Organ-specific response to nivolumab in patients with non-small cell lung cancer (NSCLC)

Abstract

Background

Response to immune checkpoint inhibitors depends on tumor intrinsic properties and also on host factors in the tumour microenvironment including the presence of immune cells (IC). We hypothesized that nivolumab efficacy varies across different metastatic sites.

Methods

We retrospectively analyzed computed tomography scans of patients with metastatic non-small cell lung carcinoma (NSCLC) receiving nivolumab. RECIST 1.1 criteria were applied to assess the overall response rate (ORR) and organ-specific response rate (OSRR).

Results

We analyzed 52 patients including 44% females, 58% adenocarcinoma and 8% never smokers. Involved organs had target-lesions in the lung (42%), liver (25%), lymph nodes (56%) and soft tissue (13%) and non-target lesions in the bones (23%). ORR and disease control rate (DCR) were 20% and 45%, respectively. Median overall survival, progression-free survival and duration of response were 11.9, 2.3 and 10.3 months. OSRR and organ-specific DCR (OSDCR) were 28% and 90% in lymph nodes, 8% and 54 in the liver, and 9% and 55% in lung metastases. Nine out of 12 patients with bone metastases had progressive lesions. The cumulative incidence probability of organ-specific progression at 6 months was 14% in lymph nodes, 42% in the liver, 36% in lung metastases and 26% in the primary tumor, 29% in soft tissue and 33% in adrenal metastases.

Conclusion

In conclusion, the efficacy of immunotherapy is dependent on the metastatic location. Treatment appears more active in lymph nodes compared to other organ sites such as liver, adrenals and bone. Future strategies may include additional local treatment in case of oligoprogression in these organs in patients with otherwise sustained treatment benefit.

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News

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Erratum

An error appeared in the 15 January 2017 issue of the journal [Lockhart S.R., Etienne K.A., Vallabhaneni S., et al. Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents by Whole-Genome Sequencing and Epidemiological Analyses. Clin Infect Dis 2017; 64(2):134–40. https://doi.org/10.1093/cid/ciw691]. The Erg11 amino acid substitution associated with South African isolates is F126L, not F126T, as originally stated. The authors regret this error.

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A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiologya

Abstract

The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.

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Yoga Culture: From Oppression Toward Liberation

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A Review of "Art Therapy in Private Practice: Theory, Practice and Research in Changing Contexts"

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Organ-specific response to nivolumab in patients with non-small cell lung cancer (NSCLC)

Abstract

Background

Response to immune checkpoint inhibitors depends on tumor intrinsic properties and also on host factors in the tumour microenvironment including the presence of immune cells (IC). We hypothesized that nivolumab efficacy varies across different metastatic sites.

Methods

We retrospectively analyzed computed tomography scans of patients with metastatic non-small cell lung carcinoma (NSCLC) receiving nivolumab. RECIST 1.1 criteria were applied to assess the overall response rate (ORR) and organ-specific response rate (OSRR).

Results

We analyzed 52 patients including 44% females, 58% adenocarcinoma and 8% never smokers. Involved organs had target-lesions in the lung (42%), liver (25%), lymph nodes (56%) and soft tissue (13%) and non-target lesions in the bones (23%). ORR and disease control rate (DCR) were 20% and 45%, respectively. Median overall survival, progression-free survival and duration of response were 11.9, 2.3 and 10.3 months. OSRR and organ-specific DCR (OSDCR) were 28% and 90% in lymph nodes, 8% and 54 in the liver, and 9% and 55% in lung metastases. Nine out of 12 patients with bone metastases had progressive lesions. The cumulative incidence probability of organ-specific progression at 6 months was 14% in lymph nodes, 42% in the liver, 36% in lung metastases and 26% in the primary tumor, 29% in soft tissue and 33% in adrenal metastases.

Conclusion

In conclusion, the efficacy of immunotherapy is dependent on the metastatic location. Treatment appears more active in lymph nodes compared to other organ sites such as liver, adrenals and bone. Future strategies may include additional local treatment in case of oligoprogression in these organs in patients with otherwise sustained treatment benefit.

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Implant‐associated gene expression in the jaw bone of smokers and nonsmokers: A human study using quantitative qPCR

Clinical Oral Implants Research, EarlyView.


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Precision of digital implant models compared to conventional implant models for posterior single implant crowns: A within‐subject comparison

Clinical Oral Implants Research, EarlyView.


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Laparoscopic versus open repair for small paraumbilical hernia: A retrospective review

Asian Journal of Endoscopic Surgery, EarlyView.


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Phase II study of ERC1671 plus bevacizumab versus bevacizumab plus placebo in recurrent glioblastoma: interim results and correlations with CD4+ T-lymphocyte counts

CNS Oncology, Ahead of Print.


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Comparison of the main components and bioactivity of Rhus verniciflua Stokes extracts by different detoxification processing methods

Rhus verniciflua Stokes is an Asian tree species that is used as a food supplement and traditional medicine in Korea. However, its use is restricted by its potential to cause allergy. Thus, allergen-free R. verni...

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Retraction

No abstract available

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WDR-23 and SKN-1/Nrf2 Coordinate with the BLI-3 Dual Oxidase in Response to Iodide-Triggered Oxidative Stress

Animals utilize conserved mechanisms to regulate oxidative stress. The Caenorhabditis elegans SKN-1 protein is homologous to the vertebrate Nrf (NF-E2-related factor) family of cap 'n' collar (CnC) transcription factors and functions as a core regulator of xenobiotic and oxidative stress responses. The WD40 repeat-containing protein WDR-23 is a key negative regulator of SKN-1 activity. We previously found that the oxidative stress induced by excess iodide can be relieved by loss of function in the BLI-3/TSP-15/DOXA-1 dual oxidase complex. To further understand the molecular mechanism of this process, we screened for new mutants that can survive in excess iodide and identified gain-of-function mutations in skn-1 and loss-of-function mutations in wdr-23. The SKN-1C isoform functions in the hypodermis to affect animal's response to excess iodide, while the SKN-1A isoform appears to play a minor role. wdr-23(lf) can interact with bli-3 mutations in a manner different from skn-1(gf). Transcriptome studies suggest that excess iodide causes developmental arrest largely independent of changes in gene expression, and wdr-23(lf) could affect the expression of a subset of genes by a mechanism different from SKN-1 activation. We propose that WDR-23 and SKN-1 coordinate with the BLI-3/TSP-15/DOXA-1 dual oxidase complex in response to iodide-triggered oxidative stress.

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Budding Yeast BFA1 Has Multiple Positive Roles in Directing Late Mitotic Events

The proper regulation of cell cycle transitions is paramount to the maintenance of cellular genome integrity. In Saccharomyces cerevisiae, the mitotic exit network (MEN) is a Ras-like signaling cascade that effects the transition from M phase to G1 during the cell division cycle in budding yeast. MEN activation is tightly regulated. It occurs during anaphase and is coupled to mitotic spindle position by the spindle position checkpoint (SPoC). Bfa1 is a key component of the SPoC and functions as part of a two-component GAP complex along with Bub2. The GAP activity of Bfa1-Bub2 keeps the MEN GTPase Tem1 inactive in cells with mispositioned spindles, thereby preventing inappropriate mitotic exit and preserving genome integrity. Interestingly, a GAP-independent role for Bfa1 in mitotic exit regulation has been previously identified. However the nature of this Bub2-independent role and its biological significance are not understood. Here we show that Bfa1 also activates the MEN by promoting the localization of Tem1 primarily to the daughter spindle pole body (dSPB). We demonstrate that the overexpression of BFA1 is lethal due to defects in Tem1 localization, which is required for its activity. In addition, our studies demonstrate a Tem1-independent role for Bfa1 in promoting proper cytokinesis. Cells lacking TEM1, in which the essential mitotic exit function is bypassed, exhibit cytokinesis defects. These defects are suppressed by the overexpression of BFA1. We conclude that Bfa1 functions to both inhibit and activate late mitotic events.

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Lying position classification based on ECG waveform and random forest during sleep in healthy people

Several different lying positions, such as lying on the left side, supine, lying on the right side and prone position, existed when healthy people fell asleep. This article explored the influence of lying posi...

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Solving the general inter-ring distances optimization problem for concentric ring electrodes to improve Laplacian estimation

Superiority of noninvasive tripolar concentric ring electrodes over conventional disc electrodes in accuracy of surface Laplacian estimation has been demonstrated in a range of electrophysiological measurement...

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High expression of GAS5 promotes neuronal death after cerebral infarction by regulating miR-365a-3p

OBJECTIVE: To investigate whether growth arrest specific5 (GAS5) could regulate the expression of DCDC2 through competitive binding to miR-365a-3p, thus leading to increased neuronal death in cerebral cortex.

MATERIALS AND METHODS: The expression levels of GAS5 and DCDC2 in cerebral cortical neurons of mice with mouse middle cerebral artery occlusion (MCAO) cerebral infarction and in control mice were detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Meanwhile, the expression levels of GAS5 and DCDC2 in primary neurons cultured in vitro were also detected by qRT-PCR. The effects of GAS5 and DCDC2 on neuronal death were evaluated by calculating the cerebral infarct area by Tunel assay and TTC staining. Dual luciferase reporter assays were performed to detect the binding of miR-365a-3p to GAS5 and DCDC2. Western blot was applied to detect the protein expression of DCDC2, Bcl-2 and Bax after overexpression and knockdown of GAS5.

RESULTS: The expression of GAS5 and DCDC2 were significantly higher in cerebral cortical neurons and primary cultured neurons in vitro than those in control mice, respectively. Inhibition of GAS5 and DCDC2 in primary neurons decreased the neuronal cells death rate, while overexpression of GAS5 and DCDC2 increased the cell death rate. The dual luciferase reporter gene results showed that GAS5 regulated the expression of DCDC2 through competitive binding of miR-365a-3p thus forming a GAS5/miR-365a-3p/DCDC2 regulatory network. In addition, GAS5 inhibited Bcl-2 while promoting the expression of Bax.

CONCLUSIONS: High expression of GAS5 could promote neuronal death after cerebral infarction in mice, possibly through competitive binding to miR-365a-3p and promoting the expression of DCDC2.

L'articolo High expression of GAS5 promotes neuronal death after cerebral infarction by regulating miR-365a-3p sembra essere il primo su European Review.

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A study on related factors of hemodynamic depression in carotid artery stenting

OBJECTIVE: To investigate the pathogenesis and related factors of carotid artery stenting (CAS) related to hemodynamic depression (HD).

PATIENTS AND METHODS: 433 CAS patients were admitted to our hospital and were selected from Jan 2013 to Jun 2016. We set up the HD diagnostic criteria for CAS and observed the whole morphology of vessels to classify carotid atherosclerotic plaques. We analyzed cerebral angiography and placed temporary cardiac pacemaker via femoral vein in order to prepare carotid artery stenting. We determined the general situation of HD after CAS according to the results.

