bluuebunny/crossref_metadata_2025 huggingface dataset:
Dying blood mononuclear cell secretome exerts antimicrobial activity
Authors: Kasiri Mohammad Mahdi , Beer Lucian , Nemec Lucas , Gruber Florian , Pietkiewicz Sabine , Haider Thomas , Simader Elisabeth Maria , Traxler Denise , Schweiger Thomas , Janik Stefan , Taghavi Shahrokh , Gabriel Christian , Mildner Michael , Ankersmit Hendrik Jan
Published: August 2016

Background

Several activities are attributed to antimicrobial peptides (AMPs), including bacterial killing, leucocyte recruitment and angiogenesis. Despite promises of advanced cellular therapies for treatment of diabetic foot ulcer, it is currently accepted that paracrine factors rather than cellular components are causative for the observed effects. Whether AMPs are present in the mononuclear cell (MNC) secretome (MNC‐sec) of white blood cells that are beneficial in experimental wound healing is not known.

Materials and methods

Antimicrobial activity of the secretomes of nonirradiated (MNC‐sec) and γ‐irradiated MNCs (MNC‐sec rad) was analysed by microdilution assay. AMPs were determined by quantitative real‐time PCR (RT‐PCR) and enzyme‐linked immunosorbent assay (ELISA). Whether human MNC‐sec rad causes AMP secretion in vivo was examined in an experimental rat model. Image flow cytometry was used to determine the type of cell death induced in MNCs after exposure to γ‐radiation.

Results

The antimicrobial activity assay revealed a bactericidal activity of MNC‐sec rad and to a lesser degree also of MNC‐sec. Image flow cytometry showed that γ‐irradiation of MNCs induced early apoptosis followed mainly by necroptosis. RT‐PCR and ELISA revealed a high abundance of different AMPs in the secretome of MNCs. In addition, human MNC‐sec elicited an increase in de novo endogenous AMP production in rats in vivo.

Conclusion

We provide evidence that the secretome of MNCs has direct and indirect positive effects on the immune defence system, including augmentation of antibacterial properties. Our data further suggest that necroptosis could play a key role for the release of paracrine factors and the therapeutic action of MNC‐sec rad.
Bone regeneration in mandibular fractures after the application of autologous mesenchymal stem cells, a randomized clinical trial
Authors: Castillo‐Cardiel Guadalupe , López‐Echaury Alejandro César , Saucedo‐Ortiz José Antonio , Fuentes‐Orozco Clotilde , Michel‐Espinoza Luis Rodrigo , Irusteta‐Jiménez Leire , Salazar‐Parra Marcela , González‐Ojeda Alejandro
Published: August 2016

Background/Aim

Facial injury in adults can commonly result in fractures of the mandible. Autologous mesenchymal stem cells (AMSCs) transplantation is proposed as an alternative to conventional graft treatment to improve bone regeneration. The aim was to evaluate the effectiveness of AMSCs application in mandibular fractures to reduce regeneration time and increase bone quality.

Materials and methods

This study was a single‐blind controlled clinical trial conducted in patients with mandibular angle fractures. Patients were divided into two groups: study group fracture reduction plus application of AMSCs and control group only fracture reduction. AMSCs were obtained from adipose tissue 24 h before the procedure. Intensity and density were evaluated in normal bone and fractured bone at 4 and 12 weeks after surgery using panoramic radiography and computed tomography.

Results

A total of 20 patients, 10 in each group, were included. The study group had a mean age of 31.2 ± 6.3 years, and the control group mean age was 29.7 ± 7.2 years. All patients were male. Bone quality measured in grey levels at week 4 was 108.82 ± 3.4 vs 93.92 ± 2.6 (P = 0.000) using panoramic radiography and 123 ± 4.53 vs 99.72 ± 5.72 (P = 0.000) using computed tomography. At week 12, the measurements were 153.53 ± 1.83 vs 101.81 ± 4.83 (P = 0.000) using panoramic radiography and 165.4 ± 4.2 vs 112.9 ± 2.0 (P = 0.000) using tomography in the study and control groups, respectively.

Conclusion

Similar ossification values were obtained after 4 weeks when the use of AMSCs was compared to simple fracture reduction. However, after 12 weeks, the AMSCs group had a 36.48% higher ossification rate.
EAN guidelines on central neurostimulation therapy in chronic pain conditions
Authors: Cruccu G. , Garcia‐Larrea L. , Hansson P. , Keindl M. , Lefaucheur J.‐P. , Paulus W. , Taylor R. , Tronnier V. , Truini A. , Attal N.
Published: August 2016

Background and purpose

Our aim was to update previous European Federation of Neurological Societies guidelines on neurostimulation for neuropathic pain, expanding the search to new techniques and to chronic pain conditions other than neuropathic pain, and assessing the evidence with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system.

Methods

A systematic review and meta‐analysis of trials published between 2006 and December 2014 was conducted. Pain conditions included neuropathic pain, fibromyalgia, complex regional pain syndrome (CRPS) type I and post‐surgical chronic back and leg pain (CBLP). Spinal cord stimulation (SCS), deep brain stimulation (DBS), epidural motor cortex stimulation (MCS), repetitive transcranial magnetic stimulation (rTMS) and transcranial direct electrical stimulation (tDCS) of the primary motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) were assessed. The GRADE system was used to assess quality of evidence and propose recommendations.

Results

The following recommendations were reached: ‘weak’ for SCS added to conventional medical management in diabetic painful neuropathy, CBLP and CRPS, for SCS versus reoperation in CBLP, for MCS in neuropathic pain, for rTMS of M1 in neuropathic pain and fibromyalgia and for tDCS of M1 in neuropathic pain; ‘inconclusive’ for DBS in neuropathic pain, rTMS and tDCS of the DLPFC, and for motor cortex tDCS in fibromyalgia and spinal cord injury pain.

