitive dysfunction in major depressive disorder (MDD) encompasses several domains, including but not limited to executive function, verbal memory, and attention. Furthermore, cognitive dysfunction is a frequent residual manifestation in depression and may persist during the remitted phase. Cognitive deficits may also impede functional recovery, including workforce performance, in patients with MDD. The overarching aims of this opinion article are to critically evaluate the effects of available antidepressants as well as novel therapeutic targets on neurocognitive dysfunction in MDD. Conventional antidepressant drugs mitigate cognitive dysfunction in some people with MDD. However, a significant proportion of MDD patients continue to experience significant cognitive impairment. Two multicenter randomized controlled trials (RCTs) reported that vortioxetine, a multimodal antidepressant, has significant precognitive effects in MDD unrelated to mood improvement. Lisdexamfetamine dimesylate was shown to alleviate executive dysfunction in an RCT of adults after full or partial remission of MDD. Preliminary evidence also indicates that erythropoietin may alleviate cognitive dysfunction in MDD. Several other novel agents may be repurposed as cognitive enhancers for MDD treatment, including minocycline, insulin, antidiabetic agents, angiotensin-converting enzyme inhibitors, S-adenosyl methionine, acetyl-L-carnitine, alpha lipoic acid, omega-3 fatty acids, melatonin, modafinil, galantamine, scopolamine, N-acetylcysteine, curcumin, statins, and coenzyme Q10. The management of cognitive dysfunction remains an unmet need in the treatment of MDD. However, it is hoped that the development of novel therapeutic targets will contribute to 'cognitive remission', which may aid functional recovery in MDD.

  5. Indoleamine 2,3-dioxygenase and immune changes under antidepressive treatment in major depression in females.

    Science.gov (United States)

    Zoga, Margarita; Oulis, Panagiotis; Chatzipanagiotou, Stylianos; Masdrakis, Vasilios G; Pliatsika, Paraskevi; Boufidou, Fotini; Foteli, Stefania; Soldatos, Constantin R; Nikolaou, Chryssoula; Papageorgiou, Charalampos

    2014-01-01

    Indoleamine 2, 3-dioxygenase (IDO) induction has been suggested as a mechanism by which immune activation affects tryptophan metabolism and serotonin synthesis in major depressive disorder (MDD). We investigated IDO and changes in inflammatory mediators in patients with MDD undergoing effective treatment. Forty female patients with MDD and 40 controls were recruited. Serum IDO was assessed by enzyme-linked immunosorbent assay (ELISA). We also determined tumor necrosis factor-α (TNFα), interferon-γ (IFNγ), C-reactive protein (CRP) and serotonin concentrations. Patients' baseline concentrations of IDO and immune mediators were higher and serotonin concentrations were lower compared to controls. IDO and TNFα concentrations decreased under treatment and IDO changes were positively correlated with patient improvement. IFNγ and CRP concentrations remained unchanged. Serotonin concentration tended to increase. IDO might play an important role in the pathophysiology of MDD. Moreover, antidepressant therapy might reduce IDO production through an IFNγ-independent pathway. Finally, peripheral concentration of IDO assessed by ELISA might be a useful marker of MDD. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  6. Abnormal Functional Connectivity of Frontopolar Subregions in Treatment-Nonresponsive Major Depressive Disorder.

    Science.gov (United States)

    Fettes, Peter W; Moayedi, Massieh; Dunlop, Katharine; Mansouri, Farrokh; Vila-Rodriguez, Fidel; Giacobbe, Peter; Davis, Karen D; Lam, Raymond W; Kennedy, Sidney H; Daskalakis, Zafiris J; Blumberger, Daniel M; Downar, Jonathan

    2018-04-01

    Approximately 30% of patients with major depressive disorder develop treatment-nonresponsive depression (TNRD); novel interventions targeting the substrates of this illness population are desperately needed. Convergent evidence from lesion, stimulation, connectivity, and functional neuroimaging studies implicates the frontopolar cortex (FPC) as a particularly important region in TNRD pathophysiology; regions functionally connected to the FPC, once identified, could present favorable targets for novel brain stimulation treatments. We recently published a parcellation of the FPC based on diffusion tensor imaging data, identifying distinct medial and lateral subregions. Here, we applied this parcellation to resting-state functional magnetic resonance imaging scans obtained in 56 patients with TNRD and 56 matched healthy control subjects. In patients, the medial FPC showed reduced connectivity to the anterior midcingulate cortex and insula. The left lateral FPC showed reduced connectivity to the right lateral orbitofrontal cortex and increased connectivity to the fusiform gyri. In addition, TNRD symptom severity correlated significantly with connectivity of the left lateral FPC subregion to a medial orbitofrontal cortex region of the classical reward network. Taken together, these findings suggest that changes in FPC subregion connectivity may underlie several dimensions of TNRD pathology, including changes in reward/positive valence, nonreward/negative valence, and cognitive control domains. Nodes of functional networks showing abnormal connectivity to the FPC could be useful in generating novel candidates for therapeutic brain stimulation in TNRD. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  7. Antibiotic treatments of a methicillin-resistant Staphylococcus pseudintermedius infection in a dog: a case presentation.

    Science.gov (United States)

    Decristophoris, P; Mauri, F; Albanese, F; Carnelli, A; Vanzetti, T; Zinsstag, J

    2011-09-01

    We report the antibiotic treatments administered to a female dog with mastitis and successive pyoderma. Microbiological investigations allowed the identification of Staphylococcus pseudintermedius after 54 days of various antibiotic treatments. The isolate carried the mecA gene and was resistant to 9 of 15 tested antibiotics. Consistent antibiotic treatment of the infection was possible only after accurate microbiological diagnosis.

  8. Potential antimicrobial agents for the treatment of multidrug-resistant tuberculosis

    NARCIS (Netherlands)

    Alsaad, Noor; Wilffert, Bob; van Altena, Richard; de Lange, Wiel C. M.; van der Werf, Tjip S.; Kosterink, Jos G. W.; Alffenaar, Jan-Willem C.

    2014-01-01

    Treatment of multidrug-resistant (MDR) tuberculosis (TB) is challenging because of the high toxicity of second-line drugs and the longer treatment duration than for drug-susceptible TB patients. In order to speed up novel treatment for MDR-TB, we suggest considering expanding the indications of

  9. The Bi-Directional Relationship between Parent-Child Conflict and Treatment Outcome in Treatment-Resistant Adolescent Depression

    Science.gov (United States)

    Rengasamy, Manivel; Mansoor, Brandon M.; Hilton, Robert; Porta, Giovanna; He, Jiayan; Emslie, Graham J.; Mayes, Taryn; Clarke, Gregory N.; Wagner, Karen Dineen; Keller, Martin B.; Ryan, Neal D.; Birmaher, Boris; Shamseddeen, Wael; Asarnow, Joan Rosenbaum; Brent, David A.

    2013-01-01

    Objective: To examine the bidirectional relationship between parent-child discord and treatment outcome for adolescent treatment-resistant depression. Method: Depressed youth who had not responded to an adequate course of a selective serotonin reuptake inhibitor (SSRI) were randomized to either a switch to another SSRI or venlafaxine, with or…

  10. Definition, identification and treatment of resistant hypertension in chronic kidney disease patients.

    Science.gov (United States)

    Drexler, Yelena R; Bomback, Andrew S

    2014-07-01

    Resistant hypertension, the inability to achieve goal blood pressure despite the use of three or more appropriately dosed antihypertensive drugs (including a diuretic), remains a common clinical problem, especially in patients with chronic kidney disease (CKD). While the exact prevalence and prognosis of resistant hypertension in CKD patients remain unknown, resistant hypertension likely contributes significantly to increased cardiovascular risk and progression of kidney disease in this population. We review the identification and evaluation of patients with resistant hypertension, including the importance of 24-h ambulatory blood pressure monitoring in the identification of 'white-coat', 'masked' and 'non-dipper' hypertension, the latter of which has particular clinical and therapeutic importance in patients with resistant hypertension and CKD. We then discuss treatment strategies for resistant hypertension that target the pathophysiologic mechanisms underlying resistance to treatment, including persistent volume excess, incomplete renin-angiotensin-aldosterone system blockade and inadequate nocturnal blood pressure control. Finally, we propose a treatment algorithm for evaluation and treatment of resistant hypertension in patients with CKD. © The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  11. Treatment Failure Due to Emergence of Resistance to Carbapenem during Therapy for Shewanella algae Bacteremia

    OpenAIRE

    Kim, Dong-Min; Kang, Cheol-In; Lee, Chang Seop; Kim, Hong-Bin; Kim, Eui-Chong; Kim, Nam Joong; Oh, Myoung-don; Choe, Kang-Won

    2006-01-01

    We describe a case of bacteremia due to imipenem-susceptible Shewanella algae. Despite treatment with imipenem, the patient developed a spinal epidural abscess, from which imipenem-resistant S. algae was isolated. The development of resistance should be monitored when S. algae infection is treated with imipenem, even though the strain is initially susceptible to imipenem.

  12. Efficacy of verapamil as an adjunctive treatment in children with drug-resistant epilepsy

    DEFF Research Database (Denmark)

    Nicita, Francesco; Spalice, Alberto; Papetti, Laura

    2014-01-01

    Verapamil, a voltage-gated calcium channel blocker, has been occasionally reported to have some effect on reducing seizure frequency in drug-resistant epilepsy or status epilepticus. We aimed to investigate the efficacy of verapamil as add-on treatment in children with drug-resistant epilepsy....

  13. The effect of vilazodone on sexual function during the treatment of major depressive disorder.

    Science.gov (United States)

    Clayton, Anita H; Kennedy, Sidney H; Edwards, John B; Gallipoli, Susan; Reed, Carol R

    2013-10-01

      Sexual dysfunction is common in major depressive disorder (MDD), and many serotonergic antidepressants adversely affect sexual function. Vilazodone, a novel serotonin (5-HT) reuptake inhibitor and 5-HT1A partial agonist approved for MDD, exerts its effects at the 5-HT transporter and at both presynaptic and postsynaptic 5-HT1A receptors. This mechanism may limit sexual dysfunction.   To summarize effects of vilazodone (40 mg/day, with food) on sexual function in adults with MDD.   Data sources were three Phase III studies: two 8-week, placebo-controlled studies (NCT00285376 and NCT00683592) and a 52-week open-label study (NCT00644358). Sexual function was assessed by analyzing changes from baseline to end of treatment (EOT) using validated measures.   Arizona Sexual Experience Scale or Changes in Sexual Functioning Questionnaire.   Population included 869 patients (vilazodone, 436; placebo, 433) from placebo-controlled studies and 599 patients from the open-label study. Sexual dysfunction prevalence was high (50%, men; 68%, women) before treatment and declined during treatment in vilazodone and placebo groups, indicating improvement on average. At EOT, stable/improved sexual function was observed in ≥91% of patients in placebo-controlled studies; treatment group differences in sexual dysfunction at EOT were not statistically significant for either sex. Differences vs. placebo in changes from baseline of sexual function scores were small and were generally not statistically significant; effect sizes (Cohen's D) were generally of low magnitude. In the placebo-controlled studies, 8.0% of vilazodone-treated patients and 0.9% of placebo-treated patients reported ≥1 sexual-function-related treatment-emergent adverse event (P<0.001).   Half of men and two thirds of women with MDD had sexual dysfunction at baseline; sexual function improved on average in both vilazodone and placebo groups. Results suggest that vilazodone may have a small adverse impact on

  14. Alterations in leukocyte transcriptional control pathway activity associated with major depressive disorder and antidepressant treatment.

    Science.gov (United States)

    Mellon, S H; Wolkowitz, O M; Schonemann, M D; Epel, E S; Rosser, R; Burke, H B; Mahan, L; Reus, V I; Stamatiou, D; Liew, C-C; Cole, S W

    2016-05-24

    Major depressive disorder (MDD) is associated with a significantly elevated risk of developing serious medical illnesses such as cardiovascular disease, immune impairments, infection, dementia and premature death. Previous work has demonstrated immune dysregulation in subjects with MDD. Using genome-wide transcriptional profiling and promoter-based bioinformatic strategies, we assessed leukocyte transcription factor (TF) activity in leukocytes from 20 unmedicated MDD subjects versus 20 age-, sex- and ethnicity-matched healthy controls, before initiation of antidepressant therapy, and in 17 of the MDD subjects after 8 weeks of sertraline treatment. In leukocytes from unmedicated MDD subjects, bioinformatic analysis of transcription control pathway activity indicated an increased transcriptional activity of cAMP response element-binding/activating TF (CREB/ATF) and increased activity of TFs associated with cellular responses to oxidative stress (nuclear factor erythroid-derived 2-like 2, NFE2l2 or NRF2). Eight weeks of antidepressant therapy was associated with significant reductions in Hamilton Depression Rating Scale scores and reduced activity of NRF2, but not in CREB/ATF activity. Several other transcriptional regulation pathways, including the glucocorticoid receptor (GR), nuclear factor kappa-B cells (NF-κB), early growth response proteins 1-4 (EGR1-4) and interferon-responsive TFs, showed either no significant differences as a function of disease or treatment, or activities that were opposite to those previously hypothesized to be involved in the etiology of MDD or effective treatment. Our results suggest that CREB/ATF and NRF2 signaling may contribute to MDD by activating immune cell transcriptome dynamics that ultimately influence central nervous system (CNS) motivational and affective processes via circulating mediators.

  15. An interprofessional approach to managing children with treatment-resistant enuresis: an educational review.

    Science.gov (United States)

    Caldwell, Patrina H Y; Lim, Melissa; Nankivell, Gail

    2017-11-06

    Enuresis (intermittent urinary incontinence during sleep in a child aged ≥ 5 years) is commonly seen in paediatric practice. Despite the availability of effective interventions, treatment resistance is encountered in up to 50% of children. In this educational review we attempt to provide insight into the causes of treatment resistance, and offer practical suggestions for addressing this condition using an interprofessional approach. We explore the pathophysiology of and standard treatments for enuresis and discuss why standard treatments may fail. An interprofessional approach to treatment resistance is proposed which utilises the expertise of professionals from different disciplines to address the problems and barriers to treatment. The two interprofessional approaches include a multidisciplinary approach that involves the patient being sent to experts in different disciplines at different times to address their treatment resistance utilising the skills of the respective experts, and an interdisciplinary approach that involves a patient being managed by members of interdisciplinary team who integrate their separate discipline perspectives into a single treatment plan. Although an interdisciplinary approach is ideal, interdisciplinary teams may not be available in all circumstances. Understanding the roles of other disciplines and engaging clinicians from other disciplines when appropriate can still be helpful when treatment resistance is encountered.

  16. [Resistance to first-line drugs and major genotypic lineages of Mycobacterium tuberculosis in the 3 French Department of the Americas: Profiles, evolution, and trends (1995-2011)].

    Science.gov (United States)

    Millet, J; Berchel, M; Prudenté, F; Streit, E; Bomer, A-G; Schuster, F; Vanhomwegen, J; Paasch, D; Galbert, I; Valery, E; Aga, R; Rastogi, N

    2014-05-01

    This is the first overview on resistant and multidrug resistant isolates of Mycobacterium tuberculosis circulating in the French Department of the Americas (Guadeloupe, Martinique, and French Guiana) over 17 years (January 1995-December 2011). A total of 1,239 cases were studied: 1,199 new cases (primary and multidrug resistance of 11.8 and 1.6% respectively), and 40 persistent (defined as cases with a previous history of positive culture over 6 months interval and whose spoligotypes remain unchanged), in which significantly higher proportions of resistance to at least isoniazid (22.5%, P = 0.002), rifampicin (20.0%, P < 0.001), and multidrug resistance (17.5%, P < 0.001) were observed as compared to new cases. The 281 spoligotypes obtained showed the presence of five major lineages, T (29.9%), LAM (23.9%), Haarlem (22.1%), EAI (7.1%), and X (6.7%). Two of these lineages, X and LAM, predominate among resistant and multidrug resistant isolates respectively (X: 10.5% of resistant isolates, P = 0.04; LAM: 42.3% of multidrug resistant isolates, P = 0.02). Four of the 19 major spoligo-profiles, corresponding to SIT 20, 64, 45, and 46, were significantly associated with drug resistance. Among them, genotype SIT 20, associated with monoresistance to isoniazid and multidrug resistance, would be actively and persistently in circulation, since 1999, in French Guiana, department in which one may also observe the presence of strains of M. tuberculosis phylogeographically associated to Guiana and Suriname (SIT 131 and SIT 1340).

  17. Is disorganized schizophrenia a predictor of treatment resistance? Evidence from an observational study

    Directory of Open Access Journals (Sweden)

    Bruno Bertolucci Ortiz

    2013-12-01

    Full Text Available Objective: To investigate whether inpatients with disorganized schizophrenia are more resistant to treatment. Method: Eighty-five inpatients were assessed at admission and at discharge for schizophrenia subtype, symptom severity, and treatment resistance criteria. Results: Disorganized patients were significantly more treatment-resistant than paranoid patients (60%, p = 0.001, and presented worse scores on the Positive and Negative Syndrome Scale (PANSS, the Clinical Global Impression Scale (CGI-S, and the Global Assessment of Functioning Scale (GAF (p < 0.001. Although the difference was not significant, 80% of treatment-resistant patients with disorganized schizophrenia responded to clozapine. Conclusion: Patients with the disorganized subtype of schizophrenia should benefit from clozapine as a second-line agent.

  18. Genetic Mapping of a Major Resistance Gene to Pea Aphid (Acyrthosipon pisum in the Model Legume Medicago truncatula

    Directory of Open Access Journals (Sweden)

    Lars G. Kamphuis

    2016-07-01

    Full Text Available Resistance to the Australian pea aphid (PA; Acyrthosiphon pisum biotype in cultivar Jester of the model legume Medicago truncatula is mediated by a single dominant gene and is phloem-mediated. The genetic map position for this resistance gene, APR (Acyrthosiphon pisum resistance, is provided and shows that APR maps 39 centiMorgans (cM distal of the A. kondoi resistance (AKR locus, which mediates resistance to a closely related species of the same genus bluegreen aphid (A. kondoi. The APR region on chromosome 3 is dense in classical nucleotide binding site leucine-rich repeats (NLRs and overlaps with the region harbouring the RAP1 gene which confers resistance to a European PA biotype in the accession Jemalong A17. Further screening of a core collection of M. truncatula accessions identified seven lines with strong resistance to PA. Allelism experiments showed that the single dominant resistance to PA in M. truncatula accessions SA10481 and SA1516 are allelic to SA10733, the donor of the APR locus in cultivar Jester. While it remains unclear whether there are multiple PA resistance genes in an R-gene cluster or the resistance loci identified in the other M. truncatula accessions are allelic to APR, the introgression of APR into current M. truncatula cultivars will provide more durable resistance to PA.

  19. Treatment and Outcome of Carbapenem-Resistant Gram-Negative Bacilli Blood-Stream Infections in a Tertiary Care Hospital.

    Science.gov (United States)

    Shah, Pooja G; Shah, Sweta R

    2015-07-01

    Infections caused by carbapenem-resistant bacteria constitute a major challenge for current medical practice. To describe treatment and outcome of carbapenem-resistant Gram-negative bacilli (GNB) blood-stream infection (BSI) caused by these organisms at a tertiary care hospital in Mumbai. Carbapenem-resistant isolates from blood cultures were collected from January 2013 to April 2013. Identification and antimicrobial susceptibility testing were performed using Vitek 2 analyzer (Biomerieux Ltd.). Carbapenemase production was detected by modified Hodge's test (MHT). Patient's medical history, treatment and co-morbid conditions were noted. Outcomes of BSIs were evaluated. Forty-two isolates of carbapenem-resistant GNB isolated from BSIs were Enterobacteriaceae spp. (19), Acinetobacter baumannii (15), and Pseudomonas aeruginosa (8). Colistin had maximum in vitro activity with 97% against Enterobacteriaceae, 100% against Acinetobacter, and 100% activity against Pseudomonas aeruginosa isolates. Positivity of MHT was 92.9%. Outcome of colistin mono and combination therapy was comparable with 83% and 79%, respectively. Outcome of colistin and carbapenem combination therapy was found to be 100 percent. High incidences of bacteremia by carbapenem-resistant GNB including Enterobacteriaceae is a worrisome trend. Treatment options are compromised and only available option is colistin which has its own limitation. Colistin monotherapy may be non-inferior compared to combination therapy for treating BSIs caused by isolates with minimum inhibitory concentration (MIC) for colistin as ≤0.5 mg/l. Combined use of the colistin and carbapenem may provide good therapeutic options for BSI caused by carbapenem-resistant GNB and warrants further investigations.

  20. Repurposing ebselen for treatment of multidrug-resistant staphylococcal infections

    OpenAIRE

    Shankar Thangamani; Waleed Younis; Mohamed N. Seleem

    2015-01-01

    Novel antimicrobials and new approaches to developing them are urgently needed. Repurposing already-approved drugs with well-characterized toxicology and pharmacology is a novel way to reduce the time, cost, and risk associated with antibiotic innovation. Ebselen, an organoselenium compound, is known to be clinically safe and has a well-known pharmacology profile. It has shown potent bactericidal activity against multidrug-resistant clinical isolates of staphylococcus aureus, including methic...

  1. Antibiotic-Resistant Infections and Treatment Challenges in the Immunocompromised Host.

    Science.gov (United States)

    Dumford, Donald M; Skalweit, Marion

    2016-06-01

    This article reviews antibiotic resistance and treatment of bacterial infections in the growing number of patients who are immunocompromised: solid organ transplant recipients, the neutropenic host, and persons with human immunodeficiency virus and AIDS. Specific mechanisms of resistance in both gram-negative and gram-positive bacteria, as well as newer treatment options are addressed elsewhere, and are only briefly discussed in the context of the immunocompromised host. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Effect of Tetracycline Dose and Treatment Mode on Selection of Resistant Coliform Bacteria in Nursery Pigs.

