bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of the NLRP3 inflammasome in microglia: the role of ceramide
Authors: Scheiblich Hannah , Schlütter Anna , Golenbock Douglas T. , Latz Eicke , Martinez‐Martinez Pilar , Heneka Michael T.
Published: September 2017

Inflammation within the CNS is a major component of many neurodegenerative diseases. A characteristic feature is the generation of microglia‐derived factors that play an essential role in the immune response. IL‐1β is a pro‐inflammatory cytokine released by activated microglia, able to exacerbate injury at elevated levels. In the presence of caspase‐1, pro‐IL‐1β is cleaved to the mature cytokine following NOD‐like receptor pyrin domain containing 3 (NLRP3) inflammasome activation. Growing evidence suggests that ceramide plays a critical role in NLRP3 inflammasome assembly, however, the relationship between ceramide and inflammasome activation in microglia remains unknown. Here, we investigated potential mechanistic links between ceramide as a modulator of NLRP3 inflammasome assembly and the resulting secretion of IL‐1β using small bioactive enzyme stimulators and inhibitors of ceramide signaling in wild‐type and apoptosis‐associated speck‐like protein containing a CARD knockout (ASC−/−) primary microglia. To induce the expression of inflammasome components, microglia were primed prior to experiments. Treatment with sodium palmitate (PA) induced de novo ceramide synthesis via modulation of its synthesizing protein serine palmitoyl transferase resulting in increased IL‐1β secretion in microglia. Exposure of microglia to the serine palmitoyl transferase‐inhibitor l‐cycloserine significantly prevented PA‐induced IL‐1β secretion. Application of the ceramide analogue C2 and the sphingosine‐1‐phosphate‐receptor agonist Fingolimod (FTY720) up‐regulated levels of IL‐1β and cleaved caspase‐1 in wild‐type microglia, whereas ASC−/− microglia were unaffected. HPA‐12 inhibition of ceramide transport did not affect inflammasome activation. Taken together, our findings reveal a critical role for ceramide as a positive modulator of NLRP3 inflammasome assembly and the resulting release of IL‐1β.

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Considering the role of adolescent sex steroids in schizophrenia
Authors: Owens S. J. , Murphy C. E. , Purves‐Tyson T. D. , Weickert T. W. , Shannon Weickert C.
Published: September 2017

Schizophrenia is a disabling illness that is typically first diagnosed during late adolescence to early adulthood. It has an unremitting course and is often treatment‐resistant. Many clinical aspects of the illness suggest that sex steroid‐nervous system interactions may contribute to the onset, course of symptoms and the cognitive impairment displayed by men and women with schizophrenia. Here, we discuss the actions of oestrogen and testosterone on the brain during adolescent development and in schizophrenia from the perspective of experimental studies in animals, human post‐mortem studies, magnetic resonance imaging studies in living humans and clinical trials of sex steroid‐based treatments. We present evidence of potential beneficial, as well as detrimental, effects of both testosterone and oestrogen. We provide a rationale for the necessity to further elucidate sex steroid mechanisms of action at different ages, sexes and brain regions to more fully understand the role of testosterone and oestrogen in the pathophysiology of schizophrenia. The weight of the evidence suggests that sex steroid hormones influence mammalian brain function, including both cognition and emotion, and that pharmaceutical agents aimed at sex steroid receptors appear to provide a novel treatment avenue to reduce symptoms and improve cognition in men and women with schizophrenia.
Seven‐Tesla Magnetization Transfer Imaging to Detect Multiple Sclerosis White Matter Lesions
Authors: Chou I‐Jun , Lim Su‐Yin , Tanasescu Radu , Al‐Radaideh Ali , Mougin Olivier E. , Tench Christopher R. , Whitehouse William P. , Gowland Penny A. , Constantinescu Cris S.
Published: September 2017

BACKGROUND AND PURPOSE

Fluid‐attenuated inversion recovery (FLAIR) imaging at 3 Tesla (T) field strength is the most sensitive modality for detecting white matter lesions in multiple sclerosis. While 7T FLAIR is effective in detecting cortical lesions, it has not been fully optimized for visualization of white matter lesions and thus has not been used for delineating lesions in quantitative magnetic resonance imaging (MRI) studies of the normal appearing white matter in multiple sclerosis. Therefore, we aimed to evaluate the sensitivity of 7T magnetization‐transfer‐weighted (MTw) images in the detection of white matter lesions compared with 3T‐FLAIR.

METHODS

Fifteen patients with clinically isolated syndrome, 6 with multiple sclerosis, and 10 healthy participants were scanned with 7T 3‐dimensional (D) MTw and 3T‐2D‐FLAIR sequences on the same day. White matter lesions visible on either sequence were delineated.

RESULTS

Of 662 lesions identified on 3T‐2D‐FLAIR images, 652 were detected on 7T‐3D‐MTw images (sensitivity, 98%; 95% confidence interval, 97% to 99%). The Spearman correlation coefficient between lesion loads estimated by the two sequences was .910. The intrarater and interrater reliability for 7T‐3D‐MTw images was good with an intraclass correlation coefficient (ICC) of 98.4% and 81.8%, which is similar to that for 3T‐2D‐FLAIR images (ICC 96.1% and 96.7%).

