Oxidative stress and bronchopulmonary dysplasia.

Abstract: Bronchopulmonary dysplasia (BPD) is the major cause of pulmonary disease in infants. The pathophysiology and management of BPD changed with the improvement of neonatal intensive care unit (NICU) management and with the increase of survival rates. Despite the improvements made, BPD is still a public health concern, resulting in frequent hospitalizations with high rates of mortality, impaired weight and height growth, and neurodevelopmental disorders. Lung injury in the neonatal period has multiple etiologic factors - genetic, hemodynamic, metabolic, nutritional, mechanical, and infectious mechanisms - act in a cumulative and synergic way. Free radical (FR) generation is largely recognized as the major cause of lung damage. Oxidative stress (OS) is the final common endpoint for a complex convergence of events, some genetically determined and some triggered by in utero stressors. Inflammatory placental disorders and chorioamnionitis also play an important role due to the coexistence of inflammatory and oxidative lesions. In addition, the contribution of airway inflammation has been extensively studied. The link between inflammation and OS injury involves the direct activation of inflammatory cells, especially granulocytes, which potentiates the inflammatory reaction. Individualized interventions to support ventilation, minimize oxygen exposure, minimize apnea, and encourage growth should decrease both the frequency and severity of BPD. Future perspectives suggest supplementation with enzymatic and/or non-enzymatic antioxidants. The use of antioxidants in preterm newborns particularly exposed to OS and at risk for BPD represents a logical strategy to ameliorate FRs injury, but further studies are needed to support this hypothesis.

Perrone|Serafina|S|
Tataranno|Maria Luisa|ML|
Buonocore|Giuseppe|G|

oxidative stress
Bronchopulmonary dysplasia
preterm newborns


Atorvastatin attenuates plaque vulnerability by downregulation of EMMPRIN expression via COX-2/PGE2 pathway.

Abstract: Extracellular matrix metalloproteinase inducer (EMMPRIN) reportedly has a key regulatory role in matrix metalloproteinase (MMP) activities and the progression of atherosclerosis. Statins, which are anti-atherosclerotic pharmacological agents, are widely applied in clinical settings. The aim of the present study was to investigate the pharmaceutical effect of atorvastatin on EMMPRIN expression in atherosclerotic plaques. An atherosclerotic mouse model was established using apoliprotein E-deficient (ApoE-/-) mice raised on a high-fat diet. Additionally, a low (5 mg/kg/day) or high dosage (10 mg/kg/day) of atorvastatin suspension was administered orally for eight weeks, beginning on week 7 or 11 respectively. The effects of atorvastatin on atherosclerotic plaque formation and EMMPRIN expression were subsequently determined. The THP-1 cell line was used to investigate the effect of atorvastatin on EMMPRIN expression in vitro. The results demonstrated that the high-fat diet led to vulnerable plaques (VPs) and increased EMMPRIN expression in VPs in ApoE-/- mice. Atorvastatin treatment decreased EMMPRIN expression in the aortas and plaques of ApoE-/- mice. In vitro, oxidized low-density lipoprotein (ox-LDL) induced the expression of cyclooxygenase-2 (COX-2) and EMMPRIN in THP-1 macrophages, and atorvastatin inhibited ox-LDL-induced expression of PGE2, EMMPRIN and COX-2 in THP-1 macrophages. Therefore, the present data indicated that atorvastatin treatment reduces the vulnerability of atherosclerotic plaques and expression of EMMPRIN, and that the inhibitory effect of atorvastatin on EMMPRIN may occur via the COX-2/PGE2 signaling pathway in macrophages.

Liang|Xing|X| Yang|Li-Xia|LX| Guo|Ruiwei|R| Shi|Yankun|Y| Hou|Xianhua|X| Yang|Zhihua|Z| Zhou|Xiaobin|X| Liu|Hong|H|

extracellular matrix metalloproteinase inducer


RNA-Cleaving Deoxyribozymes Differentiate Methylated Cytidine Isomers in RNA.

Abstract: Deoxyribozymes are emerging as modification-specific endonucleases for the analysis of epigenetic RNA modifications. Here, we report RNA-cleaving deoxyribozymes that differentially respond to the presence of natural methylated cytidines, 3-methylcytidine (m3 C), N4 -methylcytidine (m4 C), and 5-methylcytidine (m5 C), respectively. Using in vitro selection, we found several DNA catalysts, which are selectively activated by only one of the three cytidine isomers, and display 10- to 30-fold accelerated cleavage of their target m3 C-, m4 C- or m5 C-modified RNA. An additional deoxyribozyme is strongly inhibited by any of the three methylcytidines, but effectively cleaves unmodified RNA. The mX C-detecting deoxyribozymes are programmable for the interrogation of natural RNAs of interest, as demonstrated for human mitochondrial tRNAs containing known m3 C and m5 C sites. The results underline the potential of synthetic functional DNA to shape highly selective active sites.

Liaqat|Anam|A|
Sednev|Maksim V|MV|0000-0001-6746-1598
Stiller|Carina|C|
Höbartner|Claudia|C|0000-0002-4548-2299

D020029:Base Pairing
D003562:Cytidine
D021881:DNA, Catalytic
D009690:Nucleic Acid Conformation
D012313:RNA
D059367:RNA Cleavage
D013379:Substrate Specificity

deoxyribozymes
RNA modification
in vitro selection
epitranscriptomics
site-specific RNA cleavage


Current insights into the laboratory diagnosis of HIT.

Abstract: Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction and prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. After antibody binding to PF4/heparin complexes, HIT antibodies are capable of intravascular platelet activation by cross-linking Fc gamma receptor IIa (FcγRIIa) on the platelet surface leading to a platelet count decrease and/or thrombosis. In contrast to most other immune-mediated disorders, the currently available laboratory tests for anti-PF4/heparin antibodies show a high sensitivity also for clinically irrelevant antibodies. This makes the diagnosis of HIT challenging and bears the risk to substantially overdiagnose HIT. The strength of the antigen assays for HIT is in ruling out HIT when the test is negative. Functional assays have a higher specificity for clinically relevant antibodies, but they are restricted to specialized laboratories. Currently, a Bayesian approach combining the clinical likelihood estimation for HIT with laboratory tests is the most appropriate approach to diagnose HIT. In this review, we give an overview on currently available diagnostic procedures and discuss their limitations.

diagnosis HIT thrombocytopenia Heparin antibody


Co-evolution as Tool for Diversifying Flavor and Aroma Profiles of Wines.

Abstract: The products of microbial metabolism form an integral part of human industry and have been shaped by evolutionary processes, accidentally and deliberately, for thousands of years. In the production of wine, a great many flavor and aroma compounds are produced by yeast species and are the targets of research for commercial breeding programs. Here we demonstrate how co-evolution with multiple species can generate novel interactions through serial co-culture in grape juice. We find that after ~65 generations, co-evolved strains and strains evolved independently show significantly different growth aspects and exhibit significantly different metabolite profiles. We show significant impact of co-evolution of Candida glabrata and Pichia kudriavzevii on the production of metabolites that affect the flavor and aroma of experimental wines. While co-evolved strains do exhibit novel interactions that affect the reproductive success of interacting species, we found no evidence of cross-feeding behavior. Our findings yield promising avenues for developing commercial yeast strains by using co-evolution to diversify the metabolic output of target species without relying on genetic modification or breeding technologies. Such approaches open up exciting new possibilities for harnessing microbial co-evolution in areas of agriculture and food related research generally.

Morrison-Whittle|Peter|P|
Lee|Soon A|SA|
Fedrizzi|Bruno|B|
Goddard|Matthew R|MR|

co-evolution
co-culture
metabolite analysis
microbial interactions
wine yeast


Meiotic and pedigree segregation analyses in carriers of t(4;8)(p16;p23.1) differing in localization of breakpoint positions at 4p subband 4p16.3 and 4p16.1.

Abstract:
PURPOSE
The purpose of this study was to compare meiotic segregation in sperm cells from two carriers with t(4;8)(p16;p23.1) reciprocal chromosome translocations (RCTs), differing in localization of the breakpoint positions at the 4p subband-namely, 4p16.3 (carrier 1) and 4p16.1 (carrier 2)-and to compare data of the pedigree analyses performed by direct method.

METHODS
Three-color fluorescent in situ hybridization (FISH) on sperm cells and FISH mapping for the evaluation of the breakpoint positions, data from pedigrees, and direct segregation analysis of the pedigrees were performed.

RESULTS
Similar proportions of normal/balanced and unbalanced sperm cells were found in both carriers. The most common was an alternate type of segregation (about 52 % and about 48 %, respectively). Unbalanced adjacent I and adjacent II karyotypes were found in similar proportions about 15 %. The direct segregation analysis (following Stengel-Rutkowski) of the pedigree of carriers of t(4;8)(p16.1;p23.1) was performed and results were compared with the data of the pedigree segregation analysis obtained earlier through the indirect method. The probability of live-born progeny with unbalanced karyotype for carriers of t(4;8)(p16.1;p23.1) was moderately high at 18.8 %-comparable to the value obtained using the indirect method for the same carriership, which was 12 %. This was, however, markedly lower than the value of 41.2 % obtained through the pedigree segregation indirect analysis estimated for carriers of t(4;8)(p16.3;p23.1), perhaps due to the unique composition of genes present within the 4p16.1-4p 16.3 region.

CONCLUSIONS
Revealed differences in pedigree segregation analysis did not correspond to the very similar profile of meiotic segregation patterns presented by carrier 1 and carrier 2. Most probably, such discordances may be due to differences in embryo survival rates arising from different genetic backgrounds.

Midro|Alina T|AT|
Zollino|Marcella|M|
Wiland|Ewa|E|
Panasiuk|Barbara|B|
Iwanowski|Piotr S|PS|
Murdolo|Marina|M|
Śmigiel|Robert|R|
Sąsiadek|Maria|M|
Pilch|Jacek|J|
Kurpisz|Maciej|M|

D017404:In Situ Hybridization, Fluorescence

Reciprocal chromosome translocation
FISH mapping
Pedigree segregation analysis
Meiotic segregation pattern
Genetic counseling


Melanocortin-4 Receptor Signalling: Importance for Weight Regulation and Obesity Treatment.

Abstract: The melanocortin-4 receptor (MC4R) - embedded in the leptin-melanocortin pathway - is activated by proopiomelanocortin (POMC)-derived neuropeptides such as α- and β-melanocyte-stimulating hormone (MSH) and plays an important role in hypothalamic body-weight regulation. Accordingly, MC4R is a potential drug target to combat obesity. Previous attempts to develop MC4R agonists failed due to ineffectiveness or severe adverse events. Recently, a new generation of MC4R ligands was developed. Specifically, setmelanotide was found to be effective by inducing biased signalling of the MC4R and thereby reducing feelings of hunger and leading to substantial weight loss in patients with POMC or leptin receptor deficiency. This new potential pharmacological treatment option could be beneficial for further groups of obese patients with defects in the leptin-melanocortin signalling pathway.

signalling obesity treatment MC4R mutation


A-ONE - an accessible online nutrition & exercise program for youth with physical disabilities.

Abstract:
BACKGROUND
Pediatric disability prevalence has increased to 17.8% in recent years. This youth population faces a range of individual, social, and environmental level barriers to a healthy lifestyle. This is particularly concerning because this population is at a higher risk of obesity and lifestyle-related morbidity and mortality. Therefore, A-ONE: An Accessible and Online Nutrition & Exercise Program was designed to provide a comprehensive and holistic online program for youth with physical disabilities.

