"Oncotarget"[jour]; +110 new citations

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Erinnerungsräume in doppelter Buchführung

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Entwicklung heisst Befreiung

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Gregory I the Great

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Late Quaternary landscape evolution in a region of stable postglacial relative sea levels, British Columbia central coast, Canada

After retreat of the Cordilleran Ice Sheet (CIS) and subsequent glacio-isostatic adjustment of the central coast of British Columbia (BC), Canada, a complex coastline emerged as relative sea level rapidly reached equilibrium and maintained stability over the end of the Late Pleistocene and Holocene. This study provides a late Quaternary reconstruction of the landscape evolution of a geographically distinct location on the central BC coast, northwest Calvert Island, which experienced a re-advance of the CIS near the end of the Late Pleistocene and minimal subsequent relative sea-level change. Geomorphological observations from LiDAR imagery, sedimentological and palaeoecological evidence from exposures, cores and shovel pits, and a robust luminescence and ¹⁴C-based chronology spanning the last 15 000 years are used to reconstruct the landscape of northwest Calvert Island following CIS retreat. A single-aliquot regenerative dose protocol that was developed specifically for luminescence dating of the sediments on Calvert Island was utilized in this study. Localized proglacial sedimentation was linked to the glacial re-advance experienced at the end of the Late Pleistocene. Extensive coastal reconfiguration (e.g. rapid shoreline progradation of >1 m a⁻¹) occurred in the absence of extensive RSL change, which was the main driver of coastal change elsewhere along the BC coast. Changes in climate, small magnitude changes in RSL, and fire all probably played a role in isolated aeolian landform development and stabilization in the study area. An important contribution of this study is the documentation of the multi-disciplinary approach for reconstructing palaeogeography, using multiple geochronological methods, micro- and macro-sedimentology, the palaeoecology inferred from both macro and microfossils (e.g. diatoms and foraminifers), stratigraphy, field mapping and remote sensing. In addition, these findings inform our understanding of the drivers of coastal sedimentary processes, particularly in the temperate coastal rainforest region of BC, and the role that fire may play in those processes. Coastal palaeogeography studies in the region will become increasingly important as discoveries of Late Pleistocene human habitation along the coastal migration route continue to be documented.

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Asymmetrical trunk movement during walking improved to normal range at 3 months after corrective posterior spinal fusion in adolescent idiopathic scoliosis

Abstract

Purpose

To investigate the effects of posterior spinal fusion (PSF) and curve type on upper body movements in Adolescent Idiopathic Scoliosis (AIS) patients during gait.

Methods

Twenty-four girls (12–18 years) with AIS underwent PSF. 3D-Gait-analyses were performed preoperatively, at 3 months and 1 year postoperatively. Mean position (0° represents symmetry) and range of motion (ROM) of the trunk (thorax-relative-to-pelvis) in all planes were assessed. Lower body kinematics and spatiotemporal parameters were also evaluated.

Results

Mean trunk position improved from 7.0° to 2.9° in transversal plane and from 5.0° to − 0.8° in frontal plane at 3 months postoperative (p < 0.001), and was maintained at 1 year. Trunk ROM in transverse plane decreased from 9.6° to 7.5° (p < 0.001) after surgery. No effects of PSF were observed on the lower body kinematics during the gait cycle. Patients with a double curve had a more axial rotated trunk before and after surgery (p = 0.013).

Conclusion

In AIS patients, during gait an evident asymmetrical position of the trunk improved to an almost symmetric situation already 3 months after PSF and was maintained at 1 year. Despite a reduction of trunk ROM, patients were able to maintain the same walking pattern in the lower extremities after surgery. This improvement of symmetry and maintenance of normal gait can explain the rapid recovery and well functioning in daily life of AIS patients, despite undergoing a fusion of large parts of their spine.

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Cardiovascular Profile of Valbenazine: Analysis of Pooled Data from Three Randomized, Double-Blind, Placebo-Controlled Trials

Abstract

Introduction

Valbenazine is a novel vesicular monoamine transporter 2 inhibitor approved for the treatment of tardive dyskinesia in adults.

Objective

Using data from double-blind, placebo-controlled trials, analyses were conducted to evaluate the cardiovascular effects of once-daily valbenazine in patients with a psychiatric disorder who developed tardive dyskinesia after exposure to a dopamine-blocking medication.

Methods

Data were pooled from three 6-week, double-blind, placebo-controlled trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), and KINECT 3 (NCT02274558). Data from the 42-week valbenazine extension period of KINECT 3 were also analyzed. Outcomes of interest included cardiovascular-related treatment-emergent adverse events, vital sign measurements, and electrocardiogram parameters.

Results

The pooled safety population included 400 participants (placebo, n = 178; valbenazine 40 mg/day, n = 110; valbenazine 80 mg/day, n = 112). A history of cardiac disorders was present in 11.8% of participants, and 74.3% were taking a concomitant medication with known potential for QT prolongation. Mean changes from baseline to week 6 in supine vital signs and QTcF (Fridericia correction) were as follows for placebo, valbenazine 40 mg/day, and valbenazine 80 mg/day, respectively: systolic blood pressure (0.2, − 2.1, − 1.8 mmHg), diastolic blood pressure (− 0.1, − 1.6, − 1.2 mmHg), heart rate (− 1.7, − 2.2, − 1.7 bpm), QTcF interval (1.2, 1.1, 2.1 ms); all p > 0.05 for valbenazine vs. placebo. No statistically significant differences were observed between placebo and valbenazine in cardiovascular-related, treatment-emergent adverse events. No notable additional effects on cardiovascular outcomes were found with up to 48 weeks of valbenazine treatment.

Conclusions

Results from double-blind, placebo-controlled trials showed no apparent difference between valbenazine and placebo on cardiovascular outcomes. No additional cardiovascular risk was detected during a longer extension study with valbenazine.

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Management Strategies to Facilitate Optimal Outcomes for Patients Treated with Delayed-release Dimethyl Fumarate

Abstract

Delayed-release dimethyl fumarate is an oral disease-modifying therapy that has demonstrated significant efficacy in adults with relapsing–remitting multiple sclerosis. Incidences of flushing and gastrointestinal adverse events are common in the first month after delayed-release dimethyl fumarate initiation. Our objective was to propose mitigation strategies for adverse events related to initiation of delayed-release dimethyl fumarate in the treatment of patients with multiple sclerosis. Studies of individually developed mitigation strategies and chart reviews were evaluated. Those results, as well as mitigation protocols developed at multiple sclerosis care centers, are summarized. Key steps to optimize the effectiveness of delayed-release dimethyl fumarate treatment include education prior to and at the time of delayed-release dimethyl fumarate initiation, initiation dose protocol gradually increasing to maintenance dose, dietary suggestions for co-administration with food, gastrointestinal symptom management with over-the-counter medications, flushing symptom management with aspirin, and temporary dose reduction. Using the available evidence from clinical trials and evaluations of post-marketing studies, these strategies to manage gastrointestinal and flushing symptoms can be effective and helpful to the patient when initiating delayed-release dimethyl fumarate.

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Spin-Crossover Materials: Magnetic Susceptibility Study of Sub-Pico-emu Sample Using a Micromagnetometer: An Investigation through Bistable Spin-Crossover Materials (Adv. Mater. 46/2017)

Spin switching in a nanosized material without an external applied magnetic field can be evidenced using a highly sensitive sub-picoemu magnetometer working at room temperature. In article 1703073, CheolGi Kim, Azzedine Bousseksou, Ferial Terki, and co-workers present an advanced approach based on an induced AC magnetic field and discuss nanoscale magnetic signatures with a resolution of 4 × 10⁻¹⁴ emu at room temperature.

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Masthead: (Adv. Mater. 46/2017)

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Humidity Sensors: Multiscale Humidity Visualization by Environmentally Sensitive Fluorescent Molecular Rotors (Adv. Mater. 46/2017)

In article number 1703900, Ben Zhong Tang and co-workers present a visual-sensing approach based on fluorescence imaging by assembling aggregation-induced emission (AIE)-active molecular rotors into a moisture-captured network; the resulting AIE humidity sensors are compatible with diverse applications given their tunable geometries and desirable architectures. The invisible information of relative humidity (RH) is transformed into different fluorescence colors, which enables direct observation by the naked eye. Multiscale applications, such as regional environmental RH detection, internal humidity mapping, and sensitive human-body humidity sensing, are demonstrated.

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Contents: (Adv. Mater. 46/2017)

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Osteopromotive Coatings: Diatom-Inspired Silica Nanostructure Coatings with Controllable Microroughness Using an Engineered Mussel Protein Glue to Accelerate Bone Growth on Titanium-Based Implants (Adv. Mater. 46/2017)

Silica nanoparticles can be utilized to construct nanostructures comprising surface topographic features and osteoinductivity. In article number 1704906, Chang Sup Kim, Hyung Joon Cha, and co-workers describe a diatom-inspired silica-nanoparticle nanostructure coating with controllable micro-roughness on titanium surfaces through the multilayer assembly of an organic–inorganic composite using an engineered silica-forming mussel protein glue, which enhances osteogenic cell behavior in a roughness-dependent manner, as well as promotes bone-tissue formation and maturation.

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Cell-Membrane Engineering: Engineering Cell Surface Function with DNA Origami (Adv. Mater. 46/2017)

DNA-origami nanodevices are embedded on the membrane of two cells by Jonathan W. Song, Carlos E. Castro, and co-workers in article number 1703632. The devices are anchored to the cell via a DNA base-pairing attachment to a cholesterol-labeled DNA strand embedded in the membrane. The two pairs of nanostructures (shown here on the right) mediate adhesion between the cells via a sequence-specific DNA binding interaction.

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Nanofluidic Channels: Engineering 2D Nanofluidic Li-Ion Transport Channels for Superior Electrochemical Energy Storage (Adv. Mater. 46/2017)

In article number 1703909, Gang Chen, Guihua Yu, and co-workers present a novel concept of 2D nanofluidic lithium-ion transport channels based on stacked Co₃O₄ nanosheets for high-performance lithium batteries. This unique nanoarchitecture exhibits exceptional capacity and outstanding long-term cycling stability for lithium-ion storage at high-rates in both half- and full-cells.

