CE-MS for anionic metabolic profiling: An overview of methodological developments.

Abstract: The efficient profiling of highly polar and charged metabolites in biological samples remains a huge analytical challenge in metabolomics. Over the last decade, new analytical techniques have been developed for the selective and sensitive analysis of polar ionogenic compounds in various matrices. Still, the analysis of such compounds, notably for acidic ionogenic metabolites, remains a challenging endeavor, even more when the available sample size becomes an issue for the total analytical workflow. In this paper, we give an overview of the possibilities of capillary electrophoresis-mass spectrometry (CE-MS) for anionic metabolic profiling by focusing on main methodological developments. Attention is paid to the development of improved separation conditions and new interfacing designs in CE-MS for anionic metabolic profiling. A complete overview of all CE-MS-based methods developed for this purpose is provided in table format (Table 1) which includes information on sample type, separation conditions, mass analyzer and limits of detection (LODs). Selected applications are discussed to show the utility of CE-MS for anionic metabolic profiling, especially for small-volume biological samples. On the basis of the examination of the reported literature in this specific field, we conclude that there is still room for the design of a highly sensitive and reliable CE-MS method for anionic metabolic profiling. A rigorous validation and the availability of standard operating procedures would be highly favorable in order to make CE-MS an alternative, viable analytical technique for metabolomics.

van Mever|Marlien|M|
Hankemeier|Thomas|T|
Ramautar|Rawi|R|0000-0002-1673-4848

Anionic metabolic profiling
Methodological Developments
Metabolomics
Applications
Mass Spectrometry


Assessment of the mechanical properties of the muscle-tendon unit by supersonic shear wave imaging elastography: a review.

Abstract: This review aimed to describe the state of the art in muscle-tendon unit (MTU) assessment by supersonic shear wave imaging (SSI) elastography in states of muscle contraction and stretching, during aging, and in response to injury and therapeutic interventions. A consensus exists that MTU elasticity increases during passive stretching or contraction, and decreases after static stretching, electrostimulation, massage, and dry needling. There is currently no agreement regarding changes in the MTU due to aging and injury. Currently, the application of SSI for the purpose of diagnosis, rehabilitation, and physical training remains limited by a number of issues, including the lack of normative value ranges, the lack of consensus regarding the appropriate terminology, and an inadequate understanding of the main technical limitations of this novel technology.

Lima|Kelly Mônica Marinho E|KMME|0000-0002-0589-9452

Costa Júnior|José Francisco Silva|JFS|0000-0002-6526-2760

Pereira|Wagner Coelho de Albuquerque|WCA|0000-0001-5880-3242

Biomechanics
Elastic modulus
Elasticity imaging techniques
Shear modulus
Supersonic shearwave imaging
Ultrasound


Poly(butylene succinate-co-ε-caprolactone) Copolyesters: Enzymatic Synthesis in Bulk and Thermal Properties.

Abstract: This work explores for the first time the enzymatic synthesis of poly(butylene-co-ε-caprolactone) (PBSCL) copolyesters in bulk using commercially available monomers (dimethyl succinate (DMS), 1,4-butanediol (BD), and ε-caprolactone (CL)). A preliminary kinetic study was carried out which demonstrated the higher reactivity of DMS over CL in the condensation/ring opening polymerization reaction, catalyzed by Candida antarctica lipase B. PBSCL copolyesters were obtained with high molecular weights and a random microstructure, as determined by 13C NMR. They were thermally stable up to 300 °C, with thermal stability increasing with the content of CL in the copolyester. All of them were semicrystalline, with melting temperatures and enthalpies decreasing up to the eutectic point observed at intermediate compositions, and glass transition temperatures decreasing with the content of CL in the copolyester. The use of CALB provided copolyesters free from toxic metallic catalyst, which is very useful if the polymer is intended to be used for biomedical applications.


Development of Promitil®, a lipidic prodrug of mitomycin c in PEGylated liposomes: From bench to bedside.

Abstract: Several liposome products have been approved for the treatment of cancer. In all of them, the active agents are encapsulated in the liposome water phase passively or by transmembrane ion gradients. An alternative approach in liposomal drug delivery consists of chemically modifying drugs to form lipophilic prodrugs with strong association to the liposomal bilayer. Based on this approach, we synthesized a mitomycin c-derived lipidic prodrug (MLP) which is entrapped in the bilayer of PEGylated liposomes (PL-MLP, Promitil®), and activated by thiolytic cleavage. PL-MLP is stable in plasma with thiolytic activation of MLP occurring exclusively in tissues and is more effective and less toxic than conventional chemotherapy in various tumor models. PL-MLP has completed phase I clinical development where it has shown a favorable safety profile and a 3-fold reduction in toxicity as compared to free mitomycin c. Clinical and pharmacokinetic studies in patients with advanced colo-rectal carcinoma have indicated a significant rate of disease stabilization (39%) in this chemo-refractory population and significant prolongation of median survival in patients attaining stable disease (13.9 months) versus progressive disease patients (6.35 months). The pharmacokinetics of MLP was typically stealth with long T½ (~1 day), slow clearance and small volume of distribution. Interestingly, a longer T½, and slower clearance were both correlated with disease stabilization and longer survival. This association of pharmacokinetic parameters with patient outcome suggests that arrest of tumor growth is related to the enhanced tumor localization of long-circulating liposomes and highlights the importance of personalized pharmacokinetic evaluation in the clinical use of nanomedicines. Another important area where PL-MLP may have an added value is in chemoradiotherapy, where it has shown a strong radiosensitizing effect in animal models based on a unique mechanism of enhanced prodrug activation and encouraging results in early human testing.

Gabizon|Alberto|A| Shmeeda|Hilary|H| Tahover|Esther|E| Kornev|Gleb|G| Patil|Yogita|Y| Amitay|Yasmine|Y| Ohana|Patricia|P| Sapir|Eli|E| Zalipsky|Samuel|S|

Prodrug
Mitomycin c
Liposome
Cancer
Thiolytic cleavage
Chemotherapy
Stealth
Nanomedicine
Radiosensitization
EPR
Phase 1


Scope of practice of optometrists working in the UK Hospital Eye Service: a national survey.

Abstract:
PURPOSE
The role of the optometrist in the Hospital Eye Service (HES) has undergone significant development in recent years to include extended areas of clinical practice more traditionally undertaken by ophthalmologists, commensurate with a growing demand for increased capacity in ophthalmic services. In this report, we present the findings from a national survey of the scope of practice of optometrists working in the UK HES.

METHODS
A survey was designed to incorporate questions on the provision of core services before seeking detailed information on the scope of practice within extended roles to include: ophthalmic sub-specialist areas where optometrists currently practice; the undertaking of specific procedures within these services; the relative autonomy of practice within these extended roles; and the training and accreditation requirements for working within extended roles. SurveyMonkey was used to disseminate the survey to the head of optometry in 79 HES units throughout the UK.

