Efficacy Of Different Treatments Research Articles

Sex differences in hippocampal response to endocannabinoids after exposure to severe stress.

Women are more vulnerable to stress-related mental disorders than men and the naturally occurring fluctuation in estrogen that occur across the estrus cycle can dramatically influence the pathophysiology observed following traumatic events. It has been demonstrated that the endocannabinoid (eCB) system could represent a therapeutic target for the treatment of post-traumatic stress disorder (PTSD) in males. The current study aimed to examine the effects of exposure to a traumatic event and acute enhancement of eCB signaling on hippocampal-dependent learning and plasticity in male and female rats. Males and females were exposed to the single prolonged stress (SPS) model of PTSD (restraint, forced swim, and sedation) followed by acute administration of the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.3 mg/kg). Females were in diestrus during SPS exposure. SPS exposure impaired extinction and hippocampal plasticity tested a week later in males and females. Sex differences were observed in the effects of URB597 on hippocampal plasticity of SPS-exposed rats. Also, URB597 normalized the SPS-induced upregulation in CB1 receptor levels in the amygdala, prefrontal cortex (PFC), and hippocampus in males. In females, URB597 normalized the SPS-induced up regulation in CB1 receptors in the amygdala and PFC, but not hippocampus. Our findings support the eCB system as a therapeutic target for the treatment of disorders associated to inefficient fear coping in males and females. There are differences in the hippocampal response of males and females to the enhancement of eCB signaling after intense stress suggesting sex differences in treatment efficacy. © 2016 Wiley Periodicals, Inc.

Novel GRN Mutations in Patients with Corticobasal Syndrome.

Loss-of-function GRN mutations lead to GRN haploinsufficiency and consequently neurodegeneration with significant heterogeneity in clinical presentation of various syndromes. The aim of this study was to investigate the genetics and clinical features of patients with GRN-related frontotemporal lobar degeneration (FTLD) syndromes. We performed mutation analysis of GRN in 45 unrelated Canadian patients with a broad spectrum of FTLD-like syndromes (mean age at onset of 64.0 ± 11.2 years). In our cohort, two patients were carriers of two novel heterozygous alterations in GRN: 2 bp insertion (c.769–770insCC:p.Q257fs) and 12 bp deletion (c.1009–1020del:p.337–340del). Both patients presented with corticobasal syndrome supported by clinical and radiological findings. The absence of the mutant allele in the RT–PCR product was only observed for the sample with 2 bp insertion in GRN. In contrast, the allele with 12 bp deletion in GRN was not down-regulated at the RNA level and did not segregate with FTLD in the family. Our report extends the evidence for genetic and phenotypic variability in FTLD disorders, and detects a novel pathogenic GRN mutation, carriers of which could eventually help to evaluate the efficacy of different treatments at early stages of dementia.

Treatments for the Fifth Metacarpal Neck Fractures: A Network Meta-analysis of Randomized Controlled Trials.

The fifth metacarpal neck fractures (commonly termed boxer's fractures) are the most common type of metacarpal fractures. Many types of treatments are available in clinical practice, some of which have already been compared with other treatments by various researchers. However, a comprehensive treatment comparison is lacking. We estimated the comparative efficacy of different interventions for total complications, through a network meta-analysis of randomized controlled trials.We conducted a systematic search of the literature through October 2015. The outcome measurements were the total complications. We used a Bayesian network meta-analysis to combine direct and indirect evidence and to estimate the relative effects of treatment.We identified 6 RCTs registering a total of 288 patients who were eligible for our network meta-analysis. The literature's quality is relatively high. The median Structured Effectiveness for Quality Evaluation of Study score for the included trials was 33.8. The overall methodological quality was high. Of the 6 studies, all were 2-arm controlled trials comparing active intervention. Among the 4 treatments—conservative treatment (CT), antegrade intramedullary nailing (AIMN), transverse pinning (TP) with K-wires, and plate fixation (PF)—CT had the best rankings (ie, lowest risk of total complications), followed by PF, AIMN, and TP (ie, highest risk of total complications). Furthermore, we also presented the results using surface under the cumulative ranking curve. The surface under the cumulative ranking curve probabilities were 94.1%, 52.9%, 37.3%, and 15.7% for CT, PF, AIMN, and TP, respectively.In conclusion, current evidence suggested that conservative treatment is the optimum treatment for the fifth metacarpal neck fractures because of reduced total complication rates. Moreover, the TP with K-wires is the worst option with highly total complication rates. PF and AIMN therapy should be considered as the first-line choices. Larger and higher-quality randomized controlled trials are required to confirm these conclusions and better inform clinical decision-making.