CONCLUSION

Seven‐Tesla MTw sequences detected most of the white matter lesions identified by FLAIR at 3T. This suggests that 7T‐MTw imaging is a robust alternative for detecting demyelinating lesions in addition to 3T‐FLAIR. Future studies need to compare the roles of optimized 7T‐FLAIR and of 7T‐MTw imaging.
Anomalies and Normal Variants of the Cerebral Arterial Supply: A Comprehensive Pictorial Review with a Proposed Workflow for Classification and Significance
Authors: Hakim Arsany , Gralla Jan , Rozeik Christoph , Mordasini Pasquale , Leidolt Lars , Piechowiak Eike , Ozdoba Christoph , El‐Koussy Marwan
Published: September 2017

Cerebral arteries may exhibit a wide range of variation from normal anatomy, which can be incidentally discovered during imaging. Knowledge of such variants is crucial to differentiate them from pathologies, to understand the etiology of certain pathologies directly related to a vascular variant, and to depict the changes in collateral circulation in patients with certain variants. Detection of particular variants may lead to the discovery of other nonvascular or vascular anomalies, especially aneurysms, and may also affect planning of endovascular or neurosurgical interventions. In this review, we summarize the variants and anomalies of cerebral arteries seen on cross‐sectional imaging classified by a morphological approach and categorize their significance from a clinical perspective. This structured review is intended to serve as a guide for daily use in clinical practice.
A systematic review and meta‐analysis of 3‐unit fixed dental prostheses: Are the results of 2 abutment implants comparable to the results of 2 abutment teeth?
Authors: Pol C. W. P. , Raghoebar G. M. , Kerdijk W. , Boven G. C. , Cune M. S. , Meijer H. J. A.
Published: September 2017

The purpose of the systematic review and meta‐analysis was to compare the performance of 3‐unit bridges on teeth with 3‐unit bridges on implants, evaluating survival of the bridges, survival of the teeth or implants, condition of the hard and soft tissues surrounding the supports, complications and patient‐reported outcome measures (PROM) after a mean observation period of at least 1 year. A literature search was conducted using a combination of the search terms: fixed partial denture and fixed dental prostheses (FDPs). An electronic search for data published until January 2017 was undertaken using the MEDLINE, EMBASE and Cochrane Library databases. Eligibility criteria included clinical human studies, either randomised or not, interventional or observational, which evaluated the results of 3‐unit FDPs on either 2 implants or 2 abutment teeth. The search identified 1686 unique references. After applying eligibility criteria, 66 articles were included in the analysis. A total of 1973 3‐unit FDPs were supported by teeth, and 765 were implant‐supported. No significant differences were found either in the survival of the supporting abutments (P = .52; 99% vs 98.7% survival per year) or in the survival of the prostheses (P = .34; 96.4% vs 97.4% survival per year). Both treatments show an almost equally low complication rate, but there is a low level of reporting of hard and soft tissue conditions and PROM. It is concluded that implant‐supported 3‐unit FDPs seem to be a reliable treatment with survival rates not significantly different from the results of teeth‐supported 3‐unit FDPs.
Long‐term responses of canopy–understorey interactions to disturbance severity in primary Picea abies forests
Authors: Bače Radek , Schurman Jonathan S. , Brabec Marek , Čada Vojtěch , Després Tiphaine , Janda Pavel , Lábusová Jana , Mikoláš Martin , Morrissey Robert C. , Mrhalová Hana , Nagel Thomas A. , Nováková Markéta H. , Seedre Meelis , Synek Michal , Trotsiuk Volodymyr , Svoboda Miroslav
Published: September 2017

Questions

How do canopy–understorey interactions respond to variation in disturbance severity over extended periods of time? For forests with different disturbance histories, do light availability and understorey cohort densities converge towards a common old‐growth structure, or do historical legacies influence populations indefinitely?

Locations

Remnants of primary spruce (Picea abies (L.) Karst.) forests throughout Germany, Slovakia, Ukraine and Romania.

Methods

A disturbance history of >200 yr was reconstructed from 11 278 tree cores collected from forest plots (n = 520). Understorey tree densities of two size classes and hemispherical photo‐based light availabilities were inventoried and modelled as functions of the severity of the main disturbance and time since the event.

Results

Variation in understorey tree densities had a hump‐shaped distribution through time. Stem densities were approximately static in the least disturbed sites, and declined in relation to disturbance severity over approx. 100 yr. Similar to patterns of stem densities, initially high understorey light availability also reached a minimum at 100 yr, which indicated crown closure. Following this, light availability and stem densities both increased as stands transitioned from stem exclusion to understorey re‐initiation. The effect of disturbance severity on understorey densities and patchiness in light availability persisted for >200 yr.