Conclusions

Given the poor to moderate quality of evidence identified by this review, future large‐scale multicentre studies of non‐invasive and invasive neurostimulation are encouraged. The collection of higher quality evidence of the predictive factors for the efficacy of these techniques, such as the duration, quality and severity of pain, is also recommended.
Green fluorescent protein chromophore derivative suppresses ultraviolet A‐induced JNK‐signalling and apoptosis in keratinocytes and adverse effects in zebrafish embryos
Authors: Wu Nan‐Lin , Lee Te‐An , Wang Sheng‐Fen , Li Hsin‐Ju , Chen Hui‐Ting , Chien Tun‐Cheng , Huang Chieh‐Chen , Hung Chi‐Feng
Published: August 2016

Solar ultraviolet (UV) light has been recognized as the important environmental hazard and contributes to diverse skin damage such as cell death, photoageing and even carcinogenesis. Revelation of harmful responses attributed to UVA radiation has promoted the development of photoprotective agents against UVA‐induced skin damage. In the present study, we tried to evaluate the potential protective effects of a synthetic green fluorescent protein (GFP) chromophore derivative, 4‐chlorobenzyldene‐1, 2‐dimethylimidazolinone (Cl‐BDI, called TC‐22) on UVA‐ and UVB‐ induced stress responses in skin. The HaCaT keratinocytes were used to evaluate the cellular effects. Zebrafish (Danio rerio), which is regarded as a useful and cost‐effective alternative to some mammalian models, was applied as the in vivo animal model. In HaCaT keratinocytes, TC‐22 was able to obviously decrease UVA‐induced cell death. Dissection of the UVA‐induced signalling pathways revealed that TC‐22 could suppress the activation of JNK and caspase 3, but not of ERK and p38. Reduction of UVA‐induced cleavage of caspase 3 and sub‐G1 phase accumulation by pretreatment of TC‐22 was also observed. In zebrafish, we showed that UVA irradiation could decrease the survival and hatching rate, suppress heart beats of embryos and enhance the pigmentation of larvae. Pretreatment of TC‐22 could significantly reverse UVA‐induced the suppression in hatching of eggs and heart beating of embryos and also lowered the UVA‐induced pigmentation in zebrafish. Collectively, we demonstrate that TC‐22, a GFP chromophore derivative, can ameliorate the UVA‐induced stress responses in both epidermal keratinocytes and zebrafish, suggesting the potential use of TC‐22 in photoprotection in the future.
Spatial and temporal dimensions of fire activity in the fire‐prone eastern Canadian taiga
Authors: Erni Sandy , Arseneault Dominique , Parisien Marc‐André , Bégin Yves
Published: August 2016

The forest age mosaic is a fundamental attribute of the North American boreal forest. Given that fires are generally lethal to trees, the time since last fire largely determines the composition and structure of forest stands and landscapes. Although the spatiotemporal dynamics of such mosaics has long been assumed to be random under the overwhelming influence of severe fire weather, no long‐term reconstruction of mosaic dynamics has been performed from direct field evidence. In this study, we use fire length as a proxy for fire extent across the fire‐prone eastern Canadian taiga and systematically reconstruct the spatiotemporal variability of fire extent and fire intervals, as well as the resulting forest age along a 340‐km transect for the 1840–2013 time period. Our results indicate an extremely active fire regime over the last two centuries, with an overall burn rate of 2.1% of the land area yr−1, mainly triggered by seasonal anomalies of high temperature and severe drought. However, the rejuvenation of the age mosaic was strongly patterned in space and time due to the intrinsically lower burn rates in wetland‐dominated areas and, more importantly, to the much‐reduced likelihood of burning of stands up to 50 years postfire. An extremely high burn rate of ~5% yr−1 would have characterized our study region during the last century in the absence of such fuel age effect. Although recent burn rates and fire sizes are within their range of variability of the last 175 years, a particularly severe weather event allowed a 2013 fire to spread across a large fire refuge, thus shifting the abundance of mature and old forest to a historic low. These results provide reference conditions to evaluate the significance and predict the spatiotemporal dynamics and impacts of the currently strengthening fire activity in the North American boreal forest.
Suction samplers for grassland invertebrates: comparison of numbers caught using Vortis™ and G‐vac devices
Authors: Zentane Eman , Quenu Henry , Graham Robert I. , Cherrill Andrew
Published: August 2016

The efficiency of Vortis™ and a modified garden leaf‐blower/vacuum ‘G‐vac’ sampler were compared by sampling invertebrates using standardised sample areas and suction times at three grassland sites. The G‐vac caught more individuals of Araneae, Auchenorrhyncha, Thysanoptera and Hymenoptera than the Vortis. Numbers of Diptera did not differ between devices, but the Vortis™ captured greater numbers of Coleoptera.

Estimated air velocity within the collecting nozzle was greater for the G‐vac and its mode of application resulted in greater disturbance of the grass sward than with the Vortis™. These differences may have contributed to the larger captures of certain taxa by the G‐vac.