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Discrimination of Schisandrae Chinensis Fructus and Schisandrae Sphenantherae Fructus based on fingerprint profiles of hydrophilic components by high-performance liquid chromatography with ultraviolet detection

Abstract

High-performance liquid chromatography with ultraviolet detection (HPLC–UV) using 20 mM phosphate mobile phase and an octadecylsilyl column (Triart C18, 150 × 3.0 mm i.d., 3 μm) has been developed for the analysis of hydrophilic compounds in the water extract of Schisandrae Fructus samples. The present HPLC–UV method permits the accurate and precise determination of malic, citric, and protocatechuic acids in the Japanese Pharmacopoeia (JP) Schisandrae Fructus, Schisandrae Chinensis Fructus and Schisandrae Sphenantherae Fructus. The JP Schisandrae Fructus studied contains 27.98 mg/g malic, 107.08 mg/g citric, and 0.42 mg/g protocatechuic acids, with a relative standard deviation (RSD) of repeatability of <0.9% (n = 6). The content of malic acids in Schisandrae Chinensis Fructus is approximately ten times that in Schisandrae Sphenantherae Fructus. To examine whether the HPLC–UV method is applicable to the fingerprint-based discrimination of Schisandrae Fructus samples obtained from Chinese markets, principal component analysis (PCA) was performed using the determined contents of organic acids and the ratio of six characteristic unknown peaks derived from hydrophilic components to internal standard peak areas. On the score plots, Schisandrae Chinensis Fructus and Schisandrae Sphenantherae Fructus samples are clearly discriminated. Therefore, the HPLC–UV method for the analysis of hydrophilic components coupled with PCA has been shown to be practical and useful in the quality control of Schisandrae Fructus.

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Noisy Commutes Could Cause Long-Lasting Damage

Title: Noisy Commutes Could Cause Long-Lasting DamageCategory: Health NewsCreated: 12/4/2017 12:00:00 AMLast Editorial Review: 12/5/2017 12:00:00 AM (Source: MedicineNet Hearing General)

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Identification and analysis of Eimeria nieschulzi gametocyte genes reveal splicing events of gam genes and conserved motifs in the wall-forming proteins within the genus Eimeria (Coccidia, Apicomplexa).

Identification and analysis of Eimeria nieschulzi gametocyte genes reveal splicing events of gam genes and conserved motifs in the wall-forming proteins within the genus Eimeria (Coccidia, Apicomplexa).

Parasite. 2017;24:50

Authors: Wiedmer S, Erdbeer A, Volke B, Randel S, Kapplusch F, Hanig S, Kurth M

Abstract
The genus Eimeria (Apicomplexa, Coccidia) provides a wide range of different species with different hosts to study common and variable features within the genus and its species. A common characteristic of all known Eimeria species is the oocyst, the infectious stage where its life cycle starts and ends. In our study, we utilized Eimeria nieschulzi as a model organism. This rat-specific parasite has complex oocyst morphology and can be transfected and even cultivated in vitro up to the oocyst stage. We wanted to elucidate how the known oocyst wall-forming proteins are preserved in this rodent Eimeria species compared to other Eimeria. In newly obtained genomics data, we were able to identify different gametocyte genes that are orthologous to already known gam genes involved in the oocyst wall formation of avian Eimeria species. These genes appeared putatively as single exon genes, but cDNA analysis showed alternative splicing events in the transcripts. The analysis of the translated sequence revealed different conserved motifs but also dissimilar regions in GAM proteins, as well as polymorphic regions. The occurrence of an underrepresented gam56 gene version suggests the existence of a second distinct E. nieschulzi genotype within the E. nieschulzi Landers isolate that we maintain.

PMID: 29210668 [PubMed - in process]

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Scharfrandige Erosionen und Ulzerationen im Anschluss an ein Arzneimittelexanthem nach Sultamicillin-Gabe

Zusammenfassung

Es wird über den Fall einer Patientin mit neu aufgetretenen Erosionen und Ulzerationen im Anschluss an ein Arzneimittelexanthem durch Sultamicillin berichtet. Die Effloreszenzen traten nach topischer Behandlung mit Clobetasol und Prednicarbat sowie systemischer Gabe von Methylprednisolon auf. Im Hautabstrich wurden massiv Escherichia-coli-Bakterien nachgewiesen. Blutkulturen waren unauffällig. Ursächlich für Ecthymata gangraenosa bei unserer Patientin war eine iatrogene Immunsuppression bei transienter Bakteriämie.

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How frequent does peri-implantitis occur? A systematic review and meta-analysis

Abstract

Objectives

The objective of this study is to estimate the overall prevalence of peri-implantitis (PI) and the effect of different study designs, function times, and implant surfaces on prevalence rate reported by the studies adhering to the case definition of Sanz & Chapple 2012.

Material and methods

Following electronic and manual searches of the literature published up to February 2016, data were extracted from the studies fitting the study criteria. Meta-analysis was performed for estimation of overall prevalence of PI while the effects of the study design, function time, and implant surface type on prevalence rate were investigated using meta-regression method.

Results

Twenty-nine articles were included in this study. The prevalence rate in all subset meta-analyses was always higher at patient level when compared to the prevalence rate at the implant level. Prevalence of PI was 18.5% at the patient level and 12.8% at the implant level. Meta-regression analysis did not identify any association for different study designs and function times while it was demonstrated the significant association between moderately rough surfaces with lower prevalence rate of PI (p = 0.011).

Conclusions

The prevalence rate of PI remains highly variable even following restriction to the clinical case definition and it seems to be affected by local factors such as implant surface characteristics. The identification of adjuvant diagnostic markers seems necessary for more accurate disease classification.

Clinical relevance

The occurrence of PI is affected by local factors such as implant surface characteristics hence the careful assessment of the local factors should be performed within treatment planning.

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Correction: Albträume: Ätiologie, Prävalenzen, gesundheitliche Folgen und Behandlungsansätze

Correction:

Somnologie 2015

http://ift.tt/2k5RIqz

Bei diesem Beitrag wurde der Zweitautor, Jan-Christopher Gumm, Humboldt-Universität zu Berlin, Berlin, Deutschland, vergessen.

Wir bitten, diesen Fehler zu entschuldigen.

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Suppressive oligodeoxynucleotides containing TTAGGG motifs Inhibit cGAS activation in human monocytes

Abstract

Type I interferon (IFN) is a critical mediator of autoimmune diseases such as systemic lupus erythematosus (SLE) and Aicardi–Goutières Syndrome (AGS). The recently discovered cyclic-GMP-AMP (cGAMP) synthase (cGAS) induces the production of type I IFN in response to cytosolic DNA and is potentially linked to SLE and AGS. Suppressive oligodeoxynucleotides (ODN) containing repetitive TTAGGG motifs present in mammalian telomeres have proven useful in the treatment of autoimmune diseases including SLE. In this study, we demonstrate that the suppressive ODN A151 effectively inhibits activation of cGAS in response to cytosolic DNA, thereby inhibiting type I IFN production by human monocytes. In addition, A151 abrogated cGAS activation in response to endogenous accumulation of DNA using TREX1-deficient monocytes. We demonstrate that A151 prevents cGAS activation in a manner that is competitive with DNA. This suppressive activity of A151 was dependent on both telomeric sequence and phosphorothioate backbone. To our knowledge this report presents the first cGAS inhibitor capable of blocking self-DNA. Collectively, these findings might lead to the development of new therapeutics against IFN-driven pathologies due to cGAS activation.

This article is protected by copyright. All rights reserved

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Correction to: Acute and chronic neuromuscular adaptations to local vibration training

Abstract

The author would like to correct the reference in the publication of the original article. The corrected reference is given below for your reading.

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Kreisleriana (1814/15)

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Vertragsrechtliche Anforderungen an die Gestaltung von „Self-Tracking“-Tarifen in der Privatversicherung

Zusammenfassung

Mit der zunehmenden Digitalisierung des Alltags wird „Self Tracking", die Erhebung eigener Vital- und Verhaltensdaten durch technische Hilfsmittel, zu einem Massenphänomen, das auch Versicherer zur Optimierung ihrer Kalkulation und Personalisierung ihrer Produkte nutzen können. Der folgende Beitrag untersucht den Self-Tracking-Tarif, einen Tarif, der durch Self-Tracking-Daten dokumentiertes, risikobewusstes Verhalten des Versicherungsnehmers mit einem Prämiennachlass honoriert. Für die Vertragsgestaltung stehen dem Versicherer hier zwei Grundformen zur Auswahl, der Self-Tracking-Tarif mit Prämienanpassungsklausel und der Self-Tracking-Tarif im Überschussbeteiligungsmodell. Der Beitrag zeigt, welche Anforderungen insbesondere das AGB-Recht an die jeweilige Form des Self-Tracking-Tarifs stellt und inwieweit eine Trennung von Versicherungsvertrag und Self-Tracking-Abreden zulässig ist.

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Efficacy of Secukinumab in the Treatment of Moderate to Severe Plaque Psoriasis in the North American Subgroup of Patients: Pooled Analysis of Four Phase 3 Studies

Abstract

Introduction

Demographic and disease characteristics may impact response to psoriasis therapies. The objective of this study is to explore the safety and efficacy profile of secukinumab in North American (NA) versus non-NA patients with moderate to severe psoriasis.

Methods

Data were pooled from four phase 3 studies of secukinumab. Secukinumab (300 and 150 mg) was administered at baseline, weeks 1, 2, and 3, then every 4 weeks from week 4 to 48.

Results

Peak efficacy was observed at week 16 in NA and non-NA patients with secukinumab 300 mg and secukinumab 150 mg, and disease clearance was maintained to week 52. At week 52 with secukinumab 300 mg, Psoriasis Area and Severity Index (PASI) 90/100 response was achieved by 62.9%/37.9% of NA patients, respectively, and 70.2%/42.0% of non-NA patients, respectively. At week 52 with secukinumab 150 mg, PASI 90/100 response was achieved by 30.9%/17.5% of NA patients, respectively, and 53.9%/26.9% of non-NA patients, respectively. Response to secukinumab was rapid, and 50% reduction in mean PASI was achieved in both groups after 2.9 weeks with secukinumab 300 mg and 3.7 weeks with secukinumab 150 mg.

