Auditory Acclimatization to Bilateral Hearing Aids: Effects on Sentence-in-Noise Processing Times and Speech-Evoked Potentials.

Objectives: Using a longitudinal design, the present study sought to substantiate indications from two previous cross-sectional studies that hearing aid (HA) experience leads to improved speech processing abilities as quantified using eye-gaze measurements. Another aim was to explore potential concomitant changes in event-related potentials (ERPs) to speech stimuli. Design: Groups of elderly novice (novHA) and experienced (expHA) HA users matched in terms of age and working memory capacity participated. The novHA users were acclimatized to bilateral HA fittings for up to 24 weeks. The expHA users continued to use their own HAs during the same period. The participants' speech processing abilities were assessed after 0 weeks (novHA: N = 16; expHA: N = 14), 12 weeks (novHA: N = 16; expHA: N = 14), and 24 weeks (N = 10 each). To that end, an eye-tracking paradigm was used for estimating how quickly the participants could grasp the meaning of sentences presented against background noise together with two similar pictures that either correctly or incorrectly depicted the meaning conveyed by the sentences (the "processing time"). Additionally, ERPs were measured with an active oddball paradigm requiring the participants to categorize word stimuli as living (targets) or nonliving (nontargets) entities. For all measurements, the stimuli were spectrally shaped according to individual real-ear insertion gains and presented via earphones. Results: Concerning the processing times, no changes across time were found for the expHA group. After 0 weeks of HA use, the novHA group had significantly longer (poorer) processing times than the expHA group, consistent with previous findings. After 24 weeks, a significant mean improvement of ~30% was observed for the novHA users, leading to a performance comparable with that of the expHA group. Concerning the ERPs, no changes across time were found. Conclusions: The results from this exploratory study are consistent with the view that auditory acclimatization to HAs positively impacts speech comprehension in noise. Further research is needed to substantiate them. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2wufcdt

Surveillance of the use of adrenaline auto-injectors in Japanese children

Publication date: Available online 4 August 2017
Source:Allergology International
Author(s): Komei Ito, Manabu Ono, Naoyuki Kando, Teruaki Matsui, Tomoko Nakagawa, Shiro Sugiura, Motohiro Ebisawa
BackgroundThe appropriate usage of an adrenaline auto-injector (AAI, Epipen^®) is a key aspect of patient and social education in the management of anaphylaxis. However, although AAIs are being prescribed increasingly frequently, there are few reports on their actual use.MethodsThe Anaphylaxis Working Group of the Japanese Society of Pediatric Allergy and Clinical Immunology requested that society members register cases in which AAIs were used. Two hundred and sixty-six cases were collected from March 2014 to March 2016.ResultsThe cases included 240 events of immediate-type food allergies caused by cow's milk (n = 100), hen's egg (n = 42), wheat (n = 40), and peanuts (n = 11). Exercise-related events were reported in 19 cases; however, the diagnosis of food-dependent exercise-induced anaphylaxis with a specific causative food was only made in 4 cases (wheat, n = 2; fish, n = 1; squid, n = 1). The frequent reasons for the causative intake included programmed intake (n = 48), failure to check the food labeling (n = 43), and consuming an inappropriate food (n = 26). AAIs were used at schools or nurseries in 67 cases, with school or nursery staff members administering the AAI in 39 cases (58%). On arriving at the hospital, the symptom grade was improved in 71% of the cases, while grade 4 symptoms remained in 20% of the cases. No lethal cases or sequelae were reported.ConclusionsAAIs were used effectively, even by school teachers. The need to visit a hospital after the use of an AAI should be emphasized because additional treatment might be required.



http://ift.tt/2ucArnx

Low blood lead levels and attention-deficit hyperactivity disorder in children: a systematic review and meta-analysis

Abstract

Attention-deficit hyperactivity disorder (ADHD) of children is one of the most common neurodevelopmental diseases; the etiology remains unclear. We reviewed and meta-analyzed case-control studies to assess the effects of blood lead levels in children on ADHD symptoms. Relevant studies were identified by searching electronic databases. A meta-analysis was performed using the fixed model of Review Manager 5.3 software. Seven relevant studies were identified. The case groups exhibited significant increases in ADHD symptoms [mean difference (MD), 0.59; 95% confidence interval (CI), 0.50–0.68; p < 0.0001]. Subgroup assessment showed that even children with blood lead levels <3 μg/dL exhibited significant increases in ADHD symptoms (MD, 0.47; 95% CI, 0.39–0.56; p < 0.0001). Subgroup assessment also showed that children aged 5–12 years exhibited more significant increases in ADHD symptoms (MD, 1.35; 95% CI, 0.28–2.41; p < 0.0001) than children aged >12 years. Our findings suggest that low blood lead levels may be associated with ADHD symptoms in children. However, caution is needed when interpreting the results because among-study heterogeneity was in play. Primary interventions should focus on children with low blood lead levels.

http://ift.tt/2vBHmGV

Level, source identification, and risk analysis of heavy metal in surface sediments from river-lake ecosystems in the Poyang Lake, China

Abstract

The concentrations, sources, and risks of heavy metals (Fe, Al, Mn, Cr, Co, Ni, Cu, Zn, As, Cd, W, Pb, and Tl) in sediments in five river-lake ecosystems in the Poyang Lake region were studied. The concentrations of the heavy metals varied spatially, with most of the highest concentrations in the Raohe river-lake ecosystem (RH). All heavy metals except As, Cd, W, and Tl were enriched in sediments possessing high total organic carbon contents or in finer sediments. Based on enrichment factors and statistical methods, it was found that Cd in sediments in the Xiushui (XS), Ganjiang (GJ), Xinjiang (XJ) river-lake ecosystems, and RH; Mn in the XS, GJ, and RH; and W in the XS and GJ were greatly affected by anthropogenic inputs. Moreover, the origins of Cu, Zn, and As require more attention due to the high concentrations found. The high enrichment factor of Cd in the sediments indicated that this metal might cause significant pollution in the environment. The results of the modified potential ecological risk index revealed that the XS, GJ, RH, and XJ were at considerable ecological risk, while the sediments in the Fuhe river-lake ecosystem (FH) were at moderate ecological risk, with Cd contributing the highest proportion of risk. The hazard score fundamentally validated the modified potential ecological risk analysis and revealed a mean toxicity of 57.80% to the benthic organisms in the RH.

http://ift.tt/2wg9QDl

Reverberatory furnaces in the Puna of Jujuy, Argentina, during colonial times (from the end of the 16th to the beginning of the 19th century A.D.)

Publication date: December 2017
Source:Journal of Anthropological Archaeology, Volume 48
Author(s): Carlos I. Angiorama, M. Florencia Becerra
This paper presents the study of the extractive metallurgical technology that was employed in four colonial mining-metallurgical sites in the high plateau (Puna) of Jujuy, Argentina, dedicated to silver exploitation during the 17th and 18th centuries. In these archaeological sites, we have identified the presence of reverberatory furnaces. We explore the development of this technology and show the results of the study of the furnaces found in the Puna of Jujuy, their functions and performance, based on our fieldwork and on the results of archaeometric analyses of smelting slag and vitrified clay samples. The excellent conservation of most of the furnaces makes them not only a great source of information for the study of colonial metallurgy in this region, but also a contribution to our understanding of mining and extractive metallurgy in the Andes, of the circulation of workers and technical knowledge and of the changes generated by the Spanish conquest.



http://ift.tt/2v5iHJi

Influences of microgap and micromotion of implant–abutment interface on marginal bone loss around implant neck

Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Yang Liu, Jiawei Wang
ObjectiveTo review the influences and clinical implications of micro-gap and micro-motion of implant-abutment interface on marginal bone loss around the neck of implant.DesignLiteratures were searched based on the following Keywords: implant-abutment interface/implant-abutment connection/implant-abutment conjunction, microgap, micromotion/micromovement, microleakage, and current control methods available. The papers were then screened through titles, abstracts, and full texts.ResultsA total of 83 studies were included in the literature review. Two-piece implant systems are widely used in clinics. However, the production error and masticatory load result in the presence of microgap and micromotion between the implant and the abutment, which directly or indirectly causes microleakage and mechanical damage. Consequently, the degrees of microgap and micromotion further increase, and marginal bone absorption finally occurs. We summarize the influences of microgap and micromotion at the implant-abutment interface on marginal bone loss around the neck of the implant. We also recommend some feasible methods to reduce their effect.ConclusionsClinicians and patients should pay more attention to the mechanisms as well as the control methods of microgap and micromotion. To reduce the corresponding detriment to the implant marginal bone, suitable Morse taper or hybrid connection implants and platform switching abutments should be selected, as well as other potential methods.



http://ift.tt/2vzkwik

Relationships between chewing rate, occlusion, cephalometric anatomy, muscle activity, and masticatory performance

Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Brent A. Fulks, Kathryn X. Callaghan, Claire D. Tewksbury, Geoffrey E. Gerstner
ObjectiveMastication consists of rhythmic jaw openings and closings. Recent studies suggest that muscle mechanical properties determine the rhythmic rate; however, speed-accuracy tradeoffs may also play a role. This study evaluated how variation in chewing rate affected chewing performance, how masticatory muscle activity varied with chewing rate, and whether morphology and demographics contributed to performance.DesignChewing performance and muscle activity were sampled in 23 healthy, fully-dentate adults, who chewed a standardized test food to a metronome set at 0.5, 0.75, 1, 2 and 3 times their 'natural' chewing rates. Subjects produced ten chews per trial, and five trials for each of the five rates. Surface electromyographic (EMG) activity was sampled from masseter and temporalis muscles bilaterally. Demographic, occlusal, and cephalometric data were also obtained.ResultsChewing performance, defined by median particle size, was inversely related to chewing rate; however, performance was not remarkably improved at rates slower than the natural chewing rate. Above the natural chewing rate, variability in EMG bursts diminished, suggesting a reduction in muscle activity modulation at fast rates. Occlusal contacts and most morphological features appeared to play a limited or no role in performance.ConclusionsResults support the hypothesis that the 'natural' chewing rate is selected to be as fast as possible while providing sufficient time to allow EMG modulation for improved performance. The interplay between EMG modulation and individual variation in skeletal morphology is likely critical for optimal chewing performance.



http://ift.tt/2ua8CYW

Characterization of the clustered regularly interspaced short palindromic repeats sites in Streptococcus mutans isolated from early childhood caries patients

Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Jing Chen, Tiancheng Li, Xuedong Zhou, Lei Cheng, Yuanyuan Huo, Jing Zou, Yuqing Li
ObjectiveThe aim of this study was to analyze the characteristics of the clustered regularly interspaced short palindromic repeats (CRISPR) sites in 45 clinical Streptococcus mutans strains and their relationship to the clinical manifestations of early childhood caries (ECC).MethodsForty-five S. mutans strains were isolated from the plaque samples taken from sixty-three children. CRISPR sites were sequenced and BLAST was used to compare these sites to those in the CRISPRTarget database. The association between the distribution of CRISPR sites and the manifestation of caries was analyzed by Chi-Square test. Further, biofilm formation (by crystal violet staining) and the synthesis of polysaccharide (by anthrone-sulfuric method) of all clinical isolated S. mutans strains with both CRISPR sites and no CRISPR site were comapared. Finally, acidogenicity and acidurity of two typical strains were determined using pH drop and acid tolerance assays. Biofilm formation and EPS synthesis by two typical strains were compared by 3D CLSM (Confocal Laser Scanning Microscope) assays and the expression of gtf genes were evaluated using qPCR.ResultsWe found that most of the spacers in the clinical S. mutans strains were derived from Streptococcus phages APCM01 and M102. The number of CRISPR sites in these strains was associated with the clinical manifestations of ECC. Moreover, we found that the biofilm formation and EPS synthesis ability of the S. mutans strains with both CRISPR sites was significant improved.ConclusionsAn association was found between the distribution of CRISPR sites and the clinical manifestations of caries. The CRISPR sites might contribute to the cariogenic potential of S. mutans.