RESULTS
Responses were received from 70 of the 79 (89%) survey invitations. A substantial majority of respondents (N = 67/70, 96%) indicated that optometrists undertook extended roles. Glaucoma is the leading extended role service provided by optometrists (92% of respondents providing extended role services), with roles in macula (71%), medical retina/diabetes (67%), cataract (55%) and corneal services (55%) also being relatively common. A wide variety of clinical procedures or interventions are undertaken as part of these services, which for a small number of optometrists now also includes the undertaking of specific laser procedures. There is evidence for a significant degree of autonomy within these extended roles. The primary mode of training is an 'apprentice' model, incorporating sessions worked under supervision in ophthalmology clinics. Methods of accreditation for optometric participation in extended role services are varied.

CONCLUSIONS
While optometrists working within the UK HES continue to undertake the traditional clinical roles of refraction, clinically necessary contact lenses, and low vision rehabilitation, it is clear that these professionals now undertake a wide range of extended clinical roles, with a transformed scope of practice now incorporating diverse roles traditionally undertaken by medical practitioners.

Harper|Robert|R| Creer|Rosalind|R| Jackson|Jonathan|J| Ehrlich|Daniel|D| Tompkin|Andrew|A| Bowen|Michael|M| Tromans|Cindy|C|

scope of practice
Hospital Eye Service
extended roles
optometry


Temporary Nerve Block at Selected Digits Revealed Hand Motor Deficits in Grasping Tasks.

Abstract: Peripheral sensory feedback plays a crucial role in ensuring correct motor execution throughout hand grasp control. Previous studies utilized local anesthesia to deprive somatosensory feedback in the digits or hand, observations included sensorimotor deficits at both corticospinal and peripheral levels. However, the questions of how the disturbed and intact sensory input integrate and interact with each other to assist the motor program execution, and whether the motor coordination based on motor output variability between affected and non-affected elements (e.g., digits) becomes interfered by the local sensory deficiency, have not been answered. The current study aims to investigate the effect of peripheral deafferentation through digital nerve blocks at selective digits on motor performance and motor coordination in grasp control. Our results suggested that the absence of somatosensory information induced motor deficits in hand grasp control, as evidenced by reduced maximal force production ability in both local and non-local digits, impairment of force and moment control during object lift and hold, and attenuated motor synergies in stabilizing task performance variables, namely the tangential force and moment of force. These findings implied that individual sensory input is shared across all the digits and the disturbed signal from local sensory channel(s) has a more comprehensive impact on the process of the motor output execution in the sensorimotor integration process. Additionally, a feedback control mechanism with a sensation-based component resides in the formation process for the motor covariation structure.

Carteron|Aude|A| McPartlan|Kerry|K| Gioeli|Christina|C| Reid|Emily|E| Turturro|Matt|M| Hahn|Barry|B| Benson|Cynthia|C| Zhang|Wei|W|

hand
anesthesia
motor coordination
force
moment
motor synergy
anticipatory control


Infant feeding: beyond the nutritional aspects.

Abstract:
OBJECTIVE
To draw attention to the importance of interaction between caregiver and child during feeding and the influence of parenting style on dietary habit formation.

SOURCE OF DATA
A search was performed in the PubMed and Scopus databases for articles addressing responsive feeding; the articles considered most relevant by the authors were selected.

SYNTHESIS OF DATA
The way children are fed is decisive for the formation of their eating habits, especially the strategies that parents/caregivers use to stimulate feeding. In this context, responsive feeding has been emphasized, with the key principles: feed the infant directly and assist older children when they already eat on their own; feed them slowly and patiently, and encourage children to eat but do not force them; if the child refuses many types of foods, experiment with different food combinations, tastes, textures, and methods of encouragement; minimize distractions during meals; and make the meals an opportunity for learning and love, talking to the child during feeding and maintaining eye contact. It is the caregiver's responsibility to be sensitive to the child's signs and alleviate tensions during feeding, and make feeding time pleasurable; whereas it is the child's role to clearly express signs of hunger and satiety and be receptive to the caregiver.

CONCLUSION
Responsive feeding is very important in dietary habit formation and should be encouraged by health professionals in their advice to families.

Silva|Giselia A P|GA|
Costa|Karla A O|KA|
Giugliani|Elsa R J|ER|

D007227:Infant Nutritional Physiological Phenomena

Infant feeding
Parenting styles
Responsive feeding
Alimentação infantil
Alimentação responsiva
Estilos parentais
Parental feedings practices
Práticas alimentares parentais


Systematic review of Real-World effectiveness of eribulin for locally advanced or metastatic breast cancer.

Abstract:
BACKGROUND
Eribulin mesylate (eribulin) is indicated for patients with metastatic breast cancer (MBC) who have previously received at least two chemotherapies in the US and for patients with locally advanced breast cancer (LABC) or MBC who have progressed after at least one chemotherapy in the European Union (EU). In both indications, prior therapy should include an anthracycline and a taxane in adjuvant or metastatic setting. Numerous studies evaluated eribulin in real-world (RW) breast cancer populations to reinforce its consistent effectiveness beyond registration randomized controlled trials (RCTs) that reported median overall survival (OS) of 13.1 and 15.9 months. In this systematic literature review (SLR), we summarize the cumulative evidence on eribulin's RW effectiveness in LABC/MBC.

METHODS
We searched through Medline/PubMed and Embase databases between 2012 and 2019 for articles reporting RW eribulin use in the second- or third-line or later LABC/MBC setting. Because eribulin showed greatest OS benefits in triple negative breast cancer (TNBC) in RCTs, we also reviewed this tumor subtype. OS and progression-free survival (PFS) were the effectiveness outcomes of interest.

RESULTS
Overall, 34 journal articles or abstracts met the selection criteria. Median OS ranged between 6.9 and 28.0 months; median PFS varied from 2.3 to 14.7 months. Eight studies reported OS outcomes for TNBC patients, and median OS ranged between 3.0 and 23.0 months.

CONCLUSION
The SLR showed high variability in OS and to a lesser extent in PFS associated with eribulin use in RW setting. Despite heterogeneity in line of use and patient subtypes, this SLR supports effectiveness of eribulin for LABC/MBC in clinical practice.

D064726:Triple Negative Breast Neoplasms

systematic review
real-world
effectiveness
eribulin
metastatic breast cancer
chemotherapy
Advanced breast cancer
overall survival
progression-free survival
triple-negative breast cancer


Fluid management: An update for perioperative practitioners.

Abstract: An interprofessional team approach is required to achieve optimum fluid balance for patients during the perioperative period. Incorrect management of fluid assessment and monitoring is associated with adverse outcomes. The scientific understanding of perioperative fluid balance has improved over recent years leading to changes in clinical practice with regard to volume and choice of intravenous fluid. It is important that perioperative practitioners have an understanding of intravenous fluid, fluid compartmentalisation, fluid mechanics and intravascular fluid control mechanisms. Optimum fluid status not only shortens hospital stay but also reduces the incidence of postoperative nausea and vomiting and complication profiles. This article aims to provide perioperative practitioners with a comprehensive overview of fluid management. It will cover important issues surrounding physiological control of fluid balance, choice of intravenous fluid therapy, methods to monitor intravascular volume and factors which influence delivery.

D020250:Postoperative Nausea and Vomiting

Fluid management
Perioperative practitioners
Intravenous fluids
Physiology
Perioperative outcome


Synaptic pattern of nicotinic acetylcholine receptor α7 and β2 subunits on the direction-selective retinal ganglion cells in the postnatal mouse retina.