It is concluded that G‐vacs can be applied with confidence as a credible alternative to the bespoke Vortis™, and particularly for taxa which are most frequently sampled using suction samplers.
Does cryotherapy improve skin circulation compared with compression and elevation in preventing venous leg ulcers?
Authors: Kelechi Teresa J , Mueller Martina , Madisetti Mohan , Prentice Margie A , Dooley Mary J
Published: August 2016

This trial compared skin blood flow, temperature and incidence of venous leg ulcers in patients with chronic venous disease using compression wraps and elevation pillows. Patients with CEAP C4 skin damage and C5 history of ulcers were randomly assigned to a cryotherapy intervention (n = 138) or placebo cuff control (n = 138) applied to the lower legs over 9 months. The time the ulcers healed prior to enrollment in the study for the cryotherapy group ranged from 1 to 2218 days (n = 8, median = 32 days); for the control group, the range was 24 to 489 days (n = 6, median = 390 days). There were no statistically significant blood flow changes measured in perfusion units with a laser Doppler flowmetre within or between the groups; mean difference between the groups was 0·62, P = 0·619. No differences were noted in skin temperature measured with an infrared thermometer within and between the groups; mean difference between the groups was −0·17°C, P = 0·540. Cryotherapy did not improve skin blood flow or temperature and did not show efficacy in preventing ulcers. However, at least 30% of intervention and 50% of control participants were anticipated to develop an ulcer during the study; only ∼7% occurred. These findings suggest that strict adherence to standard of care decreases the incidence of leg ulcers and remains a best practice for leg ulcer prevention.
Young Psychophysiologist Award Address, 1980
Authors: Duncan‐Johnson Connie C.
Published: August 2016

The latency of the P300 component of the event‐related brain potential plays a unique role in mental chronometry. This is illustrated by presenting data from two experiments that addressed the following issues in information processing: a) the locus of the effect of stimulus probability on choice reaction time, and b) the locus of interference in performance on the Stroop color‐word test. Using P300 latency to index stimulus‐evaluation time, it is shown in the first experiment that both stimulus and response processing are affected by stimulus probability. The results suggest that more probable events are identified faster—an effect which is reflected in decreases in both P300 and response latency—and that the responses to them are emitted more rapidly—an effect which is reflected in reaction time only. In a second experiment, using the Stroop task, response time was found to vary with the congruence between the stimulus word and the color in which it was printed. However, the duration of stimulus processing, as indexed by P300 latency, remained constant. These results indicate that response competition is the primary source of Stroop interference. It is concluded that P300 latency can be viewed as an important addition to the set of dependent variables available to study human information processing.
Synthesis and cardiovascular protective effects of quercetin 7‐O‐sialic acid
Authors: Tian Hua , Liu Qingchao , Qin Shucun , Zong Chuanlong , Zhang Ying , Yao Shutong , Yang Nana , Guan Tao , Guo Shoudong
Published: August 2016

Oxidative stress and inflammation play important roles in the pathogenesis of cardiovascular disease (CVD). Oxidative stress‐induced desialylation is considered to be a primary step in atherogenic modification, and therefore, the attenuation of oxidative stress and/or inflammatory reactions may ameliorate CVD. In this study, quercetin 7‐O‐sialic acid (QA) was synthesized aiming to put together the cardiovascular protective effect of quercetin and the recently reported anti‐oxidant and anti‐atherosclerosis functions of N‐acetylneuraminic acid. The biological efficacy of QA was evaluated in vitro in various cellular models. The results demonstrated that 50 μM QA could effectively protect human umbilical vein endothelial cells (HUVEC, EA.hy926) against hydrogen peroxide‐ or oxidized low‐density lipoprotein‐induced oxidative damage by reducing the production of reactive oxygen species. QA attenuated hydrogen peroxide‐induced desialylation of HUVEC and lipoproteins. QA decreased lipopolysaccharide‐induced secretion of tumour necrosis factor‐α (TNF‐α) and monocyte chemoattractant protein‐1 (MCP‐1), and it significantly reduced the expression of intercellular adhesion molecule‐1, vascular cell adhesion molecule‐1, TNF‐α and MCP‐1. Furthermore, QA effectively promoted cholesterol efflux from Raw 264.7 macrophages to apolipoprotein A‐1 and high‐density lipoprotein by up‐regulating ATP‐binding cassette transporter A1 and G1, respectively. Results indicated that the novel compound QA exhibited a better capacity than quercetin for anti‐oxidation, anti‐inflammation, cholesterol efflux promotion and biomolecule protection against desialylation and therefore could be a candidate compound for the prevention or treatment of CVD.
RAMP1 suppresses mucosal injury from dextran sodium sulfate‐induced colitis in mice
Authors: Kawashima‐Takeda Noriko , Ito Yoshiya , Nishizawa Nobuyuki , Kawashima Rei , Tanaka Kiyoshi , Tsujikawa Kazutake , Watanabe Masahiko , Majima Masataka
Published: August 2016

Background and Aims

Calcitonin gene‐related peptide (CGRP) is thought to be involved in the modulation of intestinal motility. CGRP receptor is composed of receptor activity‐modifying protein (RAMP) 1 combined with calcitonin receptor‐like receptor (CRLR) for CGRP. The study investigated the role of CGRP in mice with experimentally induced colitis.

Methods

The study used dextran sodium sulfate (DSS) to induce colitis in mice. The study compared the severity of colitis in wild‐type (WT) mice, mice treated with a CGRP receptor antagonist (CGRP8–37), and RAMP1 knockout (−/−) mice. Pathological changes in the mucosa were assessed, and inflammatory cells and cytokine levels were measured.