http://ift.tt/2uad0H6

Extracellular HSP72 induces proinflammatory cytokines in human periodontal ligament fibroblast cells through the TLR4/NFκB pathway in vitro

Publication date: November 2017
Source:Archives of Oral Biology, Volume 83
Author(s): Chihiro Arai, Yoshiaki Nomura, Masazumi Matsuzawa, Nobuhiro Hanada, Yoshiki Nakamura
ObjectiveThe aim of the present study was to examine the effect of extracellular heat shock protein (HSP) 72 on human periodontal ligament fibroblast cells (hPDLFs) in vitro.DesignhPDLFs were stimulated by recombinant human HSP72 (rhHSP72). TAK-242 was used to inhibit toll-like receptor 4 (TLR4) activity. Interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α mRNA levels were analyzed by real-time PCR and protein levels were analyzed by enzyme-linked immunosorbent assay. p65/RelA phosphorylation was analyzed by western blot.ResultsIL-6, IL-8 and TNF-α mRNA and protein levels were significantly increased by rhHSP72 stimulation. These effects were inhibited by TAK-242 treatment. Additionally, p65/RelA phosphorylation was increased after 5-min rhHSP72 stimulation, which was inhibited by TAK-242 treatment.ConclusionExtracellular HSP72 induces proinflammatory cytokines through TLR4/NF-κB in hPDLFs.



http://ift.tt/2uajE0d

Impact of resistant vs. digested starch on starch energy value in the pig gut

Publication date: Available online 4 August 2017
Source:Bioactive Carbohydrates and Dietary Fibre
Author(s): Janelle M. Fouhse, Ruurd T. Zijlstra
A major energy substrate for monogastric species such as humans and swine is starch from cereal grains, pulses and tubers. The rate, site and extent of starch digestion in the gastro-intestinal tract are dependent on the intrinsic factors of starch origin and the extrinsic factors such as applied processing methods. In monogastric species, starch escaping small intestinal digestion becomes readily available for microbial fermentation in the hindgut and has been coined resistant starch (RS) accordingly. Host physiological and metabolic responses differ according to the site and rate of starch digestion; however, the quantity of energy derived to the host from fermented vs. digested starch remains debated. A detailed understanding of the underlying mechanisms that cause nutrient flow and substrate availability in the hindgut to alter host energy metabolism and growth potential is lacking. Dietary RS may in fact have nearly equal energetic efficiency as digested starch due adequate provision of short chain fatty acids (SCFAs) and decreased energy loss due to decreased activity. Thus, proper characterization of the energetic efficiency of purified and whole grain starch sources is required for accurate diet formulation. This review will focus on how various methodologies can be used to quantify site, extent and kinetics of starch digestion, illustrating the differences in energetic efficiency between RS vs. digested starch.



http://ift.tt/2v5EUHf

Cell‐Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta‐Analysis

AbstractBackground.Circulating DNA can be detected and quantified in the blood of cancer patients and used for detection of tumor‐specific genetic alterations. The clinical utility has been intensively investigated for the past 10 years. The majority of reports focus on analyzing the clinical potential of tumor‐specific mutations, whereas the use of total cell‐free DNA (cfDNA) quantification is somehow controversial and sparsely described in the literature, but holds important clinical information in itself. The purpose of the present report was to present a systematic review and meta‐analysis of the prognostic value of total cfDNA in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy. In addition, we report on the overall performance of cfDNA as source for KRAS mutation detection.Materials and Methods.A systematic literature search of PubMed and Embase was performed by two independent investigators. Eligibility criteria were (a) total cfDNA analysis, (b) mCRC, and (c) prognostic value during palliative treatment. The preferred reporting items for systematic reviews and meta‐analyses (PRISMA) guidelines were followed, and meta‐analysis applied on both aggregate data extraction and individual patients' data.Results.Ten eligible cohorts were identified, including a total of 1,076 patients. Seven studies used quantitative polymerase chain reaction methods, two BEAMing [beads, emulsification, amplification, and magnetics] technology, and one study digital droplet polymerase chain reaction. The baseline levels of cfDNA was similar in the presented studies, and all studies reported a clear prognostic value in favor of patients with lowest levels of baseline cfDNA. A meta‐analysis revealed a combined estimate of favorable overall survival hazard ratio (HR) in patients with levels below the median cfDNA (HR = 2.39, 95% confidence interval 2.03–2.82, p < .0001).Conclusion.The total cfDNA levels are high in patients with mCRC and bear strong prognostic information, which should be tested prospectively by using a predefined cut‐off value based on normal values in healthy cohorts. Finally, the potential use of cfDNA for detection of tumor‐specific mutations was emphasized in a large individual patients' data meta‐analysis.

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„Ökonomische Kennziffern verdrängen unsere ethischen Grundsätze“

http://ift.tt/2fgk2HZ

Verschmäht und weggepackt

Nicht sehen trennt von den Dingen, nicht hören trennt von den Menschen — dieser Satz wird oft zitiert, wenn es um die Schwächen der menschlichen Sinne geht. Da verwundert es, wie unterschiedlich beliebt Seh- und Hörhilfen bei Menschen sind, die sie benötigen. Denn während die Brille als modisches Accessoire durchgeht, fristet das Hörgerät nicht selten ein verschämtes Dasein im Verborgenen.

http://ift.tt/2hvv0Kj

Rezidiv bei Kopf-Hals-Tumoren: SBRT mit Langzeitschäden?

Bei lokal rezidivierten, zuvor bestrahlten Kopf-Hals-Tumoren, die für eine Salvage-Operation ungeeignet sind, hat sich die Körperstereotaxie (SBRT) als effizient erwiesen. Doch wie steht es mit der Langzeittoxizität?

http://ift.tt/2fgmNZK

Sensibilisierung gegen Katze und Hund erhöht Asthmarisiko deutlich

Wie stark sind Sensibilisierungen gegen Katzen- und Hunde-Epithelien mit Asthmasymptomen assoziiert? Bisher konnte der Zusammenhang nicht quantifiziert werden. Eine Studie aus einer milben- und schimmelpilzfreien Gegend liefert jetzt Daten.

http://ift.tt/2hws7J5

Gesundheitspolitik im Wahlkampf: Alles wie gehabt

http://ift.tt/2ffYqLC

Hörstörung und kognitiver Abbau im Alter

Mit zunehmendem Alter treten zum einen vermehrt Hörstörungen auf, zum anderen unterliegen auch verschiedene kognitive Funktionen einem altersassoziierten Abbau. Aktuelle wissenschaftliche Studien untersuchen mögliche Zusammenhänge zwischen Hörvermögen und kognitiven Fähigkeiten und Konsequenzen für die lautsprachliche Kommunikation im Alter.

http://ift.tt/2hvuUlV

Chronische Rhinosinusitis: erhöhte Revisionsrate nach Sinus-Op bei Polypennachweis

Kanadische Ärzte um Dr. Luke Rudmik von der Universität von Calgary sind in einer retrospektiven Studie der Frage nachgegangen, wie sich bei Patienten mit chronischer Rhinosinusitis die Ergebnisse einer endoskopischen Sinus-Chirurgie (ESS, endoscopic sinus surgery) durch Ärzte an Kliniken in Alberta unterscheiden. Primärer Studienendpunkt war die Revisionsrate fünf Jahre nach dem Eingriff.

http://ift.tt/2ffZ8Zw

Hilft Kortison gegen die ototoxische Wirkung von Cisplatin?

http://ift.tt/2fg5Fn6

Wege zu einer barrierefreien Kommunikation

Barrierefreiheit ist nicht nur wichtig für Personen mit körperlichen Einschränkungen, sondern auch für Menschen mit Sinneseinschränkungen wie z.B. beim Vorliegen einer Schwerhörigkeit. Im Folgenden wird aufgezeigt, warum Hörassistenzsysteme notwendig sind und wie eine barrierefreie Kommunikation mit technischen Hörassistenzsystemen erschlossen werden kann.

http://ift.tt/2vyG9zz

Ärztebashing 130 Jahre vor Jameda & Co.

„Nun merkt auf, wie eine simple Geschichte Euch zu nichte macht". Dieses Zitat aus Shakespeares Heinrich IV hat Morell Mackenzie 1888 seiner Verteidigungsschrift zu seiner Rolle bei der Behandlung von Kaiser Friederich III vorangestellt. Er war tief gekränkt von den Unterstellungen und Verleumdungen in der Presse. Wäre Mackenzie heute ein Fall im Bewertungsportal Jameda? Dass auch ein gutmeinender Arzt an der Kritik in den Medien zerbrechen kann, galt gestern wie heute.

http://ift.tt/2fg5sjO

Einfach mal skypen ist nicht erlaubt

Seit April können Ärzte Videosprechstunden als EBM-Leistung über ihre KV abrechnen. Allerdings nur, wenn die Kommunikationsdienste, die sie hierfür nutzen, strenge technische Voraussetzungen erfüllen. Und genau das hat noch einen Haken: Noch gibt es auf dem Markt nur eine überschaubare Zahl von Videodiensten, die das leisten.

http://ift.tt/2fg5jwM

Reduced immunoglobulin gene diversity in patients with Cornelia de Lange syndrome

Altered IGH repertoires with reduced diversity, skewed VH gene usage and reduced frequency of somatic hypermutation were observed in CdLS patients.

http://ift.tt/2wtwl6T

„Ökonomische Kennziffern verdrängen unsere ethischen Grundsätze“

http://ift.tt/2fgk2HZ

Kooperation bietet allen mehr Chancen als Nachteile

http://ift.tt/2ffyDDz

Verschmäht und weggepackt

Nicht sehen trennt von den Dingen, nicht hören trennt von den Menschen — dieser Satz wird oft zitiert, wenn es um die Schwächen der menschlichen Sinne geht. Da verwundert es, wie unterschiedlich beliebt Seh- und Hörhilfen bei Menschen sind, die sie benötigen. Denn während die Brille als modisches Accessoire durchgeht, fristet das Hörgerät nicht selten ein verschämtes Dasein im Verborgenen.

http://ift.tt/2hvv0Kj

Rezidiv bei Kopf-Hals-Tumoren: SBRT mit Langzeitschäden?

Bei lokal rezidivierten, zuvor bestrahlten Kopf-Hals-Tumoren, die für eine Salvage-Operation ungeeignet sind, hat sich die Körperstereotaxie (SBRT) als effizient erwiesen. Doch wie steht es mit der Langzeittoxizität?

http://ift.tt/2fgmNZK

Gesundheitspolitik im Wahlkampf: Alles wie gehabt

http://ift.tt/2ffYqLC

So viel verdienen niedergelassene Ärzte

Trotz steigender Betriebskosten: Die wirtschaftliche Lage in den Vertragsarztpraxen hat sich zwischen den Jahren 2011 und 2014 merklich verbessert. Die Einnahmen je Inhaber stiegen um 10,2 %, der Jahresüberschuss — also der Gewinn — um 6,7 %, während die Praxiskosten um 8,9 % zulegten. Das zeigen die Daten des Zi-Praxis-Panels (ZiPP), die aus über 5.000 Praxen generiert wurden.

