Αρχειοθήκη ιστολογίου

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Κυριακή 12 Αυγούστου 2018

Locally advanced pancreatic cancer successfully treated with high-dose helical tomotherapy

Abstract

Complete surgical resection is the potentially curative treatment for pancreatic cancer, but only fewer than 20% of those individuals will be found to be eligible for surgery. Here we report a 49-year-old man with locally advanced pancreatic cancer successfully treated with high-dose radiotherapy using helical tomotherapy (66 Gy/33 fractions, 2 Gy per day over 6.5 weeks). To our knowledge, this is the first reported case of locally advanced pancreatic cancer curatively treated with helical tomotherapy alone.



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Preoperative predictors of difficult hypopharyngeal exposure by retractor for transoral robotic surgery

Abstract

Introduction

Transoral endoscopic surgeries provide excellent oncologic outcomes while preserving speech and swallowing ability. However, feasibility has been a major concern about transoral surgery. Therefore, ensuring visualization of the surgical field and sufficient working space is required. The aim of this study was to evaluate the parameters in the preoperative assessment that affect hypopharyngeal exposure.

Methods

Before transoral surgery, parameters regarding the patient's neck and face such as modified Mallampati index, thyroid–mental distance (TMD), and ability to fully open the mouth were evaluated. Cephalometry and cervical spine radiography were performed preoperatively to evaluate the size of the mandible bone, mouth opening, and cervical spine extension. Mandibular bone parameters such as intergonion distance, mental–gonion distance, articulare–gonion distance, and aperture angle were measured. According to hypopharyngeal exposure using FKWO retractor, patients were divided into difficult hypopharyngeal exposure group (DHE) and non-difficult hypopharyngeal exposure group (non-DHE). Parameters were enrolled to evaluate the relationship between these parameters and DHE status.

Results

This study included 51 patients, 37 in the non-DHE group and 14 in the DHE group. On radiographic evaluation, there was a significant difference in the degree of cervical lordosis between non-DHE and DHE patients. A significantly higher proportion of DHE patients had a history of radiotherapy compared with non-DHE patients.

Conclusion

Patients with limited cervical extension and a history of previous radiotherapy might have difficult hypopharyngeal exposure during transoral surgery. This is the first report to suggest a classification system for hypopharyngeal exposure during transoral surgery.



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The need for Canada to tax sugar-sweetened beverages [Letters]



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Rapid repeat pregnancy among women with intellectual and developmental disabilities: a population-based cohort study [Research]

BACKGROUND:

Rapid repeat pregnancy within 12 months of a live birth is associated with adverse perinatal outcomes. We evaluated the risk for rapid repeat pregnancy among women with intellectual and developmental disabilities, with whom sharing of information about pregnancy planning and contraception may be inadequate.

METHODS:

We accessed population-based health administrative data for all women with an index live birth in Ontario, Canada, for the period 2002–2013. We used modified Poisson regression to compare relative risks (RRs) for a rapid repeat pregnancy within 12 months of the index live birth in women with and without intellectual and developmental disabilities, first adjusting for demographic factors and then additionally adjusting for social, health and health care disparities.

RESULTS:

We compared 2855 women with intellectual and developmental disabilities and 923 367 women without such disabilities. At the index live birth, women with intellectual and developmental disabilities were more likely to be younger than 25 years of age (46.8% v. 18.2%) and to be disadvantaged on each measure of social, health and health care disparities. These women had a higher rate of rapid repeat pregnancy than those without such disabilities (7.6% v. 3.9%; adjusted RR 1.34, 95% confidence interval [CI] 1.18–1.54, after controlling for demographic factors). This risk was attenuated upon further adjustment for social, health and health care disparities (adjusted RR 1.00, 95% CI 0.87–1.14).

INTERPRETATION:

Rapid repeat pregnancy, which was more common among women with intellectual and developmental disabilities, may be explained by social, health and health care disparities. To optimize reproductive health, multifactorial approaches to address the marginalization experienced by this population are likely needed.



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Individual risk prediction using data beyond the medical clinic [Commentary]



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Aligning innovations in health funding with innovations in care [Analysis]



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More doctors talking about nonclinical careers, but challenges remain [News]



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Reversible cerebellar neurotoxicity induced by metronidazole [Practice]



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When the perfect is the enemy of the good [Letters]



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Yousefs story [Humanities]



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Pre-residency boot camps calm medical graduate jitters [News]



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Setting the record straight on taxation and disparities in smoking [Letters]



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Canada among top 20 countries for skin cancer risk [News]



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Two in, two out: maintaining your marriage in EMS

Your partner at home can be your best resource in regard to your mental health

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Treatment of Complications from Immune Checkpoint Inhibition in Patients with Lung Cancer

