Αρχειοθήκη ιστολογίου

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Κυριακή 15 Απριλίου 2018

Rise of women in medicine not matched by leadership roles [News]



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What really matters at the end: perspectives from a patient, a family member and an oncologist [Humanities]



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Review calls for major overhaul of federally funded health organizations [News]



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Quality primary health care will drive the realization of universal health coverage [Commentary]



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Whole-family treatment of neonatal abstinence syndrome [Letters]



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Psychometric findings and normative values for the CLEFT-Q based on 2434 children and young adult patients with cleft lip and/or palate from 12 countries [Research]

BACKGROUND:

Patients with cleft lip and/or palate can undergo numerous procedures to improve appearance, speech, dentition and hearing. We developed a cleft-specific patient-reported outcome instrument to facilitate rigorous international measurement and benchmarking.

METHODS:

Data were collected from patients aged 8–29 years with cleft lip and/or palate at 30 hospitals in 12 countries between October 2014 and November 2016. Rasch measurement theory analysis was used to refine the scales and to examine reliability and validity. Normative CLEFT-Q values were computed for age, sex and cleft type.

RESULTS:

Analysis led to the refinement of an eating and drinking checklist and 12 scales measuring appearance (of the face, nose, nostrils, teeth, lips, jaws and cleft lip scar), health-related quality of life (psychological, social, school, speech distress) and speech function. All scales met the requirements of the Rasch model. Analysis to explore differential item functioning by age, sex and country provided evidence to support the use of a common scoring algorithm for each scale for international use. Lower (worse) scores on CLEFT-Q scales were associated with having a speech problem, being unhappy with facial appearance, and needing future cleft-related treatments, providing evidence of construct validity. Normative values for age, sex and cleft type showed poorer outcomes associated with older age, female sex and having a visible cleft.

INTERPRETATION:

The CLEFT-Q represents a rigorously developed instrument that can be used internationally to collect and compare evidence-based outcomes data from patients aged 8–29 years of age with cleft lip and/or palate.



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Resisting influence from agri-food industries on Canadas new food guide [Commentary]



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Why strengthening primary health care is essential to achieving universal health coverage [Analysis]



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Canadas future health care system [Letters]



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Mycotic aneurysm formation after bacillus Calmette-Guerin instillation for recurrent bladder cancer [Practice]



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Powassan virus -- an emerging public health concern [Practice]



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Chronic pain associations struggle to raise awareness of "silent epidemic" [News]



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Impact of Powered and Tissue-Specific Endoscopic Stapling Technology on Clinical and Economic Outcomes of Video-Assisted Thoracic Surgery Lobectomy Procedures: A Retrospective, Observational Study

Abstract

Introduction

Video-assisted thoracic surgery (VATS) lung resections are complex procedures with a critical role played by endoscopic staplers in the transection of vessels, bronchi, and lung tissue. This retrospective, observational study compared hospital resource use, costs, and complications of VATS lobectomy procedures for whom powered versus manual endoscopic surgical staplers were used.

Methods

Patients ≥ 18 years of age undergoing elective VATS lobectomy during an inpatient admission from January 1, 2012 to September 30, 2016 were identified from the Premier Healthcare Database (first admission = index admission). Use of either powered or manual endoscopic staplers during the index admission was identified from hospital administrative records. Multivariable regression analyses adjusting for patient, hospital, and provider characteristics and hospital-level clustering were carried out to compare the following outcomes between the powered and manual stapler groups: hospital length of stay (LOS), operating room time (ORT), hospital costs, complications (bleeding and/or transfusions, air leak complications, pneumonia, and infection), discharge status, and 30-, 60-, and 90-day all-cause readmissions.

Results

The powered and manual stapler groups comprised 659 patients (mean age 66.1 years; 53.6% female) and 3100 patients (mean age 66.7 years; 54.8% female), respectively. In the multivariable analyses, the powered stapler group had shorter LOS (4.9 vs. 5.9 days, P < 0.001), lower total hospital costs ($23,841 vs. $26,052, P = 0.009), and lower rates of combined hemostasis complications (bleeding and/or transfusions; 8.5% vs. 16.0%, P < 0.001) and transfusions (5.4% vs. 10.9%, P = 0.002), compared with the manual stapler group. Other outcomes did not differ significantly between the study groups. Similar trends were observed in subanalyses comparing devices across predominant manufacturers in each group, and in subanalyses of patients with comorbid chronic obstructive pulmonary disease.

Conclusion

In this analysis of VATS lobectomy procedures, powered staplers were associated with significant benefits with respect to selected types of hospital resource use, costs, and clinical outcomes when compared with manual staplers.

Funding

Johnson & Johnson.



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Antidiabetic Properties of Low-Molecular-Weight BDNF Mimetics Depend on the Type of Activation of Post-Receptor Signaling Pathways

Reduced proliferation and enhanced apoptosis of β cells in diabetes mellitus are associated with a deficiency of brain-derived neurotrophic factor (BDNF). Low-molecular weight compounds similar to different BDNF loops were synthesized at the V. V. Zakusov Research Institute of Pharmacology. They produce a potentiating effect on TrkB phosphorylation, but differently activate post-receptor signaling pathways. We compared their effects on the severity of streptozotocin-induced diabetes mellitus in C57Bl/6 mice. The antidiabetic effect (estimated from the degree of hyperglycemia and dynamics of body weight) was typical of GSB-214 compound that selectively activates PI3K/Akt. This activity was not revealed in GTS-201, selective activator of MAPK/Erk. GSB-106 compound activating both signaling pathways exhibited weak antidiabetic activity. Our results indicate that the antidiabetic effect is mainly related to activation of the PI3K/Akt signaling pathway.



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Expression of Bcl-2 Family Proteins in the Ovarian Follicular Apparatus in the Acute Period after Experimental Hyperthermia

The expression of apoptosis regulators (proapoptotic protein Bad and anti-apoptotic protein Bcl-2) was analyzed and Bcl-2/Bad ratio in the follicular apparatus of the rat ovary was determined on day 3 after hyperthermia (rectal temperature 43.5°C). Hyperthermia in the catabolic phase leads to different degrees of activation of the molecular "switches" of apoptosis in cells of ovarian follicular epithelium. This was seen from increased intensity of immunohistochemical staining for Bad protein against the background of more pronounced expression of Bcl-2 protein. On day 3 after exposure to hyperthermia, Bcl-2/Bad ratio increased, which reflects antiapoptotic protection of cells and conditions for blockade of mitochondrial pathway of apoptosis in the follicular apparatus of the ovaries during the acute period after hyperthermia.



