Estimation of primary radiation output for wide-beam computed tomography scanner.

Abstract:
PURPOSE
To estimate in-air primary radiation output in a wide-beam multidetector computed tomography (CT) scanner.

MATERIALS AND METHODS
A 6-cc ionization chamber was placed free-in-air at the isocenter, and two sheets of lead (1-mm thickness) were placed on the bottom of the gantry cover, forming apertures of 40-80 mm in increments of 8 mm. The air-kerma rate profiles were measured with and without the apertures (   ,   ) for 4.8 s at tube potentials of 80, 100, 120, and 135 kVp, tube current of 50 mA, and rotation time of 0.4 s. The nominal beam width was varied from 40 to 160 mm in increments of 40 mm. Upon completion of data acquisition, the   were plotted as a function of the measured beam width, and the extrapolated dose rates (   ) at zero beam width were calculated by second-order least-squares estimation. Similarly, the   were plotted as a function of the radiation field (measured beam width × aperture size at the isocenter), and the extrapolated dose rates (   ) were compared with the   .

RESULTS
The means and standard errors of the   with 40-, 80-, 120-, and 160-mm nominal beam widths at 120 kVp were 10.94 ± 0.01, 11.13 ± 0.01, 11.22 ± 0.01, and 11.31 ± 0.01 mGy/s, respectively, and the   was reduced to 10.67 ± 0.02 mGy/s. The   of 40-, 80-, 120-, and 160-mm beam widths were reduced to 10.6 ± 0.1, 10.6 ± 0.2, 10.5 ± 0.1, and 10.6 ± 0.1 mGy/s and were not significantly different from the   .

CONCLUSIONS
A method for describing the in-air primary radiation output in a wide-beam CT scanner was proposed that provides a means to characterize the scatter-to-primary ratio of the CT scanner.

Fukuda|Atsushi|A|
Lin|Pei-Jan P|PP|
Ichikawa|Nao|N|
Matsubara|Kosuke|K|

D015898:Tomography Scanners, X-Ray Computed

primary radiation output
CT
beam width
scattered radiation


Adaptations in trunk-pelvis coordination variability in response to fatiguing exercise.

Abstract:
BACKGROUND
During walking, variability in how movement is coordinated between body segments from stride to stride facilitates adaptation to changing environmental or task constraints. Magnitude of this inter-segmental coordination variability is reduced in patient populations and may also decrease in response to muscle fatigue. Previously, stride-to-stride variability has been quantified with the Vector Coding (VC) method, however recent research introduced a new Ellipse Area Method (EAM) to avoid statistical artifacts associated with VC.

RESEARCH QUESTION
Determine changes in trunk-pelvis coordination variability during walking turns in response to fatiguing exercise and to compare coordination variability quantified with VC to the EAM method.

METHODS
15 young adults (mean age: 23.7 (±3.2) years) performed 15 trials of a 90-degree walking turn before and after fatiguing paraspinal muscle exercise. Angular kinematics of the trunk and pelvis segments in the axial plane were quantified using three-dimensional motion capture. Stride to stride variability of axial coordination between the trunk and pelvis pre- and post-fatigue was calculated using both VC and EAM methods. Magnitudes of pre- and post-fatigue variability for VC and EAM were compared with paired t-tests and relationship between the magnitude of variability for the two methods was calculated using Pearson correlation coefficients.

RESULTS
Using both analytical approaches, trunk-pelvis coordination variability decreased significantly post-fatiguing exercise across the stride cycle and within the stance phase of the turn (p < 0.034 for all comparisons). Average magnitudes of variability calculated with VC and EAM were highly correlated. Time series cross correlations pre-post fatigue ranged from 0.81 to 0.98.

SIGNIFICANCE
In healthy individuals, magnitude of trunk-pelvis stride-to-stride coordination variability is reduced following fatiguing exercise but the temporal distribution of variability across the stride cycle is maintained. This finding is robust to the method used to quantify coordination variability.

Smith|Jo Armour|JA|
Eiteman-Pang|Wilford K|WK|
Soangra|Rahul|R|
König Ignasiak|Niklas|N|

Coordination variability
Muscle fatigue
Paraspinal muscles
Gait


Non-cytochrome P450-mediated bioactivation and its toxicological relevance.

Abstract: The bioactivation of drugs is often associated with toxicological outcomes; however, for most cases, the causal relationship between bioactivation and toxicity is not well established despite extensive research that attempts to elucidate the mechanisms leading to the formation of chemically reactive species, presumably the initial step towards adverse reactions. Due to rapid advancement in the research of cytochrome P450s (CYPs) and the prevalence of CYP involvement in the metabolic clearance of pharmaceuticals, CYP-mediated bioactivation is widely investigated and reviewed, while non-CYP-mediated bioactivation has not been emphasized. The widespread use of metabolic stability screening in drug discovery, however, has led to the identification of new chemical entities that rely on non-CYP enzymes for clearance, and the number of drugs that undergo metabolism via these enzymes has increased. Non-CYP enzymes can be divided into four general categories according to their enzymatic function, namely, oxidative, reductive, conjugative and hydrolytic. The aim of this review is to complement the existing literature on CYP-mediated metabolism by focusing on bioactivation mediated non-CYP enzymes and provide representative examples in each category.

D064420:Drug-Related Side Effects and Adverse Reactions

D050217:Metabolic Detoxication, Phase II

non-CYP enzymes
Drug bioactivation
conjugation reactions
hydrolytic reactions
reductive reactions


Emerging Priorities for Microbiome Research.

Abstract: Microbiome research has increased dramatically in recent years, driven by advances in technology and significant reductions in the cost of analysis. Such research has unlocked a wealth of data, which has yielded tremendous insight into the nature of the microbial communities, including their interactions and effects, both within a host and in an external environment as part of an ecological community. Understanding the role of microbiota, including their dynamic interactions with their hosts and other microbes, can enable the engineering of new diagnostic techniques and interventional strategies that can be used in a diverse spectrum of fields, spanning from ecology and agriculture to medicine and from forensics to exobiology. From June 19-23 in 2017, the NIH and NSF jointly held an Innovation Lab on Quantitative Approaches to Biomedical Data Science Challenges in our Understanding of the Microbiome. This review is inspired by some of the topics that arose as priority areas from this unique, interactive workshop. The goal of this review is to summarize the Innovation Lab's findings by introducing the reader to emerging challenges, exciting potential, and current directions in microbiome research. The review is broken into five key topic areas: (1) interactions between microbes and the human body, (2) evolution and ecology of microbes, including the role played by the environment and microbe-microbe interactions, (3) analytical and mathematical methods currently used in microbiome research, (4) leveraging knowledge of microbial composition and interactions to develop engineering solutions, and (5) interventional approaches and engineered microbiota that may be enabled by selectively altering microbial composition. As such, this review seeks to arm the reader with a broad understanding of the priorities and challenges in microbiome research today and provide inspiration for future investigation and multi-disciplinary collaboration.

Cullen|Chad M|CM|
Aneja|Kawalpreet K|KK|
Beyhan|Sinem|S|
Cho|Clara E|CE|
Woloszynek|Stephen|S|
Convertino|Matteo|M|
McCoy|Sophie J|SJ|
Zhang|Yanyan|Y|
Anderson|Matthew Z|MZ|
Alvarez-Ponce|David|D|
Smirnova|Ekaterina|E|
Karstens|Lisa|L|
Dorrestein|Pieter C|PC|
Li|Hongzhe|H|
Sen Gupta|Ananya|A|
Cheung|Kevin|K|
Powers|Jennifer Gloeckner|JG|
Zhao|Zhengqiao|Z|
Rosen|Gail L|GL|

gut microbiome
microbial forensics
microbiome ecology
microbiome evolution
microbiome interactions
prebiotics
probiotics
skin microbiome


Isotonitazene: Fatal intoxication in three cases involving this unreported novel psychoactive substance in Switzerland.

Abstract: The paper describes the first three deaths reported in Europe involved in isotonitazene consumption, a potent benzimidazole derivate opioid consumed in the recreational drug scene. Isotonitazene powder and purity determination was performed on the sample collected in the first death scene by NMR, HRMS, GC-FTIR, ATR-FTIR and GC-MS. Isotonitazene purity was determined by GC-MS analysis and proton NMR, and was defined to be above 95 % and 98 %, respectively. Quantification of isotonitazene in biological samples was performed using a targeted analysis based on SPE extraction and ultra-high performance liquid chromatography tandem mass spectrometry. The isotonitazene median concentration in femoral whole blood was 1.20ng/mL. Isotonitazene concentration in hair was similar or even lower compared to that seen in fentanyl abusers. Isotonitazene distribution in tissues converges in the brain, lungs and heart, respectively. Surprisingly, isotonitazene concentration in liver is the lowest measured for all tissues and fluids analyzed. Based on circumstantial evidence, autopsy findings and the results of the toxicological analysis, the medical examiner concluded that the cause of all three deaths was an acute intoxication with isotonitazene. Since isotonitazene toxic concentration levels are very low, the consumption of this new psychoactive drug is a real hazard for human health.

Mueller|F|F| Bogdal|C|C| Pfeiffer|B|B| Andrello|L|L| Ceschi|A|A| Thomas|A|A| Grata|E|E|

D017550:Spectroscopy, Fourier Transform Infrared

Human tissues post-mortem redistribution


Optimized Real-Time Biomimetic Neural Network on FPGA for Bio-hybridization.

Abstract: Neurological diseases can be studied by performing bio-hybrid experiments using a real-time biomimetic Spiking Neural Network (SNN) platform. The Hodgkin-Huxley model offers a set of equations including biophysical parameters which can serve as a base to represent different classes of neurons and affected cells. Also, connecting the artificial neurons to the biological cells would allow us to understand the effect of the SNN stimulation using different parameters on nerve cells. Thus, designing a real-time SNN could useful for the study of simulations of some part of the brain. Here, we present a different approach to optimize the Hodgkin-Huxley equations adapted for Field Programmable Gate Array (FPGA) implementation. The equations of the conductance have been unified to allow the use of same functions with different parameters for all ionic channels. The low resources and high-speed implementation also include features, such as synaptic noise using the Ornstein-Uhlenbeck process and different synapse receptors including AMPA, GABAa, GABAb, and NMDA receptors. The platform allows real-time modification of the neuron parameters and can output different cortical neuron families like Fast Spiking (FS), Regular Spiking (RS), Intrinsically Bursting (IB), and Low Threshold Spiking (LTS) neurons using a Digital to Analog Converter (DAC). Gaussian distribution of the synaptic noise highlights similarities with the biological noise. Also, cross-correlation between the implementation and the model shows strong correlations, and bifurcation analysis reproduces similar behavior compared to the original Hodgkin-Huxley model. The implementation of one core of calculation uses 3% of resources of the FPGA and computes in real-time 500 neurons with 25,000 synapses and synaptic noise which can be scaled up to 15,000 using all resources. This is the first step toward neuromorphic system which can be used for the simulation of bio-hybridization and for the study of neurological disorders or the advanced research on neuroprosthesis to regain lost function.

Khoyratee|Farad|F| Grassia|Filippo|F| Saïghi|Sylvain|S| Levi|Timothée|T|

biomimetic
bio-hybrid
spiking neural network
Hodgkin-Huxley
neuromorphic
neural diseases


Phenotypic and Genotypic Characterization of Novel Polyvalent Bacteriophages With Potent In Vitro Activity Against an International Collection of Genetically Diverse Staphylococcus aureus.

