Comparison between universal adhesives and two-step self-etch adhesives in terms of dentin bond fatigue durability in self-etch mode

This aim of this study was to compare universal adhesives and two-step self-etch adhesives in terms of dentin bond fatigue durability in self-etch mode. Three universal adhesives – Clearfil Universal, G-Premio Bond, and Scotchbond Universal Adhesive – and three-two-step self-etch adhesives – Clearfil SE Bond, Clearfil SE Bond 2, and OptiBond XTR – were used. The initial shear bond strength and shear fatigue strength of resin composite bonded to adhesive on dentin in self-etch mode were determined. Scanning electron microscopy observations of fracture surfaces after bond strength tests were also made. The initial shear bond strength of universal adhesives was material dependent, unlike that of two-step self-etch adhesives. The shear fatigue strength of Scotchbond Universal Adhesive was not significantly different from that of two-step self-etch adhesives, unlike the other universal adhesives. The shear fatigue strength of universal adhesives differed depending on the type of adhesive, unlike those of two-step self-etch adhesives. The results of this study encourage the continued use of two-step self-etch adhesive over some universal adhesives but suggest that changes to the composition of universal adhesives may lead to a dentin bond fatigue durability similar to that of two-step self-etch adhesives.

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Metal-enhanced fluorescence/visual bimodal platform for multiplexed ultrasensitive detection of microRNA with reusable paper analytical devices

Publication date: 15 September 2017
Source:Biosensors and Bioelectronics, Volume 95
Author(s): Linlin Liang, Feifei Lan, Xuemei Yin, Shenguang Ge, Jinghua Yu, Mei Yan
Convenient biosensor for simultaneous multi-analyte detection was increasingly required in biological analysis. A novel flower-like silver (FLS)-enhanced fluorescence/visual bimodal platform for the ultrasensitive detection of multiple miRNAs was successfully constructed for the first time based on the principle of multi-channel microfluidic paper-based analytical devices (µPADs). Fluorophore-functionalized DNA1 (DNA1-N-CDs) was combined with FLS, which was hybridized with quencher-carrying strand (DNA2-CeO2) to form FLS-enhanced fluorescence biosensor. Upon the addition of the target miRNA, the fluorescent intensity of DNA1-N-CDs within the proximity of the FLS was strengthened. The disengaged DNA/CeO2 complex could result in color change after joining H2O2, leading to real-time visual detection of miRNA firstly. If necessary, then the fluorescence method was applied for a accurate determination. In this strategy, the growth of FLS in µPADs not only reduced the background fluorescence but also provided an enrichment of "hot spots" for surface enhanced fluorescence detection of miRNAs. Results also showed versatility of the FLS in the enhancement of sensitivity and selectivity of the miRNA biosensor. Remarkably, this biosensor could detect as low as 0.03fM miRNA210 and 0.06fM miRNA21. Interestingly, the proposed biosensor also possessed good capability of recycling in three cycles upon change of the supplementation of DNA2-CeO2 and visual substitutive device. This method opened new opportunities for further studies of miRNA related bioprocesses and will provide a new instrument for simultaneous detection of multiple low-level biomarkers.

Graphical abstract

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Recent progress in Prussian blue films: Methods used to control regular nanostructures for electrochemical biosensing applications

Publication date: 15 October 2017
Source:Biosensors and Bioelectronics, Volume 96
Author(s): Zhenyu Chu, Yu Liu, Wanqin Jin
In the last decade, Prussian blue (PB) has attracted increased scientific interest in various research fields, such as fuel cells, gas separation and pollution treatment. Due to its advanced catalysis, biocompatibility, selectivity and stability, PB has been widely used in biosensor construction. However, the formation of regular PB nanostructures is challenging due to its fast crystallization rate. Recently, developments in this research area have increased due to emerging novel synthesis methods in nanoscale technology. Various regular nanostructures of PB films that show superior biosensing performance have been prepared. In this review, recent research progress in PB nanostructures is summarized, with special emphasis on the methodology of nanostructure control. The mechanism and key factors in regular PB crystallization are also discussed for each synthesis method. The performance of PB nanostructure-based biosensors is compared with others to show the advantages of nanostructure control. The methodology discussed in this review not only include the regular growth of PB films, but also provides information on the nanostructure control of more crystalline materials, including PB analogues, noble metals, metal oxides and coordination compounds. In addition to biosensing applications and the development of more advanced nanostructures, PB has also shown increased advanced properties in other scientific areas.



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Eggshell membrane-templated synthesis of 3D hierarchical porous Au networks for electrochemical nonenzymatic glucose sensor

Publication date: 15 October 2017
Source:Biosensors and Bioelectronics, Volume 96
Author(s): Shu-Lin Zhong, Junyang Zhuang, Da-Peng Yang, Dianping Tang
Sensitive and accurate test of blood glucose levels is necessary to monitor and prevent diabetic complications. Herein, we developed a novel and sensitive non-enzymatic glucose sensing platform by employing 3D hierarchical porous Au networks (HPANs) as electrocatalyst for glucose oxidization. The HPANs were prepared through a bio-inspired synthesis method, in which the natural eggshell membrane (ESM) was introduced as template. The structure and properties of the as-prepared HPANs were characterized by a set of techniques, including scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), powder X-ray diffraction (XRD) and cyclic voltammetry (CV). The HPANs showed high catalytic activity towards glucose oxidization due to the unique structure. Inspiringly, the HPANs-based electrochemical glucose sensor could be driven at low potential (+0.1V) and showed an outstanding performance for glucose determination with two linear ranges of 1–500μM and 4.0–12mM, a limit of detection (LOD) of 0.2μM (3σ), and fast response time (less than 2s). Moreover, the stability and anti-interference performance of developed sensor was also excellent, enabling its preliminary application in clinical sample (human serum) test. Significantly, this work offered an environmentally friendly method for fabricating 3D nanostructure by using ESM (a biowaste) as template, setting up a typical example for producing new value-added nanomaterials with sensing application.



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Characterization of the foreign body response to common surgical biomaterials in a murine model

Abstract

Background

Implanted biomaterials are subject to a significant reaction from the host, known as the foreign body response (FBR). We quantified the FBR to five materials following subcutaneous implantation in mice.

Methods

Polyvinyl alcohol (PVA) and silicone sheets are considered highly biocompatible biomaterials and were cut into 8-mm-diameter disks. Expanded PTFE (ePTFE) and polypropylene are also widely used biocompatible biomaterials and were cut into 2 cm-long cylinders. Cotton was selected as a negative control material that would invoke an intense FBR, was cut into disks, and implanted. The implants were inserted subcutaneously into female C57BL/6 mice. On post-implantation days 14, 30, 60, 90, and 180, implants were retrieved. Cellularity was assessed with DAPI stain, collagen with Masson's trichrome stain, mast cells with toluidine blue, macrophages with F4/80 immunohistochemical stain, and capsular thickness and foreign body giant cells with hematoxylin and eosin.

Results

DAPI revealed a significantly increased cellularity in both PVA and silicone, and ePTFE had the lowest cell density. Silicone showed the lowest cellularity at day 14 and day 90, whereas ePTFE showed the lowest cellularity at days 30, 60, and 180. Masson's trichrome staining demonstrated no apparent difference in collagen. Toluidine blue showed no differences in mast cells. There were, however, fewer macrophages associated with ePTFE. On day 14, PVA had highest number of macrophages, whereas polypropylene had the highest number at all time points after d14. Giant cells increased earlier and gradually decreased later. On day 90, PVA exhibited a significantly increased number of giant cells compared to polypropylene and silicone. Silicone consistently formed the thinnest capsule throughout all time points. On day 14, cotton had formed the thickest capsule. On day 30, polypropylene gas formed the thickest capsule, and on days 60, 90, and 180, PVA had formed the thickest capsule.

Conclusions

These data reveal differences in capsule thickness and cellular response in an implant-related manor, indicating that fibrotic reactions to biomaterials are implant-specific and should be carefully considered when performing studies on fibrosis when biomaterials are being used.

Level of Evidence: Not ratable

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Editorial Board and Contents

Publication date: May 2017
Source:Trends in Immunology, Volume 38, Issue 5





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Ångstrom-size exocytotic fusion pore: Implications for pituitary hormone secretion

Publication date: Available online 27 April 2017
Source:Molecular and Cellular Endocrinology
Author(s): Marko Kreft, Jernej Jorgačevski, Matjaž Stenovec, Robert Zorec
In the past, vesicle content release was thought to occur immediately and completely after triggering of exocytosis. However, vesicles may merge with the plasma membrane to form an Ångstrom diameter fusion pore that prevents the exit of secretions from the vesicle lumen. The advantage of such a narrow pore is to minimize the delay between the trigger and the release. Instead of stimulating a sequence of processes, leading to vesicle merger with the plasma membrane and a formation of a fusion pore, the stimulus only widens the pre-established fusion pore. The fusion pore may be stable and may exhibit repetitive opening of the vesicle lumen to the cell exterior accompanied by a content discharge. Such release of vesicle content is partial (subquantal), and depends on fusion pore open time, diameter and the diffusibility of the cargo. Such transient mode of fusion pore opening was not confirmed until the development of the membrane capacitance patch-clamp technique, which enables high-resolution measurement of changes in membrane surface area. It allows millisecond dwell-time measurements of fusion pores with subnanometer diameters. Currently, the soluble N-ethylmaleimide-sensitive factor-attachment protein receptor (SNARE) proteins are considered to be key entities in end-stage exocytosis, and the SNARE complex assembly/disassembly may regulate the fusion pore. Moreover, lipids or other membrane constituents with anisotropic (non-axisymmetric) geometry may also favour the establishment of stable narrow fusion pores, if positioned in the neck of the fusion pore.