Conclusions

Long‐term trends in canopy–understorey interactions validate current conceptual models of forest development. Furthermore, we empirically validate that these conceptual models generalized over gradients in disturbance severity. Higher disturbance sites exhibited a more even‐aged character with more pronounced periods of stem exclusion, canopy closure and understorey re‐initiation; forests with low‐severity disturbance histories yielded a more stationary uneven‐aged structure. The model identified the extent of variation in disturbance severity within which these P. abies forests are able to regenerate and retain their monospecific character, which is increasingly relevant as disturbance regimes continue to shift under global climate change.
High‐pressure polymorphs in Yamato‐790729 L6 chondrite and their significance for collisional conditions
Authors: Kato Yukako , Sekine Toshimori , Kayama Masahiko , Miyahara Masaaki , Yamaguchi Akira
Published: September 2017

Shock pressure recorded in Yamato (Y)‐790729, classified as L6 type ordinary chondrite, was evaluated based on high‐pressure polymorph assemblages and cathodoluminescence (CL) spectra of maskelynite. The host‐rock of Y‐790729 consists mainly of olivine, low‐Ca pyroxene, plagioclase, metallic Fe‐Ni, and iron‐sulfide with minor amounts of phosphate and chromite. A shock‐melt vein was observed in the hostrock. Ringwoodite, majorite, akimotoite, lingunite, tuite, and xieite occurred in and around the shock‐melt vein. The shock pressure in the shock‐melt vein is about 14–23 GPa based on the phase equilibrium diagrams of high‐pressure polymorphs. Some plagioclase portions in the host‐rock occurred as maskelynite. Sixteen different CL spectra of maskelynite portions were deconvolved using three assigned emission components (centered at 2.95, 3.26, and 3.88 eV). The intensity of emission component at 2.95 eV was selected as a calibrated barometer to estimate shock pressure, and the results indicate pressures of about 11–19 GPa. The difference in pressure between the shock‐melt vein and host‐rock might suggest heterogeneous shock conditions. Assuming an average shock pressure of 18 GPa, the impact velocity of the parent‐body of Y‐790729 is calculated to be ~1.90 km s−1. The parent‐body would be at least ~10 km in size based on the incoherent formation mechanism of ringwoodite in Y‐790729.
Hemolytic Activity of Leptospira interrogans Serovar canicola Cultured in Protein‐Free Medium
Authors: YANAGMARA Yasutake , KOJIMA Tsuyoshi , MIFUCHI Ichiji
Published: September 2017

Hemolytic activity of the culture supernatant of Leptospira interrogans serovar canicola strain Moulton grown in protein‐free medium was demonstrated. The activity began to appear in the late logarithmic phase of growth of the organism and reached a plateau after 2 weeks of cultivation. It was inactivated by the addition of dipotassium ethylenediaminetetraacetate, but was effectively restored by Mg2+. Hemolysis by the culture supernatant was stimulated by “hot‐cold” incubation. Sheep erythrocytes treated with the culture supernatant of the organism were transformed into spherocytes, in which invagination was observed. A hemolysin inhibitor in rabbit serum was found to be in the chloroform‐methanol soluble fraction of the serum. The hemolysin of Leptospira may be phospholipase C.
Characterization of Avian Paramyxoviruses Isolated from Feral Ducks in Northern Japan: The Presence of Three Distinct Viruses in Nature
Authors: YAMANE Nobuhisa , ARIKAWA Jiro , ODAGIRI Takato , ISHIDA Nakao
Published: September 2017

Seventy‐eight strains of avian paramyxoviruses (PMV) were isolated from cloacal and/or tracheal swabs taken from 1,342 feral ducks, comprised of spot‐bill ducks, mallards, pintails, teals, falcated teals, wigeons and buffie‐heads, in Wakuya‐cho, Miyagi Prefecture, Japan, between 1976 and 1979. Five and a half percent of the ducks were positive for virus. Serological and structural characterization indicated that three different avian paramyxoviruses arc prevalent in the Japanese feral duck population. The first group of PMV was Newcastle disease virus (NDV), and in vivo pathogenecity tests in embryonated chicken eggs and 1‐day‐old chicks revealed that all the NDV strains isolated were avirulent. The second and most prevalent strain was closely related to PMV‐4, duck/Hong Kong/D3/75 strain. The viruses of the third group were recovered only from pintails. They cross‐reacted antigenically with PMV‐3 when antisera to the PMV‐3 reference strains, turkey/Wisconsin/68 and parakeet/Netherlands/449/75, were employed. However, no cross‐reaction was observed when antiserum to pintail/ Wakuya/20/78, the prototype of this group, was used. The viruses of the third group also differed in viral polypeptide profile from the reference strains of PMV‐3.
Induction of apoptosis‐like cell death and clearance of stress‐induced intracellular protein aggregates: dual roles for Ustilago maydis metacaspase Mca1
Authors: Mukherjee Dibya , Gupta Sayandeep , Saran N. , Datta Rahul , Ghosh Anupama
Published: September 2017

Metacaspases primarily associate with induction and execution of programmed cell death in protozoa, fungi and plants. In the recent past, several studies have also demonstrated cellular functions of metacaspases other than cell death in different organisms including yeast and protozoa. This study shows similar dual function for the only metacaspase of a biotrophic phytopathogen, Ustilago maydis. In addition to a conventional role in the induction of cell death, Mca1 has been demonstrated to play a key role in maintaining the quality of the cellular proteome. On one hand, Mca1 could be shown to bring about apoptosis‐like phenotypic changes in U. maydis on exposure to oxidative stress, on the other hand, the protein was found to regulate cellular protein quality control. U. maydis metacaspase has been found to remain closely associated with the insoluble intracellular protein aggregates, generated during an event of stress exposure to the fungus. The study, therefore, provides direct evidence for a role of U. maydis metacaspase in the clearance of the stress‐induced intracellular insoluble protein aggregates. Furthermore, host infection assays with mca1 deletion strain also revealed a role of the protein in the virulence of the fungus.
Utilization of Leads After Permanent Implant in Spinal Cord Stimulator Systems
Authors: Sanders Rebecca A. , Hoelzer Bryan C. , Bendel Markus A. , Lamer Tim J. , Pittelkow Thomas P. , Eldrige Jason S. , Pingree Matthew J. , Moeschler Susan M. , Gazelka Halena M. , Mauck W. David , Rho Richard H.
Published: September 2017

Objective

The goal of this study was to determine the frequency and clinical indications associated with implantation of single vs. dual percutaneous lead spinal cord stimulator (SCS) systems and to look further into how these leads are utilized for treatment.