Abstract: Phage therapy recently passed a key milestone with success of the first regulated clinical trial using systemic administration. In this single-arm non-comparative safety study, phages were administered intravenously to patients with invasive Staphylococcus aureus infections with no adverse reactions reported. Here, we examined features of 78 lytic S. aureus phages, most of which were propagated using a S. carnosus host modified to be broadly susceptible to staphylococcal phage infection. Use of this host eliminates the threat of contamination with staphylococcal prophage - the main vector of S. aureus horizontal gene transfer. We determined the host range of these phages against an international collection of 185 S. aureus isolates with 56 different multilocus sequence types that included multiple representatives of all epidemic MRSA and MSSA clonal complexes. Forty of our 78 phages were able to infect > 90% of study isolates, 15 were able to infect > 95%, and two could infect all 184 clinical isolates, but not a phage-resistant mutant generated in a previous study. We selected the 10 phages with the widest host range for in vitro characterization by planktonic culture time-kill analysis against four isolates:- modified S. carnosus strain TM300H, methicillin-sensitive isolates D329 and 15981, and MRSA isolate 252. Six of these 10 phages were able to rapidly kill, reducing cell numbers of at least three isolates. The four best-performing phages, in this assay, were further shown to be highly effective in reducing 48 h biofilms on polystyrene formed by eight ST22 and eight ST36 MRSA isolates. Genomes of 22 of the widest host-range phages showed they belonged to the Twortvirinae subfamily of the order Caudovirales in three main groups corresponding to Silviavirus, and two distinct groups of Kayvirus. These genomes assembled as single-linear dsDNAs with an average length of 140 kb and a GC content of c. 30%. Phages that could infect > 96% of S. aureus isolates were found in all three groups, and these have great potential as therapeutic candidates if, in future studies, they can be formulated to maximize their efficacy and eliminate emergence of phage resistance by using appropriate combinations.

Whittard|Elliot|E|
Redfern|James|J|
Xia|Guoqing|G|
Millard|Andrew|A|
Ragupathy|Roobinidevi|R|
Malic|Sladjana|S|
Enright|Mark C|MC|


Contextual Positive Coping as a Factor Contributing to Resilience After Disasters.

Abstract:
OBJECTIVE
Strategy-situation fit, or contextual coping, posits that the physical and psychological demands associated with stressors are determined in part by the characteristics of each stress situation and may therefore require the use of different coping strategies. In this review, we discuss strategy-situation fit in the context of both natural and manmade disasters as it pertains to positivity and, ultimately, resilience after disasters.

METHOD
We reviewed the relevant literature on positivity and coping with disasters using a contextual approach.

RESULTS
We identified several disaster-related characteristics (i.e., cause of disaster, temporal characteristics of disasters, and degree of resource loss) that might influence the efficacy of positive coping strategies. We then discussed strategies that could be useful for promoting resilience with regard to these different characteristics.

CONCLUSION
This work represents an initial step in conceptualizing disaster resiliency within the framework of contextual positive coping. Recommendations for future avenues of research are discussed.

Shing|Elaine Z|EZ|
Jayawickreme|Eranda|E|
Waugh|Christian E|CE|

positivity
coping
resilience
disaster
strategy-situation fit
positive emotions
trauma


Caecal dermoid cyst presenting as an appendicular mucocele on abdominal imaging.

Abstract: Background: Dermoid cysts are benign tumors rarely arising from the cecum. Also, including this report, 10 cases have been described in the literature, to our knowledge. Dermoid cysts are benign tumors rarely found in the cecum. A literature research has found only 9 other cases. Case: We describe the case of a healthy 44-year-old man with no surgical history, in whom a well-defined cystic-mass was incidentally found on abdominal computed tomography, presenting as an appendicular mucocele. An hemicolectomy was performed and pathological analysis revealed a dermoid cyst of the cecum. This paper describes the case of a healthy 44-year-old male with no prior surgical history, with a well-defined cystic mass found incidentally on abdominal computed tomography, thought to be an appendicular mucocele. After hemicolectomy and pathological analysis, this was revealed to be a dermoid cyst of the cecum. Conclusion: Although dermoid cysts are a rare tumor of the cecum, they should be considered in the differential diagnosis of a nontender palpate mass in right lower quadrant (RLQ) or cecal mass on imaging. Although rarely found in the cecum, a dermoid cyst should be included in the differential diagnosis of nontender palpable masses of the RLQ, or if revealed by imagery.

Kamdem|Benedikta|B| Sgroi|Antonino|A| Yan|Pu|P| Herren|Gilles|G|

Dermoid cyst
Appendicular mucocele
Cecum
Ileocecal
Mature teratoma


Allergen immunotherapy improves defective follicular regulatory T cells in patients with allergic rhinitis.

Abstract:
BACKGROUND
The function of follicular regulatory T (TFR) cells, especially in regulating IgE production in patients with allergic diseases, is poorly understood.

OBJECTIVE
We sought to investigate the phenotype, function, and clinical relevance of TFR cells in patients with allergic rhinitis (AR).

METHODS
The phenotype and frequency of tonsillar and circulating TFR cells were characterized by using flow cytometry. TFR cell function was examined in an assay by coculturing with follicular helper T cells and B cells. The associations between TFR cells and the clinical features in patients with AR before and after allergen immunotherapy (AIT) were analyzed.

RESULTS
TFR cells were detected in germinal centers of tonsils, but compared with subjects without AR, the frequencies decreased in patients with AR who were allergic to house dust mites. Circulating TFR cells in blood were phenotypically and numerically correlated with tonsillar TFR cells, and a reduction of circulating TFR cells but not total or CXCR5- regulatory T cells was noted in patients with AR compared with healthy control subjects. Moreover, circulating TFR cells in patients with AR showed a specific defect in suppressing IgE production but were capable of suppressing production of other immunoglobulin types. We identified negative associations of circulating TFR cell frequencies and function with antigen-specific IgE levels or disease severity in patients with AR. After AIT, the frequencies and function of circulating TFR cells were improved, which positively associated with disease remission.

CONCLUSION
Impairment in TFR cells might contribute to aberrant IgE production in patients with AR, and AIT improves defective TFR cell function. TFR cells might serve as a potential biomarker to monitor clinical response to AIT.

Yao|Yin|Y| Wang|Zhi-Chao|ZC| Wang|Nan|N| Zhou|Peng-Cheng|PC| Chen|Cai-Ling|CL| Song|Jia|J| Pan|Li|L| Liao|Bo|B| Zhang|Xin-Hao|XH| Yang|Yong-Shi|YS| Xu|Xiao-Yan|XY| Zhu|Rong-Fei|RF| Yu|Di|D| Liu|Zheng|Z|

allergen immunotherapy
follicular regulatory T cells
Allergic rhinitis
IgE


Sicilian Litchi Fruit Extracts Induce Autophagy versus Apoptosis Switch in Human Colon Cancer Cells.

Abstract: Litchi chinensis Sonnerat is a tropical tree whose fruits contain significant amounts of bioactive polyphenols. Litchi cultivation has recently spread in Sicily where the climate conditions are particularly favorable for this crop. Recent findings have shown that Litchi extracts display anti-tumor and pro-apoptotic effects in vitro, but the precise underlying mechanisms have not been fully elucidated. In this study, we report for the first time the effects of Sicilian litchi fruit extracts on colon cancer cells. The results indicated that litchi exocarp, mesocarp and endocarp fractions reduce the viability and clonogenic growth of HT29 cells. These effects were due to cell cycle arrest in the G2/M phase followed by caspase-dependent cell death. Interestingly, litchi exocarp and endocarp triggered a precocious autophagic response (16⁻24 h), which was accompanied by an increase in the level of autophagy related 1/autophagy activating kinase 1 (ATG1/ULK1), beclin-1, microtubule associated protein 1 light chain 3 (LC3)-II and p62 proteins. Autophagy inhibition by bafilomycin A1 or beclin-1 silencing increased cell death, thus suggesting that autophagy was initially triggered as a pro-survival response. Significant effects of Litchi extracts were also observed in other colon cancer cells, including HCT116 and Caco-2 cells. On the other hand, differentiated Caco-2 cells, a model of human enterocytes, appeared to be insensitive to the extracts at the same treatment conditions. High-Performance Liquid Chromatography⁻Electrospray Ionization-Quadrupole-Time-Of-Flight HPLC/ESI/Q-TOF evidenced the presence of some polyphenolic compounds, specifically in exocarp and endocarp extracts, that can account for the observed biological effects. The results obtained suggest a potential therapeutic efficacy of polyphenolic compounds purified from Sicilian Litchi fractions for the treatment of colon cancer. Moreover, our findings indicate that modulation of autophagy can represent a tool to improve the effectiveness of these agents and potentiate the anti-tumor response of colon cancer cells.

autophagy
colon cancer
Litchi chinensis
anti-tumor activity


One-Step Lower Leg Reconstruction with Vascularized Functional Vastus Lateralis Muscle Flap in the Treatment of Embryonal Rhabdomyosarcoma for a Six-Month-Old Boy: A Case Report.

Abstract: Rhabdomyosarcoma (RMS) is a common soft tissue sarcoma in childhood, however, it is very rare in the neonatal period (0.4-2% of cases). This case depicts a boy, who presented with RMS at two weeks of age, but officially diagnosed at the age of three months. MRI and scintigraphy determined a soft tissue tumor in the soleus muscle, while biopsy confirmed embryonal RMS with high mitotic activity (Ki67 (monoclonal antibodies) ~80%). CWS (Cooperative Weichteilsarkom Studiengruppe)-2012 with I2VA (ifosfamide, vincristine, actinomycin) chemotherapy regimen was administered per protocol. Surgical treatment was performed at age of six months and 18 days. The operation consisted of radical tumor resection and total triceps surae with partial fibula resection. Immediate reconstruction of triceps muscle was accomplished using a vascularized functional musculocutaneous vastus lateralis flap. Functional outcome was measured using the Lower Extremity Functional Scale (LEFS) and the Foot and Ankle Outcome Score (FAOS) with the results of 92.5% and 99% respectively.

Ozols|Dzintars|D|0000-0002-2004-177X
Berezovska|Marisa Maija|MM|
Krasts|Janis|J|
Grutupa|Marika|M|
Petersons|Aigars|A|

embryonal rhabdomyosarcoma
functional vastus transplantation
infant microsurgery


Results of cataract surgery in renal transplantation and hemodialysis patients.

Abstract:
AIM
To compare the effect of cataract surgery in renal transplantation and hemodialysis patients.

METHODS
We evaluated 51 eyes of 31 renal transplantation patients, 41 eyes of 29 hemodialysis patients and 45 eyes of 32 normal control patients who received phacoemulsification and intraocular lens (IOL) implantation from January, 2000 to August, 2014 in the Beijing Friendship Hospital. Each individual underwent a blood routine and a kidney function examination. Routine ophthalmologic examination included best-corrected visual acuity (BCVA), a slit-lamp examination to detect cataract type, determination of intraocular pressure, a corneal endothelial count, and fundus examination. All patients received phacoemulsification and an IOL implantation.