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TNFα-Induced Expression of Transport Protein Genes in HUVEC Cells Is Associated with Enhanced Expression of Transcription Factor Genes RELB and NFKB2 of the Non-Canonical NF-κB Pathway

Endothelial HUVEC cells used as an in vitro model of the endothelial monolayer in placental barrier were activated by TNFα in a dose of 2 ng/ml for 24 h. Significant changes in the expression of genes of the SLC family transport protein were observed: an increase in the expression of SLC7A2, SLC12A2, SLC9B2, SLC25A37, SLC16A9, and SLC41A2 and a decrease in the expression of SLC40A1. These transporters participate in the transport of iron, magnesium, sodium, potassium, and chloride ions, protons, and amino acids. It was also found that SLC7A2, SLC12A2, SLC9B2, SLC25A37, and SLC41A2 genes have binding sites for transcriptional factor RelB that together with NFKB2 is the main effector of the non-canonical NF-κB pathway. The expression of RELB and NFKB2 genes was also significantly enhanced in TNFα-activated HUVEC cells, which can attest to the important role of the non-canonical NF-κB pathway in the regulation of gene expression of transport proteins in response to TNFα stimulation.



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Effect of Natural Cytokine Complex on the Structure and Metabolism of the Cardiac Conduction System in the Myocardium under Normally and Increased Hemodynamic Load

Effect of natural complex of cytokines with activity of IL-1, IL-2, IL-6, TNF, MIF, and GTFβ on the structure and metabolism of conduction cardiomyocytes was assessed in the control and under acute experimental aortic stenosis. After systemic administration of the cytokine complex in the control, structural abnormalities were revealed in a relatively low number of conduction cardiomyocytes; their relative number increased in the left ventricle and interventricular septum. When the complex was administered against the background of aortic stenosis, morphological changes in the conduction system were seen in a significant number of cells with their plasma imbibition, especially in the left ventricle and interventricular septum. Systemic administration of the natural cytokine complex inhibited the major metabolic processes in the conduction system, both in the control and under conditions of sharply increased hemodynamic load. In conduction cardiomyocytes, deceleration of glycolysis and citric acid cycle, inhibition of oxidation of free fatty acids and their metabolites, and suppression of shuttle mechanisms and biosynthetic reactions were observed. Increased blood levels of cytokines, primarily of the proinflammatory ones, can cause structural and metabolic disturbances in the cardiac conduction system and promote the development of arrhythmias, especially in case of sharply increased hemodynamic load.



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Injection of Multipotent Mesenchymal Stromal Cells as a Cause of Hemorrhages in the Regional Lymph Nodes: Experimental Study

Hemorrhagic changes after subcutaneous injection of autologous bone marrow multipotent mesenchymal cells with transfected GFP gene and additionally stained cell membranes to WAG rats in the projection of ligated femoral vein were studied by fluorescent microscopy. Hemorrhages in tissues with experimental acute local venous occlusion were caused by a combination of venous hypertension with inflammation around the foreign body — the ligature used for ligation of the vein. Fibrin found in tissues together with erythrocytes in the hemorrhages could stimulate the formation of granulations and new vessels instead of damaged or thrombosed ones. Multipotent mesenchymal stromal cells and their detritus getting into the regional lymph nodes initiated immune reactions morphologically confirmed by stubborn hypertrophy and hyperplasia of the lymphoid nodules, hemorrhages, and manifest diapedesis of erythrocytes to the organ parenchyma and sinus system.



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In Vivo Experimental Study of Biological Compatibility of Tissue Engineered Tracheal Construct in Laboratory Primates

Biological compatibility of a tissue engineered construct of the trachea (synthetic scaffold) and allogenic mesenchymal stem cells was studied on laboratory Papio hamadryas primates. Subcutaneous implantation and orthotopic transplantations of tissue engineered constructs were carried out. Histological studies of the construct showed chaotically located filaments and mononuclear cells fixed to them. Development of a fine connective tissue capsule was found at the site of subcutaneous implantation of the tissue engineered construct. The intact structure of the scaffold populated by various cell types in orthotopic specimens was confirmed by expression of specific proteins. The results indicated biological compatibility of the tissue engineered construct with the mesenchymal stem cells; no tissue rejection reactions were recorded; simulation of respiratory disease therapy on Papio hamadryas proved to be an adequate model.



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Effect of Nanocrystalline Particles of Chitin on Blood Components in Humans and Experimental Animals

Nanocrystalline particles of chitin in the form of hydrosol in a concentration of 0.63 mg/ml have no effect on aggregation of human platelets and clotting time of platelet-poor plasma in coagulation tests. ADP-induced aggregation of human platelets was inhibited by these nanoparticles in concentrations of 0.63 and 1.00 mg/ml in comparison with the control. Intravenous administration of nanoparticles in a dose of 1 mg/kg to guinea pigs produced no anticoagulant effect. The nanocrystalline particles of chitin can be of interest as potential drug delivery systems.



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Electrophysiological Properties of Rat Vestibular Labyrinth and Their Effect on Parameters of Transmitted Voltage Pulses

We propose a new approach to optimization of electrical stimulation of the vestibular nerve and improving the transfer function of vestibular implant. A mathematical model of the vestibular organ is developed based on its anatomy, the model premises, 3D-analysis of MRI and CT images, and mathematical description of physical processes underlying propagation of alternating electric current across the tissues of vestibular labyrinth. This approach was tested in vitro on the rat vestibular apparatus and had been examined anatomically prior to the development of its mathematical model and equivalent electrical circuit. The experimental and theoretical values of changes of the gain—phase characteristics of vestibular tissues in relation to location of the reference electrode obtained in this study can be used to optimize the electrical stimulation of vestibular nerve.