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Haben Sie auch eine fachliche Frage?

http://ift.tt/2hvvlfT

Chronische Rhinosinusitis: erhöhte Revisionsrate nach Sinus-Op bei Polypennachweis

Kanadische Ärzte um Dr. Luke Rudmik von der Universität von Calgary sind in einer retrospektiven Studie der Frage nachgegangen, wie sich bei Patienten mit chronischer Rhinosinusitis die Ergebnisse einer endoskopischen Sinus-Chirurgie (ESS, endoscopic sinus surgery) durch Ärzte an Kliniken in Alberta unterscheiden. Primärer Studienendpunkt war die Revisionsrate fünf Jahre nach dem Eingriff.

http://ift.tt/2ffZ8Zw

M. Menière: intratympanale Gabe von Methylprednisolon so wirksam wie Gentamicin

Ein klassischer Therapieansatz bei Morbus Menière ist die intratympanale Gabe von Gentamicin. Dies führt dosisabhängig zu einem Untergang der vestibulären Rezeptoren und damit zu einem Ausfall der vestibulären Funktionen. Bei etwa 20 % der so behandelten Patienten kommt es auch zu einer Hörminderung oder sogar zu einem Hörverlust. Daher ist es dringend notwendig, andere Therapien zu entwickeln, bei denen die vestibulären Funktionen intakt bleiben und insbesondere kein Risiko für eine Hörminderung besteht.

http://ift.tt/2hwqDPe

Hilft Kortison gegen die ototoxische Wirkung von Cisplatin?

http://ift.tt/2fg5Fn6

Wege zu einer barrierefreien Kommunikation

Barrierefreiheit ist nicht nur wichtig für Personen mit körperlichen Einschränkungen, sondern auch für Menschen mit Sinneseinschränkungen wie z.B. beim Vorliegen einer Schwerhörigkeit. Im Folgenden wird aufgezeigt, warum Hörassistenzsysteme notwendig sind und wie eine barrierefreie Kommunikation mit technischen Hörassistenzsystemen erschlossen werden kann.

http://ift.tt/2vyG9zz

Inhaltsverzeichnis

http://ift.tt/2u9IyNz

Todmüde ans Steuer?

Wer an Schlafapnoe leidet, hat nicht nur ein erhöhtes Risiko für Herz-Kreislauf-Erkrankungen, sondern auch ein höheres Unfallrisiko. Denn schwere Tagesschläfrigkeit und der berühmte Sekundenschlaf am Steuer sind Ursache vieler schwerer Verkehrsunfälle. Wie steht es also um die Fahreignung bei schlafbezogenen Atmungsstörungen?

http://ift.tt/2vyQhbd

Viele Ärzte reagieren allergisch auf „Dr. Google“

Erst die Symptome googeln, dann zum Doktor: Immer mehr Patienten kommen derart vorinformiert in die Praxis. Viele Ärzte erachten diese Selbstdiagnostik aber als problematisch.

http://ift.tt/2hvilHc

Ärztebashing 130 Jahre vor Jameda & Co.

„Nun merkt auf, wie eine simple Geschichte Euch zu nichte macht". Dieses Zitat aus Shakespeares Heinrich IV hat Morell Mackenzie 1888 seiner Verteidigungsschrift zu seiner Rolle bei der Behandlung von Kaiser Friederich III vorangestellt. Er war tief gekränkt von den Unterstellungen und Verleumdungen in der Presse. Wäre Mackenzie heute ein Fall im Bewertungsportal Jameda? Dass auch ein gutmeinender Arzt an der Kritik in den Medien zerbrechen kann, galt gestern wie heute.

http://ift.tt/2fg5sjO

Finanzielle Fördermittel sollen motivieren

Der Ausbau einer reibungslosen sektorübergreifenden Versorgung dürfte eines der großen Themen für das Gesundheitswesen in der nächsten Legislaturperiode werden. Niedergelassene Ärzte profitieren, wenn sie sich schon heute auf mögliche Änderungen einstellen.

http://ift.tt/2hvidHI

Amplification of near-infrared fluorescence in semiconducting polymer nanoprobe for grasping the behaviors of systemically administered endothelial cells in ischemia treatment

Publication date: October 2017
Source:Biomaterials, Volume 143
Author(s): Duo Mao, Jie Liu, Shenglu Ji, Ting Wang, Yu Hu, Donghui Zheng, Renqiang Yang, Deling Kong, Dan Ding
To date, there have been few studies on using fluorescent cell trackers for non-invasively monitoring the in vivo fate of systemically administered cells. This is because only a relatively small number of cells can reach the disease site post systemic infusion, and thus achieving ideal in vivo cell tracking requires that the fluorescent cell trackers should hold combined merits of ultrahigh near-infrared (NIR) fluorescence, negligible interference on cell behavior and function, excellent retention within cells, as well as accurate long-term cell tracking ability. To address this challenge, we herein developed a highly NIR fluorescent nanoprobe (SPN) based on semiconducting π-conjugated polymers (SPs), by synthesis of a NIR SP-emitter, employment of fluorescence resonance energy transfer (FRET) strategy, and optimization of different FRET donor SPs. Due to the 53.7-fold intra-particle amplification of NIR fluorescence, the SPN could track as few as 2000 endothelial cells (ECs) upon intra-arterial injection into critical limb ischemia (CLI)-bearing mice, showing much higher sensitivity in ECs tracking compared with the most popular commercial cell trackers. What's more, the SPN could provide precise information on the behaviors of systemically injected ECs in CLI treatment including the in vivo fate and regenerative contribution of ECs for at least 21 days.



http://ift.tt/2vpC8he

A novel delocalized lipophilic cation-chlorambucil conjugate inhibits P-glycoprotein in HepG2/ADM cells

Publication date: Available online 4 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Teng Liu, Yongbo Peng, Xiong Li, Lian Liu, Fang Liu, Leye He
Multidrug resistance (MDR) limits the application of a large number of cancer-fighting agents in clinical therapy. One reason is that P-glycoprotein (Pgp) efflux pumps are usually overexpressed and lead to drug efflux in the cancer cells, which limits the viability of many chemotherapeutics. Current available inhibitors which block the Pgp pump efflux are usually not widely used in clinical practice, because they change other drug pharmacokinetic profiles or increase side effects. Here, through covalent linkage of cancer-targeting delocalized lipophilic cation FF and DNA-damaging drug nitrogen mustard chlorambucil (CLB), we rationally designed and synthesized a tumor-targeting anticancer agent FFCLB. And we found and proved that the FFCLB was capable of reducing the outflow of Pgp substrates efficiently. This conjugate selectively improves adriamycin uptake and toxicity through reducing MDR1 mRNA and Pgp protein expression. Based on molecular targeted strategy, this study can facilitate the discovery of superior MDR reducing agents to provide a more effective and safer way of resensitizing MDR.

Graphical abstract

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Conjugates of 18β-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid as Pin1 inhibitors displaying anti-prostate cancer ability

Publication date: Available online 4 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Kun Li, Tianyi Ma, Jingjing Cai, Min Huang, Hongye Guo, Di Zhou, Shenglin Luan, Jinyu Yang, Dan Liu, Yongkui Jing, Linxiang Zhao
Twenty-six conjugates of 18β-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid were designed and synthesized as Pin1 inhibitors. Most of these semi-synthetic compounds showed improved Pin1 inhibitory activity and anti-proliferative effects against prostate cancer cells as compared to 3-(1H-benzo[d]imidazol-2-yl)propanoic acid and GA. Compounds 10a and 12i were the most potent to inhibit growth of prostate cancer PC-3 with GI50 values of 7.80 μM and 3.52 μM, respectively. The enzyme inhibition ratio of nine compounds at 10 μM was over 90%. Structure-activity relationships indicated that both appropriate structure at ring C of GA and suitable length of linker between GA skeleton and benzimidazole moiety had significant impact on improving activity. Western blot assay revealed that 10a decreased the level of cell cycle regulating protein cyclin D1. Thus, these compounds might represent a novel anti-proliferative agent working through Pin1 inhibition.

Graphical abstract

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Radiosynthesis and Preclinical PET Evaluation of 89Zr-Nivolumab (BMS-936558) in Healthy Non-Human Primates

Publication date: Available online 4 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Erin L. Cole, Joonyoung Kim, David J. Donnelly, R. Adam Smith, Daniel Cohen, Virginie Lafont, Paul E. Morin, Richard Y.-C. Huang, Patrick L. Chow, Wendy Hayes, Samuel Bonacorsi
Cancer immunotherapy, unlike traditional cytotoxic chemotherapeutic treatments, engages the immune system to identify cancer cells and stimulate immune responses. The Programmed Death-1 (PD-1) protein is an immunoinhibitory receptor expressed by activated cytotoxic T-lymphocytes (CTL) that seek out and destroy cancer cells. Multiple cancer types express and upregulate the Programmed Death-Ligand 1 (PD-L1) and 2 (PD-L2) which bind to PD-1 as an immune escape mechanism. Nivolumab is a fully human IgG4 anti-PD-1 monoclonal antibody (mAb) approved for treatment of multiple cancer types. This study reports the preparation and in vivo evaluation of ⁸⁹Zr labeled nivolumab in healthy non-human primates (NHP) as a preliminary study of biodistribution and clearance. The radiochemical and in vivo stabilities of the ⁸⁹Zr complex were shown to be acceptable for imaging. Three naïve NHPs were intravenously injected with tracer only or tracer co-injected with nivolumab followed by co-registered by positron emission tomography (PET) and magnetic resonance imaging (MRI), acquired for eight days following injection. Image-derived standardized uptake values (SUV) were quantified by region of interest (ROI) analysis. Radioactivity in the spleen was significantly reduced by addition of excess nivolumab compared to the tracer only study at all imaging time points. Liver uptake of the radiotracer was consistent as a clearance organ with minimal signal from other tissues: lung, muscle, brain, heart, and kidney. The results indicate specific biodistribution to the spleen, which can be blocked by co-administration of excess nivolumab. Distribution to other organs is consistent with elimination pathways of antibodies, with primary clearance through the liver.

Graphical abstract

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Biological evaluation of 2-pyrazolinyl-1-carbothioamide derivatives against HCT116 human colorectal cancer cell lines and elucidation on QSAR and molecular binding modes

Publication date: Available online 4 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Beom Soo Kim, Soon Young Shin, Seunghyun Ahn, Dongsoo Koh, Young Han Lee, Yoongho Lim
In the search of compounds exhibiting anticancer activity, 37 derivatives of 2-pyrazolinyl-1-carbothioamide were designed and synthesized. Clonogenic cell survival assays were adapted to measure the cytotoxicities of the synthetic derivatives against HCT116 human colon cancer cell lines. Half-maximal cell growth inhibitory concentrations (GI50) ranged from 0.49 to 41.22 µM. The compound with the lowest GI50 value, 3-(2-hydroxy-4,5-dimethoxyphenyl)-5-(naphthalen-1-yl)-N-(3,4,5-trimethoxyphenyl)-pyrazolinyl-1-carbothioamide, was subjected to further biological studies, including cell viability and apoptosis assays to examine levels of annexin-V in the outer plasma membrane layer and poly ADP-ribose polymerase cleavage. Additionally, in vitro kinase assays were performed, and Abelson murine leukemia viral oncogene homolog 1 (Abl 1) tyrosine kinase demonstrated good inhibitory activity. The binding mode between the compound of interest and Abl 1 was elucidated using in silico docking. The pharmacophores derived for 2-pyrazolinyl-1-carbothioamides based on their quantitative structure–activity relationships will help us design novel chemotherapeutic agents.