RESULTS
For the types of cataract in the three groups, transplantation group was significantly different from normal control group (P=0.04), the most kind is posterior subcapsular cataract (PSC) in transplantation group 33 (64.7%), hemodialysis group had no significantly difference from normal control group (P=0.43), and the difference between transplantation group and hemodialysis group also had significantly difference (P=0.02). For postoperative BCVA in the three groups, transplantation group had significantly difference from normal control group (P=0.03), hemodialysis group was significantly different from normal control group (P=0.00), and the difference between transplantation group and hemodialysis group also had significantly difference (P=0.00). The multiple linear regression equation is Y=0.007 hemoglobin (Hb)-0.000233 serum creatinine (Cr), R(2)=0.898. Postoperative fundus examination showed that hemorrhage, exudation, and macular degeneration were greater in the hemodialysis group.

CONCLUSION
This study showed that the PSC was more in the renal transplantation patients. BCVA was better and fundus lesions were less frequent in the renal transplantation group than in the hemodialysis group after cataract surgery. The multiple linear regression was showed that the Hb was positively correlated with postoperative BCVA, while Cr was negatively correlated with postoperative BCVA. These results may act as indicators in predicting visual acuity for the renal transplantation and hemodialysis patients.

cataract
renal transplantation
hemodialysis
phacoemulsification
intraocular lens


Airway clearance physiotherapy improves ventilatory dynamics during exercise in patients with cystic fibrosis: a pilot study.

Abstract:
BACKGROUND
Airflow limitation and dynamic hyperinflation may limit exercise capacity in patients with cystic fibrosis (CF). The aim was to investigate whether the undertaking of airway clearance physiotherapy (ACT) prior to cardiopulmonary exercise testing (CPET) results in improvements in exercise capacity.

METHODS
A prospective randomised, cross-over pilot study was performed in children aged >9 years. Spirometry, plethysmography and CPET were performed on two separate occasions-one test with ACT prior to CPET and the other without.

RESULTS
12 patients with CF were included in the study with a mean (SD) age of 12.83 (1.85) years. No significant difference in peak oxygen uptake (VO2) was found between the tests. However, lower minute ventilation (VE) and ventilatory equivalents (VEVO2 and VEVCO2) at ventilatory threshold (VT) were noted when ACT was undertaken prior to CPET. The mean(SD) VE (L/min) at VT was 26.67 (5.49) vs 28.92 (6.3) (p=0.05), VEVO2 (L/min) at VT was 24.5 (1.75) vs 26.05 (2.5) (p=0.03) and VEVCO2 (L/min) at VT was 26.58 (2.41) vs 27.98 (2.11) (p=0.03).

CONCLUSIONS
These pilot data suggest that ACT prior to exercise may lead to improved ventilatory dynamics during exercise in individuals with CF.

Vendrusculo|Fernanda Maria|FM|
Johnstone|Zoe|Z|
Dhouieb|Elaine|E|
Donadio|Márcio V F|MVF|
Cunningham|Steven|S|
Urquhart|Donald S|DS|

cystic fibrosis
exercise test
exercise physiology
physical therapy


Long-term music adjuvant therapy enhances the efficacy of sub-dose antiepileptic drugs in temporal lobe epilepsy.

Abstract:
AIMS
Noninvasive music adjuvant therapy shows great potential in improving seizure control when combined with routine antiepileptic drugs. However, the diversity of previous music protocols has resulted in disparate outcomes. The optimized protocol and features for music adjuvant therapy are still not fully understood which limits its feasibility.

METHODS
By applying different regimens of music therapy in various temporal lobe epilepsy models, we evaluated the effect of music in combination with sub-dose drugs on epileptic seizures to determine the optimized protocol.

RESULTS
A subgroup of kindled mice that were responsive to music adjuvant therapy was screened. In those mice, sub-dose drugs which were noneffective on kindled seizures, alleviated seizure severity after 12 h/day Mozart K.448 for 14 days. Shorter durations of music therapy (2 and 6 h/day) were ineffective. Furthermore, only full-length Mozart K.448, not its episodes or other music varieties, was capable of enhancing the efficacy of sub-dose drugs. This music therapeutic effect was not due to increasing cerebral drug concentration, but instead was related with the modulation of seizure electroencephalogram (EEG) spectral powers in the hippocampus.

CONCLUSION
These results indicate that long-term full-length Mozart K.448 could enhance the anti-seizure efficacy of sub-dose drugs and may be a promising noninvasive adjuvant therapy for temporal lobe epilepsy.

sub-dose antiepileptic drugs
temporal lobe epilepsy
Mozart K.448
music adjunctive therapy


Protective Effects of Evening Primrose Oil against Cyclophosphamide-Induced Biochemical, Histopathological, and Genotoxic Alterations in Mice.

Abstract: Cyclophosphamide (CP) is a well-known antineoplastic agent; however, its clinical use can be associated with various organ toxicities. Evening primrose oil (EPO) contains several phytoconstituents with potent anti-oxidant and anti-inflammatory activities. This experimental study was performed to investigate the chemoprotective effects of EPO in the liver and pancreas of CP-intoxicated mice. Thirty-two albino mice were randomly divided into 4 equal groups: group I received saline (control mice), group II were treated with CP at 100 mg/kg/day for two subsequent days, and groups III and VI were treated with 5 and 10 mg/kg/day bw EPO, respectively for 14 days, followed by two doses of CP at the 15th and 16th days of the experiment. Then, mice were sacrificed and histopathological examinations, biochemical studies, and DNA laddering tests were conducted for hepatic and pancreatic tissues. Cyclophosphamide-intoxicated mice showed significant increases (p < 0.05) in the serum levels of liver enzymes, pancreatic amylase and tissue levels of malondialdehyde, and TNF-α, as well as a significant decrease (p < 0.05) in the serum insulin level. In addition, both hepatic and pancreatic tissues showed disturbed tissue architecture, hydropic degeneration, congested vessels, and inflammatory infiltrates, as well as increased DNA fragmentation. In a dose-dependent manner, pretreatment with EPO was associated with significant improvements (p < 0.05) in all biochemical parameters and significant amelioration of histopathological alterations and DNA fragmentation in CP-intoxicated mice. Pretreatment with EPO showed significant antioxidant, anti-inflammatory, and genoprotective effects against the toxic effects of CP in mice hepatic and pancreatic tissues.

Khodeer|Dina M|DM|
Mehanna|Eman T|ET|
Abushouk|Abdelrahman I|AI|
Abdel-Daim|Mohamed M|MM|

evening primrose oil
mice
cyclophosphamide
liver
pancreas
insulin


High expression of insulin receptor on tumour-associated blood vessels in invasive bladder cancer predicts poor overall and progression-free survival.

Abstract: Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival. Furthermore, increased expression of the INSR ligand IGF-2 in invasive bladder cancers was associated with reduced overall survival. INSR may therefore represent a novel biomarker to predict cancer progression. Mechanistically, we observed pronounced hypoxia in human bladder cancer tissue, and found a positive correlation between the expression of the hypoxia marker gene GLUT1 and vascular INSR expression, indicating that hypoxia drives INSR expression in tumour-associated blood vessels. In line with this, exposure of cultured BECs and human bladder cancer cell lines to hypoxia led to increased expression of INSR and IGF-2, respectively, and IGF-2 increased BEC migration through the activation of INSR in vitro. Taken together, we identified vascular INSR expression as a potential biomarker for progression in bladder cancer. Furthermore, our data suggest that IGF-2/INSR mediated paracrine crosstalk between bladder cancer cells and endothelial cells is functionally involved in tumour angiogenesis and may thus represent a new therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Roudnicky|Filip|F|0000-0001-7156-2383
Dieterich|Lothar C|LC|
Poyet|Cedric|C|
Buser|Lorenz|L|
Wild|Peter|P|
Tang|Dave|D|
Camenzind|Peter|P|
Ho|Chien Hsien|CH|
Otto|Vivianne I|VI|
Detmar|Michael|M|

D015972:Gene Expression Regulation, Neoplastic

insulin receptor
bladder cancer
angiogenesis
insulin-like growth factor 2
tumour hypoxia
vascular endothelium


Closing the Gap on Sex Disparity in Acute Coronary Syndrome: Is It Time to Reconsider Our Definitions of "Typical"?

Abstract: See Article Ferry et al.

Editorials
acute aortic syndrome
myocardial infarction
sex‐specific
symptoms


Aspidin PB, a novel natural anti-fibrotic compound, inhibited fibrogenesis in TGF-β1-stimulated keloid fibroblasts via PI-3K/Akt and Smad signaling pathways.

Abstract: Keloid is an overgrowth of scar tissue that develops around a wound. The mechanisms of keloid formation and development still remain unknown, and no effective treatment is available. Searching for active natural resources may develop better prevention and treatment approaches for keloids. Aspidin PB is a natural resource with lower toxicity. We explored its effect on the regulation of TGF-β1-induced expression of type I collagen, CTGF, and α-SMA in keloid fibroblasts (KFs). Western blotting was used to detect the expression levels of type I collagen, CTGF, α-SMA, PI-3K/Akt and Smad-dependent and Smad-independent signaling pathway. The effect of aspidin PB on cell viability in human keloid fibroblasts was measured by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide). The percentage of the apoptotic cells was studied by flow cytometry. Based on our results, we revealed that aspidin PB inhibited the production of type I collagen, CTGF, and α-SMA in TGF-β1-induced KFs by blocking PI-3K/Akt signaling pathway. The TGF-β1-mediated phosphorylated levels of Smad2/3 were inhibited by aspidin PB pretreatment. Conclusively, our study suggests that aspidin PB has an inhibitory effect on fibrogenesis in TGF-β1-induced KFs. Our findings imply that aspidin PB has a therapeutic potential to intervene and prevent keloids and other fibrotic diseases.

D053773:Transforming Growth Factor beta1


Intramedullary Cannulated Compression Screws for Extra-Articular Phalangeal Fractures.

Abstract: Background: There is no consensus as to which is the best way to fix unstable extra-articular phalangeal fractures. We performed a literature review to determine outcomes using intramedullary cannulated compression screws. Methods: PubMed, Medline and Embase databases were searched for English language articles reporting the use of one or more intramedullary screw(s) for fixation of an acute extra-articular phalangeal fracture in adults that reported outcome data. Results: A total of 62 abstracts were identified, of which 14 full-text articles were eligible for full-text screening for the inclusion criteria. Of these 14 articles, seven articles were included in the final study. Data on 146 phalangeal fractures were aggregated with an average patient age of 36 (18-84). 89% (130/146) fractures were of the proximal phalanx, the remainder of the middle phalanx. Surgical technique was mostly a minimally invasive technique under fluoroscopy guidance using an anterograde technique. One paper described a retrograde method. Screw diameter varied from 2.2 mm to 3.2 mm. Where the radiographic union was reported, all fractures united. Range of motion averaged 231° (range 95°-295°) in four studies. Return to work was reported as 6.4 weeks (range 0.9-16.7 weeks) in one study. Different quality-of-life scores were reported by the studies (DASH 3.52 (range 1-45), QuickDASH score of 3.9 and DASH score of 3.9). Complications rate was 5% (8/146) including 5 major complications and 3 minor in the pooled results. Conclusions: This literature review demonstrates that fixation of extra-articular fractures of the proximal and middle phalanges with cannulated compression screws is a safe and successful surgical treatment with faster mobilization and return to work with fewer complications, including stiffness, than have been reported with plates and screws and percutaneous K-wires. This application is limited to transverse and short oblique extra-articular fractures.