Materials and Methods

A retrospective cohort analysis of all patients undergoing SCS implantation between January 2001 and December 2013 with a minimum of 2 years of clinical follow‐up was performed. Number of trial leads and implanted leads was recorded. For patients with dual‐lead systems, it was noted if and when the second lead was used, along with the clinical indication for lead activation.

Results

In the 259‐patient cohort, 15.8% (n = 41) patients underwent placement of a single‐lead system, 83.0% (n = 215) underwent placement of a dual‐lead system, and 1.2% (n = 3) underwent placement of 3‐lead systems. Placement of dual‐lead systems was similar among all indication groups. Of those patients with a dual‐lead system in place, 88.1% utilized both leads and average time to programming of the second lead was 2.3 months. The most common reason to activate the second lead was inadequate stimulation coverage. Five of the 41 patients with single‐lead systems underwent an additional surgery to implant a second lead due to inadequate stimulation with 1 lead.

Conclusions

To our knowledge this is the first descriptive analysis of the frequency of single‐ and dual‐lead SCS systems. This report indicates that dual‐lead systems are most often placed and both leads are required for optimal patient therapy.
Oral Prolonged‐Release Oxycodone/Naloxone for Managing Pain and Opioid‐Induced Constipation: A Review of the Evidence
Authors: Morlion Bart J. , Mueller‐Lissner Stefan A. , Vellucci Renato , Leppert Wojciech , Coffin Benoît C. , Dickerson Sara L. , O'Brien Tony
Published: September 2017

Background

Opioids provide effective relief from moderate‐to‐severe pain and should be prescribed as part of a multifaceted approach to pain management when other treatments have failed. Fixed‐dose oxycodone/naloxone prolonged‐release tablets (OXN PR) were designed to address the opioid class effect of opioid‐induced constipation (OIC) by combining the analgesic efficacy of oxycodone with the opioid receptor antagonist, naloxone, which has negligible systemic availability when administered orally. This formulation has abuse‐deterrent properties, since systemic exposure to naloxone by parenteral administration would antagonize the euphoric effects of oxycodone.

Methods

A literature search was conducted to assess the evidence base for OXN PR to treat moderate‐to‐severe pain and its impact on bowel function, based on published clinical trials and observational studies.

Results

Extensive data demonstrate that OXN PR provides effective analgesia and clinically relevant improvements in bowel function in patients with OIC and moderate‐to‐severe cancer‐related pain and noncancer pain types such as low back pain, neuropathic pain, and musculoskeletal pain. OXN PR has also been found to improve bowel function in patients with OIC refractory to multiple types of laxatives, and improve Parkinson's disease–related pain. No unanticipated safety concerns have been reported in elderly patients.

Conclusions

Evidence from clinical trials and observational studies confirms that for selected patients OXN PR significantly improves moderate‐to‐severe chronic pain and provides relief from OIC. Treatment should be tailored to individual patients to establish the lowest effective dose. An absence of analgesic ceiling effect was seen across the clinically relevant dose range investigated (≤ 160/80 mg/day).
Physiological and molecular mechanisms underlying the integration of light and temperature cues in Arabidopsis thaliana seeds
Authors: Arana María Verónica , Tognacca Rocío Soledad , Estravis‐Barcalá Maximiliano , Sánchez Rodolfo Augusto , Botto Javier Francisco
Published: September 2017

The relief of dormancy and the promotion of seed germination are of extreme importance for a successful seedling establishment. Although alternating temperatures and light are signals promoting the relief of seed dormancy, the underlying mechanisms of their interaction in seeds are scarcely known. By exposing imbibed Arabidopsis thaliana dormant seeds to two‐day temperature cycles previous of a red light pulse, we demonstrate that the germination mediated by phytochrome B requires the presence of functional PSEUDO‐RESPONSE REGULATOR 7 (PRR7) and TIMING OF CAB EXPRESSION 1 (TOC1) alleles. In addition, daily cycles of alternating temperatures in darkness reduce the protein levels of DELAY OF GERMINATION 1 (DOG1), allowing the expression of TOC1 to induce seed germination. Our results suggest a functional role for some components of the circadian clock related with the action of DOG1 for the integration of alternating temperatures and light signals in the relief of seed dormancy. The synchronization of germination by the synergic action of light and temperature through the activity of circadian clock might have ecological and adaptive consequences.
Genetics and epigenetics of autism: A Review
Authors: Waye Mary M. Y. , Cheng Ho Yu
Published: September 2017

