Lack of Association Between Proton Pump Inhibitor Use and Cognitive Decline

Studies of association between use of proton pump inhibitors (PPI) and dementia have yielded conflicting results. We investigated the effects of PPIs on cognitive decline in a study of middle-aged and elderly twins in Denmark.

http://ift.tt/2EfdoN2

Novel Computer-Enhanced Visualization of Volumetric Laser Endomicroscopy Correlates Endoscopic and Pathological Images

http://ift.tt/2FKiJJj

A Never Ending STORI

http://ift.tt/2EfJFn1

Is it significant? Is it relevant?

As outlined in the editorial by Stecker et al. (2017) in the October issue of Clinical Neurophysiology, there is little difference between the evidence for a p-value slightly less than 0.05 and another slightly larger than 0.05. However, based on a stringent cut-off of α = 0.05, a hypothesis for which p = 0.04 is conventionally accepted as true while, alternatively, with a p = 0.06 is rejected since it is "not significant". This is a common and uncomfortable "In-or-Out" scenario, but also every time a test of statistical significance is employed, researchers' interpretation of the study findings would greatly benefit from the valuable data conveyed by confidence intervals.

http://ift.tt/2DYstz1

Estimating foliar anthocyanin content of purple corn via hyperspectral model

Abstract

To date, the foliar anthocyanin content was either determined via the pH differential or HPLC methods, both of which are slow and destructive. Here, a hyperspectral model was established to estimate the foliar anthocyanin content of purple corn (Zea mays L. var. Jingzi No. 1). The reflectivity (P) of the foliar hyperspectral was inverted to 1/P, lg P, 1/lg P, , , , and . The correlation coefficient between these inversions and the foliar anthocyanin content was plotted against the hyperspectral wavelength. The wavelength of inversions around 650 nm was sensitive to the foliar anthocyanin content. The hyperspectral model was fitted via linear, polynomial, power, exponential, and logarithmic functions with the sensitive band as independent variable and the anthocyanin content as function. The hyperspectral model (y = 3,000,000,000 × W₆₈₅^4.5896) fitted via inversion of showed the highest determination coefficients (0.768) among all models. The hyperspectral model was well validated with a determination coefficient of 0.932 and an RMSE of 0.0065. Moreover, the accuracy and stability of the hyperspectral model were further enhanced with a determination coefficient of 0.954 and RMSE of 0.0047 when the anthocyanin content of the sample was below 20 mg/g. Hence, the hyperspectral model estimated the foliar anthocyanin content of purple corn quickly and nondestructively.

The foliar anthocyanin content of the purple corn was successfully estimated by the hyperspectral model. Remarkably, the accuracy and stability of the hyperspectral model in the range of 0–20 mg/g were higher than that in the range of 0–40 mg/g.

http://ift.tt/2GMzogm

Application of antimicrobial drugs in perioperative surgical incision

Infection in surgical incision often results in poor wound healing, and one of the main factors for wound infection is the use of antimicrobial agents. Rational use of antibiotics is one of the key factors to ...

http://ift.tt/2FHmrTW

STING-dependent interferon-λ1 induction in HT29 cells, a human colorectal cancer cell line following gamma-radiation

Ionizing radiation augments anti-tumor immune responses with interferons (IFN) acting as mediators. Of the three types of IFNs, type I and II IFNs are induced in irradiated tumors with induction of type III IFNs (IFNLs) currently not reported. Here, we investigated the induction of type III IFNs in human cancer cells by gamma-rays and its mechanisms.

http://ift.tt/2DZENDp

Stereotactic Ablative Radiotherapy Versus Surgery in Early Lung Cancer: A Meta-Analysis of Propensity Score Studies

As no completed randomized trials of surgery versus stereotactic ablative radiotherapy (SABR) in patients with early-stage non-small cell lung cancer are available, numerous propensity score studies have attempted to mimic the setting of clinical trials using non-randomized data. We performed a meta-analysis of propensity score studies comparing SABR and surgery.

http://ift.tt/2DYPiXj

Ki67 is an independent predictor of recurrence in the largest randomised trial of 3 radiation fractionation schedules in localised prostate cancer

External beam radiotherapy is delivered using a uniform fractionation schedule for localised prostate tumours, individualising fractionation according to tumour biology could improve outcomes. Additionally recurrence rates following radiotherapy vary considerably, better prognostic markers could improve treatment stratification. This study assessed if the cellular proliferation marker Ki67 provides prognostic information and predicts response to radiotherapy fractionation in patients participating in ", a randomised trial of three radiotherapy fractionation schedules (74Gy/37f vs 60Gy/20f vs 57Gy/19f).

http://ift.tt/2nEa9UU

Relationship Between Citation-Based Scholarly Activity of United States Radiation Oncology Residents and Subsequent Choice of Academic versus Private Practice Career

The average radiation oncology resident graduate published a minimum of four manuscripts cited at least four times. Graduates with a PhD are significantly more likely to have higher h-index scores, as are residents who choose academic over private practice careers. There is no significant difference in h-index score between male and female residents regardless of career choice. These results offer up-to-date benchmarks for evaluating resident productivity and have potential utility in predicting career choices post-residency.

http://ift.tt/2nG5eTA

Abscopal effects with hypofractionated schedules extending into the effector phase of the tumor-specific T cell response

Hypofractionated radiotherapy (hRT) combined with immune checkpoint blockade (ICB) can induce T cell-mediated local and abscopal antitumor effects. We previously observed peak levels of tumor-infiltrating lymphocytes (TILs) between day 5 and day 8 after hRT; since TILs are regarded as radiosensitive, hRT schedules extending into this period might be less immunogenic, prompting us to compare clinically relevant, short and extended schedules with equivalent biologically effective doses in combination with anti-PD1 antibody treatment.

http://ift.tt/2DYgTIe

Finger Strength, Individuation, and their Interaction: Relationship to Hand Function and Corticospinal Tract Injury after Stroke

Many activities of daily living require dexterous use of the fingers, such as opening a door, buttoning a shirt, and holding a fork. Such activities often become more effortful and slower after a stroke, and sometimes impossible to achieve with the hemiparetic hand. Thus, approximately 50% of the 700,000 individuals who survive a stroke each year in the U.S. have persistent upper extremity impairment (Dobkin, 1996; Heller et al., 1987; Ma et al., 2014; Warabi et al., 1990). Understanding the pathophysiological mechanisms that cause reduced hand function is essential for targeting stroke therapies.

http://ift.tt/2DZizkM

The Clinical Utility of Qualitative Electroencephalography during Tilt Table Testing – a Retrospective Study

Head-up tilt table testing (HUT) is often performed to aid in the diagnosis of patients with unexplained syncope (Task Force for the Diagnosis and Management of Syncope et al., 2009) or other disorders of orthostatic intolerance, such as orthostatic hypotension (OH) or postural tachycardia syndrome (POTS) (Freeman, 2008). It may also be performed to help rule out other diagnoses such as epileptic seizures, which can be difficult to differentiate from convulsive syncope, or myoclonus associated with syncope.

http://ift.tt/2nFp3dG

Diagnostic yield of standard-wake and sleep EEG recordings

Sleep influences neuronal excitability and thereby occurrence of epileptic discharges (Burr et al., 1991; Declerck, 1986; Janz, 1962; Marinig et al., 2000; Martins da Silva et al., 1984). Several studies showed that in patients suspected for epilepsy, following normal or inconclusive standard-wake EEG, recording sleep EEG increases the diagnostic yield (Bennett et al., 1964, 1969; Gunderson et al. 1973; Jovanovic, 1991; Niedermeyer, 1993; Roupakiotis et al., 2000) by activating epileptiform discharges (Degen, 1980; Geller et al., 1969; Klinger et al., 1991; Logothetis et al.

http://ift.tt/2E0lnOw

Update on the Treatment of Spontaneous Intraparenchymal Hemorrhage: Medical and Interventional Management

Abstract

Purpose of review

Spontaneous intraparenchymal hemorrhage (IPH) is a prominent challenge faced globally by neurosurgeons, neurologists, and intensivists. Over the past few decades, basic and clinical research efforts have been undertaken with the goal of delineating biologically and evidence-based practices aimed at decreasing mortality and optimizing the likelihood of meaningful functional outcome for patients afflicted with this devastating condition. Here, the authors review the medical and surgical approaches available for the treatment of spontaneous intraparenchymal hemorrhage, identifying areas of recent progress and ongoing research to delineate the scope and scale of IPH as it is currently understood and treated.