Graphical abstract

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Mandibular wing osteotomy: technical modification

Sometimes conventional orthognathic treatment cannot achieve the desired results. Mandibular wing osteotomy of the lower border, as first described by Triaca et al,1 comprises the entire inferior border under the inferior alveolar nerve (IAN). It can correct the profile of the lower face without changing the interocclusal relations.2 We present a modification of the technique, which improves safety by reducing the possibility of damage to the IAN.

http://ift.tt/2oRO1Ww

New method of arch bar fixation

Intermaxillary fixation (IMF) can be done in several ways, and arch bars, brackets, IMF screws and bone-supported arch bars are among them.

http://ift.tt/2p9KtS0

Accuracy of maxillary repositioning by computer-aided orthognathic surgery in patients with normal temporomandibular joints

Our aim was to assess the accuracy of computer-aided orthognathic surgery for maxillary repositioning in 15 patients with mandibular hyperplasia and normal temporomandibular joints (TMJ). We aligned preoperative and postoperative virtual skulls at the cranium using surface superimposition then recorded and calibrated three 3-dimensional coordinates (maxillary dental landmarks U0, 6R, and 6L) on the skulls. Errors between these preoperative and postoperative landmarks were calculated and the largest error of every patient was chosen for assessment.

http://ift.tt/2oRO1G0

Integration of mental health screening in the management of patients with temporomandibular disorders

Mental health disorders such as depression or anxiety, or both, are more common in patients with temporomandibular disorders (TMD) (16%-40%) than in the general population (16%), and failure to recognise them may be detrimental to the management of TMD. Paper-based screening tools previously reported in this group require assessment by clinicians and subsequent collation of data. We describe our experience of a new system − IMPARTS (Integrating mental and physical: research training and services), which uses validated tools to identify and to monitor the progress of patients who may benefit from psychological intervention.

http://ift.tt/2p9JrFD

Preliminary investigation of preoperative pregabalin and total intravenous anesthesia doses: a randomized controlled trial

To determine the efficacy of 2 different doses (150-300mg) of preoperative pregabalin on propofol and remifentanil doses for total intravenous anesthesia in laparoscopic cholecystectomy.

http://ift.tt/2oOUJvv

Thymus neuroendocrine tumors with CTNNB1 gene mutations, disarrayed ß-catenin expression, and dual intra-tumor Ki-67 labeling index compartmentalization challenge the concept of secondary high-grade neuroendocrine tumor: a paradigm shift

Abstract

We herein report an uncommon association of intimately admixed atypical carcinoid (AC) and large cell neuroendocrine (NE) carcinoma (LCNEC) of the thymus, occurring in two 20- and 39-year-old Caucasian males. Both tumors were treated by maximal thymectomy. The younger patient presented with a synchronous lesion and died of disease after 9 months, while the other patient was associated with a recurrent ectopic adrenocorticotropic hormone Cushing's syndrome and is alive with disease at the 2-year follow-up. MEN1 syndrome was excluded in either case. Immunohistochemically, disarrayed cytoplasmic and nuclear ß-catenin expression was seen alongside an intra-tumor Ki-67 antigen labeling index (LI) ranging from 2 to 80% in the younger patient's tumor and from 3 to 45% in the other. Both exhibited upregulated cyclin D1 and retinoblastoma, while vimentin was overexpressed in the recurrent LCNEC only. Next-generation sequencing revealed CTNNB1, TP53, and JAK3 mutations in the synchronous tumor and CTNNB1 mutation alone in the metachronous tumor (the latter with the same mutation as the first tumor of 17 years prior). None of the 23 T-NET controls exhibited this hallmarking triple alteration (p = 0.003). These findings suggested that LCNEC components developed from pre-existing CTNNB1-mutated AC upon loss-of-function TP53 and gain-of-function JAK3 mutations in one case and an epithelial-mesenchymal transition upon vimentin overexpression in the other case. Both tumors maintained intact cyclin D1–retinoblastoma machinery. Our report challenges the concept of secondary LCNEC as an entity that develops from pre-existing AC as a result of tumor progression, suggesting a paradigm shift to the current pathogenesis of NET.

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Tackling the perils of unawareness: the cluster headache case

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Response to Letter to the Editor: RE: Henry, J.A., Frederick, M., Sell, S, Griest, S., Abrams, H. (2015) Validation of a Novel Combination Hearing Aid and Tinnitus Therapy Device, Ear Hear, 36(1): 42–52

No abstract available

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Electrocochleography in Cochlear Implant Recipients With Residual Hearing: Comparison With Audiometric Thresholds

Objectives: To determine whether electrocochleography (ECoG) thresholds, especially cochlear microphonic and auditory nerve neurophonic thresholds, measured using an intracochlear electrode, can be used to predict pure-tone audiometric thresholds following cochlear implantation in ears with residual hearing. Design: Pure-tone audiometric thresholds and ECoG waveforms were measured at test frequencies from 125 to 4000 Hz in 21 Advanced Bionics cochlear implant recipients with residual hearing in the implanted ear. The "difference" and "summation" responses were computed from the ECoG waveforms measured from two alternating phases of stimulation. The interpretation is that difference responses are largely from the cochlear microphonic while summating responses are largely from the auditory nerve neurophonic. The pure-tone audiometric thresholds were also measured with same equipment used for ECoG measurements. Results: Difference responses were observed in all 21 implanted ears, whereas summation response waveforms were observed in only 18 ears. The ECoG thresholds strongly correlated (r2 = 0.87, n = 150 for difference response; r2 = 0.82, n = 72 for summation response) with audiometric thresholds. The mean difference between the difference response and audiometric thresholds was −3.2 (±9.0) dB, while the mean difference between summation response and audiometric thresholds was −14 (±11) dB. In four out of 37 measurements, difference responses were measured to frequencies where no behavioral thresholds were present. Conclusions: ECoG thresholds may provide a useful metric for the assessment of residual hearing in cochlear implant subjects for whom it is not possible to perform behavioral audiometric testing.

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The Effect of Interaural Mismatches on Contralateral Unmasking With Single-Sided Vocoders

Objectives: Cochlear-implant (CI) users with single-sided deafness (SSD)—that is, one normal-hearing (NH) ear and one CI ear—can obtain some unmasking benefits when a mixture of target and masking voices is presented to the NH ear and a copy of just the masking voices is presented to the CI ear. NH listeners show similar benefits in a simulation of SSD-CI listening, whereby a mixture of target and masking voices is presented to one ear and a vocoded copy of the masking voices is presented to the opposite ear. However, the magnitude of the benefit for SSD-CI listeners is highly variable across individuals and is on average less than for NH listeners presented with vocoded stimuli. One possible explanation for the limited benefit observed for some SSD-CI users is that temporal and spectral discrepancies between the acoustic and electric ears might interfere with contralateral unmasking. The present study presented vocoder simulations to NH participants to examine the effects of interaural temporal and spectral mismatches on contralateral unmasking. Design: Speech-reception performance was measured in a competing-talker paradigm for NH listeners presented with vocoder simulations of SSD-CI listening. In the monaural condition, listeners identified target speech masked by two same-gender interferers, presented to the left ear. In the bilateral condition, the same stimuli were presented to the left ear, but the right ear was presented with a noise-vocoded copy of the interfering voices. This paradigm tested whether listeners could integrate the interfering voices across the ears to better hear the monaural target. Three common distortions inherent in CI processing were introduced to the vocoder processing: spectral shifts, temporal delays, and reduced frequency selectivity. Results: In experiment 1, contralateral unmasking (i.e., the benefit from adding the vocoded maskers to the second ear) was impaired by spectral mismatches of four equivalent rectangular bandwidths or greater. This is equivalent to roughly a 3.6-mm mismatch between the cochlear places stimulated in the electric and acoustic ears, which is on the low end of the average expected mismatch for SSD-CI listeners. In experiment 2, performance was negatively affected by a temporal mismatch of 24 ms or greater, but not for mismatches in the 0 to 12 ms range expected for SSD-CI listeners. Experiment 3 showed an interaction between spectral shift and spectral resolution, with less effect of interaural spectral mismatches when the number of vocoder channels was reduced. Experiment 4 applied interaural spectral and temporal mismatches in combination. Performance was best when both frequency and timing were aligned, but in cases where a mismatch was present in one dimension (either frequency or latency), the addition of mismatch in the second dimension did not further disrupt performance. Conclusions: These results emphasize the need for interaural alignment—in timing and especially in frequency—to maximize contralateral unmasking for NH listeners presented with vocoder simulations of SSD-CI listening. Improved processing strategies that reduce mismatch between the electric and acoustic ears of SSD-CI listeners might improve their ability to obtain binaural benefits in multitalker environments.

http://ift.tt/2qdxUqj

Long-Term Synergistic Interaction of Cisplatin- and Noise-Induced Hearing Losses

Objective: Past experiments in the literature have shown that cisplatin interacts synergistically with noise to create hearing loss. Much of the previous work on the synergistic interaction of noise and cisplatin tested exposures that occurred very close together in time. The present study assessed whether rats that have been exposed to cisplatin continue to show increased susceptibility to noise-induced hearing loss months after conclusion of the cisplatin exposure. Design: Thirty-two Fischer 344/NHsd rats were exposed to one of five conditions: (1) cisplatin exposure followed by immediate cochlear tissue harvest, (2) cisplatin exposure and a 20-week monitoring period before tissue harvest, (3) cisplatin exposure followed immediately by noise exposure, (4) cisplatin exposure followed by noise exposure 16 weeks later, and (5) noise exposure without cisplatin exposure. The cisplatin exposure was an 8-week interval in which cisplatin was given every 2 weeks. Cochlear injury was evaluated using auditory brainstem response thresholds, P1 wave amplitudes, and postmortem outer hair cell counts. Results: The 8-week cisplatin exposure induced little threshold shift or P1 amplitude loss, and a small lesion of missing outer hair cells in the basal half of the cochlea. The rats exposed to noise immediately after the cisplatin exposure interval showed a synergistic interaction of cisplatin and noise. The group exposed to noise 16 weeks after the cisplatin exposure interval also showed more severe threshold shift and outer hair cell loss than control subjects. The controls exposed to cisplatin and monitored for 20 weeks showed little threshold shift or outer hair cell loss, but did show P1 wave amplitude changes over the 20-week monitoring period. Conclusions: The results from the groups exposed to cisplatin followed by noise, combined with the findings from the cisplatin- and noise-only groups, suggest that the cisplatin induced cochlear injuries that were not severe enough to result in threshold shift, but left the cochlea in a state of heightened susceptibility to future injury. The heightened susceptibility to noise injury was still present 16 weeks after the conclusion of the cisplatin exposure.

http://ift.tt/2qdzGri

Effects of Hearing Impairment and Hearing Aid Amplification on Listening Effort: A Systematic Review