Opinion statement

Immune checkpoint inhibitors have revolutionized the management of advanced NSCLC. With the intention of generating an anti-tumor immune response, ICIs can also lead to inflammatory side effects involving a wide variety of organs in the body, termed immune-related adverse events. Although no prospective clinical trial exists to guide recommendations for optimal and more specific immunosuppressive treatments rather than corticosteroids, further studies may lead to a more mechanistic-based approach towards these toxicities in the future. In relation to current practice, we recommend adherence to the recent published guidelines which emphasize the importance of early recognition and administration of temporary immunosuppressive therapy with corticosteroids in most cases, depending on the organ system involved, and the severity of toxicity. Recognition of these toxicities is increasingly important as the use of these agents expand within different indications for patients with lung cancers, and to other tumor types.



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Protein Arginine Methyltransferase 2 Inhibits Angiotensin II-Induced Proliferation and Inflammation in Vascular Smooth Muscle Cells

Objectives. Protein arginine methyltransferase 2 (PRMT2) protects against vascular injury-induced intimal hyperplasia; however, little is known about the role of PRMT2 in angiotensin II (Ang II)-induced VSMCs proliferation and inflammation. This research aims to determine whether PRMT2 inhibits Ang II-induced proliferation and inflammation of vascular smooth muscle cells (VSMCs). Materials and Methods. PRMT2 overexpression was used to elucidate the role of PRMT2 in Ang II-induced VSMCs proliferation and inflammation. Western blotting and reverse transcriptional PCR were adopted to detect protein and mRNA expression severally. Cell viability was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay and cell cycle distribution by flow cytometry. Results. Ang II significantly reduced mRNA and protein levels of PRMT2 in VSMCs in time-dependent and dose-dependent manner. Results of PRMT2 overexpression indicated that PRMT2 inhibited proliferation of VSMCs stimulated with 100 nmol/L Ang II for 24 hours. Furthermore, overexpression of PRMT2 reduced Ang II-induced production of proinflammatory cytokines such as interleukin 6 (IL-6) and interleukin 1β (IL-1β) in VSMCs. Conclusions. These findings suggest that PRMT2 alleviates Ang II-induced VSMCs proliferation and inflammation, providing a new mechanism about how Ang II mediated VSMCs proliferation and inflammation.

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Histogram Analysis of Perfusion Parameters from Dynamic Contrast-Enhanced MR Imaging with Tumor Characteristics and Therapeutic Response in Locally Advanced Rectal Cancer

Purpose. To explore the role of histogram analysis of perfusion parameters from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on entire tumor volume in discriminating tumor characteristics and predicting therapeutic response in rectal cancer. Materials and Methods. Thirty-seven DCE-MRIs of locally advanced rectal cancer patients who received chemoradiation therapy (CRT) before surgery were analyzed by pharmacokinetic model for quantification and histogram analysis of perfusion parameters. The results were correlated with tumor characteristics including EGFR expression, KRAS mutation, and CRT response based on the pathologic tumor regression grade (TRG). Results. The area under the contrast agent concentration-time curve (AUC) skewness was significantly lower in patients with node metastasis. The histogram parameters were significantly higher in group with perineural invasion (PNI). The receiver operating characteristics (ROC) curve analyses showed that mode revealed the best diagnostic performance of PNI. The values of and were significantly higher in the group with KRAS mutation. ROC curve analyses showed that mean and mode demonstrated excellent diagnostic performance of KRAS mutation. DCE-MRI parameters did not demonstrate statistical significance in correlating with TRG. Conclusion. These preliminary results suggest that a larger proportion of higher AUC skewness was present in LN metastasis group and a higher histogram value was present in rectal cancer with PNI. In addition, and histogram parameters showed difference according to the KRAS mutation, demonstrating the utility of the histogram of perfusion parameters derived from DCE-MRI as potential imaging biomarkers of tumor characteristics and genetic features.

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Developmental Programming of Capuchin Monkey Adrenal Dysfunction by Gestational Chronodisruption