Conclusion

Despite differences in baseline characteristics, the efficacy and safety of secukinumab were similar among NA and non-NA patients.

Funding

Novartis Pharma AG.

Plain Language Summary

Plain language summary available for this article.

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Retrocochlear impairments in systemic sclerosis: a case report study

RESUMO Objetivo Relatar três casos de pacientes portadores de Esclerose Sistêmica e que apresentaram alterações retrococleares. Método Trata-se de um estudo de relato de casos de três indivíduos com esclerose sistêmica e alteração retrococlear, acompanhados em um serviço de reumatologia. Todos os pacientes realizaram o Potencial Evocado Auditivo de Tronco Encefálico e, quando necessário, nova audiometria. Resultados Todos os indivíduos apresentaram perda auditiva do tipo sensorioneural. Não foi identificado na avaliação audiológica básica qualquer resultado que sugerisse alteração retrococlear, porém o PEATE apresentou-se alterado. Conclusão Pode-se concluir que o estudo revela alterações retrococleares nesta população, ocorrendo tanto nas latências absolutas quanto no intervalo interpico. E, neste contexto, reumatologistas e fonoaudiólogos, ao acompanharem pacientes com esclerose sistêmica, devem estar atentos para a possibilidade da ocorrência dessa alteração nessa população. Revela também, a necessidade de estudos epidemiológicos sobre o tema.

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ABSTRACT Purpose To report three cases of patients with Systemic Sclerosis (SSc) and retrocochlear impairments. Methods This is a case report of three individuals with SSc and retrocochlear impairments assisted at a rheumatology outpatient clinic. All individuals underwent Brainstem Auditory Evoked Potential (BAEP) and, when necessary, audiometry. Results All three individuals presented sensorineural hearing loss. Although no retrocochlear impairment was identified in the basic audiologic evaluation, the BAEP results were altered. Conclusion Retrocochlear impairments were present in the individuals under study, both in the absolute latencies and interpeak interval, thereby demanding the attention of rheumatologists and speech-language pathologists to such changes during the monitoring of SSc patients. The results also show a need for epidemiological studies on the theme.

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IJMS, Vol. 18, Pages 2652: Joint Effects of PON1 Polymorphisms and Vegetable Intake on Ischemic Stroke: A Family-Based Case Control Study

IJMS, Vol. 18, Pages 2652: Joint Effects of PON1 Polymorphisms and Vegetable Intake on Ischemic Stroke: A Family-Based Case Control Study

International Journal of Molecular Sciences doi: 10.3390/ijms18122652

Authors: Juan Juan Xia Jiang Xun Tang Yiqun Wu Kexin Sun Xiao Xiang Yaohua Tian Tao Wu Qi Sun Peter Kraft Yonghua Hu

Paraoxonase 1 gene (PON1) polymorphisms and dietary vegetable and fruit intake are both established determinants of ischemic stroke (IS). However, little is known about whether these factors jointly influence the risk of IS. We analyzed the main effects of PON1, as well as the interactions between PON1 and dietary vegetable or fruit intake with the risk of total IS and its subtypes in a family-based case-control study conducted among 2158 Chinese participants (1007 IS cases and 1151 IS-free controls) from 918 families. Conditional logistic regression models, with each family as a stratum, were used to examine the association between rs662 and IS. Gene-diet interactions were tested by including a cross-product term of dietary vegetable or fruit intake by rs662_G allele count in the models. Each copy of the PON1 rs662_G allele was associated with 28% higher risk of total IS (p = 0.008) and 32% higher risk of large artery atherosclerosis subtype (LAA) (p = 0.01). We observed an interaction between rs662 and vegetable intake for both total IS (p = 0.006) and LAA (p = 0.02) after adjustment for covariates. Individuals who carry the rs662_A allele may benefit to a greater extent from intake of vegetables and thus be more effectively protected from ischemic stroke, whereas carriers of the G allele may still remain at greater risk for ischemic stroke due to their genetic backgrounds even when they consume a high level of vegetables. More studies are needed to replicate our findings among other populations.

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Limb apraxia and aphasia

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Limb apraxia in aphasic patients

ABSTRACT Limb apraxia is usually associated with left cerebral hemisphere damage, with numerous case studies involving aphasic patients. The aim of this study was to verify the occurrence of limb apraxia in aphasic patients and analyze its nature. This study involved 44 healthy volunteers and 28 aphasic patients matched for age and education. AH participants were assessed using a limb apraxia battery comprising subtests evaluating lexical-semantic aspects related to the comprehension/production of gestures as well as motor movements. Aphasics had worse performances on many tasks related to conceptual components of gestures. The difficulty found on the imitation of dynamic gesture tasks also indicated that there were specific motor difficulties in gesture planning. These results reinforce the importance of conducting limb apraxia assessment in aphasic patients and also highlight pantomime difficulties as a good predictor for semantic disturbances.

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RESUMO A apraxia de membros está frequentemente associada com lesões do hemisfério esquerdo, com inúmeros casos de pacientes afásicos. O objetivo deste estudo foi verificar a ocorrência da apraxia de membros em pacientes afásicos bem como a natureza desse distúrbio. O estudo foi realizado com 28 indivíduos afásicos e 44 controles pareados segundo a idade e a escolaridade. Todos os participantes foram avaliados com uma extensa bateria de apraxia de membros, consistindo de subtestes que avaliaram a compreensão e a produção dos aspectos léxico-semânticos relacionados aos gestos bem como produção motora propriamente dita. Os pacientes afásicos apresentaram dificuldades em tarefas envolvendo aspectos conceptuais da produção gestual. A dificuldade encontrada na imitação de gestos dinâmicos também indicou déficits no processamento gestual independente do déficit conceptual observado nestes pacientes. Esses resultados reforçam a importância da avaliação da apraxia de membros e apontam para a dificuldade de realização de pantomimas como indicativa de déficits semânticos.

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Impact of disease duration on functional status of patients with spinocerebellar ataxia type 2

ABSTRACT Objective: To correlate disease duration in spinocerebellar ataxia type 2 (SCA2) with disease severity, balance and functionality. Method: Sixteen SCA2 patients were analyzed for: disease duration, disease severity (SARA score), balance (Berg balance scale score) and functionality (FIM and Lawton scores). Results: Greater severity was correlated with worse functionality (Lawton: r = −0.0561, FIM: r = −0.6402) and balance (r = −0.7188). Longer disease duration was correlated with greater severity (p = 0.0002) and reduced functionality (FIM: p = 0.005; Lawton: p = 0.0402) and balance (p = 0.0036). A year increase in disease duration corresponded to a 0.8-point increase on the SARA scale, a 1.38-point decrease in FIM score, a 2.30-point decrease on the Berg balance scale and a 0.45-point decrease on the Lawton scale. Conclusion: Longer disease duration in this series of SCA2 patients was correlated with greater disease severity, worse balance and greater functional dependency.

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RESUMO Objetivo: Correlacionar com o tempo de evolução da doença em pacientes com ataxia espinocerebelar do tipo 2 (SCA2) com a gravidade, equilíbrio e funcionalidade. Método: Foram considerados dados de 16 indivíduos: tempo de evolução, nível de gravidade (SARA) e escores de equilíbrio (BERG) e funcionalidade (MIF e LAWTON). Resultados: A maior gravidade esteve relacionada aos piores escores de funcionalidade (LAWTON: r = −0,0561, MIF: r = −0,6402) e de equilíbrio (r = −0,7188). O maior tempo de evolução esteve relacionado à maior gravidade (p = 0,0002) e menor funcionalidade (MIF: p = 0,005; Lawton (p = 0,0402) e equilíbrio (p = 0,0036) sendo que para o aumento de um ano no tempo de evolução, espera-se um aumento de 0,8 pontos no escore da SARA, e decréscimo de 1,38 pontos na MIF, 2,30, na Berg e 0,45 na Lawton. Conclusão: O tempo de evolução dos sintomas está associado a maior gravidade da doença, pior equilíbrio e maior dependência funcional em pacientes comSCA2.

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Integrity of white matter structure is related to episodic memory performance in the low-educated elderly

ABSTRACT The low-educated elderly are a vulnerable population in whom studying the role of white matter integrity on memory may provide insights for understanding how memory declines with aging and disease. Methods: Thirty-one participants (22 women), 23 cognitively healthy and eight with cognitive impairment-no dementia, aged 80.4 ± 3.8 years, with 2.2 ± 1.9 years of education, underwent an MRI scan with diffusion tensor imaging (DTI) acquisition. We verified if there were correlations between the performance on the Brief Cognitive Screening Battery (BCSB) and the Rey Auditory Verbal Learning Test (RAVLT) with DTI parameters. Results: The BCSB delayed recall task correlated with frontotemporoparietal connection bundles, with the hippocampal part of the cingulum bilaterally and with the right superior longitudinal fasciculus. The RAVLT learning and delayed recall scores also correlated with the hippocampal part of the cingulum bilaterally. Conclusions: Although preliminary, our study suggests that the integrity of white matter frontotemporoparietal fasciculi seems to play a role in episodic memory performance in the low-educated elderly. This finding opens opportunities to study potential targets for memory decline prevention in vulnerable populations.

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RESUMO Idosos de baixo nível educacional representam uma população vulnerável em que o estudo do papel da integridade da substância branca na memória pode revelar como essa declina no envelhecimento. Métodos: Trinta e um indivíduos (22 mulheres), sendo 23 cognitivamente saudáveis, oito com comprometimento cognitivo não demência, 80,4 ± 3,8 anos de idade e 2,2 ± 1,9 anos de escolaridade, foram submetidos à RM com imagem de tensor de difusão, cujos parâmetros foram correlacionados com a Bateria Cognitiva Breve (BCSB) e o Teste Auditivo Verbal de Rey (RAVLT). Resultados: A evocação tardia da BCSB correlacionou-se com fascículos de conexão frontotemporoparietal, fascículo longitudinal superior direito e cíngulo parte hipocampal bilateral, sendo que esse último também correlacionou com o RAVLT (aprendizado e evocação tardia). Conclusão: Apesar de preliminar, nosso estudo sugere que a integridade da substância branca parece ser importante para a memória em idosos de baixa escolaridade, achado que revela alvo potencial na prevenção do seu declínio em populações vulneráveis.