RESULTS: 38 patients received temporary placement of cardiac temporary pacemakers, and 241 patients (59.80%) developed HD. 403 patients were divided into HD group and non HD group and results suggested there was no significant difference between the two groups except for diabetes (p>0.05). Also, bilateral carotid stenting was performed in 26 patients (6.45%), and the HD group was significantly higher than that in non HD group (p<0.05). HD group had 31 MACCE cases, and non HD group had 2 MACCE cases. There was no occurrence of adverse cardiovascular events in this study.

CONCLUSIONS: Cardiac temporary pacemaker may be one of the effective approaches to improve HD after CAS and reduce perioperative MACCE.

L'articolo A study on related factors of hemodynamic depression in carotid artery stenting sembra essere il primo su European Review.

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Effects of recombinant activated coagulation factor VII on apoptosis and expressions of Bcl-2 and Bax in rats with intracerebral hemorrhage

OBJECTIVE: To investigate the effects of recombinant activated coagulation factor VII (rFVIIa) on apoptosis and the expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) in rats with intracerebral hemorrhage (ICH).

MATERIALS AND METHODS: A total of 90 8-week-old male Sprague-Dawley (SD) rats with similar weight were selected and randomly divided into normal group (n=30), ICH control group (n=30), and rFVIIa treatment group (n=30). Five days later, hematoxylin-eosin (HE) staining was applied to observe pathological changes in rat brain in three groups. Cell apoptosis in rat brain was detected at 6 h, 12 h, 24 h, 48 h, 72 h, and 120 h, respectively. The relative expression levels of Bcl-2 and Bax in brain tissues were measured via fluorescence quantitative Polymerase Chain Reaction (qPCR) and Western blotting, respectively.

RESULTS: Compared with those in ICH control group, rats in rFVIIa treatment group had fewer degenerated and necrotic nerve cells and milder pathological changes in the marginal zone. The number of apoptotic cells in ICH control group and rFVIIa group was gradually increased in a time-dependent manner, and achieved the peak at 72 h. The number of apoptotic cells in treatment group was significantly lower than that in ICH control group after 24 h (p<0.05). Both fluorescence qPCR and Western blotting results proved that in comparison with ICH control group, rFVIIa group had a higher relative expression level of Bcl-2 (p<0.05) and a lower expression level of Bax (p<0.05).

CONCLUSIONS: Apoptosis mechanism may be involved in secondary brain injury after ICH. RFVIIa may have an important protective effect on neuronal injury after ICH by promoting the expression of Bcl-2 and inhibiting the expression of Bax protein.

L'articolo Effects of recombinant activated coagulation factor VII on apoptosis and expressions of Bcl-2 and Bax in rats with intracerebral hemorrhage sembra essere il primo su European Review.

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Circulating exosomal miRNAs as diagnostic biomarkers in Parkinson’s disease

OBJECTIVE: This research has showed that exosomal miRNAs from cerebrospinal fluid could act as biomarkers for Parkinson's disease (PD). However, no analysis has been conducted to explore the potential value of exosomal miRNAs from plasma.

PATIENTS AND METHODS: 52 patients with PD were included in study group. 48 healthy adults were included in control group. Blood samples were collected from all those people and then exosomes were extracted from the plasma.

RESULTS: Compared with controls, patients with PD showed a significantly higher expression of circulating exosomal miR-331-5p. ROC curve showed that the area values under the curve of miR-331-5p and miR-505 were 0.849 and 0.898, respectively.

CONCLUSIONS: Exosomal miRNAs, including miR-331-5p and miR-505, could potentially act as biomarkers for PD.

L'articolo Circulating exosomal miRNAs as diagnostic biomarkers in Parkinson's disease sembra essere il primo su European Review.

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Longitudinal Liquid Biopsy and Mathematical Modeling of Clonal Evolution Forecast Time to Treatment Failure in the PROSPECT-C Phase II Colorectal Cancer Clinical Trial [Research Articles]

Sequential profiling of plasma cell-free DNA (cfDNA) holds immense promise for early detection of patient progression. However, how to exploit the predictive power of cfDNA as a liquid biopsy in the clinic remains unclear. RAS pathway aberrations can be tracked in cfDNA to monitor resistance to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer. In this prospective phase II clinical trial of single-agent cetuximab in RAS wild-type patients, we combine genomic profiling of serial cfDNA and matched sequential tissue biopsies with imaging and mathematical modeling of cancer evolution. We show that a significant proportion of patients defined as RAS wild-type based on diagnostic tissue analysis harbor aberrations in the RAS pathway in pretreatment cfDNA and, in fact, do not benefit from EGFR inhibition. We demonstrate that primary and acquired resistance to cetuximab are often of polyclonal nature, and these dynamics can be observed in tissue and plasma. Furthermore, evolutionary modeling combined with frequent serial sampling of cfDNA allows prediction of the expected time to treatment failure in individual patients. This study demonstrates how integrating frequently sampled longitudinal liquid biopsies with a mathematical framework of tumor evolution allows individualized quantitative forecasting of progression, providing novel opportunities for adaptive personalized therapies.

SIGNIFICANCE: Liquid biopsies capture spatial and temporal heterogeneity underpinning resistance to anti-EGFR monoclonal antibodies in colorectal cancer. Dense serial sampling is needed to predict the time to treatment failure and generate a window of opportunity for intervention. Cancer Discov; 8(10); 1–16. ©2018 AACR.

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Is GPNMB the Achilles heel of Mo-MDSC while marking their suppressive activity?

GPNMB/DC-Hil/Osteoactivin on MDSC impairs T lymphocytes through the binds of Syndecan-4, delineating a new checkpoint pair to be targeted perhaps in combination with PD1/PD-L1 blockage.

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Shedding of bevacizumab in tumour cells-derived extracellular vesicles as a new therapeutic escape mechanism in glioblastoma

Abstract

Glioblastoma (GBM) is the most aggressive type of primary brain tumours. Anti-angiogenic therapies (AAT), such as bevacizumab, have been developed to target the tumour blood supply. However, GBM presents mechanisms of escape from AAT activity, including a speculated direct effect of AAT on GBM cells. Furthermore, bevacizumab can alter the intercellular communication of GBM cells with their direct microenvironment. Extracellular vesicles (EVs) have been recently described as main acts in the GBM microenvironment, allowing tumour and stromal cells to exchange genetic and proteomic material. Herein, we examined and described the alterations in the EVs produced by GBM cells following bevacizumab treatment. Interestingly, bevacizumab that is able to neutralise GBM cells-derived VEGF-A, was found to be directly captured by GBM cells and eventually sorted at the surface of the respective EVs. We also identified early endosomes as potential pathways involved in the bevacizumab internalisation by GBM cells. Via MS analysis, we observed that treatment with bevacizumab induces changes in the EVs proteomic content, which are associated with tumour progression and therapeutic resistance. Accordingly, inhibition of EVs production by GBM cells improved the anti-tumour effect of bevacizumab. Together, this data suggests of a potential new mechanism of GBM escape from bevacizumab activity.

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Systematic Analysis of Compounds Specifically Targeting Telomeres and Telomerase for Clinical Implications in Cancer Therapy

The targeting of telomerase and telomere maintenance mechanisms represents a promising therapeutic approach for various types of cancer. In this work, we designed a new protocol to screen for and rank the efficacy of compounds specifically targeting telomeres and telomerase. This approach used two isogenic cell lines containing a circular human artificial chromosome (HAC, lacking telomeres) and a linear HAC (containing telomeres) marked with the EGFP transgene: compounds that target telomerase or telomeres should preferentially induce loss of the linear HAC but not the circular HAC. Our assay allowed quantification of chromosome loss by routine flow cytometry. We applied this dual-HAC assay to rank a set of known and newly developed compounds, including G-quadruplex (G4) ligands. Among the latter group, two compounds -Cu-ttpy and Pt-ttpy- induced a high rate of linear HAC loss with no significant effect on the mitotic stability of a circular HAC. Analysis of the mitotic phenotypes induced by these drugs revealed an elevated rate of chromatin bridges in late mitosis and cytokinesis as well as UFB (Ultrafine Bridges). Chromosome loss after Pt-ttpy or Cu-ttpy treatment correlated with the induction of telomere-associated DNA damage. Overall, this platform enables identification and ranking of compounds that greatly increase chromosome mis-segregation rates as a result of telomere dysfunction and may expedite the development of new therapeutic strategies for cancer treatment.

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Medicare, Med Advantage Health Care Use Differs Regionally

THURSDAY, Aug. 30, 2018 -- Geographic variation in the Medicare Advantage population exceeds that of traditional Medicare for use of skilled nursing facility and hospital care, according to study published in the August issue of Health...

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FDA: Common Diabetes Meds Tied to Serious Genital Infection

THURSDAY, Aug. 30, 2018 -- A rare but serious genital infection known as necrotizing fasciitis of the perineum, also called Fournier's gangrene, has been reported in some patients taking a certain class of type 2 diabetes medicine, according to the...

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China Withholding H7N9 Bird Flu Virus Samples From U.S.

THURSDAY, Aug. 30, 2018 -- Chinese officials have not sent lab samples of H7N9 bird flu virus to their U.S. counterparts despite repeated requests and an international agreement. U.S. officials say the specimens of the rapidly evolving virus are...

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Vascular Risk Factors for Brain Calcification in Seniors Identified

THURSDAY, Aug. 30, 2018 -- Diabetes and smoking are vascular risk factors associated with hippocampal calcification in older patients with memory issues, according to a study published in the September issue of Radiology. In an effort to identify...

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Effect of orthodontic treatment and comorbidity risk factors on interdental alveolar crest level: A radiographic evaluation

Alveolar bone loss is regarded as a potential adverse event during orthodontic treatment, especially in adults. The purposes of this study were to evaluate the prevalence and severity of interdental alveolar crest height loss in adult orthodontic patients compared with an untreated control group and to identify comorbidity risk factors for such bone loss (high BMI score, high blood pressure, high cholesterol levels, and smoking).

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Information for readers

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Editorial Board

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Novel method of constructing a stable reference frame for 3-dimensional cephalometric analysis

Three-dimensional (3D) cephalometric analysis has provided the ability to overcome the limitations of 2-dimensional cephalometrics. However, there is no international standard method for 3D cephalometric analysis yet. Determining the position of the midsagittal plane (MSP) practically is the most important step when constructing a 3D cephalometric reference frame. Recent studies have used several approaches to construct the MSP. In this study, we aimed to determine the true MSP of the skull to establish a stable reference frame for 3D cephalometric analysis.

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Determinant factors of malocclusion in children and adolescents with cerebral palsy

Cerebral palsy (CP) is an encephalic static lesion characterized as a nonprogressive disorder of movements and posture with functional deficits that may favor the occurrence of various malocclusions. We looked for a possible association between overall functional impairment and malocclusion in this population.