Objectives: To undertake a systematic review of available evidence on the effect of hearing impairment and hearing aid amplification on listening effort. Two research questions were addressed: Q1) does hearing impairment affect listening effort? and Q2) can hearing aid amplification affect listening effort during speech comprehension? Design: English language articles were identified through systematic searches in PubMed, EMBASE, Cinahl, the Cochrane Library, and PsycINFO from inception to August 2014. References of eligible studies were checked. The Population, Intervention, Control, Outcomes, and Study design strategy was used to create inclusion criteria for relevance. It was not feasible to apply a meta-analysis of the results from comparable studies. For the articles identified as relevant, a quality rating, based on the 2011 Grading of Recommendations Assessment, Development, and Evaluation Working Group guidelines, was carried out to judge the reliability and confidence of the estimated effects. Results: The primary search produced 7017 unique hits using the keywords: hearing aids OR hearing impairment AND listening effort OR perceptual effort OR ease of listening. Of these, 41 articles fulfilled the Population, Intervention, Control, Outcomes, and Study design selection criteria of: experimental work on hearing impairment OR hearing aid technologies AND listening effort OR fatigue during speech perception. The methods applied in those articles were categorized into subjective, behavioral, and physiological assessment of listening effort. For each study, the statistical analysis addressing research question Q1 and/or Q2 was extracted. In seven articles more than one measure of listening effort was provided. Evidence relating to Q1 was provided by 21 articles that reported 41 relevant findings. Evidence relating to Q2 was provided by 27 articles that reported 56 relevant findings. The quality of evidence on both research questions (Q1 and Q2) was very low, according to the Grading of Recommendations Assessment, Development, and Evaluation Working Group guidelines. We tested the statistical evidence across studies with nonparametric tests. The testing revealed only one consistent effect across studies, namely that listening effort was higher for hearing-impaired listeners compared with normal-hearing listeners (Q1) as measured by electroencephalographic measures. For all other studies, the evidence across studies failed to reveal consistent effects on listening effort. Conclusion: In summary, we could only identify scientific evidence from physiological measurement methods, suggesting that hearing impairment increases listening effort during speech perception (Q1). There was no scientific, finding across studies indicating that hearing aid amplification decreases listening effort (Q2). In general, there were large differences in the study population, the control groups and conditions, and the outcome measures applied between the studies included in this review. The results of this review indicate that published listening effort studies lack consistency, lack standardization across studies, and have insufficient statistical power. The findings underline the need for a common conceptual framework for listening effort to address the current shortcomings.

http://ift.tt/2qdzTuB

Prevalence, Incidence Proportion, and Heritability for Tinnitus: A Longitudinal Twin Study

Objectives: The purpose of this longitudinal twin study was to explore the effect of tinnitus on hearing thresholds and threshold shifts over two decades and to investigate the genetic contribution to tinnitus in a male twin cohort (n = 1114 at baseline and 583 at follow-up). The hypothesis was that participants with faster hearing deterioration had a higher risk for developing tinnitus and there is an underlying role of genetic influences on tinnitus. Design: Male mono- and dizygotic twin pairs, born between 1914 and 1958 were included. Mixed models were used for comparison of hearing threshold shifts, adjusted for age. A co-twin comparison was made within pairs discordant for tinnitus. The relative influence of genetic and environmental factors was estimated by genetic modeling. Results: The overall prevalence of tinnitus was 13.5% at baseline ( age 50) and 34.4% at follow-up ( age 67). The overall incidence proportion was 27.8%. Participants who reported tinnitus at baseline or at both time points were older. At baseline, the hearing thresholds differed between tinnitus cases and controls at all frequencies. New tinnitus cases at follow-up had the greatest hearing threshold shift at the high-frequency area compared with the control group. Within pairs, the tinnitus twin had poorer hearing than his unaffected co-twin, more so for dizygotic than monozygotic twin pairs. The relative proportion of additive genetic factors was approximately 0.40 at both time points, and the influence of individual-specific environment was 0.56 to 0.61. The influence of genetic factors on tinnitus was largely independent of genetic factors for hearing thresholds. Conclusions: Our hypotheses were confirmed: The fastest hearing deterioration occurred for new tinnitus cases. A moderate genetic influence for tinnitus was confirmed.

http://ift.tt/2qdzGaM

Sequential Bilateral Cochlear Implantation in Children: Outcome of the Second Implant and Long-Term Use

Objectives: The aim of this retrospective cohort study was to assess speech perception outcomes of second-side cochlear implants (CI2) relative to first-side implants (CI1) in 160 participants who received their CI1 as a child. The predictive factors of CI2 speech perception outcomes were investigated. In addition, CI2 device use predictive models were assessed using the categorical variable of participant's decision to use CI2 for a minimum of 5 years after surgery. Findings from a prospective study that evaluated the bilateral benefit for speech recognition in noise in a participant subgroup (n = 29) are also presented. Design: Participants received CI2 between 2003 and 2009 (and CI1 between 1988 and 2008), and were observed from surgery to a minimum of 5 years after sequential surgery. Group A (n = 110) comprised prelingually deaf children (severe to profound) with no or little acquired oral language before implantation, while group B (n = 50) comprised prelingually deaf children with acquired language before implantation, in addition to perilingually and postlingually deaf children. Speech perception outcomes included the monosyllable test score or the closed-set Early Speech Perception test score if the monosyllable test was too difficult. To evaluate bilateral benefit for speech recognition in noise, participants were tested with the Hearing in Noise test in bilateral and "best CI" test conditions with noise from the front and noise from either side. Bilateral advantage was calculated by subtracting the Hearing in Noise test speech reception thresholds in noise obtained in the bilateral listening mode from those obtained in the unilateral "best CI" mode. Results: On average, CI1 speech perception was 28% better than CI2 performance in group A, the same difference was 20% in group B. A small bilateral speech perception benefit of using CI2 was measured, 3% in group A and 7% in group B. Longer interimplant interval predicted poorer CI2 speech perception in group A, but only for those who did not use a hearing aid in the interimplant interval in group B. At least 5 years after surgery, 25% of group A and 10% of group B did not use CI2. In group A, prediction factors for nonuse of CI2 were longer interimplant intervals or CI2 age. Large difference in speech perception between the two sides was a predictor for CI2 nonuse in both groups. Bilateral advantage for speech recognition in noise was mainly obtained for the condition with noise near the "best CI"; the addition of a second CI offered a new head shadow benefit. A small mean disadvantage was measured when the noise was located opposite to the "best CI." However, the latter was not significant. Conclusions: Generally, in both groups, if CI2 did not become comparable with CI1, participants were more likely to choose not to use CI2 after some time. In group A, increased interimplant intervals predicted poorer CI2 speech perception results and increased the risk of not using CI2 at a later date. Bilateral benefit was mainly obtained when noise was opposite to CI2, introducing a new head shadow benefit.

http://ift.tt/2qdzEzG

Effect of Context and Hearing Loss on Time-Gated Word Recognition in Children

Objectives: The purpose of this study was to examine word recognition in children who are hard of hearing (CHH) and children with normal hearing (CNH) in response to time-gated words presented in high- versus low-predictability sentences (HP, LP), where semantic cues were manipulated. Findings inform our understanding of how CHH combine cognitive-linguistic and acoustic-phonetic cues to support spoken word recognition. It was hypothesized that both groups of children would be able to make use of linguistic cues provided by HP sentences to support word recognition. CHH were expected to require greater acoustic information (more gates) than CNH to correctly identify words in the LP condition. In addition, it was hypothesized that error patterns would differ across groups. Design: Sixteen CHH with mild to moderate hearing loss and 16 age-matched CNH participated (5 to 12 years). Test stimuli included 15 LP and 15 HP age-appropriate sentences. The final word of each sentence was divided into segments and recombined with the sentence frame to create series of sentences in which the final word was progressively longer by the gated increments. Stimuli were presented monaurally through headphones and children were asked to identify the target word at each successive gate. They also were asked to rate their confidence in their word choice using a five- or three-point scale. For CHH, the signals were processed through a hearing aid simulator. Standardized language measures were used to assess the contribution of linguistic skills. Results: Analysis of language measures revealed that the CNH and CHH performed within the average range on language abilities. Both groups correctly recognized a significantly higher percentage of words in the HP condition than in the LP condition. Although CHH performed comparably with CNH in terms of successfully recognizing the majority of words, differences were observed in the amount of acoustic-phonetic information needed to achieve accurate word recognition. CHH needed more gates than CNH to identify words in the LP condition. CNH were significantly lower in rating their confidence in the LP condition than in the HP condition. CHH, however, were not significantly different in confidence between the conditions. Error patterns for incorrect word responses across gates and predictability varied depending on hearing status. Conclusions: The results of this study suggest that CHH with age-appropriate language abilities took advantage of context cues in the HP sentences to guide word recognition in a manner similar to CNH. However, in the LP condition, they required more acoustic information (more gates) than CNH for word recognition. Differences in the structure of incorrect word responses and their nomination patterns across gates for CHH compared with their peers with NH suggest variations in how these groups use limited acoustic information to select word candidates.

http://ift.tt/2qdzKaw

Dichotic Digits Test Performance Across the Ages: Results From Two Large Epidemiologic Cohort Studies

Objectives: The Dichotic Digits test (DDT) has been widely used to assess central auditory processing but there is limited information on observed DDT performance in a general population. The purpose of the study was to determine factors related to DDT performance in a large cohort spanning the adult age range. Design: The study was cross-sectional and subjects were participants in the Epidemiology of Hearing Loss Study (EHLS), a population-based investigation of age-related hearing loss, or the Beaver Dam Offspring Study (BOSS), a study of aging in the adult offspring of the EHLS members. Subjects seen during the 4th EHLS (2008 to 2010) or the 2nd BOSS (2010 to 2013) examination were included (N = 3655 participants [1391 EHLS, 2264 BOSS]; mean age = 61.1 years, range = 21 to 100 years). The free and right ear-directed recall DDTs were administered using 25 sets of triple-digit pairs with a 70 dB HL presentation level. Pure-tone audiometric testing was conducted and the pure-tone threshold average (PTA) at 0.5, 1, 2, and 4 kHz was categorized using the worse ear: no loss = PTA ≤ 25 dB HL; mild loss = 25 40 dB HL. Cognitive impairment was defined as a Mini-Mental State Examination score

http://ift.tt/2qdkF9a

Directional Microphone Contralateral Routing of Signals in Cochlear Implant Users: A Within-Subjects Comparison

Objectives: For medical or financial reasons, bilateral cochlear implantation is not always possible in bilaterally deafened patients. In such cases, a contralateral routing of signals (CROS) device could complement the monaural implant. The goal of our study was to compare the benefit of three different conditions: (1) unilateral cochlear implant (CI) alone, (2) unilateral CI complemented with a directional CROS microphone, and (3) bilateral CIs. Design: Twelve bilateral experienced CI users were tested. Speech reception in noise and sound localization were measured in the three above-mentioned conditions. Patients evaluated which condition they presumed to be activated and the subjective benefit on a hearing scale. Results: Compared with the unilateral CI condition, the additional CROS device provided significantly better speech intelligibility in noise when speech signals came from the front or side of the CROS microphone. Only small subjective improvement was observed. Bilateral-activated CIs further improved the hearing performance. This was the only condition where sound localization was possible. Subjective evaluation showed a clear preference for the bilateral CI treatment. Conclusions: In bilateral deafened patients, bilateral implantation is the most preferable form of treatment. However, patients with one implant only could benefit from an additional directional microphone CROS device.