Treatment and outcome of recurrent cervical lymph nodes in patients with nasopharyngeal carcinoma after radiotherapy

To evaluate the efficacies of different treatments for recurrent cervical lymph nodes and the factors contributing to prognosis in patients with nasopharyngeal carcinoma after radiotherapy. Clinical data of 79 patients with nasopharyngeal carcinoma after radiotherapy were retrospectively analyzed, and all cases were diagnosed as having recurrent cervical lymph nodes by pathological examination. The factors including sex, age, the interval between completion of radiotherapy and recurrence, rN stage, treatment methods, and the location relationship between recurrent lesion and primary tumor in the neck were analyzed for prognosis. Kaplan-Meier curves, Log-rank test and Cox's proportional hazards regression mode were used in the statistical analysis. The median recurrence time was 26 months, and the 1- , 3- and 5-year overall survival rates were 77.9%, 53.4% and 39.7%. Cox's proportional hazards regression mode analysis indicated that age, rN stage, treatment methods, and the location relationship between recurrent lesion and primary tumor were significantly prognostic factors. Neck dissection is superior to re-radiotherapy in treatment of recurrent cervical lymph nodes in nasopharyngeal carcinoma after radiotherapy. The patients younger than 45 years old, in early rN stage and for recurrence in the center region of primary tumor have a better prognosis.

Results of Yet Another Antibiotics vs Appendectomy Randomized Trial: Still Not Enough to Change My Practice.

RESULTS There were 273 patients in the surgical group and 257 in the antibiotic group. Of 273 patients in the surgical group, all but 1 underwent successful appendectomy, resulting in a success rate of 99.6% (95% CI, 98.0% to 100.0%). In the antibiotic group, 70 patients (27.3%; 95% CI, 22.0% to33.2%) underwent appendectomy within 1 year of initial presentation for appendicitis. Of the 256 patients available for follow-up in the antibiotic group, 186 (72.7%; 95% CI, 66.8% to 78.0%) did not require surgery. The intention-to-treat analysis yielded a difference in treatment efficacy between groups of −27.0% (95% CI, −31.6% to) (P = .89). Given the prespecified noninferiority margin of 24%, we were unable to demonstrate noninferiority of antibiotic treatment relative to surgery. Of the 70 patients randomized to antibiotic treatment who subsequently underwent appendectomy, 58 (82.9%; 95% CI, 72.0% to 90.8%) had uncomplicated appendicitis, 7 (10.0%; 95% CI 4.1% to 19.5%) had complicated acute appendicitis, and 5 (7.1%; 95% CI 2.4% to 15.9%) did not have appendicitis but received appendectomy for suspected recurrence. There were no intra-abdominal abscesses or other major complications associated with delayed appendectomy in patients randomized to antibiotic treatment.

Alternative agents versus prophylactic platelet transfusion for preventing bleeding in patients with thrombocytopenia due to chronic bone marrow failure: a network meta-analysis and systematic review.

This is the protocol for a review and there is no abstract. The objectives are as follows: To compare the relative efficacy of different treatments for thrombocytopenia (artificial platelet substitutes, platelet-poor plasma, fibrinogen, rFVIIa, rFXIII, thrombopoietin mimetics, antifibrinolytic drugs or platelet transfusions) in patients with chronic bone marrow failure and to derive a hierarchy of potential alternate treatments to platelet transfusions.

Analysis of upper esophageal sphincter pressure with symptoms and prognosis in 158 patients with achalasia