D001863:Bone Screws
D004185:Disability Evaluation
D050278:Finger Phalanges
D005593:Fracture Fixation, Internal
D050723:Fractures, Bone
D006801:Humans
D062707:Return to Work

Intramedullary
Cannulated compression screws
Extra-articular
Phalangeal
Fracture


Reverse total shoulder arthroplasty clinical and patient-reported outcomes and complications stratified by preoperative diagnosis: a systematic review.

Abstract:
OBJECTIVE
This systematic review aimed to investigate differences in clinical outcomes, patient-reported outcomes (PROs), and complication types and rates among preoperative diagnoses following reverse total shoulder arthroplasty (RTSA): rotator cuff tear arthropathy, primary osteoarthritis, massive irreparable rotator cuff tear, proximal humeral fracture, rheumatoid arthritis (RA), and revision of anatomic arthroplasty (Rev).

LITERATURE SEARCH
Three electronic databases were searched from inception to January 2020.

STUDY SELECTION CRITERIA
The inclusion criteria were (1) patients with a minimum age of 60 years who underwent RTSA for the stated preoperative diagnoses, (2) a minimum of 2 years' follow-up, and (3) preoperative and postoperative values for clinical outcomes and PROs.

DATA SYNTHESIS
Risk of bias was determined by the Methodological Index for Non-randomized Studies tool and the modified Downs and Black tool. Weighted means for clinical outcomes and PROs were calculated for each preoperative diagnosis.

RESULTS
A total of 53 studies were included, of which 36 (68%) were level IV retrospective case series. According to the Methodological Index for Non-randomized Studies tool, 33 studies (62%) showed a high risk of bias; the 3 randomized controlled trials showed a low risk of bias on the modified Downs and Black tool. RTSA improved clinical outcomes and PROs for all preoperative diagnoses. The Rev group had poorer final outcomes as noted by a lower American Shoulder and Elbow Surgeons score (69) and lower pain score (1.8) compared with the other preoperative diagnoses (78-82 and 0.4-1.4, respectively). The RA group showed the highest complication rate (28%), whereas the osteoarthritis group showed the lowest rate (1.4%).

CONCLUSION
Studies in the RTSA literature predominantly showed a high risk of bias. All preoperative diagnoses showed improvements; Rev patients showed the worse clinical outcomes and PROs, and RA patients showed higher complication rates. The preoperative diagnosis in RTSA patients can impact outcomes and complications.

Kennedy|June|J|
Klifto|Christopher S|CS|
Ledbetter|Leila|L|
Bullock|Garrett S|GS|

D000071066:Patient Reported Outcome Measures

cuff tear arthropathy
primary osteoarthritis
massive irreparable rotator cuff tear
proximal humeral fracture
rheumatoid arthritis
Rehabilitation
revision shoulder


Biomechanics of thoracolumbar burst fractures: methods of induction and treatments.

Abstract: Much controversy exists regarding the mechanism of burst fracture (BF) induction and the proper techniques to treat such fractures. As such, there is a great need for validated preclinical models in which to study these injuries. In this study, an electronic search of the PubMed database (MEDLINE) was performed and the results were filtered to obtain only studies with a biomechanical focus. Forty five biomechanical studies were obtained, from which four distinct methods of injury induction were identified. Twenty one (46.7%) involved clinically relevant techniques for treating BF, involving anterior, posterior, circumferential, or a combination of approaches. Fifteen (71.4%) of the treatment studies used unstable spine specimens that do not fit the classical characteristics of BF. Given the consistent use of BF models that do not adhere to classical definitions, the clinical value of ex vivo induction is uncertain.

Fakurnejad|Shayan|S|
Scheer|Justin K|JK|
Patwardhan|Avinash G|AG|
Havey|Robert M|RM|
Voronov|Leonard I|LI|
Smith|Zachary A|ZA|

Biomechanics
Thoracolumbar
Burst fracture
Spine


Postoperative Esophageal Leaks in Malignant Pathology - Optimal Management: A Systematic Review.

Abstract:
BACKGROUND AND AIMS
Postoperative esophageal leaks are one of the major causes of postoperative mortality and morbidity. The purpose of this study was to review current knowledge of current methods of diagnosis and management of postoperative esophageal leaks. Methods: A systematic literature search was performed in the PubMed/Medline database using the terms "postoperative esophageal leaks" and "postesophagectomy complications" to identify articles relevant to the current diagnostic and prophylactic and curative treatment of post-oesophagectomy anastomotic fistulas. Results: Several papers have shown that the incidence of fistulas varies and is dependent on several factors: the location of the anastomosis, the type of suture used, the biological condition of the patient. Due to the severity of the mediastinal anastomotic fistula, great importance is being given to the methods of preventing its occurrence by intraoperative testing or improving the gastric tube vascularity. The most recent articles present endoscopic methods of treating this complication by using coated esophageal stents and endoluminal vacuum therapy.

CONCLUSION
In patients with mediastinal postoperative esophageal fistulas, diagnosis and management represent a real challenge for the surgeon-endoscopist-therapist team. The early diagnosis and the establishment of an optimal therapy to address the parietal defect and the biological status of the patient are mandatory conditions for resolving this postoperative complication.

Birla|Rodica|R| Hoara|Petre|P| Dinu|Daniela|D| Rosianu|Cristian|C| Constantinoiu|Silviu|S|

esophagealcancer esophagealleaks esophagealstents postesophagectomycomplications


AFQ056/mavoglurant, a novel clinically effective mGluR5 antagonist: identification, SAR and pharmacological characterization.

Abstract: Here we describe the identification, structure-activity relationship and the initial pharmacological characterization of AFQ056/mavoglurant, a structurally novel, non-competitive mGlu5 receptor antagonist. AFQ056/mavoglurant was identified by chemical derivatization of a lead compound discovered in a HTS campaign. In vitro, AFQ056/mavoglurant had an IC50 of 30 nM in a functional assay with human mGluR5 and was selective over the other mGluR subtypes, iGluRs and a panel of 238 CNS relevant receptors, transporter or enzymes. In vivo, AFQ056/mavoglurant showed an improved pharmacokinetic profile in rat and efficacy in the stress-induced hyperthermia test in mice as compared to the prototypic mGluR5 antagonist MPEP. The efficacy of AFQ056/mavoglurant in humans has been assessed in L-dopa induced dyskinesia in Parkinson's disease and Fragile X syndrome in proof of principle clinical studies.

Vranesic|Ivo|I|
Ofner|Silvio|S|
Flor|Peter Josef|PJ|
Bilbe|Graeme|G|
Bouhelal|Rochdi|R|
Enz|Albert|A|
Desrayaud|Sandrine|S|
McAllister|Kevin|K|
Kuhn|Rainer|R|
Gasparini|Fabrizio|F|

D064529:Receptor, Metabotropic Glutamate 5

mGluR5 Antagonist Non-competitive Allosteric


Molecular phylogenetic analysis supports a Gondwanan origin of the Hyriidae (Mollusca: Bivalvia: Unionida) and the paraphyly of Australasian taxa.

Abstract: The freshwater mussel family Hyriidae (Mollusca: Bivalvia: Unionida) has a disjunct trans-Pacific distribution in Australasia and South America. Previous phylogenetic analyses have estimated the evolutionary relationships of the family and the major infra-familial taxa (Velesunioninae and Hyriinae: Hyridellini in Australia; Hyriinae: Hyriini, Castaliini, and Rhipidodontini in South America), but taxon and character sampling have been too incomplete to support a predictive classification or allow testing of biogeographical hypotheses. We sampled 30 freshwater mussel individuals representing the aforementioned hyriid taxa, as well as outgroup species representing the five other freshwater mussel families and their marine sister group (order Trigoniida). Our ingroup included representatives of all Australian genera. Phylogenetic relationships were estimated from three gene fragments (nuclear 28S, COI and 16S mtDNA) using maximum parsimony, maximum likelihood, and Bayesian inference, and we applied a Bayesian relaxed clock model calibrated with fossil dates to estimate node ages. Our analyses found good support for monophyly of the Hyriidae and the subfamilies and tribes, as well as the paraphyly of the Australasian taxa (Velesunioninae, (Hyridellini, (Rhipidodontini, (Castaliini, Hyriini)))). The Hyriidae was recovered as sister to a clade comprised of all other Recent freshwater mussel families. Our molecular date estimation supported Cretaceous origins of the major hyriid clades, pre-dating the Tertiary isolation of South America from Antarctica/Australia. We hypothesize that early diversification of the Hyriidae was driven by terrestrial barriers on Gondwana rather than marine barriers following disintegration of the super-continent.

Graf|Daniel L|DL|
Jones|Hugh|H|
Geneva|Anthony J|AJ|
Pfeiffer|John M|JM|
Klunzinger|Michael W|MW|

Hyriidae
Freshwater mussel
Australasia
Gondwana
Phylogeny


Lack of interleukin-13 receptor α1 delays the loss of dopaminergic neurons during chronic stress.

Abstract:
BACKGROUND
The majority of Parkinson's disease (PD) cases are sporadic and idiopathic suggesting that this neurodegenerative disorder is the result of both environmental and genetic factors. Stress and neuroinflammation are among the factors being investigated for their possible contributions to PD. Experiments in rodents showed that severe chronic stress can reduce the number of dopaminergic neurons in the substantia nigra pars compacta (SNc); the same cells that are lost in PD. These actions are at least in part mediated by increased oxidative stress. Here, we tested the hypothesis that the interleukin-13 receptor alpha 1 (IL-13Rα1), a cytokine receptor whose activation increases the vulnerability of dopaminergic neurons to oxidative damage, participates in the stress-dependent damage of these neurons.

METHODS
Mice were subject to daily sessions of 8 h (acute) stress for 16 weeks (5 days a week), a procedure previously showed to induce loss of dopaminergic neurons in the SNc. The source and the kinetics of interleukin-13 (IL-13), the endogenous ligand of IL-13Rα1, were evaluated 0, 1, 3, 6, and 8 h and at 16 weeks of stress. Identification of IL-13 producing cell-type was performed by immunofluorescent and by in situ hybridization experiments. Markers of oxidative stress, microglia activation, and the number of dopaminergic neurons in IL-13Rα1 knock-out animals (Il13ra1 Y/ - ) and their wild-type littermates (Il13ra1 Y/+ ) were evaluated at 16 weeks of stress and at 20 weeks, following a 4 week non-stressed period and compared to non-stressed mice.

RESULTS
IL-13 was expressed in microglial cells within the SN and in a fraction of the tyrosine hydroxylase-positive neurons in the SNc. IL-13 levels were elevated during daily stress and peaked at 6 h. 16 weeks of chronic restraint stress significantly reduced the number of SNc dopaminergic neurons in Il13ra1 Y/+ mice. Neuronal loss at 16 weeks was significantly lower in Il13ra1 Y/- mice. However, the loss of dopaminergic neurons measured at 20 weeks, after 4 weeks of non-stress following the 16 weeks of stress, was similar in Il13ra1 Y/+ and Il13ra1 Y/- mice.

CONCLUSIONS
IL-13, a cytokine previously demonstrated to increase the susceptibility of SNc dopaminergic neurons to oxidative stress, is elevated in the SN by restraint stress. Lack of IL-13Rα1 did not prevent nor halted but delayed neuronal loss in the mouse model of chronic restraint stress. IL-13/IL-13Rα1 may represent a target to reduce the rate of DA neuronal loss that can occur during severe chronic restraint stress.