METHODS
A-ONE will offer two individualized fitness workouts and one accessible cooking session per week for 16-weeks. In addition, A-ONE will offer one social-mentoring session per week. All programming (4 sessions per week) will occur during after-school hours. The program will be offered 6 times during the 2-year grant period, enrolling 10 youth per cohort, for a total of 60 youth with physical disabilities. Outcomes to be examined include physical activity, fruit and vegetable consumption, independent meal preparation, quality of life, and self-efficacy. They will be assessed pre, post, and 4-weeks following the end of the program. Program fidelity and feasibility will also be assessed.

CONCLUSION
While children with physical disabilities benefit from opportunities to engage in physical activity and nutrition, accessible programming is unavailable. Despite decades of disability rights legislation mandating access to equal education, there is still a lack of system level solutions to improve the health inequity for youth experiencing disabilities. This program represents a sustainable and scalable way to remove barriers and improve the trajectories of health among youth with a physical disability.

Hauck|Janet L|JL|
Pasik|Piotr J|PJ|
Ketcheson|Leah R|LR|

Nutrition
Physical disability
Physical activity
Healthy behaviors
Telehealth


Physiotherapy for Patients with Sciatica Awaiting Lumbar Micro-discectomy Surgery: A Nested, Qualitative Study of Patients' Views and Experiences.

Abstract:
BACKGROUND AND PURPOSE
Sciatica is a common clinical condition that can be extremely painful, disabling and life-changing. Whether conservative or surgical treatment for sciatica secondary to an intervertebral disc prolapse is most effective is still much debated. An important component of conservative treatment is physiotherapy, which aims to promote physical and psychological health for the patient, whilst resorption of the disc takes place. This paper reports a qualitative study of patients' views and experiences of a bespoke physiotherapy intervention for the treatment of sciatica.

METHODS
A qualitative study nested within a pilot randomized controlled trial of bespoke physiotherapy for the treatment of patients with sciatica awaiting lumbar microdiscectomy surgery. Patients randomized to receive bespoke physiotherapy in the intervention arm of the trial were invited to take part in semi-structured interviews. Twenty-one in-depth, semi-structured interviews took place. All interviews were recorded, fully transcribed and thematically analysed.

RESULTS
Most patients in the sample found the physiotherapy valuable, appreciating the individual nature of the approach, the exercises to reduce pain and discomfort, techniques for improving functional spinal movement, walking and dynamic posture, and manual therapy and cardiovascular exercise. A small number did not find the physiotherapy of benefit. Sixteen patients in the sample went on to proceed with surgery, but most of these found value in having had the physiotherapy first.

DISCUSSION
Many patients with sciatica appreciate the value of physiotherapy prior to surgery. Future research should examine patients' experiences of bespoke physiotherapy delivered within primary care. Copyright © 2016 The Authors Physiotherapy Research International published by John Wiley & Sons Ltd.

Boote|Jonathan|J| Newsome|Ruth|R| Reddington|Michael|M| Cole|Ashley|A| Dimairo|Munyaradzi|M|

sciatica
physical therapy modalities
qualitative research


Solvent-Controlled Synthesis of NiO-CoO/Carbon Fiber Nanobrushes with Different Densities and Their Excellent Properties for Lithium Ion Storage.

Abstract: NiO-CoO nanoneedles are grown on carbon fibers by a solvothermal strategy to form nanobrushes. The density of nanobrushes can be easily controlled by altering the solvents. The synthesis mechanism of NiO-CoO/carbon fiber nanobrushes is investigated by the time-dependent experiments in detail. As anodes for lithium ion batteries, the NiO-CoO/carbon fiber nanobrushes synthesized in ethanol show excellent properties with a discharge capacity of 801 mA h g(-1) after 200 cycles at a current density of 200 mA g(-1). The improvement can be ascribed to the carbon fibers as the highway for electrons and the interspace between NiO-CoO nanoneedles to accommodate the volume change and maintain the structural stability.

Wei|Yuehua|Y| Yan|Feilong|F| Tang|Xuan|X| Luo|Yazi|Y| Zhang|Ming|M| Wei|Weifeng|W| Chen|Libao|L|

carbon fibers
solvents
lithium ion batteries
NiO/carbon fiber nanobrushes
NiO−CoO nanoneedles
NiO−CoO/carbon fiber nanobrushes


Soft Tissue Special Issue: Perivascular and Vascular Tumors of the Head and Neck.

Abstract: Perivascular and vascular neoplasms of the head and neck are a rare group of tumors comprising a spectrum of clinical/biologic and histological features. They are frequently diagnostically challenging, due to their morphologic and immunohistochemical overlap. In this review, we summarize the pathology of these neoplasms, discussing morphology, immunohistochemistry, associated genetic findings, and the differential diagnoses.

D006258:Head and Neck Neoplasms
D006801:Humans
D012983:Soft Tissue Neoplasms
D019043:Vascular Neoplasms

Angiosarcoma
Hemangioendothelioma
Hemangioma
Perivascular neoplasms
Vascular malformations


Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer.

Abstract: RAS (rat sarcoma virus) mutant cancers remain difficult to treat despite the advances in targeted therapy and immunotherapy. Targeted therapies against the components of mitogen-activated protein kinase (MAPK) pathways, including RAS, RAF, MEK, and ERK, have demonstrated activity in BRAF mutant and, in limited cases, RAS mutant cancer. RAS mutant cancers have been found to activate adaptive resistance mechanisms such as autophagy during MAPK inhibition. Here, we review the recent clinically relevant advances in the development of the MAPK pathway and autophagy inhibitors and focus on their application to RAS mutant cancers. We provide analysis of the preclinical rationale for combining the MAPK pathway and autophagy and highlight the most recent clinical trials that have been launched to capitalize on this potentially synthetic lethal approach to cancer therapy.

Lee|Jennifer J|JJ|
Jain|Vaibhav|V|0000-0002-9235-6236
Amaravadi|Ravi K|RK|


Back gated multilayer InSe transistors with enhanced carrier mobilities via the suppression of carrier scattering from a dielectric interface.

Abstract: The back gate multilayer InSe FETs exhibit ultrahigh carrier mobilities, surpassing all the reported layer semiconductor based electronics with the same device configuration, which is achieved by the suppression of the carrier scattering from interfacial coulomb impurities or surface polar phonons at the interface of an oxidized dielectric substrate. The room-temperature mobilities of multilayer InSe transistors increase from 64 cm(2)V(-1)s(-1) to 1055 cm(2)V(-1)s(-1) using a bilayer dielectric of poly-(methyl methacrylate) (PMMA)/Al2O3. The transistors also have high current on/off ratios of 1 × 10(8), low standby power dissipation, and robust current saturation in a broad voltage range.

Feng|Wei|W| Zheng|Wei|W| Cao|Wenwu|W| Hu|PingAn|P|

mobility
carrier scatter
field-effect transistor
indium selenide
two dimensional layer semiconductor


Bi-allelic Loss-of-Function Variants in NUP188 Cause a Recognizable Syndrome Characterized by Neurologic, Ocular, and Cardiac Abnormalities.

Abstract: Nucleoporins (NUPs) are an essential component of the nuclear-pore complex, which regulates nucleocytoplasmic transport of macromolecules. Pathogenic variants in NUP genes have been linked to several inherited human diseases, including a number with progressive neurological degeneration. We present six affected individuals with bi-allelic truncating variants in NUP188 and strikingly similar phenotypes and clinical courses, representing a recognizable genetic syndrome; the individuals are from four unrelated families. Key clinical features include congenital cataracts, hypotonia, prenatal-onset ventriculomegaly, white-matter abnormalities, hypoplastic corpus callosum, congenital heart defects, and central hypoventilation. Characteristic dysmorphic features include small palpebral fissures, a wide nasal bridge and nose, micrognathia, and digital anomalies. All affected individuals died as a result of respiratory failure, and five of them died within the first year of life. Nuclear import of proteins was decreased in affected individuals' fibroblasts, supporting a possible disease mechanism. CRISPR-mediated knockout of NUP188 in Drosophila revealed motor deficits and seizure susceptibility, partially recapitulating the neurological phenotype seen in affected individuals. Removal of NUP188 also resulted in aberrant dendrite tiling, suggesting a potential role of NUP188 in dendritic development. Two of the NUP188 pathogenic variants are enriched in the Ashkenazi Jewish population in gnomAD, a finding we confirmed with a separate targeted population screen of an international sampling of 3,225 healthy Ashkenazi Jewish individuals. Taken together, our results implicate bi-allelic loss-of-function NUP188 variants in a recessive syndrome characterized by a distinct neurologic, ophthalmologic, and facial phenotype.

Muir|Alison M|AM|
Cohen|Jennifer L|JL|
Sheppard|Sarah E|SE|
Guttipatti|Pavithran|P|
Lo|Tsz Y|TY|
Weed|Natalie|N|
Doherty|Dan|D|
DeMarzo|Danielle|D|
Fagerberg|Christina R|CR|
Kjærsgaard|Lars|L|
Larsen|Martin J|MJ|
Rump|Patrick|P|
Löhner|Katharina|K|
Hirsch|Yoel|Y|
Zeevi|David A|DA|
Zackai|Elaine H|EH|
Bhoj|Elizabeth|E|
Song|Yuanquan|Y|
Mefford|Heather C|HC|

NUP188
nucleoporin
congenital cataracts
congenital heart defects
Ashkenazi Jewish
autosomal recessive
dendritic arborization
microcephaly
negative geotaxis
nuclear pore complex


Using mobile health technology to improve behavioral skill implementation through homework in evidence-based parenting intervention for disruptive behavior disorders in youth: study protocol for intervention development and evaluation.

Abstract:
BACKGROUND
Disruptive behavior disorders (DBDs) (oppositional defiant disorder (ODD) and conduct disorder (CD)) are prevalent, costly, and oftentimes chronic psychiatric disorders of childhood. Evidence-based interventions that focus on assisting parents to utilize effective skills to modify children's problematic behaviors are first-line interventions for the treatment of DBDs. Although efficacious, the effects of these interventions are often attenuated by poor implementation of the skills learned during treatment by parents, often referred to as between-session homework. The multiple family group (MFG) model is an evidence-based, skills-based intervention model for the treatment of DBDs in school-age youth residing in urban, socio-economically disadvantaged communities. While data suggest benefits of MFG on DBD behaviors, similar to other skill-based interventions, the effects of MFG are mitigated by the poor homework implementation, despite considerable efforts to support parents in homework implementation. This paper focuses on the study protocol for the development and preliminary evaluation of a theory-based, smartphone mobile health (mHealth) application (My MFG) to support homework implementation by parents participating in MFG.

METHODS/DESIGN
This paper describes a study design proposal that begins with a theoretical model, uses iterative design processes to develop My MFG to support homework implementation in MFG through a series of pilot studies, and a small-scale pilot randomised controlled trial to determine if the intervention can demonstrate change (preliminary efficacy) of My MFG in outpatient mental health settings in socioeconomically disadvantaged communities.

DISCUSSION
This preliminary study aims to understand the implementation of mHealth methods to improve the effectiveness of evidence-based interventions in routine outpatient mental health care settings for youth with disruptive behavior and their families. Developing methods to augment the benefits of evidence-based interventions, such as MFG, where homework implementation is an essential mediator of treatment benefits is critical to full adoption/implementation of these intervention in routine practice settings and maximizing benefits for youth with DBDs and their families.

TRIAL REGISTRATION
ClinicalTrials.gov NCT01917838.