    Science.gov (United States)

    Græsbøll, Kaare; Damborg, Peter; Mellerup, Anders; Herrero-Fresno, Ana; Larsen, Inge; Holm, Anders; Nielsen, Jens Peter; Christiansen, Lasse Engbo; Angen, Øystein; Ahmed, Shahana; Folkesson, Anders; Olsen, John Elmerdahl

    2017-06-15

    This study describes the results of a randomized clinical trial investigating the effect of oxytetracycline treatment dose and mode of administration on the selection of antibiotic-resistant coliform bacteria in fecal samples from nursery pigs. Nursery pigs (pigs of 4 to 7 weeks of age) in five pig herds were treated with oxytetracycline for Lawsonia intracellularis -induced diarrhea. Each group was randomly allocated to one of five treatment groups: oral flock treatment with a (i) high (20 mg/kg of body weight), (ii) medium (10 mg/kg), or (iii) low (5 mg/kg) dose, (iv) oral pen-wise (small-group) treatment (10 mg/kg), and (v) individual intramuscular injection treatment (10 mg/kg). All groups were treated once a day for 5 days. In all groups, treatment caused a rise in the numbers and proportions of tetracycline-resistant coliform bacteria right after treatment, followed by a significant drop by the time that the pigs left the nursery unit. The counts and proportions of tetracycline-resistant coliforms did not vary significantly between treatment groups, except immediately after treatment, when the highest treatment dose resulted in the highest number of resistant coliforms. A control group treated with tiamulin did not show significant changes in the numbers or proportions of tetracycline-resistant coliforms. Selection for tetracycline-resistant coliforms was significantly correlated to selection for ampicillin- and sulfonamide-resistant strains but not to selection for cefotaxime-resistant strains. In conclusion, the difference in the dose of oxytetracycline and the way in which the drug was applied did not cause significantly different levels of selection of tetracycline-resistant coliform bacteria under the conditions tested. IMPORTANCE Antimicrobial resistance is a global threat to human health. Treatment of livestock with antimicrobials has a direct impact on this problem, and there is a need to improve the ways that we use antimicrobials in livestock

  3. Effect of Tetracycline Dose and Treatment Mode on Selection of Resistant Coliform Bacteria in Nursery Pigs

    Science.gov (United States)

    Græsbøll, Kaare; Damborg, Peter; Mellerup, Anders; Herrero-Fresno, Ana; Larsen, Inge; Holm, Anders; Nielsen, Jens Peter; Christiansen, Lasse Engbo; Angen, Øystein; Ahmed, Shahana

    2017-01-01

    ABSTRACT This study describes the results of a randomized clinical trial investigating the effect of oxytetracycline treatment dose and mode of administration on the selection of antibiotic-resistant coliform bacteria in fecal samples from nursery pigs. Nursery pigs (pigs of 4 to 7 weeks of age) in five pig herds were treated with oxytetracycline for Lawsonia intracellularis-induced diarrhea. Each group was randomly allocated to one of five treatment groups: oral flock treatment with a (i) high (20 mg/kg of body weight), (ii) medium (10 mg/kg), or (iii) low (5 mg/kg) dose, (iv) oral pen-wise (small-group) treatment (10 mg/kg), and (v) individual intramuscular injection treatment (10 mg/kg). All groups were treated once a day for 5 days. In all groups, treatment caused a rise in the numbers and proportions of tetracycline-resistant coliform bacteria right after treatment, followed by a significant drop by the time that the pigs left the nursery unit. The counts and proportions of tetracycline-resistant coliforms did not vary significantly between treatment groups, except immediately after treatment, when the highest treatment dose resulted in the highest number of resistant coliforms. A control group treated with tiamulin did not show significant changes in the numbers or proportions of tetracycline-resistant coliforms. Selection for tetracycline-resistant coliforms was significantly correlated to selection for ampicillin- and sulfonamide-resistant strains but not to selection for cefotaxime-resistant strains. In conclusion, the difference in the dose of oxytetracycline and the way in which the drug was applied did not cause significantly different levels of selection of tetracycline-resistant coliform bacteria under the conditions tested. IMPORTANCE Antimicrobial resistance is a global threat to human health. Treatment of livestock with antimicrobials has a direct impact on this problem, and there is a need to improve the ways that we use antimicrobials in

  4. Effect of tetracycline dose and treatment mode on selection of resistant coliform bacteria in nursery pigs

    DEFF Research Database (Denmark)

    Græsbøll, Kaare; Damborg, Peter; Mellerup, Anders

    2017-01-01

    This study describes the results of a randomized clinical trial investigating the effect of oxytetracycline treatment dose and mode of administration on the selection of antibiotic-resistant coliform bacteria in fecal samples from nursery pigs. Nursery pigs (pigs of 4 to 7 weeks of age) in five pig...... by the time that the pigs left the nursery unit. The counts and proportions of tetracyclineresistant coliforms did not vary significantly between treatment groups, except immediately after treatment, when the highest treatment dose resulted in the highest number of resistant coliforms. A control group treated...

  5. Clustering of antibiotic resistance of E. coli in couples: suggestion for a major role of conjugal transmission

    Directory of Open Access Journals (Sweden)

    von Baum Heike

    2006-07-01

    Full Text Available Abstract Background Spread of antibiotic resistance in hospitals is a well-known problem, but studies investigating the importance of factors potentially related to the spread of resistant bacteria in outpatients are sparse. Methods Stool samples were obtained from 206 healthy couples in a community setting in Southern Germany in 2002–2003. E. coli was cultured and minimal inhibition concentrations were tested. Prevalences of E. coli resistance to commonly prescribed antibiotics according to potential risk factors were ascertained. Results Prevalences of ampicillin resistance were 15.7% and 19.4% for women and men, respectively. About ten percent and 15% of all isolates were resistant to cotrimoxazole and doxycycline, respectively. A partner carrying resistance was the main risk factor for being colonized with resistant E. coli. Odds ratios (95% CI for ampicillin and cotrimoxazole resistance given carriage of resistant isolates by the partner were 6.9 (3.1–15.5 and 3.3 (1.5–18.0, respectively. Conclusion Our data suggest that conjugal transmission may be more important for the spread of antibiotic resistance in the community setting than commonly suspected risk factors such as previous antibiotic intake or hospital contacts.

  6. A major QTL corresponding to the Rk locus for resistance to root-knot nematodes in cowpea (Vigna unguiculata L. Walp.).

    Science.gov (United States)

    Huynh, Bao-Lam; Matthews, William C; Ehlers, Jeffrey D; Lucas, Mitchell R; Santos, Jansen R P; Ndeve, Arsenio; Close, Timothy J; Roberts, Philip A

    2016-01-01

    Genome resolution of a major QTL associated with the Rk locus in cowpea for resistance to root-knot nematodes has significance for plant breeding programs and R gene characterization. Cowpea (Vigna unguiculata L. Walp.) is a susceptible host of root-knot nematodes (Meloidogyne spp.) (RKN), major plant-parasitic pests in global agriculture. To date, breeding for host resistance in cowpea has relied on phenotypic selection which requires time-consuming and expensive controlled infection assays. To facilitate marker-based selection, we aimed to identify and map quantitative trait loci (QTL) conferring the resistance trait. One recombinant inbred line (RIL) and two F2:3 populations, each derived from a cross between a susceptible and a resistant parent, were genotyped with genome-wide single nucleotide polymorphism (SNP) markers. The populations were screened in the field for root-galling symptoms and/or under growth-chamber conditions for nematode reproduction levels using M. incognita and M. javanica biotypes. One major QTL was mapped consistently on linkage group VuLG11 of each population. By genotyping additional cowpea lines and near-isogenic lines derived from conventional backcrossing, we confirmed that the detected QTL co-localized with the genome region associated with the Rk locus for RKN resistance that has been used in conventional breeding for many decades. This chromosomal location defined with flanking markers will be a valuable target in marker-assisted breeding and for positional cloning of genes controlling RKN resistance.

  7. Current treatment options for vulvovaginal candidiasis caused by azole-resistant Candida species.

    Science.gov (United States)

    Sobel, J D; Sobel, R

    2018-06-22

    Clinicians are increasingly challenged by patients with refractory vulvovaginal candidiasis (VVC) caused by azole-resistant Candida species. Fluconazole resistant C.albicans is a growing and perplexing problem following years of indiscriminate drug prescription and unnecessary drug exposure and for which there are few therapeutic alternatives. Regrettably, although the azole class of drugs has expanded, new classes of antifungal drugs have not been forthcoming, limiting effective treatment options in patients with azole resistant Candida vaginitis. Areas covered: This review covers published data on epidemiology, pathophysiology and treatment options for women with azole-resistant refractory VVC. Expert opinion: Fluconazole resistant C.albicans adds to the challenge of azole resistant non-albicans Candida spp. Both issues follow years of indiscriminate drug prescription and unnecessary fluconazole exposure. Although an understanding of azole resistance in yeast has been established, this knowledge has not translated into useful therapeutic advantage. Treatment options for such women with refractory symptoms are extremely limited. New therapeutic options and strategies are urgently needed to meet this challenge of azole drug resistance.

  8. Diversity and antibiotic resistance of Aeromonas spp. in drinking and waste water treatment plants.

    Science.gov (United States)

    Figueira, Vânia; Vaz-Moreira, Ivone; Silva, Márcia; Manaia, Célia M

    2011-11-01

    The taxonomic diversity and antibiotic resistance phenotypes of aeromonads were examined in samples from drinking and waste water treatment plants (surface, ground and disinfected water in a drinking water treatment plant, and raw and treated waste water) and tap water. Bacteria identification and intra-species variation were determined based on the analysis of the 16S rRNA, gyrB and cpn60 gene sequences. Resistance phenotypes were determined using the disc diffusion method. Aeromonas veronii prevailed in raw surface water, Aeromonas hydrophyla in ozonated water, and Aeromonas media and Aeromonas puntacta in waste water. No aeromonads were detected in ground water, after the chlorination tank or in tap water. Resistance to ceftazidime or meropenem was detected in isolates from the drinking water treatment plant and waste water isolates were intrinsically resistant to nalidixic acid. Most of the times, quinolone resistance was associated with the gyrA mutation in serine 83. The gene qnrS, but not the genes qnrA, B, C, D or qepA, was detected in both surface and waste water isolates. The gene aac(6')-ib-cr was detected in different waste water strains isolated in the presence of ciprofloxacin. Both quinolone resistance genes were detected only in the species A. media. This is the first study tracking antimicrobial resistance in aeromonads in drinking, tap and waste water and the importance of these bacteria as vectors of resistance in aquatic environments is discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Mapping and pyramiding of two major genes for resistance to the brown planthopper (Nilaparvata lugens [St?l]) in the rice cultivar ADR52

    OpenAIRE

    Myint, Khin Khin Marlar; Fujita, Daisuke; Matsumura, Masaya; Sonoda, Tomohiro; Yoshimura, Atsushi; Yasui, Hideshi

    2011-01-01

    The brown planthopper (BPH), Nilaparvata lugens (St?l), is one of the most serious and destructive pests of rice, and can be found throughout the rice-growing areas of Asia. To date, more than 24 major BPH-resistance genes have been reported in several Oryza sativa ssp. indica cultivars and wild relatives. Here, we report the genetic basis of the high level of BPH resistance derived from an Indian rice cultivar, ADR52, which was previously identified as resistant to the whitebacked planthoppe...

  10. Antibiotic resistance reservoirs

    NARCIS (Netherlands)

    Versluis, Dennis

    2016-01-01

    One of the major threats to human health in the 21st century is the emergence of pathogenic bacteria that are resistant to multiple antibiotics, thereby limiting treatment options. An important route through which pathogens become resistant is via acquisition of resistance genes from

  11. Levomilnacipran Extended-Release Treatment in Patients With Major Depressive Disorder: Improvements in Functional Impairment Categories

    Science.gov (United States)

    Gommoll, Carl P.; Chen, Changzheng; Greenberg, William M.; Ruth, Adam

    2015-01-01

    Objective: In this post hoc analysis, improvement in functional impairment in patients with major depressive disorder (MDD) treated with levomilnacipran extended release (ER) was evaluated by assessing shifts from more severe to less severe functional impairment categories on individual Sheehan Disability Scale (SDS) subscales. Method: SDS data were pooled from 5 phase II/III studies conducted between December 2006 and March 2012 of levomilnacipran ER versus placebo in adult patients with MDD (DSM-IV-TR criteria). Proportions of patients shifting from moderate-extreme baseline impairment (score ≥ 4) to mild-no impairment (score ≤ 3) at end of treatment were assessed for each SDS subscale. Proportions of patients shifting from marked-extreme (score ≥ 7) baseline impairment to moderate-no (score ≤ 6) or mild-no impairment (score ≤ 3) at end of treatment, and shifts in which patients worsened from moderate-no to marked-extreme impairment, were also evaluated. Results: A significantly higher proportion of patients treated with levomilnacipran ER than placebo-treated patients improved from more severe categories of functional impairment at baseline to less severe impairment categories across all SDS subscales: work/school, social life, and family life/home responsibilities (P impairment at baseline improved to mild or no impairment, compared with no more than 40% of placebo patients on any subscale. Almost half (42%–47%) of levomilnacipran ER–treated patients versus only about one-third (29%–34%) of placebo patients improved from marked-extreme to mild or no impairment across functional domains. Conclusions: These results suggest that functional improvement was observed across the SDS functional domains. To our knowledge, this is the first such categorical analysis of functional improvement, as measured by the SDS, for an antidepressant. Trial Registration: ClinicalTrials.gov identifiers: NCT00969709, NCT01377194, NCT00969150, and NCT01034462 and Eudra

  12. Resistance to treatment and change in anorexia nervosa [corrected]: a clinical overview.

    Science.gov (United States)

    Abbate-Daga, Giovanni; Amianto, Federico; Delsedime, Nadia; De-Bacco, Carlotta; Fassino, Secondo

    2013-11-07

    Current literature on Eating Disorders (EDs) is devoid of evidence-based findings providing support to effective treatments, mostly for anorexia nervosa (AN). This lack of successful guidelines may play a role in making these disorders even more resistant. In fact, many individuals do not respond to the available treatments and develop an enduring and disabling illness. With this overview we aimed to highlight and discuss treatment resistance in AN--with an in-depth investigation of resistance-related psychological factors.A literature search was conducted on PubMed and PsychINFO; English-language articles published between 1990 and 2013 investigating the phenomenon of resistance to treatment in AN have been considered. The selected papers have been then grouped into four main thematic areas: denial of illness; motivation to change; maintaining factors and treatment outcome; and therapeutic relationship. Eating symptomatology was found to only partially explain resistance to treatment. The role of duration of illness has been questioned whilst some maintaining factors seemed promising in providing a useful framework for this phenomenon. Emotive and relational aspects have been investigated on their role in resistance as well as therapists' countertransference. Remarkably there has been little research done on resistance to treatment in the ED field, in spite of its clinical relevance. Motivation, insight and subjective meaning of the illness can be useful tools to manage the resistance phenomenon when coupled with a wider approach. The latter enables the therapists to be aware of their role in the therapeutic alliance through countertransference aspects and to consider the EDs as disorders of the development of both personality and self, entailing severe impairments as regards identity and relationships.

  13. Economic outcomes of eszopiclone treatment in insomnia and comorbid major depressive disorder.

    Science.gov (United States)

    Snedecor, Sonya J; Botteman, Marc F; Schaefer, Kendyl; Sarocco, Phillip; Barry, Nadine; Pickard, A Simon

    2010-03-01

    Eszopiclone is effective for the treatment of insomnia in patients with insomnia and comorbid major depressive disorder (MDD). Both conditions impose significant economic burden, with the US societal cost of depression estimated at USD 50 billion annually. The purpose of this analysis was to examine the costs and benefits of eszopiclone co-administered with fluoxetine (ESZ+FLX) compared to placebo co-administered with fluoxetine (PBO+FLX) in adults meeting the DSM-IV criteria for insomnia and MDD. Data from 434 patients enrolled in an 8-week clinical trial who met the economic-subanalysis criteria were examined. The costs of medical care (in 2007 USUSD ) and lost work time were estimated from the Hamilton Depression Scale (HAM-D17) scores using published algorithms. Cost of lost productivity while at work was based on responses to the Work Limitations Questionnaire. The impact of therapy on quality-adjusted life years (QALYs) was estimated by transforming HAM-D17 (base case analysis) or Short Form Health Survey (SF-12) (scenario analyses) responses into health utility scores using published algorithms. Drug costs were estimated based on average wholesale price. The mean 8-week increases in QALYs from baseline were 0.0392 and 0.0334 for the ESZ+FLX and PBO+FLX groups, respectively. Mean per-patient costs were USD 1,279 and USD 1,198 for the respective groups. Thus, co-treatment resulted in net increases of 0.0058 QALYs and USD 81, leading to an incremental cost per QALY gained of approximately USD 14,000. Co-administration of eszopiclone and fluoxetine improved patients' insomnia symptoms and appeared to be a cost-effective treatment strategy for patients with insomnia and comorbid MDD. One limitation of this study is that optimal utility estimation techniques were not available. Utilities were instead derived indirectly using the HAM-D17 (disease-specific, not generic) or SF-12 (generic, but potentially insensitive to important changes in some conditions

  14. An Integrative Approach to Treatment-Resistant Obsessive-Compulsive Disorder.

    Science.gov (United States)

    Woon, Luke Sy-Cherng; Kanapathy, Anita; Zakaria, Hazli; Alfonso, César A

    2017-01-01

    Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder that often runs a chronic unremitting course. Treatment outcomes can be unsatisfactory despite the availability of various somatic and psychological therapies. Psychodynamic psychotherapy in combination with cognitive behavioral therapy (CBT) with exposure and response prevention (ERP) could help patients with treatment-resistant OCD achieve better outcomes. An integrative approach can help patients gain insight, strengthen the therapeutic alliance, improve treatment adherence, and provide symptomatic relief when other treatments seem insufficient or have failed. We describe the treatment process of a person with treatment-resistant OCD who received pharmacotherapy, concurrent CBT/ERP, and a brief course of psychodynamic psychotherapy. Case formulations from cognitive behavioral and psychodynamic perspectives are presented. The authors discuss the advantages of doing a psychodynamic assessment and formulation in treatment refractory cases and the wisdom of integrating psychotherapy interventions for OCD, as well as the unique clinical features of cases that warrant a multimodal treatment approach.

  15. HIV-1 resistance testing influences treatment decision-making

    Directory of Open Access Journals (Sweden)

    Ricardo Sobhie Diaz

    Full Text Available OBJECTIVE: To investigates how the use of HIV-1 resistance tests influences physician decision-making. METHODS: Ten experienced reference physicians from the Brazilian Network for Drug Resistance each received ten patients' case histories. The selected patients had experienced at least two virological failures. First, reference physicians were asked to empirically select a new regimen for each patient. Second, after genotype report (ViroSeq 2.6 was provided, and physicians were again asked to select a new regimen considering this additional information. Finally, they were asked to select a regimen after receiving a virtual phenotype result (vircoTYPE 3.9.00. RESULTS: In 79% of the cases, physicians changed their empirical choice of regimen after receiving the genotype report, resulting in an increase in the mean number of active drugs from 1.8 to 2.2 (p = 0.0003, while the average number of drugs/regimen remained at 4.0. After receipt of the virtual phenotype report, additional changes were made in 75% of the patient cases, resulting in an increase in the number of active drugs to 2.8 (p < 0.0001, while the average number of drugs/regimen remained at 4.0. After receipt of the genotype report, 48% of the changes were in NRTIs, 29% were in NNRTIs and 60% were in PIs; after consideration of the virtual phenotype, 61%, 10% and 49% of the changes, respectively, were in these categories of drugs. Fourteen percent of the physicians rated the genotype report as "extremely useful", whereas 34% rated the subsequent virtual phenotype report as "extremely useful" (p = 0.0003. CONCLUSIONS: Resistance testing has a significant impact on physicians' choices of antiretroviral salvage therapies, and it promotes the selection of more active drugs

  16. The genetics of resistance to powdery mildew in cultivated oats (Avena sativa L.): current status of major genes.

    Science.gov (United States)

    Hsam, Sai L K; Mohler, Volker; Zeller, Friedrich J

    2014-05-01

    The genetics of resistance to powdery mildew caused by Blumeria graminis f. sp. avenae of four cultivated oats was studied using monosomic analysis. Cultivar 'Bruno' carries a gene (Pm6) that shows a recessive mode of inheritance and is located on chromosome 10D. Cultivar 'Jumbo' possesses a dominant resistance gene (Pm1) on chromosome 1C. In cultivar 'Rollo', in addition to the gene Pm3 on chromosome 17A, a second dominant resistance gene (Pm8) was identified and assigned to chromosome 4C. In breeding line APR 122, resistance was conditioned by a dominant resistance gene (Pm7) that was allocated to chromosome 13A. Genetic maps established for resistance genes Pm1, Pm6 and Pm7 employing amplified fragment length polymorphism (AFLP) markers indicated that these genes are independent of each other, supporting the results from monosomic analysis.

  17. Treatment of acute otitis media - challenges in the era of antibiotic resistance.

    Science.gov (United States)

    Dagan, R

    2000-12-08

    The last decade is characterized by the increase in antibiotic resistance among respiratory bacterial pathogens in the presence of only modest progress in the development of new antibacterial agents to overcome this resistance. A series of recent studies show clearly that the increased resistance among the main AOM pathogens (namely Streptococcus pneumoniae and Haemophilus influenzae) is associated with a dramatic decrease in bacteriologic response to antibiotic treatment, which in turn has an impact on clinical response. Thus, the individual patient is affected by the increasing antibiotic resistance. Moreover, the society as a whole is now also affected because the carriage and spread of antibiotic resistant AOM pathogens is remarkably impacted by antibiotic treatment. New studies show the remarkable ability of antibiotics to rapidly promote nasopharyngeal carriage and spread of antibiotic-resistant AOM pathogens. In these studies, the increase in carriage of antibiotic resistant S. pneumoniae is shown already after 3-4 days from initiation of antibiotic treatment and may last for weeks to months after treatment. Children carrying antibiotic-resistant organisms transmit those organisms to their family and to their day care centers and thus a vicious cycle is created in which increased antibiotic resistance with decreased response leads to increased antibiotic use, which in turn leads to further increase in resistance. New antibiotics are not likely to improve this situation. It is clear that the challenge in the next decade is to prevent AOM rather than to treat it. Efforts to prevent AOM include improved environmental factors, immunization with bacterial and viral vaccines and some creative measures such as prevention of colonization and attachment to epithelium of AOM pathogens. Whether these efforts will prove successful or, even if successful, will only modify the clinical and bacteriologic picture presenting new challenges, only time will tell.