Recent findings

The approaches to IPH have broadly focused on arresting expansion of hemorrhage using a number of approaches. Recent trials have addressed the effectiveness of rapid blood pressure lowering in hypertensive patients with IPH, with rapid lowering demonstrated to be safe and at least partially effective in preventing hematoma expansion. Hemostatic therapy with platelet transfusion in patients on anti-platelet medications has been recently demonstrated to have no benefit and may be harmful. Hemostasis with administration of clotting complexes has not been shown to be effective in reducing hematoma expansion or improving outcomes although correcting these abnormalities as soon as possible remains good practice until further data are available. Stereotactically guided drainage of IPH with intraventricular hemorrhage (IVH) has been shown to be safe and to improve outcomes. Research on new stereotactic surgical methods has begun to show promise.

Summary

Patients with IPH should have rapid and accurate diagnosis with neuroimaging with computed tomography (CT) and computed tomography angiography (CTA). Early interventions should include control of hypertension to a systolic BP in the range of 140 mmHg for small hemorrhages without intracranial hypertension with beta blockers or calcium channel blockers, correction of any coagulopathy if present, and assessment of the need for surgical intervention. IPH and FUNC (Functional Outcome in Patients with Primary Intracerebral Hemorrhage) scores should be assessed. Patients should be dispositioned to a dedicated neurologic ICU if available. Patients should be monitored for seizures and intracranial pressure issues. Select patients, particularly those with intraventricular extension, may benefit from evacuation of hematoma with a ventriculostomy or stereotactically guided catheter. Once stabilized, patients should be reassessed with CT imaging and receive ongoing management of blood pressure, cerebral edema, ICP issues, and seizures as they arise. The goal of care for most patients is to regain capacity to receive multidisciplinary rehabilitation to optimize functional outcome.

http://ift.tt/2s3wiRT

Hot snare polypectomy with or without saline solution/epinephrine lift for the complete resection of small colorectal polyps

/Aim: The criterion standard polypectomy technique for the complete removal of small colorectal polyps has not yet been established. This study aimed to compare the complete resection rate of hot snare polypectomy (HSP) with that of endoscopic mucosal resection (EMR) for small, sessile, or flat polyps.

http://ift.tt/2GGpNrv

Impact of 2 generational improvements of colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study

Numerous randomized studies have shown that changing certain features of colonoscopes, usually incorporated when switching from one endoscope generation to the next, mostly do not increase adenoma yield. There is, however, indirect evidence that it may be necessary to skip one instrument generation (ie, changing from one generation to the next but one) to achieve this effect.

http://ift.tt/2s3P3VD

Hepatitis C

http://ift.tt/2nEVk4E

The Upper Esophageal Sphincter Assist Device is Associated with Symptom Response in Reflux Associated Laryngeal Symptoms

http://ift.tt/2E0gipq

A schwannoma of the small bowel

http://ift.tt/2nDq71q

A Unique Finding of Small Intestinal Leiomyoma

http://ift.tt/2DW5b0G

An Unusual Cause of Gastric Outlet Obstruction

http://ift.tt/2nGiCab

Among Patients with Nonalcoholic Fatty Liver Disease, Modest Alcohol Use is Associated with Less Improvement in Histologic Steatosis and Steatohepatitis

In patients with biopsy proven nonalcoholic fatty liver disease modest amounts of alcohol are not beneficial and may decrease the likelihood of improvement in liver disease over time.

http://ift.tt/2DZABUb

Efficacy of Granulocyte Colony Stimulating Factor and N-acetyl Cysteine Therapies in Patients with Severe Alcoholic Hepatitis

Patients with alcoholic hepatitis (AH) have high mortality, so new therapies are needed. Administration of granulocyte colony stimulating factor (GCSF) increases survival times of patients with AH. It is not known whether addition of N-acetyl cysteine (NAC) to GCSF could further increase survival time. We performed a randomized controlled pilot study to compare the efficacy of standard medical therapy with pentoxifylline to treatment with a combination of GCSF and standard medical therapy as well as to the combination of NAC, GCSF, and standard medical therapy in patients with severe AH.

http://ift.tt/2nJrw71

Human Pluripotent Stem Cell Culture on Polyvinyl Alcohol-Co-Itaconic Acid Hydrogels with Varying Stiffness Under Xeno-Free Conditions

A protocol is presented to prepare polyvinyl alcohol-co-itaconic acid hydrogels with varying stiffness, which were grafted with and without oligopeptides, to investigate the effect of the stiffness of biomaterials on the differentiation and proliferation of stem cells. The stiffness of the hydrogels was controlled by the crosslinking time.

http://ift.tt/2E2wmqA

Autocrine Activation of Platelet Derived Growth Factor Receptor Alpha in Metastatic Papillary Thyroid Cancer

Metastatic dissemination of papillary thyroid cancer has been reported to be strongly associated with expression of platelet derived growth factor alpha (PDGFRα) and altered TTF1 function. However, the status of PDGF ligands in papillary thyroid cancer and the potential role of these ligands in metastatic disease are obscure. We assessed the prevalence of PDGF ligands in benign and malignant thyroid tumors to determine if ligand up-regulation is associated with alpha-isoform (PDGF-AA or PDGF-BB) or the beta-isoform (PDGF-BB or PDGF-DD) of PDGFR in individual tumors.

http://ift.tt/2EBGUtY

KRAS and Two Rare PI3KCA Mutations Coexisting in a Metastatic Colorectal Cancer Patient With Aggressive and Resistant Disease

We describe a metastatic colorectal cancer (mCRC) patient, treated with first-line FIr-B/FOx (5-fluorouracil, irinotecan, bevacizumab, oxaliplatin) therapy, with aggressive and resistant disease. KRAS, NRAS, BRAF, PI3KCA were analyzed in primary tumor and liver metastasis. KRAS c.34G>A mutation was detected in primary tumor and liver metastasis, which, additionally, revealed two rare PI3KCA mutations (c.1633G>C, c.1645G>C). The c.1645G>C was never reported in CRC. Akt/p-AktSer473, PTEN, mismatch repair (MMR), epidermal growth factor receptor (EGFR) expression was evaluated.

http://ift.tt/2DULPF9

Cell of origin markers identify different prognostic subgroups of lung adenocarcinoma

Strong prognostic markers able to stratify lung adenocarcinoma (ADC) patients are lacking. We evaluated whether a six-immunohistochemical markers panel (TTF1, SP-A, Napsin A, MUC5AC, CDX2 and CK5), defining the putative neoplastic "cell of origin", allows to identify prognostic subgroups among lung ADC. We screened a large cohort of ADC specimens (2003–2013) from Torino Institutional Repository identifying: i) marker positivity by immunohistochemistry ii) main morphological appearance by light microscopy, iii) presence of "hot spot" mutations of candidate genes by Sequenom technology.

http://ift.tt/2EDRalt

Effect of Radiation Treatment Volume Reduction on Lymphopenia in Patients Receiving Chemoradiotherapy for Glioblastoma

Acute severe lymphopenia (ASL) in glioblastoma (GBM) patients after radiation therapy (RT) and concurrent temozolomide (TMZ) predicts for poorer overall survival (OS). This study aims to evaluate whether reduction in radiation treatment volume can reduce risk of ASL.

http://ift.tt/2nFOeNd

Long-Term Outcomes and Prognostic Factors Following Pencil-Beam Scanning Proton Radiotherapy for Spinal Chordomas: A Large, Single-Institution Cohort

To evaluate the efficacy and safety of high-dose pencil-beam scanning proton therapy (PBS-PT) in the adjuvant treatment of spinal chordomas.

http://ift.tt/2DYCQ9Z

Single and Multi-fraction Stereotactic Radiosurgery Dose Tolerances of the Optic Pathways

Data were pooled from published reports; from this data, dosimetric and clinical predictors of radiation-induced optic nerve/chiasm injury (RION) after stereotactic radiosurgery in 1 to 5 fractions were analyzed. RION risks are low (<1%) in the modern era with optic apparatus maximum point doses <10 Gy in 1 fraction, 20 Gy in 3 fractions and 25 Gy in 5 fractions (in patients without prior radiotherapy). More standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses and better define RION NTCP.

http://ift.tt/2s7AYWY

The impact of HIV infection on survival and acute toxicities from chemoradiation therapy for cervical cancer patients in a limited resource setting

Cervical cancer is the leading cause of cancer death for women in sub-Saharan Africa. Human immunodeficiency virus (HIV) infection increases the risk of cervical cancer. However, prospective data on the outcomes of cervical cancer patients with HIV infection treated with curative intent are limited.

http://ift.tt/2GM3xN8

Intraoperative Hippocampal Electrocorticography Frequently Captures Electrographic Seizures and Correlates with Hippocampal Pathology