Abstract: Direction-selective retinal ganglion cells (DS RGCs) respond strongly to a stimulus that moves in their preferred direction, but respond weakly or do not respond to a stimulus that moves in the opposite or null direction. DS RGCs are sensitive to acetylcholine, and starburst amacrine cells (SACs) make cholinergic synapses on DS RGCs. We studied the distributions of nicotinic acetylcholine receptor (nAChR) α7 and β2 subunits on the dendritic arbors of DS RGCs to search for anisotropies that contribute to the directional preferences of DS RGCs. The DS RGCs from the retinas of postnatal mice (postnatal day P5, P10, and P15) were injected with Lucifer yellow, and injected cells were identified by their dendritic morphology. The dendrites of the DS RGCs were labeled with antibodies for either the nAChR α7 or β2 subunit as well as postsynaptic density protein-95 (PSD-95), visualized by confocal microscopy, and reconstructed from high-resolution confocal images. The distribution of nAChR subunits on the dendritic arbors in both the ON and OFF layers of the RGCs revealed an asymmetrical pattern on early postnatal day P5. However, the distributions of nAChR subunits on the dendritic arbors were not asymmetric on P10 and P15. Our results therefore provide anatomical and developmental evidence suggesting that the nAChR α7 and β2 subunits may involve in the early direction-selectivity formation of DS RGCs in the mouse retina.

D064569:alpha7 Nicotinic Acetylcholine Receptor

nicotinic acetylcholine receptor
direction-selectivity
retinal ganglion cell
starburst amacrine cells
immunocytochemistry
living cell injection


Schizophrenia and Hereditary Polyneuropathy: PMP22 Deletion as a Common Pathophysiological Link?

Abstract: Background: Schizophrenic disorders are common and debilitating due to their symptoms, which can include delusions, hallucinations, and other negative symptoms. Organic forms can result from various cerebral disorders. In this paper, we discuss a potential association between schizophrenia and hereditary polyneuropathies (PNPs). Case presentation: We present the case of a 55-year-old female patient with chronically paranoid-hallucinatory schizophrenia, severe cognitive deficits since the age of 30, and comorbid repeated focal pressure neuropathies beginning at age 20. At the age of 35, genetic testing revealed a deletion on chromosome 17p12 covering the peripheral myelin protein 22 gene (PMP22), which led to the diagnosis of hereditary neuropathy with liability to pressure palsy (HNPP). Cerebral magnetic resonance imaging showed internal atrophy, magnetic resonance spectroscopy found alteration of the glutamate and myo-inositol levels in the anterior cingulate cortex, neuropsychological testing showed deficits in working memory and psychomotor speed, and electrophysiological testing detected signs of sensorimotor demyelinating PNP (accentuated in the legs). Conclusion: There may be an association between schizophrenia and HNPP. In observational studies, the deletion of interest (chromosome 17p12) was nearly 10 times more common in schizophreniform patients than in controls. This potential association could be pathophysiologically explained by the role of PMP22, which is mainly expressed in the peripheral nervous system. However, PMP22 mRNA and protein can also be found in the brain. PMP22 seems to play an important role in regulating cell growth and myelination, functions that are disturbed in schizophrenia. Such a connection obviously cannot be clarified on the basis of one case. Future studies should analyze whether patients with HNPP exhibit increased rates of psychotic disorders, and patients with schizophrenia and repeated focal pressure neuropathies should be examined for the PMP22 mutation. Alternatively, the co-occurrence of schizophrenia and HNPP could be coincidental.

Endres|Dominique|D|
Maier|Simon J|SJ|
Ziegler|Christiane|C|
Nickel|Kathrin|K|
Riering|Anne N|AN|
Berger|Benjamin|B|
Lambeck|Johann|J|
Fritz|Miriam|M|
Gläser|Birgitta|B|
Stock|Friedrich|F|
Dacko|Michael|M|
Lange|Thomas|T|
Mader|Irina|I|
Domschke|Katharina|K|
Tebartz van Elst|Ludger|L|


Dimeric prodrug-based nanomedicines for cancer therapy.

Abstract: With the rapid development of conjugation chemistry and biomedical nanotechnology, prodrug-based nanosystems (PNS) have emerged as promising drug delivery nanoplatforms. Dimeric prodrug, as an emerging branch of prodrug, has been widely investigated by covalently conjugating two same or different drug molecules. In recent years, great progress has been made in dimeric prodrug-based nanosystems (DPNS) for cancer therapy. Many advantages offered by DPNS have significantly facilitated the delivery efficiency of anticancer drugs, such as high drug loading capacity, favorable pharmacokinetics, tumor stimuli-sensitive drug release and facile combination theranostics. Given the rapid developments in this field, we here outline the latest updates of DPNS in cancer treatment, focusing on dimeric prodrug-encapsulated nanosystems, dimeric prodrug-nanoassemblies and tumor stimuli-responsive DPNS. Moreover, the design principle, advantages and challenges of DPNS for clinical cancer therapy are also highlighted.

Li|Shumeng|S| Shan|Xinzhu|X| Wang|Yuequan|Y| Chen|Qin|Q| Sun|Jin|J| He|Zhonggui|Z| Sun|Bingjun|B| Luo|Cong|C|

Nanomedicine
Cancer therapy
Conjugation chemistry
Biomedical nanotechnology
Dimeric prodrug


Associations between digit ratio (2D4D), mood, and autonomic stress response in healthy men.

Abstract: The ratio between the length of the second (index) and the fourth (ring) finger (2D4D) is a putative biomarker of prenatal testosterone (T) exposure, with higher exposure leading to a smaller ratio. 2D4D has further been linked to mental and somatic disorders. Healthy male Swiss recruits (N = 245; Mage = 20.30 years) underwent a psychosocial stress test. Mood and salivary alpha-amylase (sAA) were assessed before and after the stress test, while heart rate (HR) and heart rate variability (HRV) were measured continuously. Additionally, 2D4D (right: R2D4D; left: L2D4D) was determined and divided into quartile groups. Correlation analysis showed no associations between R/L2D4D and outcome measures. Comparing calculated quartiles for R2D4D, subjects in the lowest R2D4D quartile expressed trendwise (p < 0.10) lower positive and higher negative affect, significantly elevated sAA activity (p < 0.05), but no HR and HRV differences at baseline as compared to subjects in the upper three quartiles. With regard to acute stress, subjects in the lowest as compared to subjects in the upper three R2D4D quartiles showed a higher increase of negative affect and a stronger cardiac response (p < 0.05), but no alterations in positive affect and sAA activity. Young healthy men in the lowest R2D4D quartile revealed a more negative affect and increased physiological activity at baseline and in response to acute stress. An exposure to high levels of prenatal T might constitute a risk factor potentially increasing vulnerability to stress-related disorders in men.

Walther|A|A|0000-0003-4516-1783
Breidenstein|J|J|
Bösch|M|M|
Sefidan|S|S|
Ehlert|U|U|
Annen|H|H|
Wyss|T|T|
La Marca|R|R|

D011297:Prenatal Exposure Delayed Effects

2D4D
salivary alpha-amylase
heart rate
heart rate variability
TSST-G
prenatal testosterone exposure


Studying the Evolution of the Vertebrate Circadian Clock: The Power of Fish as Comparative Models.

