Avoidance Of Side Effects Research Articles

Novel Expanding Renal Cell Carcinoma Biomarkers

Identification of reliable molecular biomarkers that can complement clinical practice represents a fascinating challenge in any cancer field. Renal tumors are usually asymptomatic and incidentally identified during imaging studies undertaken for unrelated causes. However, in 25% to 30% of patients the first diagnosis is accompanied by symptoms and associated with distant metastasis. Thus, early diagnosis may reduce the risk of disease progression also avoiding side effects of inadequate treatments. Moreover, the ability to categorize patients' risk of recurrence after radical treatment, or even predict benefit from a target therapy, represents a compelling challenge. Here we review the current state-of-the-art on RCC biomarkers, particularly focusing on the new approaches of genomics, liquid biopsy, proteomics, and metabolomics.

Comparison of Varying Bolus Doses of Oxytocin in Patients Undergoing Caesarean Spinal Delivery

Objective: To determine the lowest effective bolus dose of oxytocin to produce adequate uterine tone during elective caesarean delivery avoiding side effects. Study design and setting: A study was conducted at Rawal General and Dental Hospital, from 10th Oct, 2018 to 27th May, 2019. Methodology: Patients undergoing elective cesarean spinal delivery were randomly divided by computer generated numbers(n=155) into 5 groups A, B, C, D and E receiving 0.5, 1, 3, 5 and 10 units of injection oxytocin as bolus respectively after delivery of baby. Uterine contraction was assessed by gynecologist by manual palpation of uterus on a linear scale. Value of 8 was considered adequate and 8 inadequate uterine tone respectively. Heart rate, non-invasive blood pressure and oxygen saturation were noted before and after oxytocin bolus. All patients received oxytocin infusion. The primary outcome measure was the assessment of uterine tone at 2 minute of oxytocin bolus. The secondary outcome variables included shortness of breath, chest discomfort, top-up bolus administered, hemodynamic variables, epigastric discomfort and oxytocin related effects (tachycardia, epigastric discomfort and hypotension). Results: The use of 5 units oxytocin (group-D) showed most optimal uterine contractions, 61.3% in comparison to commonly used 10 units bolus dose (group-E) 48.4% with minimal side effects like, less tachycardia(12.9% versus 72.9%) and hypotension (12.9% versus 32.3%), no top-up bolus dose was required in 54.8% cases and no complain of epigastric discomfort was observed. Conclusion: Low doses of oxytocin are effective in terms of uterine contraction with minimal side effects

Antimicrobial Efficiency of Moringa oleifera Leave Extracts against Some Multidrug Resistant Pathogen

THE MEDICINAL plants have vital sources of natural antimicrobial substances for human health avoiding side effects precipitated by using synthetic chemical. The decreasing effectiveness of traditional antibiotics towards multi drug resistant microorganism is a global public health. It was found that the mixtures between different plant extract and commercial antibiotics increased the effectiveness of antibiotics multi drug resistant bacteria. The combinations between different plant extract and commercial antibiotics increased the effectiveness of antibiotics against multi drug resistant strains. Extracts of Moringa oleifera leaves showed remarkable antimicrobial activity against the growth of the gram positive and negative bacteria drug resistant clinical strains (Escherichia coli ATCC 10536, Pseudomonas aeruginosa ATCC 9027, Staphylococcus aureus ATCC 29737 and Staph epidermidis ATCC 12228, Bacillus pumilis ATCC 14884, Micrococcus luteus ATCC 10240, Bordetella sp, Bacillus subtilis and Klebsiella sp . Antimicrobial activity of methanol extract of Moringa oleifera leaves (MML) using well diffusion method was higher (30mm inhibition zone) than ethanolic and aqueous extract. The minimum inhibition concentration (MIC) of the selected pathogenic bacteria ranged between 23 -800μg/ml. The interactions between different extract of Moringa oleifera leaves and different antibiotic groups of Ampicillin (Am10), Amoxicillin (AMC30), Amikacin (AK30), Gentamycin (CN10), Tetracycline (TE30), Erythromycin (E15), Bacitracin (B10) were conducted using agar diffusion method against the selected pathogenic bacteria. Methanol extract of Moringa oleifera leaves could be used as a source for resistance-modifying agents against infectious multi-drug resistant bacteria.