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The critical influence of nocturnal breathing complaints on the quality of sleep after stroke: the Pittsburgh Sleep Quality Index and STOP-BANG

ABSTRACT In stroke patients particularly, many factors, such as sleep-related respiratory disturbances, can impair sleep. Cheap and easy-to-use tools have been created to identify sleep quality and sleep disturbances in patients after stroke. This study described the scores of the sleep apnea screening questionnaire - STOP-BANG - in patients after a stroke, and correlated the findings with sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI). The scores of the STOP-BANG and PSQI were 4.3 ± 1.8 and 76 ± 3.9, respectively. The STOP-BANG scores were higher in poor sleepers (4.5 ± 1.6 versus 3.5 ± 1.9; p = 0.032). Logistic regression analysis was used to identify predictors of subjective sleep quality (PSQI) and the STOP-BANG as a predictor of poor quality sleep, with a relative risk of 1.6, controlled for age and sex. This study indicated that sleep quality was largely influenced by sleep breathing problems, which were well identified by the STOP-BANG, especially in younger stroke patients.

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RESUMO Especialmente em pacientes com acidente vascular cerebral (AVC), muitos fatores prejudicam o sono, como distúrbios respiratórios do sono (DRS). Ferramentas mais baratas foram usadas para identificar a qualidade do sono e distúrbios do sono após AVC. Este estudo verificou a influência das queixas DRS na qualidade do sono após AVC utilizando questionários. Nós investigamos a qualidade do sono eo risco de Apneia Obstrutiva do Sono com o Índice de Qualidade do Sono de Pittsburgh (PSQI) e Stop-Bang em 68 pacientes após AVC. As pontuações de STOP-BANG e PSQI foram de 4,3 ± 1,8 e 7,6 ± 3,9, respectivamente. As pontuações de STOP-BANG foram mais elevadas em pacientes com sono ruim (4,5 ± 1,6 versus 3,5 ± 1,9; p = 0,032). A regressão logística caracterizou o STOP-BANG como preditor de um sono de má qualidade. Estes achados confirmam a influência das queixas respiratórias noturnas na qualidade do sono após AVC.

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The relative frequency of common neuromuscular diagnoses in a reference center

ABSTRACT The diagnostic procedure in neuromuscular patients is complex. Knowledge of the relative frequency of neuromuscular diseases within the investigated population is important to allow the neurologist to perform the most appropriate diagnostic tests. Objective: To report the relative frequency of common neuromuscular diagnoses in a reference center. Methods: A 17-year chart review of patients with suspicion of myopathy. Results: Among 3,412 examinations, 1,603 (46.98%) yielded confirmatory results: 782 (48.78%) underwent molecular studies, and 821 (51.21%) had muscle biopsies. The most frequent diagnoses were: dystrophinopathy 460 (28.70%), mitochondriopathy 330 (20.59%), spinal muscular atrophy 158 (9.86%), limb girdle muscular dystrophy 157 (9.79%), Steinert myotonic dystrophy 138 (8.61%), facioscapulohumeral muscular dystrophy 99 (6.17%), and other diagnoses 261 (16.28%). Conclusion: Using the presently-available diagnostic techniques in this service, a specific limb girdle muscular dystrophy subtype diagnosis was reached in 61% of the patients. A neuromuscular-appropriate diagnosis is important for genetic counseling, rehabilitation orientation, and early treatment of respiratory and cardiac complications.

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RESUMO O procedimento diagnóstico neuromuscular é complexo. O conhecimento da frequência relativa das doenças neuromusculares em uma população é importante para utilização dos testes diagnósticos mais apropriados. Objetivo: Relatar a frequência relativa de doenças neuromusculares em um centro de referência. Métodos: Revisão de prontuários de pacientes com suspeita de miopatia em 17 anos. Resultados: Dentre 3412 exames, 1603 (46,98%) foram confirmatórios: 782 (48,78%) estudos moleculares e 821 (51,21%) biópsias musculares. Os diagnósticos mais frequentes foram: distrofinopatia 460 (28,70%), mitocondriopatia 330 (20.59%), atrofia muscular espinhal 158 (9,86%), distrofia muscular cintura-membros 157 (9,79%), distrofia miotônica de Steinert 138 (8,61%), distrofia muscular face-escápulo-umeral 99 (6,17%) e outros diagnósticos 261 (16,28%). Conclusão: Utilizando as técnicas diagnósticas atualmente disponíveis em nosso serviço, o diagnóstico específico do subtipo de distrofia muscular cintura-membros foi obtido em 61% dos pacientes. O diagnóstico neuromuscular apropriado é importante para o aconselhamento genético, orientações de reabilitação e tratamento precoce de complicações respiratórias e cardíacas.

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Transtemporal amygdalohippocampectomy: a novel minimally-invasive technique with optimal clinical results and low cost

ABSTRACT Mesial temporal sclerosis creates a focal epileptic syndrome that usually requires surgical resection of mesial temporal structures. Objective: To describe a novel operative technique for treatment of temporal lobe epilepsy and its clinical results. Methods: Prospective case-series at a single institution, performed by a single surgeon, from 2006 to 2012. A total of 120 patients were submitted to minimally-invasive keyhole transtemporal amygdalohippocampectomy. Results: Of the patients, 55% were male, and 85% had a right-sided disease. The first 70 surgeries had a mean surgical time of 2.51 hours, and the last 50 surgeries had a mean surgical time of 1.62 hours. There was 3.3% morbidity, and 5% mild temporal muscle atrophy. There was no visual field impairment. On the Engel Outcome Scale at the two-year follow-up, 71% of the patients were Class I, 21% were Class II, and 6% were Class III. Conclusion: This novel technique is feasible and reproducible, with optimal clinical results.

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RESUMO A esclerose mesial temporal é uma síndrome epiléptica focal que requer ablação de estruturas mesiais temporais. Objetivo: Descrever e padronizar a técnica operatória e resultados clínicos. Métodos: Série prospectiva de casos de uma única instituição, realizadas por um único cirurgião, de 2006 a 2012. 120 doentes foram submetidos a amigdalo-hipocampectomia transtemporal por acesso mínimo (keyhole). Resultados: 55% eram do sexo masculino, 85% apresentavam doença do lado direito. As primeiras 70 cirurgias tiveram um tempo cirúrgico médio de 2,51 horas, e as últimas 50 cirurgias tiveram um tempo cirúrgico médio de 1,62 horas. Houve morbidade de 3,3%. 5% dos doentes apresentaram atrofia leve de músculo temporal. O controle das convulsões foi avaliado com a Escala de Engel no segundo ano de pós operatorio, 71% eram Classe I, 21% Classe II, 6% Classe III. Conclusão: Esta nova técnica é viável, reprodutível e com resultados clínicos adequados.

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The number of burr holes and use of a drain do not interfere with surgical results of chronic subdural hematomas

ABSTRACT Burr hole evacuation has been the most frequently-used procedure for the treatment of chronic subdural hematomas (CSDH). Objective: To evaluate whether the use of a drain and/or the number of burr holes for treatment of CSDH modifies the rates of recurrence and complications. Methods: A retrospective review of 142 patients operated on because of CSDH, between 2006 and 2015, analyzing recurrence and complications of the use of one or two burr holes with or without the use of a drain. Results: Thirty-seven patients had bilateral CSDH (26%) and 105 (73.9%) patients had unilateral CSDH. Twenty-two (59.4%) patients were given a drain and 15 (40.6%) were not. A total number of recurrences occurred in 22 (15.5%) patients and the total number of complications was in six (4.2%) patients. Mean follow-up time was 7.67 months. Conclusions: The number of burr holes and the use of the drain did not alter the rates of recurrence and complications in the treatment of CSDH.

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RESUMO A trepanação é o procedimento mais utilizado para o tratamento de hematomas subdurais crônicos (HSDC). Objetivo: Avaliar o uso de dreno subdural e / ou o número de trepanações para tratamento de HSDC modifica as taxas de recidiva e complicações. Métodos: Uma revisão retrospectiva de 142 pacientes operados por HSDC entre 2006 e 2015 analisando recidiva e complicações usando um ou dois orifícios com ou sem uso de dreno. Resultados: Trinta e sete casos apresentaram HSDC bilaterais (26%) e 105 (73,9%) unilaterais. Em vinte e dois (59,4%) casos houve uso de dreno e em 15 (40,6%) não houve. O número total de recidivas foi de 22 casos (15,5%) e o número total de complicações foi de 6 casos (4,2%). O tempo médio de seguimento foi de 7,67 meses. Conclusões: O número de trepanações e o uso do dreno não alteraram as taxas de recidiva e complicações no tratamento de HSDC.

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Hereditary spastic paraplegia from 1880 to 2017: an historical review

ABSTRACT The authors have constructed a brief timeline of major clinical research related to hereditary spastic paraplegia (HSP). This timeline summarizes the evolution of HSP research, from the first clinical descriptions by Adolf von Strümpell in 1880 to the present day, with the transformation of these diseases into a rapidly-growing and heterogeneous group of neurogenetic diseases.

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RESUMO Os autores constroem uma breve linha do tempo com as principais pesquisas clinicas relacionadas as paraplegias espásticas hereditárias. Desde a descrição clínica inicial em 1880, feita por Adolf von Strümpell, até os dias atuais com a transformação dessas doenças em um grupo de doenças neurogenéticas com grande variabilidade na apresentação fenotípica e genotípica.

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Conservative therapeutic management of carpal tunnel syndrome

ABSTRACT Carpal tunnel syndrome is the most prevalent nerve compression and can be clinically or surgically treated. In most cases, the first therapeutic alternative is conservative treatment but there is still much controversy regarding the most effective modality of this treatment. In this study, we critically evaluated the options of conservative treatment for carpal tunnel syndrome, aiming to guide the reader through the conventional options used in this therapy.