Chacko|Anil|A|0000-0002-3275-4726
Isham|Andrew|A|
Cleek|Andrew F|AF|
McKay|Mary M|MM|

Mobile health technology
Homework
Parenting intervention
Disruptive behavior
mHealth
Children’s mental health


Ranging Behaviour of Commercial Free-Range Laying Hens.

Abstract: In this study, the range use and behaviour of laying hens in commercial free-range flocks was explored. Six flocks were each visited on four separate days and data collected from their outdoor area (divided into zones based on distance from shed and available resources). These were: apron (0-10 m from shed normally without cover or other enrichments); enriched belt (10-50 m from shed where resources such as manmade cover, saplings and dust baths were provided); and outer range (beyond 50 m from shed with no cover and mainly grass pasture). Data collection consisted of counting the number of hens in each zone and recording behaviour, feather condition and nearest neighbour distance (NND) of 20 birds per zone on each visit day. In addition, we used techniques derived from ecological surveys to establish four transects perpendicular to the shed, running through the apron, enriched belt and outer range. Number of hens in each 10 m × 10 m quadrat was recorded four times per day as was the temperature and relative humidity of the outer range. On average, 12.5% of hens were found outside. Of these, 5.4% were found in the apron; 4.3% in the enriched zone; and 2.8% were in the outer range. This pattern was supported by data from quadrats, where the density of hens sharply dropped with increasing distance from shed. Consequently, NND was greatest in the outer range, least in the apron and intermediate in the enriched belt. Hens sampled in outer range and enriched belts had better feather condition than those from the apron. Standing, ground pecking, walking and foraging were the most commonly recorded activities with standing and pecking most likely to occur in the apron, and walking and foraging more common in the outer range. Use of the outer range declined with lower temperatures and increasing relative humidity, though use of apron and enriched belt was not affected by variation in these measures. These data support previous findings that outer range areas tend to be under-utilized in commercial free-range flocks and suggest positive relationships between range use, feather condition and increased behavioural opportunities and decline in the use of range in cold and/or damp conditions.

Chielo|Leonard Ikenna|LI|
Pike|Tom|T|
Cooper|Jonathan|J|

ranging behaviour
free-range laying hens
enrichment
feather condition
ecological survey


124-Color Super-resolution Imaging by Engineering DNA-PAINT Blinking Kinetics.

Abstract: Optical super-resolution techniques reach unprecedented spatial resolution down to a few nanometers. However, efficient multiplexing strategies for the simultaneous detection of hundreds of molecular species are still elusive. Here, we introduce an entirely new approach to multiplexed super-resolution microscopy by designing the blinking behavior of targets with engineered binding frequency and duration in DNA-PAINT. We assay this kinetic barcoding approach in silico and in vitro using DNA origami structures, show the applicability for multiplexed RNA and protein detection in cells, and finally experimentally demonstrate 124-plex super-resolution imaging within minutes.

Wade|Orsolya K|OK|
Woehrstein|Johannes B|JB|
Nickels|Philipp C|PC|
Strauss|Sebastian|S|
Stehr|Florian|F|
Stein|Johannes|J|0000-0002-1335-1120
Schueder|Florian|F|
Strauss|Maximilian T|MT|
Ganji|Mahipal|M|
Schnitzbauer|Joerg|J|
Grabmayr|Heinrich|H|
Yin|Peng|P|0000-0002-2769-6357
Schwille|Petra|P|0000-0002-6106-4847
Jungmann|Ralf|R|0000-0003-4607-3312

DNA-PAINT
multiplexing
Super-resolution microscopy
barcoding
DNA nanotechnology


Phenanthridine based rapid "turn-on" fluorescent sensor for selective detection of Th4+ ion and its real-time application.

Abstract: A new and highly sensitive and selective phenanthridine based sensor, 9-(7,8,13,14-tetrahydrodibenzo[a,i]phenanthridin-5-yl)benzo[h]quinolin-10-ol (PHBQ), was developed for the fluorescent ''turn-on'' detection of Th4+ ion in acetonitrile: water (8:2) medium. The fluorescence intensity of PHBQ diminished in the region of pH 1 to 3 and could be recovered by adjusting the pH to above 4. The sensor PHBQ showed distinct spectral changes in response to Th4+ ion over other competitive metal ions. The fluorescence displayed good linearity with the Th4+ concentration in the equivalence of 0-0.5 equivalents. The detection limit was calculated to be as low as 99 nM, which was less than that of previously reported sensors. The recognizing mechanism of PHBQ towards Th4+ was investigated in detail using HR-MS, NMR, and IR spectroscopy. The economically viable Whatman filter paper was fabricated with PHBQ to develop a paper-based fluorescence kit to detect the Th4+ in an aqueous medium efficiently. Furthermore, the application of sensor ligand in fluorescence imaging was studied in E-coli cells due to its minimal cytotoxicity and good optical properties. The obtained data suggest that the ligand PHBQ can be used as a fluorescent sensor for tracking Th4+ in multiple applications.


European Consumers' Perceptions and Attitudes towards Non-Thermally Processed Fruit and Vegetable Products.

Abstract: In order to meet the demand for high-quality fruit and vegetable (F&V) products, a wide variety of novel non-thermal processing (NTP) technologies are under development. This study used a qualitative focus group approach to investigate consumers' perception and attitudes towards non-thermally processed F&V products among young (18-30 years old) and middle-aged (45-60 y.o.) consumers across six European countries: Denmark, Germany, Italy, Serbia, Spain, and the Netherlands. Findings show that the expected benefits and social concerns are important factors which affect consumers' attitudes toward non-thermally processed F&V. Extending shelf-life, being healthier and more nutritious, and better hygiene and safety were important benefits, whilst impacts on product quality, safety risks, higher price and environmental costs were the concerns most often mentioned by participants. However, due to a lack of knowledge and trustworthy information sources, consumers have difficulties in assessing relevant benefits and risks. Targeted communication that could explicitly and efficiently reveal benefits and risks is highly recommended to enhance consumer awareness and trust. This may especially be needed to reach middle-aged consumers who showed less confidence in NTP, compared to young consumers. Consumers from Spain, Denmark, and the Netherlands appeared more interested in consuming NTP F&V, compared to Italy, Serbia, and Germany. These findings are expected to provide recommendations to better communicate non-thermally processed F&V with consumers in the EU.

fruit and vegetables
consumer perception
food processing
non-thermal processing technologies


What causes a small increase in radiographic progression in rheumatoid arthritis patients tapering TNF inhibitors?

Abstract:
OBJECTIVE
In a randomised controlled trial investigating tapering of TNF inhibitors (TNFi) compared with usual care (UC) in rheumatoid arthritis patients, minimal radiographic progression was more frequent in patients who attempted tapering. Possible explanations include higher incidence of flaring, higher mean disease activity or lower TNFi use.

METHODS
18 months data from the DRESS study were used. Change in Sharp-van der Heijde (ΔSvdH) score (linear regression) and proportion of patients with >0.5 ΔSvdH (logistic regression) were used as outcomes. The cumulative incidence and number of short-lived and major flares per patient, mean time-weighted disease activity (MTW-DAS28-CRP) and TNFi use were used as independent variables. Regression models were performed stratified per study group and corrected for possible confounders.

RESULTS
175 of 180 patients had 18-month data available. The mean ΔSvdH were 0.75 and 0.15 units with 37 of 116 (32%) and 9 of 59 (15%) patients exceeding 0.5 points in the tapering and UC group, respectively (both p<0.05). MTW-DAS28-CRP, but not incidence or number of short-lived or major flares, or TNFi use, was independently associated with the mean progression score, but only in the tapering group. Additional analyses on DAS28-CRP subcomponents showed that this was mainly caused by MTW swollen joint count. No confounders were identified.

CONCLUSIONS
Radiographic progression was associated with higher MTW-DAS28-CRP (and especially swollen joint count), but only in patients who tapered TNFi. This finding stresses the importance of maintaining disease activity as low as possible in patients in whom TNFi is tapered and to check for radiographic progression regularly.

TRIAL REGISTRATION NUMBER
NTR 3216; Post-results.

Bouman|Chantal A M|CA|
den Broeder|Alfons A|AA|
van der Maas|Aatke|A|
van den Hoogen|Frank H J|FH|
Landewé|Robert B M|RB|
van Herwaarden|Noortje|N|

Rheumatoid Arthritis
Disease Activity
Anti-TNF
DMARDs (biologic)
Treatment


CD47 regulates the phagocytic clearance and replication of the Plasmodium yoelii malaria parasite.

Abstract: Several Plasmodium species exhibit a strong age-based preference for the red blood cells (RBC) they infect, which in turn is a major determinant of disease severity and pathogenesis. The molecular basis underlying this age constraint on the use of RBC and its influence on parasite burden is poorly understood. CD47 is a marker of self on most cells, including RBC, which, in conjunction with signal regulatory protein alpha (expressed on macrophages), prevents the clearance of cells by the immune system. In this report, we have investigated the role of CD47 on the growth and survival of nonlethal Plasmodium yoelii 17XNL (PyNL) malaria in C57BL/6 mice. By using a quantitative biotin-labeling procedure and a GFP-expressing parasite, we demonstrate that PyNL parasites preferentially infect high levels of CD47 (CD47(hi))-expressing young RBC. Importantly, C57BL/6 CD47(-/-) mice were highly resistant to PyNL infection and developed a 9.3-fold lower peak parasitemia than their wild-type (WT) counterparts. The enhanced resistance to malaria observed in CD47(-/-) mice was associated with a higher percentage of splenic F4/80(+) cells, and these cells had a higher percentage of phagocytized parasitized RBC than infected WT mice during the acute phase of infection, when parasitemia was rapidly rising. Furthermore, injection of CD47-neutralizing antibody caused a significant reduction in parasite burden in WT C57BL/6 mice. Together, these results strongly suggest that CD47(hi) young RBC may provide a shield to the malaria parasite from clearance by the phagocytic cells, which may be an immune escape mechanism used by Plasmodium parasites that preferentially infect young RBC.

Banerjee|Rajdeep|R| Khandelwal|Sanjay|S| Kozakai|Yukiko|Y| Sahu|Bikash|B| Kumar|Sanjai|S|


Extra-Virgin Olive Oil with Natural Phenolic Content Exerts an Anti-Inflammatory Effect in Adipose Tissue and Attenuates the Severity of Atherosclerotic Lesions in Ldlr-/-.Leiden Mice.

Abstract:
SCOPE
The present study investigates the effect of olive oils with different phenolic content in high-fat diets (HFDs) on hypertrophy and inflammation in adipose tissue and associated atherosclerosis, in the context of obesity.

METHODS AND RESULTS
Ldlr-/-.Leiden mice were fed three different HFDs for 32 weeks and were compared with mice fed the standard low-fat diet (LFD). The different fats provided in the HFDs were lard (HFD-L), extra-virgin olive oil (EVOO; 79 mg kg-1 of phenolic compounds, HFD-EVOO), or EVOO rich in phenolic compounds (OL, 444 mg kg-1 of phenolic compounds, HFD-OL). All HFD-fed mice became obese, but only HFD-L-induced adipocyte hypertrophy. HFD-EVOO mice exhibited the greatest levels of Adiponectin in adipose tissue and presented atherosclerotic lesions similar to the LFD group, with a very low count of monocyte/macrophage compared with HFD-L and HFD-OL mice. Enrichment of the phenolic content of olive oil reduced the secretion of nitrites/nitrates in the aorta, but atherosclerosis was not attenuated in HFD-OL mice compared to other HFD mice.