COVID-19 in children and adolescents with chronic lung diseases

HintergrundKinder und Jugendliche mit chronischen Lungenerkrankungen standen zu Beginn der SARS-CoV-2-Pandemie im Fokus der Aufmerksamkeit. Mangels epidemiologischer Daten und klinischer Erfahrung war zu befürchten, dass Kinder mit respiratorischen Vorerkrankungen – ähnlich wie im Erwachsenenalter – eine Risikogruppe für besonders schwere Verläufe von COVID-19 darstellen.Ziel der ArbeitEs erfolgen die Darstellung der aktuellen vorliegenden Daten zu dieser Patientengruppe und Schilderung der eigenen Erfahrungen anhand von 3 ausgewählten Fällen.Material und MethodenEs erfolgen die Auswertung der aktuellen (epidemiologischen) Daten, Beschreibung dreier ausgewählter Fälle und Diskussion aktueller Empfehlungen und Handlungsstrategien.ErgebnisseDie Inzidenz von COVID-19-Erkrankungen ist bei Kindern und Jugendlichen deutlich niedriger als bei Erwachsenen. Weiterhin lassen sich die bei Erwachsenen bekannten Risikofaktoren nicht einfach auf das pädiatrische Patientenkollektiv übertragen. Kinder und Jugendliche mit chronischen Lungenerkrankungen zeigen in der Mehrzahl der Fälle einen milden Verlauf einer SARS-CoV-2-Infektion.DiskussionDie insgesamt ermutigenden Erfahrungen sollten nicht darüber hinwegtäuschen, dass es auch bei Kindern und Jugendlichen zu teilweise schweren Verläufen kommt. Weiterhin können Spätfolgen wie das „pediatric inflammatory multisystem syndrome“ (PIMS) mit teilweise fatalem Ausgang auftreten. Dennoch ist darauf zu achten, dass diese vulnerable Patientengruppe nicht durch Isolationsmaßnahmen und Einschränkungen vermeidbare Schäden erleidet. Als Beispiel genannt seien hier aus Corona-Angst abgesagte Ambulanztermine, sodass Verschlechterungen der Grunderkrankung verspätet erkannt werden.

Patient preferences and predicted relative uptake for targeted therapies in metastatic colorectal cancer: a discrete choice experiment

Objective Ras wild-type metastatic colorectal cancers (mCRC) may be treated with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) agents. We aim to estimate patients’ preferences for mCRC treatment and relative importance of cost, efficacy improvement, avoidance of side effects and therapy convenience, and relative uptake between profiles that resemble Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), two commonly prescribed mCRC targeted therapies. Methods Discrete choice experiment (DCE) was administered to English- or Chinese-speaking Stage 2 or 3 colon cancer patients at the National Cancer Centre Singapore. DCE attributes comprise progression-free survival (PFS), severity of acne-like skin rashes, severity of bleeding, out-of-pocket cost per month and frequency of drug administration. Mixed logit model was used to calculate preference weights for all attribute levels. Subgroup analyses were conducted by interacting attribute levels with selected respondent characteristics. Relative uptake rates for various medication scenarios were studied. Results 169 respondents aged 61.5 ± 10.5 years completed the survey. They placed the greatest weight on cost, followed by bleeding and skin rashes, then PFS and finally frequency of drug administration. This was similarly observed in the subgroup analyses. A scenario with shorter PFS but less severe side effects has a slightly higher relative uptake at 55%. One quarter of respondents reported that they would not take the treatment they preferred in the choice task. Conclusion Patients were willing to trade off some degree of efficacy to avoid certain severity of side effects. It is therefore crucial for patients and physicians to discuss patients’ preferences and circumstances to understand which attributes are more important, as well as patients’ views on the trade-offs between treatment benefits and risks.