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Table of Contents

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Midfacial changes in the coronal plane induced by microimplant-supported skeletal expander, studied with cone-beam computed tomography images

Our objectives were to evaluate midfacial skeletal changes in the coronal plane and the implications of circummaxillary sutures and to localize the center of rotation for the zygomaticomaxillary complex after therapy with a bone-anchored maxillary expander, using high-resolution cone-beam computed tomography.

https://ift.tt/2ww9fix

No deal

The last time you saw your favorite niece, you told her father, Ed, that she's ready for braces. The problem is that you cannot locate a trusted colleague in the town where the family lives, which is over 100 miles away. So Ed vowed to scour the Internet and seek referrals for a qualified orthodontist. A week after you suggest treatment, he calls you with an interesting discovery.

https://ift.tt/2PjI5m8

Alternative cone-beam computed tomography method for the analysis of bone density around impacted maxillary canines

Genetic and environmental etiologic factors have been described for maxillary canine impaction, except for the trabecular bone characteristics in the impacted area. The aim of this study was to evaluate the surface area and fractal dimension of the alveolar bone on cone-beam computed tomography (CBCT) images of patients with maxillary impacted canines.

https://ift.tt/2ww9zxL

Esthetic preferences of orthodontists, oral surgeons, and laypersons for Persian facial profiles

The patient's perception of facial esthetics is not necessarily consistent with that of the practitioner. The aim of this study was to compare the perceptions of Persian orthodontists, oral surgeons, and laypersons with regard to facial profile attractiveness and the most favorable mandibular position.

https://ift.tt/2N2oEAO

Vertical control in impacted mandibular molar uprighting

We read with great interest the Clinician's Corner article in the April 2018 issue and commend the authors for their creative idea to upright the "kissing molars" (Barros SE, Janson G, Chiqueto K, Ferreira E, Rösing C. Expanding torque possibilities: A skeletally anchored torqued cantilever for uprighting "kissing molars." Am J Orthod Dentofacial Orthop 2018;153:588-98). Certain statements on the biomechanics and periodontal issues during the molar uprighting concern us.

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Age-dependent response to force

We discussed this original article in the May 2018 issue, "Age-dependent biologic response to orthodontic forces" (Alikhani M, Chou MY, Khoo E, Alansari S, Kwal R, Elfersi T, Almansour A, Sangsuwon C, Al Jearah M, Nervina JM, Teixeira CC. Am J Orthod Dentofacial Orthop 2018;153:632-44), in our journal club with great interest and would like to offer a few comments from the discussion.

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Directory: AAO Officers and Organizations

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Developing patient-centered communication skills in orthodontics

According to Stephen Covey, we should "seek first to understand, then to be understood" to achieve effective interpersonal communication.1 The purpose of clinical communication is to link the patient's needs and preferences with the clinician's knowledge, skills, and performance so that both work together to accomplish therapy goals and are satisfied with treatment outcomes. This face-to-face interaction should be patient-centered, and the clinician must integrate his or her skills in the use of communication strategies and techniques with a set of desirable personality traits or soft skills.

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September 2018:154(3)

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Physical properties of root cementum: Part 27. Effect of low-level laser therapy on the repair of orthodontically induced inflammatory root resorption: A double-blind, split-mouth, randomized controlled clinical trial

The purpose of this 2-arm-parallel split-mouth trial was to investigate the effect of low-level laser therapy (LLLT) on the repair of orthodontically induced inflammatory root resorption (OIIRR).

https://ift.tt/2wv5JVB

The golden age of orthodontics: Decline and aftermath. A history of the business of orthodontics

Norman Wahl, an eminent dental and orthodontic historian, presents to the reader a carefully researched history of the business of orthodontics. The book is divided into 2 parts. Part I deals with the 19th and 20th centuries and was originally a thesis that Dr Wahl completed to partially fulfill the requirements for a master's degree in history at California State University Northridge in 1994. Part II takes the reader into the 21st century and gives a good summary of, and explanation for, the increasingly complex problems that orthodontists face in managing a practice today.

https://ift.tt/2PkN3ia

Opioid exposure safety, superglottic airways and other EMS news of the week

Our co-hosts discuss hot topics related to EMS personnel, from cardiac arrest survival to a DOJ video regarding opioid exposure while on the job

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Harvesting responses to single pulse electrical stimulation for presurgical evaluation in epilepsy

A Single Pulse Electrical Stimulation (SPES) protocol consists of pulses (repetition rate 0.1 – 1 Hz) of short lasting current stimuli (2-8 mA, pulse width <=1 ms) delivered to adjacent electrodes that are either part of intracranial grids (ECoG) or depth electrodes (SEEG) implanted in epilepsy patients for presurgical evaluation. Early studies using such a protocol aimed at confirming specific functional cortical connections in eloquent cortex by means of what was later called the cortico-cortical evoked potential (CCEP) (Wilson et al., 1990), or influencing cortical excitability in order to evoke (subclinical) habitual seizures (Kahane et al., 1993).

https://ift.tt/2C1Wa5R

The effects of aging on early stages of the auditory deviance detection system

The ability of the auditory system in extracting acoustic regularities and signaling deviance detection is critical for survival as it enables fast processing of novel events and preparing the organism to react quickly to potentially significant stimuli. Moreover, these two functional properties underlie the formation and segregation of auditory objects, which are necessary for solving the cocktail party problem and understanding speech in complex and noisy environments.

https://ift.tt/2wqgRTG

Effects of Noise and Age on the Infant Brainstem Response to Speech

Speech perception depends on healthy sound transduction and faithful encoding of speech sound acoustics. Background noise can distort frequency analysis in the inner ear and disrupt auditory processing more centrally, making speech sounds difficult to decode. Problems in the middle ear, inner ear or central nervous system can exacerbate difficulties in hearing speech in noise, including early conductive hearing impairment (Keogh et al., 2010), sensorineural hearing loss at low or high frequencies (Laukli et al., 1985, Horwitz et al., 2002), diminished linguistic content during development (Cooper et al., 1989, Lieu, 2004, Stelmachowicz et al., 2004, Eisenberg, 2007, Moeller et al., 2015), and attention (Soderlund et al., 2016) or memory problems (McCreery et al., 2017, Millman et al., 2017).

https://ift.tt/2NAe54Q

Auditory gamma oscillations predict global symptomatic outcome in the early stages of psychosis: a longitudinal investigation

The gamma-band auditory steady-state response (ASSR) is hypothesized to be a useful biomarker for psychosis (Uhlhaas and Singer, 2010). Kwon et al. (1999) performed the first study of 40-Hz ASSR in patients with schizophrenia using electroencephalography (EEG) and demonstrated a reduced power and synchronization in response to 40-Hz stimulation, but not to the 20-Hz stimulation, in these patients. This initial finding has been replicated in many studies using EEG (Brenner et al., 2003; Hamm et al., 2015; Hirano et al., 2015; Kirihara et al., 2012; Light et al., 2006; Spencer et al., 2008; Tada et al., 2016) or magnetoencephalography (MEG; Edgar et al., 2014; Teale et al., 2008; Tsuchimoto et al., 2011; Vierling-Claassen et al., 2008; Wilson et al., 2008).

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Effect of subthalamic nucleus deep brain stimulation on visual scanning

Since saccades reflect the activity of the superior colliculus, which receives projections from the basal ganglia, studies on saccades provide insights into the function of basal ganglia in various neurological conditions, including Parkinson's disease (PD) (Terao et al., 2011; Gorges et al., 2014). In fact, many studies have studied the performance of saccades in PD (White et al., 1983; Crawford et al., 1989; Nakamura et al., 1994; Vermersch et al., 1994; Kimmig et al., 2002; Yugeta et al., 2010; Terao et al., 2011; Matsumoto et al., 2011, 2012; Gorges et al., 2014).

https://ift.tt/2NFgBXm

Electrodiagnosis and nerve ultrasound: “Castor and Pollux” in the management of neuropathies

The image of Dioscuri is used to describe the efficient union of two elements contributing to achieve a goal. They were Castor and Pollux, two strong brothers of Greek mythology, defenders of the sailors, during the sea storms. Similarly, electrodiagnosis (EDx) and nerve ultrasound (US) together "defend" the complex and "stormy" management of patients with peripheral neuropathies. A large amount of papers has shown the efficacy of association of EDx and US in nerve evaluation. Now, as hoped years ago, the association between US and EDx is often part of neurophysiological activity (Padua et al., 2013).

https://ift.tt/2wqhoFa

Laboratory methods for case finding in human psittacosis outbreaks: a systematic review

Psittacosis outbreak investigations require rapid identification of cases in order to trace possible sources and perform public health risk assessments. In recent outbreaks in the Netherlands, such investigati...

https://ift.tt/2NBKHeq

Temporal instability of the post-surgical maxillary sinus microbiota

Chronic rhinosinusitis is an inflammatory disorder in which the role of bacteria remains uncertain. While sinus outflow obstruction is often an initiating event, mucosal inflammation and dysbiosis may persist ...

https://ift.tt/2N1vRRs

An unexpected guest?

https://ift.tt/2NzpGku

MicroRNA-494-dependent WDHDI inhibition suppresses epithelial-mesenchymal transition, tumor growth and metastasis in cholangiocarcinoma

Cholangiocarcinoma (CCA) represents a devastating malignancy characterized by high mortality, and notoriously problematic to diagnose. Recently, microRNAs (miRs) have been intensively investigated due to their potential usefulness from a tumor treatment perspective.

https://ift.tt/2wsFD5A

When Numbers Lie: The Lessons the True Hurricane Maria Death Toll Should Teach Us About the Necessity of Addressing Radiation Therapy Access Disparities in the United States

To the Editor: The recent examination of the state of radiation oncology in Puerto Rico after the devastation wrought by Hurricane Maria in September 2017 by Lopez-Araujo and Burnett was a sobering depiction of the great need to address the dearth of radiation therapy (RT) access, which is exponentially exacerbated after natural disasters (1). Even more recently, a May 2018 study in New England Journal of Medicine indicates the true death toll from Hurricane Maria was 4645, more than 72 times the official death toll of 64 reported by the government (2).

https://ift.tt/2MG6JAr

Pre‐analytic error: A significant patient safety risk

Cancer Cytopathology, Volume 126, Issue S8, Page 738-744, August 2018.


https://ift.tt/2LH8w2L

Ancillary studies in cytology: Secondary or necessary?