In the capuchin monkey (Cebus apella), a new-world nonhuman primate, maternal exposure to constant light during last third of gestation induces precocious maturation of the fetal adrenal and increased plasma cortisol in the newborn. Here, we further explored the effects of this challenge on the developmental programming of adrenal function in newborn and infant capuchin monkeys. We measured (i) plasma dehydroepiandrosterone sulphate (DHAS) and cortisol response to ACTH in infants with suppressed endogenous ACTH, (ii) plasma DHAS and cortisol response to ACTH in vitro, and (iii) adrenal weight and expression level of key factors in steroid synthesis (StAR and 3β-HSD). In one-month-old infants from mothers subjected to constant light, plasma levels of cortisol and cortisol response to ACTH were twofold higher, whereas plasma levels of DHAS and DHAS response to ACTH were markedly reduced, compared to control conditions. At 10 months of age, DHAS levels were still lower but closer to control animals, whereas cortisol response to ACTH was similar in both experimental groups. A compensatory response was detected at the adrenal level, consisting of a 30% increase in adrenal weight and about 50% reduction of both StAR and 3β-HSD mRNA and protein expression and the magnitude of DHAS and cortisol response to ACTH in vitro. Hence, at birth and at 10 months of age, there were differential effects in DHAS, cortisol production, and their response to ACTH. However, by 10 months of age, these subsided, leading to a normal cortisol response to ACTH. These compensatory mechanisms may help to overcome the adrenal alterations induced during pregnancy to restore normal cortisol concentrations in the growing infant.

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A Rare Cause of Acute Kidney Injury: Primary Renal Lymphoma in a Patient with Human Immunodeficiency Virus

We reported a case of primary renal lymphoma (PRL) presented with non-oliguric acute kidney injury and bilateral kidney infiltrates in an individual with human immunodeficiency virus (HIV) disease. Acute kidney injury secondary to lymphoma infiltrates is very rare (less than 1% of hematological malignancy). A 37-year-old gentleman with underlying human immunodeficiency virus (HIV) disease was on combined antiretroviral therapy since diagnosis. He presented to our center with uremic symptoms and gross hematuria. Clinically, bilateral kidneys massively enlarged and were ballotable. Blood investigations showed hemoglobin of 3.7 g/L, urea of 65.6 mmol/L, and serum creatinine of 1630 µmol/L with hyperkalemia and metabolic acidosis. An urgent hemodialysis was initiated, and he was dependent on regular hemodialysis subsequently. Computed tomography renal scan showed diffuse nonenhancing hypodense lesion in both renal parenchyma. Diagnosis of diffuse large B cell lymphoma with germinal center type, CD20 positive, and proliferative index 95% was confirmed via renal biopsy, and there was no bone marrow infiltrates. Unfortunately, the patient succumbs prior to initiation of chemotherapy.

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The Study of Viral RNA Diversity in Bird Samples Using De Novo Designed Multiplex Genus-Specific Primer Panels

Advances in the next generation sequencing (NGS) technologies have significantly increased our ability to detect new viral pathogens and systematically determine the spectrum of viruses prevalent in various biological samples. In addition, this approach has also helped in establishing the associations of viromes with many diseases. However, unlike the metagenomic studies using 16S rRNA for the detection of bacteria, it is impossible to create universal oligonucleotides to target all known and novel viruses, owing to their genomic diversity and variability. On the other hand, sequencing the entire genome is still expensive and has relatively low sensitivity for such applications. The existing approaches for the design of oligonucleotides for targeted enrichment are usually involved in the development of primers for the PCR-based detection of particular viral species or genera, but not for families or higher taxonomic orders. In this study, we have developed a computational pipeline for designing the oligonucleotides capable of covering a significant number of known viruses within various taxonomic orders, as well as their novel variants. We have subsequently designed a genus-specific oligonucleotide panel for targeted enrichment of viral nucleic acids in biological material and demonstrated the possibility of its application for virus detection in bird samples. We have tested our panel using a number of collected samples and have observed superior efficiency in the detection and identification of viral pathogens. Since a reliable, bioinformatics-based analytical method for the rapid identification of the sequences was crucial, an NGS-based data analysis module was developed in this study, and its functionality in the detection of novel viruses and analysis of virome diversity was demonstrated.

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Transcriptional regulation of human defense peptides: a new direction in infection control

Journal Name: Biological Chemistry
Issue: Ahead of print


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Ulnar neuropathy with abnormal non-localizing electrophysiology: clinical, electrophysiological and ultrasound findings

Ulnar neuropathy, the second most common mono-neuropathy, is usually due to focal nerve pathology at the elbow, with an estimated incidence of 24.7/105/year (Mondelli et al., 2005). It typically presents with paraesthesia or sensory loss in the little and ring fingers and weakness of ulnar innervated muscles. Diagnosis is usually based on clinical findings and abnormal electrophysiology. Electrodiagnostic tests can localize the lesion by demonstrating focal conduction slowing, with or without temporal dispersion and conduction block across the elbow (AAEM, 1999a), with a sensitivity varying from 38 to 89% (AAEM,1999b).

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Intra-operative cortical motor mapping using subdural grid electrodes in children undergoing epilepsy surgery evaluation and comparison with the conventional extra-operative motor mapping

Epilepsy surgery can be highly effective and associated with favourable cognitive, functional and seizure-free outcomes in carefully selected patients.(Dwivedi et al., 2017) Epileptogenic foci in children with epilepsy are commonly extra-temporal and may be in close proximity to eloquent areas, such as the motor cortex. Thus, it is vital to accurately map the motor cortex to prevent post-operative motor deficits.