Abstract: The utility of any model species cannot be judged solely in terms of the tools and approaches it provides for genetic analysis. A fundamental consideration is also how its biology has been shaped by the environment and the ecological niche which it occupies. By comparing different species occupying very different habitats we can learn how molecular and cellular mechanisms change during evolution in order to optimally adapt to their environment. Such knowledge is as important as understanding how these mechanisms work. This is illustrated by the use of fish models for studying the function and evolution of the circadian clock. In this review we outline our current understanding of how fish clocks sense and respond to light and explain how this differs fundamentally from the situation with mammalian clocks. In addition, we present results from comparative studies involving two species of blind cavefish, Astyanax mexicanus and Phreatichthys andruzzii. This work reveals the consequences of evolution in perpetual darkness for the circadian clock and its regulation by light as well as for other mechanisms such as DNA repair, sleep, and metabolism which directly or indirectly are affected by regular exposure to sunlight. Major differences in the cave habitats inhabited by these two cavefish species have a clear impact on shaping the molecular and cellular adaptations to life in complete darkness.

Foulkes|N S|NS|
Whitmore|D|D|
Vallone|D|D|
Bertolucci|C|C|

Evolution
Circadian clock
Comparative models
Light
Cavefish
Sleep
Metabolism
Opsins
Photoreceptors


The apoplastic antioxidant system and altered cell wall dynamics influence mesophyll conductance and the rate of photosynthesis.

Abstract: Mesophyll conductance (gm ), the diffusion of CO2 from substomatal cavities to the carboxylation sites in the chloroplasts, is a highly complex trait driving photosynthesis (net CO2 assimilation, AN ). However, little is known concerning the mechanisms by which it is dynamically regulated. The apoplast is considered as a 'key information bridge' between the environment and cells. Interestingly, most of the environmental constraints affecting gm also cause apoplastic responses, cell wall (CW) alterations and metabolic rearrangements. Since CW thickness is a key determinant of gm , we hypothesize that other changes in this cellular compartiment should also influence gm . We study the relationship between the antioxidant apoplastic system and CW metabolism and the gm responses in tobacco plants (Nicotiana sylvestris L.) under two abiotic stresses (drought and salinity), combining in vivo gas-exchange measurements with analyses of antioxidant activities, CW composition and primary metabolism. Stress treatments imposed substantial reductions in AN (58-54%) and gm (59%), accompanied by a strong antioxidant enzymatic response at the apoplastic and symplastic levels. Interestingly, apoplastic but not symplastic peroxidases were positively related to gm . Leaf anatomy remained mostly stable; however, the stress treatments significantly affected the CW composition, specifically pectins, which showed significant relationships with AN and gm . The treatments additionally promoted a differential primary metabolic response, and specific CW-related metabolites including galactose, glucosamine and hydroxycinnamate showed exclusive relationships with gm independent of the stress. These results suggest that gm responses can be attributed to specific changes in the apoplastic antioxidant system and CW metabolism, opening up more possibilities for improving photosynthesis using breeding/biotechnological strategies.

apoplast
cell wall
mesophyll conductance
photosynthesis
Nicotiana sylvestris
reactive oxygen species
stress responses


Communicating science in public controversies: Strategic considerations of the German climate scientists.

Abstract: In public controversies on scientific issues, scientists likely consider the effects of their findings on journalists and on the public debate. A representative survey of 123 German climate scientists (42%) finds that although most climate scientists think that uncertainties about climate change should be made clearer in public they do not actively communicate this to journalists. Moreover, the climate scientists fear that their results could be misinterpreted in public or exploited by interest groups. Asking scientists about their readiness to publish one of two versions of a fictitious research finding shows that their concerns weigh heavier when a result implies that climate change will proceed slowly than when it implies that climate change will proceed fast.

D001290:Attitude
D057231:Climate Change
D034462:Dissent and Disputes
D005858:Germany
D033181:Information Dissemination
D008402:Mass Media
D011639:Public Opinion

public controversy
Climate change
media and science
media representations
science communication
scientists’ attitudes


Biocompatible nanocarrier fortified with a dipyridinium-based amphiphile for eradication of biofilm.

Abstract: Annihilation of bacterial biofilms is challenging owing to their formidable resistance to therapeutic antibiotics and thus there is a constant demand for development of potent antibiofilm agents that can abolish established biofilms. In the present study, the activity of a dipyridinium-based cationic amphiphile (compound 1) against established bacterial biofilms and the subsequent development of a compound 1-loaded nanocarrier for potential antibiofilm therapy are highlighted. Solution-based assays and microscopic analysis revealed the antagonistic effect of compound 1 on biofilms formed by Staphylococcus aureus MTCC 96 and Pseudomonas aeruginosa MTCC 2488. In combination studies, compound 1 could efficiently potentiate the action of tobramycin and gentamicin on P. aeruginosa and S. aureus biofilm, respectively. A human serum albumin (HSA)-based nanocarrier loaded with compound 1 was generated, which exhibited sustained release of compound 1 at physiological pH. The compound 1-loaded HSA nanocarrier (C1-HNC) displayed the signature membrane-directed activity of the amphiphile on target bacteria, efficiently eliminated established bacterial biofilms, and was observed to be nontoxic to a model human cell line. Interestingly, compound 1 as well as the amphiphile-loaded HSA nanocarrier could eradicate established S. aureus biofilm from the surface of a Foley's urinary catheter. On the basis of its biocompatibility and high antibiofilm activity, it is conceived that the amphiphile-loaded nanocarrier may hold potential in antibiofilm therapy.

Goswami|Sudeep|S| Thiyagarajan|Durairaj|D| Das|Gopal|G| Ramesh|Aiyagari|A|

amphiphile
antibiotic
antibiofilm
HSA nanocarrier
catheter
antibacterial


Effects of Bni5 Binding on Septin Filament Organization.

Abstract: Septins are a protein family found in all eukaryotes (except higher plants) that have roles in membrane remodeling and formation of diffusion barriers and as a scaffold to recruit other proteins. In budding yeast, proper execution of cytokinesis and cell division requires the formation of a collar of circumferential filaments at the bud neck. These filaments are assembled from apolar septin hetero-octamers. Currently, little is known about the mechanisms that control the arrangement and dynamics of septin structures. In this study, we utilized both Förster resonance energy transfer and electron microscopy to analyze the biophysical properties of the septin-binding protein Bni5 and how its association with septin filaments affects their organization. We found that the interaction of Bni5 with the terminal subunit (Cdc11) at the junctions between adjacent hetero-octamers in paired filaments is highly cooperative. Both the C-terminal end of Bni5 and the C-terminal extension of Cdc11 make important contributions to their interaction. Moreover, this binding may stabilize the dimerization of Bni5, which, in turn, forms cross-filament braces that significantly narrow, and impose much more uniform spacing on, the gap between paired filaments.