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Bimodal Electrical Properties of Rat Major Artery Segment In Situ

In experiments on narcotized rats, BP in the left femoral artery as well as local electrical potential and electrical impedance of the symmetric segment of the right femoral artery were simultaneously recorded in situ with two extracellular nonpolarizable Ag/AgCl electrodes located along the artery at a distance of 3 mm from each other. The pulsatile arterial electrical potentials with amplitude of 100-200 μV and duration of about 50 msec were recorded, which coincided with the front of BP wave corrected for a 10-msec delay of the pressure transducer. Under normal conditions, the pulsatile oscillations of arterial electroimpedance were in-phase with BP oscillations, so the rising phase of BP was paralleled by elevation of electroimpedance reflecting constriction of the arterial segment. This finding is viewed as indicative of periodic myogenic Ostroumov—Bayliss effect triggered by arterial pulse. After local application of tetrodotoxin (3×10—7 М), procaine (0.5%), or lidocaine (spray 10%) to isolated arterial segment, its electroimpedance oscillated out-of-phase with BP, so the changes of electroimpedance were similar to the response of a passive elastic tube to pulsatile BP. The applied agents completely (tetrodotoxin) or pronouncedly (procaine, lidocaine) inhibited the pulsatile arterial electrical potential. The present data indicate the possibility of passive and active modes of arterial pulsing, which differ by the amplitude of pulsatile arterial electrical potential as well as by phasic relations between BP and electroimpedance. The possible physiological role of various modes of pulsing in major arteries is discussed.



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Induced Pluripotent Stem Cell-Derived Hematopoietic Embryoid Bodies Secrete Sphingosine-1-Phosphate and Revert Endothelial Injury

The possibility of sphingosine-1-phosphate production by induced pluripotent stem cells is examined to assess their potential in treatment of sepsis. The hematopoietic embryoid bodies were derived from the culture of 6-day-old differentiated induced pluripotent stem cells. These embryoid bodies secreted sphingosine-1-phosphate, an important bioactive lipid that regulates integrity of the pulmonary endothelial barrier, prevents elevation of its permeability, and impedes the formation of stress fibers in human endotheliocytes derived from umbilical vein. The data attest to potentiality of induced pluripotent stem cells in treatment of sepsis.



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Changes in Activity of Matrix Metalloproteinases and Serum Concentrations of Proinsulin and C-Peptide Depending on the Compensation Stage of Type 2 Diabetes Mellitus

In patients with type 2 diabetes mellitus, serum activities of MMP-2 and MMP-7 were substantially decreased in comparison with apparently healthy individuals. At the decompensation stage, along with the increased content of glucose and glycated hemoglobin, a pronounced (3-fold) increase in proinsulin concentration was observed. On the contrary, MMP activity and C-peptide concentration decreased at this stage. The ratio of proinsulin concentration to MMP activity at the stages of diabetes mellitus compensation and subcompensation was approximately 1:50, while at the stage of decompensation it was 1:12. Thus, the ratio of these blood serum parameters can be used as an additional diagnostic marker of diabetes decompensation and severity of its complications.



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Coupling of Lipoperoxidation Reactions with Changes in Arterial Blood Pressure in Hypertensive ISIAH Rats under Conditions of Chronic Stress

Mature normotensive male WAG rats and stress-sensitive hypertensive ISIAH rats were exposed to "everyday life stress" modelled by alternation of immobilization and adaptation. Increased LPO intensity (increased content of substrates with unsaturated double bonds and primary and secondary LPO products) and reduced content of some antioxidant protection components (reduced retinol level and GSH/GSSG ratio) were revealed in the blood of ISIAH rats. These changes correlated with elevated mean BP. The results can reflect the significant role of LPO changes in the pathogenesis of stress-induced arterial hypertension.



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Effect of Oxidized Dextran on Cytokine Production and Activation of IRF3 Transcription Factor in Macrophages from Mice of Opposite Strains with Different Sensitivity to Tuberculosis Infection

We studied differences in the production of pro- and anti-inflammatory cytokines and IRF3 transcription factor by peritoneal macrophages from mice of opposite strains CBA/J and C57Bl/6 and the effect of 60-kDa oxidized dextran on these parameters. Macrophages from C57Bl/6 mice were mainly characterized by the production of proinflammatory cytokines TNFα, IL-12, and MCP-1 (markers of M1 polarization). By contrast, CBA/J mice exhibited a relatively high level of anti-inflammatory cytokine IL-10 and lower expression of proinflammatory cytokines (M2 phenotype). IRF3 content in peritoneal macrophages of CBA/J mice was higher than in C57Bl/6 mice. Oxidized dextran decreased the expression of IRF3 upon stimulation of cells from CBA/J mice with LPS, but increased this process in C57Bl/6 mice. Despite a diversity of oxidized dextran-induced changes in cytokine production, the data confirm our hypothesis that this agent can stimulate the alternative activation of macrophages.



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Modeling of 3D Structure of Chimeric Constructs Based on Hemagglutinin of Influenza Virus and Immunogenic Epitopes of Streptococcus Agalactiae

A project of an experimental recombinant vector vaccine for prevention of diseases caused by pathogenic streptococci based on ScaAB lipoprotein of Streptococcus agalactiae and a coldadapted strain of live influenza vaccine as a vector was developed. The sequence of ScaAB lipoprotein was analyzed and fragments forming immunodominant epitopes were determined. Chimeric molecules of influenza virus hemagglutinin H7 carrying insertions of bacterial origin were constructed. Based on the results of simulation, the most promising variants were selected; they represented fragments of lipoprotein ScaAB lacking N-terminal domain bound to hemagglutinin via a flexible linker. These insertions should minimally modulate the properties of the influenza strain, while retaining potential immunogenicity to a wide group of pathogenic streptococci.



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Complex Analysis of Total and Fetal DNA and Cytokines in Blood Plasma of Pregnant Women with Preeclampsia

We performed a complex analysis of total and fetal extracellular DNA, 8 cytokines (IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage CSF, IFNγ, and TNFα) in blood plasma obtained from women with preeclampsia prior to labor onset. Total (sensitivity 89.47%, specificity 93.75%) and fetal extracellular DNA (sensitivity 73.68%, specificity 87.5%) were the most accurate parameters determining preeclampsia. We revealed a high correlation (p=3×10—6) between total and fetal extracellular DNA levels in the group of preeclampsia. Preeclampsia significantly increased the levels of macrophage factors IL-10 and IL-6. These cytokines significantly correlated with the levels of total and fetal extracellular DNA in the preeclampsia group. In the control group, such correlations were not observed. These findings obtained suggest that preeclampsia develops upon increased macrophage activity, leading to destruction of the placenta trophoblast cells.



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Pathogenetic Role of Endothelial Dysfunction in Idiopathic Vestibulopathy

Comparative analysis of the groups of patients with idiopathic bilateral vestibular hypofunction and a group of vestibulopathy patients with vertebrobasilar insufficiency demonstrated identity of the basic and additional diagnostic parameters in these syndromes as well as similarity in clinical diagnostic and anamnesis data. In all cases, functional assessment of endothelium-dependent vasodilation and selected biochemical marker sICAM-1 revealed endothelial dysfunction. Drug correction of endothelial dysfunction positively affected the manifestations of major and minor features of the syndrome, which confirmed the contribution of endothelial functional disturbances to the pathogenesis of bilateral vestibular hypofunction.