In patients with pharmacoresistant temporal lobe epilepsy (TLE), the epileptogenic zone commonly involves the medial temporal lobe structures including the hippocampus. Removal of the hippocampus by resecting the medial temporal lobe either selectively or along with the temporal neocortex provides lasting seizure freedom (Datta et al., 2009; Kumar et al., 2013; Mittal et al., 2005; Olivier, 2000; Tanriverdi et al., 2008; Wiebe et al., 2001; Wieser et al., 2003; Wieser and Yasargil, 1982; Yasargil et al., 2010).

http://ift.tt/2BSA54a

A Novel, Fast and Efficient Single-Sensor Automatic Sleep-Stage Classification Based on Complementary Cross-Frequency Coupling Estimates

Sleep as a basic human function is characterized by continuous alterations in brain, muscle, eye, heart and respiratory activity. These multi-dimensional alterations are monitored with appropriate equipment in a sleep laboratory and are measured during a full night of sleep. Typically, these polysomnographic recordings include the electroencephalogram (EEG), electro-oculogram (EOG), electromyogram (EMG) and electrocardiogram (ECG). Physiologically, sleep stages can be split into two types: rapid eye movement (REM sleep) and non-rapid eye movement (non-REM sleep) (Steriade and McCarley, 1990).

http://ift.tt/2nz8KQ9

Randomized EEG Functional Brain Networks in Major Depressive Disorders with Greater Resilience and Lower Rich-club Coefficient

With the development of brain imaging technology, abnormalities in the structure and function of multiple brain regions have been frequently found in the brains of major depressive disorder (MDD) patients (Arnone et al., 2012; Brakowski et al., 2017; Liang et al., 2013; Liu et al., 2013; Osoba et al., 2013). However, the results associated with these abnormal brain regions are widely distributed, and it is still difficult to understand and explore the pathological characteristics of MDD patients at the whole-brain level (Hulshoff Pol and Bullmore, 2013).

http://ift.tt/2BSzzmK

Ablative Hypofractionated Radiotherapy Enhances Non-Small Cell Lung Cancer Cell Killing Via Preferential Stimulation Of Necroptosis In Vitro And In Vivo

The cellular mechanisms behind death of non-small cell lung cancer (NSCLC) treated with ablative hypofractionated radiotherapy (HFRT) are poorly understood. Our purpose is to investigate how necroptosis, i.e. programmed necrosis, is involved in killing of NSCLC after ablative HFRT.

http://ift.tt/2BRH6SY

CREPT overexpression is associated with proliferation behaviors and poor prognosis in non-small cell lung cancer

Summary

The cell-cycle-related and expression-elevated protein in tumor (CREPT) is overexpressed in several human malignancies. However, the clinical relevance of CREPT expression and its biological role in non-small cell lung cancer (NSCLC) remains unclear.In this study, we detected the expression of CREPT in both NSCLC tissues and cell lines by immunohistochemistry, Western Blot and RT-PCR. The correlation between CREPT expression and clinical pathologic features was analyzed in 271 NSCLC patients. Prognostic value of CREPT expression was evaluated by Kaplan-Meier analysis and Cox regression analysis. CREPT was overexpressed in Calu-1 cell lines by using plasmid vector and its biological function was explored both in vitro and in vivo. We found that CREPT was significantly overexpressed in NSCLC compared with paired adjacent non-tumor tissues, and the expression level of CREPT was correlated with tumor differentiation, lymph node metastasis and clinical stage. Kaplan-Meier analysis showed that the RFS and OS of high CREPT expression groups were significantly shorter than those of the low CREPT expression group. Multivariate analysis was identified that CREPT might be an independent biomarker for the prediction of NSCLC prognosis. Overexpression of CRPET increased cell proliferation enhanced the migration and invasion ability of Calu-1 cells (a human NSCLC cell line with relative low CRPET expression) in vitro. Moreover, CREPT overexpression promoted tumor growth in nude mice model. These results suggest that CREPT is closely relevant to the proliferation of NSCLC cells and it might be a potential prognostic marker in NSCLC patients.

This article is protected by copyright. All rights reserved.

http://ift.tt/2GGej7n

Application of Electrophysiology Measurement to Study the Activity of Electro-Neutral Transporters

This manuscript describes the applications of proton-selective electrodes and patch clamping methods to measure the activity of proton transport systems. These methods overcome some limitations of techniques commonly used to study proton transport activity, such as moderate sensitivity, time resolution and insufficient intracellular milieu control.

http://ift.tt/2nG5TnV

Activin receptors regulate the oligodendrocyte lineage in health and disease

Abstract

The most prevalent neurological disorders of myelin include perinatal brain injury leading to cerebral palsy in infants and multiple sclerosis in adults. Although these disorders have distinct etiologies, they share a common neuropathological feature of failed progenitor differentiation into myelin-producing oligodendrocytes and lack of myelin, for which there is an unmet clinical need. Here, we reveal that a molecular pathology common to both disorders is dysregulation of activin receptors and that activin receptor signaling is required for the majority of myelin generation in development and following injury. Using a constitutive conditional knockout of all activin receptor signaling in oligodendrocyte lineage cells, we discovered this signaling to be required for myelination via regulation of oligodendrocyte differentiation and myelin compaction. These processes were found to be dependent on the activin receptor subtype Acvr2a, which is expressed during oligodendrocyte differentiation and axonal ensheathment in development and following myelin injury. During efficient myelin regeneration, Acvr2a upregulation was seen to coincide with downregulation of Acvr2b, a receptor subtype with relatively higher ligand affinity; Acvr2b was shown to be dispensable for activin receptor-driven oligodendrocyte differentiation and its overexpression was sufficient to impair the abovementioned ligand-driven responses. In actively myelinating or remyelinating areas of human perinatal brain injury and multiple sclerosis tissue, respectively, oligodendrocyte lineage cells expressing Acvr2a outnumbered those expressing Acvr2b, whereas in non-repairing lesions Acvr2b+ cells were increased. Thus, we propose that following human white matter injury, this increase in Acvr2b expression would sequester ligand and consequently impair Acvr2a-driven oligodendrocyte differentiation and myelin formation. Our results demonstrate dysregulated activin receptor signaling in common myelin disorders and reveal Acvr2a as a novel therapeutic target for myelin generation following injury across the lifespan.

http://ift.tt/2DZZOxs

In Situ Detection and Single Cell Quantification of Metal Oxide Nanoparticles Using Nuclear Microprobe Analysis

We describe a procedure for the detection of chemical elements present in situ in human cells as well as their in vitro quantification. The method is well-suited to any cell type and is particularly useful for quantitative chemical analyses in single cells following in vitro metal oxide nanoparticles exposure.

http://ift.tt/2EF0vcU

Too Hot to Handle? When Vaporizers Explode

A 17-year-old boy presented with complaints of a burned left thumb with sensory loss, decreased motor control, and heavy bleeding (Figure 1). The patient was about to take a puff of his electronic cigarette (e-cigarette) when his electronic nicotine-delivery system (ENDS) device exploded. Radiographs of the left hand demonstrated a soft tissue defect at the level of the interphalangeal joint of the thumb, with extensive subcutaneous emphysema and streaky radiodense material infiltrating the soft tissues, presumably ENDS material (Figure 2; available at www.jpeds.com).

http://ift.tt/2DYsabr

SMACC NYC Party

If you are anything like me, you have been wondering when the heck the dasSMACC videos are going to be posted. Well the answer is–they debut on March 10, 2018. That is so big that it deserves its own party, in fact it deserves 3 parties! So if you are anywhere close to one of […]

EMCrit Project by Scott Weingart.

http://ift.tt/2nFMWBJ

Early Post-Therapy Prescription Drug Usage among Childhood and Adolescent Cancer Survivors

To describe the patterns of prescription drug use among child and adolescent survivors of cancer in the early post-therapy period compared with matched peers without a cancer history.

http://ift.tt/2FHb6n1

The Inverse Relationship between Digital Media Exposure and Childhood Flourishing

To describe the relationship between digital media exposure (DME) and parental perception of childhood flourishing, or overall positive well-being. It is hypothesized that there is an inverse association between parent-reported measures of childhood flourishing and increasing daily DME.

http://ift.tt/2Ee4xes

Delirium is a Common and Early Finding in Patients in the Pediatric Cardiac Intensive Care Unit

To determine incidence, associated risk factors, and characteristics of delirium in a pediatric cardiac intensive care unit (CICU). Delirium is a frequent and serious complication in adults after cardiac surgery, but there is limited understanding of its impact in children with critical cardiac disease.