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RESUMO A síndrome do túnel do carpo é a compressão de nervo mais prevalente e seu tratamento pode ser clínico ou cirúrgico. Na maioria dos casos o tratamento conservador é a primeira alternativa terapêutica mas ainda há muitas controvérsias a respeito do tratamento mais eficaz. Neste estudo avaliamos de forma crítica as opções de tratamento conservador da síndrome do túnel do carpo, objetivando guiar o leitor no uso racional deste tipo de terapêutica.

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Mary Broadfoot Walker: 83 years since a historical discovery

ABSTRACT Mary Broadfoot Walker was a Scottish physician who, in 1935, described in great detail the effect of an anticholinesterase drug (physostigmine) on the signs and symptoms of myasthenia gravis. An original five-minutes movie is available online and the skepticism of her contemporary British medical doctors is understandable when the drastic effect of the treatment is shown in this movie. What Mary Walker taught us, more than eight decades ago, about myasthenia gravis continues to be the basis of a pharmacological diagnostic test and treatment of this disease.

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RESUMO Mary Broadfoot Walker foi uma médica escocesa que em 1935 descreveu em grande detalhe o efeito de uma droga anticolinesterásica (fisostigmina) nos sinais e sintomas da myasthenia gravis. Um filme original com cinco minutos de duração está disponível online e a reação cética dos colegas médicos contemporâneos de Mary é compreensível dado o drástico efeito terapêutico mostrado neste filme. O que Mary Walker nos ensinou mais de oito décadas atrás continua a ser a base de um teste diagnóstico farmacológico e do tratamento da myasthenia gravis.

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Long-Term Effects of G-CSF Therapy in Cyclic Neutropenia

To the Editor: Cyclic neutropenia is a rare hematologic disease that is characterized by regular oscillations in blood neutrophil counts from normal levels (absolute neutrophil count [ANC], >1.5×109 per liter) to severe neutropenia (ANC, 9 per liter), usually with a cycle length of about 21 days.…

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Justin Curry's Favorite Theorem

The University at Albany mathematician talks about why he just can't get enough of those Platonic solids

-- Read more on ScientificAmerican.com

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A Three-Layer Network Model of Direction Selective Circuits in the Optic Tectum.

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A Three-Layer Network Model of Direction Selective Circuits in the Optic Tectum.

Front Neural Circuits. 2017;11:88

Authors: Abbas F, Triplett MA, Goodhill GJ, Meyer MP

Abstract
The circuit mechanisms that give rise to direction selectivity in the retina have been studied extensively but how direction selectivity is established in retinorecipient areas of the brain is less well understood. Using functional imaging in larval zebrafish we examine how the direction of motion is encoded by populations of neurons at three layers of the optic tectum; retinal ganglion cell axons (RGCs), a layer of superficial inhibitory interneurons (SINs), and periventricular neurons (PVNs), which constitute the majority of neurons in the tectum. We show that the representation of motion direction is transformed at each layer. At the level of RGCs and SINs the direction of motion is encoded by three direction-selective (DS) subtypes tuned to upward, downward, and caudal-to-rostral motion. However, the tuning of SINs is significantly narrower and this leads to a conspicuous gap in the representation of motion in the rostral-to-caudal direction at the level of SINs. Consistent with previous findings we demonstrate that, at the level of PVNs the direction of motion is encoded by four DS cell types which include an additional DS PVN cell type tuned to rostral-to-caudal motion. Strikingly, the tuning profile of this emergent cell type overlaps with the gap in the representation of rostral-to-caudal motion at the level of SINs. Using our functional imaging data we constructed a simple computational model that demonstrates how the emergent population of PVNs is generated by the interactions of cells at each layer of the tectal network. The model predicts that PVNs tuned to rostral-to-caudal motion can be generated via convergence of DS RGCs tuned to upward and downward motion and feedforward tuned inhibition via SINs which suppresses responses to non-preferred directions. Thus, by reshaping directional tuning that is inherited from the retina inhibitory inputs from SINs can generate a novel subtype of DS PVN and in so doing enhance the encoding of directional stimuli.

PMID: 29209178 [PubMed - in process]

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What can autism teach us about the role of sensorimotor systems in higher cognition? New clues from studies on language, action semantics, and abstract emotional concept processing

Publication date: Available online 7 December 2017
Source:Cortex
Author(s): Rachel L. Moseley, Friedemann Pulvermüller
Within the neurocognitive literature there is much debate about the role of the motor system in language, social communication and conceptual processing. We suggest, here, that autism spectrum conditions (ASC) may afford an excellent test case for investigating and evaluating contemporary neurocognitive models, most notably a neurobiological theory of action perception integration where widely-distributed cell assemblies linking neurons in action and perceptual brain regions act as the building blocks of many higher cognitive functions. We review a literature of functional motor abnormalities in ASC, following this with discussion of their neural correlates and aberrancies in language development, explaining how these might arise with reference to the typical formation of cell assemblies linking action and perceptual brain regions. This model gives rise to clear hypotheses regarding language comprehension, and we highlight a recent set of studies reporting differences in brain activation and behaviour in the processing of action-related and abstract-emotional concepts in individuals with ASC. At the neuroanatomical level, we discuss structural differences in long-distance frontotemporal and frontoparietal connections in ASC, such as would compromise information transfer between sensory and motor regions. This neurobiological model of action perception integration may shed light on the cognitive and social-interactive symptoms of ASC itself, building on and extending earlier proposals linking autistic symptomatology to motor disorder and dysfunction in action perception integration. Further investigating the contribution of motor dysfunction to higher cognitive and social impairment, we suggest, is timely and promising as it may advance both neurocognitive theory and the development of new clinical interventions for this population and others characterised by early and pervasive motor disruption.



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Spatially generalizable representations of facial expressions: Decoding across partial face samples

Publication date: Available online 6 December 2017
Source:Cortex
Author(s): Steven G. Greening, Derek G.V. Mitchell, Fraser W. Smith
A network of cortical and sub-cortical regions is known to be important in the processing of facial expression. However, to date no study has investigated whether representations of facial expressions present in this network permit generalization across independent samples of face information (e.g. eye region Vs mouth region). We presented participants with partial face samples of five expression categories in a rapid event-related fMRI experiment. We reveal a network of face-sensitive regions that contain information about facial expression categories regardless of which part of the face is presented. We further reveal that the neural information present in a subset of these regions: dorsal prefrontal cortex (dPFC), superior temporal sulcus (STS), lateral occipital and ventral temporal cortex, and even early visual cortex, enables reliable generalization across independent visual inputs (faces depicting the 'eyes only' versus 'eyes removed'). Furthermore, classification performance was correlated to behavioral performance in STS and dPFC. Our results demonstrate that both higher (e.g. STS, dPFC) and lower level cortical regions contain information useful for facial expression decoding that go beyond the visual information presented, and implicate a key role for contextual mechanisms such as cortical feedback in facial expression perception under challenging conditions of visual occlusion.



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Investigating the Differential Contributions of Sex and Brain Size to Gray Matter Asymmetry

Publication date: Available online 6 December 2017
Source:Cortex
Author(s): Florian Kurth, Paul M. Thompson, Eileen Luders
Scientific reports of sex differences in brain asymmetry – the difference between the two hemispheres – are rather inconsistent. Some studies report no sex differences whatsoever, others reveal striking sex effects, with large discrepancies across studies in the magnitude, direction, and location of the observed effects. One reason for the lack of consistency in findings may be the confounding effects of brain size as male brains are usually larger than female brains. Thus, the goal of this study was to investigate the differential contributions of sex and brain size to asymmetry with a particular focus on gray matter. For this purpose, we applied a well-validated workflow for voxel-wise gray matter asymmetry analyses in a sample of 96 participants (48 males/48 females), in which a subsample of brains (24 males/24 females) were matched for size. By comparing outcomes based on three different contrasts – all males vs. all females; all large brains vs. all small brains; matched males vs. matched females – we were able to disentangle the contributing effects of sex and brain size, to reveal true (size-independent) sex differences in gray matter asymmetry: Males show a significantly stronger rightward asymmetry than females within the cerebellum, specifically in lobules VII, VIII, and IX. This finding agrees closely with prior research suggesting sex differences in sensorimotor, cognitive and emotional function, which are all moderated by the respective cerebellar sections. No other significant sex effects were detected across the remainder of the brain.



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Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis

Despite the use of anticoagulant therapy, the post-thrombotic syndrome develops within 2 years in approximately half of patients with proximal deep-vein thrombosis. The post-thrombotic syndrome commonly causes chronic limb pain and swelling and can progress to cause major disability, leg ulcers,…

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Ecthyma Gangrenosum

Figure 1.

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Necrotizing Soft-Tissue Infections

Necrotizing fasciitis is a surgical diagnosis characterized by friability of the superficial fascia, dishwater-gray exudate, and a notable absence of pus. This and other necrotizing soft-tissue infections have multiple causes, risk factors, anatomical locations, and pathogenic mechanisms, but all…

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Mechanisms of Resistance to Neoadjuvant Chemotherapy in Breast Cancer

Metastatic cancer occurs in 30% of women who receive a diagnosis of breast cancer, although some types of breast cancer are more likely to recur than others (Figure 1). Recurrent cancer is thought to arise from tumor cells that escape from the primary breast lesion and enter the lymphatic system,…

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Contemporary Hormonal Contraception and the Risk of Breast Cancer

An estimated 140 million women worldwide use hormonal contraception; this number accounts for approximately 13% of women between the ages of 15 and 49 years. In Denmark, this percentage increased from 24% in 1995 to 39% in 2012. Estrogen promotes the development of breast cancer, the leading cancer…

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Oral Contraceptives and the Small Increased Risk of Breast Cancer

In this issue of the Journal, Mørch et al. present the results of a large prospective study of the association between the use of hormonal contraceptives and the risk of breast cancer among women in Denmark who were younger than 50 years of age. They observed a 20% higher risk among women who were…

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Closing In on Treatment for Hemophilia B

Hemophilia is an X-linked recessive genetic bleeding disorder that occurs in two major forms. Approximately 80% of patients with hemophilia have mutations in the factor VIII clotting-factor gene (hemophilia A), and approximately 20% have mutations in the factor IX clotting factor gene (hemophilia…

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Angiogenesis inhibitor; +18 new citations

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Angiogenesis inhibitor

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PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Charomers-Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery.