Graphical abstract

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Synthesis and evaluation of analogs of 5'-(((Z)-4-amino-2-butenyl)methylamino)-5'-deoxyadenosine (MDL 73811, or AbeAdo) – an inhibitor of S-adenosylmethionine decarboxylase with antitrypanosomal activity

Publication date: Available online 3 August 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Anthony J. Brockway, Oleg A. Volkov, Casey C. Cosner, Karen S. MacMillan, Stephen A. Wring, Thomas E. Richardson, Michael Peel, Margaret A. Phillips, Jef K. De Brabander
We describe our efforts to improve the pharmacokinetic properties of a mechanism-based suicide inhibitor of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (AdoMetDC), essential for the survival of the eukaryotic parasite Trypanosoma brucei responsible for Human African Trypanosomiasis (HAT). The lead compound, 5'-(((Z)-4-amino-2-butenyl)methylamino)-5'-deoxyadenosine (1, also known as MDL 73811, or AbeAdo), has curative efficacy at a low dosage in a hemolymphatic model of HAT but displayed no demonstrable effect in a mouse model of the CNS stage of HAT due to poor blood-brain barrier permeation. Therefore, we prepared and evaluated an extensive set of analogs with modifications in the aminobutenyl side chain, the 5'-amine, the ribose, and the purine fragments. Although we gained valuable structure-activity insights from this comprehensive dataset, we did not gain traction on improving the prospects for CNS penetration while retaining the potent antiparasitic activity and metabolic stability of the lead compound 1.

Graphical abstract

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Lysocardiolipin acyltransferase regulates TGF-β mediated lung fibroblast differentiation

Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Long Shuang Huang, Peiyue Jiang, Carol Feghali-Bostwick, Sekhar P. Reddy, Joe G.N. Garcia, Viswanathan Natarajan
Lysocardiolipin acyltransferase (LYCAT), a cardiolipin remodeling enzyme, plays a key role in mitochondrial function and vascular development. We previously reported that reduced LYCAT mRNA levels in peripheral blood mononuclear cells correlated with poor pulmonary function outcomes and decreased survival in IPF patients. Further LYCAT overexpression reduced lung fibrosis, and LYCAT knockdown accentuated experimental pulmonary fibrosis. NADPH Oxidase 4 (NOX4) expression and oxidative stress are known to contribute to lung fibroblast differentiation and progression of fibrosis. In this study, we investigated the role of LYCAT in TGF-β mediated differentiation of human lung fibroblasts to myofibroblasts, and whether this occurred through mitochondrial superoxide and NOX4 mediated hydrogen peroxide (H2O2) generation. Our data indicated that LYCAT expression was up-regulated in primary lung fibroblasts isolated from IPF patients and bleomycin-challenged mice, compared to controls. In vitro, siRNA-mediated SMAD3 depletion inhibited TGF-β stimulated LYCAT expression in human lung fibroblasts. ChIP immunoprecipitation assay revealed TGF-β stimulated SMAD2/3 binding to the endogenous LYCAT promoter, and mutation of the SMAD2/3 binding sites (−179/−183 and −540/−544) reduced TGF-β-stimulated LYCAT promoter activity. Overexpression of LYCAT attenuated TGF-β-induced mitochondrial and intracellular oxidative stress, NOX4 expression and differentiation of human lung fibroblasts. Further, pretreatment with Mito-TEMPO, a mitochondrial superoxide scavenger, blocked TGF-β-induced mitochondrial superoxide, NOX4 expression and differentiation of human lung fibroblasts. Treatment of human lung fibroblast with NOX1/NOX4 inhibitor, GKT137831, also attenuated TGF-β induced fibroblast differentiation and mitochondrial oxidative stress. Collectively, these results suggest that LYCAT is a negative regulator of TGF-β-induced lung fibroblast differentiation by modulation of mitochondrial superoxide and NOX4 dependent H2O2 generation, and this may serve as a potential therapeutic target for human lung fibrosis.

Graphical abstract

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The theory of autoimmunity in Meniere’s disease is lacking evidence

The role of immunological factors in the pathophysiology of Meniere's disease (MD) has been hypothesized. In order to evaluate the current level of evidence on autoimmunity in MD, original articles relevant to the matter (1970–2016) were reviewed. The following has been considered to support the theory of autoimmunity in MD (1) the increased prevalence of autoimmune diseases among MD patients, (2) the elevated levels of antibodies and immunocomplexes in MD patients, (3) the association of MD with HLA-types and genetic polymorphisms and (4) the positive corticosteroid-responsiveness detected in some MD patients.

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Trends in dermatology practices and the implications for the workforce

The American Academy of Dermatology (AAD) practice profile surveys have been conducted for more than a decade to gauge trends in our workforce supply and demand.

http://ift.tt/2vyCNwn

In silico approaches for unveiling novel glycobiomarkers in cancer

Publication date: Available online 4 August 2017
Source:Journal of Proteomics
Author(s): Rita Azevedo, André M.N. Silva, Celso A. Reis, Lúcio Lara Santos, José Alexandre Ferreira
Glycosylation is one of the most common and dynamic post-translational modification of cell surface and secreted proteins. Cancer cells display unique glycosylation patterns that decisively contribute to drive oncogenic behavior, including disease progression and dissemination. Moreover, alterations in glycosylation are often responsible for the creation of protein signatures holding significant biomarker value and potential for targeted therapeutics. Accordingly, many analytical protocols have been outlined for the identification of abnormally glycosylated proteins by mass spectrometry. Nevertheless, very few studies undergo a comprehensive mining of the generated data. Herein, we build on bladder cancer O-glycoproteomics datasets resulting from a hyphenated technique comprising enrichment by Vicia villosa agglutinin (VVA) lectin and nanoLC-ESI-MS/MS to propose an in silico step-by-step tutorial (Panther, NetOGlyc, NetNGlyc, Oncomine, Cytoscape) for biomarker discovery in cancer. We envisage that this approach may be generalized to other mass spectrometry-based analytical approaches, including N-glycoproteomics studies, and different types of cancers.SignificanceThe glycoproteome is an important source of cancer biomarkers holding tremendous potential for targeted therapeutics. We now present an in silico roadmap for comprehensive interpretation of big data generated by mass spectrometry-based glycoproteomics envisaging the identification of clinically relevant glycobiomarkers.



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Effect of ferrate on green algae removal

Abstract

Green algae Cladophora aegagropila, present in cooling water of thermal power plants, causes many problems and complications, especially during summer. However, algae and its metabolites are rarely eliminated by common removal methods. In this work, the elimination efficiency of electrochemically prepared potassium ferrate(VI) on algae from cooling water was investigated. The influence of experimental parameters, such as Fe(VI) dosage, application time, pH of the system, temperature and hydrodynamics of the solution on removal efficiency, was optimized. This study demonstrates that algae C. aegagropila can be effectively removed from cooling water by ferrate. Application of ferrate(VI) at the optimized dosage and under the suitable conditions (temperature, pH) leads to 100% removal of green algae Cladophora from the system. Environmentally friendly reduction products (Fe(III)) and coagulation properties favour the application of ferrate for the treatment of water contaminated with studied microorganisms compared to other methods such as chlorination and use of permanganate, where harmful products are produced.

http://ift.tt/2uctMd2

Diagnostic accuracy of automatic normalization of CBV in glioma grading using T1- weighted DCE-MRI

Publication date: Available online 4 August 2017
Source:Magnetic Resonance Imaging
Author(s): Prativa Sahoo, Rakesh K. Gupta, Pradeep K. Gupta, Ashish Awasthi, Chandra M. Pandey, Mudit Gupta, Rana Patir, Sandeep Vaishya, Sunita Ahlawat, Indrajit Saha
PurposeAim of this retrospective study was to compare diagnostic accuracy of proposed automatic normalization method to quantify the relative cerebral blood volume (rCBV) with existing contra-lateral region of interest (ROI) based CBV normalization method for glioma grading using T1-weighted dynamic contrast enhanced MRI (DCE-MRI).Material and methodsSixty patients with histologically confirmed gliomas were included in this study retrospectively. CBV maps were generated using T1-weighted DCE-MRI and are normalized by contralateral ROI based method (rCBV_contra), unaffected white matter (rCBV_WM) and unaffected gray matter (rCBV_GM), the latter two of these were generated automatically. An expert radiologist with >10years of experience in DCE-MRI and a non-expert with one year experience were used independently to measure rCBVs. Cutoff values for glioma grading were decided from ROC analysis. Agreement of histology with rCBV_WM, rCBV_GM and rCBV_contra respectively was studied using Kappa statistics and intra-class correlation coefficient (ICC).ResultThe diagnostic accuracy of glioma grading using the measured rCBV_contra by expert radiologist was found to be high (sensitivity=1.00, specificity=0.96, p<0.001) compared to the non-expert user (sensitivity=0.65, specificity=0.78, p<0.001). On the other hand, both the expert and non-expert user showed similar diagnostic accuracy for automatic rCBV_WM (sensitivity=0.89, specificity=0.87, p=0.001) and rCBV_GM (sensitivity=0.81, specificity=0.78, p=0.001) measures. Further, it was also observed that, contralateral based method by expert user showed highest agreement with histological grading of tumor (kappa=0.96, agreement 98.33%, p<0.001), however; automatic normalization method showed same percentage of agreement for both expert and non-expert user. rCBV_WM showed an agreement of 88.33% (kappa=0.76,p<0.001) with histopathological grading.ConclusionIt was inferred from this study that, in the absence of expert user, automated normalization of CBV using the proposed method could provide better diagnostic accuracy compared to the manual contralateral based approach.



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Copper-tolerant yeasts: Raman spectroscopy in determination of bioaccumulation mechanism

Abstract

Modern, efficient, and cost-effective approach to remediation of heavy metal-contaminated soil is based on the application of microorganisms. In this paper, four isolates from agricultural and urban contaminated soil showed abundant growth in the presence of copper(II) sulfate pentahydrate (CuSO₄·5H₂O) up to 2 mM. Selected yeasts were identified by molecular methods as Candida tropicalis (three isolates) and Schwanniomyces occidentalis (one isolate). C. tropicalis (4TD1101S) showed the highest percentage of bioaccumulation capabilities (94.37%), determined by the inductively coupled plasma optical emission spectrometry (ICP-OES). The Raman spectra of C. tropicalis (4TD1101S) analyzed in a medium with the addition of 2 mM CuSO₄·5H₂O showed certain increase in metallothionein production, which represents a specific response of the yeast species to the stress conditions. These results indicate that soil yeasts represent a potential for practical application in the bioremediation of contaminated environments.

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Three-dimensional assessment of the temporal bone and mandible deformations in patients with congenital aural atresia

To investigate the deformations of temporal bone and mandible combined with congenital aural atresia.

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Ultrasonographic assessment of tonsillar volume in children

We read with great interest the recent article by Asimakopoulos et Al. entitled "Ultrasonographic assessment of tonsillar volume in children" [1]. The study has been well planned and we would like to appreciate the effort made by the Authors to shed light on this topic. However there are few points regarding the methodology with which we have some reservations and would like to highlight these through your prestigious journal. First, the clinical utility of tonsillar volume as a predictor of OSAS severity has not been clearly demonstrated despite its widespread use.

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Response to: Ultrasonographic assessment of tonsillar volume in children

Thank you for the opportunity to respond to this correspondence. The principle aim of our study was to assess the suitability and validity of ultrasound as an objective tool for measuring tonsillar size and volume in children. This was tested as a pilot study of children undergoing adenotonsillectomy or tonsillectomy alone for obstructive sleep apnoea syndrome (OSAS) or recurrent tonsillitis, respectively. History and clinical assessment with polysomnography, in cases of diagnostic uncertainty, remains the gold standard investigations for diagnosing obstructing sleep apnoea.

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Comment on: ‘Impact of the method and success of pharyngeal reconstruction on the outcome of treating laryngeal and hypopharyngeal cancers with pharyngolaryngectomy: A national analysis’

Nouraei et al1 present an analysis of 1589 patients undergoing pharyngolaryngectomy in the UK between 2002–2012. This is a very interesting study that provides important information for reflection by specialist head and neck teams. Based upon the study findings, the authors conclude that alimentary conduits worsen short and long-term survival and advocate the centralisation of care within 3-4 specialised centres.