  18. Strengthening of oxidation resistant materials for gas turbine applications. [treatment of silicon ceramics for increased flexural strength and impact resistance

    Science.gov (United States)

    Kirchner, H. P.

    1974-01-01

    Silicon nitride and silicon carbide ceramics were treated to form compressive surface layers. On the silicon carbide, quenching and thermal exposure treatments were used, and on the silicon nitride, quenching, carburizing, and a combination of quenching and carburizing were used. In some cases substantial improvements in impact resistance and/or flexural strength were observed. The presence of compressive surface stresses was demonstrated by slotted rod tests.

  19. An Open Trial of a New Acceptance-Based Behavioral Treatment for Major Depression with Psychotic Features

    Science.gov (United States)

    Gaudiano, Brandon A.; Nowlan, Kathryn; Brown, Lily A.; Epstein-Lubow, Gary; Miller, Ivan W.

    2013-01-01

    Research suggests that cognitive and behavioral therapies produce significant benefits over medications alone in the treatment of severe, nonpsychotic major depression or primary psychotic disorders such as schizophrenia. However, previous research has not demonstrated the efficacy of psychotherapy for major depression with psychotic features. In…

  20. Linezolid in the treatment of drug-resistant tuberculosis: the challenge of its narrow therapeutic index.

    Science.gov (United States)

    Wasserman, Sean; Meintjes, Graeme; Maartens, Gary

    2016-10-01

    Linezolid is an oxazolidinone with potent activity against M tuberculosis, and improves culture conversion and cure rates when added to treatment regimens for drug resistant tuberculosis. However, linezolid has a narrow therapeutic window, and the optimal dosing strategy that minimizes the substantial toxicity associated with linezolid's prolonged use in tuberculosis treatment has not been determined, limiting the potential impact of this anti-mycobacterial agent. This paper aims to review and summarize the current knowledge on linezolid for the treatment of drug-resistant tuberculosis. The focus is on the pharmacokinetic-pharmacodynamic determinants of linezolid's efficacy and toxicity in tuberculosis, and how this relates to defining an optimal dose. Mechanisms of linezolid toxicity and resistance, and the potential role of therapeutic drug monitoring are also covered. Expert commentary: Prospective pharmacokinetic-pharmacodynamic studies are required to define optimal therapeutic targets and to inform improved linezolid dosing strategies for drug-resistant tuberculosis.

  1. Treatment of Resistant Idiopathic Hiccups with Pulse Radio ...

    African Journals Online (AJOL)

    2016-10-20

    Oct 20, 2016 ... relief from symptoms, the patient accepted oral therapy this time. Gabapentin 300 .... A venous catheter was ... recommended in single or combined treatment of chronic ... Gastric distension, peptic ulcer disease, gastric cancer, ...

  2. Role of Old Antibiotics in the Era of Antibiotic Resistance. Highlighted Nitrofurantoin for the Treatment of Lower Urinary Tract Infections

    Directory of Open Access Journals (Sweden)

    Maria Jose Munoz-Davila

    2014-02-01

    Full Text Available Bacterial infections caused by antibiotic-resistant isolates have become a major health problem in recent years, since they are very difficult to treat, leading to an increase in morbidity and mortality. Nitrofurantoin is a broad-spectrum bactericidal antibiotic that, through a complex mode of action which is not completely understood, affects both Gram-negative and Gram-positive bacteria. Nitrofurantoin has been used successfully for a long time for the prophylaxis and treatment of acute lower urinary tract infections in adults, children and pregnant women, but the increased emergence of antibiotic resistance has made nitrofurantoin a suitable candidate for the treatment of infections caused by multidrug-resistant pathogens. Here, we review the mechanism of action, antimicrobial spectrum, pharmacology and safety profile of nitrofurantoin. We also investigate the therapeutic use of nitrofurantoin, including recent data which highlight its role in the management of community urinary tract infection, especially in cases of multidrug-resistant isolates, in which oral active antimicrobials are limited resources nowadays.

  3. Beyond conventional antibiotics for the future treatment of methicillin-resistant Staphylococcus aureus infections: two novel alternatives.

    LENUS (Irish Health Repository)

    Fitzgerald-Hughes, Deirdre

    2012-08-01

    The majority of antibiotics currently used to treat methicillin-resistant Staphylococus aureus (MRSA) infections target bacterial cell wall synthesis or protein synthesis. Only daptomycin has a novel mode of action. Reliance on limited targets for MRSA chemotherapy, has contributed to antimicrobial resistance. Two alternative approaches to the treatment of S. aureus infection, particularly those caused by MRSA, that have alternative mechanisms of action and that address the challenge of antimicrobial resistance are cationic host defence peptides and agents that target S. aureus virulence. Cationic host defence peptides have multiple mechanisms of action and are less likely than conventional agents to select resistant mutants. They are amenable to modifications that improve their stability, effectiveness and selectivity. Some cationic defence peptides such as bactenecin, mucroporin and imcroporin have potent in vitro bactericidal activity against MRSA. Antipathogenic agents also have potential to limit the pathogenesis of S aureus. These are generally small molecules that inhibit virulence targets in S. aureus without killing the bacterium and therefore have limited capacity to promote resistance development. Potential antipathogenic targets include the sortase enzyme system, the accessory gene regulator (agr) and the carotenoid biosynthetic pathway. Inhibitors of these targets have been identified and these may have potential for further development.

  4. Dietary supplementation with Cynodon dactylon (L.) enhances innate immunity and disease resistance of Indian major carp, Catla catla (Ham.).

    Science.gov (United States)

    Kaleeswaran, B; Ilavenil, S; Ravikumar, S

    2011-12-01

    Indian major carp (Catla catla) was subjected to study the immunostimulatory effects when the grass Cynodon dactylon(L) ethanolic extract administrated as feed supplement. C. catla was fed with 0% (Control), 0.05% (group I), 0.5% (group II) and 5% (group III) extract provided for 60 days. Blood samples were collected at every 10 days of interval up to 60 days for analyzing the non-specific humoral (lysozyme activity, antiprotease activity and haemolytic complement) and cellular (production of reactive oxygen and nitrogen species, myeloperoxidase activity) immune response study. The results indicate that C. dactylon ethanolic extract administered as feed supplement significantly (P < 0.05) enhanced most of the non-specific immune parameters tested. Among the experimental diet groups, significantly increased response of non-specific immunity was seen in group III (5%). Disease resistant analysis against Aeromonas hydrophila was performed in control group and plant extract treated fish for 7, 14, 21 and 28 days. Relative percent survival rate (RPS) was observed in treated samples, which is directly proportional to concentration of the extract. Additionally, electron microscopic studies and gelatin zymography for Matrix Metalo Proteinase (MMPs) were examined in spleen at 7th and 28th days of feeding. Administration of C. dactylon mixed diet delayed the lymphocyte destruction with positive ultrastructural changes. An induced stress (A. hydrophila infection) was observed by using MMPs expression, which was reduced in the experimental diet groups than the control. All these experimental results prove that C. dactylon ethanolic extract enhances the immunity of Catla fish. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Deep brain stimulation and treatment-resistant obsessive-compulsive disorder: A systematic review.

    Science.gov (United States)

    Vázquez-Bourgon, Javier; Martino, Juan; Sierra Peña, María; Infante Ceberio, Jon; Martínez Martínez, M Ángeles; Ocón, Roberto; Menchón, José Manuel; Crespo Facorro, Benedicto; Vázquez-Barquero, Alfonso

    2017-07-01

    At least 10% of patients with Obsessive-compulsive Disorder (OCD) are refractory to psychopharmacological treatment. The emergence of new technologies for the modulation of altered neuronal activity in Neurosurgery, deep brain stimulation (DBS), has enabled its use in severe and refractory OCD cases. The objective of this article is to review the current scientific evidence on the effectiveness and applicability of this technique to refractory OCD. We systematically reviewed the literature to identify the main characteristics of deep brain stimulation, its use and applicability as treatment for obsessive-compulsive disorder. Therefore, we reviewed PubMed/Medline, Embase and PsycINFO databases, combining the key-words 'Deep brain stimulation', 'DBS' and 'Obsessive-compulsive disorder' 'OCS'. The articles were selected by two of the authors independently, based on the abstracts, and if they described any of the main characteristics of the therapy referring to OCD: applicability; mechanism of action; brain therapeutic targets; efficacy; side-effects; co-therapies. All the information was subsequently extracted and analysed. The critical analysis of the evidence shows that the use of DBS in treatment-resistant OCD is providing satisfactory results regarding efficacy, with assumable side-effects. However, there is insufficient evidence to support the use of any single brain target over another. Patient selection has to be done following analyses of risks/benefits, being advisable to individualize the decision of continuing with concomitant psychopharmacological and psychological treatments. The use of DBS is still considered to be in the field of research, although it is increasingly used in refractory-OCD, producing in the majority of studies significant improvements in symptomatology, and in functionality and quality of life. It is essential to implement random and controlled studies regarding its long-term efficacy, cost-risk analyses and cost/benefit. Copyright

  6. A longitudinal population-based study exploring treatment utilization and suicidal ideation and behavior in major depressive disorder.

    Science.gov (United States)

    Chartrand, Hayley; Robinson, Jennifer; Bolton, James M

    2012-12-10

    This study aimed to longitudinally examine the relationship between treatment utilization and suicidal behavior among people with major depressive disorder in a nationally representative sample. Data came from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) (Wave 1: N=43,093; Wave 2: N=34,653). Suicidal and non-suicidal individuals at Wave 1 were compared based on subsequent treatment utilization. Suicidal behavior at Wave 2 was compared between people with major depressive disorder who had sought treatment at Wave 1 versus those that had not. Individuals with past year major depressive disorder at Wave 1 who attempted suicide were more likely to be hospitalized at follow up compared to non-suicidal people with major depressive disorder [adjusted odds ratio (AOR)=4.46; 95% confidence interval [95% CI]: 2.54-7.85]; however, they were not more likely to seek other forms of treatment. Among those with past year major depressive disorder who sought treatment at baseline, visiting an emergency room (AOR=3.08; 95% CI: 1.61-5.89) and being hospitalized (AOR=2.41; 95% CI: 1.13-5.14), was associated with an increased likelihood of attempting suicide within 3 years even after adjusting for mental disorder comorbidity, depression severity, and previous suicidal behavior. Unable to draw conclusions about completed suicide or adequacy of treatment. Suicidal behavior does not lead individuals with major depressive disorder to seek treatment with professionals or use antidepressant medications; instead, they are more likely to use emergency services. These findings suggest that treatment efforts for people with major depressive disorder who are suicidal need improvement. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Effect of alternating voltage treatment on corrosion resistance of AZ91D magnesium alloy

    Energy Technology Data Exchange (ETDEWEB)

    Liu, X. [Corrosion and Protection Laboratory, Key Laboratory of Superlight Materials and Surface Technology (Harbin Engineering University), Ministry of Education, Harbin (China); Zhang, T.; Shao, Y.; Meng, G.; Wang, F. [Corrosion and Protection Laboratory, Key Laboratory of Superlight Materials and Surface Technology (Harbin Engineering University), Ministry of Education, Harbin (China); State Key Laboratory for Corrosion and Protection, Institute of Metal Research, Chinese Academy of Sciences, Shenyang (China)

    2012-06-15

    AZ91D magnesium alloy was treated by the alternating voltage (AV) treatment technique. The optimal AV-treatment parameters of the alloy were determined by orthogonal experiments. Polarization curve, electrochemical impedance spectroscopy (EIS), and scanning electrochemical microscopy (SECM) were used to understand the effect of AV-treatment on the corrosion resistance of the alloy. AFM, contact angle, and XPS were employed to investigate further the influence of AV-treatment on the properties of the surface film formed on the alloy after AV-treatment. The results showed that a uniform and stable film was formed and the corrosion resistance of AZ91D magnesium alloy was significantly improved after AV-treatment. This was caused by the noticeable change of the chemical structure and semi-conducting properties of the surface film after AV-treatment. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  8. Using SNP markers to dissect linkage disequilibrium at a major quantitative trait locus for resistance to the potato cyst nematode Globodera pallida on potato chromosome V.

    Science.gov (United States)

    Achenbach, Ute; Paulo, Joao; Ilarionova, Evgenyia; Lübeck, Jens; Strahwald, Josef; Tacke, Eckhard; Hofferbert, Hans-Reinhard; Gebhardt, Christiane

    2009-02-01

    The damage caused by the parasitic root cyst nematode Globodera pallida is a major yield-limiting factor in potato cultivation . Breeding for resistance is facilitated by the PCR-based marker 'HC', which is diagnostic for an allele conferring high resistance against G. pallida pathotype Pa2/3 that has been introgressed from the wild potato species Solanum vernei into the Solanum tuberosum tetraploid breeding pool. The major quantitative trait locus (QTL) controlling this nematode resistance maps on potato chromosome V in a hot spot for resistance to various pathogens including nematodes and the oomycete Phytophthora infestans. An unstructured sample of 79 tetraploid, highly heterozygous varieties and breeding clones was selected based on presence (41 genotypes) or absence (38 genotypes) of the HC marker. Testing the clones for resistance to G. pallida confirmed the diagnostic power of the HC marker. The 79 individuals were genotyped for 100 single nucleotide polymorphisms (SNPs) at 10 loci distributed over 38 cM on chromosome V. Forty-five SNPs at six loci spanning 2 cM in the interval between markers GP21-GP179 were associated with resistance to G. pallida. Based on linkage disequilibrium (LD) between SNP markers, six LD groups comprising between 2 and 18 SNPs were identified. The LD groups indicated the existence of multiple alleles at a single resistance locus or at several, physically linked resistance loci. LD group C comprising 18 SNPs corresponded to the 'HC' marker. LD group E included 16 SNPs and showed an association peak, which positioned one nematode resistance locus physically close to the R1 gene family.

  9. Attachment as Moderator of Treatment Outcome in Major Depression: A Randomized Control Trial of Interpersonal Psychotherapy versus Cognitive Behavior Therapy

    Science.gov (United States)

    McBride, Carolina; Atkinson, Leslie; Quilty, Lena C.; Bagby, R. Michael

    2006-01-01

    Anxiety and avoidance dimensions of adult attachment insecurity were tested as moderators of treatment outcome for interpersonal psychotherapy (IPT) and cognitive-behavioral therapy (CBT). Fifty-six participants with major depression were randomly assigned to these treatment conditions. Beck Depression Inventory-II, Six-Item Hamilton Rating Scale…

  10. Mycoplasma genitalium infection: current treatment options, therapeutic failure, and resistance-associated mutations

    Directory of Open Access Journals (Sweden)

    Couldwell DL

    2015-05-01

    Full Text Available Deborah L Couldwell,1,2 David A Lewis1,21Western Sydney Sexual Health Centre, Parramatta, 2Centre for Infectious Diseases and Microbiology and Marie Bashir Institute for Infectious Diseases and Biosecurity, Westmead Clinical School, University of Sydney, Sydney, NSW, Australia Abstract: Mycoplasma genitalium is an important cause of non-gonococcal urethritis, cervicitis, and related upper genital tract infections. The efficacy of doxycycline, used extensively to treat non-gonococcal urethritis in the past, is relatively poor for M. genitalium infection; azithromycin has been the preferred treatment for several years. Research on the efficacy of azithromycin has primarily focused on the 1 g single-dose regimen, but some studies have also evaluated higher doses and longer courses, particularly the extended 1.5 g regimen. This extended regimen is thought to be more efficacious than the 1 g single-dose regimen, although the regimens have not been directly compared in clinical trials. Azithromycin treatment failure was first reported in Australia and has subsequently been documented in several continents. Recent reports indicate an upward trend in the prevalence of macrolide-resistant M. genitalium infections (transmitted resistance, and cases of induced resistance following azithromycin therapy have also been documented. Emergence of antimicrobial-resistant M. genitalium, driven by suboptimal macrolide dosage, now threatens the continued provision of effective and convenient treatments. Advances in techniques to detect resistance mutations in DNA extracts have facilitated correlation of clinical outcomes with genotypic resistance. A strong and consistent association exists between presence of 23S rRNA gene mutations and azithromycin treatment failure. Fluoroquinolones such as moxifloxacin, gatifloxacin, and sitafloxacin remain highly active against most macrolide-resistant M. genitalium. However, the first clinical cases of moxifloxacin treatment

  11. Treatment outcomes for isoniazid-resistant tuberculosis under program conditions in British Columbia, Canada.

    Science.gov (United States)

    Romanowski, Kamila; Chiang, Leslie Y; Roth, David Z; Krajden, Mel; Tang, Patrick; Cook, Victoria J; Johnston, James C

    2017-09-04

    Every year, over 1 million people develop isoniazid (INH) resistant tuberculosis (TB). Yet, the optimal treatment regimen remains unclear. Given increasing prevalence, the clinical efficacy of regimens used by physicians is of interest. This study aims to examine treatment outcomes of INH resistant TB patients, treated under programmatic conditions in British Columbia, Canada. Medical charts were retrospectively reviewed for cases of culture-confirmed INH mono-resistant TB reported to the BC Centre for Disease Control (BCCDC) from 2002 to 2014. Treatment regimens, patient and strain characteristics, and clinical outcomes were analysed. One hundred sixty five cases of INH mono-resistant TB were included in analysis and over 30 different treatment regimens were prescribed. Median treatment duration was 10.5 months (IQR 9-12 months) and treatment was extended beyond 12 months for 26 patients (15.8%). Fifty six patients (22.6%) experienced an adverse event that resulted in a drug regimen modification. Overall, 140 patients (84.8%) had a successful treatment outcome while 12 (7.2%) had an unsuccessful treatment outcome of failure (n = 2; 1.2%), relapse (n = 4; 2.4%) or all cause mortality (n = 6; 3.6%). Our treatment outcomes, while consistent with findings reported from other studies in high resource settings, raise concerns about current recommendations for INH resistant TB treatment. Only a small proportion of patients completed the recommended treatment regimens. High quality studies to confirm the effectiveness of standardized regimens are urgently needed, with special consideration given to trials utilizing fluoroquinolones.

  12. Influence of Heat Treatment on Abrasive Wear Resistance of Silumin Matrix Composite Castings

    Directory of Open Access Journals (Sweden)

    Gawdzińska K.

    2016-03-01

    Full Text Available The authors attempted at examining the effect of heat treatment on abrasive wear resistance of metal composite castings. Metal matrix composites were made by infiltrating preforms created from unordered short fibers (graphite or silumin with liquid aluminium alloy AlSi12(b. Thus prepared composites were subject to solution heat treatment at a temperature of 520°C for four hours, then aging at a temperature of 220°C for four hours. Abrasion resistance of the material was tested before and after thermal treatment.

  13. The Three Major Spanish Clones of Penicillin-Resistant Streptococcus pneumoniae Are the Most Common Clones Recovered in Recent Cases of Meningitis in Spain

    Science.gov (United States)

    Enright, Mark C.; Fenoll, Asunción; Griffiths, David; Spratt, Brian G.

    1999-01-01

    One hundred six isolates of Streptococcus pneumoniae recovered in Spain from patients with meningitis in 1997 and 1998 were characterized by multilocus sequence typing. A heterogeneous collection of genotypes was associated with meningitis in Spain: 65 different sequence types were resolved and, even at a genetic distance of 0.43, there were 37 distinct lineages. Thirty-eight percent of the isolates, including all isolates of serotypes 6B, 9V, 14, and 23F, were resistant to penicillin, and 24% of the isolates were members of the three major Spanish penicillin-resistant or multidrug-resistant clones of serotypes 6B, 9V, and 23F or serotype variants of these clones. These three clones (MICs, 1 to 2 μg of penicillin/ml) were the most common clones associated with pneumococcal meningitis in Spain during 1997 and 1998. Only two of the other clones associated with meningitis were penicillin resistant (MICs, 0.12 to 0.5 μg/ml). One of the two most prevalent penicillin-susceptible clones causing meningitis (serotype 3) has not been detected outside of Spain, whereas the other (serotype 18C) has been recovered from patients with meningitis in the United Kingdom, The Netherlands, and Denmark. The prevalence of meningitis caused by isolates of the three major Spanish penicillin-resistant or multiply antibiotic-resistant clones, which are now globally distributed, is disturbing and clearly establishes their ability to cause life-threatening disease. PMID:10488179

  14. On electrical resistivity of AISI D2 steel during various stages of cryogenic treatment

    Science.gov (United States)

    Lomte, Sachin Vijay; Gogte, Chandrashekhar Laxman; Peshwe, Dilip

    2012-06-01

    The effect of dislocation densities and residual stresses is well known in tool steels. Measurement of electrical resistivity in order to monitor dislocation densities or residual stresses has seldom been used in investigating the effect of cryogenic treatment on tool steels. Monitoring residual stresses during cryogenic treatment becomes important as it is directly related to changes due to cryogenic treatment of tool steels. For high carbon high chromium (HCHC- AISI D2) steels, not only wear resistance but dimensional stability is an important issue as the steels are extensively used in dies, precision measuring instruments. This work comprises of study of measurement of electrical resistivity of AISI D2 steel at various stages of cryogenic treatment. Use of these measurements in order to assess the dimensional stability of these steels is discussed in this paper.

  15. Study of critical dependence of stable phases in Nitinol on heat treatment using electrical resistivity probe

    International Nuclear Information System (INIS)

    Uchil, J.; Mohanchandra, K.P.; Kumara, K.G.; Mahesh, K.K.