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Children With Cochlear Implants and Their Parents: Relations Between Parenting Style and Children’s Social-Emotional Functioning

Objectives: Parenting a child who has a severe or profound hearing loss can be challenging and at times stressful, and might cause parents to use more adverse parenting styles compared with parents of hearing children. Parenting styles are known to impact children's social-emotional development. Children with a severe to profound hearing loss may be more reliant on their parents in terms of their social-emotional development when compared with their hearing peers who typically have greater opportunities to interact with and learn from others outside their family environment. Identifying the impact which parenting styles pertain on the social-emotional development of children who have cochlear implants (CIs) could help advance these children's well-being. Therefore, the authors compared parenting styles of parents with hearing children and of parents with children who have a CI, and examined the relations between parenting styles and two key aspects of children's social-emotional functioning: emotion regulation and empathy. Design: Ninety-two hearing parents and their children (aged 1 to 5 years old), who were either hearing (n = 46) or had a CI (n = 46), participated in this cross-sectional study. Parents completed questionnaires concerning their parenting styles (i.e., positive, negative and uninvolved), and regarding the extent to which their children expressed negative emotions (i.e., anger and sadness) and empathy. Furthermore, an emotion-regulation task measuring negative emotionality was administered to the children. Results: No differences in reported parenting styles were observed between parents of hearing children and parents of children with a CI. In addition, negative and uninvolved parenting styles were related to higher levels of negative emotionality in both groups of children. No relation was found between positive parenting and children's social-emotional functioning. Hearing status did not moderate these relationships. Language mediated the relationship between parenting styles and children's social-emotional functioning. Conclusions: Children's hearing status did not impact parenting styles. This may be a result of the support that parents of children with a CI receive during their enrollment in the rehabilitation program preceding and after implantation. Rehabilitation programs should dedicate more attention to informing parents about the impact of parenting behaviors on children's social-emotional functioning. Offering parenting courses as part of the program could promote children's well-being. Future longitudinal research should address the directionality of the relations between parenting styles and children's social-emotional functioning.

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Letter to the Editor: Reporting of Data to Inform the Design of a Definitive Trial Re: Henry, J.A., Frederick, M., Sell, S., Griest, S., Abrams, H. (2015). Validation of a Novel Combination Hearing Aid and Tinnitus Therapy Device, Ear Hear, 36(1): 42–52

No abstract available

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Effects of Stimulus Polarity and Artifact Reduction Method on the Electrically Evoked Compound Action Potential

Objective: Previous research from our laboratory comparing electrically evoked compound action potential (ECAP) artifact reduction methods has shown larger amplitudes and lower thresholds with cathodic-leading forward masking (CathFM) than with alternating polarity (AltPol). One interpretation of this result is that the anodic-leading phase used with AltPol elicits a less excitatory response (in contrast to results from recent studies with humans), which when averaged with responses to cathodic-leading stimuli, results in smaller amplitudes. Another interpretation is that the latencies of the responses to anodic- and cathodic-leading pulses differ, which when averaged together, result in smaller amplitudes than for either polarity alone due to temporal smearing. The purpose of this study was to separate the effects of stimulus polarity and artifact reduction method to determine the relative effects of each. Design: This study used a within-subjects design. ECAP growth functions were obtained using CathFM, anodic-leading forward masking (AnodFM), and AltPol for 23 CI recipients (N = 13 Cochlear and N = 10 Advanced Bionics). N1 latency, amplitude, slope of the amplitude growth function, and threshold were compared across methods. Data were analyzed separately for each manufacturer due to inherent differences between devices. Results: N1 latencies were significantly shorter for AnodFM than for CathFM and AltPol for both Cochlear and Advanced Bionics participants. Amplitudes were larger for AnodFM than for either CathFM or AltPol for Cochlear recipients; amplitude was not significantly different across methods for Advanced Bionics recipients. Slopes were shallowest for CathFM for Cochlear subjects, but were not significantly different among methods for Advanced Bionics subjects. Thresholds with AltPol were significantly higher than both FM methods for Cochlear recipients; there was no difference in threshold across methods for the Advanced Bionics recipients. Conclusions: For Cochlear devices, the smaller amplitudes and higher thresholds observed for AltPol seem to be the result of latency differences between polarities. These results suggest that AltPol is not ideal for managing stimulus artifact for ECAP recordings. For the Advanced Bionics group, there were no significant differences among methods for amplitude, slope, or threshold, which suggests that polarity and artifact reduction method have little influence in these devices. We postulate that polarity effects are minimized for symmetrical biphasic pulses that lack an interphase gap, such as those used with Advanced Bionics devices; however, this requires further investigation.

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Normative Wideband Reflectance, Equivalent Admittance at the Tympanic Membrane, and Acoustic Stapedius Reflex Threshold in Adults

Objectives: Wideband acoustic immittance (WAI) measures such as pressure reflectance, parameterized by absorbance and group delay, equivalent admittance at the tympanic membrane (TM), and acoustic stapedius reflex threshold (ASRT) describe middle ear function across a wide frequency range, compared with traditional tests employing a single frequency. The objective of this study was to obtain normative data using these tests for a group of normal-hearing adults and investigate test–retest reliability using a longitudinal design. Design: A longitudinal prospective design was used to obtain normative test and retest data on clinical and WAI measures. Subjects were 13 males and 20 females (mean age = 26 years). Inclusion criteria included normal audiometry and clinical immittance. Subjects were tested on two separate visits approximately 1 month apart. Reflectance and equivalent admittance at the TM were measured from 0.25 to 8.0 kHz under three conditions: at ambient pressure in the ear canal and with pressure sweeps from positive to negative pressure (downswept) and negative to positive pressure (upswept). Equivalent admittance at the TM was calculated using admittance measurements at the probe tip that were adjusted using a model of sound transmission in the ear canal and acoustic estimates of ear-canal area and length. Wideband ASRTs were measured at tympanometric peak pressure (TPP) derived from the average TPP of downswept and upswept tympanograms. Descriptive statistics were obtained for all WAI responses, and wideband and clinical ASRTs were compared. Results: Mean absorbance at ambient pressure and TPP demonstrated a broad band-pass pattern typical of previous studies. Test–retest differences were lower for absorbance at TPP for the downswept method compared with ambient pressure at frequencies between 1.0 and 1.26 kHz. Mean tympanometric peak-to-tail differences for absorbance were greatest around 1.0 to 2.0 kHz and similar for positive and negative tails. Mean group delay at ambient pressure and at TPP were greatest between 0.32 and 0.6 kHz at 200 to 300 μsec, reduced at frequencies between 0.8 and 1.5 kHz, and increased above 1.5 kHz to around 150 μsec. Mean equivalent admittance at the TM had a lower level for the ambient method than at TPP for both sweep directions below 1.2 kHz, but the difference between methods was only statistically significant for the comparison between the ambient method and TPP for the upswept tympanogram. Mean equivalent admittance phase was positive at all frequencies. Test–retest reliability of the equivalent admittance level ranged from 1 to 3 dB at frequencies below 1.0 kHz, but increased to 8 to 9 dB at higher frequencies. The mean wideband ASRT for an ipsilateral broadband noise activator was 12 dB lower than the clinical ASRT, but had poorer reliability. Conclusions: Normative data for the WAI test battery revealed minor differences for results at ambient pressure compared with tympanometric methods at TPP for reflectance, group delay, and equivalent admittance level at the TM for subjects with middle ear pressure within ±100 daPa. Test–retest reliability was better for absorbance at TPP for the downswept tympanogram compared with ambient pressure at frequencies around 1.0 kHz. Large peak-to-tail differences in absorbance combined with good reliability at frequencies between about 0.7 and 3.0 kHz suggest that this may be a sensitive frequency range for interpreting absorbance at TPP. The mean wideband ipsilateral ASRT was lower than the clinical ASRT, consistent with previous studies. Results are promising for the use of a wideband test battery to evaluate middle ear function.

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Some Neurocognitive Correlates of Noise-Vocoded Speech Perception in Children With Normal Hearing: A Replication and Extension of Eisenberg et al. (2002)

Objectives: Noise-vocoded speech is a valuable research tool for testing experimental hypotheses about the effects of spectral degradation on speech recognition in adults with normal hearing (NH). However, very little research has utilized noise-vocoded speech with children with NH. Earlier studies with children with NH focused primarily on the amount of spectral information needed for speech recognition without assessing the contribution of neurocognitive processes to speech perception and spoken word recognition. In this study, we first replicated the seminal findings reported by Eisenberg et al. (2002) who investigated effects of lexical density and word frequency on noise-vocoded speech perception in a small group of children with NH. We then extended the research to investigate relations between noise-vocoded speech recognition abilities and five neurocognitive measures: auditory attention (AA) and response set, talker discrimination, and verbal and nonverbal short-term working memory. Design: Thirty-one children with NH between 5 and 13 years of age were assessed on their ability to perceive lexically controlled words in isolation and in sentences that were noise-vocoded to four spectral channels. Children were also administered vocabulary assessments (Peabody Picture Vocabulary test-4th Edition and Expressive Vocabulary test-2nd Edition) and measures of AA (NEPSY AA and response set and a talker discrimination task) and short-term memory (visual digit and symbol spans). Results: Consistent with the findings reported in the original Eisenberg et al. (2002) study, we found that children perceived noise-vocoded lexically easy words better than lexically hard words. Words in sentences were also recognized better than the same words presented in isolation. No significant correlations were observed between noise-vocoded speech recognition scores and the Peabody Picture Vocabulary test-4th Edition using language quotients to control for age effects. However, children who scored higher on the Expressive Vocabulary test-2nd Edition recognized lexically easy words better than lexically hard words in sentences. Older children perceived noise-vocoded speech better than younger children. Finally, we found that measures of AA and short-term memory capacity were significantly correlated with a child's ability to perceive noise-vocoded isolated words and sentences. Conclusions: First, we successfully replicated the major findings from the Eisenberg et al. (2002) study. Because familiarity, phonological distinctiveness and lexical competition affect word recognition, these findings provide additional support for the proposal that several foundational elementary neurocognitive processes underlie the perception of spectrally degraded speech. Second, we found strong and significant correlations between performance on neurocognitive measures and children's ability to recognize words and sentences noise-vocoded to four spectral channels. These findings extend earlier research suggesting that perception of spectrally degraded speech reflects early peripheral auditory processes, as well as additional contributions of executive function, specifically, selective attention and short-term memory processes in spoken word recognition. The present findings suggest that AA and short-term memory support robust spoken word recognition in children with NH even under compromised and challenging listening conditions. These results are relevant to research carried out with listeners who have hearing loss, because they are routinely required to encode, process, and understand spectrally degraded acoustic signals.