Cancer Cytopathology, Volume 126, Issue S8, Page 584-589, August 2018.


https://ift.tt/2N1q4eB

Issue Information

Cancer Cytopathology, Volume 126, Issue S8, Page 576-580, August 2018.


https://ift.tt/2LH8tE7

Ancillary studies in fine needle aspiration of the kidney

Cancer Cytopathology, Volume 126, Issue S8, Page 711-723, August 2018.


https://ift.tt/2N5vyVR

Ancillary Studies in Cytology: Recommendations from the Experts

Cancer Cytopathology, Volume 126, Issue S8, Page 575-575, August 2018.


https://ift.tt/2C3dIhU

Navigating the diverse array of ancillary markers available for cytology

Cancer Cytopathology, Volume 126, Issue S8, Page 581-583, August 2018.


https://ift.tt/2MZPedP

A practical guide for ancillary studies in pulmonary cytologic specimens

Cancer Cytopathology, Volume 126, Issue S8, Page 599-614, August 2018.


https://ift.tt/2PM8RVf

Ancillary tests in the diagnosis of liver and pancreatic neoplasms

Cancer Cytopathology, Volume 126, Issue S8, Page 672-690, August 2018.


https://ift.tt/2LH8oQP

Ancillary testing in salivary gland cytology: A practical guide

Cancer Cytopathology, Volume 126, Issue S8, Page 627-642, August 2018.


https://ift.tt/2N25Ykr

Ancillary studies in pleural, pericardial, and peritoneal effusion cytology

Cancer Cytopathology, Volume 126, Issue S8, Page 590-598, August 2018.


https://ift.tt/2C2HOSF

Ancillary molecular testing of indeterminate thyroid nodules

Cancer Cytopathology, Volume 126, Issue S8, Page 654-671, August 2018.


https://ift.tt/2PSXdYq

cancer of unknown primary: Ancillary testing of cytologic and small biopsy specimens in the era of targeted therapy

Cancer Cytopathology, Volume 126, Issue S8, Page 724-737, August 2018.


https://ift.tt/2PRuenZ

Lymph node cytopathology: Essential ancillary studies as applied to lymphoproliferative neoplasms

Cancer Cytopathology, Volume 126, Issue S8, Page 615-626, August 2018.


https://ift.tt/2C3YWaM

The paris system: A valuable new approach, but there is more to find in urine than high‐grade urothelial carcinoma

Cancer Cytopathology, Volume 126, Issue 8, Page 513-517, August 2018.


https://ift.tt/2PM8KZP

Issue Information

Cancer Cytopathology, Volume 126, Issue 8, Page 505-508, August 2018.


https://ift.tt/2LHHnfX

The curious case of repurposed remedies

Cancer Cytopathology, Volume 126, Issue 8, Page 509-510, August 2018.


https://ift.tt/2LH7Ydd

Effects of methylphenidate on cognition and behaviour in children with neurofibromatosis type 1: a study protocol for a randomised placebo-controlled crossover trial

Introduction

Dopamine dysregulation has been identified as a key modulator of behavioural impairment in neurofibromatosis type 1 (NF1) and a potential therapeutic target. Preclinical research demonstrates reduced dopamine in the brains of genetically engineered NF1 mouse strains is associated with reduced spatial-learning and attentional dysfunction. Methylphenidate, a stimulant medication that increases dopaminergic and noradrenergic neurotransmission, rescued the behavioural and dopamine abnormalities. Although preliminary clinical trials have demonstrated that methylphenidate is effective in treating attention deficit hyperactivity disorder (ADHD) symptoms in children with NF1, its therapeutic effect on cognitive performance is unclear. The primary aim of this clinical trial is to assess the efficacy of methylphenidate for reducing attention deficits, spatial working memory impairments and ADHD symptoms in children with NF1.

Methods and analysis

A randomised, double-blind, placebo-controlled trial of methylphenidate with a two period crossover design. Thirty-six participants with NF1 aged 7–16 years will be randomised to one of two treatment sequences: 6 weeks of methylphenidate followed by 6 weeks of placebo or; 6 weeks of placebo followed by 6 weeks of methylphenidate. Neurocognitive and behavioural outcomes as well as neuroimaging measures will be completed at baseline and repeated at the end of each treatment condition (week 6, week 12). Primary outcome measures are omission errors on the Conners Continuous Performance Test-II (attention), between-search errors on the Spatial Working Memory task from the Cambridge Neuropsychological Test Automated Battery (spatial working memory) and the Inattentive and Hyperactivity/Impulsivity Symptom Scales on the Conners 3-Parent. Secondary outcomes will examine the effect of methylphenidate on executive functions, attention, visuospatial skills, behaviour, fine-motor skills, language, social skills and quality of life.

Ethics and dissemination

This trial has hospital ethics approval and the results will be disseminated through peer-reviewed publications and international conferences.

Trial registration number

ACTRN12611000765921.

https://ift.tt/2PfEg0Y

Implications of parental lifestyle changes and education level on adolescent offspring weight: a population based cohort study - The HUNT Study, Norway

Objective

Obesity tends to cluster in families reflecting both common genetics and shared lifestyle patterns within the family environment. The aim of this study was to examine whether parental lifestyle changes over time, exemplified by changes in weight and physical activity, could affect offspring weight in adolescents and if parental education level influenced the relationship.

Design, setting and participants

The population-based cohort study included 4424 parent-offspring participants from the Nord-Trøndelag Health Study, Norway. Exposition was parental change in weight and physical activity over 11 years, and outcome was offspring weight measured in z-scores of body mass index (BMI) in mixed linear models.

Results

Maternal weight reduction by 2–6 kg was significantly associated with lower offspring BMI z-scores: –0.132 (95% CI –0.259 to –0.004) in the model adjusted for education. Parental weight change displayed similar effect patterns on offspring weight regardless of parents' education level. Further, BMI was consistently lower in families of high education compared with low education in the fully adjusted models. In mothers, reduced physical activity level over time was associated with higher BMI z-scores in offspring: 0.159 (95% CI 0.030 to 0.288). Associations between physical activity change and adolescent BMI was not moderated by parental education levels.

Conclusion

Lifestyle changes in mothers were associated with offspring BMI; reduced weight with lower—and reduced physical activity with higher BMI. Father's lifestyle changes, however, did not significantly affect adolescent offspring's weight. Overall, patterns of association between parental changes and offspring's BMI were independent of parental education levels, though adolescents with parents with high education had lower weight in general.

https://ift.tt/2opUcTg

Global prevalence and incidence of surgical site infections after appendectomy: a systematic review and meta-analysis protocol

Introduction

Acute appendicitis is a surgical emergency and the most frequent aetiology of acute surgical abdominal pain in developed countries. Universally, its widely approved treatment is appendectomy. Like all surgical procedures, appendectomy can be associated with many complications among which are surgical site infections (SSIs).

Despite the increasing number of appendectomies done around the world and the associated morbidities related to SSI after appendectomy, there is still scarcity of data concerning the global epidemiology of SSI after appendectomy. The current review aims at providing a summary of the published data on epidemiology of SSI after appendectomy.

Methods and design

We will include randomised controlled trials, cohort studies, case–control and cross-sectional studies. Electronic databases including Embase, MEDLINE and ISI Web of Science (Science Citation Index) will be searched for relevant abstracts of studies published between 1 January 2000 and 30 December 2017, without language restriction. The review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. After screening of abstracts, study selection, data extraction and assessment of risk of bias, we shall assess the studies individually for clinical and statistical heterogeneity. Appropriate meta-analytic techniques will then be used to pool studies judged to be clinically homogenous. Visual inspection of funnel plots and Egger's test will be used to detect publication bias. Results will be presented by country and continent.

Ethics and dissemination

Since primary data are not collected in this study, ethical approval is not required. This review is expected to provide relevant data to help in quantifying the global burden of SSI after appendectomy. The final report will be published in a peer-reviewed journal.

Trial registration number

CRD42017075257.

https://ift.tt/2LAWech

To what extent is the elevated risk of psychological distress in people with diabetes accounted for by physical disability? Findings from a large population-based study

Objectives

People with diabetes experience an elevated risk of psychological distress compared with people without diabetes. It is unclear how much of this elevated risk is attributable to the greater levels of physical disability in people with diabetes, and how this risk varies according to sociodemographic and health-behavioural characteristics. This study quantified levels of psychological distress in people with and without diabetes, considering these factors.

Design

Cross-sectional analysis of questionnaire data.

Setting

Men and women aged ≥45 years, in the 45 and Up Study, from New South Wales, Australia.

Participants

236 441 people who completed the baseline postal questionnaire (distributed from 1 January 2006–31 December 2008), with valid data for diabetes status and psychological distress.

Primary outcome measures

High psychological distress (Kessler-10 >22). Modified Poisson regression with robust error variance was used to estimate prevalence ratios (PRs), comparing prevalence of high psychological distress among those with and without diabetes and across physical functional limitation (PFL) levels, adjusting for potential confounders.

Results

Overall, 8.4% (19 803/236 441) of participants reported diabetes. 11.8% (2339) of individuals with diabetes and 7.2% (15 664) without diabetes had high psychological distress: age-adjusted and sex-adjusted PR=1.89 (95% CI 1.81 to 1.97), becoming 1.58 (1.52 to 1.65) and 1.22 (1.17 to 1.27) following additional adjustment for sociodemographic factors, health behaviours and additionally for PFL, respectively. Compared with individuals with neither diabetes nor PFL, the adjusted PRs for high psychological distress were: 1.37 (1.17 to 1.60) with diabetes but no PFL, 7.33 (7.00 to 7.67) without diabetes but with severe PFL and 8.89 (8.36 to 9.46) with both diabetes and severe PFL.

Conclusions

People with diabetes have a 60% greater risk of high psychological distress than people without diabetes; a substantial proportion of this elevation is attributable to higher levels of disability with diabetes, especially factoring in measurement error. Psychological distress is strongly related to physical impairment.

https://ift.tt/2ony7Vl

Effect of vitamin D on ventricular remodelling in heart failure: a meta-analysis of randomised controlled trials

Objectives

The level of vitamin D is considered to be associated with the development and progression of heart failure (HF). However, it is still unclear whether supplementation of vitamin D could improve ventricular remodelling in patients with HF. This study aimed to systematically evaluate the influence and safety of additional vitamin D supplementation on ventricular remodelling in patients with HF.

Design

This study is a meta-analysis of randomised controlled trials (RCTs).

Setting

The PubMed, EMBASE, CNKI, Cochrane library, Web of Science databases and grey literature were searched for RCTs regarding the effect of vitamin D on ventricular remodelling in patients with HF (from database creation to October 2017). RevMan V.5.3 software was employed for data analysis.

Participants

Seven RCTs with a total of 465 patients, including 235 cases in the vitamin D group and 230 cases in the control group, were included.

Primary and secondary outcome measures

Left ventricular end-diastolic dimension (LVEDD), left ventricular ejection fraction (LVEF) and the incidence of adverse reactions.

Results

Compared with the control group, a decrease in the LVEDD (mean difference (MD)=–2.31 mm, 95% CI –4.15 to –0.47, p=0.01) and an increase in the LVEF (MD=4.18%, 95% CI 0.36 to 7.99, p=0.03) were observed in the vitamin D group. Subgroup analysis also revealed a reduced LVEDD in adults (>18 years) and adolescents (<18 years) of the vitamin D group relative to that in those of the control group. High-dose vitamin D (>4000 IU/day) was more effective at reducing the LVEDD than low-dose vitamin D (<4000 IU/day). Moreover, vitamin D supplementation was more effective at reducing the LVEDD and increasing the LVEF in patients with reduced ejection fraction than in patients without reduced ejection fraction.

Conclusion

Vitamin D supplementation inhibits ventricular remodelling and improves cardiac function in patients with HF.

Trial registration number

CRD42017073893.

https://ift.tt/2PikXEv

Factors influencing the decision to convey or not to convey elderly people to the emergency department after emergency ambulance attendance: a systematic mixed studies review

Background

The decision over whether to convey after emergency ambulance attendance plays a vital role in preventing avoidable admissions to a hospital's emergency department (ED). This is especially important with the elderly, for whom the likelihood and frequency of adverse events are greatest.

Objective

To provide a structured overview of factors influencing the conveyance decision of elderly people to the ED after emergency ambulance attendance, and the outcomes of these decisions.