Objective To investigate upper esophageal sphincter (UES) abnormalities in patients with achalasia (AC), and to analyze the correlation between UES abnormalities and clinical symptoms, treatment efficacy. Methods From February 2012 to December 2014, 158 patients with AC and received high resolution manometry (HRM) examination were retrospectivly analyzed. According to whether with UES abnormalities, patients were divided into UES normal group and UES abnormal group. Patients of UES abnormal group were sub-divided into UES hypotensive group (UES resting pressure 104 mmHg) and impaired relaxation group (residual pressure>12 mmHg). Analysis of Variance, Kruskal-Wallis H test and Chi square test were performed to compare the clinical data and dynamic characteristics of the patients in each group. Results A total of 74 (46.8%) AC patients had UES abnormalities, the majority of whom were impaired relaxation (35 cases, 47.3%). The age of patients in hypotensive group ((60.6±10.1) years) was significantly older than that of hypertensive group ((43.9±11.1) years) and impaired relaxation group ((46.8±16.3) years), and the disease course (10 years, 4 to 30 years) was obviously longer than that of hypertensive group (6 years, 1 to 10 years) and impaired relaxation group (8 years, 3 to 15 years), and the differences were statistically significant (F=7.983, H=13.816, both P 0.05). The results of AC subtyping indicated that type Ⅱ AC accounted 55.7% (88/158). Type Ⅱ AC cases number of UES normal group and abnormal group was 46 and 42 cases, both was majority (54.8% and 56.8%). Among these patients, 123 patients finally received peroral endoscopic myotomy (POEM), 47.2%(58/123) of whom had abnormal UES. More than 85% patients were satisfied at one month after the operation. And Eckardt scores significantly decreased. There was no significant difference in treatment efficacy between the two groups. Conclusions Most AC patients are with UES abnormality, and impaired relaxation is more common. There is no correlation between UES abnormalities and major symptoms. There is no predictive role of UES abnormalities in treatment efficacy of POEM in AC patients. Key words: High resolution esophageal manometry; Esophageal sphincter, upper; Achalasia; Peroral endoscopic myotomy

Comparative efficacy of fixed-dose combinations of long-acting muscarinic antagonists and long-acting β2-agonists: a systematic review and network meta-analysis

A number of long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) fixed-dose combinations (FDCs) for treatment of moderate-to-very severe chronic obstructive pulmonary disease (COPD) have recently become available, but none have been directly compared in head-to-head randomized controlled trials (RCTs). The purpose of this study was to assess the relative clinical benefit of all currently available LAMA/LABA FDCs using a Bayesian network meta-analysis (NMA). A systematic literature review identified RCTs investigating the efficacy, safety and quality of life associated with licensed LAMA/LABA FDCs for the treatment of moderate-to-very severe COPD. RCTs were screened for inclusion in the NMA using prespecified eligibility criteria. Data were extracted for outcomes of interest, including change in trough forced expiratory volume in 1 second (tFEV1) from baseline, St. George Respiratory Questionnaire (SGRQ) percentage of responders, Transition Dyspnea Index (TDI) percentage of responders, change in SGRQ score from baseline, change in TDI focal score from baseline, moderate-to-severe exacerbations, all-cause discontinuation, and discontinuation due to adverse events. Following screening, a total of 27 trials from 26 publications with 30,361 subjects were eligible for inclusion in the NMA. Nonsignificant results were seen in most analyses comparing efficacy, exacerbations and discontinuation rates of included LAMA/LABA FDCs (i.e. aclidinium/formoterol 400/12 µg, glycopyrronium/indacaterol 110/50 µg, tiotropium + olodaterol 5/5 µg, umeclidinium/vilanterol 62.5/25 µg). Meta-regression controlling for post-bronchodilator percentage of tFEV1 predicted at baseline as well as meta-regression adjusting for concomitant use of inhaled corticosteroids at baseline was performed to assess the magnitude of effect modification and produced similar results as observed in the base case analysis. All LAMA/LABA FDCs were found to have similar efficacy and safety. Definitive assessment of the relative efficacy of different treatments can only be performed through direct comparison in head-to-head RCTs. In the absence of such data, this indirect comparison may be of value in clinical and health economic decision-making.

Near-infrared spectrometry in pregnancy: progress and perspectives, a review of literature.

Near-infrared spectroscopy (NIRS) allows continuous noninvasive monitoring of in vivo oxygenation in selected tissues. It has been used primarily as a research tool for several years, but it is seeing wider application in the clinical arena all over the world. It was recently used to monitor brain circulation in cardiac surgery, carotid endarteriectomy, neurosurgery and robotic surgery. According to the few studies used NIRS in pregnancy, it may be helpful to assess the impact of severe forms of preeclampsia on brain circulation, to evaluate the efficacy of different treatments. It may also be used during cesarean section to detect earlier sudden complications. The evaluation of placental function via abdominal maternal approach to detect fetal growth restriction is a new field of application of NIRS.

Chemotherapy for advanced non-small cell lung cancer with a focus on squamous cell carcinoma.