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Analysis of the Role of Carriership of Polymorphic Genotypes of ESR1 , eNOS , and APOE4 Genes in the Development of Arterial Hypertension in Men

We studied the role of the carrier status for polymorphic loci of genes encoding estrogen receptors (ESR1), endothelial NO synthase (eNOS), and apolipoprotein E (APOE4) and products of their expression nitrogen oxide (NO) and apolipoprotein (ApoE) in the development of arterial hypertension in men. Conventionally healthy volunteers and 149 men with clinical manifestations of stage I-II arterial hypertension were examined. In men with arterial hypertension, the frequency of minor allele A of ESR1 gene was higher (27.5 vs. 9.5% in the reference group; χ2=4.43, p=0.04). The level of NO in the peripheral blood was also higher in the main group (χ2=3.93, p=0.047). The increase in NO concentration did not depend on the presence of polymorphic genotypes (GG and GT) of eNOS gene, but the decrease in ApoE level in blood serum was associated with TC genotype of APOE4 gene (p=0.04). Our results suggest that minor allele A of ESR1 gene is associated with the development of arterial hypertension in men. Reduced content of ApoE in blood serum of men with arterial hypertension was associated with APOE4 gene polymorphism. However, increased level of NO did not depend on polymorphic genotypes GG and GT of eNOS gene. These polymorphisms are of specific interest as additional markers of genetic predisposition to the development of arterial hypertension in middle-age men.



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Chest wall mass in a 15-year-old female patient



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Anesthetized by chloroform before hanging

Abstract

We present a unique case of suicidal hanging. The deceased was a 31-year-old male who was found hanging from a tree in a dense thicket, with his lower limbs in contact with the ground (partial suspension). There was an apparatus similar to a facial mask placed around his nose and mouth. A strong chemical smell was emanating from the apparatus, which was identified as chloroform (Formyl trichloride/CHCl3). A ligature with a soft cloth beneath it was around his neck. A ligature mark was present around the neck. The decedent's blood alcohol levels were 112 mg/dl. The blood and stomach contents were negative for chloroform. A complete death investigation, including scene investigation and complete autopsy examination, confirmed the cause of death as hanging. The manner of death was suicide. This case highlights how the deceased had used several methods whilst committing suicide to minimize pain, including the inhalation of chloroform, which would have also resulted in the inability to engage in protective actions during the act.



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BLU-667 Targets RET-Altered Cancers [News in Brief]

Investigational drug is safe, shows early promise in patients with medullary thyroid cancer and NSCLC.



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Adjuvant Therapy for Melanoma Prolongs RFS [News in Brief]

PD-1 inhibitor pembrolizumab reduces recurrence risk in patients with stage III disease.



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Precision Targeted Therapy With BLU-667 for RET-Driven Cancers [Research Articles]

The receptor tyrosine kinase, rearranged during transfection (RET), is an oncogenic driver activated in multiple cancers including non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC). No approved therapies have been designed to target RET; treatment has been limited to multi-kinase inhibitors (MKIs) which can have significant off-target toxicities and limited efficacy. BLU-667 is a highly potent and selective RET inhibitor designed to overcome these limitations. In vitro, BLU-667 demonstrated ≥10-fold increased potency over approved MKIs against oncogenic RET variants and resistance mutants. In vivo, BLU-667 potently inhibited growth of NSCLC and thyroid cancer xenografts driven by various RET mutations and fusions without inhibiting vascular endothelial growth factor receptor 2 (VEGFR-2). In first-in-human testing, BLU-667 significantly inhibited RET signaling and induced durable clinical responses in patients with RET-altered NSCLC and MTC without notable off target toxicity, providing clinical validation for selective RET targeting.



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Pathological Remodeling of the Myocardium in Chronic Heart Failure: Role of PGC-1α

Pathological remodeling of the myocardium in chronic heart failure includes the development of pathological cardiac hypertrophy, reactivation of the fetal genetic program, and disorders in cardiac energy metabolism. Coactivator-1α of receptor γ activated by peroxisome proliferator (PGC-1α), a transcription coactivator of nuclear receptors and metabolism master regulator, plays an important role in cardiac metabolism regulation. Studies on the animals models of chronic heart failure have demonstrated the development of pathological cardiac hypertrophy, metabolic disorders, and reactivation of the fetal genetic program; these processes are mutually related. An important role in regulation of these processes belongs to PGC-1α; its low expression indicates low activity and down-regulation of this coactivator. Pathological cardiac hypertrophy, decrease of PGC-1α activity, and reactivation of the fetal genetic program in chronic heart failure are demonstrated.



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Circular RNA: New Regulatory Molecules

Circular RNA are a family of covalently closed circular RNA molecules, formed from pre-mRNA of coding genes by means of splicing (canonical and alternative noncanonical splicing). Maturation of circular RNA is regulated by cis- and trans-elements. Complete list of biological functions of these RNA is not yet compiled; however, their capacity to interact with specific microRNA and play a role of a depot attracts the greatest interest. This property makes circular RNA active regulatory transcription factors. Circular RNA have many advantages over their linear analogs: synthesis of these molecules is conservative, they are universal, characterized by clearly determined specificity, and are resistant to exonucleases. In addition, the level of their expression is often higher than that of their linear forms. It should be noted that expression of circular RNA is tissue-specific. Moreover, some correlations between changes in the repertoire and intensity of expression of circular RNA and the development of some pathologies have been detected. Circular RNA have certain advantages and can serve as new biomarkers for the diagnosis, prognosis, and evaluation of response to therapy.



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Comparative Characteristics of Discrimination of S. enterica Isolates by Phagotyping Test and Dienes Test

We propose an original methodological approach to discrimination of newly isolated Salmonella enterica strains with the use of Dienes test. Dienes test is used for identification of P. vulgaris and P. mirabilis strains. It consists in growth suppression by mobile bacterial strain cultures and the formation of a demarcation line (Dienes line) between the strains growing towards each other. Similarities and differences between salmonella phagotyping method and Dienes test-based discrimination of the strains are detected. The studied sample of salmonellas was divided into 12 phagotypes. Cluster analysis has shown that most of the salmonella strains could not be clusterized by both methods. Discrimination by different methods has shown that the largest clusters contain the same strains. Clusterization of salmonella strains by different methods shows moderate congruency. Rand index used for comparison of the results of the sample clusterization by different methods is 0.88. High heterogeneity of salmonella strains is presumably explained by heterogeneity of antagonism factors within the S. enterica species. Intraspecies antagonism is essential for limitation of the horizontal gene transfer in closely related strains and for increase of the genetic heterogeneity of salmonella population in the host.