Data sources

A mixed studies review of empirical studies was performed based on systematic searches, without date restrictions, in PubMed, CINAHL and Embase (April 2018). Twenty-nine studies were included.

Study eligibility criteria

Only studies with evidence gathered after an emergency medical service (EMS) response in a prehospital setting that focused on factors that influence the decision whether to convey an elderly patient were included.

Setting

Prehospital, EMS setting; participants to include EMS staff and/or elderly patients after emergency ambulance attendance.

Study appraisal and synthesis methods

The Mixed Methods Appraisal Tool was used in appraising the included articles. Data were assessed using a 'best fit' framework synthesis approach.

Results

ED referral by EMS staff is determined by many factors, and not only the acuteness of the medical emergency. Factors that increase the likelihood of non-conveyance are: non-conveyance guidelines, use of feedback loop, the experience, confidence, educational background and composition (male–female) of the EMS staff attending and consulting a physician, EMS colleague or other healthcare provider. Factors that boost the likelihood of conveyance are: being held liable, a lack of organisational support, of confidence and/or of baseline health information, and situational circumstances. Findings are presented in an overarching framework that includes the impact of these factors on the decision's outcomes.

Conclusion

Many non-medical factors influence the ED conveyance decision after emergency ambulance attendance, and this makes it a complex issue to manage.

https://ift.tt/2onVwG3

Effects of a 6-month self-rehabilitation programme in addition to botulinum toxin injections and conventional physiotherapy on limitations of patients with spastic hemiparesis following stroke (ADJU-TOX): protocol study for a randomised controlled, investigator blinded study

Introduction

Home-based self-rehabilitation programmes combined with botulinum toxin injections (BTIs) appear to be a relevant approach to increase the recommended intensive rehabilitation of patients with spasticity following a stroke. The literature highlights a lack of evidence of beneficial effects of this adjuvant therapy to reduce limitations of patients with stroke. The aim of this study is to assess the effects of a 6-month self-rehabilitation programme in adjunction to BTI, in comparison with BTI alone, to reduce limitations of patients with spasticity following a stroke.

Methods and analysis

220 chronic patients will participate to this multicentre, prospective, randomised, controlled, assessor blinded study. All patients will benefit from two successive BTI (3 months apart), and patients randomised in the self-rehabilitation group will perform in adjunction 6 months of self-rehabilitation at home. All patients continue their conventional physiotherapy. The main outcome is the primary treatment goal (PTG), which will be determined jointly by the patient and the medical doctor using Goal Attainment Scaling. Impairments and functions, quality of life, mood and fatigue will be assessed. Botulinum toxin will be injected into the relevant muscles according to the PTG. Patients in the self-rehab group will be taught the self-rehabilitation programme involving respectively 10 min of stretching, 10 min of strengthening and 10 min of task-oriented exercises, corresponding to their PTG. Compliance to the self-rehabilitation programme will be monitored.

Ethics and dissemination

Patients will sign written informed consent. Ethical approval was obtained from ethics committee. The results will be disseminated in a peer-reviewed journal and presented at international congresses. The results will also be disseminated to patients.

Trial registration number

NCT02944929.

https://ift.tt/2LGrabb

Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART): a multiarm phase IIb randomised, double-blind, placebo-controlled clinical trial comparing the efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis

Introduction

The major unmet need in multiple sclerosis (MS) is for neuroprotective therapies that can slow (or ideally stop) the rate of disease progression. The UK MS Society Clinical Trials Network (CTN) was initiated in 2007 with the purpose of developing a national, efficient, multiarm trial of repurposed drugs. Key underpinning work was commissioned by the CTN to inform the design, outcome selection and drug choice including animal models and a systematic review. This identified seven leading oral agents for repurposing as neuroprotective therapies in secondary progressive MS (SPMS). The purpose of the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) will be to evaluate the neuroprotective efficacy of three of these drugs, selected with distinct mechanistic actions and previous evidence of likely efficacy, against a common placebo arm. The interventions chosen were: amiloride (acid-sensing ion channel antagonist); fluoxetine (selective serotonin reuptake inhibitor) and riluzole (glutamate antagonist).

Methods and analysis

Patients with progressing SPMS will be randomised 1:1:1:1 to amiloride, fluoxetine, riluzole or matched placebo and followed for 96 weeks. The primary outcome will be the percentage brain volume change (PBVC) between baseline and 96 weeks, derived from structural MR brain imaging data using the Structural Image Evaluation, using Normalisation, of Atrophy method. With a sample size of 90 per arm, this will give 90% power to detect a 40% reduction in PBVC in any active arm compared with placebo and 80% power to detect a 35% reduction (analysing by analysis of covariance and with adjustment for multiple comparisons of three 1.67% two-sided tests), giving a 5% overall two-sided significance level. MS-SMART is not powered to detect differences between the three active treatment arms. Allowing for a 20% dropout rate, 110 patients per arm will be randomised. The study will take place at Neuroscience centres in England and Scotland.

Ethics and dissemination

MS-SMART was approved by the Scotland A Research Ethics Committee on 13 January 2013 (REC reference: 13/SS/0007). Results of the study will be submitted for publication in a peer-reviewed journal.

Trial registration numbers

NCT01910259; 2012-005394-31; ISRCTN28440672.

https://ift.tt/2N6b0fK

Validating traditional Chinese syndrome features in varied stages of chronic gastritis malignant transformation: study protocol for a cross-sectional study

Introduction

The transition from chronic non-atrophic gastritis (CNAG) to chronic atrophic gastritis (CAG) and gastric carcinoma (GC) is regarded as a representative disease model of gastric mucosa malignant transformation led by uncontrolled inflammation. Traditional Chinese medicine (TCM) syndrome-targeted therapies have been applied in treating chronic gastritis (CG) malignant transformation in China with satisfying efficacy. This study aims to validate TCM syndrome features in each stage of CG malignant transformation. The findings may shed light on the TCM hypothesis of CG malignant transformation, and thus optimise syndrome-targeted treatment strategies of CNAG, CAG and GC, respectively.

Methods and analysis

The present study is a cross-sectional study conducted in China. A total of 2000 eligible patients, including 500 CNAG cases, 1000 CAG cases and 500 GC cases, will be recruited from four TCM hospitals. Primary outcome measures include the prevalence of TCM syndrome patterns in varied stages of CG malignant transformation. Secondary outcome measures include prevalence and severity of all the presenting signs and symptoms collected by using TCM four diagnostic methods. Descriptive analysis, comparative analysis and correlation analysis of all the measurement data will be performed by biostatisticians. Unsupervised data mining analyses, including exploratory factor analysis, association rule analysis, hierarchical clustering analysis, complex system entropy clustering analysis, and so on, will also be performed by data scientists respectively for in-depth analyses of TCM syndrome-related indicators.

Ethics and dissemination

The protocol has been approved by the Ethical Review Board of Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine (No ECPJ-BDY-2014-02). All the study outcomes will be disseminated through national conference reports and in the meantime published on peer-reviewed journals.

Trial registration number

NCT03314038; Pre-results.

https://ift.tt/2PkOSvK

Early prediction of lenvatinib treatment efficacy by using 18F-FDG PET/CT in patients with unresectable or advanced thyroid carcinoma that is refractory to radioiodine treatment: a protocol for a non-randomized single-arm multicenter observational study

Introduction

Lenvatinib, an oral molecular targeted drug, is used to treat patients with unresectable or advanced thyroid carcinoma that is refractory to radioiodine treatment. Effective methods for evaluating molecular targeted drugs are a critical unmet need owing to their expensive costs and unique adverse events. The aim of this study is to determine whether ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT at 1 week after commencing lenvatinib can predict treatment outcomes.

Design and methods

This study is planned as a non-randomised single-arm multicentre study; patients with pathologically confirmed differentiated thyroid carcinoma (DTC) with lesions that are refractory to radioiodine treatment are eligible. The main exclusion criteria are medullary or anaplastic carcinoma, prior treatment with chemotherapy, poor general condition and thromboembolism-requiring treatment. Patients to be included in the study will be treated with lenvatinib and undergo FDG-PET/CT examination twice: before and 1 week after the initiation of treatment. Contrast-enhanced CT, the gold standard for evaluation, will be performed at least 4 weeks after the initiation of treatment. The primary objective is to evaluate the ability of the lesion maximum standard uptake value for FDG PET/CT performed 1 week after the initiation of treatment to predict outcomes compared with the response evaluation obtained via contrast-enhanced CT performed at least 4 weeks after the initiation of treatment.

Ethics and dissemination

This study is conducted in accordance with the Declaration of Helsinki and has received ethical approval from the institutional review board of the Hokkaido University Hospital (approval number: 015-402). The results of this study will be disseminated through a presentation at a conference and the publication of the data in a peer-reviewed journal. The study will be implemented and reported in line with the SPIRIT statement.

Trial registration number

UMIN000022592.

https://ift.tt/2LFU8I1

Development and evaluation of a hospital discharge information package to empower parents in caring for a child with a fever

Objectives

First, to explore parents' views on and experiences of managing their febrile child and to assess their behaviour and needs when in search of information about fever; second, to develop and evaluate a hospital discharge information package about fever in children.

Design

Mixed methods: (A) qualitative study with semistructured interviews and a focus group discussion (FGD) and (B) quantitative survey.

Setting

Emergency department, non-acute hospital setting and day nursery in Rotterdam, The Netherlands.

Participants

Parents of children <18 years (interviews, n=22) parents of children under 5 years (FGD (n=14), survey (n=38)).

Intervention

Information package about fever in children (leaflet and website including videos).

Outcome measures quantitative survey

Knowledge of fever and confidence in caring for a febrile child (Likert scale 0–5).

Results

Parents found fever mostly alarming, especially high fever. Help-seeking behaviour was based on either specific symptoms or on an undefined intuition. When parents did not feel recognised in their concern or felt criticised, anxiety increased as well as the threshold to seek healthcare for future illnesses. Information was needed, especially for situations when the general practitioner or social network were less easily available. This information should be reliable, consistent, available in multiple formats and include advice on management of fever at home and precise referral to medical services. Parents reported improved knowledge about fever (p<0.05) and mentioned improved confidence in caring for a child with fever at home after consulting the information package.

Conclusion

Parents of children with a fever visiting the hospital are concerned about specific symptoms or based on an undefined intuition. Rather than telling parents that they should manage their child's illness at home, healthcare professionals should recognise parental intuition and provide clear information on alarming signs and potential diagnoses to empower parents in the management of their febrile child.

https://ift.tt/2N4ofO4

Clinical and multi-omics cross-phenotyping of patients with autoimmune and autoinflammatory diseases: the observational TRANSIMMUNOM protocol

Introduction

Autoimmune and autoinflammatory diseases (AIDs) represent a socioeconomic burden as the second cause of chronic illness in Western countries. In this context, the TRANSIMMUNOM clinical protocol is designed to revisit the nosology of AIDs by combining basic, clinical and information sciences. Based on classical and systems biology analyses, it aims to uncover important phenotypes that cut across diagnostic groups so as to discover biomarkers and identify novel therapeutic targets.