Lung cancers are broadly divided into small-cell lung cancer (SCLC) and non-SCLC (NSCLC), and the treatments for each differ. NSCLC includes squamous cell carcinoma, adenocarcinoma, large cell carcinoma, and others. However, because there is little difference in treatment efficacy between these histological types, they have collectively been treated as a single entity. Cytotoxic anti-cancer agents, mainly platinum-based drugs, are the first-line treatment for unresectable advanced NSCLC, and the standard therapy is combination chemotherapy with two drugs, usually involving one platinum-based and one unrelated cytotoxic drug. Such regimens have been used for all the different histological types. In recent years, however, genetic abnormalities in NSCLCs known as driver mutations have been identified. These include epidermal growth factor receptor mutations and anaplastic lymphoma kinase translocations, which are responsible for both carcinogenesis and cancer growth and survival. The advent of molecular targeted therapies that target these mutations has clearly improved the prognosis for NSCLC. However, effective molecular targeted drugs or novel anti-cancer agents that greatly prolong survival have not yet been developed to treat squamous cell carcinoma or 30% of adenocarcinomas. For patients with these types of cancers, it is important to use existing cytotoxic anti-cancer agents appropriately in their treatment. In this paper, we review the treatment options for unresectable advanced NSCLC on the basis of recent findings, with a particular focus on squamous cell carcinoma, for which groundbreaking drugs have yet to be discovered.

Interventions for the management of external root resorption.

External root resorption is a pathological process, which tends to occur following a wide range of mechanical or chemical stimuli such as infection, pressure, trauma or orthodontic tooth movement. Although it is predominantly detected by radiography, in some cases root resorption may be identified by clinical symptoms such as pain, swelling and mobility of the tooth. Treatment alternatives are case-dependent and aim to address the cause of the resorption and aid the regeneration of the resorptive lesion. To evaluate the effectiveness of any interventions that can be used in the management of external root resorption in permanent teeth. The following electronic databases were searched: the Cochrane Oral Health Group Trials Register (to 14 October 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2015, Issue 9), MEDLINE via OVID (1946 to 14 October 2015) and EMBASE via OVID (1980 to 14 October 2015). We searched the US National Institutes of Health Trials Register (http://clinicaltrials.gov) and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. We included randomised controlled trials of permanent teeth with any type of external root resorption, which has been confirmed by clinical and radiological examination, comparing one type of intervention (root canal medications and canal filling, splinting or extraction of teeth or the surgical removal of any relevant pathology) with another, or with placebo or no treatment. Two review authors screened search records independently. Full papers were obtained for potentially relevant trials. If data had been extracted, the statistical guidelines set out in the Cochrane Handbook would have been followed. No randomised controlled trials that met the inclusion criteria were identified. However, we identified one ongoing study that is potentially relevant to this review and will be assessed when it is published. We were unable to identify any reports of randomised controlled trials regarding the efficacy of different interventions for the management of external root resorption. In view of the lack of reliable evidence on this topic, clinicians must decide on the most appropriate means of managing this condition according to their clinical experience with regard to patient-related factors. There is a need for well designed and conducted clinical trials on this topic, which conform to the CONSORT statement (www.consort-statement.org/).

Efficacy Assessment of Treatment Methods against Powdery Mildew Disease of Pea ( Pisum sativum L.) Caused by Erysiphe pisi var. pisi

The experiment was conducted to find out the efficacy of different treatments against powdery mildew of pea (Erysiphepisi var. pisi) in Rampur, Chitwan, Nepal during Dec. 2014 to April 2015. Four treatments viz. Skimmed cow milk (250 ml/plot), Karathane (2 ml/L), Trichoderma (107condia/ml) and Control (distilled water) were used as foliar spray on plants. Considering Disease severity (%), Disease control (%) and Total Area under Disease Progress Curve, Trichoderma was found to be effective than Skimmed cow milk and Control but was at par with Karathane, in controlling over Powdery mildew disease. Number of pods/plant and weight of grains/plant were observed highest in Trichodermawhich was followed by Karathane. There was no significant difference between treatments in case of weight of pods/plant and dry weight/plant. AUDPC/day value increased in control in different sprayings but AUDPC value/day initially increased and later decreased for Trichoderma, Karathane and skimmed cow milk. All the yield and yield attributing characters were negatively correlated with AUDPC but number of pods/plant and weight of pods/plant were positively correlated. Reduction in yield was also caused by infection of Rust (Uromycespisi) in field. Four foliar sprays of Trichoderma (107condia/ml) or Karathane@ 0.2% at interval of 7 days may be the option for the management of powdery mildew in severe condition. Trichoderma can be alternative method for farmers to have eco-friendly management of Powdery mildew as Karathane has negative impact on human and plant health.

Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis

Importance An increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis. Objective To compare antibiotic therapy with appendectomy in the treatment of uncomplicated acute appendicitis confirmed by computed tomography (CT). Design, Setting, and Participants The Appendicitis Acuta (APPAC) multicenter, open-label, noninferiority randomized clinical trial was conducted from November 2009 until June 2012 in Finland. The trial enrolled 530 patients aged 18 to 60 years with uncomplicated acute appendicitis confirmed by a CT scan. Patients were randomly assigned to early appendectomy or antibiotic treatment with a 1-year follow-up period. Interventions Patients randomized to antibiotic therapy received intravenous ertapenem (1 g/d) for 3 days followed by 7 days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times per day). Patients randomized to the surgical treatment group were assigned to undergo standard open appendectomy. Main Outcomes and Measures The primary end point for the surgical intervention was the successful completion of an appendectomy. The primary end point for antibiotic-treated patients was discharge from the hospital without the need for surgery and no recurrent appendicitis during a 1-year follow-up period. Results There were 273 patients in the surgical group and 257 in the antibiotic group. Of 273 patients in the surgical group, all but 1 underwent successful appendectomy, resulting in a success rate of 99.6% (95% CI, 98.0% to 100.0%). In the antibiotic group, 70 patients (27.3%; 95% CI, 22.0% to 33.2%) underwent appendectomy within 1 year of initial presentation for appendicitis. Of the 256 patients available for follow-up in the antibiotic group, 186 (72.7%; 95% CI, 66.8% to 78.0%) did not require surgery. The intention-to-treat analysis yielded a difference in treatment efficacy between groups of −27.0% (95% CI, −31.6% to ∞) ( P = .89). Given the prespecified noninferiority margin of 24%, we were unable to demonstrate noninferiority of antibiotic treatment relative to surgery. Of the 70 patients randomized to antibiotic treatment who subsequently underwent appendectomy, 58 (82.9%; 95% CI, 72.0% to 90.8%) had uncomplicated appendicitis, 7 (10.0%; 95% CI, 4.1% to 19.5%) had complicated acute appendicitis, and 5 (7.1%; 95% CI, 2.4% to 15.9%) did not have appendicitis but received appendectomy for suspected recurrence. There were no intra-abdominal abscesses or other major complications associated with delayed appendectomy in patients randomized to antibiotic treatment. Conclusions and Relevance Among patients with CT-proven, uncomplicated appendicitis, antibiotic treatment did not meet the prespecified criterion for noninferiority compared with appendectomy. Most patients randomized to antibiotic treatment for uncomplicated appendicitis did not require appendectomy during the 1-year follow-up period, and those who required appendectomy did not experience significant complications. Trial Registration clinicaltrials.gov Identifier:NCT01022567

Effect of electrical energy on the efficacy of biofilm treatment using the bioelectric effect.

Background/Objectives:The use of electric fields in combination with small doses of antibiotics for enhanced treatment of biofilms is termed the ‘bioelectric effect’ (BE). Different mechanisms of action for the AC and DC fields have been reported in the literature over the last two decades. In this work, we conduct the first study on the correlation between the electrical energy and the treatment efficacy of the bioelectric effect on Escherichia coli K-12 W3110 biofilms.Methods:A thorough study was performed through the application of alternating (AC), direct (DC) and superimposed (SP) potentials of different amplitudes on mature E. coli biofilms. The electric fields were applied in combination with the antibiotic gentamicin (10 μg/ml) over a course of 24 h, after the biofilms had matured for 24 h. The biofilms were analysed using the crystal violet assay, the colony-forming unit method and fluorescence microscopy.Results:Results show that there is no statistical difference in treatment efficacy between the DC-, AC- and SP-based BE treatment of equivalent energies (analysis of variance (ANOVA) P>0.05) for voltages <1 V. We also demonstrate that the efficacy of the BE treatment as measured by the crystal violet staining method and colony-forming unit assay is proportional to the electrical energy applied (ANOVA P<0.05). We further verify that the treatment efficacy varies linearly with the energy of the BE treatment (r2 =0.984). Our results thus suggest that the energy of the electrical signal is the primary factor in determining the efficacy of the BE treatment, at potentials less than the media electrolysis voltage.Conclusions:Our results demonstrate that the energy of the electrical signal, and not the type of electrical signal (AC or DC or SP), is the key to determine the efficacy of the BE treatment. We anticipate that this observation will pave the way for further understanding of the mechanism of action of the BE treatment method and may open new doors to the use of electric fields in the treatment of bacterial biofilms.