Quality of care for Black and Latina women living with HIV in the U.S.: a qualitative study

BackgroundEnding the HIV epidemic requires that women living with HIV (WLWH) have access to structurally competent HIV-related and other health care. WLWH may not regularly engage in care due to inadequate quality; however, women’s perspectives on the quality of care they receive are understudied.MethodsWe conducted 12 focus groups and three in-depth interviews with Black (90%) and Latina (11%) WLWH enrolled in the Women’s Interagency HIV Study in Atlanta, GA, Birmingham, AL, Brooklyn, NY, Chapel Hill, NC, Chicago, IL, and Jackson, MS from November 2017 to May 2018 (n = 92). We used a semi-structured format to facilitate discussions about satisfaction and dissatisfaction with health care engagement experiences, and suggestions for improvement, which were audio-recorded, transcribed, and coded using thematic analysis.ResultsThemes emerged related to women’s health care satisfaction or dissatisfaction at the provider, clinic, and systems levels and across Institute of Medicine-defined quality of care domains (effectiveness, efficiency, equity, patient-centeredness, safety and timeliness). Women’s degree of care satisfaction was driven by: 1) knowledge-based care resulting in desired outcomes (effectiveness); 2) coordination, continuity and necessity of care (efficiency); 3) perceived disparities in care (equity); 4) care delivery characterized by compassion, nonjudgment, accommodation, and autonomous decision-making (patient-centeredness); 5) attention to avoiding side effects and over-medicalization (safety); and 6) limited wait time (timeliness).ConclusionsQuality of care represents a key changeable lever affecting engage in care among WLWH. The communities most proximally affected by HIV should be key stakeholders in HIV-related quality assurance. Findings highlight aspects of the health care experience valued by WLWH, and potential participatory, patient-driven avenues for improvement.

Clinical Value of Noncontrast-Enhanced Radial Quiescent-Interval Slice-Selective (QISS) Magnetic Resonance Angiography for the Diagnosis of Acute Pulmonary Embolism Compared to Contrast-Enhanced Computed Tomography and Cartesian Balanced Steady-State Free Precession.

Free-breathing noncontrast-enhanced (non-CE) magnetic resonance angiography (MRA) techniques are of considerable interest for the diagnosis of acute pulmonary embolism (APE), due to the possibility for repeated examinations, avoidance of side effects from iodine-based contrast agents, and the absence of ionizing radiation exposure as compared to CE-computed tomographic angiography (CTA). To analyze the clinical performance of free-breathing and electrocardiogram (ECG)-gated radial quiescent-interval slice-selective (QISS)-MRA compared to CE-CTA and to Cartesian balanced steady-state free precession (bSSFP)-MRA. Prospective. Thirty patients with confirmed APE and 30 healthy volunteers (HVs). Radial QISS- and bSSFP-MRA at 1.5T. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were computed to compare the pulmonary imaging quality between MRA methods. The pulmonary arterial tree was divided into 25 branches and an ordinal scoring system was used to assess the image quality of each pulmonary branch. The clinical performance of the two MRA techniques in accurately assessing APE was evaluated with respect to CE-CTA as the clinical reference standard. Wilcoxon signed-rank and Spearman's correlation tests were performed. Sensitivity and specificity of the MRA techniques were determined using CE-CTA as the clinical reference standard. Thrombus-mimicking artifacts appeared more frequently in lobar and peripheral arteries of patients with Cartesian bSSFP than with radial QISS-MRA (pulmonary trunk: 12.2% vs. 14.0%, P = 0.64; lobar arteries: 35.6% vs. 22.0%, P = 0.005, peripheral arteries: 74.4% vs. 49.0%, P < 0.001). The relative increases in SNR and of CNR provided by radial QISS-MRA with respect to Cartesian bSSFP-MRA were 30-35% (P-values of SNR/CNR, HVs: 0.09/0.09, patients: 0.03/0.02). The image quality of pulmonary arterial branches was considered good to excellent in 77.2% of patients with radial QISS-MRA and in 43.2% with Cartesian bSSFP-MRA (P < 0.0001). The clinical performance of radial QISS-MRA was higher than Cartesian bSSFP-MRA for grading embolism, with a total sensitivity of 86.0% vs. 80.6% and a specificity of 93.3% vs. 84.0%, respectively. Radial QISS-MRA is a reliable and safe non-CE angiographic technique with promising clinical potential compared to Cartesian bSSFP-MRA and as an alternative technique to CE-CTA for the diagnosis of APE. 1 TECHNICAL EFFICACY STAGE: 3.