Methods and analysis

TRANSIMMUNOM is an observational clinical protocol that aims to cross-phenotype a set of 19 AIDs, six related control diseases and healthy volunteers . We assembled a multidisciplinary cohort management team tasked with (1) selecting informative biological (routine and omics type) and clinical parameters to be captured, (2) standardising the sample collection and shipment circuit, (3) selecting omics technologies and benchmarking omics data providers, (4) designing and implementing a multidisease electronic case report form and an omics database and (5) implementing supervised and unsupervised data analyses.

Ethics and dissemination

The study was approved by the institutional review board of Pitié-Salpêtrière Hospital (ethics committee Ile-De-France 48–15) and done in accordance with the Declaration of Helsinki and good clinical practice. Written informed consent is obtained from all participants before enrolment in the study. TRANSIMMUNOM's project website provides information about the protocol (https://www.transimmunom.fr/en/) including experimental set-up and tool developments. Results will be disseminated during annual scientific committees appraising the project progresses and at national and international scientific conferences.

Discussion

Systems biology approaches are increasingly implemented in human pathophysiology research. The TRANSIMMUNOM study applies such approach to the pathophysiology of AIDs. We believe that this translational systems immunology approach has the potential to provide breakthrough discoveries for better understanding and treatment of AIDs.

Trial registration number

NCT02466217; Pre-results.

https://ift.tt/2LFTNVL

Neonatal intensive care nurses knowledge and beliefs regarding kangaroo care in China: a national survey

Objective

Kangaroo care (KC), a well-established parent-based intervention in neonatal intensive care units (NICUs), with documented benefits for infants and their parents. However, in China there remains a lack of knowledge and a reluctance to implement KC in hospitals. Therefore, our aim was to investigate the current knowledge, beliefs and practices regarding KC among NICU nurses in China using the 'Kangaroo Care Questionnaire'.

Methods

A quantitative descriptive survey was designed. This questionnaire comprised 90 items classified according to four domains: knowledge, practice, barriers and perception. Data were analysed using SPSS V.20.0, and content analysis was used to summarise data derived from open-ended questions.

Results

The survey involved 861 neonatal nurses from maternity and general hospitals across China (response rate=95.7%). The findings showed that 47.7% (n=411) of the nurses had participated in the implementation of KC. Neonatal nurses in the 'experienced in KC' group showed an overall better understanding of KC and its benefits with a higher 'correct response' rate than those in the 'not experienced in KC' group. In the 'experienced in KC' group, over 90% considered KC beneficial to the parent-baby relationship and attachment, and over 80% believed that KC positively affected outcomes of preterm infants. The 'not experienced in KC' group perceived more barriers to KC implementation than did the 'experienced in KC' group.

Conclusion

Although most nurses working in NICUs in China were aware of the benefits of KC, there remain substantial barriers to its routine use in practice. Education for both staff and parents is necessary, as is the provision of appropriate facilities and policies to support parents in providing this evidence-based intervention.

https://ift.tt/2opQite

Defining good health and care from the perspective of persons with multimorbidity: results from a qualitative study of focus groups in eight European countries

Objectives

The prevalence of multimorbidity is increasing in many Western countries. Persons with multimorbidity often experience a lack of alignment in the care that multiple health and social care organisations provide. As a response, integrated care programmes are appearing. It is a challenge to evaluate these and to choose appropriate outcome measures. Focus groups were held with persons with multimorbidity in eight European countries to better understand what good health and a good care process mean to them and to identify what they find most important in each.

Methods

In 2016, eight focus groups were organised with persons with multimorbidity in: Austria, Croatia, Germany, Hungary, the Netherlands, Norway, Spain and the UK (total n=58). Each focus group followed the same two-part procedure: (1) defining (A) good health and well-being and (B) a good care process, and (2) group discussion on prioritising the most important concepts derived from part one and from a list extracted from the literature. Inductive and deductive analyses were done.

Results

Overall, the participants in all focus groups concentrated more on the care process than on health. Persons with multimorbidity defined good health as being able to conduct and plan normal daily activities, having meaningful social relationships and accepting the current situation. Absence of shame, fear and/or stigma, being able to enjoy life and overall psychological well-being were also important facets of good health. Being approached holistically by care professionals was said to be vital to a good care process. Continuity of care and trusting professionals were also described as important. Across countries, little variation in health definitions were found, but variation in defining a good care process was seen.

Conclusion

A variety of health outcomes that entail well-being, social and psychological facets and especially experience with care outcomes should be included when evaluating integrated care programmes for persons with multimorbidity.

https://ift.tt/2PhLpOy

Association between type 1 diabetes mellitus and educational attainment in childhood: a systematic review protocol

Introduction

Type 1 diabetes has the potential to significantly impact children's educational attainment. With the increase in incidence, quantifying this effect would be useful to assess how much additional support should be focused on children with type 1 diabetes in school.

Methods and analysis

We will conduct a systematic review of all observational studies and randomised controlled trials, including individuals both with and without a diagnosis of type 1 diabetes who have undertaken high stakes testing at the end of compulsory schooling when under 18 years of age. The search will cover both peer-reviewed and grey literature available from January 2004 to January 2018. The following seven databases will be searched: Ovid MEDLINE (1946 to present), Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid EMBASE (1947 to present), Thomson Reuters Web of Science, EBSCO Education Resources Information Center, EBSCO British Education Index and EBSCO Cumulative Index to Nursing and Allied Health Literature. Study selection and data extraction will be performed independently by two reviewers with any disagreements resolved via a third reviewer. The quality and risk of bias in the observational studies included in this review will be assessed using the Newcastle-Ottawa Scale. We aim to conduct a meta-analysis and will assess heterogeneity between the included studies and potential for publication bias if sufficient (>10) studies are included.

Results and dissemination

Formal ethical approval is not required as individual patient data will not be collected. Results will be disseminated through peer-reviewed publication and conference presentations.

PROSPERO registration number

CRD42017084078.

https://ift.tt/2MZcdFR

Perioperative urinary thromboxane metabolites and outcome of coronary artery bypass grafting: a nested case-control study

Objective

As a marker of in vivo thromboxane generation, high-level urinary thromboxane metabolites (TXA-M) increase the occurrence of cardiovascular events in high-risk patients. To investigate whether perioperative urinary TXA-M level is associated with major adverse cardiac and cerebrovascular events (MACCE) after coronary artery bypass graft (CABG) surgery, we designed a nested case-control study.

Design

Observational, nested case-control study.

Setting

Single-centre outcomes research in Fuwai Hospital, Beijing, China.

Participants

One thousand six hundred and seventy Chinese patients undergoing CABG surgery from September 2011 to October 2013.

Methods

We obtained urinary samples from 1670 Chinese patients undergoing CABG 1 hour before surgery (pre-CABG), and 6 hours (post-CABG 6 hours) and 24 hours after surgery (post-CABG 24 hours). Patients were followed up for 1 year, and we observed 56 patients had MACCE. For each patient with MACCE, we matched three control subjects. Perioperative urinary TXA-M of the three time spots was detected in these 224 patients.

Results

Post-CABG 24 hours TXA-M is significantly higher than that of patients without MACCE (11 101vs8849 pg/mg creatine, P=0.007). In addition, patients in the intermediate tertile and upper tertile of post-CABG 24 hours urinary TXA-M have a 2.2 times higher (HR 2.22, 95% CI 1.04 to 4.71, P=0.038) and a 2.8 times higher (HR 2.81, 95% CI 1.35 to 5.85, P=0.006) risk of 1 year MACCE than those in the lower tertile, respectively.

Conclusions

In conclusion, post-CABG 24 hours urinary TXA-M elevation is associated with an increase of 1 year adverse events after CABG, indicating that the induction of cyclo-oxygenase-2 by surgery-related inflammatory stimuli or platelet turnover may be responsible for the high levels of post-CABG urinary TXA-M.

Trial registration number

NCT01573143.

https://ift.tt/2LFTqdP

Use of a patient-centred educational exchange (PCEE) to improve patients self-management of medicines after a stroke: a randomised controlled trial study protocol

Introduction

National and international guidelines make recommendations for secondary prevention of stroke including the use of medications. A strategy which engages patients in a conversation to personalise evidence-based educational material (patient-centred educational exchange; PCEE) may empower patients to better manage their medications.

Methods and analysis

This protocol outlines a non-blinded randomised controlled trial. Consenting patients admitted with a diagnosis of stroke or transient ischaemic attack will be randomised 1:1 to receive either a PCEE composed of two sessions, one at the bedside before discharge and one by telephone at least 10 days after discharge from hospital in addition to usual care (intervention) or usual care alone (control). The primary aim of this study is to determine whether a PCEE improves adherence to antithrombotic, antihypertensive and lipid-lowering medications prescribed for secondary prevention of stroke over the 3 months after discharge, measured using prescription-refill data. Secondary aims include investigation of the impact of the PCEE on adherence over 12 months using prescription-refill data, self-reported medication taking behaviour, self-reported clinical outcomes (blood pressure, cholesterol, adverse medication events and readmission), quality of life, the cost utility of the intervention and changes in beliefs towards medicines and illness.

Ethics and dissemination

Communication of the trial results will provide evidence to aid clinicians in conversations with patients about medication taking behaviour related to stroke prevention. The targeted audiences will be health practitioners and consumers interested in medication taking behaviour in chronic diseases and in particular those interested in secondary prevention of stroke.

The trial has ethics approval from Metro South Human Research Ethics Committee (HREC/15/QPAH/531) and The University of Queensland Institutional Human Research Ethics (2015001612).

Trial registration number

ACTRN12615000888561; Pre-results.

https://ift.tt/2N6aVIY

Prospective cohort study of overweight and obesity among rural Indian adults: sociodemographic predictors of prevalence, incidence and remission

Objectives

To assess sociodemographic predictors of prevalence, incidence and remission of overweight including obesity among adults (aged ≥18 years) in rural Eastern India.

Design

Prospective cohort study.

Setting

Birbhum Health and Demographic Surveillance System, West Bengal, India.

Participants

Self-weighted sample of 24 115 adults (men: 10915, women: 13200) enrolled in 2008 were followed up for body mass index (BMI) reassessment in 2017.

Primary and secondary outcome measures

Measured BMI was categorised as: underweight (<18.5 kg/m²), normal weight (18.5–22.9 kg/m²) and overweight including obesity (≥23 kg/m²; hereinafter overweight). Incident overweight was defined as transition from normal weight in 2008 to overweight in 2017, whereas if overweight individuals in 2008 measured normal BMI in 2017, it was classified as remission from overweight.

Results

In 2008, 10.1% of men and 14.6% of women were overweight, whereas 17.3% of men and 24.7% of women were overweight in 2017. At the same time, in 2017, 35.6% of men and 33.3% of women were underweight. Incident overweight was 19.0% among men and 27.2% among women, whereas remission among men was higher (15.4%) than women (11.5%). Women were more likely to be overweight in 2008 and to experience incident overweight than men. For men and women, education level and wealth were positively associated with prevalence and incidence of overweight. Remission from overweight was less likely in Sainthia, a business hub in the district, as compared with Mohammad Bazar, a more rural area.