Mori|Simone|S|
Sugama|Shuei|S|
Nguyen|William|W|
Michel|Tatiana|T|
Sanna|M Germana|MG|
Sanchez-Alavez|Manuel|M|
Cintron-Colon|Rigo|R|
Moroncini|Gianluca|G|
Kakinuma|Yoshihiko|Y|
Maher|Pamela|P|
Conti|Bruno|B|0000-0002-9185-5201

D053661:Interleukin-13 Receptor alpha1 Subunit

Stress
Neuroinflammation
Oxidative stress
Microglia
Interleukin
Parkinson’s disease


Structure-function similarities in deep brain stimulation targets cross-species.

Abstract: Deep Brain Stimulation (DBS) is an effective neurosurgical treatment to alleviate motor symptoms of advanced Parkinson's disease. Due to its potential, DBS usage is rapidly expanding to target a large number of brain regions to treat a wide range of diseases and neuropsychiatric disorders. The identification and validation of new target regions heavily rely on the insights gained from rodent and primate models. Here we present a large-scale automatic meta-analysis in which the structure-function associations within and between species are compared for 21 DBS targets in humans. The results indicate that the structure-function association for the majority of the 21 included subcortical areas were conserved cross-species. A subset of structures showed overlapping functional association. This can potentially be attributed to shared brain networks and might explain why multiple brain areas are targeted for the same disease or neuropsychiatric disorder.

Keuken|Max C|MC|
Alkemade|Anneke|A|
Stevenson|Niek|N|
Innes|Reilly J|RJ|
Forstmann|Birte U|BU|

DBS
Cross-species comparison
LDA topic modeling


Impact of Von Willebrand Factor on Bacterial Pathogenesis.

Abstract: Von Willebrand factor (VWF) is a mechano-sensitive protein with crucial functions in normal hemostasis, which are strongly dependant on the shear-stress mediated defolding and multimerization of VWF in the blood stream. Apart from bleeding disorders, higher plasma levels of VWF are often associated with a higher risk of cardiovascular diseases. Herein, the disease symptoms are attributed to the inflammatory response of the activated endothelium and share high similarities to the reaction of the host vasculature to systemic infections caused by pathogenic bacteria such as Staphylococcus aureus and Streptococcus pneumoniae. The bacteria recruit circulating VWF, and by binding to immobilized VWF on activated endothelial cells in blood flow, they interfere with the physiological functions of VWF, including platelet recruitment and coagulation. Several bacterial VWF binding proteins have been identified and further characterized by biochemical analyses. Moreover, the development of a combination of sophisticated cell culture systems simulating shear stress levels of the blood flow with microscopic visualization also provided valuable insights into the interaction mechanism between bacteria and VWF-strings. In vivo studies using mouse models of bacterial infection and zebrafish larvae provided evidence that the interaction between bacteria and VWF promotes bacterial attachment, coagulation, and thrombus formation, and thereby contributes to the pathophysiology of severe infectious diseases such as infective endocarditis and bacterial sepsis. This mini-review summarizes the current knowledge of the interaction between bacteria and the mechano-responsive VWF, and corresponding pathophysiological disease symptoms.

von Willebrand
Streptococcus pneumoniae
sepsis
Staphylococcus areus
microfluidic


Nasopharyngeal carcinoma presenting as a sixth nerve palsy and Horner's syndrome.

Abstract: The combination of a sixth nerve palsy and ipsilateral Horner's syndrome localises the disease process to the posterior cavernous sinus and can be a result of various pathologies in this region. A 74-year-old Chinese woman presented with a 9-month history of binocular horizontal diplopia worse when looking left. She was found to have a left sixth nerve palsy and Horner's syndrome and MRI revealed an enhancing soft tissue mass in the nasopharynx with involvement of the bones of the skull base and invasion of the left cavernous sinus. Endoscopic biopsy of the mass confirmed the diagnosis of non-keratinising squamous cell carcinoma, which was Epstein-Barr virus positive. She was treated with radiation therapy. Patients with a sixth nerve palsy and ipsilateral Horner's syndrome should have urgent neuroimaging with careful attention to the cavernous sinus since sympathetic fibres join the sixth nerve for a short distance in this location.


MOMENTUM: A Phase I Trial Investigating 2 Schedules of Capecitabine With Aflibercept in Patients With Gastrointestinal and Breast Cancer.

Abstract:
BACKGROUND
Although data from preclinical and clinical studies provide a strong rationale for combining capecitabine with anti-angiogenic agents, clinical development of this fluoropyrimidine in combination with aflibercept has lagged behind other treatments. We conducted a nonrandomized, noncomparative, 2-arm, phase I trial to address this unmet need.

PATIENTS AND METHODS
Patients with chemorefractory gastrointestinal and breast cancer were sequentially recruited into a continuous (Arm A, starting dose 1100 mg/m2/day) or intermittent (Arm B, 2 weeks on/1 week off, starting dose 1700 mg/m2/day) capecitabine dosing arm. Aflibercept was administered at a flat dose of 6 mg/kg every 3 weeks in both arms. A classical 3 + 3, dose-escalation design was used. The primary objective was to establish the maximum tolerated dose, dose-limiting toxicities (DLTs), and recommended dose for phase II trials.

RESULTS
Thirty-eight eligible patients were recruited of whom 33 were assessable for DLTs (15 in arm A and 18 in arm B). Fourteen had colorectal cancer, 8 gastric cancer, and 11 breast cancer. DLTs included grade 2 hand-foot syndrome, grade 2 anorexia considered unacceptable by the patient, and grade 3 hypertension. The recommended dose for phase II trials for capecitabine was established at 1300 mg/m2/day in Arm A and 2500 mg/m2/day in Arm B with treatment-related grade ≥ 3 adverse events occurring in 47% and 50% of patients, respectively. Among 26 assessable patients, the objective response rate was 15.4% in Arm A and 7.7% in Arm B.

CONCLUSION
Combining capecitabine with aflibercept is feasible and associated with a manageable safety profile and some anti-tumor activity in patients with chemorefractory gastrointestinal and breast cancer.

Camera|Silvia|S|
Deleporte|Amélie|A|
Bregni|Giacomo|G|
Trevisi|Elena|E|
Pretta|Andrea|A|
Telli|Tugba Akin|TA|
Polastro|Laura|L|
Gombos|Andrea|A|
Kayumba|Aline|A|
Ameye|Lieveke|L|
Piccart-Gebhart|Martine|M|
Awada|Ahmad|A|
Sclafani|Francesco|F|
Hendlisz|Alain|A|

D000971:Antineoplastic Combined Chemotherapy Protocols

D040262:Receptors, Vascular Endothelial Growth Factor

D066066:Response Evaluation Criteria in Solid Tumors

Fluoropyrimidine
Colorectal cancer
gastric cancer
Anti-angiogenic therapy
Metronomic chemotherapy


Application of QMRA to prioritise water supplies for Cryptosporidium risk in New South Wales, Australia.

Abstract: A Quantitative Microbial Risk Assessment (QMRA) framework was applied to assess 312 drinking water supply systems across regional New South Wales (NSW). The framework was needed to support the implementation of a recommendation in the Australian Drinking Water Guidelines (ADWG) for appropriate treatment barriers to be operating in systems 'at risk' for Cryptosporidium. The objective was to prioritise systems so that those with the highest risk could be identified and addressed first. The framework was developed in a pilot study of 30 systems, selected to represent the range of water supplies across regional NSW. From these, source water categories were defined to represent local conditions with reference to the literature and Cryptosporidium risk factors. Values for Cryptosporidium oocyst concentration were assigned to the categories to allow quantification of the health risk from those water sources. The framework was then used to assess the risks in all 312 regional drinking water supply systems. Combining the disciplined approach of QMRA with simple catchment and treatment information and categorical risk outputs provided a useful and transparent method for prioritising systems for further investigation and potential risk management intervention. The risk rankings for drinking water supplies from this QMRA process have been used to set priorities for a large State Government funding program.

Petterson|S|S| Bradford-Hartke|Z|Z| Leask|S|S| Jarvis|L|L| Wall|K|K| Byleveld|P|P|

QMRA
Cryptosporidium
Risk assessment
Drinking water


The effect of CYP2D6 and CYP2C9 gene polymorphisms on the efficacy and safety of the combination of tramadol and ketorolac used for postoperative pain management in patients after video laparoscopic cholecystectomy.

Abstract:
OBJECTIVES
One of the key components of ERAS is adequate pain control in the postoperative period. There are no rational schemes for postoperative pain relief. At the same time, adequate postoperative pain relief promotes early activation and early rehabilitation of patients and shortens the duration of the postoperative stay, and does not cause postoperative complications associated with analgesia (weakness, intestinal paresis, nausea and vomiting). The aims of the present study are to assess the possible association of CYP2D6 and CYP2C9 polymorphisms with the efficacy and safety of tramadol and ketorolac in postoperative pain.

METHODS
A total of 107 patients were genotyped for CYP2D6 and CYP2C9 polymorphisms. All patients underwent laparoscopic cholecystectomy. Postoperative pain relief was carried out with ketorolac and tramadol. Postoperative pain syndrome was assessed using a visual analogue scale and McGill pain questionnaire. The profile of side effects was assessed by the dynamics of red blood counts as a possible trigger for the development of gastrointestinal bleeding according to the method of global assessment of triggers.

RESULTS
Pain was statistically significantly lower in CYP2C9*2 carriers, according to visual analogue scale (VAS): after 12 h - by 1.5 (p=0.002); after 24 h - by 1.1 (p=0.012); after 36 h - by 1.05 (p=0.004); after 48 h - by 0.7 (p=0.026). In CYP2C9*3 carriers the results were not statistically significant. In carriers of CYP2D6*4 pain syndromes were higher at all-time intervals, but statistically reliable results were obtained only after 2 h - by 1.01 (p=0.054) and after 24 h - by 0.8 (p=0.035). The profile of adverse reactions for NSAIDs was evaluated by the dynamics of hemoglobin and erythrocyte indices. A more pronounced decrease in the relative difference in hemoglobin levels was noted in CYP2C9*2 and CYP2C9*3 polymorphism carriers - by 1.7 (p=0.00268) and-by 2.2 (p=0.000143), respectively.

CONCLUSIONS
CYP2D6 and CYP2C9 can predict analgesic effectiveness of tramadol and ketorolac. CYP2C9 can predict the risk of gastrointestinal bleeding, including those hidden to ketorolac.

non-steroidal anti-inflammatory drugs (NSAIDs)


Idiopathic granulomatous mastitis in a male breast following intravesical Bacille Calmette-Guerin treatment.

Abstract: Idiopathic granulomatous mastitis (IGM) is a benign chronic inflammatory disorder of the breast tissue, with unknown etiology. IGM is extremely rare among male gender. In this case report, we present a male patient with superficial high grade bladder cancer, who was complaining of a palpable mass in his right breast for two weeks following intravesical Bacillus Calmette-Guerin (BCG) treatment. There was an assymetrical, mass-like density without distinct contours in retroareolar area of the right breast. US guided core-needle biopsy was performed. Histopathology confirmed the diagnosis of IGM. To our knowledge, this is the first case of IGM following intravesical BCG administration.