Designed Manipulation of the Brassinosteroid Signal to Enhance Crop Yield.

Brassinosteroid (BR), a plant steroid hormone, plays crucial role in modulating plant growth and development, which affect crop architecture and yield. However, BR application cannot highly benefit to agricultural production as expectation, because it regulates multiple processes in different tissues and leads to side effect. In addition, accurately modifying BR signal at transcriptional level is difficult. Effective manipulation of the BR signal and avoidance of side effects are required to enhance yield in different crops. Application of BR by spraying at specific developmental stages can enhance crop yield, but this method is impractical for use on a large scale. The accurate molecular design of crops would be much more helpful to manipulate the BR signal in specific organs and/or at particular developmental stages to enhance crop yield. This minireview summarizes the BR regulation of yield in different crops, especially horticultural crops, and the strategies used to regulate the BR signal to enhance crop yield. One popular strategy is to directly modulate the BR signal through modifying the functions of important components in the BR signal transduction pathway. Another strategy is to identify and modulate regulators downstream of, or in crosstalk with, the BR signal to manipulate its role in specific processes and increase crop yield. Efforts to accurately design a BR manipulation strategy will ultimately lead to effective control of the BR signal to avoid side effects and enhance crop yield.

CD279 mediates the homeostasis and survival of regulatory T cells by enhancing T cell and macrophage interactions.

CD279 is a cell surface protein predominantly expressed on T cells. Its ligands CD273 and CD274 are expressed on antigen‐presenting cells and tumors. CD279 has been shown to act as an important immune check point by inhibiting CD8 T cell activation, and antibodies against CD279 enhance T cell‐mediated cytotoxic function. However, whether CD279 has other functions in CD4 T cell homeostasis or in mediating T cell interactions with antigen‐presenting cells remains unclear. In the present study, we show that antibody‐mediated inhibition of CD279 reduces T cell survival in bone marrow in vivo. Unexpectedly, CD279 blockade also compromised regulatory T cell and macrophage interactions by reducing their contact time. The observation that the CD273 antagonist had little effect suggests that CD274 (the second ligand of CD279) plays a more central role in contact between conventional T cells (Tcon) and macrophages. The results of the present study suggest that both CD279 ligands contribute to the interaction length between T cells and macrophages as a mechanism of maintaining Treg homeostasis. Furthermore, CD273 and CD274 are not redundant ligands because CD274 may have unique effects on Tcon in this complex immune axis. Therefore, ligand selection for check point blockade as a tool for cancer immunotherapy has important implications with respect to anti‐tumor T cell activation and the avoidance of side effects.

Abstract IA11: Autoimmune rheumatic diseases and cancer: An example of natural cancer immunoediting?

Abstract A relationship between cancer and autoimmune rheumatic diseases has been observed for many decades, although the relevance of, and mechanisms underlying, this association have remained unclear. Investigating this relationship has been extremely challenging, due to heterogeneity of the rheumatic diseases across multiple dimensions, including kinetics of association of cancer and autoimmunity, the occurrence of cancer in only a subgroup of patients, variable exposure to drugs that are associated with increased incidence of malignancy, and the large number of tumor types associated with rheumatic disease. Several recent observations have provided important opportunities to understand the mechanisms underlying this relationship. (i) Increased cancer incidence across different autoimmune rheumatic diseases is associated with specific autoantibodies. For example, in scleroderma, patients with autoantibodies against RNA polymerase III or components of the minor spliceosome have increased cancer incidence both within cohort and compared to the general population. Similarly, in dermatomyositis, the majority of patients with concomitant cancer are found among patients with autoantibodies directed against either TIF1g or NXP2. (ii) In patients presenting with scleroderma and RNA polymerase 3 autoantibodies who have a concomitant cancer (within 3 years of scleroderma onset), there is evidence of somatic mutation and loss of heterozygosity at the POLR3A locus. There is evidence for T-cell immunity recognizing the specific mutations as well as the wild-type antigens. These findings are specific to patients with POLR3 antibodies and are not observed in patients with other autoantibody specificities. (iii) When comparing cancer incidence in different scleroderma subgroups defined by their autoantibody specificities to the SEER registry, there are striking differences in the SIRs in the different scleroderma subgroups. For example, patients with autoantibodies to POLR3 have an increased SIR for various cancers, while patients with autoantibodies to components of the centromere have strikingly decreased SIRs for cancer. (iv) A subgroup of scleroderma patients with autoantibodies recognizing POLR3 who do not manifest cancer have additional autoantibodies that recognize components of POLR1, suggesting that orthogonal immune responses might play important anticancer roles. Taken together, these data suggest a model in which autoantigen mutations in cancer induce immune responses to mutated and wild-type autoantigens. These immune responses are variably effective at preventing cancer emergence (in the majority of cases, either eliminating the cancers or maintaining them in equilibrium). Understanding the various mechanisms underlying those patients with autoimmune diseases where cancer does or does not emerge may provide important opportunities to understand natural cancer immunoediting, and how these mechanisms might be harnessed for treatment of cancer and avoidance of side effects in cancer immunotherapies. Citation Format: Antony Rosen. Autoimmune rheumatic diseases and cancer: An example of natural cancer immunoediting? [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr IA11.