Results

The severity of inflammation in DSS‐induced colitis increased markedly in CGRP8–37‐treated mice and RAMP1−/− mice compared with WT mice. RAMP1−/− mice showed more severe damage compared with CGRP8–37‐treated mice. The number of periodic acid‐Schiff‐positive cells decreased in CGRP8–37‐treated mice compared with WT mice and was even further decreased in RAMP1−/− mice. RAMP1 was expressed by macrophages, mast cells, and T‐cells. RAMP1−/− mice exhibited excessive accumulation of macrophages and mast cells into the colonic tissue with increased levels of tumor necrosis factor‐α and interleukin‐1β as compared with WT mice. Infiltration of T‐cells into the colonic mucosa, which was associated with the expression of T helper (Th) cytokines including Th1 (interferon gamma) and Th17 (IL‐17), was augmented in RAMP1−/− mice.

Conclusions

The findings of this study suggest that RAMP1 exerted mucosal protection in DSS‐induced colitis via attenuation of recruitment of inflammatory cells and of pro‐inflammatory cytokines.
Real‐world efficacy and safety of daclatasvir and asunaprevir therapy for hepatitis C virus‐infected cirrhosis patients
Authors: Morio Kei , Imamura Michio , Kawakami Yoshiiku , Morio Reona , Kobayashi Tomoki , Yokoyama Satoe , Nagaoki Yuko , Kawaoka Tomokazu , Tsuge Masataka , Hiramatsu Akira , Makokha Grace Naswa , Hayes C Nelson , Aikata Hiroshi , Miki Daiki , Ochi Hidenori , Honda Yoji , Mori Nami , Takaki Shintaro , Tsuji Keiji , Chayama Kazuaki
Published: August 2016

Background and Aims

Daclatasvir and asunaprevir combination therapy has shown a high virological response for chronic genotype 1 hepatitis C virus (HCV) infected‐patients. However, the real‐world efficacy and safety of the therapy for patients with cirrhosis are unknown.

Methods

A total of 252 patients with genotype 1 HCV infection (158 with chronic hepatitis and 94 with compensated liver cirrhosis) were treated with 24 weeks of daclatasvir and asunaprevir combination therapy. Plasma concentrations of daclatasvir and asunaprevir at day 5 of treatment, end‐of‐treatment response, sustained virological response (SVR), and the frequencies of adverse events were analyzed.

Result

Plasma asunaprevir concentration was significantly higher, and daclatasvir concentration tended to be higher, in cirrhosis patients compared with chronic hepatitis patients. End‐of‐treatment response was achieved in 95.6% and 94.7% of chronic hepatitis and cirrhosis patients, respectively, and SVR was achieved in 94.3% and 92.6%. Although pre‐treatment NS5A drug resistant‐associated variants were detected, a high SVR rate was achieved when the population frequency of the variant was low. The frequencies of treatment‐related adverse events in cirrhosis patients were similar to those in chronic hepatitis patients. Treatment discontinuation due to adverse events occurred in three and two patients in chronic hepatitis and cirrhosis groups, respectively; however, four out of five patients with treatment discontinuation nonetheless achieved SVR.

Conclusion

Patients with compensated liver cirrhosis have similar virological response and tolerance for daclatasvir plus asunaprevir therapy to patients with chronic hepatitis. This combination therapy might offer a safe and effective treatment for chronic HCV infected‐patients with compensated cirrhosis.
3D correlative morphological and elemental characterization of materials at the deep submicrometre scale
Authors: PRIEBE A. , GORET G. , BLEUET P. , AUDOIT G. , LAURENCIN J. , BARNES J.‐P.
Published: August 2016

This paper shows how X‐ray computed nanotomography (CNT) can be correlated with focused ion beam time‐of‐flight secondary ion mass spectrometry (FIB‐TOF‐SIMS) tomography on the same sample to investigate both the morphological and elemental structure. This methodology is applicable to relatively large specimens with dimensions of several tens of microns whilst maintaining a high spatial resolution of the order of 100 nm. However, combining X‐ray CNT and FIB‐TOF‐SIMS tomography requires innovative sample preparation protocols to allow both experiments to be conducted on exactly the same sample without chemically or structurally modifying the sample between measurements. Moreover, dedicated algorithms have been developed for effective data fusion that is biased with nine degrees of freedom. This methodology has been tested using a porous and heterogeneous solid oxide fuel cell (SOFC) that has features varying in size by three orders of magnitude – from hundreds of nanometre large pores and grains to tens of micron wide functional layers.
Calpain inhibition reduces structural and functional impairment of retinal ganglion cells in experimental optic neuritis
Authors: Smith Amena W. , Rohrer Baerbel , Wheless Lee , Samantaray Supriti , Ray Swapan K. , Inoue Jun , Azuma Mitsuyoshi , Banik Naren L.
Published: August 2016

Optic neuritis (ON), inflammation of the optic nerve, is strongly associated with multiple sclerosis. ON pathology is characterized by attack of autoreactive T cells against optic nerve antigens, resulting in demyelination, death of retinal ganglion cells, and cumulative visual impairment. A model of experimental autoimmune encephalomyelitis (EAE) was utilized to study the onset and progression of ON and the neuroprotective efficacy of oral treatment with the calpain inhibitor SNJ 1945. EAE was actively induced in B10.PL mice with myelin basic protein on Days 0 and 2, and mice received twice daily oral dosing of SNJ 1945 from Day 9 until sacrificing (Day 26). Visual function was determined by electroretinogram recordings and daily measurement of optokinetic responses (OKR) to a changing pattern stimulus. Optic nerve and retinal histopathology was investigated by immunohistochemical and luxol fast blue staining. EAE mice manifested losses in OKR thresholds, a measurement of visual acuity, which began early in the disease course. There was a significant bias toward unilateral OKR impairment among EAE‐ON eyes. Treatment with SNJ 1945, initiated after the onset of OKR threshold decline, improved visual acuity, pattern electroretinogram amplitudes, and paralysis, with attenuation of retinal ganglion cell death. Furthermore, calpain inhibition spared oligodendrocytes, prevented degradation of axonal neurofilament protein, and attenuated reactive astrocytosis. The trend of early, unilateral visual impairment in EAE‐ON parallels the clinical presentation of ON exacerbations associated with multiple sclerosis. Calpain inhibition may represent an ideal candidate therapy for the preservation of vision in clinical ON.