CONCLUSION
Consumption of olive oil with a natural content of phenolic compounds attenuates adipose tissue hypertrophy and inflammation and exerts antiatherosclerotic effects in mice. A higher phenolic content of olive oil did not provide further benefits in the prevention of atherosclerosis.

Luque-Sierra|Amparo|A|
Alvarez-Amor|Leticia|L|
Kleemann|Robert|R|
Martín|Franz|F|
Varela|Lourdes M|LM|

extra-virgin olive oil
high-fat diet
inflammation
atherosclerosis
obesity


CDKN2A(p16) and HRAS are frequently mutated in vulvar squamous cell carcinoma.

Abstract:
BACKGROUND
Two etiologic pathways of vulvar cancer are known, a human papillomavirus (HPV)- and a TP53-associated route, respectively, but other genetic changes may also play a role. Studies on somatic mutations in vulvar cancer other than TP53 are limited in number and size. In this study, we investigated the prevalence of genetic mutations in 107 vulvar squamous cell carcinomas (VSCCs).

METHODS
A total of 107 paraffin-embedded tissue samples of primarily surgically treated VSCCs were tested for HPV infection and screened for mutations in 14 genes (BRAF, CDKN2A(p16), CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, PTEN, and TP53) using Sanger sequencing and mass spectrometry.

RESULTS
Mutations were detected in 7 genes. Of 107 VSCCs, 66 tumors (62%) contained at least one mutation (TP53=58, CDKN2A(p16)=14, HRAS=10, PIK3CA=7, PPP2R1A=3, KRAS=1, PTEN=1). Mutations occurred most frequently in HPV-negative samples. Five-year survival was significantly worse for patients with a mutation (47% vs 59%, P=.035), with a large effect from patients carrying HRAS-mutations.

CONCLUSION
Somatic mutations were detected in 62% of VSCCs. As expected, HPV infection and TP53-mutations play a key role in the development of VSCC, but CDKN2A(p16), HRAS, and PIK3CA-mutations were also frequently seen in HPV-negative patients. Patients with somatic mutations, especially HRAS-mutations, have a significantly worse prognosis than patients lacking these changes, which could be of importance for the development of targeted therapy.

Trietsch|Marjolijn D|MD|
Spaans|Vivian M|VM|
ter Haar|Natalja T|NT|
Osse|Elisabeth M|EM|
Peters|Alexander A W|AA|
Gaarenstroom|Katja N|KN|
Fleuren|Gert Jan|GJ|

D019941:Cyclin-Dependent Kinase Inhibitor p16

HRAS
Squamous cell carcinoma
Somatic mutation
Survival
CDKN2A
Vulva


Effects of Escitalopram on Endoplasmic Reticulum Stress and Oxidative Stress Induced by Tunicamycin.

Abstract: Background: Major depressive disorder (MDD) was reported to be associated with endoplasmic reticulum stress (ERS) combined with oxidative stress (OS) (ERS/OS). Here, we aimed to investigate the effects of escitalopram (ESC) on blood-brain barrier (BBB) permeability and ERS/OS-related pathways in brain microvascular endothelial cells (bEnd.3 cells) induced by tunicamycin (TM). Methods: bEnd.3 cells were divided into four groups: control, TM, ESC, and ESC + TM groups. CCK-8 and flow cytometry were used to detect cell survival and apoptosis, respectively. The expression levels of proteins involved in cell permeability and ERS/OS-related pathways were assessed by western blot and immunofluorescence. Malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity were determined by commercial kits. Results: We revealed that TM-induced bEnd.3 cells exhibited remarkably decreased viability and increased apoptosis rate, while ESC treatment reversed these changes. Additionally, TM treatment resulted in markedly increased PERK, GRP78, ATF6, XBP1, and CHOP protein expression levels. On the contrary, the expression of PERK, GRP78, XBP1, and CHOP was obviously reduced in TM-induced bEnd.3 cells after ESC treatment. Moreover, TM significantly reduced the expression of p-eNOS and P-gp and increased the expression of CaMKII and MMP9 compared with the control group. However, ESC reversed these changes in TM-induced bEnd.3 cells. Furthermore, the expression of SOD was significantly decreased, while MDA was significantly increased by TM treatment. In contrast, the expression of SOD was dramatically increased, while MDA was remarkably decreased by ESC treatment. Conclusion: Our results demonstrated that ESC can inhibit ERS/OS and BBB permeability of TM-induced bEnd.3 cells. ESC may alleviate cognitive impairment and prevent comorbidities in MDD patients through ERS/OS.

Yang|Lixia|L| Chen|ZhengHong|Z| Li|Jie|J| Ding|PengJin|P| Wang|Yiming|Y|

escitalopram
endoplasmic reticulum stress
oxidative stress
tunicamycin
major depressive disorder


The prognostic value of long noncoding RNA HOTTIP on clinical outcomes in breast cancer.

Abstract: Although a few studies have assessed the prognostic value of long noncoding RNA HOTTIP in patients with malignant tumors, the relationship between HOTTIP and clinical outcome of breast cancer remains elusive. The aim of this study is to explore the prognostic significance of HOTTIP in breast cancer patients. A meta-analysis was performed to involve the eligible studies to investigate the association of HOTTIP expression level with outcome in cancer patients. Pooled hazard ratios (HRs) and 95% confidence interval (CI) of HOTTIP for cancer survival were calculated. Five relevant articles involving 460 patients with various solid carcinomas were included in this meta-analysis. For overall survival, high HOTTIP expression could significantly predict worse outcome with the pooled HR of 2.29 (95 % CI 1.72-3.03, P < 0.00001). Furthermore, Gene Expression Omnibus was performed to evaluate the association of HOTTIP expression with the prognosis in breast cancer patients. It was also found an indication that high HOTTIP expression was associated with worse survival in breast cancer patients by microarray analysis (GSE20711, GSE16446 and GSE9195). Finally, association between HOTTIP levels and clinicopathological factors and prognosis was also analyzed in an independent validation cohort including 100 breast cancer cases. HOTTIP expression was correlated with tumor size (P=0.025), lymph node status (P=0.009) and TNM stage (P=0.0001) in the breast cancer validation cohort. The Kaplan-Meier survival curves indicated that breast cancer patients with high HOTTIP expression had worse overall survival (P=0.0139) and disease-free survival (P=0.0003). Multivariate survival analysis based on the Cox proportional hazards model showed that HOTTP is considered as an independent prognostic factor in breast cancer patients. Together, our combined results suggest that high HOTTIP expression may be serving as an unfavorable prognosis predictor for breast cancer patients.

Yang|Yinlong|Y| Qian|Jinxian|J| Xiang|Youqun|Y| Chen|Yizuo|Y| Qu|Jinmiao|J|

D020411:Oligonucleotide Array Sequence Analysis

HOTTIP
breast cancer
prognosis
long non-coding RNA


Comparative Analysis of Inflammatory Cytokine Release and Alveolar Epithelial Barrier Invasion in a Transwell® Bilayer Model of Mucormycosis.

Abstract: Understanding the mechanisms of early invasion and epithelial defense in opportunistic mold infections is crucial for the evaluation of diagnostic biomarkers and novel treatment strategies. Recent studies revealed unique characteristics of the immunopathology of mucormycoses. We therefore adapted an alveolar Transwell® A549/HPAEC bilayer model for the assessment of epithelial barrier integrity and cytokine response to Rhizopus arrhizus, Rhizomucor pusillus, and Cunninghamella bertholletiae. Hyphal penetration of the alveolar barrier was validated by 18S ribosomal DNA detection in the endothelial compartment. Addition of dendritic cells (moDCs) to the alveolar compartment led to reduced fungal invasion and strongly enhanced pro-inflammatory cytokine response, whereas epithelial CCL2 and CCL5 release was reduced. Despite their phenotypic heterogeneity, the studied Mucorales species elicited the release of similar cytokine patterns by epithelial and dendritic cells. There were significantly elevated lactate dehydrogenase concentrations in the alveolar compartment and epithelial barrier permeability for dextran blue of different molecular weights in Mucorales-infected samples compared to Aspergillus fumigatus infection. Addition of monocyte-derived dendritic cells further aggravated LDH release and epithelial barrier permeability, highlighting the influence of the inflammatory response in mucormycosis-associated tissue damage. An important focus of this study was the evaluation of the reproducibility of readout parameters in independent experimental runs. Our results revealed consistently low coefficients of variation for cytokine concentrations and transcriptional levels of cytokine genes and cell integrity markers. As additional means of model validation, we confirmed that our bilayer model captures key principles of Mucorales biology such as accelerated growth in a hyperglycemic or ketoacidotic environment or reduced epithelial barrier invasion upon epithelial growth factor receptor blockade by gefitinib. Our findings indicate that the Transwell® bilayer model provides a reliable and reproducible tool for assessing host response in mucormycosis.

Belic|Stanislav|S|
Page|Lukas|L|
Lazariotou|Maria|M|
Waaga-Gasser|Ana Maria|AM|
Dragan|Mariola|M|
Springer|Jan|J|
Loeffler|Juergen|J|
Morton|Charles Oliver|CO|
Einsele|Hermann|H|
Ullmann|Andrew J|AJ|
Wurster|Sebastian|S|

cytokines
mucormycosis
dendritic cells
alveolar epithelium
in vitro model


Beyond aphasia: Altered EEG connectivity in Broca's patients during working memory task.

Abstract: Broca's region and adjacent cortex presumably take part in working memory (WM) processes. Electrophysiologically, these processes are reflected in synchronized oscillations. We present the first study exploring the effects of a stroke causing Broca's aphasia on these processes and specifically on synchronized functional WM networks. We used high-density EEG and coherence analysis to map WM networks in ten Broca's patients and ten healthy controls during verbal WM task. Our results demonstrate that a stroke resulting in Broca's aphasia also alters two distinct WM networks. These theta and gamma functional networks likely reflect the executive and the phonological processes, respectively. The striking imbalance between task-related theta synchronization and desynchronization in Broca's patients might represent a disrupted balance between task-positive and WM-irrelevant functional networks. There is complete disintegration of left fronto-centroparietal gamma network in Broca's patients, which could reflect the damaged phonological loop.

Rutar Gorišek|Veronika|V|
Zupanc Isoski|Vlasta|V|
Belič|Aleš|A|
Manouilidou|Christina|C|
Koritnik|Blaž|B|
Bon|Jure|J|
Pečarič Meglič|Nuška|N|
Vrabec|Matej|M|
Žibert|Janez|J|
Repovš|Grega|G|
Zidar|Janez|J|

Working memory
Synchronized oscillations
Theta
Gamma
Phonological loop
Broca’s aphasia
Default mode network
EEG coherence
Multiple demand network


Does an interaction exist between ketamine hydrochloride and Becton Dickinson syringes?

Abstract:
Introduction
An international alert from Becton Dickinson (BD) has noted the possibility of interaction between several molecules and some syringes. The Centralized IntraVenous Additives Service of the institution was using 3 mL BD syringes to store ketamine HCl. This study evaluated the interaction between ketamine and these syringes.

Method
A batch of BD syringes produced in Europe and left in quarantine from the day of the international alert has been tested at 22, 29, 36, 43 and 50 days of storage at room temperature. At each time, the pH of the solutions was measured. The solutions were inspected visually and by microscope, and spectrophotometric measurements were performed. The concentrations were measured by a validated ultra-high-performance liquid chromatography-diode array detector.

Results
Neither physical change nor pH modification was observed during the study. According to a lower limit of the 95% unilateral CI on the mean >90% of the theoretical concentration, the solutions remain stable for at least 50 days.