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Fungal, Bacterial, and Archaeal Diversity in the Digestive Tract of Several Beetle Larvae (Coleoptera)

Interpretation of how partnerships between fungi, bacteria, archaea, and insects are maintained through the life of the hosts is a big challenge within the framework of symbiosis research. The main goal of this work was to characterize the gut microbiota in larvae of several Coleoptera species using sequencing of the bacterial and archaeal 16S rRNA genes and fungal internal transcribed spacer (ITS) region. Thus, larvae with various food preferences, including Amphimallon solstitiale, Oryctes nasicornis, Cucujus cinnaberinus, Schizotus pectinicornis, Rhagium mordax, and Rhagium inquisitor, were thoroughly investigated in this work. We revealed an association of these beetle species mainly with four bacterial phyla, Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes, as well as with three fungal phyla, Ascomycota, Zygomycota, and Basidiomycota, but microbial communities varied depending on the beetle host, individual organism, and surrounding environment. Moreover, archaea within the phyla Euryarchaeota and Crenarchaeota in the hindgut content of O. nasicornis and A. solstitiale were additionally detected. The identified microbial communities suggest their potential role in the exploitation of various resources, providing nutritional needs for the host organism. These microorganisms can also represent a valuable source of novel metabolic capacities for their application in different biotechnologies.

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Couple honor fallen responders with cross-county 'Move Over' campaign

By Bill Hand Sun Journal HAVELOCK, N.C. — It's the law: slow down and move over. The message, American Towman Magazine believes, should go a long way toward protecting first responders, and it has made the slogan its mission, sending a husband and wife team across the country in a special RV, carrying a symbolic coffin, to remind drivers of what happens when they don't give emergency personnel ...

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Nurse saves cardiac arrest victim in spin class

Heather Fleming, a 34-year-old intensive care nurse, was in a morning spin class when a fellow spinner collapsed and appeared to go into cardiac arrest

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The molecular mechanism of serum microRNA124b induced coronary heart disease by inducing myocardial cell senescence

OBJECTIVE: The incidence and mortality of coronary heart disease are rapidly increasing in recent years. Myocardial cell dysfunction and cell senescence may play a role in coronary heart disease. MicroRNA controls a variety of biological processes, but leaving its role in coronary heart disease has yet to be explored.

PATIENTS AND METHODS: Patients with coronary heart disease were regarded as subjects, and healthy volunteers as the control, on both of which microRNA124b level of serum was studied by Real-time PCR, and the heart function of patients was detected by using ultrasound. The relationship between serum microRNA124b level and cardiac function was analyzed along with the model of rat coronary artery disease; the level of aging proteins P21 and P53 in cardiac muscle cells was also tested.

RESULTS: MicroRNA124b in the serum of patients with coronary heart disease was increased, and the heart function of patients was decreased (p < 0.05). Serum level of microRNA124b in a rat model of coronary heart disease was increased, and the cardiac function was decreased (p < 0.05). When myocardial cell appeared ageing, the level of P21 and P53 was increased, and the level of microRNA124b was related with P53.

CONCLUSIONS: The level of microRNA124b in the serum of coronary heart disease patients and rat model may be related to the occurrence of coronary heart disease; microRNA124b may lead to the occurrence of coronary heart disease by causing cell senescence.

L'articolo The molecular mechanism of serum microRNA124b induced coronary heart disease by inducing myocardial cell senescence sembra essere il primo su European Review.



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Evaluation of thyroid nodule characteristics in subclinical hypothyroid patients under a myo-inositol plus selenium treatment

OBJECTIVE: The anticancer effect of myo-inositol (MI) is catching researchers' attention worldwide. Thyroid nodules (TNs) have been detected by ultrasound (US) in up to 76% of the general population and, although most of them are benign, thyroid cancer is the most common malignancy of the endocrine system.

PATIENTS AND METHODS: A retrospective, observational study was conducted in 642 patients with suspected hypothyroidism undergoing US. The analysis was addressed exclusively to patients with subclinical hypothyroidism (SCH) or thyroid-stimulating hormone (TSH) levels borderline associated to TNs classified as class I and II; 1 group (control, no. 16) no treatment was prescribed; the other group (treated, no. 18) underwent treatment with 1 tablet containing MI plus selenium (Se) every day, for six months. Clinical data were collected to evaluate the nodular size, number, and elasticity, as well as TSH levels.

RESULTS: Final data were analyzed from 34 patients: in 76% of mixed TNs was observed a significant reduction of their size and 56% of them significantly regressed nodule stiffness following oral supplementation with MI plus Se. The mean number of mixed nodules for patient shifted from 1.39 ± 0.16 to 1.05 ± 0.15 (p ≤ 0.05). TSH levels dropped from 4.2 ± 0.21 mIU/L at baseline to 2.1 ± 0.20 mIU/L post-treatment (p < 0.001). In the control group, 38% of TNs reduced their diameter but TSH levels significantly increased up to the threshold after six months (from 3.95 ± 0.18 mIU/L to 4.30 ± 0.22 mIU/L, p ≤ 0.05).

CONCLUSIONS: In SCH patients undergoing treatment with MI plus Se, a reduction of the size, number and elasticity score of TNs as well as TSH levels was observed. Further studies are required, either in vitro and in vivo, to investigate the use of MI plus Se for the management of TNs.

L'articolo Evaluation of thyroid nodule characteristics in subclinical hypothyroid patients under a myo-inositol plus selenium treatment sembra essere il primo su European Review.



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Renal ischemia-reperfusion injury attenuated by splenic ischemic preconditioning

OBJECTIVE: To investigate the therapeutic effect of splenic ischemic preconditioning (sIPC) on renal ischemia-reperfusion (IR) injury.