Charomers-Interleukin-6 Receptor Specific Aptamers for Cellular Internalization and Targeted Drug Delivery.

Int J Mol Sci. 2017 Dec 06;18(12):

Authors: Hahn U

Abstract
Interleukin-6 (IL-6) is a key player in inflammation and the main factor for the induction of acute phase protein biosynthesis. Further to its central role in many aspects of the immune system, IL-6 regulates a variety of homeostatic processes. To interfere with IL-6 dependent diseases, such as various autoimmune diseases or certain cancers like multiple myeloma or hepatocellular carcinoma associated with chronic inflammation, it might be a sensible strategy to target human IL-6 receptor (hIL-6R) presenting cells with aptamers. We therefore have selected and characterized different DNA and RNA aptamers specifically binding IL-6R. These IL-6R aptamers, however, do not interfere with the IL-6 signaling pathway but are internalized with the receptor and thus can serve as vehicles for the delivery of different cargo molecules like therapeutics. We succeeded in the construction of a chlorin e6 derivatized aptamer to be delivered for targeted photodynamic therapy (PDT). Furthermore, we were able to synthesize an aptamer intrinsically comprising the cytostatic 5-Fluoro-2'-deoxy-uridine for targeted chemotherapy. The α6β4 integrin specific DNA aptamer IDA, also selected in our laboratory is internalized, too. All these aptamers can serve as vehicles for targeted drug delivery into cells. We call them charomers-in memory of Charon, the ferryman in Greek mythology, who ferried the deceased into the underworld.

PMID: 29211023 [PubMed - in process]

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Celebrating Two Centuries of Research in Selenium Chemistry: State of the Art and New Prospective.

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Celebrating Two Centuries of Research in Selenium Chemistry: State of the Art and New Prospective.

Molecules. 2017 Dec 02;22(12):

Authors: Santi C, Bagnoli L

Abstract
In 2017, the 200th anniversary of the discovery of selenium was celebrated. In 1817, the Swedish chemists, Berzelius and Gahn, on roasting 200 kg of sulfur from a pyrite from the Falun mine, obtained about 3 g of a precipitate that they first wrongly identified as tellurium. Berzelius doubted this result and repeated the analysis some months later realizing that a new element was in his hands and he named this element Selenium (Greek: Selene, moon) in consideration of its resemblance to Tellurium (Latin: Tellus, earth). Several events were organized in the year for this special celebration and this Special Issue would like to be an additional contribution to the success of a research that, especially during the last decades, rapidly grew in different fields: synthesis, medicinal chemistry, biology, material, and environment. These studies are strongly characterized by multi- and interdisciplinary connections, and, for this reason, we collected here contributions coming from different areas and disciplines, not exclusively synthetic organic chemistry.

PMID: 29207462 [PubMed - in process]

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Endoscopic modified Lothrop procedure after failure of primary endoscopic sinus surgery: a meta-analysis.

Endoscopic modified Lothrop procedure after failure of primary endoscopic sinus surgery: a meta-analysis.

Int Forum Allergy Rhinol. 2017 Dec 06;:

Authors: Abuzeid WM, Vakil M, Lin J, Fastenberg J, Akbar NA, Fried MP, Fang CH

Abstract
BACKGROUND: The endoscopic modified Lothrop procedure (EMLP) has been used as a salvage technique for frontal sinusitis following failed endoscopic sinus surgery (ESS). We aim to examine the safety and efficacy of the EMLP following failure of primary ESS.
METHODS: All English-language publications from 2000 to 2016 reporting the use of EMLP after primary ESS were identified using the PubMed database and evaluated per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Random effects summaries of patient demographics, comorbidities, and surgical outcomes were obtained through meta-analysis.
RESULTS: Eleven studies constituting 778 patients were included and 86.5% had chronic rhinosinusitis (CRS). Mean follow-up duration was 28.4 months. The mean number of surgeries prior to EMLP was 3.5. Symptom improvement was reported in 82.3%. Subgroup analysis of 7 studies in which all 357 patients had CRS revealed a mean follow-up of 31.5 months. Symptom improvement occurred in 75.9% of cases and 23.1% experienced polyp recurrence. The cerebrospinal fluid leak rate was 2.5%. Restenosis of the neo-ostium occurred in 17.1% with complete closure occurring in 3.9% of cases. The reoperation rate after EMLP was 9.0%. Aspirin sensitivity was associated with an increased risk of cerebrospinal fluid (CSF) leak (p = 0.0339) and a reduced incidence of neo-ostium closure (p = 0.0001). Aspirin sensitivity and asthma were associated with a reduced incidence of reoperation (p ≤ 0.001) and increased symptom improvement (p < 0.005). Restenosis or closure of the frontal neo-ostium was associated with less symptom improvement (p < 0.04) but not with reoperation.
CONCLUSION: The EMLP is an effective salvage procedure for refractory frontal sinusitis based on data from higher-volume centers.

PMID: 29210504 [PubMed - as supplied by publisher]

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The "Hyperdense Paraspinal Vein" Sign: A Marker of CSF-Venous Fistula.

Related Articles

The "Hyperdense Paraspinal Vein" Sign: A Marker of CSF-Venous Fistula.

AJNR Am J Neuroradiol. 2016 Jul;37(7):1379-81

Authors: Kranz PG, Amrhein TJ, Schievink WI, Karikari IO, Gray L

Abstract
CSF-venous fistula is a recently reported cause of spontaneous intracranial hypotension that may occur in the absence of myelographic evidence of CSF leak. Information about this entity is currently very limited, but it is of potential importance given the large percentage of cases of spontaneous intracranial hypotension associated with negative myelography findings. We report 3 additional cases of CSF-venous fistula and describe the "hyperdense paraspinal vein" sign, which may aid in its detection.

PMID: 26869470 [PubMed - indexed for MEDLINE]

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Imaging Signs in Spontaneous Intracranial Hypotension: Prevalence and Relationship to CSF Pressure.

Related Articles

Imaging Signs in Spontaneous Intracranial Hypotension: Prevalence and Relationship to CSF Pressure.

AJNR Am J Neuroradiol. 2016 Jul;37(7):1374-8

Authors: Kranz PG, Tanpitukpongse TP, Choudhury KR, Amrhein TJ, Gray L

Abstract
BACKGROUND AND PURPOSE: Patients with spontaneous intracranial hypotension often exhibit low CSF pressure and changes on brain MR imaging and/or evidence of CSF leak on myelography. We investigated whether individual imaging signs of spontaneous intracranial hypotension correlate with measured CSF pressure and how frequently these 2 markers of spontaneous intracranial hypotension were concordant.
MATERIALS AND METHODS: We performed a retrospective, cross-sectional study of 99 subjects with spontaneous intracranial hypotension. Prevalence of brain and myelographic imaging signs of spontaneous intracranial hypotension was recorded. CSF pressure among subjects with or without individual imaging signs was compared by using a 2-tailed t test and ANOVA. Concordance between low CSF pressure (≤6 cm H2O) and imaging was defined as the presence of the sign in a subject with low CSF pressure or absence of the sign when pressure was not low.
RESULTS: Dural enhancement, brain sagging, and venous distension sign were present in 83%, 61%, and 75% of subjects, respectively, and myelographic evidence of CSF leak was seen in 55%. Marginal correlations between CSF pressure and brain sagging (P = .046) and the venous distension sign (P = .047) were found. Dural enhancement and myelographic evidence of leak were not significantly correlated with CSF pressure. Rates of concordance between imaging signs and low CSF pressure were generally low, ranging from 39% to 55%.
CONCLUSIONS: Brain and myelographic signs of spontaneous intracranial hypotension correlate poorly with CSF pressure. These findings reinforce the need to base the diagnosis of spontaneous intracranial hypotension on multiple diagnostic criteria and suggest the presence of patient-specific variables that influence CSF pressure in these individuals.

PMID: 26869465 [PubMed - indexed for MEDLINE]

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Clinical Firsts — Christiaan Barnard’s Heart Transplantations

Clinical firsts often trigger sensational media reporting, both celebratory and critical. Such moments highlight the promissory nature of medicine and surgery, the boldness of physicians and patients who dare to go first, the assessment of risks and benefits, and the decision to transition a…

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Cirrhosis and LI-RADS

Abstract

Chronic liver disease, irrespective of cause, can eventually lead to cirrhosis, which is the primary risk factor for developing hepatocellular carcinoma (HCC). In patients with cirrhosis or appropriate risk factors, HCC can be diagnosed by imaging with high specificity using liver imaging reporting and data system v2017, obviating the need for histologic confirmation. Confident recognition of cirrhosis by conventional imaging alone can be challenging, as radiologists are not always provided with the requisite information to determine if the patient has cirrhosis or other risk factors for HCC. Moreover, cirrhosis-associated abnormalities may impair the diagnostic accuracy of imaging for HCC. This article addresses the diagnosis of cirrhosis by non-invasive imaging and the implications of cirrhosis for imaging interpretation and accuracy.