image

As in multiple sclerosis (MS) patients, optic neuritis (ON) and early, primarily monocular loss in spatial acuity is observed in a rodent model (EAE, experimental autoimmune encephalomyelitis). Daily oral treatment with the calpain inhibitor SNJ 1945 preserves visual acuity and preserves retinal ganglion cells (Brn3a, brain‐specific homeobox/POU domain protein 3A) and their axons (MOSP, myelin oligodendrocyte‐specific protein). Calpain inhibition may represent a candidate therapy for the preservation of vision in ON.
Uncertainty and the Voluntary Provision of a Pure Public Good in a Two‐Moment Decision Model
Authors: CAPLAN ARTHUR J.
Published: August 2016

In this paper, we explore the potential benefits of uncertainty that may arise in a two‐moment model of the voluntary provision of a pure public good. We find that an increase in a given contributor i’s risk associated with the aggregate contribution level of the other contributors (i.e., an increase in social uncertainty) induces that contributor to increase his own contribution level if and only if the uncertainty's incremental effect on the expected value of his net marginal utility is negative. Contributor i’s welfare likewise increases when a closely related condition is met, namely that the uncertainty's marginal effect on his expected marginal utility value of the public good exceeds its countervailing effect on the numeraire. Further, the corresponding aggregate contribution to the public good increases in the presence of free‐riding if and only if the incremental effect of contributor i’s contribution on the aggregate expected value of all other contributors’ net marginal utilities is small‐enough positive. We derive similar conditions for the case of private uncertainty, where the increase in contributor i’s risk is associated with his own marginal valuation of the public good. A simple example illustrates these conceptual results. Numerical analysis demonstrates that an increase in private uncertainty can have a nonmonotonic impact on contributor i’s welfare.
Information Provision in Procurement Auctions
Authors: COLEFF JOAQUÍN , GARCIA DANIEL
Published: August 2016

We study the optimal provision of information in a procurement auction with horizontally differentiated goods. The buyer has private information about her preferred location on the product space and has access to a costless communication device. A seller who pays the entry cost may submit a bid comprising a location and a minimum price. We characterize the optimal information structure and show that the buyer prefers to attract only two bids. Further, additional sellers are inefficient since they reduce total and consumer surplus, gross of entry costs. We show that the buyer will not find it optimal to send public information to all sellers. On the other hand, she may profit from setting a minimum price and that a severe hold‐up problem arises if she lacks commitment to set up the rules of the auction ex ante.
Local wound healing biomarkers for real‐time assessment of periodontal regeneration: pilot study
Authors: Pellegrini G. , Rasperini G. , Pagni G. , Giannobile W. V. , Milani S. , Musto F. , Dellavia C.
Published: August 2016

Background and Objectives

Within the same surgical procedure, a great variability on achievement of clinical outcomes exists and may be associated to different molecular factors related to tissue healing. The aim of the present study was to assess the distribution of clinical success separately in regenerative therapy (REG) and open flap debridement (OFD) to evaluate if factors related with healing of epithelium, connective tissue and bone may be associated to the clinical outcome within each surgical procedure.

Material and Methods

Sixteen patients underwent periodontal REG and nine patients underwent OFD. Periodontal wound fluid was collected at baseline, 3–5, 7, 14 and 21 d after surgery, and expression of wound healing proteins was assessed. Pocket depth and clinical attachment level were taken at baseline and at 6 mo of follow‐up. Percentage pocket depth reduction and percentage clinical attachment level gain were computed. Patients were regarded as better or worse responders depending on their percentage pocket depth reduction or percentage clinical attachment level gain.

Results

Higher percentage of better responders was observed in the REG group (68.7%) compared to the OFD group (22.2%). At 21 d, no difference in the profile of most of the proteins emerged, with two exceptions, both regarding REG treatment. Bone morphogenetic protein‐7 tended to increase in better responders and to decrease in worse responders. Matrix metalloproteinase‐1 increased in worse responders and remained substantially unchanged in better responders.

Conclusion

Local expression of matrix metalloproteinase‐1 and bone morphogenetic protein‐7 during wound healing is associated with the clinical performance of periodontal regenerative surgery. The use of local biomarkers offers the potential for real‐time assessment of the periodontal healing process.
A matched comparison study of hepatitis C treatment outcomes in the prison and community setting, and an analysis of the impact of prison release or transfer during therapy
Authors: Aspinall E. J. , Mitchell W. , Schofield J. , Cairns A. , Lamond S. , Bramley P. , Peters S. E. , Valerio H. , Tomnay J. , Goldberg D. J. , Mills P. R. , Barclay S. T. , Fraser A. , Dillon J. F. , Martin N. K. , Hickman M. , Hutchinson S. J.
Published: August 2016