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Trends in dermatology practices and the implications for the workforce

Publication date: Available online 4 August 2017
Source:Journal of the American Academy of Dermatology
Author(s): Alison Ehrlich, James Kostecki, Helen Olkaba
BackgroundThe American Academy of Dermatology (AAD) practice profile surveys have been conducted for more than a decade to gauge trends in our workforce supply and demand.ObjectiveTo update the trends and current workforce issues for the field of dermatology.MethodsThe AAD Practice Profile Survey is sent by both e-mail and postal mail to a random sample of practicing dermatologists who are AAD members.ResultsShifts are noted in the primary practice setting; fewer dermatologists are in solo practice and more are in group practices than in previous years. Teledermatology use trended upward from 7% to 11% between 2012 and 2014. The implementation of electronic health records increased from 51% in 2011 to 70% in 2014.LimitationsThere is potential for response bias and inaccurate self-reporting. Survey responses collected may not be representative of all geographic areas.ConclusionThe demand for dermatology services remains strong. Shifts in the practice setting may be related to increases in overhead costs that are partially associated with the implementation of technology-based medical records. Integration of electronic health records and utilization of telemedicine are increasing.



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Facile synthesis of β-functionalized “push-pull” Zn(II) porphyrins for DSSC applications

Publication date: December 2017
Source:Dyes and Pigments, Volume 147
Author(s): Kamal Prakash, Shweta Manchanda, Vediappan Sudhakar, Nidhi Sharma, Muniappan Sankar, Kothandam Krishnamoorthy
Three new β-substituted "push-pull" Zn(II) porphyrin dyes with various electron donors at meso-positions and cyanoacetic acid as acceptor at β-position have been designed and synthesized. These porphyrins have been characterized by UV-Vis, Fluorescence, ¹H NMR and ¹³C NMR spectroscopic techniques and cyclic voltammetric studies. The Soret and Q band of Zn(II) porphyrin dyes were found to be red-shifted (30–35 nm) as compared to ZnTPP. The fluorescence quenching and the decrement in quantum yield and lifetime suggest intramolecular charge transfer from donor to acceptor. Zn porphyrins exhibited anodic shift in their first redox potentials (0.03–0.11 V) as compared to ZnTPP. The HOMO-LUMO energy levels of Zn porphyrin dyes were compared with the conduction band of TiO2 and the electrolyte I⁻/I3⁻. The HOMO levels of all the dyes are sufficiently higher than the energy level of electrolyte I⁻/I3⁻ and LUMO levels significantly lower than the conduction band of TiO2 which reflect the feasibility of facile electron-transfer. ZnT(Mes)P(CN-COOH) has been co-sensitized with N719 dye to further improve the PCE efficiency. These dyes displayed power conversion efficiency (PCE) of η = 1.72–3.13% where co-sensitized ZnT(Mes)P(CN-COOH) (N719) dye demonstrated maximum PCE efficiency up to 5.35%, with a Jsc of 11.8 mA cm⁻², a Voc of 630 mV and a fill factor (FF) of 72% due to better light harvesting capacity.

Graphical abstract

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Cleaved kininogen as a biomarker for bradykinin release in hereditary angioedema

Publication date: Available online 4 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Zonne L.M. Hofman, Steven de Maat, Chiara Suffritti, Andrea Zanichelli, Cassandra van Doorn, Silvie A.E. Sebastian, Nora Veszeli, Dorottya Csuka, Thomas Renné, Gerard Pasterkamp, Marco Cicardi, Henriette Farkas, C. Erik Hack, Coen Maas

Teaser

Cleaved high-molecular weight kininogen (cHK) in plasma is a biomarker for bradykinin formation. We developed an immuno-assay to detect cHK in plasma. cHK plasma levels are increased in asymptomatic C1-INH-HAE patients, and increase further during angioedema attacks.


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A new allergen family involved in pollen food associated syndrome: snakin/gibberellin regulated proteins

Publication date: Available online 4 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Hélène Sénéchal, Jiří Šantrůček, Magdalena Melčová, Petr Svoboda, Jarmila Zídková, Denis Charpin, Laurence Guilloux, Youcef Shahali, Marie-Ange Selva, Rémy Couderc, Tomoyasu Aizawa, Pascal Poncet

Teaser

At least two pollen food associated syndromes were described with cypress pollen allergy involving peach and citrus. Snakin/gibberellin regulated proteins are described herein to be the cross-reactive allergens between Cupressus sempervirens pollen and fruit/vegetables.


http://ift.tt/2v58zR5

Plasma cell deficiency in humans with heterozygous mutations in SEC61A1

Publication date: Available online 4 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Desirée Schubert, Marie-Christine Klein, Sarah Hassdenteufel, Andrés Caballero-Oteyza, Linlin Yang, Michele Proietti, Alla Bulashevska, Janine Kemming, Johannes Kühn, Sandra Winzer, Stephan Rusch, Manfred Fliegauf, Alejandro A. Schäffer, Stefan Pfeffer, Roger Geiger, Adolfo Cavalié, Hongzhi Cao, Fang Yang, Yong Li, Marta Rizzi, Hermann Eibel, Robin Kobbe, Amy L. Marks, Brian P. Peppers, Robert W. Hostoffer, Jennifer M. Puck, Richard Zimmermann, Bodo Grimbacher
BackgroundPrimary antibody deficiencies (PAD) are the most frequent primary immunodeficiencies in humans. The genetic causes for PADs are largely unknown. Sec61 translocon alpha 1 subunit (SEC61A1) is the major subunit of the Sec61 complex, which is the main polypeptide-conducting channel in the endoplasmic reticulum (ER) membrane. SEC61A1 is a target gene of XBP1s and strongly induced during plasma cell differentiation.ObjectiveCharacterization of a novel genetic defect and its pathological mechanism in eleven patients from two unrelated families with PAD.MethodsWhole exome sequencing (WES) and targeted sequencing were conducted to identify novel genetic mutations. Functional studies were carried out ex vivo in primary cells of patients and in vitro in different cell lines to assess the effect of SEC61A1 mutations on B cell differentiation and survival.ResultsWe investigated two families with patients suffering from hypogammaglobulinemia, severe recurrent respiratory tract infections and normal peripheral B- and T cell subpopulations. Upon in vitro stimulation, B cells showed an intrinsic deficiency to develop into plasma cells (PCs). Genetic analysis and targeted sequencing identified novel heterozygous missense (c.254T>A, p.V85D) and nonsense (c.1325G>T, p.E381*) mutations in SEC61A1, segregating with the disease phenotype. SEC61A1-V85D was deficient in co-translational protein translocation and it disturbed the cellular calcium homeostasis in HeLa cells. Moreover, SEC61A1-V85D triggered the terminal unfolded protein response (UPR) in multiple myeloma (MM) cell lines.ConclusionWe describe a monogenic defect leading to a specific plasma cell deficiency in humans, expanding our knowledge about the pathogenesis of antibody deficiencies.

Teaser

Heterozygous mutations in SEC61A1 are associated with plasma cell deficiency in patients with early-onset hypogammaglobulinemia and severe, recurrent respiratory tract infections but with normal B cell subpopulations in the peripheral blood.


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CDHR3 gene variation and childhood bronchiolitis

Publication date: Available online 4 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): A. Husby, A. Pasanen, J. Waage, A. Sevelsted, H. Hodemaekers, R. Janssen, M.K. Karjalainen, J. Stokholm, B.L. Chawes, M. Korppi, G. Wennergren, A. Heinzmann, L. Bont, H. Bisgaard, K. Bønnelykke

Teaser

This genetic study combining data from five countries shows that the CDHR3 rs6967330 polymorphism is not associated to bronchiolitis triggered by RSV but might increase risk of bronchiolitis triggered by other infectious agents.


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Blocking Bcl-2 resolves IL-13–mediated mucous cell hyperplasia in a Bik-dependent manner

Publication date: Available online 4 August 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Hitendra S. Chand, Yohannes A. Mebratu, Philip J. Kuehl, Yohannes Tesfaigzi




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Imaging of Intrathoracic Paragangliomas

Publication date: Available online 4 August 2017
Source:Seminars in Ultrasound, CT and MRI
Author(s): Daniel Ocazionez, Girish S. Shroff, Daniel Vargas, Demetrius Dicks, Abhishek Chaturvedi, Arun Nachiappan, Horacio Murillo, Ameya Baxi, Carlos S. Restrepo
Intrathoracic paragangliomas are uncommon and only represent 1–2% of paragangliomas. They are most commonly found in mediastinal compartments (aortopulmonary (AP) window or posterior mediastinum). Computed tomography, magnetic resonance and specific nuclear medicine radiotracers are routinely used to characterize these lesions and help exclude other more common conditions. Selective angiography is currently used for preoperative embolization and mapping of the vascular supply before surgical resection, rather than for diagnostic purposes alone.



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Prognostic value of programmed death ligand 1, p53, and Ki-67 in patients with advanced stage colorectal cancer

Publication date: Available online 4 August 2017
Source:Human Pathology
Author(s): Lisha Wang, Zebing Liu, Kurt W. Fisher, Fei Ren, Jiaojie Lv, Darrell D. Davidson, Lee A. Baldridge, Xiang Du, Liang Cheng
Current prognostic indicators are ineffective for identifying advanced stage colorectal cancer (CRC) patients with high risk of recurrence after surgical resection. We investigated the prognostic value of p53, Ki-67, and programmed death ligand 1 (PD-L1) in 254 patients with stage II and III CRC. The expression of p53 was positive in 63% of cases. Up-regulation of p53 was associated with smaller tumor size (P=.001) and higher Ki-67 labeling index (LI) (P=.031). The tumor Ki-67 LI was high (≥ 20%) in 197 (78%) of the patients. High Ki-67 LI was associated with higher TNM stage (P=.031), positive p53 expression (P=.031), and negative PD-L1 expression (P=.003). The five-year relapse-free survivals (RFS) were 53% and 89%, respectively, for the p53-positive and Ki-67 LI-high patients and the p53-negative and Ki-67 LI-low patients (P<.001). In univariate analysis, negative p53 (P=.001), low Ki-67 LI (P=.006), low PD-L1 expression (P=.044), low TNM stage (P<.001), recto-sigmoid location (P=.026), and small size (P=.013) were significantly related to RFS. In multivariate Cox regression analysis, positive p53 expression (hazard ratio [HR]: 2.48; 95% confidence interval: 1.34–4.59, P=.004), high Ki-67 LI (HR: 2.62; 95% CI: 1.12–6.14, P=.027) and high TNM stage (HR: 2.598, 95% CI: 1.55–4.37, P<.001,) were independent predictors of unfavorable prognosis. In summary, PD-L1, Ki-67, and p53 staining individually had significant prognostic value for patients with stage II and III CRC. Moreover, combining p53 H-score≥35 and Ki-67 LI≥20% identifies patients with poor clinical outcome.