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Multifactorial etiology for tolerance to Deep Brain Stimulation for “essential tremor syndrome”

We write this letter in response to the commentary by Wagle Shukla and Okun (2018) on our recently published article in Clinical Neurophysiology, 'Objective predictors of 'early tolerance' to ventral intermediate nucleus of thalamus deep brain stimulation in essential tremor patients' (Merchant et al. 2018), which makes for a worthwhile follow-up discussion on this topic. Based on the recently published MDS consensus criteria, essential tremor (ET) can be best described as a syndrome (Bhatia et al.

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Pseudo–“solid pseudopapillary neoplasms” of the testis: in reality Sertoli cell tumors

We read with interest and concern two reports published in Human Pathology [1,2] concerning testicular neoplasms that were felt to be "testicular analogues" of the well-known "solid pseudopapillary neoplasm" (SPN) of the pancreas, albeit in one of the 2 papers the authors preferred to designate the tumors as primary signet ring stromal tumors of the testis [1]. Although we acknowledge that the pseudopapillae in the SPNs may be limited in amount, their apparent absence, according to the descriptions of the microscopic findings in all of the 14 tumors in these 2 reports, struck us as unusual for a tumor the authors were placing in the SPN category.

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W. Va. fire dept. receives 2 donated AEDs

"These devices will enable the department to access a person who is in sudden cardiac arrest and take the required steps to provide care," Chief Rick Cary said

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Detection and Isolation of Apoptotic Bodies to High Purity

A workflow using flow cytometry or differential centrifugation is developed to detect, quantify and isolate apoptotic bodies from an apoptotic sample to high purity.

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Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima

Mitophagy, the selective degradation of mitochondria, has been implicated in mitochondrial homeostasis and is deregulated in various human diseases. However, convenient experimental methods for measuring mitophagy activity are very limited. Here, we provide a sensitive assay for measuring mitophagy activity using flow cytometry.

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A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence

Intracellular ROS has been shown to play an important role in the induction of cellular senescence. Here, we describe a sensitive assay for quantifying ROS levels during cellular senescence. We also provide protocols for assessing the senescence-associated secretory phenotype, which reportedly contributes to various age-related dysfunctions.

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Targeting Neuronal Fiber Tracts for Deep Brain Stimulation Therapy Using Interactive, Patient-Specific Models

The goal of this project is to develop an interactive, patient-specific modeling pipeline to simulate the effects of deep brain stimulation in near real-time and provide meaningful feedback as to how these devices influence neural activity in the brain.

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Short-Term Efficacy of Pulsed Radiofrequency Thermal Stimulation on Acupoints for Chronic Low Back Pain: A Preliminary Study of a Randomized, Single-Blinded, Placebo-Controlled Trial

Background. The objective of this study was to evaluate the pain-relief efficacy of thermal stimulation induced by a pulsed radiofrequency (PRF) thermal stimulation applied to acupoints (APs) in patients with low back pain (LBP). The study was designed as a randomized, single-blinded, placebo-controlled trial. Methods. Fifty-six LBP patients whose minimum pain intensity score on a visual analogue scale (VAS, 0-100 mm) was more than 30 mm were randomly allocated to either the placebo-controlled or the treatment group at a 1:1 ratio. The treatment and placebo-controlled groups received PRF thermal stimulation plus cupping therapy and cupping therapy only, respectively. Each patient was scheduled to receive a total of three treatment sessions over one week with allowing a window up to 4 days. Six of the 13 predefined APs were selected differently for each session depending on the change in patient's symptoms and intensity of pain. The primary outcome was the mean difference between the placebo-controlled and treatment group of VAS changes from the baseline to the end of the follow-up period. Results. The patients' reported VAS scores from baseline to the end of follow-up (average: 9.8 days) were significantly decreased by 8.036 points (two-sided 95% CI, -11.841 to -4.231) and 13.393 points (two-sided 95% CI: 17.198 to -9.588) in the treatment and the placebo-controlled groups, respectively. However, the change in VAS scores between the treatment group and the placebo-controlled group was not significantly different (2.015 mm, two-sided 95% CI: -5.288 to 9.317). Conclusion. The trial results indicated that treatment with either PRF thermal stimulation with cupping therapy or cupping therapy alone effectively relieved LBP. The efficacy of PRF thermal stimulation combined with cupping therapy was not superior to that of cupping therapy alone. Trial registration number: Clinical Research Information Service (KCT0002137). The trial was registered retrospectively on 10 November, 2016.