Conclusion
In our study conditions, ketamine can be stored for at least 50 days without risk of sorption with syringes.

Closset|M|M|
Hecq|J D|JD|
Gonzalez|E|E|
Bihin|B|B|
Jamart|J|J|
Galanti|L|L|


Immunotoxins and nanobody-based immunotoxins: review and update.

Abstract: Immunotoxins (ITs) are protein-based drugs that compose of targeting and cytotoxic moieties. After binding the IT to the specific cell-surface antigen, the IT internalises into the target cell and kills it. Targeting and cytotoxic moieties usually include monoclonal antibodies and protein toxins with bacterial or plant origin, respectively. ITs have been successful in haematologic malignancies treatment. However, ITs penetrate poorly into solid tumours because of their large size. Use of camelid antibody fragments known as nanobodies (Nbs) as a targeting moiety may overcome this problem. Nbs are the smallest fragment of antibodies with excellent tumour tissue penetration. The ability to recognise cryptic (immuno-evasive) target antigens, low immunogenicity, and high-affinity are other fundamental characteristics of Nbs that make them suitable candidates in targeted therapy. Here, we reviewed and discussed the structure and function of ITs, Nbs, and nanobody-based ITs. To gain sound insight into the issue at hand, we focussed on nanobody-based ITs.

variable fragment of heavy-chain only antibody


Unveiling the stimulatory effects of tartrazine on human and bovine serum albumin fibrillogenesis: Spectroscopic and microscopic study.

Abstract: Amyloid fibrils are playing key role in the pathogenesis of various neurodegenerative diseases. Generally anionic molecules are known to induce amyloid fibril in several proteins. In this work, we have studied the effect of anionic food additive dye i.e., tartrazine (TZ) on the amyloid fibril formation of human serum albumins (HSA) and bovine serum albumin (BSA) at pHs7.4 and 3.5. We have employed various biophysical methods like, turbidity measurements, Rayleigh Light Scattering (RLS), Dynamic Light Scattering (DLS), intrinsic fluorescence, Congo red assay, far-UV CD, transmission electron microscopy (TEM) and atomic force microscopy (AFM) to decipher the mechanism of TZ-induce amyloid fibril formation in both the serum albumins at pHs7.4 and 3.5. The obtained results suggest that both the albumins forms amyloid-like aggregates in the presence of 1.0 to 15.0mM of TZ at pH3.5, but no amyloid fibril were seen at pH7.4. The possible cause of TZ-induced amyloid fibril formation is electrostatic and hydrophobic interaction because sulfate group of TZ may have interacted electrostatically with positively charged amino acids of the albumins at pH3.5 and increased protein-protein and protein-TZ interactions leading to amyloid fibril formation. The TEM, RLS and DLS results are suggesting that BSA forms bigger size amyloids compared to HSA, may be due to high surface hydrophobicity of BSA.

Al-Shabib|Nasser Abdulatif|NA|
Khan|Javed Masood|JM|
Alsenaidy|Mohammad A|MA|
Alsenaidy|Abdulrahman M|AM|
Khan|Mohd Shahnawaz|MS|
Husain|Fohad Mabood|FM|
Khan|Mohammad Rashid|MR|
Naseem|Mohammad|M|
Sen|Priyankar|P|
Alam|Parvez|P|
Khan|Rizwan Hasan|RH|

D057927:Hydrophobic and Hydrophilic Interactions

Human and bovine serum albumin
Amyloid fibril
Food additive dye
Tartrazine (TZ)
Protein aggregation
pH


Clinical signs, lethal dose and histopathological lesions in grass carp, Ctenopharyngodon idella experimentally infected with Edwardsiella tarda.

Abstract: An experiment was conducted to study the lethal dose (LD50-96h) and histopathological changes occurring in several organs of grass carp challenged with different concentrations of Edwardsiella tarda. The healthy grass carps were challenged with the bacterial suspension of 106,107, 108, 109 and 1010 CFU ml-1. The study demonstrated that the lethal dose (LD50-96h) of E. tarda for grass carp is 1.3 × 109 CFU ml-1. The infected fish showed abnormal swimming behavior, slower movements, skin necrosis, hemorrhages, and open lesion on the fontanelle of the frontal bone of the skull during the initial phase of infection. About 60% of the fish which received the bacterial suspension of 1010 CFU ml-1 died within 24 h of infection. The histopathological examination of the infected tissue section demonstrated the severe damages in the internal organs. In gills, oedema, secondary lamellae fusion, and hyperplasia of basal epithelial lining between secondary lamellae were reported. The microscopic observation showed the disruption of submucosa to the mucosa, which finally led to degenerative changes in the intestine, necrosis of hepatocytes and infiltration of red blood cells in the liver. The tubular disintegration in kidney and loss of capsular boundary of red pulp in spleen were also reported. In conclusion, the result indicates that the infection caused by E. tarda can cause severe damages and alterations in grass carp tissues and potential mass mortality. Moreover, The bacteria isolated from the mobribund fish was characterized by biochemical tests and expression of five critical virulence genes like citC, fimA, gadB, mukF and gyrB were detected from the microorganism. The study aims to provide a research foundation for further studies on the susceptibility and pathological changes of grass carp induced by E. tarda infection.

Pandey|Vandana|V|
Hussain Bhat|Raja Aadil|RA|
Chandra|Suresh|S|
Tandel|Ritesh Shantilal|RS|
Dubey|Maneesh Kumar|MK|
Sharma|Prakash|P|
Gehlot|Bhawna|B|
Dash|Pragyan|P|
Joshi|Rini|R|

Histopathology
Grass carp
Edwardsiella tarda
LD(50)


Genetic Virulence Profile of Enteroaggregative Escherichia coli Strains Isolated from Danish Children with Either Acute or Persistent Diarrhea.

Abstract: Enteroaggregative Escherichia coli (EAEC) is frequently found in diarrheal stools worldwide. It has been associated with persistent diarrhea, weight loss, and failure to thrive in children living in developing countries. A number of important EAEC virulence genes are identified; however, their roles in acute and persistent diarrhea have not been previously investigated. The aim of this study was to identify specific EAEC virulence genes associated with duration and type of diarrhea in Danish children. We aimed to improve the current diagnostics of EAEC and enable targeting of strains with an expected severe disease course. Questionnaires answered by parents provided information regarding duration of diarrhea and presence of blood or mucus. A total of 295 EAEC strains were collected from children with acute (≤7 days) and persistent diarrhea (≥14 days) and were compared by using multiplex PCR targeting the genes sat, sepA, pic, sigA, pet, astA, aatA, aggR, aaiC, aap, agg3/4C, ORF3, aafA, aggA, agg3A, agg4A, and agg5A. Furthermore, the distribution of EAEC genes in strains collected from cases of bloody, mucoid, and watery diarrhea was investigated. The classification and regression tree analysis (CART) was applied to investigate the relationship between EAEC virulence genes and diarrheal duration and type. Persistent diarrhea was associated with strains lacking the pic gene (p = 0.002) and with the combination of the genes pic, sat, and absence of the aggA gene (p = 0.05). Prolonged diarrhea was associated with the combination of the genes aatA and astA (p = 0.03). Non-mucoid diarrhea was associated with strains lacking the aatA gene (p = 0.004). Acute diarrhea was associated with the genes aggR, aap, and aggA by individual odds ratios. Resistance toward gentamicin and ciprofloxacin was observed in 7.5 and 3% of strains, respectively. Multi-drug resistance was observed in 38% of strains. Genetic host factors have been associated with an increased risk of EAEC-associated disease. Therefore, we investigated a panel of risk factors in two groups of children-EAEC-positive and EAEC-negative-to identify additional factors predisposing to disease. The duration of breastfeeding was positively correlated with the likelihood of belonging to the EAEC-negative group of children.

Hebbelstrup Jensen|Betina|B|
Poulsen|Anja|A|
Hebbelstrup Rye Rasmussen|Stig|S|
Struve|Carsten|C|
Engberg|Jørgen H|JH|
Friis-Møller|Alice|A|
Boisen|Nadia|N|
Jønsson|Rie|R|
Petersen|Randi F|RF|
Petersen|Andreas M|AM|
Krogfelt|Karen A|KA|

D024901:Drug Resistance, Multiple, Bacterial

D060885:Multiplex Polymerase Chain Reaction

enteroaggregative Escherichia coli
EAEC
risk factors
childhood diarrhea
virulence factors


Benefits of Iron Chelators in the Treatment of Parkinson's Disease.

Abstract: As a novel discovered regulated cell death pattern, ferroptosis has been associated with the development of Parkinson's disease (PD) and has attracted widespread attention. Nevertheless, the relationship between ferroptosis and PD pathogenesis is still unclear. This study aims to investigate the effect of iron overload on dopaminergic (DA) neurons and its correlation with ferroptosis. Here we use nerve growth factor (NGF) induced PC12 cells which are derived from pheochromocytoma of the rat adrenal to establish a classical PD in vitro model. We found significantly decreased cell viability in NGF-PC12 cell under ammonium ferric citrate (FAC) administration. Moreover, excessive intracellular iron ions induced the increase of (reactive oxygen species) ROS release as well as the decrease of mitochondrial membrane potential in PC12-NGF cells. In addition, we also found that overloaded iron can activate cell apoptosis and ferroptosis pathways, which led to cell death. Furthermore, MPP-induced PD cells were characterized by mitochondrial shrinkage, decreased expression of glutathione peroxidase 4 (Gpx4) and ferritin heavy chain (FTH1), and increased divalent metal transporter (DMT1) and transferrin receptor 1 (TfR1) expression level. In contrast, Lip-1 and DFO increased the expression level of GPX4 and FTH1 compared to MPP-induced PD cell. In conclusion, we indicated that overloaded intracellular iron contributes to neurons death via apoptosis and ferroptosis pathways, while DFO, an iron chelator, can inhibit ferroptosis in order to protect the neurons in vitro.

Zeng|Xiaoyan|X| An|Hedi|H| Yu|Fei|F| Wang|Kai|K| Zheng|Lanlan|L| Zhou|Wei|W| Bao|Yiwen|Y| Yang|Jie|J| Shen|Nan|N| Huang|Dongya|D|

Iron chelator
Ferroptosis
Iron deposition
Neuroprotective effect
Parkinson’s disease


The Role of Nrf2 Transcription Factor and Sp1-Nrf2 Protein Complex in Glutamine Transporter SN1 Regulation in Mouse Cortical Astrocytes Exposed to Ammonia.

Abstract: Ammonia toxicity in the brain primarily affects astrocytes via a mechanism in which oxidative stress (OS), is coupled to the imbalance between glutamatergic and GABAergic transmission. Ammonia also downregulates the astrocytic N system transporter SN1 that controls glutamine supply from astrocytes to neurons for the replenishment of both neurotransmitters. Here, we tested the hypothesis that activation of Nrf2 is the process that links ammonia-induced OS formation in astrocytes to downregulation and inactivation of SN1 and that it may involve the formation of a complex between Nrf2 and Sp1. Treatment of cultured cortical mouse astrocytes with ammonia (5 mM NH4Cl for 24 h) evoked Nrf2 nuclear translocation, increased its activity in a p38 MAPK pathway-dependent manner, and enhanced Nrf2 binding to Slc38a3 promoter. Nrf2 silencing increased SN1 mRNA and protein level without influencing astrocytic [3H]glutamine transport. Ammonia decreased SN1 expression in Nrf2 siRNA treated astrocytes and reduced [3H]glutamine uptake. In addition, while Nrf2 formed a complex with Sp1 in ammonia-treated astrocytes less efficiently than in control cells, treatment of astrocytes with hybrid-mode inactivated Sp1-Nrf2 complex (Nrf2 silencing + pharmacological inhibition of Sp1) did not affect SN1 protein level in ammonia-treated astrocytes. In summary, the results document that SN1 transporter dysregulation by ammonia in astrocytes involves activation of Nrf2 but does not require the formation of the Sp1-Nrf2 complex.