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The differential diagnosis between pleural sarcomatoid mesothelioma and spindle cell/pleomorphic (sarcomatoid) carcinomas of the lung: Evidence-Based guidelines from the International Mesothelioma Panel and the MESOPATH National Reference Center

Publication date: Available online 4 August 2017
Source:Human Pathology
Author(s): Alberto M. Marchevsky, Nolwenn LeStang, Kenzo Hiroshima, Giuseppe Pelosi, Richard Attanoos, Andrew Churg, Lucien Chirieac, Sanja Dacic, Aliya Husain, Andras Khoor, Sonja Klebe, Silvie Lantuejoul, Victor Roggli, Jean-Michel Vignaud, Birgit Weynand, Jennifer Sauter, Douglas Henderson, Kazuki Nabeshima, Francoise Galateau-Salle
Immunohistochemistry is used to distinguish sarcomatoid malignant mesotheliomas (SMM) from spindle cell and pleomorphic carcinomas (SPC) but there are no guidelines on how to interpret cases that show overlapping or equivocal immunohistochemical findings. A systematic literature review of the immunophenotype of these lesions was performed and the experience with 587 SMM and 46 SPC at MESOPATH was collected. Data were analyzed with Comprehensive Meta-Analysis 2.0 software (Biostast, Englewood N.J.). There were insufficient data to evaluate the differential diagnosis between SPC and localized SMM or peritoneal SMM. Meta-analysis showed considerable overlap in the immunophenotype of these neoplasms and significant data heterogeneity amongst many of the results. Survival data from MESOPATH patients showed no significant differences in overall survival between SMM and SPC patients. Best-available evidence was used to formulate several evidence-based guidelines for the differential diagnosis between pleural SMM and SPC. These guidelines emphasize the need to correlate the histopathological findings with clinical and imaging information. Diffuse SMM can be diagnosed with certainty in the presence of malignant spindle cell pleural lesions showing immunoreactivity for cytokeratin and mesothelial markers and negative staining for epithelial markers. Criteria for the interpretation of various other combinations of immunoreactivity for cytokeratin, mesothelial and/or epithelial markers are proposed. Localized sarcomatoid mesotheliomas can only be diagnosed in the presence of spindle cell malignancies that exhibit immunoreactivity for cytokeratin and mesothelial markers and negative immunoreactivity for epithelial lesions, in patients that show no multifocal or diffuse pleural spread and no evidence for extrapleural lesions.



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Congenital cystic adenomatoid malformation – dangers of misdiagnosis: a case report

Congenital cystic adenomatoid malformation is a rare pulmonary malformation, but is the most common lung malformation observed in children. In developing countries, such as Morocco, prenatal diagnosis is missi...

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Inside EMS Podcast: Why does skill degradation happen in EMS?

Download this podcast on iTunes, SoundCloud or via RSS feed ​​In this Inside EMS Podcast episode, co-hosts Chris Cebollero and Kelly Grayson discuss the topic of skill degradation. The debate ranges from it being secondary to a lack of confidence, poor core knowledge, or is it really because of not using the skill" They also give some tips on how to keep your skills sharp. And after listening make ...

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Inside EMS Podcast: Why does skill degradation happen in EMS?

Download this podcast on iTunes, SoundCloud or via RSS feed ​​In this Inside EMS Podcast episode, co-hosts Chris Cebollero and Kelly Grayson discuss the topic of skill degradation. The debate ranges from it being secondary to a lack of confidence, poor core knowledge, or is it really because of not using the skill" They also give some tips on how to keep your skills sharp. And after listening make ...

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Health Services Research in Rehabilitation and Disability – The Time is Now

Publication date: Available online 4 August 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): James E. Graham, Addie Middleton, Janet Prvu Bettger, Trudy Mallinson, Pamela Roberts
Policy drives practice, and health services research (HSR) is at the intersection of policy, practice and patient outcomes. HSR specific to rehabilitation and disability is particularly needed. As rehabilitation researchers and providers, we are uniquely positioned to provide the evidence that guides reforms targeting rehabilitative care. We have the expertise to define the value of rehabilitation in a policy-relevant context. HSR is a powerful tool for providing this evidence. We need to continue building capacity for conducting rigorous, timely rehabilitation-related HSR. Fostering stakeholder engagement in these research efforts will ensure we maintain a patient-centered focus as we address the "Triple Aim" of better care, better health, and better value. In this Special Communication we discuss the role of rehabilitation researchers in HSR. We also provide information on current resources available in our field for conducting HSR and identify gaps for capacity-building and future research. Healthcare reforms are a reality, and through HSR we can give rehabilitation a strong voice during these transformative times.



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Supported Employment for Veterans with Traumatic Brain Injury: Patient Perspectives

Publication date: Available online 4 August 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Kathleen F. Carlson, Terri K. Pogoda, Tess Gilbert, Sandra G. Resnick, Elizabeth Twamley, Maya E. O'Neil, Nina A. Sayer
ObjectiveTo quantify the need for, and interest in, Supported Employment (SE) among recent military Veterans with traumatic brain injury (TBI), and to examine characteristics associated with Veterans' interest in SE.DesignStratified random sample of Iraq and Afghanistan War Veterans confirmed to have TBI through the Veterans Health Administration (VHA) screening and evaluation system.SettingCommunity-based via mailed survey.ParticipantsWe recruited 1,800 Veterans with clinician-confirmed TBI (1,080 mild TBI; 720 moderate/severe TBI) through multiple mailings. Among 1,451 whose surveys were not returned undeliverable, 616 (42%) responded.InterventionsNot applicable.Main Outcome MeasuresVeterans rated their interest in SE after reading a script describing the program. Additional measures assessed mental health and pain-related comorbidities, employment, financial/housing difficulties, demographics, and military service characteristics. Estimates were weighted to represent the population of Veterans with VHA clinician-confirmed TBI.ResultsUnemployment was reported by 45% (95% confidence interval [CI]: 43, 47) of Veterans with TBI. Although 42% (95% CI: 40, 44) reported they would be interested in using SE if it were offered to them, only 12% had heard of SE (95% CI: 11, 14) and <1% had used it. TBI severity and comorbidities were not associated with Veterans' interest in SE. However, those who were unemployed, looking for work, experiencing financial strain, or at risk for homelessness were more likely to be interested in SE.ConclusionsOur research highlights an important gap between Veterans' vocational needs and interests and their use of SE. Systematically identifying and referring those with employment and financial/housing difficulties may help close this gap.



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How Hsp90 and Cdc37 Lubricate Kinase Molecular Switches

Publication date: Available online 4 August 2017
Source:Trends in Biochemical Sciences
Author(s): Kliment A. Verba, David A. Agard
The Hsp90/Cdc37 chaperone system interacts with and supports 60% of the human kinome. Not only are Hsp90 and Cdc37 generally required for initial folding, but many kinases rely on the Hsp90/Cdc37 throughout their lifetimes. A large fraction of these 'client' kinases are key oncoproteins, and their interactions with the Hsp90/Cdc37 machinery are crucial for both their normal and malignant activity. Recently, advances in single-particle cryo-electron microscopy (cryoEM) and biochemical strategies have provided the first key molecular insights into kinase–chaperone interactions. The surprising results suggest a re-evaluation of the role of chaperones in the kinase lifecycle, and suggest that such interactions potentially allow kinases to more rapidly respond to key signals while simultaneously protecting unstable kinases from degradation and suppressing unwanted basal activity.



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Cosmetics, Vol. 4, Pages 26: Cosmeceuticals Properties of Sea Cucumbers: Prospects and Trends

Cosmetics, Vol. 4, Pages 26: Cosmeceuticals Properties of Sea Cucumbers: Prospects and Trends

Cosmetics doi: 10.3390/cosmetics4030026

Authors: Evi Siahaan Ratih Pangestuti Hendra Munandar Se-Kwon Kim

Cosmeceutical, a new term in the cosmetic industry, refers to cosmetic products that contain active ingredients and have medicinal benefits. Cosmeceuticals have attracted increased attention because of their beneficial effects on human health. Sea cucumbers, belonging to the class Holothuroidea, marine invertebrates, are rich in bioactive compounds, including saponin, chondroitin sulphate, collagen, amino acids, and phenols. These bioactive compounds have diverse functional roles as a secondary metabolite and these properties can be applied to the developments of novel cosmeceuticals. This review provides an overview the application of sea cucumber derivatives for cosmeceuticals. Further, prospects and trends of sea cucumber in cosmeceuticals industry were also discussed. The proper development of sea cucumber bioactive compounds will be helpful in cosmeceutical product development and industry.

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Autoimmune Subepidermal Bullous Diseases of the Skin and Mucosae: Clinical Features, Diagnosis, and Management

Abstract

Autoimmune subepidermal blistering diseases of the skin and mucosae constitute a large group of sometimes devastating diseases, encompassing bullous pemphigoid, gestational pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, and anti-p200 pemphigoid. Their clinical presentation is polymorphic. These autoimmune blistering diseases are associated with autoantibodies that target distinct components of the basement membrane zone of stratified epithelia. These autoantigens represent structural proteins important for maintenance of dermo-epidermal integrity. Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease of the skin and mucosae. Although the disease typically presents with a generalized blistering eruption associated with itch, atypical variants with either localized bullous lesions or "non-bullous" presentations are observed in approximately 20% of patients. A peculiar form of BP typically associated with pregnancy is pemphigoid gestationis. In anti-p200 pemphigoid, patients present with tense blisters on erythematosus or normal skin resembling BP, with a predilection for acral surfaces. These patients have antibodies targeting the 200-kDa basement membrane protein. Epidermolysis bullosa is a rare autoimmune blistering disease associated with autoantibodies against type VII collagen that can have several phenotypes including a classical form mimicking dystrophic epidermolysis bullosa, an inflammatory presentation mimicking BP, or mucous membrane pemphigoid-like lesions. Mucous membrane pemphigoid (MMP) is the term agreed upon by international consensus for an autoimmune blistering disorder, which affects one or more mucous membrane and may involve the skin. The condition involves a number of different autoantigens in the basement membrane zone. It may result in severe complications from scarring, such as blindness and strictures. Diagnosis of these diseases relies on direct immunofluorescence microscopy studies and immunoserological assays. Management of affected patients is often challenging. We will here review the clinical and immunopathological features as well as the pathophysiology of this group of organ-specific autoimmune diseases. Finally, we will discuss the diagnostic approach and the principles of management in clinical practice.

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Pathophysiology and immunological profile of myasthenia gravis and its subgroups

Publication date: December 2017
Source:Current Opinion in Immunology, Volume 49
Author(s): Fredrik Romi, Yu Hong, Nils Erik Gilhus
Myasthenia gravis (MG) is an autoimmune antibody-mediated disease characterized by muscle weakness and fatigability. It is believed that the initial steps triggering humoral immunity in MG take place inside thymic tissue and thymoma. The immune response against one or several epitopes expressed on thymic tissue cells spills over to neuromuscular junction components sharing the same epitope causing humoral autoimmunity and antibody production. The main cause of MG is acetylcholine receptor antibodies. However, many other neuromuscular junction membrane protein targets, intracellular and extracellular proteins are suggested to participate in MG pathophysiology. MG should be divided into subgroups based on clinical presentation and immunology. This includes onset age, clinical characteristics, thymic pathology and antibody profile. The immunological profile of these subgroups is determined by the antibodies present.



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Satb2 Cre/+ mouse as a tool to investigate cell fate determination in the developing neocortex

Publication date: Available online 3 August 2017
Source:Journal of Neuroscience Methods
Author(s): Mateusz Cyryl Ambrozkiewicz, Paraskevi Bessa, Andrea Salazar-Lázaro, Valentina Salina, Victor Tarabykin
BackgroundGeneration of different neuronal subtypes during neocortical development is the most important step in the establishment of cortical cytoarchitecture. The transcription factor Satb2 is expressed in neocortical projection neurons that send their axons intracortically as opposed to Satb2-negative neurons that preferentially project to subcortical targets.New MethodIn this report, we present a novel method to carry out large scale screening for molecules that control cell fate in the developing neocortex. It is based on a Satb2^Cre/+ mouse strain that expresses Cre recombinase from the Satb2 locus.ResultsBy transfecting neuronal progenitors with a Cre-inducible reporter construct by nucleofection or in utero electroporation, we could determine the proportion of cells that become Satb2-positive.Comparison with existing methods Compared to genetic tracing or lineage analysis, this method offers a fast, easy-to-perform and reliable way of determining cell fate of newly born neurons.ConclusionsWe demonstrate that the Satb2^Cre/+ mouse can be applied to study factors, such as small molecule inhibitors, sh-RNAs or overexpression constructs, that can alter the proportion of Satb2-positive cells and thus play key roles in differentiation and acquisition of cell fate.