Booth|Elizabeth A|EA|
Sterling|Sarah M|SM|
Dovala|Dustin|D|
Nogales|Eva|E|
Thorner|Jeremy|J|

D031541:Fluorescence Resonance Energy Transfer

electron microscopy
FRET analysis
analytical ultracentrifugation
field-flow fractionation
yeast (Saccharomyces cerevisiae)


Simulation of oxygen transport and estimation of tissue perfusion in extensive microvascular networks: Application to cerebral cortex.

Abstract: Advanced imaging techniques have made available extensive three-dimensional microvascular network structures. Simulation of oxygen transport by such networks requires information on blood flow rates and oxygen levels in vessels crossing boundaries of the imaged region, which is difficult to obtain experimentally. Here, a computational method is presented for estimating blood flow rates, oxygen levels, tissue perfusion and oxygen extraction, based on incomplete boundary conditions. Flow rates in all segments are estimated using a previously published method. Vessels crossing the region boundary are classified as arterioles, capillaries or venules. Oxygen levels in inflowing capillaries are assigned based on values in outflowing capillaries, and similarly for venules. Convective and diffusive oxygen transport is simulated. Contributions of each vessel to perfusion are computed in proportion to the decline in oxygen concentration along that vessel. For a vascular network in the mouse cerebral cortex, predicted tissue oxygen levels show a broad distribution, with 99% of tissue in the range of 20 to 80 mmHg under reference conditions, and steep gradients near arterioles. Perfusion and extraction estimates are consistent with experimental values. A 30% reduction in perfusion or a 30% increase in oxygen demand, relative to reference levels, is predicted to result in tissue hypoxia.

Celaya-Alcala|Jose T|JT|
Lee|Grace V|GV|
Smith|Amy F|AF|0000-0003-0964-1632
Li|Bohan|B|
Sakadžić|Sava|S|
Boas|David A|DA|
Secomb|Timothy W|TW|0000-0002-0176-5502

simulation
perfusion
networks
Blood flow
oxygen extraction
microcirculation


Laparoscopic gastrojejunostomy versus duodenal stenting in unresectable gastric cancer with gastric outlet obstruction.

Abstract:
PURPOSE
To compare the outcome between laparoscopic gastrojejunostomy (LapGJ) and duodenal stenting (DS) in terms of oral intake, nutritional status, patency duration, effect on chemotherapy and survival.

METHODS
Medical records of 115 patients, who had LapGJ or duodenal stent placement between July 2005 and September 2015 in Seoul National University Bundang Hospital, have been reviewed retrospectively. Oral intake was measured with Gastric Outlet Obstruction Scoring System. Serum albumin and body weight was measured as indicators of nutritional status. The duration of patency was measured until the date of reintervention. Chemotherapy effect was calculated after the procedures. Survival period and oral intake was analyzed by propensity score matching age, sex, T-stage, comorbidities, and chemotherapy status.

RESULTS
Forty-three LapGJ patients and 58 DS patients were enrolled. Improvement in oral intake was shown in LapGJ group versus DS group (88% vs. 59%, P = 0.011). Serum albumin showed slight but significant increase after LapGJ (+0.75 mg/dL vs. -0.15 mg/dL, P = 0.002); however, there was no difference in their body weight (+5.1 kg vs. -1.0 kg, P = 0.670). Patients tolerated chemotherapy longer without dosage reduction after LapGJ (243 days vs. 74 days, P = 0.006) and maintained the entire chemotherapy regimen after the procedure longer in LapGJ group (247 days vs. 137 days, P = 0.042). LapGJ showed significantly longer survival than DS (220 vs. 114 days, P = 0.004).

CONCLUSION
DS can provide faster symptom relief but LapGJ can provide improved oral intake, better compliance to chemotherapy, and longer survival. Therefore, LapGJ should be the first choice in gastric outlet obstruction patients for long-term and better quality of life.

Min|Sa-Hong|SH|
Son|Sang-Yong|SY|
Jung|Do-Hyun|DH|
Lee|Chang-Min|CM|
Ahn|Sang-Hoon|SH|
Park|Do Joong|DJ|
Kim|Hyung-Ho|HH|

Gastrojejunostomy
Stents
Gastric outlet obstruction
Laparoscopy
Stomach neoplasms


Compliance versus dead space for optimum positive end expiratory pressure determination in acute respiratory distress syndrome.

Abstract:
OBJECTIVE
To Compare compliance versus dead space (Vd) targeted positive end-expiratory pressure (PEEP) as regard its effect on lung mechanics and oxygenation.

MATERIALS AND METHODS
This study was carried out on 30 adult acute respiratory distress syndrome patients. The ventilator was initially set on volume controlled with tidal volume (Vt) 7 mL/kg predicted body weight (PBW), inspiratory plateau pressure (Ppl) <30 cm H2 O. If the Ppl was >30 cm H2 O with a TV of 6 mL/kg PBW, a step-wise Vt reduction of 1 mL/kg PBW to as low as 4 mL/kg/PBW was allowed. Respiratory rate adjusted to maintain pH 7.30-7.45. FiO2 start at 100%. Best PEEP determined at 2 points, one by titrating PEEP until reaching the highest static compliance (Cst) (PEEP Cst) and the other one is at the lowest Vd/Vt (PEEP Vd/Vt). The following data measured before and 30 min after setting PEEP Cst and PEEP Vd/Vt. Cst, PaCO2 - PetCO2, Vd/Vt, PaO2 /FiO2, Ppl, heart rate, mean arterial pressure and oxygen saturation.

RESULTS
optimum PEEP determined by Vd/Vt was significantly (P < 0.05) lower than the optimum PEEP determined by Cst. Best PEEP Vd/Vt showed a significant decrease (P < 0.05) in Cst, PaCO2 - PetCO2, Vd/Vt and Ppl in comparison with best PEEP Cst. The PaO2 /FiO2 showed a significant increase (P < 0.05) with best PEEP Vd/Vt in comparison with best PEEP Cst.

CONCLUSION
Vd guided PEEP improved compliance and oxygenation with less Ppl. Hence, its use as a guide for best PEEP determination may be useful.

El-Baradey|Ghada Fouad|GF|
El-Shamaa|Nagat Sayed|NS|

positive end expiratory pressure
Acute respiratory distress syndrome
static compliance
dead space fraction


Interactive effects of culture and sex hormones on the sex role self-concept.

Abstract: Sex role orientation, i.e., a person's masculinity or femininity, influences cognitive and emotional performance, like biological sex. While it is now widely accepted that sex differences are modulated by the hormonal status of female participants (menstrual cycle, hormonal contraceptive use), the question, whether hormonal status and sex hormones also modulate participants sex role orientation has hardly been addressed previously. The present study assessed sex role orientation and hormonal status as well as sex hormone levels in three samples of participants from two different cultures (Northern American, Middle European). Menstrual cycle phase did not affect participant's masculinity or femininity, but had a significant impact on reference group. While women in their follicular phase (low levels of female sex hormones) determined their masculinity and femininity in reference to men, women in their luteal phase (high levels of female sex hormones) determined their masculinity and femininity in reference to women. Hormonal contraceptive users rated themselves as significantly more feminine and less masculine than naturally cycling women. Furthermore, the impact of biological sex on the factorial structure of sex role orientation as well as the relationship of estrogen to masculinity/femininity was modulated by culture. We conclude that culture and sex hormones interactively affect sex role orientation and hormonal status of participants should be controlled for when assessing masculinity and/or femininity.