http://ift.tt/2FGFxcZ

Omega-3 Polyunsaturated Fatty Acid Supplementation to Prevent Arteriovenous Fistula and Graft Failure: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Arteriovenous access failure frequently occurs in people on hemodialysis and is associated with morbidity, mortality and large healthcare expenditures. Omega-3 polyunsaturated fatty acids (omega-3 PUFA) may improve access outcomes via pleiotropic effects on access maturation and function, but may cause bleeding complications.

http://ift.tt/2DXRDxI

One-Year Linear Trajectories of Symptoms, Physical Functioning, Cognitive Functioning, Emotional Well-being, and Spiritual Well-being Among Patients Receiving Dialysis

This study evaluated 1-year linear trajectories of patient-reported dimensions of quality of life among patients receiving dialysis.

http://ift.tt/2ECect5

The Value of Genetic Testing in Polycystic Kidney Diseases Illustrated by a Family With PKD2 and COL4A1 Mutations

The diagnosis of autosomal dominant polycystic kidney disease (ADPKD) relies on imaging criteria in the setting of a positive familial history. Molecular analysis, seldom used in clinical practice, identifies a causative mutation in >90% of cases in the genes PKD1, PKD2, or rarely GANAB. We report the clinical and genetic dissection of a 7-generation pedigree, resulting in the diagnosis of 2 different cystic disorders. Using targeted next-generation sequencing of 65 candidate genes in a patient with an ADPKD-like phenotype who lacked the familial PKD2 mutation, we identified a COL4A1 mutation (p.Gln247*) and made the diagnosis of HANAC (hereditary angiopathy with nephropathy, aneurysms, and muscle cramps) syndrome.

http://ift.tt/2DZkt0I

Variation in Dialysis Exposure Prior to Nonpreemptive Living Donor Kidney Transplantation in the United States and Its Association With Allograft Outcomes

The impact of dialysis exposure before nonpreemptive living donor kidney transplantation on allograft outcomes is uncertain.

http://ift.tt/2ECVBx6

Discussing Conservative Management With Older Patients With CKD: An Interview Study of Nephrologists

Although dialysis may not provide a large survival benefit for older patients with kidney failure, few are informed about conservative management. Barriers and facilitators to discussions about conservative management and nephrologists' decisions to present the option of conservative management may vary within the nephrology provider community.

http://ift.tt/2DYSw9r

Brain Magnetic Resonance Imaging Findings in Children and Young Adults With CKD

The neuroanatomic basis for cognitive impairment in chronic kidney disease (CKD) is incompletely characterized. We performed advanced quantitative structural magnetic resonance imaging (MRI) to determine whether CKD affects brain structure and whether poorer neurocognitive performance in CKD is associated with structural brain differences.

http://ift.tt/2ECLVT1

Efficacy of a Novel Palivizumab Prophylaxis Protocol for Respiratory Syncytial Virus Infection in Congenital Heart Disease: A Multicenter Study

To analyze the efficacy of a novel palivizumab protocol for hemodynamically significant congenital heart disease (hsCHD) in subtropical areas without clear respiratory syncytial virus seasonality.

http://ift.tt/2nzGFbM

Mercury Poisoning in a Toddler from Home Contamination due to Skin-Lightening Cream

A 17-month-old child presented with hypertension, fussiness, constipation, and arthralgia due to mercury toxicity from a skin-lightening cosmetic used by her mother and grandmother. Blood mercury level was 26 mcg/L and urine level was 243 mcg/g creatinine. She was chelated with succimer. The home was contaminated and needed remediation.

http://ift.tt/2BRkGkM

Variation in Part-Time Work among Pediatric Subspecialties

To assess the part-time workforce and average hours worked per week among pediatric subspecialists in the 15 medical subspecialties certified by the American Board of Pediatrics.

http://ift.tt/2nyPQJc

To Split or Not to Split? That is No Longer the Question

In this volume of The Journal, Mogul et al report the use of data from the Scientific Registry of Transplant Recipients to compare pediatric liver transplant patients from 2 different post-Model for End Stage Liver Disease (MELD) eras (2002-2009 vs 2010-2015) to determine if outcomes have improved.1 The authors stratify the transplants by type of donor graft, specifically whole liver transplant (WLT), split liver transplant (SLT), and living donor liver transplant (LDLT) and make comparisons not only between eras but also between donor graft types.

http://ift.tt/2BS6QP1

The Sensitivity of Clinician Diagnosis of Sepsis in Tertiary and Community-Based Emergency Settings

To assess whether the risk of missed clinician diagnosis of pediatric sepsis requiring care in the intensive care unit (ICU) was greater in community vs tertiary pediatric emergency care settings with sepsis pathways.

http://ift.tt/2nyPMsW

Prospective Cohort Study of Breastfeeding and the Risk of Childhood Asthma

To study whether the duration of breastfeeding and time for introduction of complementary foods was associated with the risk of childhood asthma.

http://ift.tt/2BRGixp

Management of Hypertension and High Low-Density Lipoprotein in Pediatric Type 1 Diabetes

To evaluate hypertension and hyperlipidemia management patterns in youth with type 1 diabetes and to assess perceived effectiveness of management strategies and barriers to management.

http://ift.tt/2nyPJgK

Impact of Discharge Components on Readmission Rates for Children Hospitalized with Asthma

To describe hospital-based asthma-specific discharge components at children's hospitals and determine the association of these discharge components with pediatric asthma readmission rates.

http://ift.tt/2BRATq4

Postoperative Diabetes Insipidus and Hyponatremia in Children after Transsphenoidal Surgery for Adrenocorticotropin Hormone and Growth Hormone Secreting Adenomas

To define the incidence and risk factors of postoperative sodium alterations in pediatric patients undergoing transsphenoidal surgery (TSS) for adrenocorticotropic hormone and growth hormone secreting pituitary adenomas.

http://ift.tt/2nypFCE

PEG 3350 Administration Is Not Associated with Sustained Elevation of Glycol Levels

To determine whether trace amounts of ethylene glycol (EG), diethylene glycol (DEG), or triethylene glycol (TEG) in PEG 3350 are associated with increased blood levels of EG, DEG, or TEG in children receiving daily PEG 3350 therapy.

http://ift.tt/2BRGbBZ

A Heterozygous NDUFV1 Variant Aggravates Mitochondrial Complex I Deficiency in a Family with a Homoplasmic ND1 Variant

We demonstrate that a heterozygous nuclear variant in the gene encoding mitochondrial complex I subunit NDUFV1 aggravates the cellular phenotype in the presence of a mitochondrial DNA variant in complex I subunit ND1. Our findings suggest that heterozygous variants could be more significant in inherited mitochondrial diseases than hitherto assumed.

http://ift.tt/2nyZtI5

Endoscopic eradication therapy for patients with Barrett’s esophagus–associated dysplasia and intramucosal cancer

Barrett's esophagus (BE) is defined by the replacement of the normal squamous epithelium of the distal esophagus with metaplastic intestinal-type columnar epithelium.1-3 BE is an adverse event of chronic GERD and the only identifiable premalignant condition for esophageal adenocarcinoma (EAC), a cancer that continues to increase in incidence. In 2014 there were approximately 18,170 incident cases of esophageal cancer in the United States, nearly 60% of which were EAC.4-6 Although uncommon, EAC is a highly lethal cancer associated with a poor 5-year survival rate of 15% to 20% and an overall median survival of <1 year in cases with advanced disease.

http://ift.tt/2s5bKIQ

Efficacy of docetaxel in castration-resistant prostate cancer patients with intraductal carcinoma of the prostate

Abstract

Background

This study aimed to investigate the efficacy of docetaxel in castration-resistant prostate cancer (CRPC) patients with intraductal carcinoma of the prostate (IDC-P).

Patients and methods

We retrospectively identified 79 CRPC patients with distant metastasis at initial diagnosis from June 2002 to January 2014. All patients received initial androgen deprivation therapy and 46 received docetaxel chemotherapy after progressing to CRPC. The primary outcome of interest was cancer-specific survival (CSS) from the time of CRPC diagnosis. The Cox regression model was used to confirm whether IDC-P and docetaxel would act as independent factors for prognosis.

Results

IDC-P was found in 62 of 79 patients. The median CSS in the IDC-P-present group was 18.2 versus 45.6 months in the IDC-P-absent group (HR 2.67; 95% CI 1.18 to 6.06; P = 0.019). Docetaxel was administered to 36 patients with IDC-P and 10 patients without IDC-P, with a median CSS of 20.5 versus 53.2 months, respectively (HR 2.98; 95% CI 1.02 to 8.64; P = 0.044). Multivariate analysis demonstrated that the presence of IDC-P and docetaxel were independent prognostic factors for CSS (P = 0.026 and 0.005, respectively) and overall survival (OS) (P = 0.029 and 0.001, respectively).