MATERIALS AND METHODS: A total of 18 adult male Sprague Dawley (SD) rats were treated by 45 min renal ischemia and followed by 24 h reperfusion. In the sIPC group, three cycles of splenic ischemic preconditioning including 5 min ischemia and 5 min reperfusion were carried out before renal ischemia. The blood samples and kidney tissues were collected after 24 h. The levels of Cr and BUN in serum were measured to evaluate the kidney function. The morphological changes in ischemia-reperfusion kidneys were determined by hematoxylin-eosin (HE) staining. The levels of pro-inflammatory cytokines including TNF-α and IL-6 in serum, and renal tissues, were measured by ELISA and Western Blotting. Furthermore, the levels of IKK-β, intra-nuclear NF-κB, p65, and IL-10 in renal tissues were also measured.

RESULTS: The results demonstrated that the level of Cr and BUN in the IR group were increased while decreased in the sIPC group. HE staining showed that the damage caused by renal ischemia-reperfusion was attenuated by sIPC with a low renal injury score in the sIPC group. ELISA and Western Blotting results showed that the production and secretion of TNF-α and IL-6 induced by IR were inhibited by sIPC. The expression level of IKK-β and intranuclear p65 in renal tissues were increased in the IR group while sIPC had exhibited the function of depressing the increased expression levels of IKK-β and intranuclear p65. Compared with the IR group, the expression level of IL-10 of serum and renal tissues in the sIPC group were increased.

CONCLUSIONS: sIPC exhibited a potent anti-inflammatory capacity to attenuated renal IR injury.

L'articolo Renal ischemia-reperfusion injury attenuated by splenic ischemic preconditioning sembra essere il primo su European Review.



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Anthracycline and trastuzumab-induced cardiotoxicity in breast cancer

OBJECTIVE: Breast cancer is the most common cancer among women. In the last twenty years early diagnosis, neoadjuvant and adjuvant systemic treatment that targeted to specific molecular targets have significantly reduced the mortality from breast cancer. However, the increase in survival has allowed to observe the cardiotoxic effects of anticancer therapy and increased mortality from cardiovascular causes, resulting in a large literature where experts try to identify the correct management of this critical problem. Even thought the increased attention in this field, many questions have not yet answers and new studies are needed.

MATERIALS AND METHODS: We conducted a broad search of the English-language literature in Medline using the following search terms: cardiotoxicity, anthracyclines, trastuzumab, breast cancer, left ventricular dysfunction, heart failure. A manual examination of the articles found has been performed.

RESULTS: We provide a comprehensive assessment of the current knowledge about cardiotoxicity induced by anthracycline plus trastuzumab in women affected by breast cancer.

CONCLUSIONS: Early identification and prompt treatment of subclinical cardiotoxicity may improve cardiologic prognosis of these patients and may allow oncologists to avoid withdrawal of chemotherapy. That is why it becomes always more important the creation of multidisciplinary teams where cardiologists and oncologists work together to ensure optimal care to oncologic patients treated with cardiotoxic agents.

L'articolo Anthracycline and trastuzumab-induced cardiotoxicity in breast cancer sembra essere il primo su European Review.



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Real-world use, safety, and survival of ipilimumab in metastatic cutaneous melanoma in The Netherlands

Phase III trials with ipilimumab showed an improved survival in patients with metastatic melanoma. We evaluated the use and safety of ipilimumab, and the survival of all patients with metastatic cutaneous melanoma (N=807) receiving ipilimumab in real-world clinical practice in The Netherlands using data from the Dutch Melanoma Treatment Registry. Patients who were registered between July 2012 and July 2015 were included and analyzed according to their treatment status: treatment-naive (N=344) versus previously-treated (N=463). Overall, 70% of treatment-naive patients and 62% of previously-treated patients received all four planned doses of ipilimumab. Grade 3 and 4 immune-related adverse events occurred in 29% of treatment-naive patients and 21% of previously-treated patients. No treatment-related deaths occurred. Median time to first event was 5.4 months [95% confidence interval (CI): 4.7–6.5 months] in treatment-naive patients and 4.4 months (95% CI: 4.0–4.7 months) in previously-treated patients. Median overall survival was 14.3 months (95% CI: 11.6–16.7 months) in treatment-naive patients and 8.7 months (95% CI: 7.6–9.6 months) in previously-treated patients. In both patient groups, an elevated lactate dehydrogenase level (hazard ratio: 2.25 and 1.70 in treatment-naive and previously-treated patients, respectively) and American Joint Committee on Cancer M1c-stage disease (hazard ratio: 1.81 and 1.83, respectively) were negatively associated with overall survival. These real-world outcomes of ipilimumab slightly differed from outcomes in phase III trials. Although phase III trials are crucial for establishing efficacy, real-world data are of great added value enhancing the generalizability of outcomes of ipilimumab in clinical practice. *Anouk Jochems and Brenda Leeneman contributed equally to the writing of this article. Correspondence to Anouk Jochems, MD, MSc, Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, 2300 RC Leiden, The Netherlands Tel: +31 71 5263486; fax: +31 71 5264036; e-mail: a.jochems@lumc.nl Received October 5, 2017 Accepted March 15, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Functional Assessment of Intermediate Vascular Disease

Interventional treatment in various vascular beds has advanced tremendously. However, there are several problems to be considered. We searched the literature and tried to analyze major parts of it. One is safety and applicability of coronary proven methods in other vascular beds. An unresolved problem is the functional assessment of intermediate lesions, as far as various target organs have quite different circulation from the coronary one and the functional tests should be modified in order to be applicable and meaningful. In the majority of the acute vascular syndromes, the culprit lesion is of intermediate size on visual assessment. On the other hand, a procedurally successfully managed high-degree stenosis is not always followed by clinical and prognostic benefit. In vascular beds, where collateral network naturally exists, the readings from the functional assessment are complicated and thus the decision for interventional treatment is even more difficult. Here come into help the functional assessment and imaging with IVUS, OCT, high-resolution MRI, and contrast enhanced CT or SPECT. The focus of the current review is on the functional assessment of intermediate stenosis in other vascular beds, unlike the coronary arteries.