Age versus frailty: What should determine treatment choice in the elderly myeloma patients these days?

The management of myeloma has largely changed since the introduction of immunomodatory drugs (iMIDs)and proteasome-inhibitors (PIs)in the last decade. Results on efficacy of different treatment result primarily from randomized controlled trials. Data on treatment effectiveness based on daily practice are sparse but necessary to provide complementary information. Within the available treatment options,choice seems to depend on frailty of the patient;primarily based on age, WHO-performance status and comorbidities.

Exploring the effect of a second closely-timed infiltration of platelet-rich plasma to treat jumper's knees

Some clinical series have evaluated the effect of platelet-rich plasma (PRP) in the treatment of jumper's knee. Although it is possible that a single infiltrative administration may prove to be an effective treatment for this indication, most of the existing studies evaluated the effects of 2 or 3 successive infiltrations. The aim of this study was to evaluate whether 2 infiltrations of PRP proves more effective than a single treatment. Twenty patients suffering from chronic jumper's knee were enrolled into our prospective and randomized study and split into two randomized groups (1 or 2 infiltrations of PRP, respectively). The 3-month follow-up evaluation consisted of VAS, IKDC and VISA-P scores, along with algometer, isokinetic and ultrasounds evaluations. After 1 year, subjects were contacted to define their functional evolution. The concentration of the PRP used for each infiltration was similar in both groups, and contained no red or white cells. Results revealed no difference in treatment efficacy between the groups. The comparison between 1 or 2 infiltrations of PRP did not reveal any difference between the 2 groups at short to mid term. A second closely-timed infiltration of PRP to treat jumper's knees is not necessary to improve the efficacy of this treatment in the short term.

Abstract 976: Metabolic eradication of treatment resistant cancer stem cells in pancreatic tumors: A clonal tracking-based platform for identifying the best personalized treatment

Abstract Pancreatic ductal adenocarcinoma (PDAC) continues to have a poor prognosis despite new drugs advancing to the clinic. We recently characterized a population of cells able to survive the genetic and pharmacologic extinction of oncogenic pathways and demonstrated that the surviving cells (SC) are tumor stem cells (CSC) able to remain in a quiescent state for months before relapsing. In-depth transcriptomics and metabolomics analyses revealed SCs to exhibit different metabolic features compared to the bulk of tumor cells. Specifically, SC relied on mitochondrial respiration (OXPHOS) and displayed impaired glycolytic capacity. In accord with their decreased dependence on glycolysis these SC were highly sensitive to OXPHOS inhibitors, which prevented tumor recurrence. Notably, preliminary results in patients suggest that SC resistant to conventional chemoradiation also have similar features. We analyzed specimens after neoadjuvant treatment and observed dormant cells positive for CSC markers and characterized by an increased mitochondrial mass. Evaluation of TMA of hundreds of treated tumors revealed that high mitochondrial content is a common feature of SC. Furthermore, functional metabolic characterization of human cells resistant to gemcitabine revealed that SC have a severely impaired glycolytic reserve, closely resembling mouse SC. Based on these findings, we posit that OXPHOS inhibitors may be an effective adjuvant therapy to eradicate resistant cells in patients. To validate the efficacy of OXPHOS inhibition, we developed a new platform to study tumor evolution in response to treatments based on clonal tracking. Lentivirus-based systems have been extensively used as a tool to investigate the clonal dynamics, but they have been limited by lack of sensitivity and the impossibility of tracking identical clones in different animals. Here, using a new version of the barcoded technology coupled with deep-sequencing, we track hundreds of thousands of clones at the single-cell level. We generated patient-derived xenograft animal cohorts in which tumors were clonal replicas of each other (each tumor is maintained by the same clones of all other tumors), representing a unique tool to evaluate responses to treatments. More importantly, resistant tumor clones generated in vivo can be isolated and fully characterized and compared to pre-treatment clones to identify new mechanisms of resistance. Our integrated analysis paves the way for new therapeutic strategies for patients to eradicate treatment-resistant CSC by specifically targeting their unique metabolism. In addition, our clonal tracking-based platform monitoring the efficacy of different treatments in eradicating resistant clones represents an unprecedented tool for exploring treatment responses at the single-cell level, which will help guide the development of personalized treatments. Citation Format: Denise Corti, Alessandro Carugo, Seth Sahil, Matteo Marchesini, Piergiorgio Pettazzoni, Luigi Nezi, Tessa Green, Joseph R Marszalek, Maria Emilia Di Francesco, Timothy P Heffernan, Giulio F Draetta, Andrea Viale. Metabolic eradication of treatment resistant cancer stem cells in pancreatic tumors: A clonal tracking-based platform for identifying the best personalized treatment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 976. doi:10.1158/1538-7445.AM2015-976