Conclusion

The presence of IDC-P is an independent prognostic factor in CRPC patients with distant metastases and IDC-P in needle biopsies at the time of initial diagnosis. Docetaxel may prolong CSS and OS in CRPC patients with distant metastases and IDC-P in needle biopsies at the time of initial diagnosis.

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Evaluation of the bioactivity of fluoride-enriched mineral trioxide aggregate on osteoblasts

Abstract

Aim

To investigate if a combination of mineral trioxide aggregate (MTA) and fluoride compounds affects bone cells.

Methodology

MTA discs (ProRoot^®, Dentsply Sirona, Ballaigues, Switzerland) with and without addition of 0.1%, 0.25%, and 0.5% sodium fluoride were characterized for their surface roughness by laser scanning microscopy and for the adhesion of human alveolar osteoblasts by scanning electron microscopy. Using eluates from fluoride-enriched MTA discs, the cell proliferation was measured by monitoring the DNA incorporation of 5-bromo-2′-deoxyuridine. Further, gene expression was evaluated by qPCR arrays, extracellular matrix mineralization was quantified by absorption measurement of Alizarin red stains, and effects were calculated with repeated measures analysis and post hoc p-value adjustment.

Results

Irrespective of fluoride addition, cell adhesion was similar on MTA discs, of which the surface roughness was comparable. Control osteoblasts had a curvilinear proliferation pattern peaking at d5, which was leveled out by incubation with MTA. The addition of fluoride partly restored the MTA-related reduction of the cellular proliferation rate in a dose-dependent manner. At the mRNA level, both fluoride and MTA modulated a number of genes involved in osteogenesis, bone mineral metabolism and extracellular matrix formation. Although MTA significantly impaired extracellular matrix mineralization, the addition of fluoride supported the formation of mineralized nodules in a dose-dependent manner.

Conclusion

The addition of fluoride modulatesd the biocompatibility of MTA in terms of supporting bone cell proliferation and hard tissue formation. Hence, fluoride enrichment is a trend-setting advancement for MTA-based endodontic therapies.

This article is protected by copyright. All rights reserved.

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Antibacterial properties of silver nanoparticles as a root canal irrigant against Enterococcus faecalis biofilm and infected dentinal tubules

Abstract

Aim

To evaluate the antimicrobial action of an irrigant containing silver nanoparticles in aqueous vehicle (AgNp), sodium hypochlorite and chlorhexidine against Enterococcus faecalis biofilm and infected dentinal tubules.

Methodology

Bovine dentine blocks were used for E. faecalis biofilm development for 21 days and irrigated with 94 ppm AgNp solution, 2.5% NaOCl and 2% Chlorhexidine for 5, 15 and 30 minutes. For infection of dentinal tubules with E. faecalis, dentine specimens from bovine incisors were submitted to a contamination protocol over five days, with 8 centrifugation cycles on every alternate day, and irrigated with the same solutions and time intervals used for the biofilm. The specimens were stained with the Live/Dead technique and evaluated using a confocal laser scanning microscope (CLSM). The bioImage_L software was used for measurement of the total biovolume of biofilm in μm³ and percentage of viable bacteria (green cells) in biofilm and in dentinal tubules found after the irrigation. Statistical analyses were performed using Kruskal-Wallis and Dunn tests for quantification of viable cells in biofilm, Friedman test for comparisons of viable bacteria in dentinal tubules in different areas of the root canal and Mann-Whitney U-test to compare the action of the irrigants between the two methods (P < 0.05).

Results

The AgNp solution eliminated fewer bacteria, but showed more ability to dissolve biofilm compared with chlorhexidine (P < 0.05). NaOCl had the greatest antimicrobial activity and biofilm dissolution capacity. AgNp solution had less antimicrobial action in infected dentinal tubules compared with NaOCl (P < 0.05). The AgNp solution after 5 minutes was more effective in eliminating planktonic bacteria in dentinal tubules than in biofilm, but at 30 minutes fewer viable bacteria were observed in the biofilm compared with intratubular dentine (P < 0.05).

Conclusions

AgNp irrigant was not as effective against E. faecalis as solutions commonly used in root canal treatment. NaOCl is appropriate as an irrigant because it was effective in disrupting biofilm and in eliminating bacteria in biofilms and in dentinal tubules.

This article is protected by copyright. All rights reserved.

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Outcome of full pulpotomy using Biodentine in adult patients with symptoms indicative of irreversible pulpitis

Abstract

Aim

To assess the outcome of full pulpotomy using Biodentine in permanent teeth with carious exposures and symptoms indicative of irreversible pulpitis.

Methodology

Sixty-four permanent molar teeth with symptomatic vital pulps in 52 patients aged 19-69 years were included. Preoperative pulpal and periapical diagnosis was established. After informed consent the tooth was anaesthetized, isolated using rubber dam and disinfected with 5% NaOCl before caries excavation; subsequently the pulp was amputated to the level of the canal orifices. Haemostasis was achieved and a 3 mm layer of Biodentine (Septodont, Saint-Maur-des-Fosses, France) was placed as the pulpotomy agent. Resin modified glass ionomer liner was placed and the tooth restored with either resin composite or amalgam, and a postoperative periapical radiograph exposed. Clinical and radiographic evaluation was completed at 6 months and 1 year postoperatively. Pain levels were scored preoperatively and 2 days post treatment.

Results

Clinical signs and symptoms indicative of irreversible pulpitis were established in all teeth, and periapical rarefaction was present in 9 teeth. After 2 days 93.8% reported complete relief of pain. At 6 months 63/64 attended recall with 98.4% clinical and radiographic success. At 1 year 59/63 attended recall, with 100% clinical and 98.4 radiographic success. Seven out of eight cases with periapical rarefaction who attended recall had improvement in the periapical index (PAI) score. A hard tissue barrier was detected radiographically in 4 cases.

Conclusion

Full pulpotomy using Biodentine was a successful treatment option for cariously exposed pulps in mature permanent molar teeth with clinical signs and symptoms indicative of irreversible pulpitis, up to one year.

This article is protected by copyright. All rights reserved.

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New perspectives to improve critical care benchmarking

http://ift.tt/2BRUDKe

Significance of microcystic, elongated, and fragmented glandular-like features in intraductal papillary mucinous neoplasm of the pancreas

Microcystic, elongated, and fragmented (MELF) glandular features are associated with epithelial-mesenchymal transition, invasion, and progression in endometrioid adenocarcinoma of the uterus. Similar histological features are also observed at the periphery of pancreatic intraductal papillary mucinous neoplasms (IPMNs). However, the clinicopathological significance of MELF-like features—particularly whether they represent regenerative or truly neoplastic conditions—in IPMNs remains unclear. We assessed a total of 152 surgically resected IPMNs.

http://ift.tt/2DXndf6

Renal outcomes in primary IgA nephropathy patients with segmental glomerular necrosis: a case–control study

The renal prognosis and treatment of primary IgA nephropathy (IgAN) patients with segmental glomerular necrosis (SGN) remain controversial. Patients with primary IgAN confirmed by renal biopsy were enrolled. Patients with SGN on renal biopsy were selected as the necrosis group, and a propensity score matching method was used to match a control group according to age, gender, weight, height and follow-up time. A total of 825 IgAN patients were enrolled in the present study. Seventy-three (8.8%) patients with SGN were selected as the necrosis group, and 292 patients without SGN were matched as the control group.

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Cluster: barriers of the central nervous system

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Somatic NRAS mutation in patient with generalized lymphatic anomaly

Abstract

Generalized lymphatic anomaly (GLA or lymphangiomatosis) is a rare disease characterized by a diffuse proliferation of lymphatic vessels in skin and internal organs. It often leads to progressive respiratory failure and death, but its etiology is unknown. Here, we isolated lymphangiomatosis endothelial cells from GLA tissue. These cells were characterized by high proliferation and survival rates, but displayed impaired capacities for migration and tube formation. We employed whole exome sequencing to search for disease-causing genes and identified a somatic mutation in NRAS. We used mouse and zebrafish model systems to initially evaluate the role of this mutation in the development of the lymphatic system, and we studied the effect of drugs blocking the downstream effectors, mTOR and ERK, on this disease.