    1998-01-01

    Phase transformations in 40% cold-worked Nitinol as a function of heat treatment have been studied using electrical resistivity variation with temperature. The stabilisation of austenitic, rhombohedral and martensitic phases is shown to critically depend on the temperatures of heat treatment by the analysis of temperature dependence of electrical resistivity in heating and cooling parts of the cycle. Characteristic values of electrical resistivity of the stable phases are determined. The R-phase has been found to form continuously with increasing heat-treatment temperature starting from room temperature and to suddenly disappear beyond heat-treatment at 683 K. The observed presence or absence of R-phase is confirmed by heat capacity measurements as a function of temperature. (orig.)

  16. Fitness and Recovery of Bacterial Communities and Antibiotic Resistance Genes in Urban Wastewaters Exposed to Classical Disinfection Treatments.

    Science.gov (United States)

    Di Cesare, Andrea; Fontaneto, Diego; Doppelbauer, Julia; Corno, Gianluca

    2016-09-20

    Antibiotic resistance genes (ARGs) are increasingly appreciated to be important as micropollutants. Indirectly produced by human activities, they are released into the environment, as they are untargeted by conventional wastewater treatments. In order to understand the fate of ARGs and of other resistant forms (e.g., phenotypical adaptations) in urban wastewater treatment plants (WWTPs), we monitored three WWTPs with different disinfection processes (chlorine, peracetic acid (PAA), and ultraviolet light (UV)). We monitored WWTPs influx and pre- and postdisinfection effluent over 24 h, followed by incubation experiments lasting for 96 h. We measured bacterial abundance, size distribution and aggregational behavior, the proportion of intact (active) cells, and the abundances of four ARGs and of the mobile element integron1. While all the predisinfection treatments of all WWTPs removed the majority of bacteria and of associated ARGs, of the disinfection processes only PAA efficiently removed bacterial cells. However, the stress imposed by PAA selected for bacterial aggregates and, similarly to chlorine, stimulated the selection of ARGs during the incubation experiment. This suggests disinfections based on chemically aggressive destruction of bacterial cell structures can promote a residual microbial community that is more resistant to antibiotics and, given the altered aggregational behavior, to competitive stress in nature.

  17. Bereavement dream? Successful antidepressant treatment for bereavement-related distressing dreams in patients with major depression.

    Science.gov (United States)

    Ishida, Mayumi; Onishi, Hideki; Wada, Mei; Wada, Tomomi; Wada, Makoto; Uchitomi, Yosuke; Nomura, Shinobu

    2010-03-01

    The death of a person is a stressful event. Such stress affects the physical and psychological well-being of the bereaved. As an associated mental disorder, major depressive disorder (MDD) is common. Some dream of the deceased, and these dreams are called bereavement dreams. Some MDD patients also experience dreams. These two types of dreams are sometimes difficult to differentiate. The dream of the bereaved might be only a bereavement-related dream, yet it might be a symptom of MDD. Herein, we report one patient who had distressing dreams after the death of her mother. A 63-year-old woman was referred for psychiatric consultation because of generalized fatigue and insomnia. Questioning her about recent events, she said that her mother had died of colonic carcinoma 5 months previously. Two months after the death, she suddenly started dreaming of her mother, getting angry with her almost every night. Generalized fatigue, insomnia, and distressing dreams appeared simultaneously. The dream caused much distress, making her afraid to fall asleep. Her psychiatric features fulfilled the DSM-IV-TR criteria for MDD, single episode. The death of her mother was considered to be one of the causes of MDD. She was administered 25 mg/day of sertraline hydrochloride. After that, her symptoms gradually disappeared, and the frequency of distressing dreams was reduced. Five months later, physical and psychiatric symptoms of MDD were completely resolved. Subsequently, she has not suffered from any distressing dreams of her mother. This case indicates that dreams experienced after the death of a loved one should not be regarded simply as bereavement dreams. Some of the dreams may be symptoms of MDD. If the dreams are the symptoms of MDD, antidepressant treatment as well as psychotherapy may be useful. Therefore, we should avoid regarding symptoms of MDD as reactions to bereavement.

  18. Comparative efficacy of escitalopram in the treatment of major depressive disorder

    Directory of Open Access Journals (Sweden)

    Mazen K Ali

    2011-02-01

    Full Text Available Mazen K Ali, Raymond W LamDepartment of Psychiatry, University of British Columbia, and Mood Disorders Centre, University of British Columbia Hospital, Vancouver, CanadaBackground: Escitalopram is an allosteric selective serotonin reuptake inhibitor (SSRI with some indication of superior efficacy in the treatment of major depressive disorder. In this systematic review, we critically evaluate the evidence for comparative efficacy and tolerability of escitalopram, focusing on pooled and meta-analysis studies.Methods: A literature search was conducted for escitalopram studies that quantitatively synthesized data from comparative randomized controlled trials in MDD. Studies were excluded if they did not focus on efficacy, involved primarily subgroups of patients, or synthesized data included in subsequent studies. Outcomes extracted from the included studies were weighted mean difference or standard mean difference, response and remission rates, and withdrawal rate owing to adverse events.Results: The search initially identified 24 eligible studies, of which 12 (six pooled analysis and six meta-analysis studies met the criteria for review. The pooled and meta-analysis studies with citalopram showed significant but modest differences in favor of escitalopram, with weighted mean differences ranging from 1.13 to 1.73 points on the Montgomery Asberg Depression Rating Scale, response rate differences of 7.0%–8.3%, and remission rate differences of 5.1%–17.6%. Pooled analysis studies showed efficacy differences compared with duloxetine and with serotonin noradrenaline reuptake inhibitors combined, but meta-analysis studies did not. The effect sizes of the efficacy differences increased in the severely depressed patient subgroups.Conclusion: Based on pooled and meta-analysis studies, escitalopram demonstrates superior efficacy compared with citalopram and with SSRIs combined. Escitalopram shows similar efficacy to serotonin noradrenaline reuptake

  19. Effect of variation in oxytetracycline treatment of Lawsonia intracellularis diahrea in nursery pigs on treatment-efficacy and resistance development

    DEFF Research Database (Denmark)

    Larsen, I.; Mellerup, Anders; Zachariasen, C.

    2015-01-01

    A Danish research project, MINIRESIST, investigated the consequences of varying doses and treatment strategies for oxytetracycline treatment of Lawsonia intracellularis diarrhea in nursery pigs. Batches of nursery pigs in five herds were randomly allocated to one of five treatment protocols (batch...... scores, which have low sensitivity for diarrhea. Simulation studies suggested that resistance development was mostly dependent on the duration of the treatment and the total amount of oxytetracycline used per pig. Ongoing field testing has been initiated to confirm this conclusion, since no field...

  20. Matching of treatment-resistant heroin-dependent patients to medical prescription of heroin or oral methadone treatment: results from two randomized controlled trials

    NARCIS (Netherlands)

    Blanken, Peter; Hendriks, Vincent M.; Koeter, Maarten W. J.; van Ree, Jan M.; van den Brink, Wim

    2005-01-01

    AIMS: To investigate which baseline patient characteristics of treatment-resistant heroin addicts differentially predicted treatment response to medical heroin prescription compared to standard methadone maintenance treatment. DESIGN: Two open-label randomized controlled trials; pooled data.

  1. Use of Ketamine in Elderly Patients with Treatment-Resistant Depression.

    Science.gov (United States)

    Medeiros da Frota Ribeiro, Carolina; Riva-Posse, Patricio

    2017-11-15

    The purpose of this paper is to provide a review of the use of ketamine as an antidepressant for treatment-resistant depression (TRD) in the geriatric population. Available treatment options for late-life treatment-resistant depression are limited and include electroconvulsive therapy and transcranial magnetic stimulation as well as possible pharmacologic augmentation. Ketamine has been shown to be a promising treatment in TRD; however, data regarding the use of ketamine in the elderly includes only five case reports. We discuss the use of ketamine for late-life TRD and present two cases where ketamine led to a significant and sustained improvement in depressive symptoms. Ketamine is a promising treatment for geriatric patients with TRD. Further studies in the elderly will provide valuable insights into the use of ketamine for a population much in need of safe and effective treatments for TRD.

  2. Influence of Heat Treatment on Mercury Cavitation Resistance of Surface Hardened 316LN Stainless Steel

    Energy Technology Data Exchange (ETDEWEB)

    Pawel, Steven J [ORNL; Hsu, Julia [Massachusetts Institute of Technology (MIT)

    2010-11-01

    The cavitation-erosion resistance of carburized 316LN stainless steel was significantly degraded but not destroyed by heat treatment in the temperature range 500-800 C. The heat treatments caused rejection of some carbon from the carburized layer into an amorphous film that formed on each specimen surface. Further, the heat treatments encouraged carbide precipitation and reduced hardness within the carburized layer, but the overall change did not reduce surface hardness fully to the level of untreated material. Heat treatments as short as 10 min at 650 C substantially reduced cavitation-erosion resistance in mercury, while heat treatments at 500 and 800 C were found to be somewhat less detrimental. Overall, the results suggest that modest thermal excursions perhaps the result of a weld made at some distance to the carburized material or a brief stress relief treatment will not render the hardened layer completely ineffective but should be avoided to the greatest extent possible.

  3. The effects of tertiary wastewater treatment on the prevalence of antimicrobial resistant bacteria

    DEFF Research Database (Denmark)

    Guardabassi, L.; Wong, Danilo Lo Fo; Dalsgaard, A.

    2002-01-01

    and anaerobically digested sludge by bacteriological counts on media selective for coliforms (MacConkey agar) and Acinetobacter spp. (Baumann agar). In addition, the level of antimicrobial susceptibility was determined by the disc-diffusion method in 442 Acinetobacter isolates identified by colony hybridisation......-resistant presumptive coliforms and Acinetobacter spp. in treated sewage and digested sludge were not significantly higher compared with raw sewage. On the contrary at one plant, statistically significant decreases were observed in the prevalence of ampicillin-resistant presumptive Acinetobacter spp. (p = 0.......0188) following sewage treatment, and in the prevalence of either ampicillin-resistant presumptive Acinetobacter spp. (p = 0.0013) or ampicillin- and gentamicin-resistant presumptive coliforms (p = 0.0273 and p = 0.0186) following sludge treatment. The results obtained by bacteriological counts were confirmed...

  4. Synergistic antimicrobial therapy using nanoparticles and antibiotics for the treatment of multidrug-resistant bacterial infection

    Science.gov (United States)

    Gupta, Akash; Saleh, Neveen M.; Das, Riddha; Landis, Ryan F.; Bigdeli, Arafeh; Motamedchaboki, Khatereh; Rosa Campos, Alexandre; Pomeroy, Kenneth; Mahmoudi, Morteza; Rotello, Vincent M.

    2017-06-01

    Infections caused by multidrug-resistant (MDR) bacteria pose a serious global burden of mortality, causing thousands of deaths each year. Antibiotic treatment of resistant infections further contributes to the rapidly increasing number of antibiotic-resistant species and strains. Synthetic macromolecules such as nanoparticles (NPs) exhibit broad-spectrum activity against MDR species, however lack of specificity towards bacteria relative to their mammalian hosts limits their widespread therapeutic application. Here, we demonstrate synergistic antimicrobial therapy using hydrophobically functionalized NPs and fluoroquinolone antibiotics for treatment of MDR bacterial strains. An 8-16-fold decrease in antibiotic dosage is achieved in presence of engineered NPs to combat MDR strains. This strategy demonstrates the potential of using NPs to ‘revive’ antibiotics that have been rendered ineffective due to the development of resistance by pathogenic bacteria.

  5. Neoadjuvant chemotherapy as ovarian cancer treatment: ever more used with major regional differences

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten L; Ottesen, Bent; Kehlet, Henrik

    2012-01-01

    The traditional first-line treatment for patients with advanced ovarian cancer with primary debulking surgery (PDS) and adjuvant chemotherapy is controversial as some authors report a potential benefit from the alternative treatment with neoadjuvant chemotherapy (NACT) and interval debulking...

  6. Personality Modulates the Efficacy of Treatment in Patients With Major Depressive Disorder

    NARCIS (Netherlands)

    Wardenaar, Klaas J.; Conradi, Henk Jan; Bos, Elisabeth H.; de Jonge, Peter

    OBJECTIVE: Effects of depression treatment are obscured by heterogeneity among patients. Personality types could be one source of heterogeneity that explains variability in treatment response. Clinically meaningful variations in personality patterns could be captured with data-driven subgroups. The

  7. Dextromethorphan/quinidine pharmacotherapy in patients with treatment resistant depression: A proof of concept clinical trial.

    Science.gov (United States)

    Murrough, James W; Wade, Elizabeth; Sayed, Sehrish; Ahle, Gabriella; Kiraly, Drew D; Welch, Alison; Collins, Katherine A; Soleimani, Laili; Iosifescu, Dan V; Charney, Dennis S

    2017-08-15

    At least one-third of patients with major depressive disorder (MDD) have treatment-resistant depression (TRD), defined as lack of response to two or more adequate antidepressant trials. For these patients, novel antidepressant treatments are urgently needed. The current study is a phase IIa open label clinical trial examining the efficacy and tolerability of a combination of dextromethorphan (DM) and the CYP2D6 enzyme inhibitor quinidine (Q) in patients with TRD. Dextromethorphan acts as an antagonist at the glutamate N-methyl-d-aspartate (NMDA) receptor, in addition to other pharmacodynamics properties that include activity at sigma-1 receptors. Twenty patients with unipolar TRD who completed informed consent and met all eligibility criteria we enrolled in an open-label study of DM/Q up to 45/10mg by mouth administered every 12h over the course of a 10-week period, and constitute the intention to treat (ITT) sample. Six patients discontinued prior to study completion. There was no treatment-emergent suicidal ideation, psychotomimetic or dissociative symptoms. Montgomery-Asberg Depression Rating Scale (MADRS) score was reduced from baseline to the 10-week primary outcome (mean change: -13.0±11.5, t 19 =5.0, p<0.001), as was QIDS-SR score (mean change: -5.9±6.6, t 19 =4.0, p<0.001). The response and remission rates in the ITT sample were 45% and 35%, respectively. Open-label, proof-of-concept design. Herein we report acceptable tolerability and preliminary efficacy of DM/Q up to 45/10mg administered every 12h in patients with TRD. Future larger placebo controlled randomized trials in this population are warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Diagnosis and interim treatment outcomes from the first cohort of multidrug-resistant tuberculosis patients in Tanzania.

    Directory of Open Access Journals (Sweden)

    Stellah G Mpagama

    Full Text Available Kibong'oto National Tuberculosis Hospital (KNTH, Kilimanjaro, Tanzania.Characterize the diagnostic process and interim treatment outcomes from patients treated for multidrug-resistant tuberculosis (MDR-TB in Tanzania.A retrospective cohort study was performed among all patients treated at KNTH for pulmonary MDR-TB between November 2009 and September 2011.Sixty-one culture-positive MDR-TB patients initiated therapy, 60 (98% with a prior history of TB treatment. Forty-one (67% were male and 9 (14% were HIV infected with a mean CD4 count of 424 (±106 cells/µl. The median time from specimen collection to MDR-TB diagnosis and from diagnosis to initiation of MDR-TB treatment was 138 days (IQR 101-159 and 131 days (IQR 32-233, respectively. Following treatment initiation four (7% patients died (all HIV negative, 3 (5% defaulted, and the remaining 54 (89% completed the intensive phase. Most adverse drug reactions were mild to moderate and did not require discontinuation of treatment. Median time to culture conversion was 2 months (IQR 1-3 and did not vary by HIV status. In 28 isolates available for additional second-line drug susceptibility testing, fluoroquinolone, aminoglycoside and para-aminosalicylic acid resistance was rare yet ethionamide resistance was present in 9 (32%.The majority of MDR-TB patients from this cohort had survived a prolonged referral process, had multiple episodes of prior TB treatment, but did not have advanced AIDS and converted to culture negative early while completing an intensive inpatient regimen without serious adverse event. Further study is required to determine the clinical impact of second-line drug susceptibility testing and the feasibility of alternatives to prolonged hospitalization.

  9. Counteracting quasispecies adaptability: extinction of a ribavirin-resistant virus mutant by an alternative mutagenic treatment.

    Directory of Open Access Journals (Sweden)

    Celia Perales

    Full Text Available BACKGROUND: Lethal mutagenesis, or virus extinction promoted by mutagen-induced elevation of mutation rates of viruses, may meet with the problem of selection of mutagen-resistant variants, as extensively documented for standard, non-mutagenic antiviral inhibitors. Previously, we characterized a mutant of foot-and-mouth disease virus that included in its RNA-dependent RNA polymerase replacement M296I that decreased the sensitivity of the virus to the mutagenic nucleoside analogue ribavirin. METHODOLOGY AND PRINCIPAL FINDINGS: Replacement M296I in the viral polymerase impedes the extinction of the mutant foot-and-mouth disease virus by elevated concentrations of ribavirin. In contrast, wild type virus was extinguished by the same ribavirin treatment and, interestingly, no mutants resistant to ribavirin were selected from the wild type populations. Decreases of infectivity and viral load of the ribavirin-resistant M296I mutant were attained with a combination of the mutagen 5-fluorouracil and the non-mutagenic inhibitor guanidine hydrocloride. However, extinction was achieved with a sequential treatment, first with ribavirin, and then with a minimal dose of 5-fluorouracil in combination with guanidine hydrochloride. Both, wild type and ribavirin-resistant mutant M296I exhibited equal sensitivity to this combination, indicating that replacement M296I in the polymerase did not confer a significant cross-resistance to 5-fluorouracil. We discuss these results in relation to antiviral designs based on lethal mutagenesis. CONCLUSIONS: (i When dominant in the population, a mutation that confers partial resistance to a mutagenic agent can jeopardize virus extinction by elevated doses of the same mutagen. (ii A wild type virus, subjected to identical high mutagenic treatment, need not select a mutagen-resistant variant, and the population can be extinguished. (iii Extinction of the mutagen-resistant variant can be achieved by a sequential treatment of a

  10. Major depressive disorder and generalized anxiety disorder and response to treatment in hepatitis C patients in Egypt.

    Science.gov (United States)

    MM, Bassiony; A, Yousef; U, Youssef; GM, Salah El-Deen; M, Abdelghani; H, Al-Gohari; E, Fouad; MM, El-Shafaey

    2015-01-01

    The aim of the study was to estimate the prevalence and associated correlates of major depressive disorder and generalized anxiety disorder in hepatitis C virus patients before and after treatment and to investigate the relationship between major depressive disorder and generalized anxiety disorder and treatment response. A total of 116 consecutive hepatitis C virus patients from hepatitis C virus treatment center in Zagazig city, Egypt, were included in the study and divided into treated group (N = 58) and untreated group (N = 58). All hepatitis C virus patients were screened for major depressive disorder and generalized anxiety disorder using hospital anxiety and depression scale, and those who screened positive were interviewed to confirm the diagnosis of major depressive disorder and generalized anxiety disorder using DSM-IV-TR diagnostic criteria. These measures were done at baseline and after 12 weeks of treatment or observation. At baseline, 3.5% and 12.1% of hepatitis C virus patients (treated group) had major depressive disorder and generalized anxiety disorder, respectively. After 12 weeks of treatment 37.9% of hepatitis C virus patients (treated group) had major depressive disorder and 46.6% had generalized anxiety disorder. There was a significant statistical difference between hospital anxiety and depression scale scores for depression (3.3 ± 2.3 vs. 6.4 ± 3.2, t = 9.6, p = 0.001) and for anxiety (4.6 ± 2.4 vs. 7.3 ± 3.0, t = 10.2, p = 0.001) before and after treatment. There was also significant statistical difference between treated group and untreated group regarding hospital anxiety and depression scale scores after treatment and observation (depression, treated group 6.4 ± 3.2 vs. untreated group 4.0 ± 2.4, t = 3.7, p = 0.001; anxiety, treated group 7.3 ± 3.0 vs. untreated group 4.5 ± 2.3, t = 4.4, p = 0.001). There was no association between major depressive disorder

  11. Ketamine Therapy for Treatment-resistant Depression in a Patient with Multiple Sclerosis: A Case Report.

    Science.gov (United States)

    Messer, Michael M; Haller, Irina V

    2017-01-01

    Objective: Depression is a common condition among patients with multiple sclerosis and often becomes resistant to oral antidepressants. We report a patient with multiple sclerosis who developed severe treatment-resistant depression and who was successfully treated with intravenous ketamine over the period of two years. Methods: Ketamine treatment protocol included an initial series of six treatments administered every other day, followed by a maintenance schedule. Ketamine was administered intravenously at 0.5mg/kg of ideal body weight over 40 minutes. Depression symptoms were measured using Beck Depression Index. Results: The patient's Beck Depression Index score prior to initiating ketamine treatment was 38, corresponding to severe depression. Response to treatment, defined as 50-percent reduction in Beck Depression Index score, was observed after five treatments. For this patient, the maintenance schedule ranged from a weekly treatment to one treatment every three weeks. During the two-year observation period, this patient was able to maintain a stable non-depressed mood and had no worsening of her MS symptoms. Conclusion: Ketamine may be an alternative treatment for resistant depression and may have a special use in patients with multiple sclerosis.

  12. Investigation of isoniazid and ethionamide cross-resistance by whole genome sequencing and association with poor treatment outcomes of multidrug-resistant tuberculosis patients in South Africa

    Directory of Open Access Journals (Sweden)

    L Malinga

    2016-01-01

    Conclusion: Baseline ETH molecular resistance before second-line treatment is a concern. Unfavorable treatment outcomes of patients with ethA, ethR, and inhA mutations highlight the importance of genotypic testing before initiation of treatment containing ETH. The clinical significance of whole genome analysis for early detection of mutations predictive of treatment failure needs further investigation.