Development and characterization of oxaceprol-loaded poly-lactide-co-glycolide nanoparticles for the treatment of osteoarthritis.

Oxaceprol is well-defined therapeutic agent as an atypical inhibitor of inflammation in osteoarthritis. In the present study, we aimed to develop and characterize oxaceprol-loaded poly-lactide-co-glycolide (PLGA) nanoparticles for intra-articular administration in osteoarthritis. PLGA nanoparticles were prepared by double-emulsion solvent evaporation method. Meanwhile, a straightforward and generally applicable high performance liquid chromatography method was developed, and validated for the first time for the quantification of oxaceprol. To examine the drug carrying capacity of nanoparticles, varying amount of oxaceprol was entrapped into a constant amount of polymer matrix. Moreover, the efficacy of drug amount on nanoparticle characteristics such as particle size, zeta potential, morphology, drug entrapment, and in vitro drug release was investigated. Nanoparticle sizes were between 229 and 509 nm for different amount of oxaceprol with spherical smooth morphology. Encapsulation efficiency ranged between 39.73 and 63.83% by decreasing oxaceprol amount. The results of Fourier transform infrared and DSC showed absence of interaction between oxaceprol and PLGA. The in vitro drug release from these nanoparticles showed a sustained release of oxaceprol over 30 days. According to cell culture studies, oxaceprol-loaded nanoparticles had no cytotoxicity with high biocompatibility. This study was the first step of developing an intra-articular system in the treatment of osteoarthritis for the controlled release of oxaceprol. Our findings showed that these nanoparticles can be beneficial for an effective treatment of osteoarthritis avoiding side effects associated with oral administration.

Porphyrin Containing Polymersomes with Enhanced ROS Generation Efficiency: In Vitro Evaluation

Porphyrins are molecules possessing unique photophysical properties making them suitable for application in photodynamic therapy. The incorporation of porphyrins into natural or synthetic nano-assemblies such as polymersomes is a strategy to improve and prolong their therapeutic capacities and to overcome their limitations as therapeutic and diagnostic agents. Here, 5,10,15,20-tetrakis(1-(6-ethoxy-6-oxohexyl)-4-pyridin-1-io)-21H,23H-porphyrin tetrabromide porphyrin is inserted into polymersomes in order to demonstrate that the encapsulation enhances its ability to generate highly reactive singlet oxygen (1 O2 ) upon irradiation in vitro. The photoactivation of the free and polymersome-encapsulated porphyrin is evaluated by electron spin resonance and cell viability assays on three different mammalian cell lines. The results indicate that by encapsulating the porphyrin, a controlled ROS delivery within the cells is achieved, at the same time avoiding side effects such as dark toxicity, non-specific porphyrin release and over time decreased activity in vitro. This work focuses on showing a not-toxic model system for modern therapeutic nanomedicine, which works under mild irradiation and dosage conditions.