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Advance Care Planning in an Accountable Care Organization Is Associated with Increased Advanced Directive Documentation and Decreased Costs

Journal of Palliative Medicine , Vol. 0, No. 0. (Source: Journal of Palliative Medicine)

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The Palliative Care Resource Nurses Pilot Survey: A Descriptive Report of Their Primary Palliative Care Role and Educational Needs

Journal of Palliative Medicine , Vol. 0, No. 0. (Source: Journal of Palliative Medicine)

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Pilot Study: The Effectiveness of Complex Decongestive Therapy for Lymphedema in Palliative Care Patients with Advanced Cancer

Journal of Palliative Medicine , Vol. 0, No. 0. (Source: Journal of Palliative Medicine)

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Is It Safe to Discontinue Statins? Does Stopping Statins Improve Quality of Life: Yes and No

Journal of Palliative Medicine , Vol. 0, No. 0. (Source: Journal of Palliative Medicine)

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External validity of two nomograms for predicting distant brain failure after radiosurgery for brain metastases in a bi-institutional independent patient cohort

Abstract

Patients treated with stereotactic radiosurgery (SRS) for brain metastases (BM) are at increased risk of distant brain failure (DBF). Two nomograms have been recently published to predict individualized risk of DBF after SRS. The goal of this study was to assess the external validity of these nomograms in an independent patient cohort. The records of consecutive patients with BM treated with SRS at Levine Cancer Institute and Emory University between 2005 and 2013 were reviewed. Three validation cohorts were generated based on the specific nomogram or recursive partitioning analysis (RPA) entry criteria: Wake Forest nomogram (n = 281), Canadian nomogram (n = 282), and Canadian RPA (n = 303) validation cohorts. Freedom from DBF at 1-year in the Wake Forest study was 30% compared with 50% in the validation cohort. The validation c-index for both the 6-month and 9-month freedom from DBF Wake Forest nomograms was 0.55, indicating poor discrimination ability, and the goodness-of-fit test for both nomograms was highly significant (p < 0.001), indicating poor calibration. The 1-year actuarial DBF in the Canadian nomogram study was 43.9% compared with 50.9% in the validation cohort. The validation c-index for the Canadian 1-year DBF nomogram was 0.56, and the goodness-of-fit test was also highly significant (p < 0.001). The validation accuracy and c-index of the Canadian RPA classification was 53% and 0.61, respectively. The Wake Forest and Canadian nomograms for predicting risk of DBF after SRS were found to have limited predictive ability in an independent bi-institutional validation cohort. These results reinforce the importance of validating predictive models in independent patient cohorts.

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upper respiratory tract infection; +37 new citations

37 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

upper respiratory tract infection

These pubmed results were generated on 2017/12/07

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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President Trump's Slur Against American Indians

Calling Elizabeth Warren "Pocahontas" re-traumatizes a population that has had more than its share

-- Read more on ScientificAmerican.com

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s8ORF2 protein of infectious salmon anaemia virus is a RNA-silencing suppressor and interacts with Salmon salar Mov10 (SsMov10) of the host RNAi machinery

Abstract

The infectious salmon anaemia virus (ISAV) is a piscine virus, a member of Orthomyxoviridae family. It encodes at least 10 proteins from eight negative-strand RNA segments. Since ISAV belongs to the same virus family as Influenza A virus, with similarities in protein functions, they may hence be characterised by analogy. Like NS1 protein of Influenza A virus, s8ORF2 of ISAV is implicated in interferon antagonism and RNA-binding functions. In this study, we investigated the role of s8ORF2 in RNAi suppression in a well-established Agrobacterium transient suppression assay in stably silenced transgenic Nicotiana xanthi. In addition, s8ORF2 was identified as a novel interactor with SsMov10, a key molecule responsible for RISC assembly and maturation in the RNAi pathway. This study thus sheds light on a novel route undertaken by viral proteins in promoting viral growth, using the host RNAi machinery.

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Company size, work-home interference, and well-being of self-employed entrepreneurs

The impact of working conditions on the health and well-being of workers of large enterprises has been widely described. This influence has not been studied as extensively in very small and medium-sized enterp...

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"Oncotarget"[jour]; +110 new citations

110 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Oncotarget"[jour]

These pubmed results were generated on 2017/12/07

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Nursing Practice: Knowledge and Care, 2nd Edition

The second edition of the successful and definitive nursing textbook, Nursing Practice is designed to support the student throughout the entire nursing degree. Structured around the latest Nursing and Midwifery Council Code of Conduct, it explores a range of clinical and professional issues that the student will need to know, in one complete and accessible volume. Thoroughly updated and with full-colour, high quality illustrations throughout, this Read More...

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Use of HuH6 and other human-derived hepatoma lines for the detection of genotoxins: a new hope for laboratory animals?

Abstract

Cell lines which are currently used in genotoxicity tests lack enzymes which activate/detoxify mutagens. Therefore, rodent-derived liver preparations are used which reflect their metabolism in humans only partly; as a consequence misleading results are often obtained. Previous findings suggest that certain liver cell lines express phase I/II enzymes and detect promutagens without activation; however, their use is hampered by different shortcomings. The aim of this study was the identification of a suitable cell line. The sensitivity of twelve hepatic cell lines was investigated in single cell gel electrophoresis assays. Furthermore, characteristics of these lines were studied which are relevant for their use in genotoxicity assays (mitotic activity, p53 status, chromosome number, and stability). Three lines (HuH6, HCC1.2, and HepG2) detected representatives of five classes of promutagens, namely, IQ and PhIP (HAAs), B(a)P (PAH), NDMA (nitrosamine), and AFB₁ (aflatoxin), and were sensitive towards reactive oxygen species (ROS). In contrast, the commercially available line HepaRG, postulated to be a surrogate for hepatocytes and an ideal tool for mutagenicity tests, did not detect IQ and was relatively insensitive towards ROS. All other lines failed to detect two or more compounds. HCC1.2 cells have a high and unstable chromosome number and mutated p53, these features distract from its use in routine screening. HepG2 was frequently employed in earlier studies, but pronounced inter-laboratory variations were observed. HuH6 was never used in genotoxicity experiments and is highly promising, it has a stable karyotype and we demonstrated that the results of genotoxicity experiments are reproducible.

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Lichen planus-like drug eruption on anti-PD-1 therapy.

Lichen planus-like drug eruption on anti-PD-1 therapy.

J Dtsch Dermatol Ges. 2017 Dec 06;:

Authors: Kratzsch D, Simon JC, Ziemer M

PMID: 29211335 [PubMed - as supplied by publisher]

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quality of care; +800 new citations

800 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

quality of care

These pubmed results were generated on 2017/12/07

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Toward Optimizing Cervical Vestibular Evoked Myogenic Potentials (cVEMP): Combining Air-Bone Gap and cVEMP Thresholds to Improve Diagnosis of Superior Canal Dehiscence.

Toward Optimizing Cervical Vestibular Evoked Myogenic Potentials (cVEMP): Combining Air-Bone Gap and cVEMP Thresholds to Improve Diagnosis of Superior Canal Dehiscence.

Otol Neurotol. 2017 Nov 28;:

Authors: Noij KS, Duarte MJ, Wong K, Cheng YS, Masud S, Herrmann BS, Curtin HD, Kanumuri VV, Guinan JJ, Kozin ED, Tarabichi O, Jung DH, Lee DJ, Rauch SD

Abstract
OBJECTIVE: To develop a novel approach combining low-frequency air-bone gap (ABG) and cervical vestibular evoked myogenic potential (cVEMP) thresholds to improve screening for superior canal dehiscence (SCD) syndrome.
STUDY DESIGN: Retrospective study.
SETTING: Tertiary care center.
PATIENTS: One hundred forty patients with SCD and 21 healthy age-matched controls were included. Ears for each patient were divided into three groups based on computed tomography (CT) findings: 1) dehiscent, 2) thin, or 3) unaffected.
MAIN OUTCOME MEASURES: cVEMP and audiometric thresholds were analyzed and differences among groups were evaluated.
RESULTS: We define the third window indicator (TWI) as the cVEMP thresholds at 500, 750, and 1000 Hz adjusted for the ABG at 250 Hz (i.e., subtracting ABG from cVEMP threshold). The TWI differentiates between dehiscent and nondehiscent control ears with a sensitivity of 82% and specificity of 100%, corresponding to a positive predictive value of 100%. ABGs and cVEMP thresholds were similar for healthy controls and patients with thin bone over the superior canal.
CONCLUSION: This is the largest study to date examining the usefulness of cVEMPs in the diagnosis of SCD. Our "third window indicator" (TWI) combines cVEMP thresholds with the ABG at 250 Hz to improve the ability to screen patients with SCD symptoms.

PMID: 29210947 [PubMed - as supplied by publisher]

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Independent component analysis for cochlear implant artifacts attenuation from electrically evoked auditory steady-state response measurements.

Independent component analysis for cochlear implant artifacts attenuation from electrically evoked auditory steady-state response measurements.

J Neural Eng. 2017 Dec 06;15(1):016006

Authors: Deprez H, Gransier R, Hofmann M, van Wieringen A, Wouters J, Moonen M

Abstract
OBJECTIVE: Electrically evoked auditory steady-state responses (EASSRs) are potentially useful for objective cochlear implant (CI) fitting and follow-up of the auditory maturation in infants and children with a CI. EASSRs are recorded in the electro-encephalogram (EEG) in response to electrical stimulation with continuous pulse trains, and are distorted by significant CI artifacts related to this electrical stimulation. The aim of this study is to evaluate a CI artifacts attenuation method based on independent component analysis (ICA) for three EASSR datasets.
APPROACH: ICA has often been used to remove CI artifacts from the EEG to record transient auditory responses, such as cortical evoked auditory potentials. Independent components (ICs) corresponding to CI artifacts are then often manually identified. In this study, an ICA based CI artifacts attenuation method was developed and evaluated for EASSR measurements with varying CI artifacts and EASSR characteristics. Artifactual ICs were automatically identified based on their spectrum.
MAIN RESULTS: For 40 Hz amplitude modulation (AM) stimulation at comfort level, in high SNR recordings, ICA succeeded in removing CI artifacts from all recording channels, without distorting the EASSR. For lower SNR recordings, with 40 Hz AM stimulation at lower levels, or 90 Hz AM stimulation, ICA either distorted the EASSR or could not remove all CI artifacts in most subjects, except for two of the seven subjects tested with low level 40 Hz AM stimulation. Noise levels were reduced after ICA was applied, and up to 29 ICs were rejected, suggesting poor ICA separation quality.
SIGNIFICANCE: We hypothesize that ICA is capable of separating CI artifacts and EASSR in case the contralateral hemisphere is EASSR dominated. For small EASSRs or large CI artifact amplitudes, ICA separation quality is insufficient to ensure complete CI artifacts attenuation without EASSR distortion.