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Glomerular endothelial cell maturation depends on ADAM10, a key regulator of Notch signaling

Abstract

The principal function of glomeruli is to filter blood through a highly specialized filtration barrier consisting of a fenestrated endothelium, the glomerular basement membrane and podocyte foot processes. Previous studies have uncovered a crucial role of endothelial a disintegrin and metalloprotease 10 (ADAM10) and Notch signaling in the development of glomeruli, yet the resulting defects have not been further characterized nor understood in the context of kidney development. Here, we used several different experimental approaches to analyze the kidneys and glomeruli from mice lacking ADAM10 in endothelial cells (A10ΔEC mice). Scanning electron microscopy of glomerular casts demonstrated enlarged vascular diameter and increased intussusceptive events in A10ΔEC glomeruli compared to controls. Consistent with these findings, genes known to regulate vessel caliber (Apln, AplnR and Vegfr3) are significantly upregulated in A10ΔEC glomeruli. Moreover, transmission electron microscopy revealed the persistence of diaphragms in the fenestrae of A10ΔEC glomerular endothelial cells, which was corroborated by the elevated expression of the protein PLVAP/PV-1, an integral component of fenestral diaphragms. Analysis of gross renal vasculature by light sheet microscopy showed no major alteration of the branching pattern, indicating a localized importance of ADAM10 in the glomerular endothelium. Since intussusceptions and fenestrae with diaphragms are normally found in developing, but not mature glomeruli, our results provide the first evidence for a crucial role of endothelial ADAM10, a key regulator of Notch signaling, in promoting the development and maturation of the glomerular vasculature.

http://ift.tt/2DYHp4f

Characteristics of Unscheduled and Scheduled Outpatient Palliative Care Clinic Patients at a Comprehensive Cancer Center

There is limited literature regarding outpatient palliative care and factors associated with unscheduled clinic visits.

http://ift.tt/2EAzirJ

Longitudinal study of radiation-induced brain microstructural alterations with S-index, a Diffusion MRI biomarker, and MR Spectroscopy

Cancer patients frequently suffer from cognitive impairments following brain radiotherapy. To monitor radiation-induced microstructural tissue damage, especially in neurogenic areas, we have investigated the potential of diffusion MRI and MR spectroscopy. The diffusion S-index calculated from diffusion MRI signal acquired at two optimized values of diffusion-weighting appeared as the most sensitive biomarker revealing subtle brain tissue alterations induced by ionizing radiation.

http://ift.tt/2DXTkiD

rIncremental yield of dysplasia detection in Barrett’s esophagus using volumetric laser endomicroscopy with and without laser marking compared with a standardized random biopsy protocol

Volumetric laser endomicroscopy (VLE) is a new wide field advanced imaging technology for Barrett's esophagus (BE). No data exist on incremental yield of dysplasia detection. Our aim is to report the incremental yield of dysplasia detection in BE using VLE.

http://ift.tt/2FIAWqK

One-pot catalytic copolymerization of unsaturated plant oils or fatty acid methyl esters with ethylene

Abstract

Until now natural fatty ester acid esters with their internal C=C-bonds could not be used as substrates for catalytic polymerization reactions. It was always necessary to convert them to terminal unsaturated fatty acid esters first. Therefore we now developed a two-catalyst system consisting of an isomerization catalyst and a Brookhart polymerization catalyst. With this system of isomerizing copolymerization (IsoCoP) it is possible to copolymerize high oleic plant oils or fatty acid methyl esters with ethylene in a one-pot reaction. The resulting polymers have molecular weights above 30 kDa and can contain more than 20 weight percent plant oils. The copolymers of fatty acid methyl esters are soluble in organic solvents. The predominant part of the copolymers from plant oils is usually soluble. The insoluble fraction is soluble after hydrolysis indicating a rare cross-linking of polyolefin chains by triglycerol units. The catalytic system is effective yielding polymers with a productivity of up to 100 kg polymer per mole catalyst and pretty robust. Plants oils need to be purified only by a simple filtration over alumina before copolymerization.

Practical applications: The possibility to copolymerize plant oils with ethylene leads to a new class of polymers and may enhance the usage of plant oils for plastics greatly. The new polymers might be used e.g. for tackifiers or primers.

http://ift.tt/2nEyHgB

Influence of Oxidised Oils on Digestibility of Caseins in O/W emulsions

Abstract

The impact of lipid oxidation on protein modifications in emulsions and the consequences on protein digestibility remains unclear. In this study, this impact was evaluated in casein (6 mg/mL) based emulsions containing oxidised soybean or fish oil (3 %) in presence (0.3 %) or absence of the emulsifier Tween 20. Emulsions were prepared using oils at three oxidation levels and subsequently the impact on protein digestibility was evaluated after 24 hours incubation at 4°C. Remarkably, protein digestibility increased in emulsions containing medium and highly oxidised fish oil: 70 ± 0.4 % and 73 ± 0.4 % of the proteins were digested respectively, whereas protein digestibility in emulsions containing low oxidised fish oil amounted to 63 ± 0.4%. Protein digestibility in emulsions containing soybean oil stabilised by Tween 20 was not influenced by the oxidation level of the oil used. A remarkable tendency is observed for the malondialdehyde content of the emulsions depending on the presence of Tween 20. For soybean oil based emulsions, malondialdehyde concentrations were consistently higher in the presence of Tween 20. On the other hand, for the fish oil based emulsions an opposite trend was observed, except at the highest oxidation level evaluated, for which no significant differences could be detected. We concluded that the composition of the interface in emulsions depends strongly upon the degree of oil oxidation and the presence of other emulsifiers. If the oil is more oxidised, less protein is present in the interface restricting the impact of lipid oxidation products on the proteins and hence their digestibility.

Practical applications: This research was done to highlight the relevance of the interfacial composition in food emulsions and its influence on dairy protein digestibility. The Food industry must be aware of the oil quality and the presence of emulsifiers in foods emulsions that allow to preserve the stability and nutritional characteristics of these food emulsions.

http://ift.tt/2DWAt7P

Acacia hydaspica R. Parker ameliorates cisplatin induced oxidative stress, DNA damage and morphological alterations in rat pulmonary tissue

Cisplatin (CP) drug is platinum compounds used for the treatment of various human malignancies. However, adverse outcomes related to CP restrict its usage. Acacia hydaspica is a natural shrub with various pharmac...

http://ift.tt/2DX8kte

Synergistic effect of the pro-apoptosis peptide kla-TAT and the cationic anticancer peptide HPRP-A1

Abstract

In this study, a peptide–peptide co-administration therapy between hybrid peptide kla-TAT and cationic anticancer peptide HPRP-A1 was designed to increase the anticancer activity of the combination peptides through synergistic effect. kla is a pro-apoptotic peptide which could induce rapid cancer cell apoptosis by disruption the mitochondrial membrane when internalized the cells. To enhance more kla peptides pass through cell membrane, a double improvement strategy was designed by chemically conjugation with cell penetration peptide TAT as well as co-administration with cationic membrane active peptide HPRP-A1, and the double anticancer mechanism of the kla-TAT peptide and HPRP-A1 including membrane disruption and apoptosis induction was verified through in vitro experiments. The CompuSyn synergism/antagonism analysis showed that kla-TAT acted synergistically with HPRP-A1 against a non-small cell lung cancer (NSCLC) A549 cell line. The anticancer activities of the two peptides were dramatically increased by co-administration, under the mechanism of cell membrane disruption, caspase-dependent apoptosis induction, as well as cyclin-D1 down-regulation based G1 phase arrest. We believe that the synergic therapeutic strategy would be a meaningful method for the anticancer peptides used in cancer treatment.

http://ift.tt/2EBPfhm

Podocyte Infolding Glomerulopathy (PIG) in a Patient With Undifferentiated Connective Tissue Disease: A Case Report

Podocyte infolding glomerulopathy (PIG) is a recently described pathologic entity characterized by diffuse podocyte infolding into the glomerular basement membrane (GBM) associated with ultrastructurally demonstrable microspherular aggregates. The clinical features, significance, and pathogenesis of this condition are still not well delineated because only a few cases have been documented to date, all from Japan. We report a case of PIG associated with undifferentiated connective tissue disease in an Indian woman who presented with nephrotic syndrome while undergoing treatment for an autoimmune disorder.

http://ift.tt/2nxXyn6

Challenges and Promises of PET Radiomics

Radiomics describes the extraction of multiple, otherwise invisible, features from medical images that, with bioinformatic approaches, can be used to provide additional information that can predict underlying tumor biology and behavior.