Pletzer|Belinda|B|
Petasis|Ourania|O|
Ortner|Tuulia M|TM|
Cahill|Larry|L|

sex hormones
sex role
menstrual cycle
hormonal contraceptives


Comparison of effectiveness of temporary positive expiratory pressure versus oscillatory positive expiratory pressure in severe COPD patients.

Abstract:
INTRODUCTION
In chronic obstructive pulmonary disease (COPD) patients few modalities of airway clearance have demonstrated effectiveness in reducing hypersecretion and bronchial obstruction. Positive expiratory pressure (PEP) is one of these.

OBJECTIVE
Our goal was to compare the effectiveness of 2 devices Temporary PEP (T-PEP) and Oscillatory PEP (O-PEP) which use PEP applied at a low expiratory pressure of 1 cm H2 O which creates oscillations that decrease bronchial obstruction in reducing COPD exacerbations and improving respiratory and health status assessment parameters. Each has different mechanism of action.

METHODS
A 26 week randomized controlled study evaluated their efficacy in reducing exacerbations and improving health status assessment tests as well as respiratory function parameters in severe to very severe COPD patients. One hundred-twenty patients were enrolled: 40 patients received T-PEP therapy; 40 underwent treatment with O-PEP; 40 constituted the control group. The primary outcome was the reduction of exacerbations after 1, 3 and 6 months; secondary outcomes were improvement of lung function and health status assessment tests [Modified Medical Research Council (MMRC) scale, Breathlessness, Cough, and Sputum Scale (BCSS) scale, and COPD Assessment Test (CAT) score].

RESULTS
Only T-PEP statistically reduced the exacerbations after 1 and 3 months compared to the control group. Both the 2 devices improved dyspnea scale (MMRC), lung function parameters, and health status assessment (CAT) tests compared to the control group. Both interventions were well-tolerated by our patients.

CONCLUSIONS
O-PEP and T-PEP are useful for COPD treatment but only T-PEP reduces exacerbations. Adding tools for airway clearance to medical therapy can help the management of COPD.

D029424:Pulmonary Disease, Chronic Obstructive

temporary PEP
oscillatory PEP
exacerbations
COPD management


Prenatal and perinatal risk factors for solid childhood malignancies: A questionnaire-based study.

Abstract:
Importance
Childhood solid tumors account for the highest proportion of childhood cancers and are one of the leading causes of death in childhood. However, their pathogenesis is unclear.

Objective
To explore prenatal and perinatal risk factors for solid malignancies in children.

Methods
We enrolled 71 consecutive pediatric patients (44 boys and 27 girls; median age, 30 months) with solid tumors who were diagnosed and treated at our center from January 2013 to December 2016 as the case group. We also enrolled 211 age- and residence-matched healthy children (ratio of approximately 3:1 with the case group) as the control group. We conducted a questionnaire-based survey with the parents of these 282 children. Univariate and multivariate conditional logistic regression analyses of the collected data were performed.

Results
Confirmed solid malignancies included neuroblastoma (n = 32), rhabdomyosarcoma (n = 18), retinoblastoma (n = 7), renal tumors (n = 3), and other tumors (n = 11). Risk factors for solid childhood tumors in the univariate analysis were the parents' age, gravidity, parity, abortion history, vaginal bleeding, family history of malignancy, and prenatal use of folic acid or hematinics/iron supplements (P < 0.05), and those in the multivariate analysis were higher parity (odds ratio [OR], 2.482; 95% confidence interval [CI], 1.521-4.048), family history of malignancy (OR, 3.667; 95% CI, 1.679-8.009), and prenatal use of hematinics/iron supplements (OR, 2.882; 95% CI, 1.440-5.767). In contrast, use of prenatal folic acid was protective (OR, 0.334; 95% CI, 0.160-0.694).

Interpretation
A family history of malignancy, use of prenatal hematinics/iron supplements, and higher parity are risk factors for solid childhood tumors, whereas use of prenatal folic acid is a protective factor.

Li|Sihui|S| Cai|Siyu|S| Huang|Cheng|C| Chai|Xi|X| Wang|Xindi|X| Wang|Xisi|X| Zhao|Wen|W| Nie|Xiaolu|X| Peng|Xiaoxia|X| Ma|Xiaoli|X|

Perinatal
Risk factors
Solid malignancies
Children
Case‐control study
Maternal


Ultralow-temperature device dedicated to soft X-ray magnetic circular dichroism experiments.

Abstract: A new ultralow-temperature setup dedicated to soft X-ray absorption spectroscopy and X-ray magnetic circular dichroism (XMCD) experiments is described. Two experiments, performed on the DEIMOS beamline (SOLEIL synchrotron), demonstrate the outstanding performance of this new platform in terms of the lowest achievable temperature under X-ray irradiation (T = 220 mK), the precision in controlling the temperature during measurements as well as the speed of the cooling-down and warming-up procedures. Moreover, owing to the new design of the setup, the eddy-current power is strongly reduced, allowing fast scanning of the magnetic field in XMCD experiments; these performances lead to a powerful device for X-ray spectroscopies on synchrotron-radiation beamlines facilities.

Kappler|J P|JP|
Otero|E|E|0000-0002-3546-3908
Li|W|W|
Joly|L|L|
Schmerber|G|G|
Muller|B|B|
Scheurer|F|F|
Leduc|F|F|
Gobaut|B|B|
Poggini|L|L|
Serrano|G|G|
Choueikani|F|F|
Lhotel|E|E|
Cornia|A|A|
Sessoli|R|R|
Mannini|M|M|
Arrio|M A|MA|
Sainctavit|Ph|P|
Ohresser|P|P|

ultralow-temperature
soft X-rays
magnetism
XMCD


Joint BAP NAPICU evidence-based consensus guidelines for the clinical management of acute disturbance: De-escalation and rapid tranquillisation.

Abstract: The British Association for Psychopharmacology and the National Association of Psychiatric Intensive Care and Low Secure Units developed this joint evidence-based consensus guideline for the clinical management of acute disturbance. It includes recommendations for clinical practice and an algorithm to guide treatment by healthcare professionals with various options outlined according to their route of administration and category of evidence. Fundamental overarching principles are included and highlight the importance of treating the underlying disorder. There is a focus on three key interventions: de-escalation, pharmacological interventions pre-rapid tranquillisation and rapid tranquillisation (intramuscular and intravenous). Most of the evidence reviewed relates to emergency psychiatric care or acute psychiatric adult inpatient care, although we also sought evidence relevant to other common clinical settings including the general acute hospital and forensic psychiatry. We conclude that the variety of options available for the management of acute disturbance goes beyond the standard choices of lorazepam, haloperidol and promethazine and includes oral-inhaled loxapine, buccal midazolam, as well as a number of oral antipsychotics in addition to parenteral options of intramuscular aripiprazole, intramuscular droperidol and intramuscular olanzapine. Intravenous options, for settings where resuscitation equipment and trained staff are available to manage medical emergencies, are also included.