  13. Maintenance Electroconvulsive Therapy in a Patient with Treatment-Resistant Paranoid Schizophrenia and Comorbid Epilepsy

    Directory of Open Access Journals (Sweden)

    Beppe Micallef-Trigona

    2012-01-01

    Full Text Available The treatment of choice for acute schizophrenia is antipsychotic drug treatment and electroconvulsive therapy (ECT and should only be considered as an option for treatment-resistant schizophrenia, where treatment with clozapine has already proven ineffective or intolerable. The use of ECT as a maintenance treatment for patients with schizophrenia and comorbid epilepsy is uncommon as scant evidence exists to support this. We describe a patient with a serious case of paranoid schizophrenia and comorbid epilepsy who had not responded to typical and atypical antipsychotic medication, but responded remarkably to acute ECT and required maintenance ECT to sustain a positive therapeutic response.

  14. Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia

    Directory of Open Access Journals (Sweden)

    Makoto Kinoshita

    2017-03-01

    Full Text Available Clozapine is an atypical antipsychotic, that is established as the treatment of choice for treatment-resistant schizophrenia (SCZ. To date, no study investigating comprehensive DNA methylation changes in SCZ patients treated with chronic clozapine has been reported. The purpose of the present study is to reveal the effects of clozapine on DNA methylation in treatment-resistant SCZ. We conducted a genome-wide DNA methylation profiling in peripheral leukocytes (485,764 CpG dinucleotides from treatment-resistant SCZ patients treated with clozapine (n = 21 in a longitudinal study. Significant changes in DNA methylation were observed at 29,134 sites after one year of treatment with clozapine, and these genes were enriched for “cell substrate adhesion” and “cell matrix adhesion” gene ontology (GO terms. Furthermore, DNA methylation changes in the CREBBP (CREB binding protein gene were significantly correlated with the clinical improvements. Our findings provide insights into the action of clozapine in treatment-resistant SCZ.

  15. Erlotinib is a viable treatment for tumors with acquired resistance to cetuximab

    Science.gov (United States)

    Brand, Toni M; Dunn, Emily F; Iida, Mari; Myers, Rebecca A; Kostopoulos, Kellie T; Li, Chunrong; Peet, Chimera R

    2011-01-01

    The epidermal growth factor receptor (EGFR) is an ubiquitously expressed receptor tyrosine kinase (RTK) and is recognized as a key mediator of tumorigenesis in many human tumors. Currently there are five EGFR inhibitors used in oncology, two monoclonal antibodies (panitumumab and cetuximab) and three tyrosine kinase inhibitors (erlotinib, gefitinib and lapatinib). Both strategies of EGFR inhibition have demonstrated clinical success; however, many tumors remain non-responsive or acquire resistance during therapy. To explore potential molecular mechanisms of acquired resistance to cetuximab we previously established a series of cetuximab-resistant clones by chronically exposing the NCI-H226 NSCLC cell line to escalating doses of cetuximab. Cetuximab-resistant clones exhibited a dramatic increase in the activation of EGFR, HER2 and HER3 receptors as well as increased signaling through the MAP K and AKT pathways. RNAi studies demonstrated dependence of cetuximab-resistant clones on the EGFR signaling network. These findings prompted investigation on whether or not cells with acquired resistance to cetuximab would be sensitive to the EGFR targeted TKI erlotinib. In vitro, erlotinib was able to decrease signaling through the EGFR axis, decrease cellular proliferation and induce apoptosis. To determine if erlotinib could have therapeutic benefit in vivo, we established cetuximab-resistant NCI-H226 mouse xenografts, and subsequently treated them with erlotinib. Mice harboring cetuximab-resistant tumors treated with erlotinib exhibited either a tumor regression or growth delay as compared with vehicle controls. Analysis of the erlotinib treated tumors demonstrated a decrease in cell proliferation and increased rates of apoptosis. The work presented herein suggests that (1) cells with acquired resistance to cetuximab maintain their dependence on EGFR and (2) tumors developing resistance to cetuximab can benefit from subsequent treatment with erlotinib, providing rationale

  16. Antipsychotic polypharmacy in clozapine resistant schizophrenia: a randomized controlled trial of tapering antipsychotic co-treatment

    Directory of Open Access Journals (Sweden)

    Jari Tiihonen

    2012-01-01

    Full Text Available There is a considerable disparity between clinical practice and recommendations based on meta-analyses of antipsychotic polypharmacy in clozapine resistant schizophrenia. For this reason, we investigated the clinical response to reducing the use olanzapine that had been previously added on clozapine treatment among seriously ill hospitalized patients. In a randomized controlled trial with crossover design, we studied volunteer patients (N = 15 who had olanzapine added on to clozapine in a state mental hospital. Clozapine monotherapy was just as effective as clozapine-olanzapine therapy, according to results from Clinical Global Impression Scale and Global Assessment of Functioning as primary outcome measures. Polypharmacy is widely used in treating schizophrenia, and usually, add-on medications are started because of worsening of the clinical state. A major confounding feature of these add-ons is whether observed improvements are caused by the medication or explained by the natural fluctuating course of the disorder. The present study, in spite of its small size, indicates the necessity of reconsidering the value of polypharmacy in treating schizophrenia.

  17. Treatment of upper airway resistance syndrome in adults: Where do we stand?

    Directory of Open Access Journals (Sweden)

    Luciana B.M. de Godoy

    2015-01-01

    Full Text Available Objective: To evaluate the available literature regarding Upper Airway Resistance Syndrome (UARS treatment. Methods: Keywords “Upper Airway Resistance Syndrome,” “Sleep-related Breathing Disorder treatment,” “Obstructive Sleep Apnea treatment” and “flow limitation and sleep” were used in main databases. Results: We found 27 articles describing UARS treatment. Nasal continuous positive airway pressure (CPAP has been the mainstay therapy prescribed but with limited effectiveness. Studies about surgical treatments had methodological limitations. Oral appliances seem to be effective but their efficacy is not yet established. Conclusion: Randomized controlled trials with larger numbers of patients and long-term follow-up are important to establish UARS treatment options.

  18. Molecular Characterization of Methicillin Resistant Staphylococcus aureus Strains Isolated from Intensive Care Units in Iran: ST22-SCCmec IV/t790 Emerges as the Major Clone.

    Science.gov (United States)

    Goudarzi, Mehdi; Goudarzi, Hossein; Sá Figueiredo, Agnes Marie; Udo, Edet E; Fazeli, Maryam; Asadzadeh, Mohammad; Seyedjavadi, Sima Sadat

    2016-01-01

    The emergence of methicillin-resistant Staphylococcus aureus (MRSA) in different patient populations is a major public health concern. This study determined the prevalence and distribution of circulating molecular types of MRSA in hospitalized patients in ICU of hospitals in Tehran. A total of 70 MRSA isolates were collected from patients in eight hospitals. Antimicrobial resistance patterns were determined using the disk diffusion method. The presence of toxin encoding genes and the vancomycin resistance gene were determined by PCR. The MRSA isolates were further analyzed using multi-locus sequence, spa, SCCmec, and agr typing. The MRSA prevalence was 93.3%. Antimicrobial susceptibility testing revealed a high resistance rate (97.1%) to ampicillin and penicillin. The rate of resistance to the majority of antibiotics tested was 30% to 71.4%. Two isolates belonging to the ST22-SCCmec IV/t790 clone (MIC ≥ 8 μg/ml) had intermediate resistance to vancomycin. The majority of MRSA isolates (24.3%) were associated with the ST22-SCCmec IV/t790 clone; the other MRSA clones were ST859-SCCmec IV/t969 (18.6%), ST239-SCCmec III/t037 (17.1%), and ST291-SCCmec IV/t030 (8.6%). The circulating MRSA strains in Iranian hospitals were genetically diverse with a relatively high prevalence of the ST22-SCCmec IV/t790 clone. These findings support the need for future surveillance studies on MRSA to better elucidate the distribution of existing MRSA clones and detect emergence of new MRSA clones.

  19. The Composition and Spatial Patterns of Bacterial Virulence Factors and Antibiotic Resistance Genes in 19 Wastewater Treatment Plants.

    Directory of Open Access Journals (Sweden)

    Bing Zhang

    Full Text Available Bacterial pathogenicity and antibiotic resistance are of concern for environmental safety and public health. Accumulating evidence suggests that wastewater treatment plants (WWTPs are as an important sink and source of pathogens and antibiotic resistance genes (ARGs. Virulence genes (encoding virulence factors are good indicators for bacterial pathogenic potentials. To achieve a comprehensive understanding of bacterial pathogenic potentials and antibiotic resistance in WWTPs, bacterial virulence genes and ARGs in 19 WWTPs covering a majority of latitudinal zones of China were surveyed by using GeoChip 4.2. A total of 1610 genes covering 13 virulence factors and 1903 genes belonging to 11 ARG families were detected respectively. The bacterial virulence genes exhibited significant spatial distribution patterns of a latitudinal biodiversity gradient and a distance-decay relationship across China. Moreover, virulence genes tended to coexist with ARGs as shown by their strongly positive associations. In addition, key environmental factors shaping the overall virulence gene structure were identified. This study profiles the occurrence, composition and distribution of virulence genes and ARGs in current WWTPs in China, and uncovers spatial patterns and important environmental variables shaping their structure, which may provide the basis for further studies of bacterial virulence factors and antibiotic resistance in WWTPs.

  20. Renal sympathetic nerve ablation for treatment-resistant hypertension

    Science.gov (United States)

    Krum, Henry; Schlaich, Markus; Sobotka, Paul

    2013-01-01

    Hypertension is a major risk factor for increased cardiovascular events with accelerated sympathetic nerve activity implicated in the pathogenesis and progression of disease. Blood pressure is not adequately controlled in many patients, despite the availability of effective pharmacotherapy. Novel procedure- as well as device-based strategies, such as percutaneous renal sympathetic nerve denervation, have been developed to improve blood pressure in these refractory patients. Renal sympathetic denervation not only reduces blood pressure but also renal as well as systemic sympathetic nerve activity in such patients. The reduction in blood pressure appears to be sustained over 3 years after the procedure, which suggests absence of re-innervation of renal sympathetic nerves. Safety appears to be adequate. This approach may also have potential in other disorders associated with enhanced sympathetic nerve activity such as congestive heart failure, chronic kidney disease and metabolic syndrome. This review will focus on the current status of percutaneous renal sympathetic nerve denervation, clinical efficacy and safety outcomes and prospects beyond refractory hypertension. PMID:23819768

  1. Pyrethroid resistance discovered in a major agricultural pest in southern Australia: the redlegged earth mite Halotydeus destructor (Acari: Penthaleidae).

    Science.gov (United States)

    Umina, Paul A

    2007-12-01

    The redlegged earth mite (Halotydeus destructor Tucker) is an important pest of field crops and pastures. Control of this pest relies heavily on chemicals, with few genuine alternatives presently available. Pesticide responses of H. destructor from the field with reported chemical control failures were compared with mites from susceptible 'control' populations. Toxicology bioassays were conducted on adult mites across multiple generations. Very high levels of resistance to two synthetic pyrethroids, bifenthrin and alpha-cypermethrin, were detected in this species for the first time. For bifenthrin, LC(50) estimates showed a difference in resistance of greater than 240 000-fold. Resistance to alpha-cypermethrin was almost 60 000-fold. This resistance was shown to be heritable, persisting after several generations of culturing. There was no evidence that resistance to organophosphorus chemicals had evolved, which is likely to be a direct consequence of the history of chemical applications these mites have experienced. These results highlight the need for more judicious management decisions in order to control pest species in a sustainable manner. The implications of these findings in regard to the management and future research of the redlegged earth mite are discussed. Copyright (c) 2007 Society of Chemical Industry.

  2. Maternal depressive symptoms in pediatric major depressive disorder: relationship to acute treatment outcome.

    Science.gov (United States)

    Kennard, Betsy D; Hughes, Jennifer L; Stewart, Sunita M; Mayes, Taryn; Nightingale-Teresi, Jeanne; Tao, Rongrong; Carmody, Thomas; Emslie, Graham J

    2008-06-01

    In the present study, we assess maternal depressive symptoms at the beginning and end of treatment to investigate the possible reciprocal relationship of maternal illness with the child's depressive illness and treatment. We present data on 146 children and their mothers who were participating in a pediatric acute treatment study of fluoxetine. Patients were assessed with the Children's Depression Rating Scale-Revised at baseline and at each treatment visit. Mothers completed the Quick Inventory of Depressive Symptomatology-Self Report at baseline and end of acute treatment. Thirty percent of mothers had moderate to severe levels of depressive symptoms at the child's baseline assessment. Overall, mothers reported improvement in maternal depressive symptoms at the end of their child's acute treatment, although maternal depression was not specifically targeted for intervention. Furthermore, mother's depressive symptoms appear to be associated with the child's depression severity both at the beginning and end of treatment. Mothers with higher levels of depressive symptoms had children with higher levels of depression severity at baseline and over the course of treatment. However, maternal depressive symptoms at baseline had no association with the rate of improvement of child depression severity. This study indicates a positive relationship between the depression severity of mothers and their children. These findings highlight potential areas of intervention in the acute treatment of childhood depression.

  3. Gas Plasma Pre-treatment Increases Antibiotic Sensitivity and Persister Eradication in Methicillin-Resistant Staphylococcus aureus

    Science.gov (United States)

    Guo, Li; Xu, Ruobing; Zhao, Yiming; Liu, Dingxin; Liu, Zhijie; Wang, Xiaohua; Chen, Hailan; Kong, Michael G.

    2018-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of serious nosocomial infections, and recurrent MRSA infections primarily result from the survival of persister cells after antibiotic treatment. Gas plasma, a novel source of ROS (reactive oxygen species) and RNS (reactive nitrogen species) generation, not only inactivates pathogenic microbes but also restore the sensitivity of MRSA to antibiotics. This study further found that sublethal treatment of MRSA with both plasma and plasma-activated saline increased the antibiotic sensitivity and promoted the eradication of persister cells by tetracycline, gentamycin, clindamycin, chloramphenicol, ciprofloxacin, rifampicin, and vancomycin. The short-lived ROS and RNS generated by plasma played a primary role in the process and induced the increase of many species of ROS and RNS in MRSA cells. Thus, our data indicated that the plasma treatment could promote the effects of many different classes of antibiotics and act as an antibiotic sensitizer for the treatment of antibiotic-resistant bacteria involved in infectious diseases. PMID:29628915

  4. Results of a randomized controlled pilot trial of intravascular renal denervation for management of treatment-resistant hypertension.

    Science.gov (United States)

    Jacobs, Lotte; Persu, Alexandre; Huang, Qi-Fang; Lengelé, Jean-Philippe; Thijs, Lutgarde; Hammer, Frank; Yang, Wen-Yi; Zhang, Zhen-Yu; Renkin, Jean; Sinnaeve, Peter; Wei, Fang-Fei; Pasquet, Agnès; Fadl Elmula, Fadl Elmula M; Carlier, Marc; Elvan, Arif; Wunder, Cora; Kjeldsen, Sverre E; Toennes, Stefan W; Janssens, Stefan; Verhamme, Peter; Staessen, Jan A

    2017-12-01

    Previous trials of catheter-based renal-artery denervation (RDN) as treatment modality in resistant hypertension (rHT) generated unconvincing results. In the Investigator-Steered Project on Intravascular Denervation for Management of Treatment-Resistant Hypertension (INSPiRED; NCT01505010), we optimized selection and management of rHT patients. With ethical clearance to randomize 18 patients, three Belgian hypertension centers screened 29 rHT patients on treatment with ≥3 drugs, of whom 17 after optimization of treatment (age efficacy endpoint, and 2.5 mL/min/1.73 m 2 (+1.5 vs. -1.1 mL/min/1.73 m 2 ; P = .86) for eGFR, the primary safety endpoint. At 6 month, ECG voltages and the number of prescribed drugs (P ≤ .036) were lower in RDN patients, but quality of life and adherence, captured by questionnaire and urine analysis were similar in both groups. Changes in BP and adherence were unrelated. No major complications occurred. The INSPiRED pilot suggests that RDN with the EnligHTN ™ system is effective and safe and generated insights useful for the design of future RDN trials.

  5. High-resolution mapping and characterization of qRgls2, a major quantitative trait locus involved in maize resistance to gray leaf spot.

    Science.gov (United States)

    Xu, Ling; Zhang, Yan; Shao, Siquan; Chen, Wei; Tan, Jing; Zhu, Mang; Zhong, Tao; Fan, Xingming; Xu, Mingliang

    2014-08-31

    Gray leaf spot (GLS) caused by Cercospora zeae-maydis (Czm) or Cercospora zeina (Cz) is a devastating maize disease and results in substantial yield reductions worldwide. GLS resistance is a quantitatively inherited trait. The development and cultivation of GLS-resistant maize hybrids are the most cost-effective and efficient ways to control this disease. We previously detected a major GLS resistance QTL, qRgls2, in bin 5.03-04, which spans the whole centromere of chromosome 5 encompassing a physical distance of ~110-Mb. With advanced backcross populations derived from the cross between the resistant Y32 and susceptible Q11 inbred lines, a sequential recombinant-derived progeny testing strategy was adapted to fine map qRgls2. We narrowed the region of qRgls2 from an initial ~110-Mb to an interval of ~1-Mb, flanked by the markers G346 and DD11. qRgls2 showed predominantly additive genetic effects and significantly increased the resistance percentage by 20.6 to 24.6% across multiple generations. A total of 15 genes were predicted in the mapped region according to the 5b.60 annotation of the maize B73 genome v2. Two pieces of the mapped qRgls2 region shared collinearity with two distant segments on maize chromosome 4. qRgls2, a major QTL involved in GLS resistance, was mapped to a ~1-Mb region close to the centromere of chromosome 5. There are 15 predicted genes in the mapped region. It is assumed that qRgls2 could be widely used to improve maize resistance to GLS.

  6. Benefits and harms in clinical trials of duloxetine for treatment of major depressive disorder

    DEFF Research Database (Denmark)

    Maund, Emma; Tendal, Britta; Hróbjartsson, Asbjørn

    2014-01-01

    , with respect to benefits and major harms. DESIGN: Data on primary efficacy analysis and major harms extracted from each data source and compared. SETTING: Nine randomised placebo controlled trials of duloxetine (total 2878 patients) submitted to the European Medicines Agency (EMA) for marketing approval.......gov and the manufacturer's online clinical trial registry were searched for trial results. RESULTS: Clinical study reports fully described the primary efficacy analysis and major harms (deaths (including suicides), suicide attempts, serious adverse events, and discontinuations because of adverse events). There were minor......, respectively. We also found publication bias in relation to beneficial effects. CONCLUSION: Clinical study reports contained extensive data on major harms that were unavailable in journal articles and in trial registry reports. There were inconsistencies between protocols and clinical study reports and within...

  7. EGFR is not a major driver for osteosarcoma cell growth in vitro but contributes to starvation and chemotherapy resistance.

    Science.gov (United States)

    Sevelda, Florian; Mayr, Lisa; Kubista, Bernd; Lötsch, Daniela; van Schoonhoven, Sushilla; Windhager, Reinhard; Pirker, Christine; Micksche, Michael; Berger, Walter

    2015-11-02

    Enhanced signalling via the epidermal growth factor receptor (EGFR) is a hallmark of multiple human carcinomas. However, in recent years data have accumulated that EGFR might also be hyperactivated in human sarcomas. Aim of this study was to investigate the influence of EGFR inhibition on cell viability and its interaction with chemotherapy response in osteosarcoma cell lines. We have investigated a panel of human osteosarcoma cell lines regarding EGFR expression and downstream signalling. To test its potential applicability as therapeutic target, inhibition of EGFR by gefitinib was combined with osteosarcoma chemotherapeutics and cell viability, migration, and cell death assays were performed. Osteosarcoma cells expressed distinctly differing levels of functional EGFR reaching in some cases high amounts. Functionality of EGFR in osteosarcoma cells was proven by EGF-mediated activation of both MAPK and PI3K/AKT pathway (determined by phosphorylation of ERK1/2, AKT, S6, and GSK3β). The EGFR-specific inhibitor gefitinib blocked EGF-mediated downstream signal activation. At standard in vitro culture conditions, clinically achievable gefitinib doses demonstrated only limited cytotoxic activity, however, significantly reduced long-term colony formation and cell migration. In contrast, under serum-starvation conditions active gefitinib doses were distinctly reduced while EGF promoted starvation survival. Importantly, gefitinib significantly supported the anti-osteosarcoma activities of doxorubicin and methotrexate regarding cell survival and migratory potential. Our data suggest that EGFR is not a major driver for osteosarcoma cell growth but contributes to starvation- and chemotherapy-induced stress survival. Consequently, combination approaches including EGFR inhibitors should be evaluated for treatment of high-grade osteosarcoma patients.

  8. The effect of interpersonal psychotherapy and other psychodynamic therapies versus 'treatment as usual' in patients with major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Janus Christian Jakobsen

    Full Text Available BACKGROUND: Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Interpersonal psychotherapy and other psychodynamic therapies may be effective interventions for major depressive disorder, but the effects have only had limited assessment in systematic reviews. METHODS/PRINCIPAL FINDINGS: Cochrane systematic review methodology with meta-analysis and trial sequential analysis of randomized trials comparing the effect of psychodynamic therapies versus 'treatment as usual' for major depressive disorder. To be included the participants had to be older than 17 years with a primary diagnosis of major depressive disorder. Altogether, we included six trials randomizing a total of 648 participants. Five trials assessed 'interpersonal psychotherapy' and only one trial assessed 'psychodynamic psychotherapy'. All six trials had high risk of bias. Meta-analysis on all six trials showed that the psychodynamic interventions significantly reduced depressive symptoms on the 17-item Hamilton Rating Scale for Depression (mean difference -3.12 (95% confidence interval -4.39 to -1.86;P<0.00001, no heterogeneity compared with 'treatment as usual'. Trial sequential analysis confirmed this result. DISCUSSION: We did not find convincing evidence supporting or refuting the effect of interpersonal psychotherapy or psychodynamic therapy compared with 'treatment as usual' for patients with major depressive disorder. The potential beneficial effect seems small and effects on major outcomes are unknown. Randomized trials with low risk of systematic errors and low risk of random errors are needed.