http://ift.tt/2DXLdTd

Schizophrenia polygenic risk score predicts mnemonic hippocampal activity

Abstract

The use of polygenic risk scores has become a practical translational approach to investigating the complex genetic architecture of schizophrenia, but the link between polygenic risk scores and pathophysiological components of this disorder has been the subject of limited research. We investigated in healthy volunteers whether schizophrenia polygenic risk score predicts hippocampal activity during simple memory encoding, which has been proposed as a risk-associated intermediate phenotype of schizophrenia. We analysed the relationship between polygenic risk scores and hippocampal activity in a discovery sample of 191 unrelated healthy volunteers from the USA and in two independent replication samples of 76 and 137 healthy unrelated participants from Europe and the USA, respectively. Polygenic risk scores for each individual were calculated as the sum of the imputation probability of reference alleles weighted by the natural log of odds ratio from the recent schizophrenia genome-wide association study. We examined hippocampal activity during simple memory encoding of novel visual stimuli assessed using blood oxygen level-dependent functional MRI. Polygenic risk scores were significantly associated with hippocampal activity in the discovery sample [P = 0.016, family-wise error (FWE) corrected within Anatomical Automatic Labeling (AAL) bilateral hippocampal-parahippocampal mask] and in both replication samples (P = 0.033, FWE corrected within AAL right posterior hippocampal-parahippocampal mask in Bari sample, and P = 0.002 uncorrected in the Duke Neurogenetics Study sample). The relationship between polygenic risk scores and hippocampal activity was consistently negative, i.e. lower hippocampal activity in individuals with higher polygenic risk scores, consistent with previous studies reporting decreased hippocampal-parahippocampal activity during declarative memory tasks in patients with schizophrenia and in their healthy siblings. Polygenic risk scores accounted for more than 8% of variance in hippocampal activity during memory encoding in discovery sample. We conclude that polygenic risk scores derived from the most recent schizophrenia genome-wide association study predict significant variability in hippocampal activity during memory encoding in healthy participants. Our findings validate mnemonic hippocampal activity as a genetic risk associated intermediate phenotype of schizophrenia, indicating that the aggregate neurobiological effect of schizophrenia risk alleles converges on this pattern of neural activity.

http://ift.tt/2DXnxKW

Gross Anatomy Examination Performances in relation to Medical Students' Knowledge of Classical Latin and Greek

Abstract

The ability of medical students to acquire anatomical and medical terminologies could be influenced by their knowledge of classical Greek and Latin. In a previous study (Stephens and Moxham, 2016), it was reported that, while newly recruited medical students have a very favourable attitude towards the need to understand these classical languages, final year students see no benefit. In this study, we tested the hypothesis that, regardless of attitude, students in the initial stages of their medical education perform better at both summative and formative anatomy examinations if they have prior knowledge of Greek and Latin. First year medical students at Cardiff University who had been involved in the previous study concerning attitudes towards the relevance of the classical languages to medical education were evaluated in terms of their examination results in anatomy. Two hundred and twenty-seven students responded to a questionnaire (83% of the class) that categorised students into their linguistic knowledge and skills and their performances in formative and summative examinations were analysed. For medical students with prior knowledge of classical Greek and Latin performed better in both summative and formative anatomy examinations. The results are therefore consistent with our hypothesis. This article is protected by copyright. All rights reserved.

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Neuronal oscillations on an ultra-slow timescale: Daily rhythms in electrical activity and gene expression in the mammalian master circadian clockwork

Abstract

Neuronal oscillations of the brain, such as those observed in the cortices and hippocampi of behaving animals and humans, span across wide frequency bands, from slow delta waves (0.1 Hz) to ultra-fast ripples (600 Hz). Here, we focus on ultra-slow neuronal oscillators in the hypothalamic suprachiasmatic nuclei (SCN), the master daily clock that operates on interlocking transcription-translation feedback loops to produce circadian rhythms in clock gene expression with a period of near 24 hours (<0.001 Hz). This intracellular molecular clock interacts with the cell's membrane through poorly understood mechanisms to drive the daily pattern in the electrical excitability of SCN neurons, exhibiting an up-state during the day and a down-state at night. In turn, the membrane activity feeds back to regulate the oscillatory activity of clock gene programs. In this review, we emphasise the circadian processes that drive daily electrical oscillations in SCN neurons, and highlight how mathematical modelling contributes to our increasing understanding of circadian rhythm generation, synchronisation and communication within this hypothalamic region and across other brain circuits.

This article is protected by copyright. All rights reserved.

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Effects of early antiplatelet therapy after splenectomy with gastro-oesophageal devascularization

Background

This study aimed to explore the effects of early antiplatelet therapy (APT) for portal vein thrombosis (PVT) in patients with cirrhotic portal hypertension after splenectomy with gastro-oesophageal devascularization.

Methods

We retrospectively analysed 139 patients who underwent splenectomy with gastro-oesophageal devascularization for portal hypertension due to cirrhosis between April 2010 and December 2016. Based on the post-operative platelet values, we used two different APT regimens: APT was started when platelet counts were increased to 200 × 10⁹/L or above (group A, n = 64) or 300 × 10⁹/L or above (group B, n = 75). We took note of the patients' clinical symptoms, operative factors and biochemical indicators.

Results

Platelet count, mean platelet volume, D-dimer and pancreatic fistula were closely related to the development of PVT. Early APT was an independent protective factor for PVT. The incidence of post-operative PVT was 15.1% (21/139) overall, 4.7% (3/64) in group A and 24% (18/75) in group B; there was a significant difference between groups A and B (χ² = 10.042, P = 0.002).

Conclusion

Platelet count, mean platelet volume, D-dimer and pancreatic fistula were independent risk factors for the development of PVT after splenectomy with gastro-oesophageal devascularization. Selection of the appropriate timing for early APT according to the post-operative platelet count was feasible. Moreover, the use of aspirin combined with dipyridamole was safe and effective for early prevention of PVT.

http://ift.tt/2EyR8LD

Cancers, Vol. 10, Pages 42: MYC Regulates α6 Integrin Subunit Expression and Splicing Under Its Pro-Proliferative ITGA6A Form in Colorectal Cancer Cells

Cancers, Vol. 10, Pages 42: MYC Regulates α6 Integrin Subunit Expression and Splicing Under Its Pro-Proliferative ITGA6A Form in Colorectal Cancer Cells

Cancers doi: 10.3390/cancers10020042

Authors: Jean-François Groulx Salah Boudjadi Jean-François Beaulieu

The α6 integrin subunit (ITGA6) pre-mRNA undergoes alternative splicing to form two splicing variants, named ITGA6A and ITGA6B. In primary human colorectal cancer cells, the levels of both ITGA6 and β4 integrin subunit (ITGB4) subunits of the α6β4 integrin are increased. We previously found that the upregulation of ITGA6 is a direct consequence of the increase of the pro-proliferative ITGA6A variant. However, the mechanisms that control ITGA6 expression and splicing into the ITGA6A variant over ITGA6B in colorectal cancer cells remain poorly understood. Here, we show that the promoter activity of the ITGA6 gene is regulated by MYC. Pharmacological inhibition of MYC activity with the MYC inhibitor (MYCi) 10058-F4 or knockdown of MYC expression by short hairpin RNA (shRNA) both lead to a decrease in ITGA6 and ITGA6A levels in colorectal cancer cells, while overexpression of MYC enhances ITGA6 promoter activity. We also found that MYC inhibition decreases the epithelial splicing regulatory protein 2 (ESRP2) splicing factor at both the mRNA and protein levels. Chromatin immunoprecipitation revealed that the proximal promoter sequences of ITGA6 and ESRP2 were occupied by MYC and actively transcribed in colorectal cancer cells. Furthermore, expression studies in primary colorectal tumors and corresponding resection margins confirmed that the up-regulation of the ITGA6A subunit can be correlated with the increase in MYC and ESRP2. Taken together, our results demonstrate that the proto-oncogene MYC can regulate the promoter activation and splicing of the ITGA6 integrin gene through ESRP2 to favor the production of the pro-proliferative ITGA6A variant in colorectal cancer cells.

http://ift.tt/2E1wmHm

Recapitulating the clinical scenario of BRCA-associated pancreatic cancer in pre-clinical models

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. BRCA-associated PDAC comprises a clinically relevant subtype. A portion of these patients are highly susceptible to DNA damaging therapeutics, however, responses are heterogeneous and clinical resistance evolves.

We have developed unique patient-derived xenograft (PDX) models from metastatic lesions of germline BRCA-mutated patients obtained at distinct time points; before treatment and at progression. Thus, closely mimicking clinical scenarios, to further investigate treatment naïve and resistant patients. DNA was isolated from six BRCA-mutated PDXs and classified by whole-genome sequencing to stable-genome or homologous recombination deficient (HRD)-genome. The sensitivity to DNA-damaging agents was evaluated in-vivo in three BRCA-associated PDAC PDXs models: 1. HRD-genome naïve to treatments; 2. Stable-genome naïve to treatment; 3. HRD-genome resistant to treatment.