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Overcoming P-Glycoprotein-Mediated Multidrug Resistance in Colorectal Cancer: Potential Reversal Agents among Herbal Medicines

Objectives. Multidrug resistance (MDR) is the major reason for the failure of chemotherapy in colorectal cancer (CRC), and the primary determinant of MDR in CRC patients is active drug efflux owing to overexpression of P-glycoprotein (P-gp) in cancer tissues. Despite research efforts to overcome P-gp-mediated drug efflux, the high toxicity of P-gp inhibitors has been a major obstacle for the clinical use of these agents. The aim of this study was to review the literature for potential P-gp reversal agents among traditional herbal medicines, which offer the advantages of safety and potential synergetic effects in CRC chemotherapy. Methods. We searched ten databases including 3 English databases, 1 Chinese medical database, and 6 Korean medical databases up to July 2018 and included in vivo and in vitro studies evaluating the effects of herbal medicines as P-gp reversal agents in CRC. Results. A total of 28 potentially related studies were identified and 16 articles were included. Involving 3 studies about Salvia miltiorrhiza and 2 studies about Curcuma longa, finally we found 14 kinds of traditional herbal medicines—Salvia miltiorrhiza, Curcuma longa, Sinomenium acutum, Stephania tetrandra, Bufo gargarizans, Coptis japonica, Piper nigrum and Piper longum, Hedyotis diffusa, Schisandra chinensis, Glycyrrhiza glabra, Glycyrrhiza inflate, Daphne genkwa, Stemona tuberosa Lour, and Andrographis paniculata—as showing efficacy as P-gp inhibitors in anticancer drug-resistant CRC cells in vitro and in vivo. Conclusions. This brief account provides insight into the relationship between P-gp and CRC. Further studies on herbal medicines with demonstrated effects against P-gp overexpression will aid in improving the efficacy of chemotherapy in CRC.

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Cabbage (Brassica oleracea var. capitata) Protects against H2O2-Induced Oxidative Stress by Preventing Mitochondrial Dysfunction in H9c2 Cardiomyoblasts

Oxidative stress plays an important role in the progression of cardiac diseases, including ischemia/reperfusion injury, myocardial infarction, and heart failure. Growing evidence indicates that cabbage has various pharmacological properties against a wide range of diseases, such as cardiovascular diseases, hepatic diseases, and cancer. However, little is known about its effects on oxidative stress in cardiomyocytes or the underlying mechanisms. Therefore, the present study examined the effects of cabbage extract on oxidative stress in H9c2 cardiomyoblasts. Cell viability, reactive oxygen species (ROS) production, apoptosis, mitochondrial functions, and expression levels of mitogen-activated protein kinase (MAPK) proteins were analyzed to elucidate the antioxidant effects of this extract. Cabbage extract protected against H2O2-induced cell death and did not elicit any cytotoxic effects. In addition, cabbage extract suppressed ROS production and increased expression of antioxidant proteins (SOD-1, catalase, and GPx). Cabbage extract also inhibited apoptotic responses and activation of MAPK proteins (ERK1/2, JNK, and p-38) in oxidative stress-exposed H9c2 cells. Notably, cabbage extract preserved mitochondrial functions upon oxidative stress. These findings reveal that cabbage extract protects against oxidative stress and suggest that it can be used as an alternative therapeutic strategy to prevent the oxidative stress in the heart.

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Time Course of Changes in Simulated Keratometry and Total Corneal Refractive Power after Corneal Collagen Cross-Linking for Progressive Keratoconus

Purpose. To assess the simulated keratometry (Sim K) and the total corneal refractive power (TCRP) in eyes undergoing conventional corneal cross-linking (CXL). Methods. This study comprised 20 eyes of 20 keratoconic patients (14 men and 6 women; median age (25th and 75th percentile), 26.5 (21.8, 38.0) years) who underwent CXL. The Sim K and TCRP were measured with a rotating Scheimpflug system (Pentacam HR, Oculus), preoperatively and 1, 3, 6, and 12 months postoperatively. Results. The values of Sim K were 52.65 (46.00, 55.70), 52.45 (45.85, 56.88), 51.70 (45.78, 55.83), 51.40 (45.68, 56.80), and 51.25 (46.08, 56.15) D preoperatively and 1, 3, 6, and 12 months postoperatively, respectively. The corresponding figures of TCRP were 52.10 (45.48, 55.08), 51.30 (45.18, 55.20), 50.95 (45.15, 54.50), 50.00 (45.18, 55.08), and 49.80 (45.48, 54.15) D, respectively. The variances of the Sim K and TCRP data were not statistically significant (p=0.994 and p=0.970, respectively, Kruskal–Wallis test). The Sim K was significantly larger than the TCRP before CXL and at 1, 3, 6, and 12 months after CXL (p