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Three-Dimensional Force Profile During Cochlear Implantation Depends on Individual Geometry and Insertion Trauma

Objectives: To preserve the acoustic hearing, cochlear implantation has to be as atraumatic as possible. Therefore, understanding the impact of the cochlear geometry on insertion forces and intracochlear trauma might help to adapt and improve the electrode insertion and reduce the probability of intracochlear trauma. Design: The study was conducted on 10 fresh-frozen human temporal bones. The inner ear was removed from the temporal bone. The bony capsule covering the scala vestibuli was removed and the dissected inner ear was mounted on the three-dimensional (3D) force measurement system (Agilent technologies, Nano UTM, Santa Clare, CA). A lateral wall electrode array was inserted, and the forces were recorded in three dimensions with a sensitivity of 2 μN. Afterwards, the bones were scanned using a Skyscan 1173 micro-computed tomography (micro-CT). The obtained 3D force profiles were correlated with the videos of the insertions recorded through the microscope, and the micro-CT images. Results: A correlation was found between intracochlear force profiles measured in three different directions with intracochlear trauma detected with micro-CT imaging. The angle of insertion and the cochlear geometry had a significant impact on the electrode array insertion forces and possible insertion trauma. Intracochlear trauma occurred frequently within the first 180° from the round window, where buckling of the proximal part of the electrode carrier inside the cochlea, and rupturing of the spiral ligament was observed. Conclusions: The combination of the 3D force measurement system and micro-CT can be used to characterize the mechanical behavior of a CI electrode array and some forms of insertion trauma. Intracochlear trauma does not always correlate with higher force amplitudes, but rather with an abrupt change of force directions.

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The Change in Electrical Stimulation Levels During 24 Months Postimplantation for a Large Cohort of Adults Using the Nucleus® Cochlear Implant

Objectives: To examine electrical stimulation data over 24 months postimplantation in adult implant users. The first aim was to calculate mean T and C levels for seven time points, for four cochlear segments, and two array types. The second aim was to (a) analyze the degree of change in each of the T and C levels as a function of dynamic range for six consecutive time point comparisons, for the four segments, and (b) to determine the proportion of participants with an acceptable degree of change. The third aim was to examine relationships between demographic factors and degree of change. Design: T levels, C levels, and dynamic ranges were extracted for 680 adults using Nucleus implants for the following postimplant time points: 2-, 3-, 6-, 9-, 12-, 18-, and 24-month. For each time point, mean levels were calculated for the four segments. The degree of change in each of the levels was analyzed for six consecutive time point comparisons. The criterion for an acceptable degree of change was ≤20% of DR. Results: Mean T level was significantly lower for the 2-month time point compared with all time points after the 3-month time point. Mean C level was significantly lower for the 2- and 3-month time points compared with all other time points. Mean T level was significantly lower for the apical compared with all other segments and for the lower-basal compared with the upper-basal segment. Mean C level was significantly different across all four segments. Mean C level for the basal segments was 4 CLs higher for the perimodiolar array compared with the straight array. No significant differences were evident for the mean degree of change between consecutive time point comparisons. For all segments, approximately 65 to 75% of the participants showed an average acceptable degree of change in levels from the 3- to 6-month comparison. The mean degree of change in T levels was significantly greater for the basal segments compared with all other segments. The mean degree of change in levels was significantly greater for the otosclerosis group compared with all other groups, and for the prelingual onset of deafness group compared with the postlingual group. Conclusion: Given the very large cohort, this study provides evidence for the mean levels and the degree of change in these levels that should be expected for four segments in the first 24 months postimplantation for adults using Nucleus implants. The mean T and C levels were consistent after the 3- and 6-month time points postimplant, respectively. The degree of change was variable between individuals. For each segment, however, a large percentage of participants showed an average change of ≤20% in each of the T and C levels from the 3- to 6-month comparison. Given the large degree of change in levels for some groups, the results provide strong evidence in favor of frequent monitoring of levels in the first 24 months postimplantation for patients with otosclerosis, prelingual onset of deafness, and those who exhibit >20% change in levels after 3 months postimplantation.

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Cold Thermal Irrigation Decreases the Ipsilateral Gain of the Vestibulo-Ocular Reflex

Objectives: During head rotations, neuronal firing rates increase in ipsilateral and decrease in contralateral vestibular afferents. At low accelerations, this "push-pull mechanism" is linear. At high accelerations, however, the change of firing rates is nonlinear in that the ipsilateral increase of firing rate is larger than the contralateral decrease. This mechanism of stronger ipsilateral excitation than contralateral inhibition during high-acceleration head rotation, known as Ewald's second law, is implemented within the nonlinear pathways. The authors asked whether caloric stimulation could provide an acceleration signal high enough to influence the contribution of the nonlinear pathway to the rotational vestibulo-ocular reflex gain (rVOR gain) during head impulses. Design: Caloric warm (44°C) and cold (24, 27, and 30°C) water irrigations of the left ear were performed in 7 healthy human subjects with the lateral semicircular canals oriented approximately earth-vertical (head inclined 30° from supine) and earth-horizontal (head inclined 30° from upright). Results: With the lateral semicircular canal oriented earth-vertical, the strongest cold caloric stimulus (24°C) significantly decreased the rVOR gain during ipsilateral head impulses, while all other irrigations, irrespective of head position, had no significant effect on rVOR gains during head impulses to either side. Conclusions: Strong caloric irrigation, which can only be achieved with cold water, reduces the rVOR gain during ipsilateral head impulses and thus demonstrates Ewald's second law in healthy subjects. This unilateral gain reduction suggests that cold-water caloric irritation shifts the set point of the nonlinear relation between head acceleration and the vestibular firing rate toward a less acceleration-sensitive zone.

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Exploring contacts of eRF1 with the 3′-terminus of the P site tRNA and mRNA stop signal in the human ribosome at various translation termination steps

Publication date: Available online 27 April 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Konstantin N. Bulygin, Dmitri M. Graifer, Codjo Hountondji, Ludmila Yu Frolova, Galina G. Karpova
Here we employed site-directed cross-linking with the application of tRNA and mRNA analogues bearing an oxidized ribose at the 3′-terminus to investigate mutual arrangement of the main components of translation termination complexes formed on the human 80S ribosome bound with P site deacylated tRNA using eRF1•eRF3•GTP or eRF1 alone. In addition, we applied a model complex obtained in the same way with eRF1•eRF3•GMPPNP. We found that eRF3 content in the complexes with GTP and GMPPNP is similar, proving that eRF3 does not leave the ribosome after GTP hydrolysis. Our cross-linking data allowed determining locations of the 3′-terminus of the P site tRNA relatively the eRF1 M domain and of the mRNA stop signal toward the N domain and the ribosomal decoding site at the nucleotide-peptide resolution level. Our results indicate that locations of these components do not change after peptide release up to post-termination pre-recycling state, and the positioning of the mRNA stop signal remains similar to that when eRF1 recognizes it. Besides, we found that in all the complexes studied eRF1 shielded the N-terminal part of ribosomal protein eS30 from the interaction with the nucleotide adjacent to stop codon observed with pre-termination ribosome free of eRFs. Altogether, our findings brought important information on contacts of the key structural elements of eRF1, tRNA and mRNA in the ribosomal complexes including those mimicking different translation termination steps, thereby providing a deeper understanding of molecular mechanisms underlying events occurring in the course of protein synthesis termination in mammals.



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Aims & Scope/Editorial board

Publication date: July 2017
Source:Archives of Oral Biology, Volume 79





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Promoter methylation of MGMT in oral carcinoma: A population-based study and meta-analysis

Publication date: August 2017
Source:Archives of Oral Biology, Volume 80
Author(s): Chinchu Jayaprakash, Raghu Radhakrishnan, Satadru Ray, Kapaettu Satyamoorthy
IntroductionThe relevance of DNA methylation of O⁶-methylguanine-DNA methyltransferase (MGMT) in relation to several cancers and other disorders has been extensively explored in several cancer types.AimsTo ascertain the significance of DNA methylation of MGMT promoter in oral squamous cell carcinoma (OSCC), we undertook a study to a) analyse the methylation patterns of MGMT gene promoter in afflicted and normal population of coastal Karnataka, b) determine the expression status of MGMT in oral cancer cell lines (CAL-27 and SCC-4) and its relationship to DNA methylation and c) performed a meta-analysis of the published data.MethodsBisulfite sequencing of MGMT promoter region was performed on non-malignant/malignant oral samples, and oral cancer cell lines, followed by gene expression studies. Further, using a systematic search, 1024 publications were retrieved from PubMed, Scopus, Google Scholar and Web of Science and 23 relevant articles were reviewed.ResultsSignificant association of MGMT promoter methylation with OSCC (p<0.0001) was observed in the case-control study. The studies chosen for meta-analysis showed predictive significance of MGMT gene promoter. Overall, we obtained a statistically significant (p<0.0001) association for both sensitivity and specificity of MGMT DNA promoter methylation in oral cancer cases without publication bias. Gene expression was significantly elevated in both oral cancer cell lines (p<0.03) after treatment with a demethylating agent (5-Aza-2′-deoxycytidine).ConclusionDNA promoter hypermethylation and gene expression of MGMT may associate with recursive mutagenesis and is a promising biomarker for OSCC prediction. Studies suggest further validation in large distinct cohorts to facilitate translation to clinics.



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Synchrotron X-ray diffraction to understand crystallographic texture of enamel affected by Hunter syndrome

Publication date: August 2017
Source:Archives of Oral Biology, Volume 80
Author(s): Malik Arshman Khan, Owen Addison, Alison James, Christian J. Hendriksz, Maisoon Al-Jawad
ObjectiveTo determine whether Hunter syndrome (MPS II) affects the crystallographic texture (preferred orientation) of enamel.DesignSynchrotron X-ray diffraction, being a state of the art technique, has been used to determine the enamel crystallite orientation in enamel affected by Hunter syndrome (MPS II). The incisal, lingual and cervical regions of the MPS II affected tooth were observed and compared to healthy tooth.ResultsIt was observed that there is a loss of organization of crystallites in deciduous incisal enamel affected by Hunter syndrome (MPS II) as compared to healthy deciduous enamel tissue. Generally it was observed that, in contrast to the healthy enamel, the enamel affected by MPS II possessed a lower crystallographic preferred orientation, with a more uniform spatial distribution; however, the enamel at the incisal tip was relatively unaffected.ConclusionHunter syndrome affects the enamel texture in the lingual and cervical regions of the tooth.