Correlation between disease course at tissue acquisition and response to PARP inhibitor (PARPi)/platinum was demonstrated in PDXs in-vivo. Only the HRD-genome PDX, naïve to treatment, was sensitive to PARP inhibitor/cisplatin treatments.

Our results demonstrate heterogeneous responses to DNA damaging agents/PARPi in BRCA associated PDX thus reflecting the wide clinical spectrum. An HRD-genome PDX generated from a naïve to treatment biopsy was sensitive to platinum/PARPi whereas no benefit was observed in treating an HRD-genome PDXs generated from a patient that had acquired resistance nor stable-genome PDXs. This article is protected by copyright. All rights reserved.

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Medications that relax the lower oesophageal sphincter and risk of oesophageal cancer: An analysis of two independent population-based databases

Abstract

Excessive lower oesophageal sphincter relaxation increases gastro-oesophageal acid reflux, an oesophageal adenocarcinoma risk factor. Medications that relax this sphincter (benzodiazepines, calcium channel blockers, nitrates, β2 agonists and xanthines) could promote cancer. These medications were investigated in two independent datasets. In the Scottish Primary Care Clinical Informatics Unit (PCCIU) database, a nested case-control study of oesophageal cancer was performed using GP prescription records. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for medication use and oesophageal cancer. In UK Biobank, a cohort study was conducted using self-reported medication use. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs for medication use and oesophageal cancer, and by tumour subtype. Overall, 1,979 oesophageal cancer patients were matched to 9,543 controls in PCCIU, and 355 of 475,768 participants developed oesophageal cancer in UK Biobank. None of the medications investigated were significantly associated with oesophageal cancer risk apart from β2 agonists, which were associated with increased oesophageal cancer risk in PCCIU (adjusted OR 1.38, 95% CI 1.12, 1.70) but not in UK Biobank (adjusted HR 1.21, 95% CI 0.70, 2.08). Medications that relax the lower oesophageal sphincter were not associated with oesophageal cancer, apart from β2 agonists. This increased cancer risk in β2 agonist users merits further investigation. This article is protected by copyright. All rights reserved.

http://ift.tt/2E0f7m4

The relationship between the CYP2D6 polymorphisms and tamoxifen efficacy in adjuvant endocrine therapy of breast cancer patients in Chinese Han population

Abstract

Variants of the CYP2D6 gene may lead to a poor prognosis of tamoxifen (TAM)-treated patients. This study validated the association between the CYP2D6 genotype and outcomes of patients receiving TAM in adjuvant endocrine therapy. A total of 778 breast cancer patients who received adjuvant TAM (n=325) or aromatase inhibitors (AIs) (n=453) at the National Cancer Center were analyzed. Nine single nucleotide polymorphisms (SNPs) in the CYP2D6 gene were selected from online databases. The associations of each SNP genotype with disease-free survival (DFS) and clinicopathological characteristics were analyzed. A total of 167 (21.5%) patients carried the CYP2D6 *10 (c.100C>T) T/T genotype. Among the 325 patients who received TAM, the 5-year DFS rate was considerably lower in CYP2D6 *10 T/T genotype patients than C/C or C/T patients (54.9% versus 70.9%, P=0.007). The T/T genotype for CYP2D6 *10 was a significant prognostic marker for DFS in multivariate analysis (hazard ratio=1.87; P=0.006). The CYP2D6 *10 genotype in women who received AIs was not significantly associated with DFS (P=0.332). Other SNPs were not related to the survival of patients who received TAM. Our finding showed patients with CYP2D6 *10 T/T received less benefit from TAM adjuvant treatment. This conclusion may optimize the individualized treatments for this subgroup of patients. This article is protected by copyright. All rights reserved.

http://ift.tt/2EAelgu

Kaempferol protects ethanol-induced gastric ulcers in mice via pro-inflammatory cytokines and NO

Abstract

Gastric ulcers (GUs) are common pathologies that affect many people around the world. Excessive alcohol consumption is one of the main causes of GUs; however, there are still lack of effective drugs for the prevention or therapy of GUs. In this study, we evaluated the protective effects and possible mechanisms of kaempferol (KAE) against acute ethanol-induced lesions to the gastric mucosa in mice. Fasted mice were orally given vehicle (0.9% saline), omeprazole (20 mg/kg), or KAE (40, 80, or 160 mg/kg) for 1 h in different experimental sets prior to the establishment of the GU model by challenge with absolute ethanol (10 ml/kg). Animals were euthanized 1 h after ethanol intake, and their plasma and stomach tissues were subject to further examination. Macroscopic and microscopic lesions, and immunological and biochemical parameters were observed. The effects of inflammation were investigated using the following indicators: tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), myeloperoxidase (MPO), and nitric oxide (NO). Results showed that KAE significantly decreased the ulcer index, increased the preventive index, completely protected the mucosa from lesions, and preserved gastric mucosal glycoprotein. KAE decreased MPO activity and pro-inflammatory cytokine (TNF-α, IL-1β) levels, and improved NO levels. The gastroprotective activity of KAE might be attributed to the preservation of gastric mucous glycoproteins levels, thus by inhibiting neutrophil accumulation and MPO activity, adjusting the levels of pro-inflammatory cytokines, and improving NO production.

http://ift.tt/2Eb038h

The Future of Combination Therapies for Peripheral T Cell Lymphoma (PTCL)

Abstract

Purpose of Review

Peripheral T cell lymphoma is a rare heterogeneous group of diseases which are characterized by poor outcomes to treatment and short overall survival. In the past decade, several new therapies targeting T cell biology have been approved in the relapsed setting. These new therapies, such as pralatrexate, romidepsin, belinostat, and brentuximab vedotin, have begun to make their way into practice. Despite these advances, outcomes have not changed dramatically. In recent years, efforts have been made to incorporate these new therapies into combination strategies to treat this challenging disease entity. Herein we will review some of the latest developments.

Recent Findings

With the new WHO classification, discrete entities of PTCL are now being identified by molecular and phenotypic markers. This new classification is critical to our ability to define disease entities which may respond to certain classes of targeted therapy. Some such mutations include genes controlling epigenetics (TET2, IDH2, DNMT3A, RHOA, CD28). As such, epigenetic therapies such as histone deacetylase (HDAC) inhibitors have become the platform to which other novel therapies or chemotherapy has been added. Early phase clinical studies have demonstrated that combination therapy with romidepsin plus other agents known to have activity in T cell lymphoma have enhanced clinical benefit for this group of diseases. In addition, the antibody drug conjugate, brentuximab vedotin has been shown to have potent activity in T cell lymphomas expressing CD30. This drug is being studied as well with other targeted therapies and chemotherapy in an effort to improve response rates and progression-free survival.

Summary

Although T cell lymphomas remain a highly challenging group of diseases to treat, new efforts to leverage drugs that discretely target the biology that drives T cell lymphomagenesis in combination provide hope that improved outcomes may be realized in the near future.

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The anti-tumor effects of Metformin are due to inhibiting NF-κB nuclear translocation in esophageal squamous cell carcinoma

Summary

Esophageal squamous cell carcinoma (ESCC) is an intractable digestive organ cancer that has proven difficult to treat despite multidisciplinary therapy, and the new treatment strategy is demanded. Metformin is used for type 2 diabetes mellitus and its antitumor effects have been reported recently. Metformin exerts antitumor effects in various respects, such as inhibiting inflammation, tumor growth and epithelial-mesenchymal transition (EMT). However, few reports have described the efficacy of metformin on ESCC, and their findings have been controversial. We analyzed the antitumor effects of metformin and clarified its effects on anti-inflammation, growth suppression and EMT inhibition. The activation of NF-κB, the major transcription factor induced by inflammation was investigated by immunostaining. We found that the localization of NF-κB in the nucleus was reduced after metformin treatment. This suggests that metformin inhibited the activation of NF-κB. Metformin inhibited tumor growth and induced apoptosis in ESCC cell lines. Associated with EMT, we examined the cell motility by a wound healing assay and the epithelial marker E-cadherin expression of various ESCC cell lines by Western blotting. Metformin inhibited the cell motility and induced E-cadherin expression. In conclusion, metformin showed multiple antitumor effects such as growth suppression, invasion inhibition, and to control EMT by inhibiting NF-κB localization on ESCC. Further exploration on the marker of treatment efficacy and combinatory therapy could bring out the possibility for novel treatment to use metformin on ESCC.

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