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Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma

The development of effective adjuvant therapies for patients with high-risk melanoma has been preceded by the recent arrival of active agents to treat metastatic melanoma, including ipilimumab (an anti-CTLA4 antibody), pembrolizumab and nivolumab (both monoclonal antibodies against programmed death…

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Addressing Risks: Mental Health, Work-Related Stress, and Occupational Disease Management to Enhance Well-Being



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Anti-Inflammatory Effects of Berberine Hydrochloride in an LPS-Induced Murine Model of Mastitis

Berberine hydrochloride is an isoquinoline type alkaloid extracted from Berberidaceae, Rutaceae, and other plants. Previous reports have shown that berberine hydrochloride has anti-inflammatory properties. However, the underlying molecular mechanisms remain unclear. In this study, a lipopolysaccharide- (LPS-) induced murine model of mastitis was established to explore the anti-inflammatory action of berberine hydrochloride. Sixty mice that had been lactating for 5–7 days were randomly divided into six groups, including control, LPS, three berberine hydrochloride treatment groups (5, 10, and 20 mg/kg), and a dexamethasone (DEX) (5 mg/kg) group. Berberine hydrochloride was administered intraperitoneally 1 h before and 12 h after LPS-induced mastitis, and all mice were sacrificed 24 h after LPS induction. The pathological and histopathological changes of the mammary glands were observed. The concentrations and mRNA expressions of TNF-α, IL-1β, and IL-6 were measured by ELISA and qRT-PCR. The activation of TLR4 and NF-κB signaling pathways was analyzed by Western blot. Results indicated that berberine hydrochloride significantly attenuated neutrophil infiltration and dose-dependently decreased the secretion and mRNA expressions of TNF-α, IL-1β, and IL-6 within a certain range. Furthermore, berberine hydrochloride suppressed LPS-induced TLR4 and NF-κB p65 activation and the phosphorylation of I-κB. Berberine hydrochloride can provide mice robust protection from LPS-induced mastitis, potentially via the TLR4 and NF-κB pathway.

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Association of Academic Physiatrists Federal Funding of Disability and Rehabilitation Research Position Statement

The Association of Academic Physiatrists (AAP) seeks to advocate for policies that are supportive of academic rehabilitation, with elected officials, agency leaders, and other policy makers. Accordingly, the AAP's Public Policy Committee identifies policy issues of importance to the organizational mission, conducts background research on those issues, and develops position statements that articulate the organization's position. These position statements require approval by the Board of Trustees and are used to support advocacy efforts by AAP members. Federal funding for disability and rehabilitation research is an important issue for the AAP and its members. This position statement addresses the need for greater federal funding in this area, better coordination of the agencies providing funding, and an appropriate balance of merit-based funding with funding targeted to building capacity in critical rehabilitation-relevant methodology and content areas. This position paper was reviewed by the Association of Academic Physiatrists Public Policy Committee and the Board of Trustees and approved as a position paper of the Association. John Whyte, MD, PhD, Moss Rehabilitation Research Institute, 50 Township Line Road, Elkins Park, PA 19027, email: jwhyte@einstein.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Older Patients Are Less Affected by Radiochemotherapeutic Treatment than Younger

Purpose. The general assumption is that cancer therapy impairs the quality of life in elderly patients more than in younger ones. We were interested in the effects of radiochemotherapeutic treatment on the quality of life of elderly patients compared to younger patients and compared to normative data of a general German population. Methods and Materials. A total of 465 patients completed the EORTC QLQ-C30 questionnaire. Repetitive completion of the questionnaire over time led to 1407 datasets. Our patient cohort contained 197 (42.4%) patients with colorectal cancer followed by 109 (23.4%) patients with head and neck cancer, 43 (9.2%) patients with lung cancer, and 116 (25%) with other types of cancer. Patients were categorized into five age groups, the respective cut-offs being 40, 50, 60, and 70 years. Normative data were drawn from a population study of a general German population. Results. Functional scores and symptom scores were approximately stable between the different age groups. Our data does not suggest a significant difference between the investigated age groups. Advancing age evened out the differences between the normative data of the general German population and the cancer patients in 11 of 15 scores. Conclusions. The general belief about younger patients having fewer physical and psychological problems related to radiochemotherapy needs to be reconsidered. Overall resilience of older patients is apparently underestimated.

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A Single Codon Optimization Enhances Recombinant Human TNF-α Vaccine Expression in Escherichia coli

As a proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α) plays a pivotal role in various autoimmune diseases such as rheumatoid arthritis (RA). Thus, TNF-α has been defined as a therapeutic target for RA. Although some TNF-α antagonists including neutralizing monoclonal antibodies and soluble receptors have been approved to be successful in attenuating symptoms in patients suffering from RA, the long-term use of these passive immunization reagents could cause some problems like a variable degree of immunogenicity. In the present study, in order to wake up active immune responses of RA patients, we developed a recombinant TNF-α therapeutic vaccine (named mrTNF-PADRE) by coupling a 12-amino acid universal Pan HLA-DR Epitope (PADRE) to the protein. Codon optimization was performed to improve the secondary structure of mrTNF-PADRE mRNA to ensure its heterologous expression. As a result, a single codon synonymous mutation greatly elevated recombinant protein expression (about 30% of the total bacteria proteins) in E. coli as compared with the undetectable expression of the unoptimized gene. Although expressed as insoluble inclusion bodies (IBs), the vaccine can be effectively prepared with a purity of over 95% by IBs washing and one-step gel-infiltration chromatography. By this strategy, a stable yield of 5.2 mg purified mrTNF-PADRE per gram of cell paste could be obtained.

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Effects of Alkaline-Reduced Drinking Water on Irritable Bowel Syndrome with Diarrhea: A Randomized Double-Blind, Placebo-Controlled Pilot Study

Objectives. The purpose of this study was to investigate whether the ingestion of alkaline-reduced water (ARW) is helpful in improving the symptoms of diarrhea-predominant irritable bowel syndrome (IBS). Methods. Twenty-seven patients (male, 25.9%; mean, 41.7 years old) with diarrhea-predominant IBS were randomly allocated to two groups. For eight weeks, the ARW group () ingested at least 2 liters/day of ARW, while the control group () ingested placebo water. IBS symptom scores (quality-of-life, abdominal pain/discomfort), stool form, and frequency were assessed before and after treatment via questionnaires. Results. Eight patients (61.5%) in the ARW group and six patients (42.9%) in the control group indicated that their symptoms had improved in more than four out of the eight weeks of treatment (). The IBS quality-of-life score significantly improved from 57.2 to 30.8 in the ARW group; this improvement was significantly greater than the slight improvement from 48.7 to 42.2 observed in the control group (). The abdominal pain score improved from 1.8 to 0.9 in the ARW group and from 1.8 to 1.1 in the control group, with no significant group difference (). Conclusions. Drinking ARW for eight weeks improves the quality of life in patients with diarrhea-predominant IBS.