Autism is a developmental disorder that starts before age 3 years, and children with autism have impairment in both social interaction and communication, and have restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. There is a strong heritable component of autism and autism spectrum disorder (ASD) as studies have shown that parents who have a child with ASD have a 2–18% chance of having a second child with ASD. The prevalence of autism and ASD have been increasing during the last 3 decades and much research has been carried out to understand the etiology, so as to develop novel preventive and treatment strategies. This review aims at summarizing the latest research studies related to autism and ASD, focusing not only on the genetics but also some epigenetic findings of autism/ASD. Some promising areas of research using transgenic/knockout animals and some ideas related to potential novel treatment and prevention strategies will be discussed.
Polarized transilluminating dermoscopy: Bedside trichoscopic diagnosis of trichothiodystrophy
Authors: Yang Yul W. , Yarbrough Kevin , Mitkov Mario , Russi Daniela , Price Harper N. , Swanson David L.
Published: September 2017

Trichothiodystrophy is a rare autosomal recessive disorder resulting in a broad range of systemic abnormalities. Polarizing microscopy of the hair reveals the pathognomic “tiger tail” of alternating light and dark bands, but the need for a microscope prevents rapid bedside diagnosis. We describe a new technique for the bedside diagnosis of trichothiodystrophy using a handheld polarizing dermatoscope, precluding the need for microscopic examination.
Immigrant Health through the Lens of Home Visitors, Supervisors, and Administrators: The Florida Maternal, Infant, and Early Childhood Home Visiting Program
Authors: Jean‐Baptiste Esther , Alitz Paige , Birriel Pamela C. , Davis Siobhan , Ramakrishnan Rema , Olson Leandra , Marshall Jennifer
Published: September 2017

Objective

The Florida Maternal, Infant, and Early Childhood Home Visiting (MIECHV) program aims to minimize the occurrence of adverse maternal and child health outcomes for mothers deemed at‐risk during pregnancy or shortly after childbirth. This study sought to understand the needs of and challenges faced by immigrant families in accessing health care through the perspective of Florida MIECHV home visitors, supervisors, and administrators.

Design and Sample

In this exploratory qualitative study, focus groups were held at each of the Florida MIECHV‐funded program sites with a total of 81 MIECHV staff to discuss how the program addresses a range of participant needs.

Measures

Data were collected through 32 semi‐structured focus groups. Transcripts were analyzed using a hybrid approach entailing the development of an a priori codebook and thematic analysis.

Results

Staff from eight of the 11 programs described social and physical isolation and economic hardship faced by immigrant families enrolled in their programs, resulting in barriers to needed health care and social services.

Conclusions

Home visitors in the Florida MIECHV program served as trusted confidants that helped families navigate social services. Future research should focus on the impact that home visiting has on immigrant health and whether this impact is maintained over time.
Creating and sustaining an academic‐practice Partnership Engagement Model
Authors: Schaffer Marjorie A. , Schoon Patricia M. , Brueshoff Bonnie L.
Published: September 2017

Public health clinical educators and practicing public health nurses (PHNs) are experiencing challenges in creating meaningful clinical learning experiences for nursing students due to an increase in nursing programs and greater workload responsibilities for both nursing faculty and PHNs. The Henry Street Consortium (HSC), a collaborative group of PHNs and nursing faculty, conducted a project to identify best practices for public health nursing student clinical learning experiences. Project leaders surveyed HSC members about preferences for teaching‐learning strategies, facilitated development of resources and tools to guide learning, organized faculty/PHN pilot teams to test resources and tools with students, and evaluated the pilot team experiences through two focus groups. The analysis of the outcomes of the partnership engagement project led to the development of the Partnership Engagement Model (PEM), which may be used by nursing faculty and their public health practice partners to guide building relationships and sustainable partnerships for educating nursing students.
LLLT Effects on Oral Keratinocytes in an Organotypic 3D Model
Authors: Basso Fernanda G. , Pansani Taisa N. , Soares Diana G. , Hebling Josimeri , de Souza Costa Carlos Alberto
Published: September 2017

Several in vitro studies evaluated the cellular and molecular events related to interactions between phototherapy and target tissues, including oral keratinocytes and fibroblasts, providing elucidative data about phototherapy‐induced healing. However, these interactions were limited to the application of a bidimensional cell culture model of oral mucosal cells. Thus, thisstudy evaluated the use of an organotypic oral epithelium model to elucidate the morphological and phenotypic responses of cells subjected to low‐level laser therapy (LLLT). Oral keratinocytes were seeded in the ex vivo‐produced oral mucosal equivalent (EVPOME) model, with a porcine acellular dermal matrix. LLLT was applied by means of the LaserTABLE device (780 nm, 25 mW) at 0.5, 1.5 and 3 J cm−2. After three irradiations, morphology, proliferation and gene expression of growth factors were assessed. LLLT and control groups presented similar morphological features, characterized by the formation of a stratified, differentiated and keratinized epithelium. LLLT enhanced the cell proliferation and gene expression of keratinocytes (hKGF) as well as epidermal (hEGF) growth factors. In general, analysis of these data shows that the three‐dimensional cell culture model can be applied for phototherapy studies and that the positive effects of LLLT were confirmed by the use of an organotypic model.
A Closer Look at Dark Toxicity of the Photosensitizer TMPyP in Bacteria
Authors: Eckl Daniel B. , Dengler Linda , Nemmert Marina , Eichner Anja , Bäumler Wolfgang , Huber Harald
Published: September 2017