Nrf2
glutamine
glutamine transport
astrocytes
Sp1
SN1 (SNAT3)


Effect of Yoga on Antiretroviral Adherence Postincarceration in HIV+ Individuals.

Abstract: The negative impacts of stress on antiretroviral therapy (ART) adherence and the many stressors faced by people returning from incarceration support the need for stress reduction interventions for this population. We hypothesized that 37 returning citizens living with HIV and substance use problems randomized to a 12-session weekly yoga intervention would experience improved ART adherence, lower viral loads, and lower heart rate and blood pressure as compared to 36 people randomized to treatment as usual (TAU). We found that ART adherence increased for yoga participants and decreased for TAU participants. There were no significant changes for viral load, heart rate, or blood pressure. The lack of statistically significant effects may be due to a small sample size and enrollment of people largely in HIV treatment. Studies with larger sample sizes and participants exhibiting low ART adherence are warranted to better understand yoga's impact.

Wimberly|Alexandra S|AS|
Gross|Robert|R|
Layde|Molly|M|

yoga
HIV
substance use
antiretroviral therapy adherence
reentry


The Emerging Role of Topical Ocular Drugs to Target the Posterior Eye.

Abstract: The prevalence of chronic fundus diseases is increasing with the aging of the general population. The treatment of these intraocular diseases relies on invasive drug delivery because of the globular structure and multiple barriers of the eye. Frequent intraocular injections bring heavy burdens to the medical care system and patients. The use of topical drugs to treat retinal diseases has always been an attractive solution. The fast development of new materials and technologies brings the possibility to develop innovative topical formulations. This article reviews anatomical and physiological barriers of the eye which affect the bioavailability of topical drugs. In addition, we summarize innovative topical formulations which enhance the permeability of drugs through the ocular surface and/or extend the drug retention time in the eye. This article also reviews the differences of eyes between different laboratory animals to address the translational challenges of preclinical models. The fast development of in vitro eye models may provide more tools to increase the clinical translationality of topical formulations for intraocular diseases. Clinical successes of topical formulations rely on continuous and collaborative efforts between different disciplines.

Wang|Lixiang|L|
Zhou|Mikael Ben|MB|
Zhang|Hui|H|

Topical formulation
In vitro eye model
Comparative anatomy of the eye
In vivo eye models
Nanoparticles
Ocular barriers
Ocular drug delivery
Ocular fundus diseases


Subjective well-being among Latino day laborers: Examining the role of religiosity, social networks, and cigarette use.

Abstract: Background: Latino day laborers (LDLs) experience chronic stressors, that adversely affects their subjective well-being (SWB). The purpose of the study was to determine whether LDLs' sociodemographic characteristics, religiosity, social networks, and cigarette use were significantly associated with SWB. Methods: AApproximately 150 LDLs from 4 informal day laborer sites in Dallas and Arlington, Texas, participated in the cross-sectional survey. Informed consent was obtained from all participants and data on SWB were collected face-to-face from April 2013 through July 2013. Results: Most respondents were of Mexican ancestry, (n = 112; 75%), were foreign-born (n = 140; 93%), and undocumented (n = 108; 72%). LDLs reported a mean satisfaction with life score of 19.07 (SD=8.52). Thirty percent of LDLs reported not smoking any cigarettes in the past 30 days. However, 20% reported smoking 20-39 cigarettes, while another 20% reported smoking 40 or more cigarettes in the past 30 days. Hierarchical multiple regression results indicated that marital status (β = 0.13, P ≤ 0.05), connectedness to friends (β = 0.21, P ≤ 0.001), the influence of religion on life (β = 0.57, P ≤ 0.01), frequency of attendance to religious institution (β = 0.11, P ≤ 0.005), and cigarette use (β = -0.15, P ≤ 0.05) were significantly associated with the SWB appraisals of LDLs. Conclusion: These findings show that LDLs are resilient and rely on noneconomic factors to enhance their perceived quality of life. The results underscore the need to identify pathways to improve SWB among LDLs. Doing so may address the broader mental health and occupational health disparities gaps that affect LDLs.

Boyas|Javier F|JF|
Valera|Pamela|P|
Ruiz|Erika|E|

Subjective well-being
Latino day laborers
Cigarette use
Undocumented status


Serum exosomes accelerate diabetic wound healing by promoting angiogenesis and ECM formation.

Abstract: Nonhealing wounds in diabetes remain a global clinical and research challenge. Exosomes are primary mediators of cell paracrine action, which are shown to promote tissue repair and regeneration. In this study, we investigated the effects of serum derived exosomes (Serum-Exos) on diabetic wound healing and its possible mechanisms. Serum-Exos were isolated from blood serum of normal healthy mice and identified by transmission electron microscopy and western blot. The effects of Serum-Exos on diabetic wound healing, fibroblast growth and migration, angiogenesis and extracellular matrix (ECM) formation were investigated. Our results showed that the isolated Serum-Exos exhibited a sphere-shaped morphology with a mean diameter at 150 nm, and expressed classical markers of exosomes including HSP70, TSG101, and CD63. Treatment with Serum-Exos elevated the percentage of wound closure and shortened the time of healing in diabetic mice. Mechanistically, Serum-Exos promoted granulation tissue formation and increased the expression of CD31, fibronectin and collagen-ɑ in diabetic mice. Serum-Exos also promoted the migration of NIH/3T3 cells, which was associated with increased expression levels of PCNA, Ki67, collagen-α and fibronectin. In addition, Serum-Exos enhanced tube formation in human umbilical vein endothelial cells and induced the expression of CD31 at both protein and messenger RNA levels. Collectively, our results suggest that Serum-Exos may facilitate the wound healing in diabetic mice by promoting angiogenesis and ECM formation, and show the potential application in treating diabetic wounds.

serum exosomes
angiogenesis
migration
extracellular matrix
diabetic healing


Reflections on a failed participatory workshop in Northern Chile: Negotiating boycotts, benefits, and the UN declaration on the rights of indigenous people.

Abstract: In this paper, we critically analyse our experiences of initiating participatory research in the challenging context of the Atacama Desert, Northern Chile. We use our experience of organising participatory workshops with Aymara and Quechua women community leaders to reflect on the politics of participation/non-participation, and explore these experiences in light of our multiple and overlapping positionalities as Chilean/British, male/female, white/mestizo. In the light of one workshop being entirely unsuccessful, we discuss the ways in which our empirical and methodological thinking has nevertheless been enriched by this experience. We situate the challenges we faced in relation to negotiating the tensions presented by debates on decolonising research from our positions within the neoliberal academy, exploring the questions raised by indigenous women activists' research 'refusal', and critically reflect upon the emotional responses this situation elicited in each of us. We argue for the importance of embracing such apparent fieldwork 'failures' and, recognising the resulting emotional swirl of panic, anxiety and inadequacy that they produce, emphasise these experiences as illustrative of the inherent tensions around decolonising research, as well as an often inevitable element of conducting research with marginalised communities involved in socio-environmental conflicts.

Jenkins|Katy|K|
Romero Toledo|Hugo|H|
Videla Oyarzo|Angélica|A|

Chile
Indigeneity
Participatory research
Decolonising research
Failure
Extractive industries
Gender


Global exponential stability and lag synchronization for delayed memristive fuzzy Cohen-Grossberg BAM neural networks with impulses.

Abstract: This paper investigates the stability and lag synchronization for memristor-based fuzzy Cohen-Grossberg bidirectional associative memory (BAM) neural networks with mixed delays (asynchronous time delays and continuously distributed delays) and impulses. By applying the inequality analysis technique, homeomorphism theory and some suitable Lyapunov-Krasovskii functionals, some new sufficient conditions for the uniqueness and global exponential stability of equilibrium point are established. Furthermore, we obtain several sufficient criteria concerning globally exponential lag synchronization for the proposed system based on the framework of Filippov solution, differential inclusion theory and control theory. In addition, some examples with numerical simulations are given to illustrate the feasibility and validity of obtained results.

Yang|Wengui|W|
Yu|Wenwu|W|
Cao|Jinde|J|
Alsaadi|Fuad E|FE|
Hayat|Tasawar|T|

D000465:Algorithms
D017143:Fuzzy Logic
D016571:Neural Networks, Computer
D013997:Time Factors

Globally exponential lag synchronization


Computed tomography and emergency department frequency in homeless patients with seizures.

Abstract: Seizures are a common presentation to emergency departments in homeless patients. Seizures and epilepsy are often poorly managed in homeless patients. In this retrospective study, conducted in a large urban university hospital; we compared the number emergency department presentations and associated head computed tomography studies in a cohort of 88 homeless patients with seizures to an age and gender-matched housed cohort of patients over a five-year period. We found that homeless patients had a significantly increased number of presentations to the emergency department and a significantly higher number of head computed tomography, with a resulting increase in radiation exposure.

Doran|Elisabeth M|EM|
Stanila|Raluca M|RM|
Healy|Laura A|LA|
Hynes|Sinead Fm|SF|
Doherty|Colin P|CP|

D004636:Emergency Service, Hospital
D006703:Homeless Persons
D006801:Humans
D012189:Retrospective Studies
D012640:Seizures
D014057:Tomography, X-Ray Computed

Computed tomography
Emergency department
Homelessness
Seizures
Epilepsy


Klp10A modulates the localization of centriole-associated proteins during Drosophila male gametogenesis.

Abstract: Mutations in Klp10A, a microtubule-depolymerising Kinesin-13, lead to overly long centrioles in Drosophila male germ cells. We demonstrated that the loss of Klp10A modifies the distribution of typical proteins involved in centriole assembly and function. In the absence of Klp10A the distribution of Drosophila pericentrin-like protein (Dplp), Sas-4 and Sak/Plk4 that are restricted in control testes to the proximal end of the centriole increase along the centriole length. Remarkably, the cartwheel is lacking or it appears abnormal in mutant centrioles, suggesting that this structure may spatially delimit protein localization. Moreover, the parent centrioles that in control cells have the same dimensions grow at different rates in mutant testes with the mother centrioles longer than the daughters. Daughter centrioles have often an ectopic position with respect to the proximal end of the mothers and failed to recruit Dplp.

Gottardo|Marco|M|
Callaini|Giuliano|G|
Riparbelli|Maria Giovanna|MG|

centriole-associated proteins
Drosophila
male gametogenesis
centrioles


Acute Transverse Myelitis in Children, Literature Review.

Abstract:
Objective
Acute transverse myelitis (ATM) is a rare inflammatory demyelinating disorder characterized by relatively acute onset of motor, sensory, and autonomic dysfunction. Children comprise 20% of total cases of ATM. In this review, we described the current literature on childhood ATM, focusing on the epidemiology, pathogenesis, clinical presentation, approach to diagnosis, differential diagnosis, treatment and outcome in the pediatric population.

Materials &Methods
We searched the related articles in electronic databases such as Scopus, EMBASE, Google Scholar, and PubMed. All study designs were included and the essential key words for searching were myelitis, acute transverse myelitis, childhood transverse myelitis, and acquired demyelinating syndromes.