D000283:Administration, Intravesical
D000970:Antineoplastic Agents
D001500:BCG Vaccine
D001707:Biopsy, Needle
D018567:Breast Neoplasms, Male
D003937:Diagnosis, Differential
D058890:Granulomatous Mastitis
D006801:Humans
D008297:Male
D008327:Mammography
D008875:Middle Aged
D014463:Ultrasonography
D001749:Urinary Bladder Neoplasms

Idiopathic granulomatous mastitis
Biopsy
Imaging
Male breast cancer


Sustained participation in community-based physical activity by adolescents with cerebral palsy: a qualitative study.

Abstract: Purpose: Short-term physical activity programs may encourage adolescents with cerebral palsy to participate in physical activity but how to sustain their involvement is not well known. This qualitative study aimed to identify facilitators that successfully sustain physical activity participation by adolescents with cerebral palsy.Materials and methods: Adolescents (12-18 years) with cerebral palsy [Gross Motor Function Classification System (GMFCS) levels I-V, without moderate-severe intellectual disability] who participated in regular physical activity were eligible, as well as one parent and an individual who facilitated their physical activity. Data were gathered using semi-structured interviews; verbatim transcripts were analysed using inductive thematic analysis within individuals (n = 15), triads (n = 5), and across participant groups (adolescents, parents and facilitators).Results: Five triads participated (male adolescents, 13-16 years, GMFCS levels I-III). Seven themes emerged: getting started, wanting to succeed, a sense of belonging, the coach is important, endorsement to continue, endorsement to support and being passionate. The themes were synthesized into the Framework for Sustained Participation, which describes the interaction among themes.Conclusions: The Framework for Sustained Participation highlights strategies that may be useful for adolescents, parents, sports facilitators, clinicians and researchers to help ambulatory male adolescents with cerebral palsy continue to participate in physical activity.Implications for rehabilitationSustaining participation in physical activity has the potential to enhance long-term health benefits of young people with cerebral palsy.Key facilitators of sustained physical activity in adolescents with cerebral palsy included tailoring the activity, getting the right coach and the adolescents' desire for health and fitness.The Framework of Sustained Participation may assist clinicians and facilitators who work with young people with cerebral palsy to structure their support in ways that will successfully sustain the adolescents' participation in physical activity.

sustained participation
physical activity
adolescents
Cerebral palsy
qualitative research


Raloxifene Administration in Women Treated with Long Term Gonadotropin-releasing Hormone Agonist for Severe Endometriosis: Effects on Bone Mineral Density.

Abstract:
OBJECTIVES
To evaluate the efficacy of raloxifene in preventing bone loss associated with long term gonadotropin-releasing hormone agonist (GnRH-a) administration.

METHODS
Twenty-two premenopausal women with severe endometriosis were treated with leuprolide acetate depot at a dosage of 3.75 mg/4 weeks, for 48 weeks. Bone mineral density (BMD) was evaluated at admission, and after 12 treatment cycles.

RESULTS
At cycle 12 of GnRH-a plus raloxifene treatment, lumbar spine, trochanter femoral neck, and Ward's BMD differed from before the treatment. A year after treatment, the lumbar spine and trochanter decreased slightly, but were not significantly different.

CONCLUSIONS
Our study shows that the administration of GnRH-a plus raloxifene in pre-menopausal women with severe endometriosis, is an effective long-term treatment to prevent bone loss.

Cho|Young Hwa|YH|
Um|Mi Jung|MJ|
Kim|Suk Jin|SJ|
Kim|Soo Ah|SA|
Jung|Hyuk|H|

Gonadotropin-releasing hormone agonist
Endometriosis
Bone mineral density
Raloxifene hydrochloride


RNA is taking its Toll: Impact of RNA-specific Toll-like receptors on health and disease.

Abstract: RNA-sensing Toll-like receptors (TLRs) are often described as antiviral receptors of the innate immune system. However, the past decade has shown that the function and relevance of these receptors are far more complex. They were found to be essential for the detection of various bacterial, archaeal, and eukaryotic microorganisms and facilitate the discrimination between dead and living microbes. The cytokine and interferon response profile that is triggered has the potential to improve the efficacy of next-generation vaccines and may prevent the development of asthma and allergy. Nevertheless, the ability to recognize foreign RNA comes with a cost as also damaged host cells can release nucleic acids that might induce an inappropriate immune response. Thus, it is not surprising that RNA-sensing TLRs play a key role in various autoimmune diseases. However, promising new inhibitors and antagonists are on the horizon to improve their treatment.


Post-stroke Constraint-induced Movement Therapy Increases Functional Recovery, Angiogenesis, and Neurogenesis with Enhanced Expression of HIF-1α and VEGF.

Abstract:
BACKGROUND
Constraint-Induced Movement Therapy (CIMT) is one efficient approach to improve functional recovery after ischemic stroke. The underlying molecular mechanism remains unclear. In the current study, we investigated the effects of CIMT on angiogenesis and neurogenesis. To start linking our findings to molecular mediators, we further examined the expression of Hypoxia-Inducible Factor-1α (HIF-1α), Factor Inhibiting HIF-1 (FIH-1) and Vascular Endothelial Growth Factor (VEGF).

METHODS
Rats were randomly assigned into three groups: a Middle Cerebral Artery Occlusion group (MCAO), a therapeutic group (CIMT+MCAO), and a sham middle cerebral artery occlusion group (Sham). Seven days after surgery, a plaster cast was placed around the unimpaired upper limb of the rats in the CIMT+MCAO group for 14 days. CIMT was performed on a horizontal ladder. Neurobehavioral consequences were evaluated using the Open-Field Test (OFT) and the Foot-Fault Test (FFT). The number of new neurons, the length of vessels as well as the expression of HIF-1α, FIH-1, and VEGF were examined before and after 14 days of CIMT.

RESULTS
The CIMT+MCAO group showed a significant increase in the total length of microvessels and increased number of Bromodeoxyuridine+ (BrdU+)/NeuN+ double-labeled cells. These changes were correlated with an increase in HIF-1α and VEGF expressions and a decrease in FIH-1expression. FFT showed that the CIMT+MCAO group exhibited marked improvement in neurobehavioral outcome when compared to the MCAO group. Adverse effects on total activities or anxiety were not observed using open field analysis.

CONCLUSION
CIMT-induced neuroprotection and functional recovery following cerebral ischemia were possibly mediated by an increase in endogenous HIF-1α and VEGF expression with subsequent neurogenesis and angiogenesis.

Li|Ce|C| Zhang|Bei|B| Zhu|Yulian|Y| Li|Yingying|Y| Liu|Peile|P| Gao|Beiyao|B| Tian|Shan|S| Du|Liang|L| Bai|Yulong|Y|

D051795:Hypoxia-Inducible Factor 1, alpha Subunit

D020244:Infarction, Middle Cerebral Artery

D015915:Motion Therapy, Continuous Passive

D042461:Vascular Endothelial Growth Factor A

constraint-induced movement therapy (CIMT)

vascular endothelial growth factor (VEGF)


Culture-Independent Analyses Reveal Novel Anaerolineaceae as Abundant Primary Fermenters in Anaerobic Digesters Treating Waste Activated Sludge.

Abstract: Anaerobic digestion for biogas production is reliant on the tightly coupled synergistic activities of complex microbial consortia. Members of the uncultured A6 phylotype, within the phylum Chloroflexi, are among the most abundant genus-level-taxa of mesophilic anaerobic digester systems treating primary and surplus sludge from wastewater treatment plants, yet are known only by their 16S rRNA gene sequence. This study applied metagenomics to obtain a complete circular genome (2.57 Mbp) from a representative of the A6 taxon. Preliminary annotation of the genome indicates these organisms to be anaerobic chemoorganoheterotrophs with a fermentative metabolism. Given their observed abundance, they are likely important primary fermenters in digester systems. Application of fluorescence in situ hybridisation probes designed in this study revealed their morphology to be short filaments present within the flocs. The A6 were sometimes co-located with the filamentous Archaea Methanosaeta spp. suggesting potential undetermined synergistic relationships. Based on its genome sequence and morphology we propose the species name Brevefilum fermentans gen. nov. sp. nov.

McIlroy|Simon J|SJ|
Kirkegaard|Rasmus H|RH|
Dueholm|Morten S|MS|
Fernando|Eustace|E|
Karst|Søren M|SM|
Albertsen|Mads|M|
Nielsen|Per H|PH|

anaerobic digestion
A6
Chloroflexi
metagenomics
Brevefilum fermentans
FISH


Managing the untoward anesthetic event in an oral and maxillofacial surgery practice.

Abstract: The safe and efficient use of outpatient surgical anesthesia modalities is a significant part of the training and expertise of the oral and maxillofacial surgeon. Although adverse outcomes are rare, they can have considerable traumatic psychological and professional consequences for the surgeon involved. The goal of this article is to develop guidelines to educate the doctor, the second victim, on how to manage a bad outcome and how to navigate through a difficult and arduous process.

Kaltman|Steven I|SI|
Ragan|Michael|M|
Borges|Osbel|O|

D000766:Anesthesia, Dental
D000776:Anesthesiology
D000777:Anesthetics
D001291:Attitude of Health Personnel
D002568:Certification
D002985:Clinical Protocols
D003815:Dentists
D004282:Documentation
D004636:Emergency Service, Hospital
D004638:Emergency Treatment
D005553:Forensic Dentistry
D006801:Humans
D007258:Informed Consent
D007351:Insurance, Liability
D033241:Lawyers
D016365:Liability, Legal
D008487:Medical History Taking
D008508:Medication Errors
D019647:Oral Surgical Procedures
D013315:Stress, Psychological
D013515:Surgery, Oral
D014481:United States

Second victim
Anesthesia certification
Apology
Emergency medicine protocol
Professional liability
Untoward anesthesia event


Printed PEDOT:PSS Trilayer: Mechanism Evaluation and Application in Energy Storage.

Abstract: Combining ink-jet printing and one of the most stable electroactive materials, PEDOT:PSS (poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)), is envisaged to pave the way for the mass production of soft electroactive materials. Despite its being a well-known electroactive material, widespread application of PEDOT:PSS also requires good understanding of its response. However, agreement on the interpretation of the material's activities, notably regarding actuation, is not unanimous. Our goal in this work is to study the behavior of trilayers with PEDOT:PSS electrodes printed on either side of a semi-interpenetrated polymer network membrane in propylene carbonate solutions of three different electrolytes, and to compare their electroactive, actuation, and energy storage behavior. The balance of apparent faradaic and non-faradaic processes in each case is discussed. The results show that the primarily cation-dominated response of the trilayers in the three electrolytes is actually remarkably different, with some rather uncommon outcomes. The different balance of the apparent charging mechanisms makes it possible to clearly select one electrolyte for potential actuation and another for energy storage application scenarios.

energy storage
ink-jet printing
three different electrolytes
PEDOT:PSS-IPN trilayer
linear actuation


Circulating Lp-PLA2 is associated with high valvuloarterial impedance and low arterial compliance in patients with aortic valve bioprostheses.

Abstract:
BACKGROUND
We previously reported that plasma Lp-PLA2 was associated with aortic valve disease progression and degeneration of bioprostheses. Low systemic arterial compliance and high valvuloarterial impedance (Z(va)) are predictors of poor survival in patients with aortic valve disease. However, the prevalence of high Z(va) after AVR is largely unknown and whether Lp-PLA2 could predict Z(va) has not been documented. We investigated the relationships between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity and valvuloarterial impedance (Z(va)), an index of global LV hemodynamic load, in patients that underwent aortic valve replacement (AVR).