PMID: 29211684 [PubMed - as supplied by publisher]

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Evaluating Safety Reporting in Paediatric Antibiotic Trials, 2000–2016: A Systematic Review and Meta-Analysis

Abstract

Background

There are very few options to treat multidrug-resistant bacterial infections in children. A major barrier is the duration and complexity of regulatory trials of new antibiotics. Extrapolation of safety data from adult trials could facilitate drug development for children.

Objective

We performed a systematic review on the safety of antibiotic clinical trials (CTs) in children (0–18 years) to evaluate the overall quality of safety trials conducted in children and to determine if age-specific adverse events (AEs) could be identified for specific antibiotic classes.

Data Sources

We searched the MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov electronic databases for trials conducted between 2000 and 2016.

Study Selection

All trials in which safety was declared a primary or secondary endpoint were included. Exclusion criteria were (1) topical or inhalational route of administration; (2) non-infectious conditions; (3) administration for prophylaxis rather than treatment; (4) selected population (i.e. cystic fibrosis, malignancies, HIV and tuberculosis); and (5) design other than randomized controlled trials. Trials reporting data on both adults and children were included only if paediatric results were reported separately.

Data Extraction and Synthesis

Two authors independently extracted the data. To assess the quality of published trials, the Extension for harms for Consolidated Standards of Reporting Trials (CONSORT) Statement 2004 was used.

Main Outcome and Measure

In order to quantitatively assess the rate of developing AEs by drug class, the numbers of overall and body-system-specific AEs were collected for each study arm, and then calculated per single drug class as median and interquartile range (IQR) of the proportions across CTs. The AEs most frequently reported were compared in the meta-analysis by selecting the CTs on the most represented drug classes.

Results

Eighty-three CTs were included, accounting for 27,693 children. Overall, 69.7% of CONSORT items were fully reported. The median proportion of children with any AE was 22.5%, but did not exceed 8% in any single body system. Serious drug-related AEs and drug-related discontinuations were very rare (median 0.3 and 0.9%, respectively). Limitations included the inability to stratify by age group, particularly neonates.

Conclusions and Relevance

Overall, AEs in paediatric antibiotic CTs were predictable and class-specific, and no unexpected (age-specific) side effects were identified. Smaller, open-label, dose-finding, high-quality, single-arm pharmacokinetic trials seem potentially sufficient for certain common antibiotic classes, extrapolating well-established safety profiles determined from large adult efficacy trials. This approach could reduce duration and enhance subsequent registration of urgently needed new antibiotics. This will need to be combined with enhanced methods of pharmacovigilance for monitoring of emerging AEs in routine clinical practice.

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Duplicate Type and Screen Testing: Waste in the Clinical Laboratory.

Duplicate Type and Screen Testing: Waste in the Clinical Laboratory.

Arch Pathol Lab Med. 2017 Dec 06;:

Authors: Compton ML, Szklarski PC, Booth GS

Abstract
CONTEXT: - In the United States, approximately 65 billion dollars is spent per year on clinical laboratory testing, of which 20% to 30% of all testing is deemed inappropriate. There have been multiple studies in the field of transfusion medicine regarding evidence-based transfusion practices, but limited data exist regarding inappropriate pretransfusion testing and its financial and clinical implications.
OBJECTIVE: - To assess duplicative testing practices in the transfusion medicine service.
DESIGN: - A 24-month retrospective review was performed at a 1025-bed tertiary care center, identifying all duplicate type and screen (TS) tests performed within 72 hours of the previous TS. Duplicative testing was classified as appropriate or inappropriate by predetermined criteria. The level of underordering was analyzed through a query of the electronic event reporting system. A cost analysis was performed to determine the financial impact of inappropriate duplicative TS.
RESULTS: - The mean rate of inappropriate, duplicative TS orders was 4.13% (standard deviation ± 4.09%). Rates of inappropriate ordering ranged from 0.01% to 15.5% depending on the clinical service and did not correlate with volume of tests ordered. There were 8 reported cases of delayed blood delivery due to lack of a valid TS during the study period, demonstrating that underordering is also a harmful practice. The laboratory cost of inappropriate testing for the study period was $80,434, and phlebotomy costs were $45,469.
CONCLUSIONS: - Our study demonstrates that inappropriate TS ordering is costly, both financially and clinically. By evaluating the percentage of inappropriate TS tests by clinical services, we have identified services that may benefit from additional education and technologic intervention.

PMID: 29210591 [PubMed - as supplied by publisher]

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A Novel DBSCAN Based on Binary Local Sensitive Hashing and Binary-KNN Representation

We revisit the classic DBSCAN algorithm by proposing a series of strategies to improve its robustness to various densities and its efficiency. Unlike the original DBSCAN, we first use the binary local sensitive hashing (LSH) which enables faster region query for the neighbors of a data point. The binary data representation method based on neighborhood is then proposed to map the dataset into the Hamming space for faster cluster expansion. We define a core point based on binary influence space to enhance the robustness to various densities. Also, we propose a seed point selection method, which is based on influence space and neighborhood similarity, to select some seed points instead of all the neighborhood during cluster expansion. Consequently, the number of region queries can be decreased. The experimental results show that the improved algorithm can greatly improve the clustering speed under the premise of ensuring better algorithm clustering accuracy, especially for large-scale datasets.

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Safety and Efficacy of First-Line Treatments for Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Indirect Comparison

Recently, several drugs have been introduced for the first-line treatment of chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), but few studies have compared treatment outcomes directly. This indirect comparison among 10 clinical trials ( = 4870 patients) retrieved from PubMed, Web of Science, Cochrane Collaboration, and ClinicalTrails.gov was performed to assess the safety and efficacy of docetaxel, cabazitaxel, abiraterone, enzalutamide, and sipuleucel-T for the initial treatment of mCRPC. No significant differences in primary outcome (overall survival) were found among initial treatments. However, docetaxel had the highest probability (37.53%) of being the most effective, but at the cost of more adverse events, while enzalutamide was associated with the best secondary outcomes (prostate-specific antigen response, progression-free survival, quality of life, and adverse event profile). Thus, docetaxel is recommended as the first agent used for the chemotherapy of mCRPC, while enzalutamide is recommended as the first nonchemotherapy treatment. Additional clinical trials are needed to confirm these findings and establish the optimal order for multidrug treatment of mCRPC.

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Analysis of Factors Associated with the Severity of Acute Pancreatitis according to Etiology

Background. The objective of this study was to determine the factors associated with severity of acute pancreatitis (AP) according to two major etiologies: alcohol and gallstones. Methods. We reviewed the medical records of consecutive patients who were admitted with AP between January 2003 and January 2013. A total of 905 patients with AP (660 alcohol-induced, 245 gallstone-induced) were enrolled. Among them, severe AP (SAP) occurred in 72 patients (53 alcohol-induced, 19 gallstone-induced). Contributing factors between patients with and without SAP were analyzed according to the etiology. Results. Multivariate analysis demonstrated that current smoking, pancreatic necrosis, and bacteremia were associated with AP severity in both alcohol- and gallstone-induced AP. Pancreatic fluid collection was significantly associated with alcohol-induced SAP (), whereas dyslipidemia was significantly associated with gallstone-induced SAP (). Body mass index was significantly correlated with the Bedside Index of Severity in Acute Pancreatitis score in both alcohol- and gallstone-induced AP ( and 0.01, resp.). Conclusions. Current smoking, pancreatic necrosis, and bacteremia can aggravate the clinical course of AP. Pancreatic fluid collection and dyslipidemia were associated with AP severity according to the different etiologies. Obesity may also be associated with AP severity in both etiologies.

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QSKL protects against myocardial apoptosis on heart failure via PI3K/Akt-p53 signaling pathway.

Related Articles

QSKL protects against myocardial apoptosis on heart failure via PI3K/Akt-p53 signaling pathway.

Sci Rep. 2017 Dec 05;7(1):16986

Authors: Chang H, Li C, Wang Q, Lu L, Zhang Q, Zhang Y, Zhang N, Wang Y, Wang W

Abstract
The ancient traditional Chinese medicine Qishenkeli (QSKL) is widely used in the treatment of heart failure (HF) in China. Previous studies have shown that QSKL has definite effects on HF. The purpose of this study is to identify the regulation of QSKL on apoptosis and clarify the underlying mechanism. An apoptosis model of H9C2 cells was induced by oxygen-glucose deprivation/recovery (OGD/R). An animal model of HF was induced by ligation of left anterior descending (LAD) coronary artery in rat. We found that QSKL reduced intracellular ROS generation, increased mitochondrial membrane potential and protected H9C2 cells against OGD/R-induced apoptosis. In vivo results showed that QSKL administration could improve cardiac functions, decrease fibrotic area, infarct size and apoptotic rate in HF model. QSKL regulated the expressions of key apoptotic molecules, including increasing Bcl-2/Bax ratio, reducing the expressions of P53, Bax and Cleaved-caspase-3. Interestingly, QSKL also regulated the phosphorylated expressions of PI3K and Akt without significantly affecting PTEN. Taken together, the protective and anti-apoptotic effects of QSKL could be mediated partly through modulating the PI3K/Akt-P53 apoptotic pathway.

PMID: 29209026 [PubMed - in process]

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Hepatoprotective effects of garlic against ethanol-induced liver injury: A mini-review.

Related Articles

Hepatoprotective effects of garlic against ethanol-induced liver injury: A mini-review.

Food Chem Toxicol. 2017 Dec 02;:

Authors: Guan MJ, Zhao N, Xie KQ, Zeng T

Abstract
Alcoholic liver disease (ALD) is a progressively aggravated liver disease with a diverse spectrum from steatosis to hepatitis, fibrosis, and cirrhosis. Epidemiological studies reveal that alcohol is one of the major causes of advanced liver disease in Europe, United States, and China. Despite the considerable harm, progression in ALD research is slow and the current therapies for ALD have less efficient. Garlic (Allium sativum) has been used as a flavoring agent and also a folk medicine since ancient time. Along with the prosperity in the use of herbal medicines for the treatment of human diseases in recent decades, a series of studies have focused on the beneficial effects of garlic against ALD. This mini-review highlighted the protective roles of garlic against ALD and the potential mechanisms.

PMID: 29208504 [PubMed - as supplied by publisher]

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2j1OQhV