Graphical abstract

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NoRMCorre: An online algorithm for piecewise rigid motion correction of calcium imaging data

Publication date: Available online 3 August 2017
Source:Journal of Neuroscience Methods
Author(s): Eftychios A. Pnevmatikakis, Andrea Giovannucci
BackgroundMotion correction is a challenging pre-processing problem that arises early in the analysis pipeline of calcium imaging data sequences. The motion artifacts in two-photon microscopy recordings can be non-rigid, arising from the finite time of raster scanning and non-uniform deformations of the brain medium.New methodWe introduce an algorithm for fast Non-Rigid Motion Correction (NoRMCorre) based on template matching. NoRMCorre operates by splitting the field of view (FOV) into overlapping spatial patches along all directions. The patches are registered at a sub-pixel resolution for rigid translation against a continuously updated template. The estimated alignments are subsequently up-sampled to create a smooth motion field for each frame that can efficiently approximate non-rigid artifacts in a piecewise-rigid manner.Existing methodsExisting approaches either do not scale well in terms of computational performance or are targeted to non-rigid artifacts arising just from the finite speed of raster scanning, and thus cannot correct for non-rigid motion observable in datasets from a large FOV.ResultsNoRMCorre can be run in an online mode resulting in comparable to or even faster than real time motion registration of streaming data. We evaluate its performance with simple yet intuitive metrics and compare against other non-rigid registration methods on simulated data and in vivo two-photon calcium imaging datasets. Open source Matlab and Python code is also made available.ConclusionsThe proposed method and accompanying code can be useful for solving large scale image registration problems in calcium imaging, especially in the presence of non-rigid deformations.



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Electrical stimulation of different retinal components and the effect of asymmetric pulses

Publication date: Available online 3 August 2017
Source:Journal of Neuroscience Methods
Author(s): Dorit Raz-Prag, Giora Beit-Yaakov, Yael Hanein
BackgroundHigh resolution electrical stimulation of neural tissue is a fundamental challenge in applications such as deep brain stimulation and artificial vision. In artificial vision, achieving and validating local selective epi-retinal stimulation of different layers in the retina is particularly challenging owing to plurality of retinal cell types and delocalized wiring.ResultsStrong selectivity and non-localized responses to epi-retinal stimulation, over a wide range of realistic stimulation parameters, was achieved and validated using asymmetric pulses.New MethodThe reported method consists of multi electrode array (MEA) stimulation and recording from a developing chick retina combined with calcium imaging. Data show direct and indirect neuronal activation in the chick retina model. In particular, axonal activation, orientation and conduction velocity are derived, and the non-local nature of the responses to direct axonal stimulation is demonstrated.Comparison with Existing MethodsSome of the previous research with mammalian retinas demonstrated local responses around the stimulating electrode, revealing little as to axonal activation. Recent studies showed activation along the nerve fibers and studied the effect of pulse duration to improve stimulation localization (Twyford and Fried, 2016; Weitz et al., 2015). The chick retina offers a straight forward mapping of axonal activation. Here we demonstrate that the chick retina, combined with MEA recording and stimulation along with calcium imaging is a powerful tool to study retinal activation and in particular the effect of asymmetry on axonal activation.ConclusionsMEA recording and stimulation from the chick retina is exceptionally powerful in distinguishing between direct and indirect responses. This method facilitates comparison between different stimulation strategies. We show that asymmetric electrical stimulations allow control over the intensity of direct activation.

Graphical abstract

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An Initial Validation of the Virtual of the Virtual Environment Grocery Store

Publication date: Available online 3 August 2017
Source:Journal of Neuroscience Methods
Author(s): Thomas D. Parsons, Timothy McMahan
BackgroundVirtual reality-based neuropsychological assessments proffer the potential to address the limited ecological validity of pen-and-paper measures of memory.New MethodTo investigate the construct validity of a newly developed virtual reality-based multiple errands task, the Virtual Environment Grocery Store (VEGS), two studies were performed.Comparison with Existing Method(s)In Study 1, we explored construct validity via comparison of traditional neuropsychological measures of memory and executive functioning with a low distraction condition of the VEGS. In Study 2, a new sample was used to compare traditional neuropsychological measures of memory and executive functioning with a high distraction condition of the VEGS.ResultsPerformances on the VEGS memory tasks (in Study 1: low distraction condition) and the traditional neuropsychological assessments of memory were positively correlated, indicating that memory for VEGS content was similar to memory for traditional paper-and-pencil measures. Again, in Study 2, performances on the VEGS memory tasks correlated with the traditional neuropsychological assessments of memory, indicating that memory for VEGS content was similar to memory for traditional paper-and-pencil measures. As expected, though, the addition of distractors into the virtual environment resulted in significant correlations with traditional measures of inhibitory control.ConclusionsThe VEGS has the advantage over traditional measures of providing objective measurement of individual components of memory in simulations of everyday activities.



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Pachychoroid pigment epitheliopathy in fellow eyes of patients with unilateral central serous chorioretinopathy

Aims

To investigate the prevalence of pachychoroid pigment epitheliopathy (PPE) in fellow eyes of patients with unilateral central serous chorioretinopathy (CSC) and to determine differences between patients with PPE, uncomplicated pachychoroid (UCP) and normal fellow eyes.

Methods

We retrospectively reviewed 536 patients with CSC. Demographic and medical data, spectral domain optical coherence tomography scans with enhanced depth imaging mode, infrared reflectance images and fundus autofluorescence images were obtained from the patients' medical records.

Results

254 (47.4%) of 536 patients had bilateral CSC. The female to male ratio was 1/2.8 in all patients with CSC. In patients with unilateral CSC (282 patients), 61% of fellow eyes had PPE, 30.8% had UCP and 8.2% were normal. There were no significant differences between patients with PPE, UCP and normal eyes in age, duration of disease, sex, presence of systemic hypertension, steroid use, psychopharmacological medication use, refractive error or central foveal thickness. Eyes with PPE and UCP did not differ regarding subfoveal choroidal thickness. In eyes with PPE (172 eyes), 77.3% had retinal pigment epithelium (RPE) bumps and 43% had pigment epithelium detachment.

Conclusion

PPE is common in fellow eyes of patients with CSC. There is no difference between PPE and UCP regarding demographic characteristics and medical features.

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Short-term vision gains at 12 weeks correlate with long-term vision gains at 2 years: results from the BEVORDEX randomised clinical trial of bevacizumab versus dexamethasone implants for diabetic macular oedema

Aim

To determine whether early vision gains predict long-term visual outcomes in the BEVORDEX randomised clinical trial of bevacizumab or dexamethasone implants for diabetic macular oedema.

Methods

Post hoc analysis of 68 study eyes (77%) that completed 2 years follow-up of the BEVORDEX multicentre randomised clinical trial set in Australia (ClinicalTrials.gov identifier: NCT01298076). Study eyes from both groups were combined and stratified by visual acuity (VA) change in the first 12 weeks in to three groups: (a) suboptimal gain: <5 letters gain (includes VA loss), (b) moderate gain: 5–9 letters gain, (c) pronounced gain: ≥10 letters gain. This was correlated with VA outcome at 104 weeks taking into account treatment allocation and baseline lens status.

Results

The change in VA in the first 12 weeks was significantly correlated with VA change at 104 weeks (p<0.001). This was independent of treatment allocation (p=0.353) and lens status at baseline (p=0.593). The change in central macular thickness at 12 weeks did not correlate with VA gain at 104 weeks (p=0.847).

Conclusion

Short-term visual gain at 12 weeks was strongly correlated with long-term vision improvement independent of treatment allocation or baseline lens status. Early improvement in central macular thickness was not predictive of long-term visual outcomes.

Trial registration number

NCT01298076, Post-results.

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Effect of Radiofrequency on DNA Damage and Oxidative Status in Patients with Turbinate Hypertrophy

Abstract

The radiofrequency devices that are used generate radiofrequency in the frequency range of 1.5 and 2.5 MHz. This study aims to demonstrate whether systematic oxidative status and DNA are influenced in this frequency range. In study, 27 patients who received radiofrequency treatment on inferior turbinate as they were diagnosed with inferior turbinate hypertrophy. DNA damage was assessed by alkaline comet assay in peripheral lymphocyte cells. Plasma levels of total antioxidant status (TAS), total oxidative status (TOS) were determined by using an automated measurement method and oxidative stress index (OSI) was calculated (OSI was calculated as: OSI = (TOS/TAS) × 100). There were increased in the OSI and TOS values on days 1 and 15 as compared to the samples taken before the radiofrequency administration. Significant decreases were seen in TAS values on days 1 and 15. As for the DNA damage, no significant differences were found on day 15 compared to the preoperative values even though there was a statistically insignificant increase on day 1. Administration of radiofrequency radiation on inferior turbinates results in increased oxidative stress in the acute period and a decrease in the anti-oxidative system. Although this effect causes a slight increase in the DNA damage in the early post-operative period, the damage is restored to the pre-operative levels on day 15. Therefore, we believe that a more conservative approach should be selected for radiofrequency treatment instead of using it routinely.

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HMGB1, an innate alarmin, plays a critical role in chronic inflammation of adipose tissue in obesity

Publication date: 15 October 2017
Source:Molecular and Cellular Endocrinology, Volume 454
Author(s): Jing Zhang, Lei Zhang, Shu Zhang, Qilin Yu, Fei Xiong, Kun Huang, Cong-Yi Wang, Ping Yang
Obesity has emerged as an imminent global public health concern over the past several decades. It has now become evident that obesity is characterized by the persistent and low-grade inflammation in the adipose tissue, and serves as an independent risk factor for many metabolic disorders such as diabetes and cardiovascular disease. Particularly, adipocytes originated from obese mice and humans likely predominate necrosis upon stressful insults, leading to passive release of cellular contents including the high mobility group box 1 (HMGB1) into the extracellular milieu. Extracellular HMGB1 acts as an innate alarmin to stimulate the activation of resident immune cells in the adipose tissue. Upon activation, those resident immune cells actively secrete additional HMGB1, which in turn activates/recruits additional immune cells, and induces adipocyte death. This review summarizes those novel discoveries in terms of HMGB1 in the initiation and maintenance of chronic inflammatory state in adipose tissue in obesity, and discusses its potential application in clinical settings.