Conclusion

A nutrition transition to higher risk of overweight is evident in this rural setting in India, especially among women and individuals with high socioeconomic status. At the same time, a high prevalence of underweight persists, resulting in a significant double burden. Culturally sensitive interventions that address both ends of the malnutrition spectrum should be prioritised.

https://ift.tt/2LHzsPL

What are the factors that contribute to the development of sexual dysfunction in breastfeeding women? A systematic scoping review protocol

Introduction

Female sexual dysfunction is a public health problem. Evidence suggests that the population of nursing women is more vulnerable to the phenomenon due to breast feeding. Thus, this protocol was developed to explore the factors that contribute to the development of sexual dysfunction in breastfeeding women.

Methods and analysis

The systematic scoping review will be conducted in six stages, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. The databases used will be: PubMed, Excerpta Medica Database, Cumulative Index for Nursing and Allied Health Literature, PsycINFO, Science Direct, Web of Science and Google Scholar. The searches were made until 1 June 2018, and no retrospective time limit was used. For the organisation of the literature retrieved from the databases, the EndNote Basic manager will be used. The Cochrane model will be used for the data extraction. The analysis of the quantitative data will be carried out through descriptive statistics and the qualitative data will be submitted to thematic analysis. The methodological quality of the empirical studies will be evaluated using the Mixed Methods Appraisal Tool.

Ethics and dissemination

As it will be a review study, without human involvement, there will be no need for ethical approval. The results will be disseminated in a scientific journal, as well as in various media, such as: conferences, seminars, congresses or symposia.

https://ift.tt/2N4oecY

Introduction: Allergy Special Issue

Allergy involves abnormal variations of normally protective immune responses that, in predisposed (atopic) subjects, trigger immediate hypersensitivity to normally harmless antigens. Many elements of the immune system are involved and a number of symptoms of varying seriousness can be triggered by a wide range of allergens from many sources and with different features. Although allergic responses are abnormal, they are very common and affect a considerable, and increasing, proportion of the population; for example, worldwide up to 50% of school children are sensitized to one or more common allergen. There is, thus, a clear drive for understanding the complex mechanisms involved in allergy and to find ways to combat it.

https://ift.tt/2Nzb6JM

Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis

Patients with infective endocarditis on the left side of the heart are typically treated with intravenously administered antibiotic agents for up to 6 weeks, according to guidelines from the European Society of Cardiology and the American Heart Association. During the initial phase after admission,…

https://ift.tt/2LJfeVU

Percutaneous Repair or Medical Treatment for Secondary Mitral Regurgitation

In patients with secondary mitral regurgitation, previously referred to as functional mitral regurgitation, the mitral-valve leaflets and chordae are structurally normal, and mitral regurgitation results from alterations in left ventricular geometry and function. Severe secondary mitral…

https://ift.tt/2Nz8vj2

Six-Month Outcomes after Restrictive or Liberal Transfusion for Cardiac Surgery

Restrictive strategies for red-cell transfusion (in which lower hemoglobin concentrations are used for transfusion) in patients undergoing cardiac surgery have been shown to result in the use of fewer units of allogeneic red cells than liberal strategies (in which higher hemoglobin concentrations…

https://ift.tt/2Nag82N

Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis

Patients with infective endocarditis on the left side of the heart are typically treated with intravenously administered antibiotic agents for up to 6 weeks, according to guidelines from the European Society of Cardiology and the American Heart Association. During the initial phase after admission,…

https://ift.tt/2LJfeVU

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

Here we present a tandem mass spectrometry-based protocol for the quantification of frequently used antibiotics in intensive care units, namely cefepime, meropenem, ciprofloxacin, moxifloxacin, linezolid, and piperacillin.

https://ift.tt/2LFIrB7

A fully defined static suspension culture system for large-scale human embryonic stem cell production

A fully defined static suspension culture system for large-scale human embryonic stem cell production

A fully defined static suspension culture system for large-scale human embryonic stem cell production, Published online: 30 August 2018; doi:10.1038/s41419-018-0863-8

A fully defined static suspension culture system for large-scale human embryonic stem cell production

https://ift.tt/2MZkF85

High NRF2 level mediates cancer stem cell-like properties of aldehyde dehydrogenase (ALDH)-high ovarian cancer cells: inhibitory role of all-trans retinoic acid in ALDH/NRF2 signaling

High NRF2 level mediates cancer stem cell-like properties of aldehyde dehydrogenase (ALDH)-high ovarian cancer cells: inhibitory role of all-trans retinoic acid in ALDH/NRF2 signaling

High NRF2 level mediates cancer stem cell-like properties of aldehyde dehydrogenase (ALDH)-high ovarian cancer cells: inhibitory role of all-<i>trans</i> retinoic acid in ALDH/NRF2 signaling, Published online: 30 August 2018; doi:10.1038/s41419-018-0903-4

High NRF2 level mediates cancer stem cell-like properties of aldehyde dehydrogenase (ALDH)-high ovarian cancer cells: inhibitory role of all-trans retinoic acid in ALDH/NRF2 signaling

https://ift.tt/2LGIaOn

The Effect of Ultraviolet Radiation on the Chemical Bath Deposition of Bis(thiourea) Cadmium Chloride Crystals and the Subsequent CdS Obtention

This article presents a protocol for the synthesis of bis(thiourea) cadmium chloride crystals by chemical bath deposition. Two experiments are described: one aided by ultraviolet light compared to one without ultraviolet light.

https://ift.tt/2wx0cgn

Concordance of biopsy and prostatectomy diagnosis of intraductal and cribriform carcinoma in a prospectively collected dataset

Histopathology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Nxn7zE

Assessment of anatomical knowledge: Approaches taken by higher education institutions by Bipasha Choudhury and Anthony Freemont

Clinical Anatomy, EarlyView.


https://ift.tt/2Pmfnkq

BMP9, but not BMP10, acts as a quiescence factor on tumor growth, vessel normalization and metastasis in a mouse model of breast cancer

Abstract

Background

Angiogenesis has become an attractive target for cancer therapy. However, despite the initial success of anti-VEGF (Vascular endothelial growth factor) therapies, the overall survival appears only modestly improved and resistance to therapy often develops. Other anti-angiogenic targets are thus urgently needed. The predominant expression of the type I BMP (bone morphogenetic protein) receptor ALK1 (activin receptor-like kinase 1) in endothelial cells makes it an attractive target, and phase I/II trials are currently being conducted. ALK1 binds with strong affinity to two ligands that belong to the TGF-ß family, BMP9 and BMP10. In the present work, we addressed their specific roles in tumor angiogenesis, cancer development and metastasis in a mammary cancer model.

Methods

For this, we used knockout (KO) mice for BMP9 (constitutive Gdf2-deficient), for BMP10 (inducible Bmp10-deficient) and double KO mice (Gdf2 and Bmp10) in a syngeneic immunocompetent orthotopic mouse model of spontaneous metastatic breast cancer (E0771).

Results

Our studies demonstrate a specific role for BMP9 in the E0771 mammary carcinoma model. Gdf2 deletion increased tumor growth while inhibiting vessel maturation and tumor perfusion. Gdf2 deletion also increased the number and the mean size of lung metastases. On the other hand, Bmp10 deletion did not significantly affect the E0771 mammary model and the double deletion (Gdf2 and Bmp10) did not lead to a stronger phenotype than the single Gdf2 deletion.

Conclusions

Altogether, our data show that in a tumor environment BMP9 and BMP10 play different roles and thus blocking their shared receptor ALK1 is maybe not appropriate. Indeed, BMP9, but not BMP10, acts as a quiescence factor on tumor growth, lung metastasis and vessel normalization. Our results also support that activating rather than blocking the BMP9 pathway could be a new strategy for tumor vessel normalization in order to treat breast cancer.

https://ift.tt/2omCnnZ

Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis

Patients with infective endocarditis on the left side of the heart are typically treated with intravenously administered antibiotic agents for up to 6 weeks, according to guidelines from the European Society of Cardiology and the American Heart Association. During the initial phase after admission,…

https://ift.tt/2LJfeVU

Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients

The prevalence of obesity has nearly tripled during the past 40 years worldwide. As of 2016, 13% of adults globally were obese, with rates as high as 40% in several countries, including the United States. (Obesity is defined as a body-mass index [BMI, the weight in kilograms divided by the square…

https://ift.tt/2MGEpOf

Comparison Between Prognostic Classifications in De Novo Metastatic Hormone Sensitive Prostate Cancer

Abstract

Background

The CHAARTED and LATITUDE trials demonstrated improved outcomes with docetaxel or abiraterone plus androgen deprivation therapy in metastatic hormone sensitive prostate cancer (mHSPC) using two different prognostic scores.

Objective

The aim of our study was to assess the concordance between the two scores and if these retained their prognostic value exclusively in de novo mHSPC.

Patients and Methods

De novo mHSPC patients referring to our institution were retrospectively stratified according to the CHAARTED and LATITUDE classifications: high volume/high risk (HV/HR), low-volume/low-risk (LV/LR), and HVorHR (HV/LR and LV/HR). The Kaplan-Meier method and Cox proportional-hazard models were used to estimate hazard ratios for overall survival.

Results

The study population included 106 patients. Concordance between the CHAARTED and LATITUDE classifications was observed in 86.8% of cases (65.1% HV/HR, 21.7% LV/LR), while 13.2% of patients fulfill the criteria of only one of the two classifications (HVorHR). When analyzed independently, the CHAARTED and LATITUDE classifications maintained their prognostic value (mOS 28.2 months in HV versus 60.9 months in LV, p = 0.006; 28.2 months in HR versus 40.6 months in LR, p = 0.017). The LR/LV population showed significantly longer mOS compared to the HR/HV group (72.6 months versus 26.3 months; p = 0.005), and to HVorHR patients (35.1 months; p = 0.003). No difference in OS was observed between HV/HR and HVorHR patients. ECOG PS ≥ 1 and patient age improved the prognostic value of the two classifications with multivariate analysis.