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Correlation between Soluble α-Klotho and Renal Function in Patients with Chronic Kidney Disease: A Review and Meta-Analysis

Objective. Over decades, numerous inconsistent studies are reported on the relationship between soluble α-Klotho and renal function in patients with chronic kidney disease (CKD). This study aims to perform a meta-analysis to figure out the correlations between soluble α-Klotho and renal function in patients with CKD. Materials and Methods. We searched medical and scientific literature databases, PubMed and EMBASE (from the inception to October 2017), for publications that reported studies on associations between soluble α-Klotho and renal function in patients with CKD. Only publications in English were extracted. Summary correlation coefficient (r) values were extracted from each study, and 95% confidence intervals (CIs) were calculated. Publication bias was tested, and sensitivity and subgroup analyses were performed to investigate potential heterogeneity. Results. Of 611 studies, 9 publications with 1457 patients were included into the analysis. The following data were extracted from the literature: first author, year of publication, research region, research index, sample size, average age and Pearson or Spearman correlation coefficient, study design, the αKlotho/FGF23 assays utilized, full length, or the C-terminal fragment of FGF23. The pooled r between α-Klotho and estimated glomerular filtration rate (eGFR), FGF-23 were 0.35 (95%CI, 0.23~0.46, and P

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Myopathy in the York Platelet Syndrome: An Underrecognized Complication

York Platelet Syndrome (YPS) is a calcium channelopathy caused by gain of function in STIM1, a gene which acts as a calcium sensor. It is characterized by platelet abnormalities and muscle weakness. Medical literature emphasizes the hematologic aspects of the cases with few data of the neuromuscular and neuropathologic evaluation. We present a patient with YPS whose myopathy was the most prominent aspect. She presented around 2 years of age with proximal weakness and easy bruisability. YPS was diagnosed in the infant at 16 months of age at the National Institutes of Health. Muscle biopsy demonstrated a severe chronic myopathy. Rimmed vacuoles and tubular aggregates were noted. Although YPS is rare, the combination of a congenital myopathy with thrombocytopenia may facilitate the diagnosis and enable further insights into the disease.

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Spine care delivery and incentives

Publication date: Available online 12 August 2018

Source: Seminars in Spine Surgery

Author(s): Alok Sharan, Dillan Prasad

Abstract

A major drive of healthcare reform is transforming the system towards one that delivers greater value to the patient which will require a realignment of the current payment model. In the current fee-for-service system providers are incentivized based on volume. Previous research has demonstrated that providers respond to changes in incentive system. The study of behavioral economics demonstrates that humans have certain cognitive biases when making decisions. Understanding how incentives drive behavior can help spine providers as they attempt to reshape the healthcare system.



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Down-regulation of 14-3-3 zeta sensitizes human glioblastoma cells to apoptosis induction

Abstract

Strong 14-3-3 zeta protein expression plays an important role in tumorigenesis, including in the maintenance of cell growth, resistance increase, and the prevention of apoptosis. In this study, we focus on two targets: (1) the expression of 14-3-3 zeta in the different grades of human astrocytoma (II–IV), (2) suppression of 14-3-3 zeta protein expression in glioblastoma derived astrocytes by 14-3-3 zeta shRNA lentiviral particles. The tissues of human astrocytoma were provided from 30 patients (ten of each grade of astrocytoma). Control tissues were obtained from the peritumoral brain zone of those patients with glioblastoma. The protein and mRNA expression levels of each astrocytoma grade were assessed via western blotting and RT-PCR, respectively. Results indicated that 14-3-3 zeta was significantly expressed in glioblastoma multiforme (grade IV) and 14-3-3 zeta expression levels enhanced according to the increase of astrocytoma malignancy. In the cellular study for knock down of the 14-3-3 zeta protein, surgical biopsy of glioblastoma was used to isolate primary astrocyte. Astrocytes were transduced with 14-3-3 zeta shRNA or non-targeted shRNA lentiviral particles. Furthermore, reduction of the 14-3-3 zeta protein expression in the astrocytes evaluated through qRT-PCR and western blot after transduction of 14-3-3 zeta shRNA lentiviral particles. Moreover, apoptosis properties, including DNA fragmentation and ratio increase of Bax/Bcl-2 were observed in astrocytes following reduction of 14-3-3 zeta protein expression. Further observation indicated that the mitochondrial pathway through release of cytochorome c and caspase-3 activity was involved in the apoptosis induction. Hence, this study demonstrates a key role of the 14-3-3 zeta protein in tumorigenesis but also indicates that 14-3-3 zeta can be considered as a target for the astrocytoma treatment specially glioblastoma.