Photodynamic inactivation of bacteria (PIB) is based on photosensitizers which absorb light and generate reactive oxygen species (ROS), killing cells via oxidation. PIB is evaluated by comparing viability with and without irradiation, where reduction of viability in the presence of the photosensitizer without irradiation is considered as dark toxicity. This effect is controversially discussed for photosensitizers like TMPyP (5,10,15,20‐Tetrakis(1‐methyl‐4‐pyridinio)porphyrin tetra(p‐toluensulfonate). TMPyP shows a high absorption coefficient for blue light and a high yield of ROS production, especially singlet oxygen. Escherichia coli and Bacillus atrophaeus were incubated with TMPyP and irradiated with different light sources at low radiant exposures (μW per cm²), reflecting laboratory conditions of dark toxicity evaluation. Inactivation of E. coli occurs for blue light, while no effect was detectable for wavelengths >450 nm. Being more susceptible toward PIB, growth of B. atrophaeus is even reduced for light with emission >450 nm. Decreasing the light intensities to nW per cm² for B. atrophaeus, application of TMPyP still caused bacterial killing. Toxic effects of TMPyP disappeared after addition of histidine, quenching residual ROS. Our experiments demonstrate that the evaluation of dark toxicity of a powerful photosensitizer like TMPyP requires low light intensities and if necessary additional application of substances quenching any residual ROS.
King County's Journey in Institutionalizing Equity and Social Justice
Authors: Valenzuela Matías
Published: September 2017

Related Content: Isett, Head, and VanLandingham (PAR November/December 2017)

Related Content: Gooden (PAR November/December 2017)
Nasal high flow therapy and PtCO2 in stable COPD: A randomized controlled cross‐over trial
Authors: McKinstry Steven , Pilcher Janine , Bardsley George , Berry James , Van de Hei Susanne , Braithwaite Irene , Fingleton James , Weatherall Mark , Beasley Richard
Published: September 2017

Background and objective

Hypercapnia is associated with worse clinical outcomes in exacerbations of COPD. The present study aimed to determine the effects of nasal high flow (NHF) therapy on transcutaneous partial pressure of carbon dioxide (PtCO2) in stable COPD patients.

Methods

In a single‐blind randomized controlled cross‐over trial, 48 participants with COPD were allocated in random order to all of four 20 min interventions: NHF at 15 L/min, 30 L/min and 45 L/min or breathing room air with each intervention followed by a washout period of 15 min. The primary outcome measure was PtCO2 at 20 min, adjusted for baseline PtCO2. Secondary outcomes included respiratory rate at 20 min, adjusted for baseline.

Results

The mean (95% CI) change in PtCO2 at 20 min was −0.6 mm Hg (−1.1 to 0.0), P = 0.06; −1.3 mm Hg (−1.9 to 0.8), P < 0.001; and −2.4 mm Hg (−2.9 to −1.8), P < 0.001; for NHF at 15 L/min, 30 L/min and 45 L/min compared with room air, respectively. The mean (95% CI) change in respiratory rate at 20 min was −1.5 (−2.7 to −0.3), P = 0.02; −4.1 (−5.3 to −2.9), P < 0.001; and −4.3 (−5.5 to −3.1), P < 0.001; breaths per minute compared with room air, respectively.

Conclusion

NHF results in a small flow‐dependent reduction in PtCO2 and respiratory rate in patients with stable COPD.
Evolution of an early Eocene pull‐apart basin in the Central Pontides (Northern Turkey): New insights into the origin of the North Anatolian Shear Zone
Authors: Ottria Giuseppe , Pandolfi Luca , Catanzariti Rita , Da Prato Simone , Ellero Alessandro , Frassi Chiara , Göncüoğlu Mehmet Cemal , Marroni Michele , Ruffini Leonardo , Sayit Kaan
Published: September 2017

Although the North Anatolian Shear Zone is one of the main lithospheric‐scale strike‐slip deformation zone in the world, playing a prominent role in the complex geodynamic interaction among the Eurasian, Anatolian and Arabian plates, the onset time of its activity remains highly controversial. Here, we tackle this issue by utilizing nannofossil biostratigraphy on deposits from the Taşcilar basin, a pull‐apart basin that we have identified inside the North Anatolian Shear Zone overprinting the Intra‐Pontide suture zone. The syn‐tectonic sedimentary succession of the Taşcilar basin developed completely during the early Eocene (Ypresian; CNE4–CNE5 Zones). The strike‐slip faulting related to the initial onset of the North Anatolian Shear Zone can likely be constrained within the Ypresian, suggesting that the westward escape of the Anatolian plate along the North Anatolian Shear Zone started in the early Eocene.
The Stem Cell Club: a model for unrelated stem cell donor recruitment
Authors: Fingrut Warren , Parmar Simran , Cuperfain Ari , Rikhraj Kiran , Charman Erin , Ptak Emilie , Kahlon Manjot , Graham Alice , Luong Susan , Wang Yongjun (George) , Yu Janice , Arora Neha , Suppiah Roopa , Li Edward W. , Lee Anna , Welsh Christopher , Benzaquen Menachem , Thatcher Alicia , Baharmand Iman , Ladd Aedan , Petraszko Tanya , Allan David , Messner Hans
Published: September 2017

BACKGROUND

Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non‐Caucasian males ages 17 to 35 years represent only 8.8% of listed donors.

STUDY DESIGN AND METHODS

The Stem Cell Club is a non‐profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada.

RESULTS

To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor‐database. Of the recruited registrants, 58.3% were male; 60.3% of males self‐reported as non‐Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality.