Conclusions

Our study showed a lack of complete concordance between the CHAARTED and LATITUDE classifications. The analysis confirmed the role of these prognostic scores to stratify de novo mHSPC patients in clinical practice.

https://ift.tt/2wBazzM

In Stroke Survivors, Cost-Related Non-Adherence Down After ACA

THURSDAY, Aug. 30, 2018 -- Among adult survivors of stroke, health insurance coverage increased and cost-related non-adherence (CRN) decreased after implementation of the Affordable Care Act (ACA), according to research published online Aug. 27 in...

https://ift.tt/2C2swgH

MICs of Isoniazid, Rifampin May Predict Tuberculosis Relapse

THURSDAY, Aug. 30, 2018 -- In pretreatment isolates of Mycobacterium tuberculosis, higher minimum inhibitory concentrations (MICs) of isoniazid and rifampin below the standard resistance breakpoint are associated with increased risk of relapse,...

https://ift.tt/2PSbUv4

Peer Support May Cut Acute Psychiatric Care Readmissions

THURSDAY, Aug. 30, 2018 -- A self-management intervention facilitated by peer support workers may reduce the rate of readmissions to acute care for people discharged from mental health crisis resolution teams, according to a study published in the...

https://ift.tt/2C2rXn5

Many Teens Are Concerned Over Societal Discrimination

THURSDAY, Aug. 30, 2018 -- Many adolescents in Los Angeles are concerned over societal discrimination, and this concern is associated with behavioral health problems one year later, according to research published online Aug. 20 in JAMA...

https://ift.tt/2ooWqCh

Oral High-Risk HPV Prevalence Appears to Be Low in England

THURSDAY, Aug. 30, 2018 -- The prevalence of oral high-risk human papillomavirus (HR-HPV) infection in adult men and women is low in England, according to a study published online Aug. 20 in BMJ Open. Vanessa Hearnden, Ph.D., from the University of...

https://ift.tt/2Pjpkim

Many ED Visits for Antibiotic Adverse Drug Events in Children

THURSDAY, Aug. 30, 2018 -- Emergency department (ED) visits for antibiotic adverse drug events (ADEs) in children account for 46.2 percent of emergency department visits for ADEs resulting from systemic medication, according to a study published...

https://ift.tt/2omiYn9

Radn Tx Alone May Be Adequate for Stage I Anal Cancer in Elderly

THURSDAY, Aug. 30, 2018 -- For older patients with stage I squamous cell carcinoma of the anus, radiation alone is associated with outcomes that do not differ significantly from those of chemoradiation, according to research published in the July...

https://ift.tt/2PjphmG

Partial Oral Abx Non-Inferior in Endocarditis on Left Side of Heart

THURSDAY, Aug. 30, 2018 -- Changing from intravenous to oral antibiotic treatment is non-inferior to continued intravenous antibiotic treatment among patients with endocarditis on the left side of the heart, according to a study published online...

https://ift.tt/2PQIf5l

Three-dimensional Printing of Thermoplastic Materials to Create Automated Syringe Pumps with Feedback Control for Microfluidic Applications

Here we present a protocol to construct a pressure-controlled syringe pump to be used in microfluidic applications. This syringe pump is made from an additively manufactured body, off-the-shelf hardware, and open-source electronics. The resulting system is low-cost, straightforward to build, and delivers well-regulated fluid flow to enable rapid microfluidic research.

https://ift.tt/2LFuG5A

Iron overload is accompanied by mitochondrial and lysosomal dysfunction in WDR45 mutant cells

Abstract

Beta-propeller protein-associated neurodegeneration is a subtype of monogenic neurodegeneration with brain iron accumulation caused by de novo mutations in WDR45. The WDR45 protein functions as a beta-propeller scaffold and plays a putative role in autophagy through its interaction with phospholipids and autophagy-related proteins. Loss of WDR45 function due to disease-causing mutations has been linked to defects in autophagic flux in patient and animal cells. However, the role of WDR45 in iron homeostasis remains elusive. Here we studied patient-specific WDR45 mutant fibroblasts and induced pluripotent stem cell-derived midbrain neurons. Our data demonstrated that loss of WDR45 increased cellular iron levels and oxidative stress, accompanied by mitochondrial abnormalities, autophagic defects, and diminished lysosomal function. Restoring WDR45 levels partially rescued oxidative stress and the susceptibility to iron treatment, and activation of autophagy reduced the observed iron overload in WDR45 mutant cells. Our data suggest that iron-containing macromolecules and organelles cannot effectively be degraded through the lysosomal pathway due to loss of WDR45 function.

https://ift.tt/2C2A2rY

Cancers, Vol. 10, Pages 295: Epigenetic Crosstalk between the Tumor Microenvironment and Ovarian Cancer Cells: A Therapeutic Road Less Traveled

Cancers, Vol. 10, Pages 295: Epigenetic Crosstalk between the Tumor Microenvironment and Ovarian Cancer Cells: A Therapeutic Road Less Traveled

Cancers doi: 10.3390/cancers10090295

Authors: Yuliya Klymenko Kenneth P. Nephew

Metastatic dissemination of epithelial ovarian cancer (EOC) predominantly occurs through direct cell shedding from the primary tumor into the intra-abdominal cavity that is filled with malignant ascitic effusions. Facilitated by the fluid flow, cells distribute throughout the cavity, broadly seed and invade through peritoneal lining, and resume secondary tumor growth in abdominal and pelvic organs. At all steps of this unique metastatic process, cancer cells exist within a multidimensional tumor microenvironment consisting of intraperitoneally residing cancer-reprogramed fibroblasts, adipose, immune, mesenchymal stem, mesothelial, and vascular cells that exert miscellaneous bioactive molecules into malignant ascites and contribute to EOC progression and metastasis via distinct molecular mechanisms and epigenetic dysregulation. This review outlines basic epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA regulators, and summarizes current knowledge on reciprocal interactions between each participant of the EOC cellular milieu and tumor cells in the context of aberrant epigenetic crosstalk. Promising research directions and potential therapeutic strategies that may encompass epigenetic tailoring as a component of complex EOC treatment are discussed.

https://ift.tt/2wvytNf

Six-Month Outcomes after Restrictive or Liberal Transfusion for Cardiac Surgery

Restrictive strategies for red-cell transfusion (in which lower hemoglobin concentrations are used for transfusion) in patients undergoing cardiac surgery have been shown to result in the use of fewer units of allogeneic red cells than liberal strategies (in which higher hemoglobin concentrations…

https://ift.tt/2Nag82N

Rivaroxaban for Thromboprophylaxis after Hospitalization for Medical Illness

Patients who are hospitalized for acute medical illnesses, such as heart failure, respiratory insufficiency, stroke, and infectious or inflammatory diseases, are at increased risk for venous thromboembolism. Validated risk scores that include additional factors, such as a lack of mobility, advanced…

https://ift.tt/2LGQvBx

Oxidative stress mediated mitochondrial damage plays roles in pathogenesis of diabetic nephropathy rat

OBJECTIVE: Diabetic nephropathy (DN) is considered as a complication of diabetes and accounts for about 40%. Reactive oxygen species (ROS) level continues to increase in DN. However, whether specific ROS levels can alleviate renal damage by improving mitochondrial function has not been investigated.

MATERIALS AND METHODS: DN model was established by intraperitoneal injection of streptozotocin (STZ). The rats were divided into normal group, STZ model group, and N-acetylcysteine (NAC) group. Fasting blood glucose was tested to assess the modeling. The renal injury was evaluated by using hematoxylin-eosin (HE) staining and periodate-Schiff staining. Serum creatinine and 24 h urinary protein levels were determined by renal function detection kit. The levels of ROS and malondialdehyde (MDA) were assessed by the kit to evaluate the effects of oxidative stress and NAC in rats. The mitochondrial damage marker Cyto C level was detected by Western blot.

RESULTS: Blood glucose, serum creatinine, and urinary protein levels were significantly increased in model group compared with the normal group (p<0.05). Blood glucose levels, serum creatinine, and urinary protein levels were markedly improved after the ROS and MDA levels reduced by NAC. Meanwhile, glomerular hypertrophy, mesangial matrix accumulation, and severe renal injury were observed in the model group. NAC administration markedly improved glomerular morphology and mesangial matrix aggregation. Cyto C expression in the model group increased significantly compared with normal control group (p<0.05), while NAC effectively inhibited Cyto C levels.

CONCLUSIONS: Oxidative stress-mediated mitochondrial damage is an important part of the pathogenesis of DN. Inhibition of ROS production can be a potential target for DN treatment.

L'articolo Oxidative stress mediated mitochondrial damage plays roles in pathogenesis of diabetic nephropathy rat sembra essere il primo su European Review.

https://ift.tt/2N51Znl

Architecture and Preparation of Hollow Catalytic Devices

Advanced Materials, EarlyView.


https://ift.tt/2C16dbl

Differentiating Polymorphs in Molybdenum Disulfide via Electron Microscopy

Advanced Materials, EarlyView.


https://ift.tt/2MCeSFS

Superoleophobic Slippery Lubricant‐Infused Surfaces: Combining Two Extremes in the Same Surface

Advanced Materials, EarlyView.


https://ift.tt/2Nv0Dz5

A Real‐Time Wearable UV‐Radiation Monitor based on a High‐Performance p‐CuZnS/n‐TiO2 Photodetector

Advanced Materials, EarlyView.


https://ift.tt/2MCeya8

A Metamaterial Analog of the Ising Model

Advanced Materials, EarlyView.


https://ift.tt/2PVQ7Tk

Efficient and Layer‐Dependent Exciton Pumping across Atomically Thin Organic–Inorganic Type‐I Heterostructures

Advanced Materials, EarlyView.


https://ift.tt/2Ny5VtR

Direct‐Write Freeform Colloidal Assembly

Advanced Materials, EarlyView.


https://ift.tt/2Pl9JyT

Nature‐Inspired Emerging Chiral Liquid Crystal Nanostructures: From Molecular Self‐Assembly to DNA Mesophase and Nanocolloids

Advanced Materials, EarlyView.


https://ift.tt/2NyBtQ2

Designing Catalysts for Chirality‐Selective Synthesis of Single‐Walled Carbon Nanotubes: Past Success and Future Opportunity

Advanced Materials, EarlyView.


https://ift.tt/2PVQs8y

Perovskites for Light Emission

Advanced Materials, EarlyView.


https://ift.tt/2BXVRJ8

Using hospital registries in Australia to extend data availability on vulval cancer treatment and survival

Abstract

Background

The value of hospital registries for describing treatment and survival outcomes for vulval cancer was investigated. Hospital registry data from four major public hospitals in 1984–2016 were used because population-based data lacked required treatment and outcomes data. Unlike population registries, the hospital registries had recorded FIGO stage, grade and treatment.

Methods

Unadjusted and adjusted disease-specific survival and multiple logistic regression were used. Disease-specific survivals were explored using Kaplan-Meier product-limit estimates. Hazards ratios (HRs) were obtained from proportional hazards regression for 1984–1999 and 2000–2016. Repeat analyses were undertaken using competing risk regression.

Results

Five-year disease-specific survival was 70%, broadly equivalent to the five-year relative survivals reported for Australia overall (70%), the United Kingdom (70%), USA (72%), Holland (70%), and Germany (Munich) (68%). Unadjusted five-year survival tended to be lower for cancers diagnosed in 2000–2016 than 1984–1999, consistent with survival trends reported for the USA and Canada, but higher for 2000–2016 than 1984–1999 after adjusting for stage and other covariates, although differences were small and did not approach statistical significance (p ≥ 0.40). Surgery was provided as part of the primary course of treatment for 94% of patients and radiotherapy for 26%, whereas chemotherapy was provided for only 6%. Less extensive surgical procedures applied in 2000–2016 than 1984–1999 and the use of chemotherapy increased over these periods. Surgery was more common for early FIGO stages, and radiotherapy for later stages with a peak for stage III. Differences in treatment by surgery and radiotherapy were not found by geographic measures of remoteness and socioeconomic status in adjusted analyses, suggesting equity in service delivery.

Conclusions

The data illustrate the complementary value of hospital-registry data to population-registry data for informing local providers and health administrations of trends in management and outcomes, in this instance for a comparatively rare cancer that is under-represented in trials and under-reported in national statistics. Hospital registries can fill an evidence gap when clinical data are lacking in population-based registries.

https://ift.tt/2wv5bz3