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Frequency of MCP-1 (rs1024611) and CCR2 (rs1799864) gene polymorphisms and its effect on gene expression level in patients with AgP

Publication date: August 2017
Source:Archives of Oral Biology, Volume 80
Author(s): Sadiye Gunpinar, Nilgun Ozlem Alptekin, V. Betul Ucar, Hasan Acar
ObjectiveTo identify the genetic risk markers of aggressive periodontitis (AgP), researchers focus on genetic components that regulate the immune response. Therefore the purpose of this study was to investigate genetic impact of monocyte chemoattractant protein (MCP)-1–2518A/G and CC chemokine receptor 2 (CCR2) −190G/A gene polymorphisms on AgP susceptibility and the effect of this polymorphism on MCP-1 gene expression in patients with AgP.Material and methodsA total of 215 subjects, 108 AgP and 107 periodontally healthy (H) were recruited in this cross-sectional study (NCT02817568). Gene polymorphisms of MCP-1–2518A/G and CCR2–190G/A were analyzed by a standard polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. MCP-1 messenger (m) RNA expression was measured using quantitative real-time (RT)-PCR in peripheral blood leukocytes from 26 AgP and 16H controls. Threshold cycles (Ct) values were obtained from the RT-PCR analysis based on SYBR Green detection and data was normalized via ΔCt.ResultsThere were no differences between AgP and H groups with regard to MCP-1 and CCR2 genotype distribution and allele frequencies (p>0.05). In contrast, the MCP-1 mRNA expression levels were higher in homozygous "AA" control subjects than having G⁺ genotype and AA homozygous AgP patients.ConclusionsIt can be concluded that MCP-1 and CCR2 polymorphisms are not associated with AgP in Turkish population. Although in AgP patients, there was AA genotype with MCP-1 mRNA expression it can be speculated that gene expression levels in peripheral blood may not reflect the cytokine/chemokine levels of local tissues.



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Doxorubicin-induced female reproductive toxicity: an assessment of ovarian follicular apoptosis, cyclicity and reproductive tissue histology in Wistar rats.

Related Articles

Doxorubicin-induced female reproductive toxicity: an assessment of ovarian follicular apoptosis, cyclicity and reproductive tissue histology in Wistar rats.

Drug Chem Toxicol. 2017 Apr 25;:1-10

Authors: Nishi K, Gunasekaran VP, Arunachalam J, Ganeshan M

Abstract
Doxorubicin is a widely used chemotherapeutic agent for various cancers, particularly for the female breast cancer patients. Although the rate of young female cancer patients is increasing every year, conversely the lack of knowledge of adverse effects of doxorubicin on female reproductive system insisted us to assess the toxic effects of doxorubicin on the female reproductive tissue histoarchitecture, cyclicity, and mammary glands in Wistar rats. The rats were divided into two groups depending on the treatment period, i.e., 24 h and 28 d and further subdivided into three subgroups and administered with doxorubicin at 3 mg/kg bw (subgroup I), 6 mg/kg bw (subgroup II), and equal volume of normal saline (subgroup III) intraperitoneally once during the whole treatment period. We observed a significantly altered estrous cycle with a prolonged diestrous and short proestrous in higher dose group and dose-dependent significant changes in the uteri and mammary gland histoarchitecture in 28 days treated rats as compared to control. Moreover, the micronuclei and chromosomal aberration frequency were increased significantly in both treatment groups. A significant increase in follicular atresia in ovaries of the 28 days treated rats was observed. The immunohistochemical analysis of ovarian tissues showed an increased p53 and caspase 3 expression and apoptosis in primordial follicles of treated rats. The results suggest that though doxorubicin is a potential chemotherapeutic drug for many tumors, but the risk of adverse effects on the female reproductive system is there even at low doses.

PMID: 28441888 [PubMed - as supplied by publisher]

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Mechanism Behind the Anti-Tumour Potential of Saffron (Crocus sativus L.): The Molecular Perspective

Publication date: Available online 27 April 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Sweta Patel, Maryam Sarwat, Tajdar H. Khan
Cancer is a disorder which has noted a significant rise in incidence worldwide and continues to be the largest cause of mortality. It has a dramatic impact on human life expectancy and quality of life in spite of the increase in technology and the treatments available for cancer patients. These new therapeutic options being chemotherapy, radiotherapy, photolytic therapy and catalytic therapy are known to have many adverse reactions and also no better positive outcomes than before. Hence, research is now focused more on utilizing the vast repertoire of traditional medicinal knowledge i.e. the use of flora for treatment of cancer rather than the use of chemicals. One such herb is the Crocus sativus L., commonly known as Saffron, rich in carotenoids − crocin, crocetin and safranal. Various studies have been carried out over the past few years to confirm the anti-cancer properties of saffron, both in vivo using animal models and in vitro using human malignant cell lines on various types of cancers with positive results. The proposed mechanism of actions have also been worked upon. This review is aimed to provide a brief overview on the anti-tumor potential of saffron focusing on the molecular mechanism involved.



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Mast cells in breast cancer angiogenesis

Publication date: Available online 27 April 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Anca Maria Cimpean, Roberto Tamma, Simona Ruggieri, Beatrice Nico, Alina Toma, Domenico Ribatti
Mast cells, accumulate in the stroma surrounding certain tumors and take part to the inflammatory reaction occurring at the periphery of the tumor. Mast cell-secreted angiogenic cytokines facilitate tumor vascularization not only by a direct effect but also by stimulating other inflammatory cells of the tumor microenvironment to release other angiogenic mediators. An increased number of mast cells have been demonstrated in angiogenesis associated with solid tumors, including breast cancer. Mast cells might act as a new target for the adjuvant treatment of breast cancer through the selective inhibition of angiogenesis, tissue remodeling and tumor promoting molecules, allowing the secretion of cytotoxic cytokines and preventing mast cell mediated immune-suppression.



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Mast cells in breast cancer angiogenesis

Publication date: Available online 27 April 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Anca Maria Cimpean, Roberto Tamma, Simona Ruggieri, Beatrice Nico, Alina Toma, Domenico Ribatti
Mast cells, accumulate in the stroma surrounding certain tumors and take part to the inflammatory reaction occurring at the periphery of the tumor. Mast cell-secreted angiogenic cytokines facilitate tumor vascularization not only by a direct effect but also by stimulating other inflammatory cells of the tumor microenvironment to release other angiogenic mediators. An increased number of mast cells have been demonstrated in angiogenesis associated with solid tumors, including breast cancer. Mast cells might act as a new target for the adjuvant treatment of breast cancer through the selective inhibition of angiogenesis, tissue remodeling and tumor promoting molecules, allowing the secretion of cytotoxic cytokines and preventing mast cell mediated immune-suppression.



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The Essence of Nursing Care.

Author: Hassmiller, Susan B. PhD, RN, FAAN

Page: 7

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Health Care and the New Administration.

Author: Fife, Patricia MPA, RN

Page: 10

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Do Health Food Store Staff Steer Teen Boys to Muscle-Enhancing Supplements?.

Author: Zolot, Joan PA

Page: 14

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Health Care and the New Administration.

Author: Jones, Kendell

Page: 10

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Adolescent Access to Reproductive Health Care.

Author: Anderson, Julianna Nursing Student; Canavan, Sara Nursing Student

Page: 10

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Monitoring Hospitalized Adult Patients for Opioid-Induced Sedation and Respiratory Depression: Erratum.

Author:

Page: 10

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In Defense of Routine Inpatient Pain Assessment.

Author: Solodiuk, Jean C. PhD, RN; Curley, Martha A. Q. PhD, RN, FAAN

Page: 11

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Should Adults Experiencing In-Hospital Cardiac Arrest Be Intubated?.

Author: Sofer, Dalia

Page: 12

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Analysis of Cancer Deaths at the County Level Pinpoints Hot Spots for Action.

Author: Stockwell, Serena

Page: 13

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AJN On the Cover.

Author: Szulecki, Diane Associate Editor

Page: 17

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NewsCAP: NPs made more house calls to Medicare patients in 2013 than all other providers delivering primary health care.

Author:

Page: 15

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NewsCAP: The racial disparity in cervical cancer mortality is much greater than previously calculated.

Author:

Page: 14

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AJN On the Web.

Author:

Page: 17

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NewsCAP: 'Dripping' is becoming popular with e-cigarette users.

Author:

Page: 14

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Laundry Detergent Pods Linked to Increased Eye Injuries in Children.

Author: Halpern, Lucy Wang

Page: 15

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New Clinical Guideline for Low Back Pain Says Try Nondrug Therapies First.

Author: Stockwell, Serena

Page: 16

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State News Roundup.

Author:

Page: 16

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Can Health Care Professionals Do Anything About Gun Violence?.

Author: Nelson, Roxanne

Page: 18-19

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Rare Allergic Reaction to Topical Chlorhexidine Gluconate.

Author: Aschenbrenner, Diane S. MS, RN

Page: 20

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FDA Warnings Nurses can Include in Patient Education.

Author: Aschenbrenner, Diane S. MS, RN

Page: 20-21

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Genetics of Infectious and Inflammatory Diseases: Overlapping Discoveries from Association and Exome-Sequencing Studies

Annual Review of Immunology, Volume 35, Issue 1, Page 1-30, April 2017.


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Protective and Harmful Immunity to RSV Infection

Annual Review of Immunology, Volume 35, Issue 1, Page 501-532, April 2017.


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Immunobiology of Long Noncoding RNAs

Annual Review of Immunology, Volume 35, Issue 1, Page 177-198, April 2017.


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Disorders of the JAK/STAT Pathway in T Cell Lymphoma Pathogenesis: Implications for Immunotherapy

Annual Review of Immunology, Volume 35, Issue 1, Page 533-550, April 2017.


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Mucosal Ecological Network of Epithelium and Immune Cells for Gut Homeostasis and Tissue Healing

Annual Review of Immunology, Volume 35, Issue 1, Page 119-147, April 2017.


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Understanding Human Autoimmunity and Autoinflammation Through Transcriptomics

Annual Review of Immunology, Volume 35, Issue 1, Page 337-370, April 2017.


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Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities

Annual Review of Immunology, Volume 35, Issue 1, Page 229-253, April 2017.


http://ift.tt/2pnB0VJ

Th2 Cells in Health and Disease

Annual Review of Immunology, Volume 35, Issue 1, Page 53-84, April 2017.


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Microbes and Cancer

Annual Review of Immunology, Volume 35, Issue 1, Page 199-228, April 2017.


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Intracellular Nucleic Acid Detection in Autoimmunity

Annual Review of Immunology, Volume 35, Issue 1, Page 313-336, April 2017.


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A Perspective on the Role of Computational Models in Immunology

Annual Review of Immunology, Volume 35, Issue 1, Page 403-439, April 2017.