  9. Resistance of Acanthamoeba Cysts to Disinfection Treatments Used in Health Care Settings▿

    Science.gov (United States)

    Coulon, Céline; Collignon, Anne; McDonnell, Gerald; Thomas, Vincent

    2010-01-01

    Free-living amoebae that belong to the genus Acanthamoeba are widespread in the environment, including water. They are responsible for human infections and can host pathogenic microorganisms. Under unfavorable conditions, they form cysts with high levels of resistance to disinfection methods, thus potentially representing a threat to public health. In the present study we evaluated the efficacies of various biocides against trophozoites and cysts of several Acanthamoeba strains. We demonstrated that disinfectant efficacy varied depending on the strains tested, with environmental strains demonstrating greater resistance than collection strains. Trophozoites were inactivated by all treatments except those using glutaraldehyde as an active compound: for these treatments, we observed resistance even after 30 min exposure. Cysts resisted many treatments, including certain conditions with glutaraldehyde and other biocides. Moist heat at 55°C was not efficient against cysts, whereas exposure at 65°C was. Several chemical formulations containing peracetic acid, hydrogen peroxide, or ortho-phthalaldehyde presented greater efficacy than glutaraldehyde, as did ethanol and sodium hypochlorite; however, some of these treatments required relatively long incubation times to achieve cyst inactivation. Amoebal cysts can be highly resistant to some high-level disinfectants, which has implications for clinical practice. These results highlight the need to consider the effective disinfection of protozoa in their vegetative and resistant forms due to their intrinsic resistance. This is important not only to prevent the transmission of protozoa themselves but also due to the risks associated with a range of microbial pathogens that are found to be associated intracellularly with these microorganisms. PMID:20519477

  10. Surgical and nonsurgical treatment of total rupture of the pectoralis major muscle in athletes: update and critical appraisal.

    Science.gov (United States)

    Kircher, Jörn; Ziskoven, Christoph; Patzer, Thilo; Zaps, Daniela; Bittersohl, Bernd; Krauspe, Rüdiger

    2010-10-11

    The complete rupture of the pectoralis major tendon is an uncommon injury but has become increasingly common among athletes in recent years. This may be due to a higher number of individuals taking part in high-impact sports and weightlifting as well as the use of anabolic substances, which can make muscles and tendons vulnerable to injury. In recent literature, there are only few recommendations to rely on conservative treatment alone, but there are a number of reports and case series recommending early surgical intervention. Comparing the results of the two treatment regimens, there is clear evidence for a superior outcome after surgical repair with better cosmesis, better functional results, regaining of muscle power, and return to sports compared with the conservative treatment. In summary, anatomic surgical repair is the treatment of choice for complete acute ruptures of the pectoralis major tendon or muscle in athletes.

  11. Molecular mapping of qBK1 WD , a major QTL for bakanae disease resistance in rice.

    Science.gov (United States)

    Lee, Sais-Beul; Hur, Yeon-Jae; Cho, Jun-Hyeon; Lee, Jong-Hee; Kim, Tae-Heon; Cho, Soo-Min; Song, You-Chun; Seo, Young-Su; Lee, Jungkwan; Kim, Tae-Sung; Park, Yong-Jin; Oh, Myung-Kyu; Park, Dong-Soo

    2018-01-10

    Bakanae or foot rot disease is a prominent disease of rice caused by Gibberella fujikuroi. This disease may infect rice plants from the pre-emergence stage to the mature stage. In recent years, raising rice seedlings in seed boxes for mechanical transplanting has increased the incidence of many seedling diseases; only a few rice varieties have been reported to exhibit resistance to bakanae disease. In this study, we attempted to identify quantitative trait loci (QTLs) conferring bakanae disease resistance from the highly resistant japonica variety Wonseadaesoo. A primary QTL study using the genotypes/phenotypes of the recombinant inbred lines (RILs) indicated that the locus qBK1 WD conferring resistance to bakanae disease from Wonseadaesoo was located in a 1.59 Mb interval delimited on the physical map between chr01_13542347 (13.54 Mb) and chr01_15132528 (15.13 Mb). The log of odds (LOD) score of qBK1 WD was 8.29, accounting for 20.2% of the total phenotypic variation. We further identified a gene pyramiding effect of two QTLs, qBK WD and previously developed qBK1. The mean proportion of healthy plant for 31 F 4 RILs that had no resistance genes was 35.3%, which was similar to that of the susceptible check variety Ilpum. The proportion of healthy plants for the lines with only qBK WD or qBK1 was 66.1% and 55.5%, respectively, which was significantly higher than that of the lines without resistance genes and that of Ilpum. The mean proportion of the healthy plant for 15 F 4 RILs harboring both qBK WD and qBK1 was 80.2%, which was significantly higher than that of the lines with only qBK WD or qBK1. Introducing qBK WD or pyramiding the QTLs qBK WD and qBK1 could provide effective tools for breeding rice with bakanae disease resistance. To our knowledge, this is the first report on a gene pyramiding effect that provides higher resistance against bakanae disease.

  12. Adjunctive treatment with transcranial magnetic stimulation in treatment resistant depression: a randomized, double-blind, sham-controlled study

    Directory of Open Access Journals (Sweden)

    Qiang LIU

    2011-02-01

    Full Text Available Background: High-frequency repetitive transcranial magnetic stimulation (rTMS to the left prefrontal cortex is a promising antidepressant treatment but the appropriate duration of treatment andits effect on cognitive symptoms in treatment resistant patients is uncertain.Hypotheis: Patients with treatment resistant depression on standard antidepressant medication who receive four weeks of adjunctive treatment with high-frequency rTMS to the left prefrontal cortex will have better clinical outcomes and better cognitive functioning than those who receive sham rTMS treatments.Methods: Thirty patients with treatment resistant depression (defined as failure to respond to two or more antidepressants of different classes administered for at least 6 weeks at or above two-thirds of the recommended maximum dose receiving selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors wererandomly assigned to receive adjundive treatment with either real rTMS (n=15 or sham rTMS (n=15 5 times a week for 4 conseculive weeks. Blinded pre-post evaluations were conducted using the 17-item Hamilton Depression Rating Scale (HAMD, the Montgomery-Asberg Depression Rating Scale (MADRS, the severity of illness measure from the Clinical Global Impression Rating scale(CGI-S, the Wechsler Adult Intelligence ScaIe (WAIS, the Wechsler Memory Scale (WMS, and the Wisconsjn Card Sorting Test(WC5T.Results:14 subjects from each group completed the study. There was no significant difference in the HAMD total scores between the two groups after 2 weeks of treatment but after 4 weeks of treatment the mean percentage drop in the HAMD total score was significantly greater in the real rTMS group (49%, SD=19% than in the sham rTMS group(29%, SD=25%, with a mean difference of 20% [95%CI=3%-37%;t26=2.42; P=0.023]. At 4 weeks the mean (SD reduction in the MADRS total score was also greater in the real rTMS group [47%(23% vs 16%(40

  13. Impact of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in children in a low resistance prevalence setting

    Science.gov (United States)

    Brandtzaeg, Petter; Høiby, E. Arne; Bohlin, Jon; Samuelsen, Ørjan; Steinbakk, Martin; Abrahamsen, Tore G.; Müller, Fredrik; Gammelsrud, Karianne Wiger

    2017-01-01

    We prospectively studied the consequences of extensive antibiotic treatment on faecal carriage of antibiotic-resistant enterobacteria in a cohort of children with cystic fibrosis (CF) and a cohort of children with cancer compared to healthy children with no or low antibiotic exposure. The study was conducted in Norway in a low resistance prevalence setting. Sixty longitudinally collected faecal samples from children with CF (n = 32), 88 samples from children with cancer (n = 45) and 127 samples from healthy children (n = 70) were examined. A direct MIC-gradient strip method was used to detect resistant Enterobacteriaceae by applying Etest strips directly onto agar-plates swabbed with faecal samples. Whole genome sequencing (WGS) data were analysed to identify resistance mechanisms in 28 multidrug-resistant Escherichia coli isolates. The prevalence of resistance to third-generation cephalosporins, gentamicin and ciprofloxacin was low in all the study groups. At inclusion the prevalence of ampicillin-resistant E. coli and trimethoprim-sulfamethoxazole-resistant E. coli in the CF group compared to healthy controls was 58.6% vs. 28.4% (p = 0.005) and 48.3% vs. 14.9% (p = 0.001), respectively, with a similar prevalence at the end of the study. The prevalence of resistant enterobacteria was not significantly different in the children with cancer compared to the healthy children, not even at the end of the study when the children with cancer had been treated with repeated courses of broad-spectrum antibiotics. Children with cancer were mainly treated with intravenous antibiotics, while the CF group mainly received peroral treatment. Our observations indicate that the mode of administration of antibiotics and the general level of antimicrobial resistance in the community may have an impact on emergence of resistance in intestinal enterobacteria during antibiotic treatment. The WGS analyses detected acquired resistance genes and/or chromosomal mutations that explained the

  14. Mapping and pyramiding of two major genes for resistance to the brown planthopper (Nilaparvata lugens [Stål]) in the rice cultivar ADR52.

    Science.gov (United States)

    Myint, Khin Khin Marlar; Fujita, Daisuke; Matsumura, Masaya; Sonoda, Tomohiro; Yoshimura, Atsushi; Yasui, Hideshi

    2012-02-01

    The brown planthopper (BPH), Nilaparvata lugens (Stål), is one of the most serious and destructive pests of rice, and can be found throughout the rice-growing areas of Asia. To date, more than 24 major BPH-resistance genes have been reported in several Oryza sativa ssp. indica cultivars and wild relatives. Here, we report the genetic basis of the high level of BPH resistance derived from an Indian rice cultivar, ADR52, which was previously identified as resistant to the whitebacked planthopper (Sogatella furcifera [Horváth]). An F(2) population derived from a cross between ADR52 and a susceptible cultivar, Taichung 65 (T65), was used for quantitative trait locus (QTL) analysis. Antibiosis testing showed that multiple loci controlled the high level of BPH resistance in this F(2) population. Further linkage analysis using backcross populations resulted in the identification of BPH-resistance (antibiosis) gene loci from ADR52. BPH25 co-segregated with marker S00310 on the distal end of the short arm of chromosome 6, and BPH26 co-segregated with marker RM5479 on the long arm of chromosome 12. To characterize the virulence of the most recently migrated BPH strain in Japan, preliminary near-isogenic lines (pre-NILs) and a preliminary pyramided line (pre-PYL) carrying BPH25 and BPH26 were evaluated. Although both pre-NILs were susceptible to the virulent BPH strain, the pre-PYL exhibited a high level of resistance. The pyramiding of resistance genes is therefore likely to be effective for increasing the durability of resistance against the new virulent BPH strain in Japan.

  15. Identification of QTLs for resistance to sclerotinia stem rot and BnaC.IGMT5.a as a candidate gene of the major resistant QTL SRC6 in Brassica napus.

    Directory of Open Access Journals (Sweden)

    Jian Wu

    Full Text Available Stem rot caused by Sclerotinia sclerotiorum in many important dicotyledonous crops, including oilseed rape (Brassica napus, is one of the most devastating fungal diseases and imposes huge yield loss each year worldwide. Currently, breeding for Sclerotinia resistance in B. napus, as in other crops, can only rely on germplasms with quantitative resistance genes. Thus, the identification of quantitative trait locus (QTL for S. sclerotiorum resistance/tolerance in this crop holds immediate promise for the genetic improvement of the disease resistance. In this study, ten QTLs for stem resistance (SR at the mature plant stage and three QTLs for leaf resistance (LR at the seedling stage in multiple environments were mapped on nine linkage groups (LGs of a whole genome map for B. napus constructed with SSR markers. Two major QTLs, LRA9 on LG A9 and SRC6 on LG C6, were repeatedly detected across all environments and explained 8.54-15.86% and 29.01%-32.61% of the phenotypic variations, respectively. Genotypes containing resistant SRC6 or LRA9 allele showed a significant reduction in disease lesion after pathogen infection. Comparative mapping with Arabidopsis and data mining from previous gene profiling experiments identified that the Arabidopsis homologous gene of IGMT5 (At1g76790 was related to the SRC6 locus. Four copies of the IGMT5 gene in B. napus were isolated through homologous cloning, among which, only BnaC.IGMT5.a showed a polymorphism between parental lines and can be associated with the SRC6. Furthermore, two parental lines exhibited a differential expression pattern of the BnaC.IGMT5.a gene in responding to pathogen inoculation. Thus, our data suggested that BnaC.IGMT5.a was very likely a candidate gene of this major resistance QTL.

  16. Drug resistance pattern of M. tuberculosis in category II treatment failure pulmonary tuberculosis patients

    Directory of Open Access Journals (Sweden)

    Fahmida Rahman

    2013-01-01

    Full Text Available This study was designed to determine the extent of drug resistance of M. tuberculosis (MTB isolated from category II treatment failure pulmonary tuberculosis (PTB patients. A total of 100 Ziehl-Neelsen (Z-N smear positive category II failure PTB patients were included in this study. Sputum culture was done in Lowenstein-Jensen (L-J media. Conventional proportion method on Lowenstein-Jensen (L-J media was used to determine the drug susceptibility of M. tuberculosis to isoniazid (INH, rifampicin (RMP, ofloxacin (OFX and kanamycin (KA. Out of 100 sputum samples, a total of 87 samples were positive by culture. Drug susceptibility test (DST revealed that 82 (94.25% isolates were resistant to one or more anti -TB drugs. Resistance to isoniazide (INH, rifampicin (RMP, ofloxacin (OFX and kanamycin (KA was 94.25%, 82.75%, 29.90% and 3.45% respectively. Among these isolates, 79.31% and 3.45% isolates were multi-drug resistant (MDR and extended drug resistant (XDR M. tuberculosis respectively. High rate of anti-tubercular drug resistance was observed among the category II treatment failure TB patients. Ibrahim Med. Coll. J. 2013; 7(1: 9-11

  17. Competitive release of drug resistance following drug treatment of mixed Plasmodium chabaudi infections.

    Science.gov (United States)

    de Roode, Jacobus C; Culleton, Richard; Bell, Andrew S; Read, Andrew F

    2004-09-14

    Malaria infections are often genetically diverse, potentially leading to competition between co-infecting strains. Such competition is of key importance in the spread of drug resistance. The effects of drug treatment on within-host competition were studied using the rodent malaria Plasmodium chabaudi. Mice were infected simultaneously with a drug-resistant and a drug-sensitive clone and were then either drug-treated or left untreated. Transmission was assessed by feeding mice to Anopheles stephensi mosquitoes. In the absence of drugs, the sensitive clone competitively suppressed the resistant clone; this resulted in lower asexual parasite densities and also reduced transmission to the mosquito vector. Drug treatment, however, allowed the resistant clone to fill the ecological space emptied by the removal of the sensitive clone, allowing it to transmit as well as it would have done in the absence of competition. These results show that under drug pressure, resistant strains can have two advantages: (1) they survive better than sensitive strains and (2) they can exploit the opportunities presented by the removal of their competitors. When mixed infections are common, such effects could increase the spread of drug resistance.

  18. Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial.

    Science.gov (United States)

    Bomback, Andrew S; Canetta, Pietro A; Beck, Laurence H; Ayalon, Rivka; Radhakrishnan, Jai; Appel, Gerald B

    2012-01-01

    Adrenocorticotropic hormone (ACTH) has shown promising results in glomerular diseases resistant to conventional therapies, but the reported data have solely been from retrospective, observational studies. In this prospective, open-label study (NCT01129284), 15 subjects with resistant glomerular diseases were treated with ACTH gel (80 units subcutaneously twice weekly) for 6 months. Resistant membranous nephropathy (MN), minimal change disease (MCD), and focal segmental glomerulosclerosis (FSGS) were defined as failure to achieve sustained remission of proteinuria off immunosuppressive therapy with at least 2 treatment regimens; resistant IgA nephropathy was defined as >1 g/g urine protein:creatinine ratio despite maximally tolerated RAAS blockade. Remission was defined as stable or improved renal function with ≥50% reduction in proteinuria to 50% reductions in proteinuria while on ACTH, with proteinuria consistently <1 g/g by 6 months. Three of 15 subjects reported significant steroid-like adverse effects with ACTH, including weight gain and hyperglycemia, prompting early termination of therapy without any clinical response. ACTH gel is a promising treatment for resistant glomerular diseases and should be studied further in controlled trials against currently available therapies for resistant disease. Copyright © 2012 S. Karger AG, Basel.

  19. Diversity of fecal coliforms and their antimicrobial resistance patterns in wastewater treatment model plant.

    Science.gov (United States)

    Luczkiewicz, A; Fudala-Ksiazek, S; Jankowska, K; Quant, B; Olańczuk-Neyman, K

    2010-01-01

    The occurrence of resistance patterns among wastewater fecal coliforms was determined in the study. Susceptibility of the isolates was tested against 19 antimicrobial agents: aminoglycosides, aztreonam, carbapenems, cephalosporines, beta-lactam/beta-lactamase inhibitors, penicillines, tetracycline, trimethoprim/sulfamethoxazole, and fluoroquinolones. Additionally the removal of resistant isolates was evaluated in the laboratory-scale wastewater treatment model plant (M-WWTP), continuously supplied with the wastewater obtained from the full-scale WWTP. Number of fecal coliforms in raw (after mechanical treatment) and treated wastewater, as well as in aerobic chamber effluent was determined using selective medium. The selected strains were identified and examined for antibiotic resistance using Phoenix Automated Microbiology System (BD Biosciences, USA). The strains were identified as Escherichia coli (n=222), Klebsiella pneumoniae ssp. ozaenae (n=9), and Pantoea agglomerans (n=1). The isolate of P. agglomerans as well as 48% of E. coli isolates were sensitive to all antimicrobials tested. The most frequent resistance patterns were found for ampicillin: 100% of K. pneumoniae ssp. ozaenae and 41% of E. coli isolates. Among E. coli isolates 12% was regarded as multiple antimicrobial resistant (MAR). In the studied M-WWTP, the applied activated sludge processes reduced considerably the number of fecal coliforms, but increased the ratio of antimicrobial-resistant E. coli isolates to sensitive ones, especially among strains with MAR patterns.

  20. Surgical and nonsurgical treatment of total rupture of the pectoralis major muscle in athletes: update and critical appraisal

    Directory of Open Access Journals (Sweden)

    Jörn Kircher

    2010-10-01

    Full Text Available Jörn Kircher, Christoph Ziskoven, Thilo Patzer, Daniela Zaps, Bernd Bittersohl, Rüdiger KrauspeUniversity Hospital, Orthopaedic Department, Heinrich-Heine University Düsseldorf, Düsseldorf, GermanyAbstract: The complete rupture of the pectoralis major tendon is an uncommon injury but has become increasingly common among athletes in recent years. This may be due to a higher number of individuals taking part in high-impact sports and weightlifting as well as the use of anabolic substances, which can make muscles and tendons vulnerable to injury. In recent literature, there are only few recommendations to rely on conservative treatment alone, but there are a number of reports and case series recommending early surgical intervention. Comparing the results of the two treatment regimens, there is clear evidence for a superior outcome after surgical repair with better cosmesis, better functional results, regaining of muscle power, and return to sports compared with the conservative treatment. In summary, anatomic surgical repair is the treatment of choice for complete acute ruptures of the pectoralis major tendon or muscle in athletes.Keywords: pectoralis major, rupture, athlete, conservative treatment, surgical treatment, steroid, tendon, sports injury

  1. Experience with tofacitinib in the treatment of resistant rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    A. R. Babaeva

    2015-01-01

    seroconversion phenomenon in one female patient.Conclusion. The findings allow TOFA to be recommended for the treatment of RA in case of the inefficiency of standard disease-modifying agents or contraindications to their use.

  2. Resistant hypertension.

    Science.gov (United States)

    Wei, Fang-Fei; Zhang, Zhen-Yu; Huang, Qi-Fang; Yang, Wen-Yi; Staessen, Jan A

    2018-06-15

    The publication of the first non-randomised proof-of-concept trial of renal denervation as a treatment modality in treatment-resistant hypertension set the stage for a search for novel devices with the expectation that technology would reduce the burden of hypertension by reducing or eliminating the costly and lifelong use of blood pressure lowering medications. As we demonstrate in this review, this idea so attractive to manufacturers and invasive cardiologists and radiologists overlooked decades of careful pathophysiological research in a disease, which still remains enigmatic but remains the major cause of cardiovascular mortality worldwide. To make our point, we first reviewed the prevalence and risks associated with treatment-resistant hypertension. Next, we highlighted the key points required for the diagnosis of treatment-resistant hypertension, including the recording of the ambulatory blood pressure and the assessment of adherence to medication. Finally, we summarised new insights in the management of treatment-resistant hypertension by medication and devices and in the future research. Throughout our review, we focused on new evidence became available since 2013. Our conclusion is that optimising medical treatment based on simple algorithms remains the state of the art in treatment-resistant hypertension.

  3. Effect of thiazolidinedione treatment on resistin levels in insulin resistant sprague dawley rats

    International Nuclear Information System (INIS)

    Yousaf, I.; Hameed, W.; Rajput, T.A.