Patel|Maxine X|MX|
Sethi|Faisil N|FN|
Barnes|Thomas Re|TR|
Dix|Roland|R|
Dratcu|Luiz|L|
Fox|Bernard|B|
Garriga|Marina|M|
Haste|Julie C|JC|
Kahl|Kai G|KG|
Lingford-Hughes|Anne|A|
McAllister-Williams|Hamish|H|
O'Brien|Aileen|A|
Parker|Caroline|C|
Paterson|Brodie|B|
Paton|Carol|C|
Posporelis|Sotiris|S|
Taylor|David M|DM|
Vieta|Eduard|E|
Völlm|Birgit|B|
Wilson-Jones|Charlotte|C|
Woods|Laura|L|
|||

D000208:Acute Disease
D000374:Aggression
D014151:Anti-Anxiety Agents
D014150:Antipsychotic Agents
D006801:Humans
D001523:Mental Disorders
D011595:Psychomotor Agitation
D013997:Time Factors
D014754:Violence

Acute disturbance
de-escalation
rapid tranquillisation
antipsychotics
aggression
benzodiazepines
psychiatric illness
violence


Epstein-Barr virus infection in gliomas.

Abstract:
PURPOSE OF THE STUDY
Epstein-Barr virus (EBV) has been involved in the development of some tumors, including Burkitt's lymphoma and Hodgkin's lymphoma. However, its potential role in glioma tumorigenesis remains debated. In this study, we investigated the EBV infection in gliomas from Tunisian patients.

PATIENTS AND METHODS
We conducted a retrospective study of 112 gliomas on archival material. The EBV DNA sequence was analyzed by polymerase chain reaction (PCR). Latent membrane protein 1 (LMP1) was detected by immunohistochemistry. In situ hybridization was used to detect EBV encoded small RNA (EBER). Clinicopathological features were recorded. Survival analysis was carried out using the Kaplan-Meier method and the Log-Rank test to compare EBV-positive and EBV-negative patients.

RESULTS
Overall, there were twenty-four EBV-positive gliomas (21.4%). EBV DNA was identified in 24 cases. LMP1 and EBER were detected in four EBV DNA-positive cases. All EBV-positive cases were glioblastomas multiforme (GBM). Median overall survival and recurrence-free survival of EBV-negative patients were better than those of EBV-positive patients (Log Rank p =  0.006).

CONCLUSION
Altogether, these findings support the occurrence of EBV infection in Tunisian GBM. Furthermore, when compared to EBV-negative tumors, EBV infection seems to be associated with the worst patient prognosis. Advanced molecular studies are recommended to confirm these results and to shed further light on the potential role of EBV in these devastating tumors.

Limam|S|S|
Missaoui|N|N|
Mestiri|S|S|
Yacoubi|M T|MT|
Krifa|H|H|
Selmi|B|B|
Mokni|M|M|

Glioma EBV Tumorigenesis Glioblastoma Prognosis


Listening to women's voices: the experience of giving birth with paramedic care in Queensland, Australia.

Abstract:
BACKGROUND
Unplanned out-of-hospital birth is generally assumed to occur for women who are multiparous, have a history of a short pushing phase of labour or are experiencing a precipitate birth. However, there is little research that examines the woman's perspective regarding factors that influenced their decision on when to access care. This research aimed to explore women's experience of unplanned out-of-hospital birth in paramedic care. Due to the size of the data in the larger study of 'Women's experience of unplanned out-of-hospital birth in paramedic care' [1], this paper will deal directly with the women's narrative concerning her decision to access care and how previous birth experience and interactions with other healthcare professionals influenced her experience.

METHOD
Narrative inquiry, underpinned from a feminist perspective, was used to guide the research. Twenty-two women who had experienced an unplanned out-of-hospital birth within the last 5 years in Queensland, Australia engaged in this research.

RESULTS
The decision of a woman in labour to attend hospital to birth her baby is influenced by information received from healthcare providers, fear of unnecessary medical intervention in birth, and previous birth experience. All themes and subthemes that emerged in the women's narratives relate to the notion of birth knowledge. These specifically include perceptions of what constitutes authoritative knowledge, who possesses the authoritative knowledge on which actions are based, and when and how women use their own embodied knowledge to assess the validity of healthcare workers' advice and the necessity for clinical intervention.

CONCLUSIONS
The women interviewed communicated a tension between women's knowledge, beliefs and experience of the birth process, and the professional models of care traditionally associated with the hospital environment. It is essential that information provided to women antenatally is comprehensive and comprehensible. The decisions women make concerning their birth plan represent the women's expectations for their birth and this should be used as a means to openly communicate issues that may impact the birth experience.

D007722:Health Knowledge, Attitudes, Practice

D010342:Patient Acceptance of Health Care

Unplanned
Narrative inquiry
Birth before arrival
women’s perspective


Increased Frequency of Th17 Cells in Children With Mycoplasma pneumoniae Pneumonia.

Abstract:
BACKGROUND
Mycoplasma pneumoniae (M. pneumoniae, MP) is recognized globally as a significant cause of primary atypical pneumonia in humans, particularly in children. Overzealous host immune responses are viewed as key mediators of the pathogenesis of M. pneumoniae infection. Although Th17 cells have been identified as key modulators in the clearance of pathogens and induction of autoimmunity caused by excessive immune responses, little is known about the role of Th17 cells in patients with M. pneumoniae infection.

METHODS
The percentages of T cells, CD4+ T cells and Th17 cells in children with M. pneumoniae infection were measured by flow cytometry.

RESULTS
We documented an increased frequency of Th17 cells in children with M. pneumoniae infection. Furthermore, we found a significantly higher percentage of Th17 cells in M. pneumoniae-infected children with extrapulmonary manifestations, compared with children without extrapulmonary manifestations. In addition, patients who experienced a short course of Mycoplasma pneumoniae pneumonia (MPP) showed an increase in the percentage of Th17 cells.

CONCLUSION
Our findings suggest that Th17 cells may be involved in the clearance of M. pneumoniae during an acute infection. Excessive Th17 cell responses may also contribute to the immuno-pathological damage observed during persistent infection.

Wang|Xiaowei|X| Chen|Xiaojun|X| Tang|Heng|H| Zhu|Jifeng|J| Zhou|Sha|S| Xu|Zhipeng|Z| Liu|Feng|F| Su|Chuan|C|

Th17 cells
children
Mycoplasma Pneumoniae
respiratory infection


Leadership through the eyes of a public health professional: A journey of 43 years.

Abstract: Leadership skills in a public health professional (PHP) are more important today in view of rapidly changing disease pattern, higher priority to universal health coverage, health in all policies, health being demanded as a human right, and emergence of pandemics from zoonotic diseases. Most of us become accidental leaders as we never receive training in leadership skills. This not only undermines the effectiveness of PHP but also undermines the credibility of public health as a specialty. Jim Collin's five levels of leadership are useful to understand the various levels of leadership for a PHP. Technical excellence which denotes first level of leadership is necessary but not sufficient to become a leader. One needs team work, emotional competencies, prioritization ( first things first), listening skills, advocacy, negotiation, networking skills, along with conviction, commitment, and courage to do what one thinks is right. Leadership is a life-long journey, not a destination. Being engaged in leadership for more than a decade, I developed a three domain leadership capacity development model very useful in designing and conducting leadership development trainings to develop leadership skills among PHPs, academicians, and health researchers.

three domains model of capacity development for leadership


Amphibious hearing in ringed seals (Pusa hispida): underwater audiograms, aerial audiograms and critical ratio measurements.