Prisoners are a priority group for hepatitis C (HCV) treatment. Although treatment durations will become shorter using directly acting antivirals (DAAs), nearly half of prison sentences in Scotland are too short to allow completion of DAA therapy prior to release. The purpose of this study was to compare treatment outcomes between prison‐ and community‐based patients and to examine the impact of prison release or transfer during therapy. A national database was used to compare treatment outcomes between prison treatment initiates and a matched community sample. Additional data were collected to investigate the impact of release or transfer on treatment outcomes. Treatment‐naïve patients infected with genotype 1/2/3/4 and treated between 2009 and 2012 were eligible for inclusion. 291 prison initiates were matched with 1137 community initiates: SVRs were 61% (95% CI 55%–66%) and 63% (95% CI 60%–66%), respectively. Odds of achieving a SVR were not significantly associated with prisoner status (P=.33). SVRs were 74% (95% CI 65%–81%), 59% (95% CI 42%–75%) and 45% (95% CI 29%–62%) among those not released or transferred, transferred during treatment, or released during treatment, respectively. Odds of achieving a SVR were significantly associated with release (P<.01), but not transfer (P=.18). Prison‐based HCV treatment achieves similar outcomes to community‐based treatment, with those not released or transferred during treatment doing particularly well. Transfer or release during therapy should be avoided whenever possible, using anticipatory planning and medical holds where appropriate.
High impact of macroaggregated albumin‐based tumour dose on response and overall survival in hepatocellular carcinoma patients treated with 90Y‐loaded glass microsphere radioembolization
Authors: Garin Etienne , Rolland Yan , Pracht Marc , Le Sourd Samuel , Laffont Sophie , Mesbah Habiba , Haumont Laure‐Anne , Lenoir Laurence , Rohou Tanguy , Brun Vanessa , Edeline Julien
Published: August 2016

Background & Aims

Efficacy of radioembolization is derived from radioinduced damage, whereas tumour dosimetry is not considered as yet in prospective clinical trials.

Objectives

This study evaluates the impact of tumour dose (TD), based on 99mTc macroaggregated albumin (MAA) quantification, on response and overall survival (OS).

Materials and Methods

We consecutively included 85 patients with hepatocellular carcinoma treated with 90Y‐loaded glass microspheres. TD was calculated using a quantitative analysis of the MAA SPECT/CT. Responses were assessed after 3 months using the European Association for the Study of the Liver criteria. OS was assessed using Kaplan–Meier tests.

Results

Response rate was 80.3% on lesion‐based analysis (n=132), and 77.5% on patient‐based analysis. The response rate was only 9.1% for patients with TD <205 Gy against 89.7% for those with TD ≥205 Gy (P<10−7). Non‐portal vein thrombosis (PVT) patients exhibited a median OS of 11.75 m (95% CI: 3–30.7 m) for TD <205 Gy, and 25 m (95% CI: 15–34.7 m) for TD ≥205 Gy (P=.0391). PVT patients exhibited a 4.35 m median OS (95% CI: 2–8 m) for TD<205 Gy, and 15.7 m (95% CI: 9.5–25.5 m) for TD ≥205 Gy, (P=.0004), with HR of 6.99. PVT patients exhibited a median OS of 3.6 m (95% CI: 2–8 m) when PVT MAA targeting was poor or with TD <205 Gy (poor candidate), vs 17.5 m (95% CI: 11–26.5 m) for the others identified as good candidates (P<.0001), with HR of 12.85.

Conclusion

This study confirms the highly predictive value of MAA‐based TD evaluation for response and OS. TD evaluation and PVT MAA targeting should be further evaluated in ongoing trials, whereas personalized dosimetry should be implemented in new trial designs.
Gamma‐glutamyltransferase—friend or foe within?
Authors: Kunutsor Setor K.
Published: August 2016

Gamma‐glutamyltransferase (GGT) is a liver enzyme, which is located on the plasma membranes of most cells and organ tissues, but more commonly in hepatocytes, and is routinely used in clinical practice to help indicate liver injury and as a marker of excessive alcohol consumption. Among the liver enzymes, important advances have especially been made in understanding the physiological functions of GGT. The primary role of GGT is the extracellular catabolism of glutathione, the major thiol antioxidant in mammalian cells, which plays a relevant role in protecting cells against oxidants produced during normal metabolism; GGT, therefore, plays an important role in cellular defence. Beyond its physiological functions, circulating serum GGT has been linked to a remarkable array of chronic conditions and diseases, which include nonalcoholic fatty liver disease, vascular and nonvascular diseases and mortality outcomes. This review summarizes the available epidemiological and genetic evidence for the associations between GGT and these adverse outcomes, the postulated biologic mechanisms underlying these associations, outlines areas of outstanding uncertainty and the implications for clinical practice.
MAB_3551c encodes the primary triacylglycerol synthase involved in lipid accumulation in Mycobacterium abscessus
Authors: Viljoen Albertus , Blaise Mickael , de Chastellier Chantal , Kremer Laurent
Published: August 2016

Slow growing pathogenic mycobacteria utilize host‐derived lipids and accumulate large amounts of triacylglycerol (TAG) in the form of intracytoplasmic lipid inclusions (ILI), serving as a source of carbon and energy during prolonged infection. Mycobacterium abscessus is an emerging and rapidly growing species capable to induce severe and chronic pulmonary infections. However, whether M. abscessus, like Mycobacterium tuberculosis, possesses the machinery to acquire and store host lipids, remains unaddressed. Herein, we aimed at deciphering the contribution of the seven putative M. abscessus TAG synthases (Tgs) in TAG synthesis/accumulation thanks to a combination of genetic and biochemical techniques and a well‐defined foamy macrophage (FM) model along with electron microscopy. Targeted gene deletion and functional complementation studies identified the MAB_3551c product, Tgs1, as the major Tgs involved in TAG production. Tgs1 exhibits a preference for long acyl‐CoA substrates and site‐directed mutagenesis demonstrated that His144 and Gln145 are essential for enzymatic activity. Importantly, in the lipid‐rich intracellular context of FM, M. abscessus formed large ILI in a Tgs1‐dependent manner. This supports the ability of M. abscessus to assimilate host lipids and the crucial role of Tgs1 in intramycobacterial TAG production, which may represent important mechanisms for long‐term storage of a rich energy supply.
Forest plant community as a driver of soil biodiversity: experimental evidence from collembolan assemblages through large‐scale and long‐term removal of oak canopy treesQuercus petraea
Authors: Henneron Ludovic , Aubert Michaël , Archaux Fréderic , Bureau Fabrice , Dumas Yann , Ningre François , Richter Claudine , Balandier Philippe , Chauvat Matthieu
Published: August 2016