    2015-01-01

    Insulin resistance is manifested by decreased effect of fixed quantity of insulin on glucose metabolism leading to type 2 diabetes mellitus. Visceral obesity has been positively correlated with insulin resistance but its mechanism is not fully defined. Insulin resistance may be the consequence of adipocytokines including visfatin and resistin. This study was designed to see the effect of thiazolidinediones on levels of resistin in insulin resistant rats. Methods: Ninety Sprague Dawley rats were randomly divided into three groups. Group I served as control. Rats in Group II and III were made insulin resistant diabetics. Group III was treated with rosiglitazone after development of diabetes. Plasma glucose, serum triglycerides, HDL, TG:HDL ratio and serum resistin levels were analysed. Results: Body weight and plasma glucose were significantly increased (p<0.05) along with TG:HDL ratio (p<0.05) in group II and group III at the end of 4th week. Serum resistin levels also increased significantly (p<0.05) in group II and III at the end of 4th week. Treatment of group III with rosiglitazone led to improvement in insulin resistance with decrease in serum resistin levels (p<0.05). Conclusion: Increased serum resistin level indicates insulin resistance and impending hyperglycaemia. Thiazolidinediones augment sensitivity of insulin to restore normoglycaemia by decreasing serum resistin level. (author)

  4. Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

    Science.gov (United States)

    Lee, Chang-Ro; Lee, Jung Hun; Park, Moonhee; Park, Kwang Seung; Bae, Il Kwon; Kim, Young Bae; Cha, Chang-Jun; Jeong, Byeong Chul; Lee, Sang Hee

    2017-01-01

    Acinetobacter baumannii is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of infections and outbreaks caused by multi-drug resistant A. baumannii, few antibiotics are effective for treating infections caused by this pathogen. To overcome this problem, knowledge of the pathogenesis and antibiotic resistance mechanisms of A. baumannii is important. In this review, we summarize current studies on the virulence factors that contribute to A. baumannii pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, and protein secretion systems. Mechanisms of antibiotic resistance of this organism, including acquirement of β-lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites, are also discussed. Lastly, novel prospective treatment options for infections caused by multi-drug resistant A. baumannii are summarized. PMID:28348979

  5. Pharmacokinetic-Pharmacodynamic Model To Evaluate Intramuscular Tetracycline Treatment Protocols To Prevent Antimicrobial Resistance in Pigs

    DEFF Research Database (Denmark)

    Ahmad, Amais; Græsbøll, Kaare; Christiansen, Lasse Engbo

    2015-01-01

    High instances of antimicrobial resistance are linked to both routine and excessive antimicrobial use, but excessive or inappropriate use represents an unnecessary risk. The competitive growth advantages of resistant bacteria may be amplified by the strain dynamics; in particular, the extent...... to which resistant strains outcompete susceptible strains under antimicrobial pressure may depend not only on the antimicrobial treatment strategies but also on the epidemiological parameters, such as the composition of the bacterial strains in a pig. This study evaluated how variation in the dosing...... protocol for intramuscular administration of tetracycline and the composition of bacterial strains in a pig affect the level of resistance in the intestine of a pig. Predictions were generated by a mathematical model of competitive growth of Escherichia coli strains in pigs under specified plasma...

  6. GENE EXPRESSION DYNAMICS IN PATIENTS WITH SEVERE THERAPY-RESISTANT ASTHMA DURING TREATMENT PERIOD

    Directory of Open Access Journals (Sweden)

    Ye. S. Kulikov

    2014-01-01

    Full Text Available Introduction: The leading mechanisms and causes of severe therapy resistant asthma are poorly understood. The aim of this study was to define global patterns of gene expression in adults with severe therapy-resistant asthma in dynamic during treatment period.Methods: Performed 24-week prospective interventional study in parallel groups. Severe asthma patients was aposterior divided at therapy sensitive and resistant patients according to ATS criteria. Global transcriptome profile was characterized using the Affymetrix HuGene ST1.0 chip. Cluster analysis was performed.Results and conclusion: According to our data several mechanisms of therapy resistance may be considered: increased levels of nitric oxide and beta2-agonists nitration, dysregulation of endogenous steroids secretion and involvement in the pathogenesis of Staphylococcus aureus. Absence of suppression of gene expression KEGG-pathway “asthma" may reflect the low efficiency or long period of anti-inflammatory therapy effect realization.

  7. Pharmacokinetic-Pharmacodynamic Model To Evaluate Intramuscular Tetracycline Treatment Protocols To Prevent Antimicrobial Resistance in Pigs

    DEFF Research Database (Denmark)

    Ahmad, Amais; Græsbøll, Kaare; Christiansen, Lasse Engbo

    2015-01-01

    protocol for intramuscular administration of tetracycline and the composition of bacterial strains in a pig affect the level of resistance in the intestine of a pig. Predictions were generated by a mathematical model of competitive growth of Escherichia coli strains in pigs under specified plasma......High instances of antimicrobial resistance are linked to both routine and excessive antimicrobial use, but excessive or inappropriate use represents an unnecessary risk. The competitive growth advantages of resistant bacteria may be amplified by the strain dynamics; in particular, the extent...... to which resistant strains outcompete susceptible strains under antimicrobial pressure may depend not only on the antimicrobial treatment strategies but also on the epidemiological parameters, such as the composition of the bacterial strains in a pig. This study evaluated how variation in the dosing...

  8. Predictors of poor retention on antiretroviral therapy as a major HIV drug resistance early warning indicator in Cameroon: results from a nationwide systematic random sampling

    Directory of Open Access Journals (Sweden)

    Serge Clotaire Billong

    2016-11-01

    Full Text Available Abstract Background Retention on lifelong antiretroviral therapy (ART is essential in sustaining treatment success while preventing HIV drug resistance (HIVDR, especially in resource-limited settings (RLS. In an era of rising numbers of patients on ART, mastering patients in care is becoming more strategic for programmatic interventions. Due to lapses and uncertainty with the current WHO sampling approach in Cameroon, we thus aimed to ascertain the national performance of, and determinants in, retention on ART at 12 months. Methods Using a systematic random sampling, a survey was conducted in the ten regions (56 sites of Cameroon, within the “reporting period” of October 2013–November 2014, enrolling 5005 eligible adults and children. Performance in retention on ART at 12 months was interpreted following the definition of HIVDR early warning indicator: excellent (>85%, fair (85–75%, poor (<75; and factors with p-value < 0.01 were considered statistically significant. Results Majority (74.4% of patients were in urban settings, and 50.9% were managed in reference treatment centres. Nationwide, retention on ART at 12 months was 60.4% (2023/3349; only six sites and one region achieved acceptable performances. Retention performance varied in reference treatment centres (54.2% vs. management units (66.8%, p < 0.0001; male (57.1% vs. women (62.0%, p = 0.007; and with WHO clinical stage I (63.3% vs. other stages (55.6%, p = 0.007; but neither for age (adults [60.3%] vs. children [58.8%], p = 0.730 nor for immune status (CD4351–500 [65.9%] vs. other CD4-staging [59.86%], p = 0.077. Conclusions Poor retention in care, within 12 months of ART initiation, urges active search for lost-to-follow-up targeting preferentially male and symptomatic patients, especially within reference ART clinics. Such sampling strategy could be further strengthened for informed ART monitoring and HIVDR prevention perspectives.

  9. Effects of oxygen plasma treatment power on Aramid fiber III/BMI composite humidity resistance properties

    Science.gov (United States)

    Wang, Jing; Shi, Chen; Feng, Jiayue; Long, Xi; Meng, Lingzhi; Ren, Hang

    2018-01-01

    The effects of oxygen plasma treatment power on Aramid Fiber III chemical structure and its reinforced bismaleimides (BMI) composite humidity resistance properties were investigated in this work. The aramid fiber III chemical structure under different plasma treatment power were measured by FTIR. The composite bending strength and interlinear shear strength with different plasma treatment power before and after absorption water were tested respectively. The composite rupture morphology was observed by SEM. The FTIR results showed that oxygen plasma treatment do not change the fiber bulk chemical structure. The composite humidity resistance of bending strength and interlinear shear strength are similar for untreated and plasma treated samples. The retention rate of composite bending strength and interlinear shear strength are about 75% and 94%, respectively. The composite rupture mode turns to be the fiber failure after water absorption.

  10. Mortality and Self-Harm in Association With Clozapine in Treatment-Resistant Schizophrenia

    DEFF Research Database (Denmark)

    Wimberley, Theresa; Maccabe, James H; Laursen, Thomas M

    2017-01-01

    Objective: This study evaluated rates of all-cause mortality and self-harm in association with clozapine treatment in individuals with treatment-resistant schizophrenia. Method: A population-based cohort of 2,370 individuals with treatment-resistant schizophrenia after Jan. 1, 1996, was followed...... until death, first episode of self-harm, emigration, or June 1, 2013. Time to all-cause death and time tofirst episode of self-harm were analyzed in Cox regression models with timevarying treatment, adjusted for clinical and sociodemographic covariates. Results: The rate of all-cause mortality...... with other antipsychotics (hazard ratio: 1.45, 95% CI: 0.86-2.45). Excess mortality was observed in the year after clozapine discontinuation (hazard ratio: 2.65, 95% CI: 1.47-4.78). The rate of self-harm was higher for nonclozapine antipsychotics than for clozapine (hazard ratio: 1.36, 95% CI: 1...

  11. Response after Infection-Associated Rise in Clozapine Levels in Treatment-Resistant Schizoaffective Disorder

    Directory of Open Access Journals (Sweden)

    Nina H. Grootendorst-van Mil

    2018-01-01

    Full Text Available The clinical management of patients with treatment-resistant psychotic disorders is still challenging despite years of extensive research. If first-line antipsychotic treatment proves ineffective, clozapine is considered golden standard. Herein, we report on a patient with schizoaffective disorder that initially showed no response to treatment with clozapine and ECT and therefore reached a therapeutic dead end. After an unintentional exposure to supratherapeutic clozapine levels, related to a pneumonia, a significant and persistent reduction of psychotic symptoms occurred. The report suggests a careful reevaluation of the clozapine dose in cases of treatment-resistant psychotic disorders with failed trials of clozapine. Further increase of dose may prove efficacious, although side effects should be closely monitored. Research to determine the upper threshold of clozapine for antipsychotic efficacy is warranted.

  12. Influence of Ultrasound Treatment on Cavitation Erosion Resistance of AlSi7 Alloy

    Directory of Open Access Journals (Sweden)

    Annalisa Pola

    2017-03-01

    Full Text Available Ultrasound treatment of liquid aluminum alloys is known to improve mechanical properties of castings. Aluminum foundry alloys are frequently used for production of parts that undergo severe cavitation erosion phenomena during service. In this paper, the effect of the ultrasound treatment on cavitation erosion resistance of AlSi7 alloy was assessed and compared to that of conventionally cast samples. Cavitation erosion tests were performed according to ASTM G32 standard on as-cast and heat treated castings. The response of the alloy in each condition was investigated by measuring the mass loss as a function of cavitation time and by analyzing the damaged surfaces by means of optical and scanning electron microscope. It was pointed out that the ultrasound treatment increases the cavitation erosion resistance of the alloy, as a consequence of the higher chemical and microstructural homogeneity, the finer grains and primary particles and the refined structure of the eutectic induced by the treatment itself.

  13. Influence of Ultrasound Treatment on Cavitation Erosion Resistance of AlSi7 Alloy.

    Science.gov (United States)

    Pola, Annalisa; Montesano, Lorenzo; Tocci, Marialaura; La Vecchia, Giovina Marina

    2017-03-03

    Ultrasound treatment of liquid aluminum alloys is known to improve mechanical properties of castings. Aluminum foundry alloys are frequently used for production of parts that undergo severe cavitation erosion phenomena during service. In this paper, the effect of the ultrasound treatment on cavitation erosion resistance of AlSi7 alloy was assessed and compared to that of conventionally cast samples. Cavitation erosion tests were performed according to ASTM G32 standard on as-cast and heat treated castings. The response of the alloy in each condition was investigated by measuring the mass loss as a function of cavitation time and by analyzing the damaged surfaces by means of optical and scanning electron microscope. It was pointed out that the ultrasound treatment increases the cavitation erosion resistance of the alloy, as a consequence of the higher chemical and microstructural homogeneity, the finer grains and primary particles and the refined structure of the eutectic induced by the treatment itself.

  14. Treatment efficacy, treatment failures and selection of macrolide resistance in patients with high load of Mycoplasma genitalium during treatment of male urethritis with josamycin.

    Science.gov (United States)

    Guschin, Alexander; Ryzhikh, Pavel; Rumyantseva, Tatiana; Gomberg, Mikhail; Unemo, Magnus

    2015-02-03

    Azithromycin has been widely used for Mycoplasma genitalium treatment internationally. However, the eradication efficacy has substantially declined recent decade. In Russia, josamycin (another macrolide) is the recommended first-line treatment for M. genitalium infections, however, no data regarding treatment efficacy with josamycin and resistance in M. genitalium infections have been internationally published. We examined the M. genitalium prevalence in males attending an STI clinic in Moscow, Russia from December 2006 to January 2008, investigated treatment efficacy with josamycin in male urethritis, and monitored the M. genitalium DNA eradication dynamics and selection of macrolide resistance in M. genitalium during this treatment. Microscopy and real-time PCRs were used to diagnose urethritis and non-viral STIs, respectively, in males (n = 320). M. genitalium positive patients were treated with recommended josamycin regimen and treatment efficacy was monitored using quantitative real-time PCR. Macrolide resistance mutations were identified using sequencing of the 23S rRNA gene. Forty-seven (14.7%) males were positive for M. genitalium only and most (85.1%) of these had symptoms and signs of urethritis. Forty-six (97.9%) males agreed to participate in the treatment efficacy monitoring. All the pre-treatment M. genitalium specimens had wild-type 23S rRNA. The elimination of M. genitalium DNA was substantially faster in patients with lower pre-treatment M. genitalium load, and the total eradication rate was 43/46 (93.5%). Of the six patients with high pre-treatment M. genitalium load, three (50%) remained positive post-treatment and these positive specimens contained macrolide resistance mutations in the 23S rRNA gene, i.e., A2059G (n = 2) and A2062G (n = 1). M. genitalium was a frequent cause of male urethritis in Moscow, Russia. The pre-treatment M. genitalium load might be an effective predictor of eradication efficacy with macrolides (and possibly

  15. Posttraumatic stress disorder (PTSD) in children after paediatric intensive care treatment compared to children who survived a major fire disaster

    NARCIS (Netherlands)

    Bronner, M.B.; Knoester, H.; Bos, AP; Last, B.F.; Grootenhuis, M.A.

    2008-01-01

    Background: The goals were to determine the presence of posttraumatic stress disorder (PTSD) in children after paediatric intensive care treatment, to identify risk factors for PTSD, and to compare this data with data from a major fire disaster in the Netherlands. Methods: Children completed the

  16. The metabolic syndrome and related characteristics in major depression: inpatients and outpatients compared metabolic differences across treatment settings

    NARCIS (Netherlands)

    Luppino, F.S.; Bouvy, P.F.; Giltay, E.J.; Penninx, B.W.J.H.; Zitman, F. G.

    2014-01-01

    Objective: We aimed to systematically compare patients with major depressive disorder from three different treatment settings (a primary care outpatient, a secondary care outpatient and one inpatient sample), with regard to metabolic syndrome (MetSyn) prevalences, individual MetSyn components and

  17. The metabolic syndrome and related characteristics in major depression : inpatients and outpatients compared Metabolic differences across treatment settings

    NARCIS (Netherlands)

    Luppino, Floriana S.; Bouvy, Paul F.; Giltay, Erik J.; Penninx, Brenda W. J. H.; Zitman, Frans G.

    Objective: We aimed to systematically compare patients with major depressive disorder from three different treatment settings (a primary care outpatient, a secondary care outpatient and one inpatient sample), with regard to metabolic syndrome (MetSyn) prevalences, individual MetSyn components and

  18. Heat, hydrogen peroxide, and UV resistance of Bacillus subtilis spores with increased core water content and with or without major DNA-binding proteins

    International Nuclear Information System (INIS)

    Popham, D.L.; Sengupta, S.; Setlow, P.

    1995-01-01

    Spores of a Bacillus subtilis strain with an insertion mutation in the dacB gene, which codes for an enzyme involved in spore cortex biosynthesis, have a higher core water content than wild-type spores. Spores lacking the two major α/β-type small, acid-soluble proteins (SASP) (termed a α - β - spores) have the same core water content as do wild-type spores, but α - β - dacB spores had more core water than did dacB spores. The resistance of α - β - , α - β - dacB, dacB, and wild-type spores to dry and moist heat, hydrogen peroxide, and UV radiation has been determined, as has the role of DNA damage in spore killing by moist heat and hydrogen peroxide. These data (1) suggest that core water content has little if any role in spore UV resistance and are consistent with binding of α/β-type SASP to DNA being the major mechanism providing protection to spores from UV radiation; (2) suggest that binding of αβ-type SASP to DNA is the major mechanism unique to spores providing protection from dry heat; (3) suggest that spore resistance to moist heat and hydrogen peroxide is affected to a large degree by the core water content, as increased core water resulted in large decreases in spore resistance to these agents; and (4) indicate that since this decreased resistance (i.e., in dacB spores) is not associated with increased spore killing by DNA damage, spore DNA must normally be extremely well protected against such damage, presumably by the saturation of spore DNA by α/β-type SASP. 19 refs., 2 figs., 5 tabs

  19. Compressive Strength, Chloride Permeability, and Freeze-Thaw Resistance of MWNT Concretes under Different Chemical Treatments

    Directory of Open Access Journals (Sweden)

    Xingang Wang

    2014-01-01

    Full Text Available This study investigated compressive strength, chloride penetration, and freeze-thaw resistance of multiwalled carbon nanotube (MWNT concrete. More than 100 cylindrical specimens were used to assess test variables during sensitivity observations, including water-cement ratios (0.75, 0.5, and 0.4 and exposure to chemical agents (including gum arabic, propanol, ethanol, sodium polyacrylate, methylcellulose, sodium dodecyl sulfate, and silane. To determine the adequate sonication time for MWNT dispersal in water, the compressive strengths of MWNT concrete cylinders were measured after sonication times ranging from 2 to 24 minutes. The results demonstrated that the addition of MWNT can increase the compressive strength of concrete by up to 108%. However, without chemical treatment, MWNT concretes tend to have poor freeze-thaw resistance. Among the different chemical treatments, MWNT concrete treated with sodium polyacrylate has the best compressive strength, chloride resistance, and freeze-thaw durability.

  20. Compressive strength, chloride permeability, and freeze-thaw resistance of MWNT concretes under different chemical treatments.

    Science.gov (United States)

    Wang, Xingang; Rhee, Inkyu; Wang, Yao; Xi, Yunping

    2014-01-01

    This study investigated compressive strength, chloride penetration, and freeze-thaw resistance of multiwalled carbon nanotube (MWNT) concrete. More than 100 cylindrical specimens were used to assess test variables during sensitivity observations, including water-cement ratios (0.75, 0.5, and 0.4) and exposure to chemical agents (including gum arabic, propanol, ethanol, sodium polyacrylate, methylcellulose, sodium dodecyl sulfate, and silane). To determine the adequate sonication time for MWNT dispersal in water, the compressive strengths of MWNT concrete cylinders were measured after sonication times ranging from 2 to 24 minutes. The results demonstrated that the addition of MWNT can increase the compressive strength of concrete by up to 108%. However, without chemical treatment, MWNT concretes tend to have poor freeze-thaw resistance. Among the different chemical treatments, MWNT concrete treated with sodium polyacrylate has the best compressive strength, chloride resistance, and freeze-thaw durability.

  1. Corrosion resistance of the welded AISI 316L after various surface treatments

    Directory of Open Access Journals (Sweden)

    Tatiana Liptáková

    2014-01-01

    Full Text Available The main aim of this work is to monitor the surface treatment impact on the corrosion resistance of the welded stainless steel AISI 316L to local corrosion forms. The excellent corrosion resistance of austenitic stainless steel is caused by the existence of stable, thin and well adhering passive layer which quality is strongly influenced by welding. Therefore surface treatment of stainless steel is very important with regard to its local corrosion susceptibility Surfaces of welded stainless steel were treated by various mechanical methods (grinding, garnet blasting. Surface properties were studied by SEM, corrosion resistance was evaluated after exposition tests in chlorides environment using weight and metalographic analysis. The experimental outcomes confirmed that the mechanical finishing has a significant effect on the corrosion behavior of welded stainless steel AISI 316L.

  2. Nucleic acid toolkit: Potential diagnosis and treatment of major infectious diseases endemic in developing countries

    CSIR Research Space (South Africa)

    Millroy, L

    2011-09-01

    Full Text Available HIV/AIDS and TB are among the major infectious diseases and defining public health problems in developing countries. This book aims to give an overview of the epidemiology and also provide an understanding of the pathology of these diseases. It also...

  3. An Efficient Microarray-Based Genotyping Platform for the Identification of Drug-Resistance Mutations in Majority and Minority Subpopulations of HIV-1 Quasispecies.

    Science.gov (United States)

    Martín, Verónica; Perales, Celia; Fernández-Algar, María; Dos Santos, Helena G; Garrido, Patricia; Pernas, María; Parro, Víctor; Moreno, Miguel; García-Pérez, Javier; Alcamí, José; Torán, José Luis; Abia, David; Domingo, Esteban; Briones, Carlos

    2016-01-01

    The response of human immunodeficiency virus type 1 (HIV-1) quasispecies to antiretroviral therapy is influenced by the ensemble of mutants that composes the evolving population. Low-abundance subpopulations within HIV-1 quasispecies may determine the viral response to the administered drug combinations. However, routine sequencing assays available to clinical laboratories do not recognize HIV-1 minority variants representing less than 25% of the population. Although several alternative and more sensitive genotyping techniques have been developed, including next-generation sequencing (NGS) methods, they are usually very time consuming, expensive and require highly trained personnel, thus becoming unrealistic approaches in daily clinical practice. Here we describe the development and testing of a HIV-1 genotyping DNA microarray that detects and quantifies, in majority and minority viral subpopulations, relevant mutations and amino acid insertions in 42 codons of the pol gene associated with drug- and multidrug-resistance to protease (PR) and reverse transcriptase (RT) inhibitors. A customized bioinformatics protocol has been implemented to analyze the microarray hybridization data by including a new normalization procedure and a stepwise filtering algorithm, which resulted in the highly accurate (96.33%) detection of positive/negative signals. This microarray has been tested with 57 subtype B HIV-1 clinical samples extracted from multi-treated patients, showing an overall identification of 95.53% and 89.24% of the queried PR and RT codons, respectively, and enough sensitivity to detect minority subpopulations representing as low as 5-10% of the total quasispecies. The developed genotyping platform represents an efficient diagnostic and prognostic tool useful to personalize antiviral treatments in clinical practice.