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Cancers, Vol. 10, Pages 118: Roles of Polyploid/Multinucleated Giant Cancer Cells in Metastasis and Disease Relapse Following Anticancer Treatment

Cancers, Vol. 10, Pages 118: Roles of Polyploid/Multinucleated Giant Cancer Cells in Metastasis and Disease Relapse Following Anticancer Treatment

Cancers doi: 10.3390/cancers10040118

Authors: Razmik Mirzayans Bonnie Andrais David Murray

Tumors and tumor-derived cell lines contain polyploid giant cells with significantly elevated genomic content, often with multiple nuclei. The frequency of giant cells can increase markedly following anticancer treatment. Although giant cells enter a dormant phase and therefore do not form macroscopic colonies (aggregates of ≥50 cells) in the conventional in vitro colony formation assay, they remain viable and metabolically active. The purpose of this commentary is to underscore the potential importance of polyploid/multinucleated giant cells in metastasis and cancer recurrence following exposure to anticancer agents. We also discuss the possibility that most preclinical (cell-based and animal model) drug discovery approaches might not account for delayed responses that are associated with dormant giant cells.



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Efficacy of Statin Therapy Related to Baseline Renal Function in Patients with Rheumatic Heart Disease Undergoing Cardiac Surgery

Background. Renal impairment increases the risk of cardiovascular events and perioperative complications in patients with heart valve disease. This study aimed to determine the perioperative benefit of statin treatment related to baseline renal function in patients with rheumatic heart disease (RHD) who had cardiac surgery. Methods and Results. We performed a retrospective study on 136 patients with RHD who underwent valve replacement surgery. The mean age of the patients was 56.2 years, 59.6% were female, 8.8% patients had diabetes mellitus, and 27.2% of patients had hypertension. Overall, 3 patients died, 2 underwent reoperation, and 25 underwent thoracentesis during the study period. For patients with renal impairment, there was a higher risk of thoracic puncture (odds ratio [OR]: 3.33; 95% confidence interval [CI]: 1.36, 8.11; ) and a longer time of drainage (difference in means: 1; 95% CI: 0.88, 1.12; ), intensive care unit (ICU) stay (difference in means: 0.2; 95% CI: 0.17, 0.23; ), and hospital stay (difference in means: 6.6; 95% CI: 6.15, 7.05; ) compared with normal renal function. Furthermore, statins were associated with a reduction in drainage time (difference in means: −1.50; 95% CI: −1.86, −1.14; ), ICU stay (difference in means: −0.30; 95% CI: −0.40, −0.20; ), and hospital stay (difference in means: −5.40; 95% CI: −6.57, −4.23; ) in patients with renal impairment (interaction, for all), but not in those with normal renal function. Conclusion. Statins have a greater clinical benefit in perioperative cardiac surgery with renal impairment. Statins are associated with a comparatively lower risk of thoracic puncture, as well as a reduced trend toward a reduction in drainage time, ICU stay, and hospital stay.

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Mental health insurance access and utilization among childhood cancer survivors: a report from the childhood cancer survivor study

Abstract

Purpose

To describe and compare the prevalence of mental health access, preference, and use among pediatric cancer survivors and their siblings. To identify factors associated with mental health access and use among survivors.

Methods

Six hundred ninety-eight survivors in the Childhood Cancer Survivor Study (median age = 39.4; median years from diagnosis = 30.8) and 210 siblings (median age = 40.4) were surveyed. Outcomes included having mental health insurance coverage, delaying care due to cost, perceived value of mental health benefits, and visiting a mental health provider in the past year.

Results

There were no differences in mental health access, preferences, and use between survivors and siblings (p > 0.05). Among respondents with a history of distress, most reported not having seen a mental health provider in the past year (80.9% survivors vs. 77.1% siblings; p = 0.60). Uninsured survivors were more likely to defer mental health services due to cost (24.6 vs. 8.4%; p < 0.001). In multivariable models, males (OR = 2.96) and survivors with public (OR = 6.61) or employer-sponsored insurance (ESI; OR = 14.37) were more likely to have mental health coverage.

Conclusions

Most childhood cancer survivors value having mental healthcare benefits; however, coverage and use of mental health services remain suboptimal. The most vulnerable of survivors, specifically the uninsured and those with a history of distress, are at risk of experiencing challenges accessing mental health care.

Implications for Cancer Survivors

Childhood cancer survivors are at risk for experiencing high levels of daily life stress that is compounded by treatment-related sequelae. Integrative, system-based approaches that incorporate financial programs with patient education about insurance benefits can help reduce some of the financial barriers survivors face.



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Machine Learning-Augmented Propensity Score-Adjusted Multilevel Mixed Effects Panel Analysis of Hands-On Cooking and Nutrition Education versus Traditional Curriculum for Medical Students as Preventive Cardiology: Multisite Cohort Study of 3,248 Trainees over 5 Years

Background. Cardiovascular disease (CVD) annually claims more lives and costs more dollars than any other disease globally amid widening health disparities, despite the known significant reductions in this burden by low cost dietary changes. The world's first medical school-based teaching kitchen therefore launched CHOP-Medical Students as the largest known multisite cohort study of hands-on cooking and nutrition education versus traditional curriculum for medical students. Methods. This analysis provides a novel integration of artificial intelligence-based machine learning (ML) with causal inference statistics. 43 ML automated algorithms were tested, with the top performer compared to triply robust propensity score-adjusted multilevel mixed effects regression panel analysis of longitudinal data. Inverse-variance weighted fixed effects meta-analysis pooled the individual estimates for competencies. Results. 3,248 unique medical trainees met study criteria from 20 medical schools nationally from August 1, 2012, to June 26, 2017, generating 4,026 completed validated surveys. ML analysis produced similar results to the causal inference statistics based on root mean squared error and accuracy. Hands-on cooking and nutrition education compared to traditional medical school curriculum significantly improved student competencies (OR 2.14, 95% CI 2.00–2.28, ) and MedDiet adherence (OR 1.40, 95% CI 1.07–1.84, ), while reducing trainees' soft drink consumption (OR 0.56, 95% CI 0.37–0.85, ). Overall improved competencies were demonstrated from the initial study site through the scale-up of the intervention to 10 sites nationally (). Discussion. This study provides the first machine learning-augmented causal inference analysis of a multisite cohort showing hands-on cooking and nutrition education for medical trainees improves their competencies counseling patients on nutrition, while improving students' own diets. This study suggests that the public health and medical sectors can unite population health management and precision medicine for a sustainable model of next-generation health systems providing effective, equitable, accessible care beginning with reversing the CVD epidemic.

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Engineering the Bone-Implant Interface



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