Plant–soil interactions are increasingly recognized to play a major role in terrestrial ecosystems functioning. However, few studies to date have focused on slow dynamic ecosystems such as forests. As they are vertically stratified by multiple vegetation strata, canopy tree removal by thinning operations could alter forest plant community through tree canopy opening. Very little is known about cascading effects on soil biodiversity.

We conducted a large‐scale, multi‐site assessment of collembolan assemblage response to long‐term canopy tree removal in sessile oakQuercus petraeatemperate forests. A total of 33 experimental plots were studied covering a large gradient of canopy tree basal area, stand age and local abiotic contexts.

Collembolan abundance strongly declined with canopy tree removal in early forest successional stage and this was mediated by negative effect of understory plant community composition changes, i.e. shift from moss and forb to tree seedling, fern, shrub and grass species. Negative effect of this composition shift on collembolan species richness was largely offset by positive effect of the increase in understory plant species richness. This gives support to both the plant mass‐ratio and functional diversity hypotheses. Collembolan functional groups had contrasting response patterns, which were mediated by different ecological factors. Epedaphic (r‐strategist) abundance and species richness increased with canopy tree removal in relation with the increase in understory plant species richness. In contrast, euedaphic (K‐strategist) abundance and species richness declined with canopy tree removal in early forest successional stage in relation with changes in understory plant community composition and species richness, as well as microclimatic conditions.

Overall, our study provides experimental evidence that forest plant community can be a strong driver of collembolan assemblages. It also emphasizes the role of trees as foundation species of forest ecosystems that can shape soil biodiversity through their regulation of understory plant community and ecosystem abiotic conditions.
Multivariable predictors of substantial blood loss in children undergoing craniosynostosis repair: implications for risk stratification
Authors: Meier Petra M. , Zurakowski David , Goobie Susan M. , Proctor Mark R. , Meara John G. , Young Vanessa J. , Rogers Gary F. , DiNardo James A.
Published: August 2016

Background

Operative treatment of craniosynostosis is associated with substantial blood loss, often requiring transfusion of packed red blood cells (PRBC) and coagulation products.

Aims

The aim of this prospective study was to analyze thromboelastographic (TEG) parameters and platelet fibrinogen product to determine predictors of substantial blood loss, and the need for PRBC transfusion and coagulation products.

Methods

With IRB approval, we enrolled 120 children undergoing craniosynostosis repair with a standardized anesthetic, fluid management, and TEG measurements at predefined times. Outcomes of interest were intraoperative blood loss, and need for PRBC transfusion and coagulation products. Multivariable logistic regression and receiver operating characteristic (ROC) curve analysis was applied to determine independent predictors of substantial blood loss and need for coagulation products.

Results

One hundred and eighteen children were included in the analysis. Forty‐four required PRBC transfusion (median 26 ml·kg−1; IQR: 22–42) with median blood loss of 56 ml·kg−1 (IQR: 43–83). Factors associated with the PRBC transfusion included type of surgery, duration of surgery, and three TEG parameters, α‐angle, MA, and K‐time (all P < 0.001). A predictive algorithm was developed by subgroup analysis of cranial vault reconstruction (CVR) patients for substantial intraoperative blood loss (defined as ≥60 ml·kg−1) and need for coagulation products with ROC‐derived cut‐off values: platelet fibrinogen product, <343; α‐angle, <62°; MA, <55 mm; K‐time, >2.1 min. The best prognostic combination included at least two of these four predictors (sensitivity 89%, specificity 90%). Multivariable regression identified MA as the only independent predictor of coagulation product administration (P < 0.001) and ROC analysis identified MA <46 mm as the optimal cut‐off (sensitivity 86%, specificity 94%).

Conclusions

Risk for substantial intraoperative blood loss can be assessed using TEG parameters and platelet fibrinogen product, whereas the need for coagulation products is strongly related to low MA. Patients susceptible to substantial blood loss can be risk stratified based on their TEG/platelet fibrinogen product profile.
A review of anesthetic techniques and outcomes following minimally invasive repair of pectus excavatum (Nuss procedure)
Authors: Frawley Geoff , Frawley Jacinta , Crameri Joe
Published: August 2016

Background

Pectus excavatum (PE) is the most common congenital chest wall deformity, occurring in 1 : 1000 children with a male to female ratio of 4 : 1. Several procedures have been described to manage this deformity, including cartilage resection with sternal osteotomy (the Ravitch procedure) and a minimally invasive repair technique (the Nuss procedure). While initially described as a nonthoracoscopic technique, the current surgical approach of the Royal Childrens Hospital involves thoracoscopic assistance. Postoperative pain is significant in patients undergoing the pectus repair and multiple analgesic regimens have been advocated with continuous thoracic epidural infusions and opioid infusions the most common. Some authors have advocated patient‐controlled analgesia (PCA), paravertebral nerve blocks (PVNB), and wound infusion catheters as alternatives.

Aims

The primary aim of this study was to assess our experience with postoperative pain and analgesia requirements associated with the minimally invasive repair of pectus excavatum in children.