Results
The related data focusing on the epidemiology, pathogenesis, clinical presentation, diagnostic approach and differential diagnosis, treatment and outcome of pediatric ATM were gathered and described.

Conclusion
ATM is a heterogeneous disorder in children with a broad spectrum of clinical presentation, etiology, and outcome. It may be the first presentation of relapsing acquired demyelinating syndromes and also must be distinguished from compressive and noninflamatory myelopathies. Correct diagnosis is crucial for treatment and prognosis.

Acute transverse myelitis
Myelitis
Childhood transverse myelitis
Acquired demyelinating syndromes


The long noncoding RNA myocardial infarction-associated transcript modulates the epithelial-mesenchymal transition in renal interstitial fibrosis.

Abstract:
AIMS
Renal interstitial fibrosis (RIF) is marked by the epithelial-mesenchymal transition (EMT) and excessive extracellular matrix deposition. The long noncoding RNA myocardial infarction-associated transcript (MIAT) facilitates RIF; however, the molecular mechanism of MIAT in RIF remains unclear. Here, we explored the possible underlying mechanisms through which MIAT modulates RIF.

MATERIALS AND METHODS
MIAT expression in human renal fibrotic tissues and unilateral ureteral obstruction (UUO) model mice was detected by qPCR. Transforming growth factor β1 (TGF-β1) was introduced to stimulate the EMT in human renal proximal tubular epithelial (HK-2) cells. CCK8, EdU, transwell and wound healing assays were employed to measure cell viability, proliferation, and migration respectively. RNA immunoprecipitation (RIP) assays and dual luciferase reporter assays were applied to determine the relationships among MIAT, miR-145, and EIF5A2.

KEY FINDINGS
MIAT was upregulated in human renal fibrotic tissues and UUO model mice compared with normal tissue adjacent to renal tumors and sham operation mice, respectively. MIAT knockdown reduced cell viability, proliferation, migration, and the EMT in HK-2 cells. Additionally, MIAT served as an endogenous sponge for miR-145 in the TGF-β1-induced-EMT in HK-2 cells, as demonstrated by dual luciferase reporter assays and RIP assays. EIF5A2 was confirmed as a target of miR-145, and MIAT knockdown suppressed EIF5A2 expression by sponging miR-145. Downregulation of EIF5A2 partly reversed induction of the EMT by miR-145 inhibitor transfection.

SIGNIFICANCE
MIAT promoted cell viability, proliferation, migration, and the EMT via regulation of the miR-145/EIF5A2 axis. These data established a potential therapy for RIF.

Wang|Zhaohui|Z| Zhang|Bo|B| Chen|Zhi|Z| He|Yao|Y| Ru|Feng|F| Liu|Peihua|P| Chen|Xiang|X|

D053773:Transforming Growth Factor beta1

Eukaryotic translation initiation factor 5A2


Oral Supplementation Using Gamma-Aminobutyric Acid and Whey Protein Improves Whole Body Fat-Free Mass in Men After Resistance Training.

Abstract:
Background
Oral gamma-aminobutyric acid (GABA) supplementation increases growth hormone (GH) serum levels and protein synthesis. Therefore, post-exercise supplementation using GABA and protein may help enhance training-induced muscle hypertrophy. We evaluated whether GABA with whey protein enhanced muscular hypertrophy in men after progressive resistance training.

Methods
Twenty-one healthy men (26 - 48 years) were randomized to receive whey protein (WP; 10 g) or whey protein + GABA (WP + GABA; 10 g + 100 mg) daily for 12 weeks. Both groups performed resistance training twice per week (three sets of 12 repetitions at 60% of maximal strength; leg press, leg extension, leg curl, chest press, and pull down). Body composition was assessed using dual-energy X-ray absorptiometry.

Results
In the WP + GABA group, resting plasma GH concentrations were significantly elevated at 4 and 8 weeks, compared to baseline. However, resting plasma GH concentrations in the WP group were only significantly elevated at 8 weeks. After 12 weeks, the WP + GABA group exhibited significantly greater increase in whole body fat-free mass than the WP group.

Conclusions
The GABA and whey protein combination was more effective for increasing whole body fat-free mass; daily GABA supplementation may help enhance exercise-induced muscle hypertrophy.

Sakashita|Maya|M| Nakamura|Utano|U| Horie|Noriko|N| Yokoyama|Yasuhiro|Y| Kim|Mujo|M| Fujita|Satoshi|S|

Supplementation
Gamma-aminobutyric acid
Whey protein
Protein
Resistance training


Tetrahydrophthalazinone Inhibitor of Phosphodiesterase with In Vitro Activity against Intracellular Trypanosomatids.

Abstract: The phosphodiesterase inhibitor tetrahydrophthalazinone NPD-008 was explored by phenotypic in vitro screening, target validation, and ultrastructural approaches against Trypanosoma cruzi NPD-008 displayed activity against different forms and strains of T. cruzi (50% effective concentration [EC50], 6.6 to 39.5 μM). NPD-008 increased cAMP levels of T. cruzi and its combination with benznidazole gave synergistic interaction. It was also moderately active against intracellular amastigotes of Leishmania amazonensis and Leishmania infantum, confirming a potential activity profile as an antitrypanosomatid drug candidate.

Soeiro|Maria de Nazaré Correia|MNC|0000-0003-0078-6106

D000981:Antiprotozoal Agents
D014355:Chagas Disease
D006801:Humans
D007894:Leishmania mexicana
D010727:Phosphoric Diester Hydrolases
D014349:Trypanosoma cruzi

in vitro activity
phosphodiesterase inhibitor
T. cruzi
cAMP
L. amazonensis
L. infantum


Epigenetic regulation of adipogenesis by histone-modifying enzymes.

Abstract: Many studies investigating the transcriptional control of adipogenesis have been published so far; recently the research is focusing on the role of epigenetic mechanisms in regulating the process of adipocyte development. Histone-modifying enzymes and the histone tails post-transcriptional modifications catalyzed by them, are fundamentally involved in the epigenetic regulation of adipogenesis. In our review, we will discuss recent advances in epigenomic regulation of adipogenesis with a focus on histone-modifying enzymes implicated in the various phases of adipocytes differentiation process from mesenchymal stem cells to mature adipocytes. Understanding adipogenesis, may provide new ways to treat obesity and related metabolic diseases.

Macchia|Paolo E|PE|
Nettore|Immacolata C|IC|
Franchini|Fabiana|F|
Santana-Viera|Laura|L|
Ungaro|Paola|P|0000-0001-5711-7187

epigenetics
adipogenesis
obesity
brown adipose tissue
histone modifications
white adipose tissue


Least-squares deconvolution of evoked potentials and sequence optimization for multiple stimuli under low-jitter conditions.

Abstract:
OBJECTIVE
Rapid presentation of stimuli in an evoked response paradigm can lead to overlap of multiple responses and consequently difficulties interpreting waveform morphology. This paper presents a deconvolution method allowing overlapping multiple responses to be disentangled.

METHODS
The deconvolution technique uses a least-squared error approach. A methodology is proposed to optimize the stimulus sequence associated with the deconvolution technique under low-jitter conditions. It controls the condition number of the matrices involved in recovering the responses. Simulations were performed using the proposed deconvolution technique.

RESULTS
Multiple overlapping responses can be recovered perfectly in noiseless conditions. In the presence of noise, the amount of error introduced by the technique can be controlled a priori by the condition number of the matrix associated with the used stimulus sequence. The simulation results indicate the need for a minimum amount of jitter, as well as a sufficient number of overlap combinations to obtain optimum results. An aperiodic model is recommended to improve reconstruction.

CONCLUSIONS
We propose a deconvolution technique allowing multiple overlapping responses to be extracted and a method of choosing the stimulus sequence optimal for response recovery.

SIGNIFICANCE
This technique may allow audiologists, psychologists, and electrophysiologists to optimize their experimental designs involving rapidly presented stimuli, and to recover evoked overlapping responses.

Bardy|Fabrice|F|
Dillon|Harvey|H|
Van Dun|Bram|B|

Multiple stimuli
Low-jitter
Least-squares (LS) deconvolution
Optimization of stimulus sequence


A low-cost transradial prosthesis controlled by the intention of muscular contraction.

Abstract: Persons with upper-limb amputations face severe problems due to a reduction in their ability to perform the activities of daily living. The prosthesis controlled by electromyography (EMG) or other signals from sensors, switches, accelerometers, etc., can somewhat regain the lost capability of such individuals. However, there are several issues with these prostheses, such as expensive cost, limited functionality, unnatural control, slow operating speed, complexity, heavyweight, large size, etc. This paper proposes an affordable transradial prosthesis, controlled by the muscular contractions from user intention. A surface EMG sensor was explicitly fabricated for capturing the muscle contraction information from the residual forearm of subjects with amputation. An under actuated 3D printed hand was developed with a prosthetic socket assembly to attach the remaining upper-limb of such subjects. The hand integrates an intuitive closed-loop control system that receives reference input from the designed sensor and feedback input from a force sensor installed at the thumb tip. The performance of the EMG sensor was compared with that of a traditional sensor in detecting muscle contractions from the subjects. The designed sensor showed a good correlation (r > 0.93) and a better signal-to-noise ratio (SNR) feature to the conventional sensor. Further, a successful trial of the developed hand prosthesis was made on five different subjects with transradial amputation. The users wearing the hand prototype were able to perform faster and delicate grasping of various objects. The implemented control system allowed the prosthesis users to control the grasp force of hand fingers with their intention of muscular contractions.

Transradial prosthesis
Electromyography
3D printing
Control system
Signal-to-noise ratio


Cytosolic DNA Sensing in Organismal Tumor Control.

Abstract: Besides constituting a first layer of defense against microbial challenges, the detection of cytosolic DNA is fundamental for mammalian organisms to control malignant transformation and tumor progression. The accumulation of DNA in the cytoplasm can initiate the proliferative inactivation (via cellular senescence) or elimination (via regulated cell death) of neoplastic cell precursors. Moreover, cytosolic DNA sensing is intimately connected to the secretion of cytokines that support innate and adaptive antitumor immunity. Here, we discuss the molecular mechanisms whereby cytosolic DNA enables cell-intrinsic and -extrinsic oncosuppression, and their relevance for the development of novel therapeutic approaches that reinstate anticancer immunosurveillance.

Vanpouille-Box|Claire|C|
Demaria|Sandra|S|
Formenti|Silvia C|SC|
Galluzzi|Lorenzo|L|

CGAS
STING
ZBP1
apoptosis
inflammasome
micronuclei
mtDNA
necroptosis
pyroptosis
type I interferon


Beta-Hemolytic Streptococcal Infective Endocarditis: Characteristics and Outcomes From a Large, Multinational Cohort.

Abstract:
Background
Beta-hemolytic streptococci (BHS) are an uncommon cause of infective endocarditis (IE). The aim of this study was to describe the clinical features and outcomes of patients with BHS IE in a large multinational cohort and compare them with patients with viridans streptococcal IE.

Methods
The International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS) is a large multinational database that recruited patients with IE prospectively using a standardized data set. Sixty-four sites in 28 countries reported patients prospectively using a standard case report form developed by ICE collaborators.

Results
Among 1336 definite cases of streptococcal IE, 823 were caused by VGS and 147 by BHS. Patients with BHS IE had a lower prevalence of native valve (P < .005) and congenital heart disease predisposition (P = .002), but higher prevalence of implantable cardiac device predisposition (P < .005). Clinically, they were more likely to present acutely (P < .005) and with fever (P = .024). BHS IE was more likely to be complicated by stroke and other systemic emboli (P < .005). The overall in-hospital mortality of BHS IE was significantly higher than that of VGS IE (P = .001). In univariate analysis, variables associated with in-hospital mortality for BHS IE were age (odds ratio [OR], 1.044; P = .004), prosthetic valve IE (OR, 3.029; P = .022), congestive heart failure (OR, 2.513; P = .034), and stroke (OR, 3.198; P = .009).