Levels of Mercury in oil companies and relation of them with the other elements for avoid side effect on the extraction and refining operation and environment

For the first time in Iraq, the estimation of the mercury amount in all the establishments of oil mininstry, is stuided in this wrok.&#x0D; It was found that the presence of mercury in the crude oil, theassociated gas, and the associated water as well as in most flare gases. Also, it was observed that the concentration of mercury on the surface of the soil near the flame is increased its concentration in winds of the flame, where most of the days of the year the wind is coming from the north West towards the south-east.&#x0D; The test of mercury has become a global provision to determine its quantity in crude oil and natural gas, which is required the effective ways, led by the Technical Department of the Ministry of Oil to request the petroleum research and development center to determine the amount of mercury in a number of oil companies.&#x0D; This work is proposed by the analytical department of the petroleum research and development center where the cold testing device was imported for the determination of the tiny amount of mercury in gases, liquids and soil and the detection limit in Nano grams. It is the first device operating in the oil sector using for the determination of mercury amount.&#x0D; However, the search results and quantification of mercury, important relationships were identified in terms of the presence of mercury and other crude oil components or tests on crude oil. It was found that there is a correlation between the concentration of mercury and the sulfur content in oil.&#x0D; Mercury is a volatile substance either vapor, dust, or sulfuric. Therefore, the oil gas contains a percentage of mercury, over time, formed by the burning of the gas and the pollution of air and the soil surrounding the flame, which constitutes an environmental hazard that must be avoided in the future. In addition, the accompanying water has a significant content of mercury.

Pharmacological MRI to investigate the functional selectivity of 5-HT1A receptor biased agonists

The emerging concept of “biased agonism” denotes the phenomenon whereby agonists can preferentially direct receptor signalling to specific intracellular responses among the different transduction pathways, thus potentially avoiding side effects and improving therapeutic effects. The aim of this study was to investigate biased agonism by using pharmacological magnetic resonance imaging (phMRI). The cerebral blood oxygen level dependent (BOLD) signal changes induced by increasing doses of two serotonin 5-HT1A receptor biased agonists, NLX-112 and NLX-101, were mapped in anaesthetized rats. Although both compounds display high affinity, selectivity and agonist efficacy for 5-HT1A receptors, NLX-101 is known to preferentially activate post-synaptic receptors, whereas NLX-112 targets both pre- and post-synaptic receptors. We used several doses of agonists in order to determine if the regional selectivity of NLX-101 was dose-dependent. NLX-112 and NLX-101 induced different positive and negative hemodynamic changes patterns at equal doses. Importantly, NLX-101 had no significant effect in regions expressing pre-synaptic receptors contrary to NLX-112. NLX-112 also produced higher BOLD changes than NLX-101 in the orbital cortex, the somatosensory cortex, and the magnocellular preoptic nuclei. In other regions such as the retrosplenial cortex and the dorsal thalamus, the drugs had similar effects. In terms of functional connectivity, NLX-112 induced more widespread changes than NLX-101. The present phMRI study demonstrates that two closely-related agonists display notable differences in their hemodynamic “fingerprints”. These data support the concept of biased agonism at 5-HT1A receptors and raise the prospect of identifying novel therapeutics which exhibit improved targeting of brain regions implicated in neuropsychiatric disorders.This article is part of the special issue entitled ‘Serotonin Research: Crossing Scales and Boundaries’.

Rapamycin for longevity: opinion article.

From the dawn of civilization, humanity has dreamed of immortality. So why didn’t the discovery of the anti-aging properties of mTOR inhibitors change the world forever? I will discuss several reasons, including fear of the actual and fictional side effects of rapamycin, everolimus and other clinically-approved drugs, arguing that no real side effects preclude their use as anti-aging drugs today. Furthermore, the alternative to the reversible (and avoidable) side effects of rapamycin/everolimus are the irreversible (and inevitable) effects of aging: cancer, stroke, infarction, blindness and premature death. I will also discuss why it is more dangerous not to use anti-aging drugs than to use them and how rapamycin-based drug combinations have already been implemented for potential life extension in humans. If you read this article from the very beginning to its end, you may realize that the time is now.

Natural Products from Mediterranean Diet: From Anti-hyperlipidemic Agents to Dietary Epigenetic Modulators.