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Clear Cell Papulosis: A Rare Pediatric Dermatosis

The diagnosis and management of pediatric hypopigmented lesions can be challenging given their wide range of differentials. In this case report, we present a case of a 3-year-old Chinese boy who was initially treated for tinea versicolor but subsequently diagnosed to have clear cell papulosis. The features, diagnosis, and management of clear cell papulosis are discussed in this article to raise awareness of this condition amongst pediatricians.

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The Toxic Effects of Aflatoxin B1 and Aflatoxin M1 on Kidney through Regulating L-Proline and Downstream Apoptosis

The toxic effects and potential mechanisms of aflatoxin B1 (AFB1), aflatoxin M1 (AFM1), and AFB1+AFM1 in the kidney were studied and compared in HEK 293 cells model and CD-1 mice model. The 35-day subacute toxicity mice model was constructed, biochemical indicators and kidney pathological staining were detected, kidney metabonomics detection was performed, and the metabolites were analyzed, and then the related toxicity mechanism was validated. Results showed that AFB1 (0.5 mg/kg), AFM1 (3.5 mg/kg), and AFB1 (0.5 mg/kg)+AFM1 (3.5 mg/kg) activated oxidative stress and caused renal damage. The relative concentration of the metabolite L-proline was found to be lower in aflatoxins treatment groups when compared with the control (). Moreover, with the treatment of aflatoxins, proline dehydrogenase (PRODH) and proapoptotic factors (Bax, Caspase-3) were upregulated, while the inhibitor of apoptosis Bcl-2 was downregulated, at both the mRNA and the protein levels, comparing with the control (). In addition, the combined effect of AFB1 and AFM1 was validated, for the toxicity of the combination was stronger than the other two groups. In conclusion, AFB1 and AFM1 caused kidney toxicity by activating oxidative stress through altering expression of PRODH and L-proline levels, which then induced downstream apoptosis.

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Combined Donepezil and Ethanolic Extract of Propolis Improved Memory Better Than Donepezil and Propolis Monotherapy in Wild Type Drosophila melanogaster

Background. Donepezil is the most common drug used in the treatment of disorders associated with memory loss, especially that in Alzheimer's disease. Healthy individuals however have continued to use it as a memory enhancer. This study was aimed at evaluating the combined therapy of donepezil and propolis on cognition in Drosophila melanogaster. Method. Drosophila melanogaster flies were divided into five groups and fed with the different treatment doses of ethanolic extract of propolis and donepezil as follows: normal food, propolis 250 mg/mL, propolis 50 mg/mL, donepezil 0.001M, and donepezil 0.001M/propolis 50 mg/mL added to their food. The flies were fed from larval stage for 30 days. The memory and learning tests were conducted after every 10 days to assess improvement with time. Results. The results obtained showed that the combination of propolis with donepezil caused a remarkable improvement in both the short- and long-term memory. In addition, there was a dose dependent improvement with the administration of propolis. Conclusion. Propolis extract obtained from different parts of Uganda expressed cognitive improvement when coadministered with donepezil in wild type Drosophila melanogaster.

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Interleukin-34 Synovial Fluid Was Associated with Knee Osteoarthritis Severity: A Cross-Sectional Study in Knee Osteoarthritis Patients in Different Radiographic Stages

Background. Inflammation might play a crucial role in the pathogenesis of osteoarthritis (OA). Interleukin-34 (IL-34) is a well-known proinflammatory cytokine. Objective. The objective of this study was to detect IL-34 levels in serum and synovial fluid (SF) of patients with OA and to investigate their correlation with radiographic and symptomatic severity. Methods. One hundred and eighty-two OA patients and 69 controls were recruited. IL-34 levels were measured by enzyme-linked immunosorbent assay (ELISA). Radiographic and symptomatic severity of OA was reflected by Kellgren-Lawrence (KL) grades and Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores, respectively. Results. SF IL-34 levels were independently associated with the KL grade (, 95% CI: 0.150–0.395; ). SF IL-34 levels were significantly correlated with WOMAC scores (, 95% CI: 0.123–0.399; ). The correlation between SF IL-34 levels and WOMAC scores was still significant after adjusting for confounding factors (, 95% CI: 0.001–0.038; ) in OA patients. Conclusions. We found that IL-34 levels in SF were significantly associated with the radiographic and symptomatic severity of knee OA.