Conclusions
BHS IE is characterized by an acute presentation and higher rate of stroke, systemic emboli, and in-hospital mortality than VGS IE. Implantable cardiac devices as a predisposing factor were more often found in BHS IE compared with VGS IE.

Fernández Hidalgo|Núria|N|
Gharamti|Amal A|AA|0000-0002-6175-299X
Aznar|María Luisa|ML|
Almirante|Benito|B|
Yasmin|Mohamad|M|
Fortes|Claudio Querido|CQ|
Plesiat|Patrick|P|
Doco-Lecompte|Thanh|T|
Rizk|Hussein|H|
Wray|Dannah|D|
Lamas|Cristiane|C|
Durante-Mangoni|Emanuele|E|
Tattevin|Pierre|P|
Snygg-Martin|Ulrika|U|
Hannan|Margaret M|MM|
Chu|Vivian H|VH|
Kanafani|Zeina A|ZA|


A Novel Dopingless Fin-Shaped SiGe Channel TFET with Improved Performance.

Abstract: In this paper, a dopingless fin-shaped SiGe channel TFET (DF-TFET) is proposed and studied. To form a high-efficiency dopingless line tunneling junction, a fin-shaped SiGe channel and a gate/source overlap are induced. Through these methods, the DF-TFET with high on-state current, switching ratio of 12 orders of magnitude and no obvious ambipolar effect can be obtained. High κ material stack gate dielectric is induced to improve the off-state leakage, interface characteristics and the reliability of DF-TFET. Moreover, by using the dopingless channel and fin structure, the difficulties of doping process and asymmetric gate overlap formation can be resolved. As a result, the structure of DF-TFET can possess good manufacture applicability and remarkably reduce footprint. The physical mechanism of device and the effect of parameters on performance are studied in this work. Finally, on-state current (ION) of 58.8 μA/μm, minimum subthreshold swing of 2.8 mV/dec (SSmin), average subthreshold swing (SSavg) of 18.2 mV/dec can be obtained. With improved capacitance characteristics, cutoff frequency of 5.04 GHz and gain bandwidth product of 1.29 GHz can be obtained. With improved performance and robustness, DF-TFET can be a very attractive candidate for ultra-low-power applications.

Dopingless
Line tunneling junction
Fin-shaped channel
Stack gate oxide
Tunnel FET


Kinetics and isotherm analysis of 2,4-dichlorophenoxyl acetic acid adsorption onto soil components under oxic and anoxic conditions.

Abstract: 2,4-dichlorophenoxyl acetic acid (2,4-D, pKa = 2.8) is used extensively as a herbicide in agricultural practices. Its sorption behavior on both untreated and soils treated to significantly remove specific components (organic and iron and manganese [Fe-Mn] oxides and hydroxides phases) was investigated under oxic and anoxic conditions. The chemical and structural heterogeneity of the soil components were characterized by elemental analysis and X-ray diffraction (XRD). The coexistence of the various components seems to either mask sorption sites on the untreated soil surfaces or inhibit interlayer diffusion of 2,4-D. All sorption data conform to the Freundlich description and a pseudo-second-order kinetic model. There was a strong positive correlation between sorption capacity K(d), and surface area (r(2) ≤ 0.704), but a negative correlation was uncovered with both pH and organic carbon (r(2) ≤ -0.860). The results indicate that 2,4-D is preferably sorbed under oxic rather than anoxic conditions and it is greater on soils containing a high Fe content. There was incomplete 2,4-D sorption reversibility, with desorption occurring more rapidly under anoxic conditions. The study suggests that stimulation of Fe III reduction could be used for the bioremediation of a 2,4-D-contaminated site.

Ololade|Isaac A|IA|
Alomaja|Folasade|F|
Oladoja|Nurudeen A|NA|
Ololade|Oluwaranti O|OO|
Oloye|Femi F|FF|

soil components
herbicide
sorption
desorption
2
4-dichlorophenoxyl acetic acid
organic matter


Risk factors affecting obesity development in high school students: a community based case-control study.

Abstract:
Aim
Obesity which is described as a "global epidemics" and qualified as "excessive accumulation of fat impairing health" by the World Health Organization is an important public health problem affecting children and adolescents as well as adults. The aim of this study was to determine the factors that affected obesity in high school students in a city center.

Material and Methods
A total of 386 students including 193 subjects and 193 controls were included in this case-control study. The data were collected by applying a questionnaire which questioned sociodemographic properties, eating and physical activity behaviors and factors which were considered to have an impact on body weight. Descriptive statistics were evaluated using chi-square and logistic regression analysis. A p value of <0.05 was considered statistically significant.

Results
In univariate analysis, presence of an obese person in the family/neighborhood, way of transportation to school, thoughts and wish of best friend of the same sex related to body weight and desire for weight loss were defined as variables which were associated with obesity. In multivariate regression analysis, it was found that presence of an obese person in the family/neighborhood, transportation to school by vehicle and having a best friend of the same sex who wanted the subject to stay at the same weight could be predictors of obesity. In the obese group, regarding oneself as obese and desire to lose weight were more common.

Conclusion
In this study, it was found that presence of an obese person in the family/neighborhood, transportation to school by vehicle and having a best friend of the same sex who wanted the subject to stay at the same weight were significant risk factors in terms of obesity. However, levels of perceiving oneself as obese and desire to lose weight were found to be higher in the obese group. Consumption of unhealthy food in the home environment should be prevented by performing awareness studies for parents. In addition, physical exercises performed together by family members will be helpful for adolescents in terms of developing healthy lifestyle behaviors.


Synergistic effect of static magnetic field and HA-Fe3O4 magnetic composites on viability of S. aureus and E. coli bacteria.

Abstract: In addressing the issue of prosthetic infection, this work demonstrated the synergistic effect of the application of static magnetic field (SMF) and ferrimagnetic substrate properties on the bactericidal property in vitro. This aspect was studied using hydroxyapatite (HA)-xFe3 O4 (x=10, 20, and 40 wt.%) substrates, which have different saturation magnetization properties. During bacteria culture experiments, 100 mT SMF was applied to growth medium (with HA-xFe3 O4 substrate) in vitro for 30, 120, and 240 min. A combination of MTT assay, membrane rupture assays, live/dead assay, and fluorescence microscopic analysis showed that the bactericidal effect of SMF increases with the exposure duration as well as increasing Fe3 O4 content in biomaterial substrates. Importantly, the synergistic bactericidal effect was found to be independent of bacterial cell type, as similar qualitative trend is measured with both gram negative Escherichia coli (E. coli) and gram positive Staphylococcus aureus (S. aureus) strains. The reduction in E. coli viability was 83% higher on HA-40 Wt % Fe3 O4 composite after 4 h exposure to SMF as compared to nonexposed control. Interestingly, any statistically significant difference in ROS was not observed in bacterial growth medium after magnetic field exposure, indicating the absence of ROS enhancement due to magnetic field. Overall, this study illustrates significant role being played by magnetic substrate compositions towards bactericidal property than by magnetic field exposure alone.

D000900:Anti-Bacterial Agents
D001422:Bacterial Adhesion
D001672:Biocompatible Materials
D002462:Cell Membrane
D002463:Cell Membrane Permeability
D004396:Coloring Agents
D017886:Durapatite
D004926:Escherichia coli
D005290:Ferric Compounds
D060526:Magnetic Fields
D008855:Microscopy, Electron, Scanning
D008856:Microscopy, Fluorescence
D017382:Reactive Oxygen Species
D013211:Staphylococcus aureus
D013778:Tetrazolium Salts
D013844:Thiazoles

static magnetic field
bactericidal effect
magnetic biocomposites


Minimally invasive approach to non-missile penetrating spinal injury with resultant retained foreign body: A case report and review of the literature.

Abstract: Non- missile penetrating spinal injury (NMPSI) is a rare entity in North America and as a result there is no clear treatment paradigm. According to the literature, NMPSI causes serious acute neurological deficits and can also lead to devastating delayed complications in cases of untreated retained foreign bodies (RFB). In this report we present an acute case of NMPSI to the thoracic spine resulting in RFB treated by operative removal using minimally invasive fluoroscopic technique. While in prior published cases of NMPSI operative intervention was accomplished through laminectomy, our case presents an alternative, less invasive approach which may results in shorter recovery time. We also review the literature on NMPSI, including reports on both acute cases and chronic presentation due to RFBs. Based on this review, we conclude that NMPSI associated with RFB should be managed with operative intervention.

Moldovan|Krisztina|K|
Telfeian|Albert E|AE|
Fridley|Jared S|JS|
Gokaslan|Ziya L|ZL|
Aghion|Daniel|D|
Oyelese|Adetokunbo A|AA|

D019060:Minimally Invasive Surgical Procedures

Retained foreign body
Minimally invasive spine surgery
Non-missile penetrating spine injury
Spinal cord injury
Spinal stab wound


Effect of gender and adiposity on in vivo vascular function in young African Americans.

Abstract: The relationship between obesity and high blood pressure is not as strong among African Americans (AA) as compared to Caucasians. We designed the current study to determine the effect of adiposity on vascular endothelial function (a harbinger of hypertension) among young healthy AA without additional cardiovascular disease risk factors. A total of 108 AA subjects (46 women) between the ages of 18 and 45 years were recruited. All the subjects were normotensive, nonsmokers, and normoglycemic. Anthropometric and cardiovascular disease risk factor measurements (lipid, insulin resistance, and inflammatory markers) were obtained. Vascular endothelial function was measured by brachial artery flow-mediated dilation (FMD). Adiposity distribution was measured by using magnetic resonance imaging scan. There were no gender differences in age and levels of blood pressure, lipids, insulin resistance, and inflammatory markers. Women had higher total body fat percentage and higher peripheral adiposity compared to men. We observed that total and central adiposity did not correlate significantly with brachial artery FMD in women (r = -0.12 and r = 0.23, respectively; P = NS). However, in men, waist circumference was positively associated with FMD (r = 0.3, P ≤ .05). Hyperemic flow was negatively correlated significantly with total and central adiposity in men (r = -0.34 and r = -0.48, respectively; P < .05), but not in women (r = -0.26 and r = 0.03, respectively; P = NS). Our study suggests that increased adiposity may pose greater risk to AA men compared to AA women by adversely affecting resistance vessel function (as measured by hyperemic flow). Larger studies are necessary to validate these findings.

Dass|Namrata|N|
Kilakkathi|Sindhu|S|
Obi|Brittaney|B|
Moosreiner|Andrea|A|
Krishnaswami|Shanthi|S|
Widlansky|Michael E|ME|
Kidambi|Srividya|S|

D050154:Adiposity
D000328:Adult
D001741:African Americans
D001783:Blood Flow Velocity
D001794:Blood Pressure
D015992:Body Mass Index
D001916:Brachial Artery
D004730:Endothelium, Vascular
D005260:Female
D006801:Humans
D006973:Hypertension
D008279:Magnetic Resonance Imaging
D008297:Male
D012307:Risk Factors
D012737:Sex Factors
D014481:United States
D014655:Vascular Resistance
D055105:Waist Circumference

obesity
high blood pressure
risk factors
women
Clinical studies
race and ethnicity