Cardiovascular Diseases (CVD) are, currently, the major contributor to global mortality and will continue to dominate mortality rates in the future. Hyperlipidemia refers to the elevated levels of lipids and cholesterol in the blood, and is also identified as dyslipidemia, manifesting in the form of different disorders of lipoprotein metabolism. These abnormalities may lead to the development of atherosclerosis, which can lead to coronary artery disease and stroke. In recent years, there is a growing interest in the quest for alternative therapeutic treatments based on natural products, offering better recovery and the avoidance of side effects. Recent technological advances have further improved our understanding of the role of epigenetic mechanisms in hyperlipidemic disorders and dietary prevention strategies. This is a comprehensive overview of the anti-hyperlipidemic effects of plant extracts, vegetables, fruits and isolated compounds thereof, with a focus on natural products from the Mediterranean region as well as the possible epigenetic changes in gene expression or cardiometabolic signaling pathways. For the purpose of this study, we searched the PubMed, Scopus and Google Scholar databases for eligible articles and publications over the last five years. The keywords included: "hyperlipidemia", "plant extract", "herbs", "natural products", "vegetables", "cholesterol" and others. We initially included all relevant articles referring to in vitro studies, animal studies, Randomized Controlled Trials (RCTs) and previous reviews. Many natural products found in the Mediterranean diet have been studied for the treatment of hyperlipidemia. The antihyperlipidemic effect seems to be dose and/or consumption frequency related, which highlights the fact that a healthy diet can only be effective in reversing disease markers if it is consistent and within the framework of a healthy lifestyle. Finally, epigenetic biomarkers are increasingly recognized as new lifestyle management tools to monitor a healthy dietary lifestyle for the prevention of hyperlipidaemic disorders and comorbidities to promote a healthy life.

Encapsulated Carbenoxolone Reduces Lung Metastases

Carbenoxolone is an anti-inflammatory compound and a derivate of a natural substance from the licorice plant. We previously showed that carbenoxolone reduces the metastatic burden in the lungs of mice through its antagonistic effect on high mobility group box 1 (HMGB1). To further enhance carbenoxolone’s activity and localization in the lungs, thereby reducing the potential adverse side effects resulting from systemic exposure, we developed a poly(lactic-co-glycolic acid) (PLGA) slow-release system for pulmonary delivery which maintains drug activity in-vitro, as demonstrated in the anoikis assay. Both systemic and intranasal administrations of carbenoxolone effectively minimize metastatic formation in a lung colonization model in mice. Our results show a decrease in the metastatic burden in the lung tissue. Notably, the therapeutic effect of a single intranasal administration of 25 mg/kg carbenoxolone, in the form of drug-loaded particles, had a similar effect in reducing metastatic lesions in the lungs to that of a 10-fold dose of the free drug via intraperitoneal injections, three times per week over the course of four weeks. These data offer new means to potentiate the anti-cancer activity of carbenoxolone and simultaneously reduce the requirement for high dosage administration; the upshot substantially improves therapeutic effect and avoidance of side effects.

Physiology in Perspective: The Dilemma of Muscle Weakness.

Physiology in Perspective: The Dilemma of Muscle Weakness.

Survey on the Prevalence of Intravenous Use of Proton Pump Inhibitors and H2-antagonists in Internal Medicine Ward

Background: Anti-acids drugs are commonly used for stress ulcer prophylaxis (SUP). Some inpatients receiving acid suppression therapy without risk factors for nosocomial upper gastrointestinal bleeding and this inappropriate usage increase time, costs and avoidable side effects such as hospital-acquired pneumonia.&#x0D; Purpose: This study was designed to evaluate the prevalence of stress ulcer prophylactic drugs use, the number of properly indicated administrations and prescription prevalence of intravenous use of proton pump inhibitors (PIPs) and H2-antagonists in preventing nosocomial gastrointestinal bleeding and pneumonia.&#x0D; Methods: This cross-sectional study was performed on 280 patients in two different time zone before and after implementing of guidelines for SUP usage on the medical service in January and March of 2014(pre-intervention period) and January and march of 2015 (post-intervention period). Indicated anti-acid therapy for stress ulcer prophylaxis was defined according to the 1999 American Society of Health-System Pharmacists (ASHP) guidelines for the use of SUP. The Patient’s data such as kind of stress ulcer prophylaxis drug, ICU admission and the indication of prophylaxis pre and post-intervention were collected. Data were analyzed by SPSS software using the Pearson Chi-square test and unpaired t-test.&#x0D; Results: There was no significant change in the administration of stress ulcer prophylaxis drugs in general, but anti-acid medications misused decreased from 63.6% to 55.2% after intervention.&#x0D; Conclusion: The use of anti-acids without proper indication had 11.4% fall. The IV administration had a dramatic decrease as opposed to PO anti-acids use, which had a significant effect on hospital financial costs. In the end, there was no significant change detected in the total use of SUP (stress ulcer prophylaxis).