  4. Comorbid thyroid disease in patients with major depressive disorder - results from the European Group for the Study of Resistant Depression (GSRD).

    Science.gov (United States)

    Fugger, Gernot; Dold, Markus; Bartova, Lucie; Kautzky, Alexander; Souery, Daniel; Mendlewicz, Julien; Serretti, Alessandro; Zohar, Joseph; Montgomery, Stuart; Frey, Richard; Kasper, Siegfried

    2018-06-01

    This multicenter study of the European Group for the Study of Resistant Depression (GSRD) aimed to explore the association between major depressive disorder (MDD) and comorbid thyroid disease. A total number of 1410 patients` characteristics in terms of demographic and clinical information were compared between MDD subjects with and without concurrent thyroid disease using descriptive statistics, analyses of covariance (ANCOVA) and binary logistic regression analyses. We determined a point prevalence rate for comorbid hypothyroidism of 13.2% and 1.6% for comorbid hyperthyroidism respectively. Patients with MDD+comorbid hypothyroidism were significantly older, more likely to be female, inpatient and suffering from other comorbid chronic somatic conditions. Furthermore, MADRS score at onset of the current depressive episode was significantly higher, psychotic features of depression were more likely pronounced. Overall, patients in the MDD+comorbid hypothyroidism group were rather treated with a combination of drugs, for example, pregabalin, antipsychotic drugs and mood stabilizers. In the MDD+comorbid hyperthyroidism group patients were significantly older, of Caucasian origin and diagnosed with other somatic comorbidities. In conclusion, our analyses suggest that abnormal thyroid function, especially hypothyroidism, is linked to depression severity and associated with distinct psychopathologic features of depression. However, comorbid thyroid disease has no influence on treatment response. A combination or augmentation of psychopharmacological drugs, especially with antipsychotics, mood stabilizers and pregabalin is more likely in patients with hypothyroid conditions. Thyroid disorder is frequently found in combination with other chronic somatic diseases including hypertension and heart disease. Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

  5. The effect of interpersonal psychotherapy and other psychodynamic therapies versus 'treatment as usual' in patients with major depressive disorder.

    Science.gov (United States)

    Jakobsen, Janus Christian; Hansen, Jane Lindschou; Simonsen, Erik; Gluud, Christian

    2011-04-27

    Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Interpersonal psychotherapy and other psychodynamic therapies may be effective interventions for major depressive disorder, but the effects have only had limited assessment in systematic reviews. Cochrane systematic review methodology with meta-analysis and trial sequential analysis of randomized trials comparing the effect of psychodynamic therapies versus 'treatment as usual' for major depressive disorder. To be included the participants had to be older than 17 years with a primary diagnosis of major depressive disorder. Altogether, we included six trials randomizing a total of 648 participants. Five trials assessed 'interpersonal psychotherapy' and only one trial assessed 'psychodynamic psychotherapy'. All six trials had high risk of bias. Meta-analysis on all six trials showed that the psychodynamic interventions significantly reduced depressive symptoms on the 17-item Hamilton Rating Scale for Depression (mean difference -3.12 (95% confidence interval -4.39 to -1.86;Pinterpersonal psychotherapy or psychodynamic therapy compared with 'treatment as usual' for patients with major depressive disorder. The potential beneficial effect seems small and effects on major outcomes are unknown. Randomized trials with low risk of systematic errors and low risk of random errors are needed.

  6. Treatment outcomes in patients with third-generation cephalosporin-resistant Enterobacter bacteremia.

    Science.gov (United States)

    O'Neal, Catherine S; O'Neal, Hollis R; Daniels, Titus L; Talbot, Thomas R

    2012-10-01

    Infections with resistant Enterobacter spp. are increasingly described, yet data on outcomes associated with these infections are limited. A retrospective cohort study was conducted to investigate outcomes of hospitalized patients with third-generation cephalosporin-resistant (CR) Enterobacter bacteremia. Cephalosporin resistance was detected using cefotaxime and cefpodoxime. Patients with Enterobacter spp. bacteremia from January 2006 through February 2008 defined the population. We defined cases as those with CR isolates; controls were patients with bacteremia due to non-CR isolates. Treatment failure was defined as persistence of the presenting signs of infection 72 h after initial culture collection. Of the 95 Enterobacter cases identified, 31 (33%) were CR. CR cases were significantly associated with treatment failure (odds ratio (OR) 2.81, 95% confidence interval (CI) 1.14-6.94). This association was not seen after adjustment for age, simplified acute physiology score (SAPS II), and inappropriate empiric antibiotic therapy. Inappropriate empiric therapy (adjusted OR 3.86, 95% CI 1.32-11.31) and SAPS II score (adjusted OR 1.09, 95% CI 1.02-1.16) were significantly associated with treatment failure in the multivariate analysis. Third-generation cephalosporin-resistant Enterobacter bacteremia is associated with treatment failure due to receipt of inappropriate empiric antibiotic therapy and severity of illness.

  7. Clinical roundtable monograph: Emerging treatment options for TKI-resistant chronic myelogenous leukemia.

    Science.gov (United States)

    Cortes, Jorge; Radich, Jerald; Mauro, Michael J

    2012-10-01

    The development of tyrosine kinase inhibitors (TKIs) that inhibit signaling of the constitutive BCR-ABL protein revolutionized the treatment of chronic myelogenous leukemia (CML). These agents have dramatically changed the treatment landscape for CML, shifting the use of allogeneic stem cell transplantation to selected patients in the salvage setting. Four BCR-ABL TKIs are now commercially available for the treatment of CML: the first-generation TKI imatinib, and the second-generation TKIs dasatinib, nilotinib, and bosutinib. Continuous treatment with these agents induces durable responses in a high proportion of patients with chronic-phase CML. Research is focused on identifying which patients can discontinue therapy without a recurrence of disease. For the group of patients with resistance to TKIs, multiple alternative therapies are being evaluated. The third-generation TKI ponatinib is a BCR-ABL inhibitor that has demonstrated significant activity, including in patients with the TKI resistance mutation T315I. The homoharringtonine derivative omacetaxine mepesuccinate, which inhibits protein synthesis, has also demonstrated clinical activity in CML, including in patients with TKI resistance due to T315I and in patients who have TKI resistance despite no evidence of ABL mutations. It is essential that clinicians implement these new agents with care and change therapies only when appropriate in order to preserve as many options as possible for future use if needed.

  8. Neurorehabilitation with versus without resistance training after botulinum toxin treatment in children with cerebral palsy

    DEFF Research Database (Denmark)

    Bandholm, Thomas Quaade; Jensen, Bente Rona; Nielsen, Lone M

    2012-01-01

    Objective: To compare the effects of physical rehabilitation with (PRT) and without (CON) progressive resistance training following treatment of spastic plantarflexors with botulinum toxin type A (BoNT) in children with cerebral palsy (CP). Methods: Fourteen children with CP performed supervised...

  9. Effect of annealing treatments on normal state resistivity of YBa 2 ...

    African Journals Online (AJOL)

    Samples of YBa2(Cu1-xTix)3Oy superconductor with x=0.00 , 0.01, 0.03 have been prepared by solide state reaction method. The effect of annealing treatments on normal electrical resistivity has been done using the bipolaron model. The results of this study show the increase of localized charge when the dopant content ...

  10. Surgery as an Adjunctive Treatment for Multidrug-Resistant Tuberculosis : An Individual Patient Data Metaanalysis

    NARCIS (Netherlands)

    Fox, Gregory J.; Mitnick, Carole D.; Benedetti, Andrea; Chan, Edward D.; Becerra, Mercedes; Chiang, Chen-Yuan; Keshavjee, Salmaan; Koh, Won-Jung; Shiraishi, Yuji; Viiklepp, Piret; Yim, Jae-Joon; Pasvol, Geoffrey; Robert, Jerome; Shim, Tae Sun; Shin, Sonya S.; Menzies, Dick; van der Werf, Tjip S.

    2016-01-01

    Background. Medical treatment for multidrug-resistant (MDR)-tuberculosis is complex, toxic, and associated with poor outcomes. Surgical lung resection may be used as an adjunct to medical therapy, with the intent of reducing bacterial burden and improving cure rates. We conducted an individual

  11. Metabolic effects of short-term GLP-1 treatment in insulin resistant heart failure patients

    DEFF Research Database (Denmark)

    Nielsen, Bent Roni Ranghøj; Wiggers, H; Halbirk, M

    2012-01-01

    calorimetry, forearm, and tracer methods.7 insulin resistant HF (EF 28%±2) patients completed the protocol. GLP-1 decreased plasma glucose levels (p=0.048) and improved glucose tolerance. 4 patients had hypoglycemic events during GLP-1 vs. none during placebo. GLP-1 treatment tended to increase whole body...

  12. Cost-effectiveness of renal denervation therapy for the treatment of resistant hypertension in the Netherlands

    NARCIS (Netherlands)

    Henry, Thea L.; De Brouwer, Bonnie F E; Van Keep, Marjolijn M L; Blankestijn, Peter J.; Bots, Michiel L.; Koffijberg, Hendrik

    2015-01-01

    Objectives: Safety and efficacy data for catheter-based renal denervation (RDN) in the treatment of resistant hypertension have been used to estimate the cost-effectiveness of this approach. However, there are no Dutch-specific analyses. This study examined the cost-effectiveness of RDN from the

  13. Improved corrosion resistance of aluminum brazing sheet by a post-brazing heat treatment

    NARCIS (Netherlands)

    Norouzi Afshar, F.; Tichelaar, F.D.; Glenn, A. M.; Taheri, P.; Sababi, M.; Terryn, H.A.; Mol, J.M.C.

    2017-01-01

    This work studies the influence of the microstructure on the corrosion mechanism and susceptibility of as-brazed aluminum sheet. Various microstructures are obtained using postbrazing heat treatments developed to enhance the corrosion resistance of an AA4xxx/AA3xxx brazing sheet. The heat

  14. Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major Gliomagenesis Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Fabliha Ahmed Chowdhury

    2018-01-01

    Full Text Available Glioblastoma multiforme (GBM is one of the most devastating brain tumors with median survival of one year and presents unique challenges to therapy because of its aggressive behavior. Current treatment strategy involves surgery, radiotherapy, immunotherapy, and adjuvant chemotherapy even though optimal management requires a multidisciplinary approach and knowledge of potential complications from both the disease and its treatment. Thymoquinone (TQ, the main bioactive component of Nigella sativa L., has exhibited anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteract carcinogenesis, malignant growth, invasion, migration, and angiogenesis. TQ can specifically sensitize tumor cells towards conventional cancer treatments and minimize therapy-associated toxic effects in normal cells. Its potential to enter brain via nasal pathway due to volatile nature of TQ adds another advantage in overcoming blood-brain barrier. In this review, we summarized the potential role of TQ in different signaling pathways in GBM that have undergone treatment with standard therapeutic modalities or with TQ. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical level to delineate its implied utility as novel therapeutics to combat the challenges for the treatment of GBM.

  15. Changes of rCBF on major depressed patients following TMS treatment: and SPM analysis

    International Nuclear Information System (INIS)

    Zheng, X.M.

    2000-01-01

    Full text: Changes of regional Cerebral Blood Flow (rCBF) on five drug-resistant depressed patients were examined by Single Photon Emission Computed Tomography (SPECT) with 99 Tc m - Hexamethylpropyleneamine Oxime ( 99 Tc m HMPAO) before and after Transcranial Magnetic Stimulation (TMS). The SPECT images were analysed by Statistical Parametric Mapping (SPM) package. TMS at the left Dorsolateral Prefrontal Cortex (DLPFC) of the depressed patients resulted in an increase of rCBF at a focal region in the vicinity of the stimulation site. No change was observed at any remote region. A 34.8% global CBF reduction for the depressed patients was found in their raw data. SPM analysis of the globally scaled images shows that there are increases of rCBF in the parietal region for the depressed patients. Global CBF scaling might contribute to these increases. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  16. Molecular mapping of qBK1 WD , a major QTL for bakanae disease resistance in rice

    OpenAIRE

    Lee, Sais-Beul; Hur, Yeon-Jae; Cho, Jun-Hyeon; Lee, Jong-Hee; Kim, Tae-Heon; Cho, Soo-Min; Song, You-Chun; Seo, Young-Su; Lee, Jungkwan; Kim, Tae-sung; Park, Yong-Jin; Oh, Myung-Kyu; Park, Dong-Soo

    2018-01-01

    Background Bakanae or foot rot disease is a prominent disease of rice caused by Gibberella fujikuroi. This disease may infect rice plants from the pre-emergence stage to the mature stage. In recent years, raising rice seedlings in seed boxes for mechanical transplanting has increased the incidence of many seedling diseases; only a few rice varieties have been reported to exhibit resistance to bakanae disease. In this study, we attempted to identify quantitative trait loci (QTLs) conferring ba...

  17. A Multiple Decrement Life Table Reveals That Host Plant Resistance and Parasitism Are Major Causes of Mortality for the Wheat Stem Sawfly.

    Science.gov (United States)

    Buteler, Micaela; Peterson, Robert K D; Hofland, Megan L; Weaver, David K

    2015-12-01

    This study investigated the dynamics of parasitism, host plant resistance, pathogens, and predation on the demography of wheat stem sawfly, Cephus cinctus Norton (Hymenoptera: Cephidae), developing in susceptible (hollow stem) and resistant (solid stem) wheat hosts. This study is also the first to investigate the prevalence and impact of cannibalism on wheat stem sawfly mortality. Wheat stem sawflies were sampled in two commercial wheat fields over 4 yr from the egg stage through adult emergence, and multiple decrement life tables were constructed and analyzed. Cannibalism, host plant resistance, or unknown factors were the most prevalent factors causing egg mortality. Summer mortality of prediapause larvae ranged from 28 to 84%, mainly due to parasitism by Bracon cephi (Gahan) and Bracon lissogaster Muesebeck, cannibalism, and host plant resistance. Winter mortality ranged from 6 to 54% of the overwintering larvae, mainly due to unknown factors or pathogens. Cannibalism is a major cause of irreplaceable mortality because it is absolute, with only a single survivor in every multiple infested stem. Subsequent to obligate cannibalism, mortality of feeding larvae due to host plant resistance was lower in hollow stem wheat than in solid stem wheat. Mortality from host plant resistance was largely irreplaceable. Irreplaceable mortality due to parasitoids was greater in hollow stem wheat than in solid stem wheat. Host plant resistance due to stem solidness and parasitism in hollow stems cause substantial mortality in populations of actively feeding larvae responsible for all crop losses. Therefore, enhancing these mortality factors is vital to effective integrated pest management of wheat stem sawfly. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder

    Science.gov (United States)

    Quilty, Lena C.; Ravitz, Paula; Rosenbluth, Michael; Pavlova, Barbara; Grigoriadis, Sophie; Velyvis, Vytas; Kennedy, Sidney H.; Lam, Raymond W.; MacQueen, Glenda M.; Milev, Roumen V.; Ravindran, Arun V.; Uher, Rudolf

    2016-01-01

    Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) has revised its 2009 guidelines for the management of major depressive disorder (MDD) in adults by updating the evidence and recommendations. The target audiences for these 2016 guidelines are psychiatrists and other mental health professionals. Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. “Psychological Treatments” is the second of six sections of the 2016 guidelines. Results: Evidence-informed responses were developed for 25 questions under 5 broad categories: 1) patient characteristics relevant to using psychological interventions; 2) therapist and health system characteristics associated with optimizing outcomes; 3) descriptions of major psychotherapies and their efficacy; 4) additional psychological interventions, such as peer interventions and computer- and technology-delivered interventions; and 5) combining and/or sequencing psychological and pharmacological interventions. Conclusions: First-line psychological treatment recommendations for acute MDD include cognitive-behavioural therapy (CBT), interpersonal therapy (IPT), and behavioural activation (BA). Second-line recommendations include computer-based and telephone-delivered psychotherapy. Where feasible, combining psychological treatment (CBT or IPT) with antidepressant treatment is recommended because combined treatment is superior to either treatment alone. First-line psychological treatments for maintenance include CBT and mindfulness-based cognitive therapy (MBCT). Patient preference, in combination with evidence-based treatments and clinician/system capacity, will yield the optimal treatment strategies for improving individual outcomes in MDD. PMID

  19. The bi-directional relationship between parent-child conflict and treatment outcome in treatment-resistant adolescent depression.

    Science.gov (United States)

    Rengasamy, Manivel; Mansoor, Brandon M; Hilton, Robert; Porta, Giovanna; He, Jiayan; Emslie, Graham J; Mayes, Taryn; Clarke, Gregory N; Wagner, Karen Dineen; Keller, Martin B; Ryan, Neal D; Birmaher, Boris; Shamseddeen, Wael; Asarnow, Joan Rosenbaum; Brent, David A

    2013-04-01

    To examine the bidirectional relationship between parent-child discord and treatment outcome for adolescent treatment-resistant depression. Depressed youth who had not responded to an adequate course of a selective serotonin reuptake inhibitor (SSRI) were randomized to either a switch to another SSRI or venlafaxine, with or without the addition of cognitive behavior therapy (CBT) in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study. The Conflict Behavior Questionnaire was used to assess adolescent (CBQ-A) and parent-reported (CBQ-P) parent-child discord. The impact of remission on parent-child conflict, and the differential impact of medication and CBT on the CBQ-A and CBQ-P, were assessed using generalized linear models. Although there were no differential treatment effects on parent or adolescent-report of conflict, remission was associated with improvement in the CBQ-P. In general, intake family conflict did not predict remission, except in the sub-group of participants whose parents reported clinically significant parent-child conflict at intake, for whom high levels of parent-reported conflict predicted a lower likelihood of remission. Conflict also did not moderate treatment response. Remission of depression may be sufficient to reduce parent-reported parent-child conflict. However, higher parent-reported conflict, in the clinically significant range, predicts a lower likelihood of remission from depression. Clinical trial registration information-Treatment of SSRI-Resistant Depression in Adolescents (TORDIA); http://clinicaltrials.gov/; NCT00018902. Copyright © 2013 American Academy of Child & Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  20. Within-host selection of drug resistance in a mouse model of repeated interrupted treatment of Plasmodium yoelii infection

    NARCIS (Netherlands)

    Nuralitha, Suci; Siregar, Josephine E; Syafruddin, Din; Hoepelman, Andy I M; Marzuki, Sangkot

    2017-01-01

    BACKGROUND: To study within-host selection of resistant parasites, an important factor in the development of resistance to anti-malarial drugs, a mouse model of repeated interrupted malaria treatment (RIT) has been developed. The characteristics of within host selection of resistance to atovaquone

  1. Benefits and harms in clinical trials of duloxetine for treatment of major depressive disorder

    DEFF Research Database (Denmark)

    Maund, Emma; Tendal, Britta; Hróbjartsson, Asbjørn

    2014-01-01

    , respectively. We also found publication bias in relation to beneficial effects. CONCLUSION: Clinical study reports contained extensive data on major harms that were unavailable in journal articles and in trial registry reports. There were inconsistencies between protocols and clinical study reports and within.......gov and the manufacturer's online clinical trial registry were searched for trial results. RESULTS: Clinical study reports fully described the primary efficacy analysis and major harms (deaths (including suicides), suicide attempts, serious adverse events, and discontinuations because of adverse events). There were minor...... clinical study reports. Clinical study reports should be used as the data source for systematic reviews of drugs, but they should first be checked against protocols and within themselves for accuracy and consistency....

  2. Cognitive–behavioral group therapy is an effective treatment for major depression in hemodialysis patients

    OpenAIRE

    Duarte, Priscila Silveira; Miyazaki, Maria Cristina; Blay, Sergio Luís; Sesso, Ricardo

    2009-01-01

    Depression is an important target of psychological assessment in patients with end-stage renal disease because it predicts their morbidity, mortality, and quality of life. We assessed the effectiveness of cognitive-behavioral therapy in chronic hemodialysis patients diagnosed with major depression by the Mini International Neuropsychiatric Interview (MINI). in a randomized trial conducted in Brazil, an intervention group of 41 patients was given 12 weekly sessions of cognitive-behavioral grou...

  3. Studying the effect of administration route and treatment dose on the selection of enrofloxacin resistance in commensal Escherichia coli in broilers.

    Science.gov (United States)

    Chantziaras, Ilias; Smet, Annemieke; Haesebrouck, Freddy; Boyen, Filip; Dewulf, Jeroen

    2017-07-01

    Factors potentially contributing to fluoroquinolone resistance selection in commensal Escherichia coli strains in poultry were studied through a series of in vivo experiments. The effect of the initial prevalence of enrofloxacin resistance in the E. coli gut microbiota, effect of the bacterial fitness of the enrofloxacin-resistant strain and effect of treatment with enrofloxacin (effect of dose and effect of route of administration) were assessed. Four in vivo studies with broiler chickens were performed. Right after hatching, the chicks were inoculated with either a bacteriologically fit or a bacteriologically non-fit fluoroquinolone-resistant strain as either a minority or the majority of the total E. coli population. Six days later, the chicks were treated for three consecutive days either orally or parenterally and using three different doses (under-, correct- and over-dose) of enrofloxacin. The faecal shedding of E. coli strains was quantified by plating on agar plates either supplemented or not supplemented with enrofloxacin. Linear mixed models were used to assess the effect of the aforementioned variables on the selection of enrofloxacin resistance. The factors that significantly contributed were treatment ( P  <   0.001), bacterial fitness of the resistant donor strain ( P  <   0.001), administration route ( P  =   0.052) and interactions between bacterial fitness and administration route ( P  <   0.001). In the currently used models, fluoroquinolone resistance selection was influenced by treatment, bacterial fitness of the inoculation strain and administration route. The use of oral treatment seems to select more for fluoroquinolone resistance, particularly in the model where a non-fit strain was used for inoculation. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Interpersonal problems and impacts: further evidence for the role of interpersonal functioning in treatment outcome in major depressive disorder.

    Science.gov (United States)

    Quilty, Lena C; Mainland, Brian J; McBride