A conceptual approach for measuring farmers’ attitudes to integrated soil fertility management in Kenya

A sustainable increase in agricultural productivity is essential in assuring food security in developing countries. Low soil fertility is a major contributing factor to the current vicious cycle of low agricultural productivity and inadequate livelihoods among smallholder farmers. Integrated soil fertility management (ISFM) is one way of achieving sustainable agricultural development, but improving soil fertility through ISFM requires interventions that match the behavioural inclinations of farmers and their decision making. Using survey data on 125 commercial peri-urban farmers growing kale (Brassica oleracea) around Nairobi, Kenya, this study examined two conceptual approaches for measuring ISFM attitudes. A Rasch model, where the odds ratio for engaging in an ISFM practice is given by the difference between farmers’ attitude and the difficulty of the practice in terms of behavioural cost, identified ISFM attitudes as a unidimensional concept. However, assessing attitudes based on a standard valence method raised problems of construct validity. Accounting for behavioural costs as determinants of ISFM, in addition to other pecuniary costs, may improve our understanding of how farmers deal with complex choices in the ISFM context. Our findings suggest that high behavioural costs in relation to use of human faeces as manure, use of crop residues and transport impede adoption of ISFM practices vital to increased productivity. These findings can be used to develop ISFM communications and improve the efficacy of different interventions intended to increase potential uptake of ISFM practices.

The adverse effects of hypothyroidism and hyperthyroidism during pregnancy

Due to the important role of thyroid disorders on reproductive health of the women of childbearing age, pregnancy outcome, fetal health, and neurodevelopment of the infant, providing comprehensive assessment of the treatments used for preventing hyperthyroidism and hypothyroidism seems to be essential. Therefore, evaluating the efficacy of different treatments of the thyroid disorders would be beneficial in better managing and controlling the disease during pregnancy. Hypothyroidism (a deficiency of thyroid hormone) is a common thyroid disorder, which might increase the incidence rate of miscarriage, pre-eclampsia, placental abruption, and preterm delivery. Hyperthyroidism, which is not a common disorder during the pregnancy not only leads to similar adverse effects as hypothyroidism but also can result in stillbirth and intrauterine growth restriction. Levothyroxine is the preferred treatment of hypothyroidism and the only drug therapy recommended for treating hyperthyroidism during pregnancy. In this study, we aimed to briefly review the adverse effects of hyperthyroidism and hypothyroidism during pregnancy and review the effects of recent suggested treatments for controlling thyroid disorders on pregnancy outcomes.

Comparative study of antidiarrheal effect of proposed new formulae from D.innoxia hydroalcoholic leave extract against E.coli O:157 induced diarrhea in goats

New proposed formulation of 5% and 7.5% of hydroalcoholic leave extract of D.innoxia were tested as new drug in order to treat induced diarrheal infection by pathogenic E.coliO:157 strain isolate in 16 healthy local goats divided in to equal four groups according to following treatment groups T1 and T2 represented (25 and 37.5 mg/kg D.innoxia),ciprofloxacine (5mg/kg) and DMSO vehicle group 0.5 ml /kg as positive control .Dosing continue orally daily for 14 days after induction of diarrheal infection .The efficacy of different treatment were evaluated according to improvement in clinical symptoms in which the formulation showed dose dependent effect with superiority of higher dose in T2 over ciprofloxacin in reduction body temperature and respiration rate , improvement in body weight gain and dehydration signs with reduction of fecal bacterial count (E.coli ) to nearly normal with completely ceasing diarrhea at the end of treatment . This was due to the presence of multiphytochemical that have not only antibacterial effect but also astringent ,anti-inflammatory ,analgesic ,antispasmodic, narcotic ,antipyretic and antiallergic that help to over come the stress that accompanied diarrheal infection.