CONCLUSION

The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor‐database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world.
The Power of Economists within the State
Authors: Christensen Johan
Published: September 2017

The final chapter revisits the overarching argument about the varying power of economists within the state and its impact on the adoption of market-conforming policies. It points out that although economists often played a central role in tax reform processes, their influence depended crucially on the institutionalization of economic knowledge within the state in the postwar period. The chapter also considers what general lessons can be drawn from this analysis and discusses the future prospects for the role of economists in public policy making. Although many studies stress the resilience of economists as providers of market-oriented policies, this conclusion also points to some potential sources of change.
Review Article: Case studies in future trends of computational and experimental nanomechanics
Authors: Gerberich William , Tadmor Ellad B. , Kysar Jeffrey , Zimmerman Jonathan A. , Minor Andrew M. , Szlufarska Izabela , Amodeo Jonathan , Devincre Benoit , Hintsala Eric , Ballarini Roberto
Published: September 2017

With rapidly increasing numbers of studies of new and exotic material uses for perovskites and quasicrystals, these demand newer instrumentation and simulation developments to resolve the revealed complexities. One such set of observational mechanics at the nanoscale is presented here for somewhat simpler material systems. The expectation is that these approaches will assist those materials scientists and physicists needing to verify atomistic potentials appropriate to the nanomechanical understanding of increasingly complex solids. The five following segments from nine University, National and Industrial Laboratories both review and forecast where some of the important approaches will allow a confirming of how in situ mechanics and nanometric visualization might unravel complex phenomena. These address two-dimensional structures, temporal models for the nanoscale, atomistic and multiscale friction fundamentals, nanoparticle surfaces and interfaces and nanomechanical fracture measurements, all coupled to in situ observational techniques. Rapid future advances in the applicability of such materials science solutions appear guaranteed.
Deep-water measurements of container ship radiated noise signatures and directionality
Authors: Gassmann Martin , Wiggins Sean M. , Hildebrand John A.
Published: September 2017

Underwater radiated noise from merchant ships was measured opportunistically from multiple spatial aspects to estimate signature source levels and directionality. Transiting ships were tracked via the Automatic Identification System in a shipping lane while acoustic pressure was measured at the ships' keel and beam aspects. Port and starboard beam aspects were 15°, 30°, and 45° in compliance with ship noise measurements standards [ANSI/ASA S12.64 (2009) and ISO 17208-1 (2016)]. Additional recordings were made at a 10° starboard aspect. Source levels were derived with a spherical propagation (surface-affected) or a modified Lloyd's mirror model to account for interference from surface reflections (surface-corrected). Ship source depths were estimated from spectral differences between measurements at different beam aspects. Results were exemplified with a 4870 and a 10 036 twenty-foot equivalent unit container ship at 40%–56% and 87% of service speeds, respectively. For the larger ship, opportunistic ANSI/ISO broadband levels were 195 (surface-affected) and 209 (surface-corrected) dB re 1 μPa2 1 m. Directionality at a propeller blade rate of 8 Hz exhibited asymmetries in stern-bow (<6 dB) and port-starboard (<9 dB) direction. Previously reported broadband levels at 10° aspect from McKenna, Ross, Wiggins, and Hildebrand [(2012b). J. Acoust. Soc. Am. 131, 92–103] may be ∼12 dB lower than respective surface-affected ANSI/ISO standard derived levels.
Relative contributions of specific frequency bands to the loudness of broadband sounds
Authors: Jesteadt Walt , Walker Sara M. , Ogun Oluwaseye A. , Ohlrich Brenda , Brunette Katyarina E. , Wróblewski Marcin , Schmid Kendra K.
Published: September 2017

Listeners with normal hearing (NH) and sensorineural hearing loss (SNHL) were asked to compare pairs of noise stimuli and choose the louder noise in each pair. Each noise was made up of 15, two-ERBN (equivalent rectangular bandwidth) wide frequency bands that varied independently over a 12-dB range from one presentation to the next. Mean levels of the bands followed the long-term average speech spectrum (LTASS) or were set to 43, 51, or 59 dB sound pressure level (SPL). The relative contribution of each band to the total loudness of the noise was determined by computing the correlation between the difference in levels for a given band on every trial and the listener's decision on that trial. Weights for SNHL listeners were governed by audibility and the spectrum of the noise stimuli, with bands near the spectral peak of the LTASS noise receiving greatest weight. NH listeners assigned greater weight to the lowest and highest bands, an effect that increased with overall level, but did not assign greater weight to bands near the LTASS peak. Additional loudness-matching and paired-comparison studies using stimuli missing one of the 15 bands showed a significant contribution by the highest band, but properties other than loudness may have contributed to the decisions.
Yes We Can! A Phenomenological Study of a Sports Camp for Young People With Cerebral Palsy
Authors: Aggerholm Kenneth , Moltke Martiny Kristian Møller
Published: September 2017