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Patch Based Grid Artifact Suppressing in Digital Mammography

The mammography is the first choice of breast cancer screening, which has proven to be the most effective screening method. An antiscatter grid is usually employed to enhance the contrast of image by absorbing unexpected scattered signals. However, the grid pattern casts shadows and grid artifacts, which severely degrade the image quality. To solve the problem, we propose the patch based frequency signal filtering for fast grid artifacts suppressing. As opposed to whole image processing synchronously, the proposed method divides image into a number of blocks for tuning filter simultaneously, which reduces the frequency interference among image blocks and saves computation time by multithread processing. Moreover, for mitigating grid artifacts more precisely, characteristic peak detection is employed in each block automatically, which can accurately identify the location of the antiscatter grid and its motion pattern. Qualitative and quantitative studies were performed on simulation and real machine data to validate the proposed method. The results show great potential for fast suppressing grid artifacts and generating high quality of digital mammography.

https://ift.tt/2B3KW04

Programmed Cell Death-1/Programmed Death-Ligand 1 Blockade Improves Survival of Animals with Sepsis: A Systematic Review and Meta-Analysis

Object. To investigate effects of programmed cell death-1 (PD-1) related blockade in sepsis animals. Methods. Two reviewers independently searched electronic databases including PubMed, EMBASE, and the Cochrane Library up to February 2017. Strict literature retrieval and data extraction were performed to extract relevant data. Data analysis was conducted using RevMan 5.3 software and Stata version 12.0. And relative risks (RRs) for survival rate were calculated. A fixed-effect model was selected to pool and a forest plot was used to display RRs. Results. Four studies involving 394 animals were finally included. Nine control groups are used to pool. A fixed-effect model was applied to estimate a pooled RR of 2.19 (95% CI: 1.74–2.76), indicating that PD-1 related blockade increased survival rate in sepsis animals. Conclusion. We concluded that PD-1 related blockade can improve survival of animals with sepsis. But robust standardized clinical experiments for sepsis patients are highly desirable.

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Nonunion Humerous Fracture Infection Caused by Rhizobium radiobacter in a 24-Year-Old Healthy Patient: A Rare Case Report

Although Rhizobium radiobacter is a pathogen commonly found in soil and plants, human disease caused by the Rhizobium genus is rare and cited in immunocompromised patients and in those who carry foreign plastic bodies such as catheters. We present a case of a 24-year-old woman with an adequate immune system who underwent surgery for an open fracture of the right tibia and humerus due to a car accident. One year later, she was readmitted to the hospital, due to a nonunion of the humeral fracture for surgical debridement and revision of the internal fixation with iliac crest autograft. Rhizobium radiobacter was isolated from the nonunion site, and the patient was treated with intramuscular administration of amikacin for 3 weeks followed by doxycycline per os for 8 weeks. After 3 months, the patient showed complete remission of the infection, substantial improvement, and union on the X-ray images. This is the first case of Rhizobium radiobacter infection in a patient with an adequate immune system that did not carry any foreign body and probably was initially infected due to open wound exposure to soil. Treatment of R. radiobacter infections should be individualised according to the antimicrobial susceptibility test for a successful infection management.

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Neural Network Prediction of Corn Stover Saccharification Based on Its Structural Features

The classic assay for a large population biomass is time-consuming, labor intensive, and chemically expensive. This paper would find out a rapid assay for predicting biomass digestibility from biomass structural features without hydrolysis. We examined the 62 representative corn stover accessions that displayed a diverse cell-wall composition and varied biomass digestibility. Correlation analysis was firstly to detect effects of cell-wall compositions and wall polymer features on corn stover digestibility. Based on the dependable relationship of structural features and digestibility, a neural networks model has been developed and successfully predicted the corn stover saccharification based on the features without enzymatic hydrolysis. The actual measured and net-simulated predicted corn stover saccharification had good results as mean square error of 1.80E-05, coefficient of determination of 0.942 and average relative deviation of 3.95. The trained networks satisfactorily predicted the saccharification results based on the features of corn stover. Predicting the corn stover saccharification without hydrolysis will reduce capital and operational costs for corn stover purchasing and storage.

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Periprosthetic Joint Infection Does Not Preclude Good Outcomes after a Revision Total Knee Arthroplasty: A 7-Year Follow-Up Study of 144 Retrospective Cases

Background and Purpose. Debate exists on whether septic revision total knee arthroplasty (TKA) results in inferior clinical outcomes, and limited information is available regarding the factors associated with such outcomes. This study aimed to (1) compare clinical outcomes and characteristics of aseptic versus septic revision TKA and (2) identify the risk factors associated with inferior clinical outcomes. Methods. We retrospectively reviewed 144 revision TKAs (90 aseptic and 54 septic revisions) that were followed for a minimum of 3 years (mean = 7 years). Clinical outcome data, namely, Knee Society knee and function scores and the Hospital for Special Surgery knee score, were collected. We reviewed 13 pre- and intraoperative variables. Results. Postoperative clinical outcomes were inferior in septic revision surgeries (p

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