Methods

This is a retrospective cohort study with a contemporaneous comparison group examining patients treated between January 2005 and December 2015 for minimally invasive repair of pectus excavatum by the Nuss procedure.

Results

Two hundred and seventeen patients [mean age 14.9 (sd 1.9) years] with pectus excavatum treated at the Royal Childrens Hospital between 2005 and 2015 were identified. All patients were managed with thoracic epidural analgesia and intravenous morphine infusions. The epidural was effective in the postanesthesia care unit in 97.3% (failure to place an epidural rate was 4 (1.9%); no block on awakening 0.9%). A further 4 (1.8%) were removed within 24 h. The mean morphine equivalent dose in the first 24 h was 0.8 mg·kg−1·day−1. PCA was continued for a mean of 3.8 days and the total mean morphine equivalent dose was 2.2 mg·kg−1·day−1. Minor complications occurred in 67 (30.9%) with postoperative nausea and vomiting in 36 patients (16.6%) and urinary retention requiring an indwelling catheter in 40 patients (18.4%).

Conclusion

An epidural‐based analgesic regime is associated with low pain scores and few acute complications. The continuation of morphine analgesia after the first postoperative day is common but associated with an increased incidence of urinary retention and nausea and vomiting.
The in silico identification and characterization of a bread wheat/Triticum militinae introgression line
Authors: Abrouk Michael , Balcárková Barbora , Šimková Hana , Komínkova Eva , Martis Mihaela M. , Jakobson Irena , Timofejeva Ljudmilla , Rey Elodie , Vrána Jan , Kilian Andrzej , Järve Kadri , Doležel Jaroslav , Valárik Miroslav
Published: August 2016

The capacity of the bread wheat (Triticum aestivum) genome to tolerate introgression from related genomes can be exploited for wheat improvement. A resistance to powdery mildew expressed by a derivative of the cross‐bread wheat cv. Tähti × T. militinae (Tm) is known to be due to the incorporation of a Tm segment into the long arm of chromosome 4A. Here, a newly developed in silico method termed rearrangement identification and characterization (RICh) has been applied to characterize the introgression. A virtual gene order, assembled using the GenomeZipper approach, was obtained for the native copy of chromosome 4A; it incorporated 570 4A DArTseq markers to produce a zipper comprising 2132 loci. A comparison between the native and introgressed forms of the 4AL chromosome arm showed that the introgressed region is located at the distal part of the arm. The Tm segment, derived from chromosome 7G, harbours 131 homoeologs of the 357 genes present on the corresponding region of Chinese Spring 4AL. The estimated number of Tm genes transferred along with the disease resistance gene was 169. Characterizing the introgression's position, gene content and internal gene order should not only facilitate gene isolation, but may also be informative with respect to chromatin structure and behaviour studies.
Integrating gross pathology into teaching of undergraduate medical science students using human cadavers
Authors: Gopalan Vinod , Dissabandara Lakal , Nirthanan Selvanayagam , Forwood Mark R. , Lam Alfred King‐yin.
Published: August 2016

Human cadavers offer a great opportunity for histopathology students for the learning and teaching of tissue pathology. In this study, we aimed to implement an integrated learning approach by using cadavers to enhance students' knowledge and to develop their skills in gross tissue identification, handling and dissection techniques. A total of 35 students enrolled in the undergraduate medical science program participated in this study. A 3‐hour laboratory session was conducted that included an active exploration of cadaveric specimens to identify normal and pathological tissues as well as tissue dissection. The majority of the students strongly agreed that the integration of normal and morbid anatomy improved their understanding of tissue pathology. All the students either agreed or strongly agreed that this laboratory session was useful to improve their tissue dissection and instrument handling skills. Furthermore, students from both cohorts rated the session as very relevant to their learning and recommended that this approach be added to the existing histopathology curriculum. To conclude, an integrated cadaver‐based practical session can be used effectively to enhance the learning experience of histopathology science students, as well as improving their manual skills of tissue treatment, instrument handling and dissection.
Risk factors for morbidities and mortality in children following pneumonectomy
Authors: Giubergia Verónica , Alessandrini Florencia , Barrias Carolina , Giuseppucci Carlos , Reusmann Aixa , Barrenechea Marcelo , Castaños Claudio
Published: August 2016

ABSTRACT

Background and objective

Pneumonectomy (PNE) is a procedure infrequently performed in children. A high morbidity/mortality rate associated with PNE has been described. Few series have been published in the last 15 years. Risk factors associated with morbidity/mortality after PNE were evaluated. Indications, course, survival and complications of PNE in children were also analized.

Methods

In a case series of 51 children who underwent PNE, death within 30 days of surgery, pneumonia, empyema, sepsis, adult respiratory distress syndrome, bronchopleural fistula, bleeding, pneumothorax and post‐PNE syndrome were considered major morbidities. Scoliosis, wound infection and atelectasis were considered minor morbidities.

Results

Median age at PNE was 7.4 years; 45% were males. Indications of pneumonectomy were postinfectious bronchiectasis (61%), tumours (17%), pulmonary malformations (17%), aspiration syndrome (14%), cystic fibrosis (6%), immunodeficiency (4%) and trauma (2%). Mortality rate was 4% at 1 month. Major and minor morbidities were present in 23% and 27% of patients, respectively. Risk factors for development of morbidities after PNE were age ≤ 3 years (OR: 16.7; 95% CI: 2.4–117) and the need for mechanical ventilation for at least 4 days (OR: 8; 95% CI: 1.5–43.6).

Conclusion

Children are at high risk of death, major and minor morbidities following PNE. Caution is recommended for this group of patients.