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Corrigendum to “Transplantation of alginate-encapsulated seminiferous tubules and interstitial tissue into adult rats: Leydig stem cell differentiation in vivo?” [Mol. Cell. Endocrinol. 436 (2016) 250–258]

Publication date: 15 October 2017
Source:Molecular and Cellular Endocrinology, Volume 454
Author(s): Haolin Chen, Shiying Jin, Shengsong Huang, Janet Folmer, June Liu, Renshan Ge, Barry R. Zirkin




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Corrigendum to “Leydig cell stem cells: Identification, proliferation and differentiation” [Mol. Cell. Endocrinol. XXX (2016) 1–9]

Publication date: 15 October 2017
Source:Molecular and Cellular Endocrinology, Volume 454
Author(s): Haolin Chen, Yiyan Wang, Renshan Ge, Barry R. Zirkin




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Corrigendum to “A multi-step, allosteric model of testosterone's binding to sex hormone binding globulin” [Mol. Cell. Endocrinol. 399 (2015) 190–200]

Publication date: 15 October 2017
Source:Molecular and Cellular Endocrinology, Volume 454
Author(s): Mikhail N. Zakharov, Shalender Bhasin, Thomas G. Travison, Ran Xue, Jagadish Ulloor, Vasan Ramachandran, Emma Carter, Frederick Wu, Ravi Jasuja




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A neoplasm with FIP1L1-PDGFRA fusion presenting as pediatric T-cell lymphoblastic leukemia/lymphoma without eosinophilia

Publication date: Available online 3 August 2017
Source:Cancer Genetics
Author(s): Matthew J. Oberley, Christopher Denton, Jianling Ji, Matthew Hiemenz, Deepa Bhojwani, Dejerianne Ostrow, Samuel Wu, Paul Gaynon, Gordana Raca
The 2016 World Health Organization (2016 WHO) classification of hematopoietic malignancies classifies neoplasms with a fusion between the FIP1L1 and PDGFRA genes in 4q12 into a group called "myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 or with PCM1-JAK2". Neoplasms characterized by this fusion are pluripotent stem cell disorders that can show both myeloid and lymphoid differentiation. They typically occur in adult patients and most are characterized by eosinophilia. We describe identification of a FIP1L1-PDGFRA fusion in a 13-year-old boy who presented with T-lymphoblastic leukemia/lymphoma without eosinophilia. Detection of FIP1L1- PDGFRA driven neoplasms at diagnosis is usually critical for proper treatment, since almost all reported cases responded to tyrosine kinase inhibitors. However, our patient's leukemia was refractory to standard chemotherapy, and did not show a meaningful response to tyrosine kinase inhibitor therapy. Testing for a FIP1L1- PDGFRA rearrangement is at present limited to patients with idiopathic hypereosinophilia, and we hypothesize that this abnormality may be under-diagnosed in children with acute leukemias.



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Lack of NOD2 attenuates ovariectomy-induced bone loss via inhibition of osteoclasts

Nucleotide-binding oligomerization domain-2 (NOD2) is a pattern recognition receptor of the innate immune system. It interacts with serine-threonine kinases to induce activation of nuclear factor B (NF-B), which is important for receptor activator of nuclear factor kappa-B ligand (RANKL) signaling. We tested the idea that NOD2 modulates bone metabolism via an action on osteoclasts (OCs). The absence of NOD2 reduced ovariectomy-induced bone loss in mice, and lowered the area and the activity of OCs, by impairing RANKL signaling. It also reduced the level of reactive oxygen species (ROS), as well as of NF-B-DNA binding upon RANKL exposure. NOD2 was found to physically interact with nicotinamide adenine dinucleotide phosphate oxidase 1 and this led to increased production of ROS in OCs. Our data suggest that NOD2 contributes to bone loss in estrogen deficiency by elevating ROS levels in OCs.

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Pituitary stem cell regulation: who is pulling the strings?

The pituitary gland plays a pivotal role in the endocrine system, steering fundamental processes of growth, metabolism, reproduction and coping with stress. The adult pituitary contains resident stem cells, which are highly quiescent in homeostatic conditions. However, the cells show marked signs of activation during processes of increased cell remodeling in the gland, including maturation at neonatal age, adaptation to physiological demands, regeneration upon injury and growth of local tumors. Although functions of pituitary stem cells are slowly but gradually uncovered, their regulation largely remains virgin territory. Since postnatal stem cells in general reiterate embryonic developmental pathways, attention is first being given to regulatory networks involved in pituitary embryogenesis. Here, we give an overview of the current knowledge on the NOTCH, WNT, epithelial–mesenchymal transition, SHH and Hippo pathways in the pituitary stem/progenitor cell compartment during various (activation) conditions from embryonic over neonatal to adult age. Most information comes from expression analyses of molecular components belonging to these networks, whereas functional extrapolation is still very limited. From this overview, it emerges that the 'big five' embryonic pathways are indeed reiterated in the stem cells of the 'lazy' homeostatic postnatal pituitary, further magnified en route to activation in more energetic, physiological and pathological remodeling conditions. Increasing the knowledge on the molecular players that pull the regulatory strings of the pituitary stem cells will not only provide further fundamental insight in postnatal pituitary homeostasis and activation, but also clues toward the development of regenerative ideas for improving treatment of pituitary deficiency and tumors.

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Improvement of obesity-linked skeletal muscle insulin resistance by strength and endurance training

Obesity-linked insulin resistance is mainly due to fatty acid overload in non-adipose tissues, particularly skeletal muscle and liver, where it results in high production of reactive oxygen species and mitochondrial dysfunction. Accumulating evidence indicates that resistance and endurance training alone and in combination can counteract the harmful effects of obesity increasing insulin sensitivity, thus preventing diabetes. This review focuses the mechanisms underlying the exercise role in opposing skeletal muscle insulin resistance-linked metabolic dysfunction. It is apparent that exercise acts through two mechanisms: (1) it stimulates glucose transport by activating an insulin-independent pathway and (2) it protects against mitochondrial dysfunction-induced insulin resistance by increasing muscle antioxidant defenses and mitochondrial biogenesis. However, antioxidant supplementation combined with endurance training increases glucose transport in insulin-resistant skeletal muscle in an additive fashion only when antioxidants that are able to increase the expression of antioxidant enzymes and/or the activity of components of the insulin signaling pathway are used.

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Metabolic and neuroprotective effects of dapagliflozin and liraglutide in diabetic mice

This study assessed the metabolic and neuroprotective actions of the sodium glucose cotransporter-2 inhibitor dapagliflozin in combination with the GLP-1 agonist liraglutide in dietary-induced diabetic mice. Mice administered low-dose streptozotocin (STZ) on a high-fat diet received dapagliflozin, liraglutide, dapagliflozin-plus-liraglutide (DAPA-Lira) or vehicle once-daily over 28 days. Energy intake, body weight, glucose and insulin concentrations were measured at regular intervals. Glucose tolerance, insulin sensitivity, hormone and biochemical analysis, dual-energy X-ray absorptiometry densitometry, novel object recognition, islet and brain histology were examined. Once-daily administration of DAPA-Lira resulted in significant decreases in body weight, fat mass, glucose and insulin concentrations, despite no change in energy intake. Similar beneficial metabolic improvements were observed regarding glucose tolerance, insulin sensitivity, HOMA-IR, HOMA-β, HbA1c and triglycerides. Plasma glucagon, GLP-1 and IL-6 levels were increased and corticosterone concentrations decreased. DAPA-Lira treatment decreased alpha cell area and increased insulin content compared to dapagliflozin monotherapy. Recognition memory was significantly improved in all treatment groups. Brain histology demonstrated increased staining for doublecortin (number of immature neurons) in dentate gyrus and synaptophysin (synaptic density) in stratum oriens and stratum pyramidale. These data demonstrate that combination therapy of dapagliflozin and liraglutide exerts beneficial metabolic and neuroprotective effects in diet-induced diabetic mice. Our results highlight important personalised approach in utilising liraglutide in combination with dapagliflozin, instead of either agent alone, for further clinical evaluation in treatment of diabetes and associated neurodegenerative disorders.

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Kritische Bemerkungen zu den neuen diagnostischen Kriterien des M. Menière

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Kritische Bemerkungen zu den neuen diagnostischen Kriterien des M. Menière

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Impact of aging immune system on neurodegeneration and potential immunotherapies

Publication date: Available online 4 August 2017
Source:Progress in Neurobiology
Author(s): Zhanfeng Liang, Yang Zhao, Linhui Ruan, Linnan Zhu, Kunlin Jin, Qichuan Zhuge, Dong-Ming Su, Yong Zhao
The interaction between the nervous and immune systems during aging is an area of avid interest, but many aspects remain unclear. This is due, not only to the complexity of the aging process, but also to a mutual dependency and reciprocal causation of alterations and diseases between both the nervous and immune systems. Aging of the brain drives whole body systemic aging, including aging-related changes of the immune system. In turn, the immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution that are sources of chronic inflammation in the elderly (termed inflammaging), potentially induces brain aging and memory loss in a reciprocal manner. Therefore, immunotherapeutics including modulation of inflammation, vaccination, cellular immune therapies and "protective autoimmunity" provide promising approaches to rejuvenate neuroinflammatory disorders and repair brain injury. In this review, we summarize recent discoveries linking the aging immune system with the development of neurodegeneration. Additionally, we discuss potential rejuvenation strategies, focusing aimed at targeting the aging immune system in an effort to prevent acute brain injury and chronic neurodegeneration during aging.



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Effect of Radiofrequency on DNA Damage and Oxidative Status in Patients with Turbinate Hypertrophy

Abstract

The radiofrequency devices that are used generate radiofrequency in the frequency range of 1.5 and 2.5 MHz. This study aims to demonstrate whether systematic oxidative status and DNA are influenced in this frequency range. In study, 27 patients who received radiofrequency treatment on inferior turbinate as they were diagnosed with inferior turbinate hypertrophy. DNA damage was assessed by alkaline comet assay in peripheral lymphocyte cells. Plasma levels of total antioxidant status (TAS), total oxidative status (TOS) were determined by using an automated measurement method and oxidative stress index (OSI) was calculated (OSI was calculated as: OSI = (TOS/TAS) × 100). There were increased in the OSI and TOS values on days 1 and 15 as compared to the samples taken before the radiofrequency administration. Significant decreases were seen in TAS values on days 1 and 15. As for the DNA damage, no significant differences were found on day 15 compared to the preoperative values even though there was a statistically insignificant increase on day 1. Administration of radiofrequency radiation on inferior turbinates results in increased oxidative stress in the acute period and a decrease in the anti-oxidative system. Although this effect causes a slight increase in the DNA damage in the early post-operative period, the damage is restored to the pre-operative levels on day 15. Therefore, we believe that a more conservative approach should be selected for radiofrequency treatment instead of using it routinely.

http://ift.tt/2vpos5P

The protective effects of electro-acupuncture in thoracic surgery on trauma stressed rats involve the rostral ventrolateral medulla and supraoptic nucleus

Publication date: Available online 3 August 2017
Source:Brain Research Bulletin
Author(s): Huan-Huan Zhang, Yi-Nan Tao, Mei-Yan Jiang, Jin Wang, Jun Chen, Chun-Mei Xia, Lin-Lin Shen, Meng-Ya Wang, Da-Nian Zhu
The present study was designed to explore whether the rostral ventrolateral medulla (RVLM) and supraoptic nucleus (SON) were involved in the protective effects of electro-acupuncture (EA) on cardiac function in thoracic surgery on trauma-stressed rats. The rats were randomly divided into a non-stressed group (Control), surgical trauma-stressed group (Trauma), and Neiguan EA applied on the surgical trauma-stressed group (Trauma+EA-PC 6). RVLM neuron discharge was observed by using an in vivo electrophysiological method, and micro-dialysis combining high-performance liquid chromatography with fluorometric detection (HPLC-FD) was used to assess expression of amino acids in the RVLM. Immunohistochemical methods were used to assess c-Fos expression in SON neurons. The trauma of surgical stress was shown to dramatically increase the discharge frequency of RVLM neurons and promote the release of glutamate and taurine in the RVLM. The expression of c-Fos was also significantly increased in the SON of traumatized rats. EA application at Neiguan acupoints significantly suppressed trauma-induced increase of discharge frequency of the RVLM neurons, almost completely suppressed the trauma-induced increase of glutamate release but only very slightly reduced the trauma-enhanced taurine release, and inhibited the increase of c-Fos expression in these SON neurons of traumatized rats. These results indicate that Neiguan EA may regulate cardiac function by modulating neurons in the RVLM and the SON in surgically traumatized rats. The taurine-mediated negative feedback may be involved in the protective effect of EA on cardiac function.



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