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Microglia Function in the Central Nervous System During Health and Neurodegeneration

Annual Review of Immunology, Volume 35, Issue 1, Page 441-468, April 2017.


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Antigen-Presenting Cells in the Skin

Annual Review of Immunology, Volume 35, Issue 1, Page 469-499, April 2017.


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Metabolite-Sensing G Protein–Coupled Receptors—Facilitators of Diet-Related Immune Regulation

Annual Review of Immunology, Volume 35, Issue 1, Page 371-402, April 2017.


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Signaling by Antibodies: Recent Progress

Annual Review of Immunology, Volume 35, Issue 1, Page 285-311, April 2017.


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Thymic Epithelial Cells

Annual Review of Immunology, Volume 35, Issue 1, Page 85-118, April 2017.


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The Lymphatic System: Integral Roles in Immunity

Annual Review of Immunology, Volume 35, Issue 1, Page 31-52, April 2017.


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Memory B Cells of Mice and Humans

Annual Review of Immunology, Volume 35, Issue 1, Page 255-284, April 2017.


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The Biology and Underlying Mechanisms of Cross-Presentation of Exogenous Antigens on MHC-I Molecules

Annual Review of Immunology, Volume 35, Issue 1, Page 149-176, April 2017.


http://ift.tt/2pEK3Vf

Unique features in the presentation of insulin epitopes in autoimmune diabetes: an update

Xiaoxiao Wan | Emil R Unanue

http://ift.tt/2oOquoJ

Mortality of Necrotising Fasciitis: relative influence of individual and hospital-level factors, a Nationwide Multi-Level Study, France, 2007-2012

Abstract

Background

Necrotising soft-tissue infections (NSTI) are rare, life-threatening conditions.

Objectives

We aimed to assess whether admitting hospital characteristics were associated with NSTI mortality.

Methods

We studied the French nationwide hospital discharge database (retrospective national cohort). All patients admitted in 2007-2012 with an ICD-10 code of necrotising fasciitis were eligible. We extracted data on the patients (age, sex, ICU admission, co-morbidities) and hospitals (public vs private proprietary; for public hospitals, teaching, yes/no; and number of NSTI admissions, ≥3 NSTI cases/year, yes/no). Multivariable analyses were performed to identify independent predictors of day-28 mortality and in-hospital mortality using mixed logistic regression and Cox proportional hazards models, respectively.

Results

We identified 1537 patients (915 males) with a median age of 60 (IQR, 48-75) years, admitted to 326 hospitals, public (82%) and admitting fewer than three NSTI cases/year (93%). Overall, 364 patients died (23·7%; 95%CI, 21·6-25·9). Patients treated in public teaching centres with ≥3NSTI cases annually had lower day-28 mortality (adjusted odds ratio [aOR], 0·68; 95%CI, 0·46-0·99; p=0·045) and in-hospital mortality rates than patients treated in local hospitals, even after adjusting for potentially relevant individual risk factors. No significant association was found between mortality and inter-hospital transfer.

Conclusions

Our finding highlighted an increased survival in teaching centres with high NSTI volume procedures. If confirmed in other settings, these findings reinforce the importance of expertise in early diagnosis and management of this condition.

This article is protected by copyright. All rights reserved.

http://ift.tt/2qcEOt8

Mortality of Necrotising Fasciitis: relative influence of individual and hospital-level factors, a Nationwide Multi-Level Study, France, 2007-2012

Abstract

Background

Necrotising soft-tissue infections (NSTI) are rare, life-threatening conditions.

Objectives

We aimed to assess whether admitting hospital characteristics were associated with NSTI mortality.

Methods

We studied the French nationwide hospital discharge database (retrospective national cohort). All patients admitted in 2007-2012 with an ICD-10 code of necrotising fasciitis were eligible. We extracted data on the patients (age, sex, ICU admission, co-morbidities) and hospitals (public vs private proprietary; for public hospitals, teaching, yes/no; and number of NSTI admissions, ≥3 NSTI cases/year, yes/no). Multivariable analyses were performed to identify independent predictors of day-28 mortality and in-hospital mortality using mixed logistic regression and Cox proportional hazards models, respectively.

Results

We identified 1537 patients (915 males) with a median age of 60 (IQR, 48-75) years, admitted to 326 hospitals, public (82%) and admitting fewer than three NSTI cases/year (93%). Overall, 364 patients died (23·7%; 95%CI, 21·6-25·9). Patients treated in public teaching centres with ≥3NSTI cases annually had lower day-28 mortality (adjusted odds ratio [aOR], 0·68; 95%CI, 0·46-0·99; p=0·045) and in-hospital mortality rates than patients treated in local hospitals, even after adjusting for potentially relevant individual risk factors. No significant association was found between mortality and inter-hospital transfer.

Conclusions

Our finding highlighted an increased survival in teaching centres with high NSTI volume procedures. If confirmed in other settings, these findings reinforce the importance of expertise in early diagnosis and management of this condition.

This article is protected by copyright. All rights reserved.

http://ift.tt/2qcEOt8

Editorial Board

Publication date: May 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 169





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Highlights from the 5th International Conference on Vitamin D Deficiency, Nutrition and Human Health, Abu Dhabi, United Arab Emirates, March 24-25, 2016

Publication date: Available online 27 April 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Afrozul Haq, Sunil J. Wimalawansa, Carsten Carlberg




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DHRS7 (SDR34C1) – A new player in the regulation of androgen receptor function by inactivation of 5α-dihydrotestosterone?

Publication date: Available online 27 April 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Selene Araya, Denise V. Kratschmar, Maria Tsachaki, Simon Stücheli, Katharina R. Beck, Alex Odermatt
DHRS7 (SDR34C1) has been associated with potential tumor suppressor effects in prostate cancer; however, its function remains largely unknown. Recent experiments using purified recombinant human DHRS7 suggested several potential substrates, including the steroids cortisone and Δ4-androstene-3,17-dione (androstenedione). However, the substrate and cofactor concentrations used in these experiments were very high and the physiological relevance of these observations needed to be further investigated. In the present study, recombinant human DHRS7 was expressed in intact HEK-293 cells in order to investigate whether glucocorticoids and androgens serve as substrates at sub-micromolar concentrations and at physiological cofactor concentrations. Furthermore, the membrane topology of DHRS7 was revisited using redox-sensitive green-fluorescent protein fusions in living cells. The results revealed that (1) cortisone is a substrate of DHRS7; however, it is not reduced to cortisol but to 20β-dihydrocortisone, (2) androstenedione is not a relevant substrate of DHRS7, (3) DHRS7 catalyzes the oxoreduction of 5α-dihydrotestosterone (5αDHT) to 3α-androstanediol (3αAdiol), with a suppressive effect on androgen receptor (AR) transcriptional activity, and (4) DHRS7 is anchored in the endoplasmic reticulum membrane with a cytoplasmic orientation. Together, the results show that DHRS7 is a cytoplasmic oriented enzyme exhibiting 3α/20β-hydroxysteroid dehydrogenase activity, with a possible role in the modulation of AR function. Further research needs to address the physiological relevance of DHRS7 in the inactivation of 5αDHT and AR regulation.



http://ift.tt/2oBVw81

The value of surrogate markers to monitor cholesterol absorption, synthesis and bioconversion to bile acids under lipid lowering therapies

Publication date: May 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 169
Author(s): Frans Stellaard, Klaus von Bergmann, Thomas Sudhop, Dieter Lütjohann
IntroductionRegulation of cholesterol (Chol) homeostasis is controlled by three main fluxes, i.e. intestinal absorption, de novo synthesis (ChS) and catabolism, predominantly as bile acid synthesis (BAS). High serum total Chol and LDL-Chol concentrations in particular are considered risk factors and markers for the development of atherosclerosis. Pharmaceutical treatments to lower serum Chol have focused on reducing absorption or ChS and increasing BAS. Monitoring of these three parameters is complex involving isotope techniques, cholesterol balance experiments and advanced mass spectrometry based analysis methods. Surrogate markers were explored that require only one single fasting blood sample collection. These markers were validated in specific, mostly physiological conditions and during statin treatment to inhibit ChS. They were also applied under cholesterol absorption restriction, but were not validated in this condition. We retrospectively evaluated the use of serum campesterol (Camp), sitosterol (Sit) and cholestanol (Cholol) as markers for cholesterol absorption, lathosterol (Lath) as marker for ChS and 7α-hydroxycholesterol (7α-OH-Ch) and 27-hydroxycholesterol (27-OH-Ch) as markers for BAS under conditions of Chol absorption restriction. Additionally, their values were corrected for Chol concentration (R_sterol or oxysterols).MethodsThirty-seven healthy male omnivore subjects were studied under treatments with placebo (PLAC), ezetimibe (EZE) to inhibit cholesterol absorption, simvastatin (SIMVA) to reduce cholesterol synthesis and a combination of both (EZE+SIMVA). Results were compared to those obtained in 18 pure vegetarian subjects (vegans) whose dietary Chol intake is extremely low. Relative or fractional Chol absorption (FrChA) was measured with the continuous feeding stable isotope procedure, ChS and BAS with the cholesterol balance method. The daily Chol intake (DICh) was inventoried and the daily Chol absorption (DACh) calculated.ResultsMonitoring cholesterol absorption, R_Camp, R_Sit and R_Cholol responded sensitively to changes in FrChA. R_Camp correlated well with FrChA in all omnivore treatment groups and in the vegan group. R_Camp confirmed reduced FrChA under EZE treatment and reduced DACh in the vegan subjects. R_Sit and R_Cholol did not accurately reflect FrChA or DACh in all situations. Monitoring endogenous cholesterol synthesis, R_Lath correlated with ChS in the vegan group, but in none of the omnivore treatment groups. R_Lath confirmed increased ChS under EZE treatment and was reduced under SIMVA treatment, while ChS was not. An increased ChS under EZE+SIMVA treatment could not be confirmed with R_Lath. R_Lath responded very insensitively to a change in ChS. Monitoring BAS, R_7α-OH-Ch but not R_27-OH-Ch correlated with BAS during PLAC, EZE and SIMVA treatments. In line with BAS, R_7α-OH-Ch did not differ in any of the omnivore treatment groups. R_7α-OH-Ch responded insensitively to a change in BAS.ConclusionsUnder Chol absorption restriction, serum R_Camp is a sensitive and valid marker to monitor FrChA in a population with a normal DICh. Also, major changes in DACh can be detected in vegans. Serum R_Lath does not reflect ChS measured with the cholesterol balance method during EZE treatment. This result initiates the question whether the measured ChS reflects pure de novo synthesis. Serum R_7α-OH-Ch appears to be a valid but insensitive marker for BAS.