METHODS
A total of 195 patients with aortic bioprostheses underwent echocardiographic assessment of the prosthetic aortic valve function 8±3.4 years after AVR. Lp-PLA2 mass and activity were measured.

RESULTS
In this group of patients, the mean Z(va) was elevated (5.73±1.21 mm Hg·ml(-1)·m(2)). In univariate analyses, Lp-PLA2 mass (p=0.003) and Lp-PLA2 activity (p=0.046) were associated with Z(va). After adjustment for covariates including age, gender, clinical risk factors, anti-hypertensive medications, body mass index and prosthesis size, Lp-PLA2 mass was associated with high Z(va) (≥4.5 mm Hg·ml(-1)·m(2)) (OR: 1.29, 95%CI: 1.10-1.53; p=0.005) and was inversely related with the systemic arterial compliance (β=-0.01, SEM=0.003; p=0.003).

CONCLUSIONS
An increased Z(va), an index of excessive hemodynamic load, was highly prevalent 8-year post-AVR and was independently related to circulating Lp-PLA2.

Mahmut|Ablajan|A|
Mahjoub|Haïfa|H|
Boulanger|Marie-Chloé|MC|
Dahou|Abdellaziz|A|
Bouchareb|Rihab|R|
Capoulade|Romain|R|
Arsenault|Benoît J|BJ|
Larose|Eric|E|
Bossé|Yohan|Y|
Pibarot|Philippe|P|
Mathieu|Patrick|P|

Lp-PLA2
Valvuloarterial impedance
Arterial compliance
Lipoprotein-associated phospholipase A2
Bioprosthesis
Calcific aortic valve disease


On the role of material properties in ascending thoracic aortic aneurysms.

Abstract: One of the obstacles standing before the biomechanical analysis of an ascending thoracic aortic aneurysm (ATAA) is the difficulty in obtaining patient-specific material properties. This study aimed to evaluate differences on ATAA-related stress predictions resulting from the elastostatic analysis based on the optimization of arbitrary material properties versus the application of patient-specific material properties determined from ex-vivo biaxial testing. Specifically, the elastostatic analysis relies the on the fact that, if the aortic wall stress does not depend on material properties, the aorta has to be statistically determinate. Finite element analysis (FEA) was applied to a group of nine patients who underwent both angio-CT imaging to reconstruct ATAA anatomies and surgical repair of diseased aorta to collect tissue samples for experimental material testing. Tissue samples cut from excised ATAA rings were tested under equibiaxial loading conditions to obtain experimentally-derived material parameters by fitting stress-strain profiles. FEAs were carried out using both optimized and experimentally-derived material parameters to predict and compare the stress distribution using the mean absolute percentage error (MAPE). Although physiological strains were below yield point (range of 0.08-0.25), elastostatic analysis led to errors on the stress predictions that depended on the type of constitutive model (highest MAPE of 0.7545 for Yeoh model and 0.7683 for Fung model) and ATAA geometry (lowest MAPE of 0.0349 for patient P.7). Elastostatic analysis needs better understanding of its application for determining aneurysm mechanics, and patient-specific material parameters are essential for reliable accurate stress predictions in ATAAs.

Cosentino|Federica|F|
Agnese|Valentina|V|
Raffa|Giuseppe M|GM|
Gentile|Giovanni|G|
Bellavia|Diego|D|
Zingales|Massimiliano|M|
Pilato|Michele|M|
Pasta|Salvatore|S|

Material parameters
Aortic aneurysm failure
Ascending aortic aneurysm
Finite-element analysis
Inverse approach


Experimental Study of Drilling Temperature, Geometrical Errors and Thermal Expansion of Drill on Hole Accuracy When Drilling CFRP/Ti Alloy Stacks.

Abstract: The drilling of holes in CFRP/Ti (Carbon Fiber-Reinforced Plastic/Titanium alloy) alloy stacks is one of the frequently used mechanical operations during the manufacturing of fastening assemblies in temporary civil aircraft. A combination of inhomogeneous behavior and poor machinability of CFRP/Ti alloy stacks in one short drilling brought challenges to the manufacturing community. The impact of the drilling temperature and time delay factor under various cutting conditions on hole accuracy when machining CFRP/Ti alloy stacks is poorly studied. In this paper, the drilling temperature, the phenomenon of thermal expansion of the drill tool, and hole accuracy are investigated. An experimental study was carried out using thermocouples, the coordinate measuring machine method, and finite element analysis. The results showed that the time delay factor varied from 5 (s) to 120 (s), influences the thermal-dependent properties of CFRP, and leads to an increase in hole roundness. Additionally, the thermal expansion of the drill significantly contributes to the deviation of the hole diameter in Ti alloy.

drilling temperature
CFRP/Ti alloy stack
roundness
hole diameter
drill thermal expansion


The Cryptic Bombus lucorum Complex (Hymenoptera: Apidae) in Austria: Phylogeny, Distribution, Habitat Usage and a Climatic Characterization Based on COI Sequence Data.

Abstract: Silas Bossert, Barbara-Amina Gereben-Krenn, Johann Neumayer, Bernhard Schneller, and Harald W. Krenn (2016) The Bombus lucorum complex represents a group of three distinct but cryptic bumblebee species in Europe. With the advent of DNA-based identification methods, their species status was confirmed and the use of COI barcoding proved to be an especially useful tool for species identification within the group. Meanwhile, the identification based on morphology remains difficult and recent studies challenged the general distinguishability by revealing an important character to be unreliable. This has consequences for our understanding of the distribution and ecology of the species in Europe and aggravates our patchy knowledge of the situation in Austria and the whole area of the European Alps. In this study, we investigate the exact species composition and distribution of the Bombus lucorum complex in Austria based on the reliable species identification with COI sequence data. The habitat usage is studied and the first extensive investigation of altitudinal and climatic differentiation is provided. The results support three distinct genotypic groups in the Bombus lucorum complex. B. lucorum and B. cryptarum co-occur in several areas across the country, with B. lucorum being the most common and most widespread species. The study provides no evidence for the presence of B. magnus in Austria. The less common species, B. cryptarum, mainly occurs in the high mountains and is the predominant species of the complex above altitudes of 2100 m a.s.l. Further, B. cryptarum is almost absent from woodlands and is relatively more abundant in habitats with colder climate than B. lucorum in Austria. Additionally, the results indicate a very low intraspecific genetic variation within B. lucorum and B. cryptarum. This study confirms previous findings of three distinct species within the species complex. Based on reliable COI identification, the first coherent overview of the species complex in Austria can be achieved. The climatic data allows us to explain the differences in the distribution patterns. Moreover, the low intraspecific variation may indicate past bottleneck conditions for B. lucorum and B. cryptarum.

Bossert|Silas|S|
Gereben-Krenn|Barbara-Amina|BA|
Neumayer|Johann|J|
Schneller|Bernhard|B|
Krenn|Harald W|HW|

Bombus lucorum complex
Distribution patterns
Austrian Alps
Bombus cryptarum
Cryptic species
Ecological differentiation


CuO nanosheets-enhanced flow-injection chemiluminescence system for determination of vancomycin in water, pharmaceutical and human serum.

Abstract: A novel, rapid and sensitive CuO nanosheets (NSs) amplified flow-injection chemiluminescence (CL) system, luminol-H2O2-CuO nanosheets, was developed for determination of the vancomycin hydrochloride for the first time. It was found that vancomycin could efficiently inhibit the CL intensity of luminol-H2O2-CuO nanosheets system in alkaline medium. Under the optimum conditions, the inhibited CL intensity was linearly proportional to the concentration of vancomycin over the ranges of 0.5-18.0 and 18.0-40.0 mg L(-1), with a detection limit (3σ) of 0.1 mg L(-1). The precision was calculated by analyzing samples containing 5.0 mg L(-1) vancomycin (n=11) and the relative standard deviation (RSD) was 2.8%. Also, a high injection throughput of 120 sample h(-1) was obtained. The CuO nanosheets were synthesized by a sonochemical method. Also, X-ray diffraction (XRD) and scanning electron microscopy (SEM) analyses were employed to characterize the CuO nanosheets. The method was successfully employed to determine vancomycin hydrochloride in environmental water samples, pharmaceutical formulation and spiked human serum.

Khataee|A R|AR|
Hasanzadeh|A|A|
Iranifam|M|M|
Fathinia|M|M|
Hanifehpour|Y|Y|
Joo|S W|SW|

Vancomycin
CuO nanosheets
Sonochemical
Flow-chemiluminescence
Luminol


Enteral Baicalin, a Flavone Glycoside, Reduces Indicators of Cardiac Surgery-Associated Acute Kidney Injury in Rats.

Abstract:
BACKGROUND/AIMS
Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most common postoperative complications in intensive care medicine. Baicalin has been shown to have anti-inflammatory and antioxidant roles in various disorders. We aimed to test the protective effects of baicalin on CSA-AKI using a rat model.

METHODS
Sprague-Dawley rats underwent 75 min of cardiopulmonary bypass (CPB) with 45 min of cardioplegic arrest (CA) to establish the AKI model. Baicalin was administered at different doses intragastrically 1 h before CPB. The control and treated rats were subjected to the evaluation of different kidney injury index and inflammation biomarkers.

RESULTS
Baicalin significantly attenuated CPB/CA-induced AKI in rats, as evidenced by the lower levels of serum creatinine, serum NGAL, and Kim1. Baicalin remarkably inhibited oxidative stress, reflected in the decreased malondialdehyde and myeloperoxidase activity, and enhanced superoxide dismutase activity and glutathione in renal tissue. Baicalin suppressed the expression of IL-18 and iNOS, and activated the Nrf2/HO-1 pathway.

CONCLUSION
Our data indicated that baicalin mediated CPB/CA-induced AKI by decreasing the oxidative stress and inflammation in the renal tissues, and that baicalin possesses the potential to be developed as a therapeutic tool in clinical use for CSA-AKI.

Shi|Jing|J| Wu|Guofeng|G| Zou|Xiaohua|X| Jiang|Ke|K|

Baicalin
Acute kidney injury
Cardiopulmonary bypass
Nrf2/HO-1 pathway
Cardiac surgery


Dynamic changes of histone acetylation and methylation in bovine oocytes, zygotes, and preimplantation embryos.

Abstract: Histone modifications play important roles in regulating chromatin dynamic changes. In this study, acetylated histone H3 lysine 9 and 18 (H3K9ac and H3K18ac), acetylated histone H4 lysine 5 and 8 (H4K5ac and H4K8ac), tri-methylation histone H3 lysine 4 (H3K4me3), di-methylation histone H3 lysine 9 (H3K9me2) are investigated in bovine oocytes, zygote, and preimplantation. During meiosis, H3K9ac and H3K18ac are erased after germinal vesicle breakdown, H4K8ac is erased after metaphase I (MI). Although H4K5ac is erased at MI, it is redetectable after this stage. However, histone methylations have no significant change during meiosis. During fertilization, intensive H4K5ac and H4K8ac are resumed on male and female chromatins at postfertilization 4 and 8 hr, respectively. H3K9ac and H3K18ac are resumed on both male and female chromatins at postfertilization 8 and 12 hr, respectively. H3K4me3 and H3K9me2 gradually increased on male chromatin after postfertilization 8 hr, while these two signals on female chromatin are detectable from postfertilization 2-18 hr. During embryo cleavage, H3K9ac, H3K18ac, and H3K4me3 are reduced at 8-cell stage, and then start to increase. H4K5ac, H4K8ac, and H3K9me2 increase after the 4-cell stage. At interphase, H4K5ac and H4K8ac are more intensive in nuclear periphery from 2- to 8-cell stages. During mitosis, the signal of H4K8ac is intensive at chromosome periphery. In summary, during both oocyte meiosis and fertilization, the dynamic changes of both histone acetylations and methylations happen in a process of lysine residue-specific and species-specific. During preimplantation development, the dynamic patterns of both H3K9ac and H3K18ac are similar to that of H3K4me3, while the dynamic pattern of H4K5ac is similar to that of H4K8ac. These results will be helpful for understanding the effect of histone posttranslational modifications on bovine reproduction and development.