PS1243 JAK‐INHIBITION WITH RUXOLITINIB IN PATIENTS WITH RELAPSED OR REFRACTORY CLASSICAL HODGKIN LYMPHOMA: A PHASE II, OPEN LABEL, MULTICENTER CLINICAL TRIAL (JERICHO)

Background:About 15 % of classical Hodgkin Lymphoma (cHL) patients relapse after 1st‐line therapy of which only half, if transplant‐eligible, can be cured with high dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Patients relapsing after HDCT and ASCT have a dismal prognosis and eventually progress also after subsequent administration of brentuximab vedotin (BV) or anti‐PD1‐antibodies. New therapeutic approaches exploiting specific cHL pathways in thereby avoiding side effects known from conventional therapies are hence warranted in relapsed or refractory (r/r) cHL.Aims:In cHL 9p24.1 amplification is a disease‐specific structural alteration that induces Janus kinase 2 (JAK2) signaling and increases PD‐1 ligand expression. As the JAK/STAT pathway is involved in PD‐L1 upregulation, which is a hallmark of cHL, it is a highly attractive clinical target. Ruxolitinib is an oral potent selective inhibitor of JAK1 and JAK2 kinases. Potentially leveraging this promising data, the phase II JeRICHO trial evaluated treatment with ruxolitinib in patients with r/r cHL.Methods:JeRICHO (NCT02164500) adopted a two‐stage phase II design (Simon 1989). If ≥1 overall response (OR) was observed among the 12 evaluable patients enrolled into the first stage, 25 additional patients would be recruited for the second stage. Patients aged 18–99 years with histologically confirmed r/r cHL requiring treatment after at least one appropriate therapy regimen, including HDCT + ASCT if transplant eligible, were included. 25 mg ruxolitinib were administered orally twice daily in continuous 28‐day cycles until progression or unacceptable toxicity. The primary endpoint was the PET/CT‐based OR‐rate (ORR, complete response (CR) or partial response (PR)) after two cycles. Secondary endpoints included progression free survival (PFS) and overall survival (OS) as well as treatment feasibility (dose reductions, treatment duration and adverse events).Results:From 10/2015 to 05/2017 14 patients were enrolled, 2 were excluded afterwards due to disconfirmed cHL diagnosis. At the time of recruitment patients were between 18 and 76 years old (median = 55.5 years) and had received up to 11 (median = 4) previous HL‐therapies (7/12 HDCT + ASCT, 2/12 allogeneic SCT, 12/12 BV). For qualified patients, median treatment duration was 10 weeks (range: 7–38) and the median number of ruxolitinib cycles received was 3 (range: 2–13). Response evaluation was performed at least once for 11 of 12 qualified patients. After 2 cycles, PR was observed in 2, stable disease (SD) in 3 and progressive disease (PD) in 6 patients (ORR: 2/11 evaluable patients, 18%). Best response to treatment was PR, SD or PD for 3, 2, and 6 patients, respectively. Median PFS was 3.6 months and the 1‐year PFS estimate was 8.3 %. The 1‐year OS estimate was 50.6% (median not reached). The toxicity profile was favorable with no grade 4 or 5 toxicities observed. Hematological toxicity was low with no grade 3/4 toxicity except for one case of grade 3 leukocytopenia. Two observed deaths were considered Hodgkin lymphoma related. Detailed data on efficacy, toxicity and treatment administration will be presented.Summary/Conclusion:Ruxolitinib showed modest activity and a favorable side effect profile in r/r cHL. However, the median PFS was only 3.6 months, and no CR was achieved. Even though the formal stopping criterion after stage I was not met, it was decided, that the trial would not continue to stage II due to the low response rate observed.