Graphical abstract

http://ift.tt/1Sf1mP3

Effect of broccoli extract enriched diet on liver cholesterol oxidation in rats subjected to exhaustive exercise

Publication date: May 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology, Volume 169
Author(s): Vladimiro Cardenia, Maria Teresa Rodriguez-Estrada, Antonello Lorenzini, Erika Bandini, Cristina Angeloni, Silvana Hrelia, Marco Malaguti
The effect of broccoli extract (BE)-enriched diet was studied in order to evaluate its ability to counteract liver cholesterol oxidation products (COPs) induced by acute strenuous exercise in rats. Thirty-two female Wistar rats were randomly divided into four groups: control diet without exercise (C), BE-enriched diet without exercise (B), control diet with acute exhaustive exercise (S) and BE-enriched diet with acute exhaustive exercise (BS). The study lasted 45days and on the last day, rats of S and BS groups were forced to run until exhaustion on a treadmill. Glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT) and cholesterol oxidation products (COPs) were determined in liver. Exhaustive exercise was clearly responsible for tissue damage, as evidenced by the increase of lactate dehydrogenase (LDH) plasma activity in the S group. Moreover, the exercise protocol reduced CAT activity in liver, while it did not affect GST, GR and GPx. BE-enriched diet raised GST, GR and CAT activities in rats of BS group. The main COPs found were 7α-hydroxycholesterol, 7β-hydroxycholesterol, 7-ketocholesterol, cholestanetriol, 24-hydroxycholesterol and 27-hydroxycholesterol. The BE-enriched diet led to reduced cholesterol oxidation following exhaustive exercise; the highest level of COPs was found in the S group, whereas the BS rats showed the lowest amount. This study indicates that the BE-enriched diet increases antioxidant enzyme activities and exerts an antioxidant effect towards cholesterol oxidation in rat liver, suggesting the use of phytochemicals in the prevention of oxidative damage and in the modulation of the redox environment.

Graphical abstract

http://ift.tt/23FC98P

Cytotoxic CD8+ T cells ablation enhances the capacity of regulatory T cells to delay viral elimination in Theiler's murine encephalomyelitis

Abstract

Theiler's murine encephalomyelitis (TME) of susceptible mouse strains is a commonly used infectious animal model for multiple sclerosis. The study aim was to test the hypothesis whether cytotoxic T cell responses account for the limited impact of regulatory T cells on antiviral immunity in TME virus-induced demyelinating disease (TMEV-IDD) resistant C57BL/6 mice. TME virus-infected C57BL/6 mice were treated with (i) interleukin-2/-anti-interleukin-2-antibody-complexes to expand regulatory T cells ('Treg-expansion'), (ii) anti-CD8-antibodies to deplete cytotoxic T cells ('CD8-depletion') or (iii) with a combination of Treg-expansion and CD8-depletion ('combined treatment') prior to infection. Results showed that 'combined treatment' but neither sole 'Treg-expansion' nor 'CD8-depletion', leads to sustained hippocampal infection and virus spread to the spinal cord in C57BL/6 mice. Prolonged infection reduces myelin basic protein expression in the spinal cord together with increased accumulation of β-amyloid precursor protein in axons, characteristic of myelin loss and axonal damage. Chronic spinal cord infection upon 'combined treatment' mice was also associated with increased T and B cell recruitment, accumulation of CD107b⁺ microglia/macrophages and enhanced mRNA expression of interleukin (IL)-1α, IL-10 and tumor necrosis factor. In conclusion, data revealed that the suppressive capacity of Treg on viral elimination is efficiently boosted by CD8-depletion, which renders C57BL/6 mice susceptible to develop chronic neuroinfection and TMEV-IDD. This article is protected by copyright. All rights reserved.

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Duration and exclusiveness of breastfeeding and risk of childhood atopic diseases

Abstract

Background

Breastfeeding may have immune modulatory effects that influence the development of childhood allergic sensitization and atopic diseases. We aimed to examine the associations of breastfeeding with childhood allergic sensitization, inhalant or food allergy and eczema, and whether any association was affected by disease-related modification of the exposure or modified by maternal history of maternal history of allergy, eczema or asthma.

Methods

This study among 5,828 children was performed in a population-based prospective cohort from fetal life onwards. We collected information on duration (<2 months, 2-4 months, 4-6 months and ≥6 months) and exclusiveness (non-exclusive vs. exclusive for 4 months) of breastfeeding in infancy by postal questionnaires. At age 10 years, inhalant and food allergic sensitization were measured by skin prick tests, and physician-diagnosed inhalant and food allergy by a postal questionnaire. Data on parental-reported eczema were available from birth until age 10 years.

Results

We observed no association of breastfeeding with any allergic sensitization, physician-diagnosed allergy, or combination of these outcomes. Shorter breastfeeding duration was associated with an overall increased risk of eczema (p-value for trend <0.05). Non-exclusively breastfed children had an overall increased risk of eczema (aOR (95% CI): 1.11 (1.01, 1.23)), compared with children exclusively breastfed for 4 months. Risk period-specific sensitivity analyses, additional adjustment for ointment use for eczema at age 2 months, and cross-lagged modeling showed no consistent results for disease-related modification of the exposure. Results were not modified by maternal history of allergy, eczema or asthma (lowest p-value for interaction =0.13).

Conclusions

Shorter duration or non-exclusiveness of breastfeeding is associated with a weak overall increased risk of eczema but not allergic sensitization or physician-diagnosed allergy at age 10 years

This article is protected by copyright. All rights reserved.

http://ift.tt/2oBXPrt

Duration and exclusiveness of breastfeeding and risk of childhood atopic diseases

Abstract

Background

Breastfeeding may have immune modulatory effects that influence the development of childhood allergic sensitization and atopic diseases. We aimed to examine the associations of breastfeeding with childhood allergic sensitization, inhalant or food allergy and eczema, and whether any association was affected by disease-related modification of the exposure or modified by maternal history of maternal history of allergy, eczema or asthma.

Methods

This study among 5,828 children was performed in a population-based prospective cohort from fetal life onwards. We collected information on duration (<2 months, 2-4 months, 4-6 months and ≥6 months) and exclusiveness (non-exclusive vs. exclusive for 4 months) of breastfeeding in infancy by postal questionnaires. At age 10 years, inhalant and food allergic sensitization were measured by skin prick tests, and physician-diagnosed inhalant and food allergy by a postal questionnaire. Data on parental-reported eczema were available from birth until age 10 years.

Results

We observed no association of breastfeeding with any allergic sensitization, physician-diagnosed allergy, or combination of these outcomes. Shorter breastfeeding duration was associated with an overall increased risk of eczema (p-value for trend <0.05). Non-exclusively breastfed children had an overall increased risk of eczema (aOR (95% CI): 1.11 (1.01, 1.23)), compared with children exclusively breastfed for 4 months. Risk period-specific sensitivity analyses, additional adjustment for ointment use for eczema at age 2 months, and cross-lagged modeling showed no consistent results for disease-related modification of the exposure. Results were not modified by maternal history of allergy, eczema or asthma (lowest p-value for interaction =0.13).

Conclusions

Shorter duration or non-exclusiveness of breastfeeding is associated with a weak overall increased risk of eczema but not allergic sensitization or physician-diagnosed allergy at age 10 years

This article is protected by copyright. All rights reserved.

http://ift.tt/2oBXPrt

Serum phosphorus levels and fracture following renal transplantation

Abstract

Purpose

Increased fracture rates are observed in renal transplant recipients (RTRs) compared with the general population. Risk factors include age, diabetes, dialysis vintage, immunosuppression, and mineral and bone disorders(1). Low serum phosphorus levels occur post-transplantation; however its relationship with fracture risk has not been evaluated. The purpose of this study was to evaluate risk factors for fracture in RTRs at a single tertiary referral centre.

Methods

A retrospective cross-sectional analysis of 146 patients (75M, 71F) who had been referred for dual energy x-ray densitometry (DXA) post-renal transplantation was performed. Aetiology of end stage kidney disease (ESKD), duration of dialysis, parathyroidectomy history, immunosuppression regimen, bone mineral density (BMD), biochemistry and fractures were documented. Statistical analyses included univariable and multivariable regression.

Results

The mean age of patients was 54 years and mean time post-transplantation 6.7 years. 79 fractures occurred in 52 patients (35%), with 40 fractures occurring post-transplantation. Ankle/foot fractures were most common (48%). Lower serum phosphorus levels and declining FN T-score and were associated with fractures in both univariable and multivariable regression analyses after adjusting for age, gender, weight, eGFR and pre-transplant history of fracture (p=0.011 and p=0.042 respectively). The relationship between serum phosphorus and fracture remained significant independent of FN T-score, parathyroid hormone levels, parathyroidectomy status and prednisolone use.

Conclusion

Fracture was common post-renal transplantation. Lower serum phosphorus levels and declining FN T-scores were associated with fractures. The mechanism of this previously unreported observation requires further evaluation in prospective studies.

This article is protected by copyright. All rights reserved.

http://ift.tt/2oRaSBH

Outcome of three screening questions for temporomandibular disorders (3Q/TMD) on clinical decision-making

Abstract

Patients with temporomandibular disorders (TMD) seem to go undetected and not adequately managed within dentistry. To identify these patients, three screening questions (3Q/TMD) have been introduced within dentistry in parts of Sweden. It is not known whether 3Q/TMD affects the clinical decision-making for these patients.

Objectives

To evaluate the outcome of 3Q/TMD on the clinical decision-making, and to analyse if gender, age, and the fee-system the individual was assigned to, were related to prescribed TMD treatment.

Methods

This cohort study was carried out within the Public Dental Health service in Västerbotten, Sweden. As part of the routine dental check-up, a health declaration including 3Q/TMD was completed. The study population was randomly selected based on their 3Q/TMD answers. In total, 300 individuals with an affirmative answer to any of the 3Q/TMD, and 500 individuals with all negative answers were selected. The 3Q/TMD includes questions on weekly jaw-face-temple pain (Q1), pain on function (Q2), and catching/locking of the jaw (Q3). The 3Q/TMD was analysed in relation to prescribed treatment assessed from dental records.

Results

There was significantly more treatment performed or recommended for 3Q-positives (21.5%), compared to 3Q-negatives (2.2%) (P<0.001). The odds ratio for TMD-related treatment for 3Q-positives versus 3Q-negatives was 12.1 (95% CI:6.3-23.4).

Conclusion

Although affirmative answers to the 3Q/TMD was related to TMD treatment, the majority of individuals with a screen positive still did not, according to dental records, receive assessment or treatment. Further studies are needed to better understand the clinical decision-making process for patients with TMD.

This article is protected by copyright. All rights reserved.

http://ift.tt/2qccVky