Wu|Xia|X|0000-0002-0504-469X Hu|Shuxiang|S| Wang|Lingling|L| Li|Yan|Y| Yu|Haiquan|H|

histone acetylation
histone methylation
fertilization
oocyte meiosis
preimplantation development


Identification of research priorities in infertility and assisted reproduction: an international, multicentre study.

Abstract:
RESEARCH QUESTION
What are the main research interests among patients of assisted reproductive technologies (ART)?

DESIGN
Cross-sectional study consisting of an anonymous online survey sent to 2112 patients from eight centres in four countries in 2018. Patients were asked to identify research questions relevant to them in the field of infertility and ART. Answers were categorized into topics and ranked by frequency. A long list of the top 30 research topics was extracted from the aggregate results, from which a short list of the top 10 research topics was created. Ten research questions were finally formulated.

RESULTS
A total of 945 responses were analysed. Main interests were side-effects, success rates, infertility prevention and emotional support. The 10 research questions were: 1. What are the side-effects of drugs used in ART treatments? (51.6%). 2. What are the most effective methods to cope with infertility from the psychological point of view? (35.7%). 3. What effects could diet have on fertility? (25.9%). 4. What are ART success rates per clinical profile? (24.8%). 5. Are there some habits and lifestyle factors that could prevent infertility? (20.0%). 6. What are the long-term risks associated with ART in mother and child? (18.5%). 7. Are alternative therapies such as acupuncture, yoga and meditation effective to treat/prevent infertility? (18.5%). 8. What is the impact of exercise on fertility? (15.4%). 9. How does oocyte quantity and quality affect fertility? (9.5%). 10. What are the genetic patterns or hereditary conditions causing/related to infertility? (9.5%).

CONCLUSIONS
Researchers and clinicians should keep in mind that, in addition to success rates and safety, patients greatly value research into causes, prevention and emotional aspects of infertility.

García|Désirée|D|
Brazal|Sarai|S|
Lindenberg|Frederikke|F|
Toft|Eva|E|
La Marca|Antonio|A|
Borrás|Rosa|R|
Lorenzon|Aline Rodrigues|AR|
Chehin|Mauricio Barbour|MB|
Silva|Leticia|L|
da Motta|Eduardo Leme Alves|ELA|
Ripero|Maider|M|
Madero|José Ignacio|JI|
Marinho|Ricardo Mello|RM|
de Oliveira|Cristiane Araújo|CA|
Caetano|João Pedro Junqueira|JPJ|
Bolívar|Anna|A|
Rodríguez|Amelia|A|
Vassena|Rita|R|

Infertility prevention
ART treatments
Fertility protection
Healthy habits
Patient involvement
Psychological effects


Polyhexamethylene guanidine phosphate aerosol particles induce pulmonary inflammatory and fibrotic responses.

Abstract: Polyhexamethylene guanidine (PHMG) phosphate was used as a disinfectant for the prevention of microorganism growth in humidifiers, without recognizing that a change of exposure route might cause significant health effects. Epidemiological studies reported that the use of humidifier disinfectant containing PHMG-phosphate can provoke pulmonary fibrosis. However, the pulmonary toxicity of PHMG-phosphate aerosol particles is unknown yet. This study aimed to elucidate the toxicological relationship between PHMG-phosphate aerosol particles and pulmonary fibrosis. An in vivo nose-only exposure system and an in vitro air-liquid interface (ALI) co-culture model were applied to confirm whether PHMG-phosphate induces inflammatory and fibrotic responses in the respiratory tract. Seven-week-old male Sprague-Dawley rats were exposed to PHMG-phosphate aerosol particles for 3 weeks and recovered for 3 weeks in a nose-only exposure chamber. In addition, three human lung cells (Calu-3, differentiated THP-1 and HMC-1 cells) were cultured at ALI condition for 12 days and were treated with PHMG-phosphate at set concentrations and times. The reactive oxygen species (ROS) generation, airway barrier injuries and inflammatory and fibrotic responses were evaluated in vivo and in vitro. The rats exposed to PHMG-phosphate aerosol particles in nanometer size showed pulmonary inflammation and fibrosis including inflammatory cytokines and fibronectin mRNA increase, as well as histopathological changes. In addition, PHMG-phosphate triggered the ROS generation, airway barrier injuries and inflammatory responses in a bronchial ALI co-culture model. Those results demonstrated that PHMG-phosphate aerosol particles cause pulmonary inflammatory and fibrotic responses. All features of fibrogenesis by PHMG-phosphate aerosol particles closely resembled the pathology of fibrosis that was reported in epidemiological studies. Finally, we expected that PHMG-phosphate infiltrated into the lungs in the form of aerosol particles would induce an airway barrier injury via ROS, release fibrotic inflammatory cytokines, and trigger a wound-healing response, leading to pulmonary fibrosis. A simultaneous state of tissue destruction and inflammation caused by PHMG-phosphate had whipped up a "perfect storm" in the respiratory tract.

Kim|Ha Ryong|HR|
Lee|Kyuhong|K|
Park|Chang We|CW|
Song|Jeong Ah|JA|
Shin|Da Young|DY|
Park|Yong Joo|YJ|
Chung|Kyu Hyuck|KH|

Polyhexamethylene guanidine phosphate
Aerosol particles
Humidifier disinfectant
Pulmonary fibrosis


Developing a comprehensive framework of community integration for people with acquired brain injury: a conceptual analysis.

Abstract:
PURPOSE
Despite increasing emphasis on the importance of community integration as an outcome for acquired brain injury (ABI), there is still no consensus on the definition of community integration. The aim of this study was to complete a concept analysis of community integration in people with ABI.

MATERIALS AND METHODS
The method of concept clarification was used to guide concept analysis of community integration based on a literature review. Articles were included if they explored community integration in people with ABI. Data extraction was performed by the initial coding of (1) the definition of community integration used in the articles, (2) attributes of community integration recognized in the articles' findings, and (3) the process of community integration. This information was synthesized to develop a model of community integration.

RESULTS
Thirty-three articles were identified that met the inclusion criteria. The construct of community integration was found to be a non-linear process reflecting recovery over time, sequential goals, and transitions. Community integration was found to encompass six components including: independence, sense of belonging, adjustment, having a place to live, involved in a meaningful occupational activity, and being socially connected into the community. Antecedents to community integration included individual, injury-related, environmental, and societal factors.

CONCLUSION
The findings of this concept analysis suggest that the concept of community integration is more diverse than previously recognized. New measures and rehabilitation plans capturing all attributes of community integration are needed in clinical practice. Implications for rehabilitation Understanding of perceptions and lived experiences of people with acquired brain injury through this analysis provides basis to ensure rehabilitation meets patients' needs. This model highlights the need for clinicians to be aware and assess the role of antecedents as well as the attributes of community integration itself to ensure all aspects are addressed in in a manner that will enhance the recovery and improve the level of integration into the community. The finding that community integration is a non-linear process also highlights the need for rehabilitation professionals to review and revise plans over time in response to a person's changing circumstances and recovery journey. This analysis provides the groundwork for an operational model of community integration for the development of a measure of community integration that assesses all six attributes revealed in this review not recognized in previous frameworks.

Shaikh|Nusratnaaz M|NM|
Kersten|Paula|P|
Siegert|Richard J|RJ|
Theadom|Alice|A|

framework
Community integration
acquired brain injury
concept analysis
concept clarification


A randomised trial comparing a brief online delivery of mindfulness-plus-values versus values only for symptoms of depression: Does baseline severity matter?

Abstract:
BACKGROUND
Acceptance/mindfulness-based interventions often focus on (a) developing dispositional mindfulness and (b) pursuing personally meaningful and valued activities. Acceptance/mindfulness-based interventions can reduce depression, but little is known about the combined effects of components or the influence of baseline variables on outcomes. This study tested whether practicing a brief (10-min) mindfulness meditation over a 2-week period followed by a single values session (mindfulness+values) was more effective than values alone (values only) in reducing symptoms of depression. The study was delivered online and modules were fully self-help (i.e., no therapist contact).

METHODS
206 participants (Mage=23.4 years, SD=6.53) with elevated depression scores (DASS-depression ≥ 10) were randomised to: mindfulness+values condition or a 2-week wait period followed by the values session (i.e., values only condition). Symptoms of depression were assessed at baseline, after the 2-week mindfulness practice/wait period, and 1-week following the values session.

RESULTS
Reductions in depression and recovery rates were significantly greater following mindfulness+values than values only. Baseline severity affected outcomes: mindfulness+values was significantly more beneficial than values only for individuals with high baseline levels of depression. Outcomes did not differ for those with low levels of depression. Rates of deterioration were higher than expected for values only participants.

LIMITATIONS
Conclusions are preliminary and tentative due to no follow-up period and a small sample. Drop-out was high (50%) and findings cannot be assumed to generalise to treatment seeking or more diverse samples.

CONCLUSIONS
Tentatively, results suggest mindfulness+values can significantly reduce depression, especially for individuals with higher baseline depression.

Kingston|J|J| Becker|L|L| Woeginger|J|J| Ellett|L|L|

Values Depression Acceptance Mindfulness eHealth


Application of Cydia pomonella expressed sequence tags: Identification and expression of three general odorant binding proteins in codling moth.

Abstract: The codling moth, Cydia pomonella, is one of the most important pests of pome fruits in the world, yet the molecular genetics and the physiology of this insect remain poorly understood. A combined assembly of 8 341 expressed sequence tags was generated from Roche 454 GS-FLX sequencing of eight tissue-specific cDNA libraries. Putative chemosensory proteins (12) and odorant binding proteins (OBPs) (18) were annotated, which included three putative general OBP (GOBP), one more than typically reported for other Lepidoptera. To further characterize CpomGOBPs, we cloned cDNA copies of their transcripts and determined their expression patterns in various tissues. Cloning and sequencing of the 698 nt transcript for CpomGOBP1 resulted in the prediction of a 163 amino acid coding region, and subsequent RT-PCR indicated that the transcripts were mainly expressed in antennae and mouthparts. The 1 289 nt (160 amino acid) CpomGOBP2 and the novel 702 nt (169 amino acid) CpomGOBP3 transcripts are mainly expressed in antennae, mouthparts, and female abdomen tips. These results indicate that next generation sequencing is useful for the identification of novel transcripts of interest, and that codling moth expresses a transcript encoding for a new member of the GOBP subfamily.

Garczynski|Stephen F|SF|
Coates|Brad S|BS|
Unruh|Thomas R|TR|
Schaeffer|Scott|S|
Jiwan|Derick|D|
Koepke|Tyson|T|
Dhingra|Amit|A|

odorant binding proteins
codling moth
EST