This article contributes to the understanding of embodied practices and experiences within adapted physical activity. It presents a study of a 4-day winter sports camp for young people with cerebral palsy. The experiences of the participants were investigated through qualitative interviews. The findings are analyzed through a phenomenological framework of embodiment and the notions of body schema and body image. By paying special attention to the bodily experience of “I can,” this study shows that participants learned new ways of approaching challenges, gained bodily control in challenging situations, expanded their fields of possible actions through practicing, as well as learned to understand and accept themselves. These findings reveal central values of bodily interventions for people with cerebral palsy and have the potential to inform pedagogical work within the area of adapted physical activity.
Inward H
+
pump xenorhodopsin: Mechanism and alternative optogenetic approach
Authors: Shevchenko Vitaly , Mager Thomas , Kovalev Kirill , Polovinkin Vitaly , Alekseev Alexey , Juettner Josephine , Chizhov Igor , Bamann Christian , Vavourakis Charlotte , Ghai Rohit , Gushchin Ivan , Borshchevskiy Valentin , Rogachev Andrey , Melnikov Igor , Popov Alexander , Balandin Taras , Rodriguez-Valera Francisco , Manstein Dietmar J. , Bueldt Georg , Bamberg Ernst , Gordeliy Valentin
Published: September 2017

Neurons expressing a novel rhodopsin can be activated by light; a complete story of protein structure and function follows.
Depth Distribution and Assembly of Sulfate-Reducing Microbial Communities in Marine Sediments of Aarhus Bay
Authors: Jochum Lara M. , Chen Xihan , Lever Mark A. , Loy Alexander , Jørgensen Bo Barker , Schramm Andreas , Kjeldsen Kasper U.
Published: September 2017

Most sulfate-reducing microorganisms (SRMs) present in subsurface marine sediments belong to uncultured groups only distantly related to known SRMs, and it remains unclear how changing geochemical zones and sediment depth influence their community structure. We mapped the community composition and abundance of SRMs by amplicon sequencing and quantifying the
dsrB
gene, which encodes dissimilatory sulfite reductase subunit beta, in sediment samples covering different vertical geochemical zones ranging from the surface sediment to the deep sulfate-depleted subsurface at four locations in Aarhus Bay, Denmark. SRMs were present in all geochemical zones, including sulfate-depleted methanogenic sediment. The biggest shift in SRM community composition and abundance occurred across the transition from bioturbated surface sediments to nonbioturbated sediments below, where redox fluctuations and the input of fresh organic matter due to macrofaunal activity are absent. SRM abundance correlated with sulfate reduction rates determined for the same sediments. Sulfate availability showed a weaker correlation with SRM abundances and no significant correlation with the composition of the SRM community. The overall SRM species diversity decreased with depth, yet we identified a subset of highly abundant community members that persists across all vertical geochemical zones of all stations. We conclude that subsurface SRM communities assemble by the persistence of members of the surface community and that the transition from the bioturbated surface sediment to the unmixed sediment below is a main site of assembly of the subsurface SRM community.

IMPORTANCE
Sulfate-reducing microorganisms (SRMs) are key players in the marine carbon and sulfur cycles, especially in coastal sediments, yet little is understood about the environmental factors controlling their depth distribution. Our results suggest that macrofaunal activity is a key driver of SRM abundance and community structure in marine sediments and that a small subset of SRM species of high relative abundance in the subsurface SRM community persists from the sulfate-rich surface sediment to sulfate-depleted methanogenic subsurface sediment. More generally, we conclude that SRM communities inhabiting the subsurface seabed assemble by the selective survival of members of the surface community.
A Lytic Providencia rettgeri Virus of Potential Therapeutic Value Is a Deep-Branching Member of the
T5virus
Genus
Authors: Oliveira Hugo , Pinto Graça , Hendrix Hanne , Noben Jean-Paul , Gawor Jan , Kropinski Andrew M. , Łobocka Małgorzata , Lavigne Rob , Azeredo Joana
Published: September 2017

Providencia rettgeri
is emerging as a new opportunistic pathogen with high antibiotic resistance. The need to find alternative methods to control antibiotic-resistant bacteria and the recent advances in phage therapy motivate the search for new phages able to infect
Providencia
spp. This study describes the isolation and characterization of an obligatory lytic phage, vB_PreS_PR1 (PR1), with therapeutic potential against drug-resistant
P. rettgeri
. PR1 is a siphovirus. Its virion DNA size (118,537 bp), transcriptional organization, terminal repeats (10,461 bp), and nicks in the 3′-to-5′ strand are similar to those of phage T5. However, sequence similarities of PR1 to phages of the
T5virus
genus at the DNA and protein levels are limited, suggesting that it belongs to a new species within the
Siphoviridae
family. PR1 exhibits the ability to kill
P. rettgeri
antibiotic-resistant strains, is highly specific to the species, and did not present known genomic markers indicating a temperate lifestyle. The lack of homologies between its proteins and proteins of the only other sequenced
Providencia
prophage, Redjac, suggests that these two phages evolved separately and may target different host proteins.

IMPORTANCE
The alarming increase in the number of bacteria resistant to antibiotics has been observed worldwide. This is particularly true for Gram-negative bacteria. For certain of their strains, no effective antibiotics are available.
Providencia
sp. has been a neglected pathogen but is emerging as a multidrug-resistant bacterium. This has revived interest in bacteriophages as alternative therapeutic agents against this bacterium. We describe the morphological, physiological, and genomic characterization of a novel lytic virus, PR1, which is able to kill drug-resistant
P. rettgeri
clinical isolates. Genomic and phylogenetic analyses indicate that PR1 is a distant relative of
T5virus
genus representatives. The lack of known virulence- or temperate lifestyle-associated genes in the genome of PR1 makes this phage a potential candidate for therapeutic use. Analysis of its genome also improves our knowledge of the ecology and diversity of T5-like siphoviruses, providing a new link for evolutionary studies of this phage group.