Abstract: Ringed seals (Pusa hispida) are semi-aquatic marine mammals with a circumpolar Arctic distribution. In this study, we investigate the amphibious hearing capabilities of ringed seals to provide auditory profiles for this species across the full range of hearing. Using psychophysical methods with two trained ringed seals, detection thresholds for narrowband signals were measured under quiet, carefully controlled environmental conditions to generate aerial and underwater audiograms. Masked underwater thresholds were measured in the presence of octave-band noise to determine critical ratios. Results indicate that ringed seals possess hearing abilities comparable to those of spotted seals (Phoca largha) and harbor seals (Phoca vitulina), and considerably better than previously reported for ringed and harp seals. Best sensitivity was 49 dB re. 1 µPa (12.8 kHz) in water, and -12 dB re. 20 µPa (4.5 kHz) in air, rivaling the acute hearing abilities of some fully aquatic and terrestrial species in their respective media. Critical ratio measurements ranged from 14 dB at 0.1 kHz to 31 dB at 25.6 kHz, suggesting that ringed seals--like other true seals--can efficiently extract signals from background noise across a broad range of frequencies. The work described herein extends similar research on amphibious hearing in spotted seals recently published by the authors. These parallel studies enhance our knowledge of the auditory capabilities of ice-living seals, and inform effective management strategies for these and related species in a rapidly changing Arctic environment.

Sills|Jillian M|JM|
Southall|Brandon L|BL|
Reichmuth|Colleen|C|

Amphibious
Hearing
Ringed seal
Audiogram
Arctic
Noise


An atypical presentation of herpes simplex virus infection in Harlequin ichthyosis.

Abstract: We present an atypical presentation of herpes simplex virus infection in a patient with Harlequin ichthyosis, which we attribute to abnormal cornification.


Spectanoids A-H: Eight undescribed sesterterpenoids from Aspergillus spectabilis.

Abstract: Ten sesterterpenoids, including eight undescribed ones named spectanoids A-H and two known analogs, were obtained from Aspergillus spectabilis. Their structures, including absolute configurations, were determined based on HRESIMS, NMR, ECD calculations and single-crystal X-ray diffraction analyses. Spectanoids A-G are tricyclic sesterterpenoids with an unusual 5/12/5 ring system, while spectanoid H possesses a 5/8/6/5 ring system. All of these compounds were evaluated for their cytotoxic activities against three human cancer cells, and spectanoid A, spectanoid C and spectanoid F exhibited moderate cytotoxic activities with IC50 values ranging from 12.1 to 26.1 μM.

Wei|Mengsha|M| Zhou|Peng|P| Huang|Liping|L| Yin|Jie|J| Li|Qin|Q| Dai|Chong|C| Wang|Jianping|J| Gu|Lianghu|L| Tong|Qingyi|Q| Zhu|Hucheng|H| Zhang|Yonghui|Y|

D001230:Aspergillus
D018360:Crystallography, X-Ray
D009682:Magnetic Resonance Spectroscopy
D015394:Molecular Structure

Sesterterpenoids
Aspergillus spectabilis
Cytotoxic activities
Aspergillaceae


Highly efficient hydrogen storage system based on ammonium bicarbonate/formate redox equilibrium over palladium nanocatalysts.

Abstract: A highly efficient, reversible hydrogen storage-evolution process has been developed based on the ammonium bicarbonate/formate redox equilibrium over the same carbon-supported palladium nanocatalyst. This heterogeneously catalyzed hydrogen storage system is comparable to the counterpart homogeneous systems and has shown fast reaction kinetics of both the hydrogenation of ammonium bicarbonate and the dehydrogenation of ammonium formate under mild operating conditions. By adjusting temperature and pressure, the extent of hydrogen storage and evolution can be well controlled in the same catalytic system. Moreover, the hydrogen storage system based on aqueous-phase ammonium formate is advantageous owing to its high volumetric energy density.

Su|Ji|J| Yang|Lisha|L| Lu|Mi|M| Lin|Hongfei|H|

efficiency
hydrogenation
palladium
carbamate
co2 conversion


Cardiovascular Risk/Benefit Profile of MHT.

Abstract: Background and Objectives: Data emerging from the Women's Health Initiative (WHI) study point toward an association between menopausal hormone therapy (MHT) and cardiovascular (CV) risk. However, post hoc subgroup analyses stratifying participants according to their age and time since menopause, have opened the way to a better understanding of the relationship between estrogen and CV risk. The aim of this review was to revise the current literature and evaluate the CV risk or benefit following administration of MHT considering several factors such as MHT timing, dose, route of administration, and formulation. Materials and Methods: An electronic databases search of MEDLINE (PubMed), Cochrane Central Register of Controlled Trials, Web of Science, SCOPUS, congress abstracts, and Grey literature (Google Scholar; British Library) was performed, with the date range from each database's inception until June 2019. All the studies evaluating MHT and cardiovascular risk, including thromboembolism or stroke, were selected. Results: Timing of MHT initiation was shown to be a critical factor in CV risk assessment. In concordance with the "timing hypothesis", healthy symptomatic women who initiated MHT when aged younger than 60 years, or who were within 10 years of menopause onset, have demonstrated a reduction in both coronary heart disease (CHD) risk and all-cause mortality. In particular, MHT therapy was associated with improvement of subclinical signs of atherosclerosis. Venous thromboembolism (VTE) risk is reduced when low doses of oral estrogen are used. Moreover, transdermal hormonal application significantly reduces CV risk compared with oral administration. MHT impact on the CV system is influenced by either factors inherent to the specific regimen, or factors inherent to the specific patient. Hence, individualization of care is necessary. Conclusion: CV risk calculation should be considered by clinicians in order to exclude patients with high CV risk, in whom MHT is contraindicated. Assessing risks and benefits in a patient-centered approach according to individual's features, health status, and personal preferences is important in order to realize a safe and effective treatment.

Villa|Paola|P|
Amar|Inbal Dona|ID|
Shachor|Maayan|M|
Cipolla|Clelia|C|
Ingravalle|Fabio|F|
Scambia|Giovanni|G|

menopausal hormone therapy
menopause
cardiovascular disease prevention


Target HER four in breast cancer?

Abstract: The HER4 receptor tyrosine kinase is known to have promiscuous activity in malignant cells, last but not least in breast cancer. Evidently, the prognostic and predictive impact of HER4 expression depends on the expression of different receptor isotypes, the way of receptor activation (ligand dependent vs. independent), and on the complex interaction of the HER4 intracellular domain (4ICD) with intracellular regulative molecules which results in either oncogenic or rather tumor suppressive HER4 activity. Recent data suggest that HER4 unfavorably affects the endocrine treatment of postmenopausal breast cancer patients with tamoxifen and therefore might represent an additional therapeutic target in luminal breast cancer.


Bilateral auditory ossicular expansions in a child with beta-thalassemia major: Case report and literature review.

Abstract: Marrow proliferation of the ossicular chain is a rare phenomenon. To date, only two other cases have described this rarity. We report a third paediatric case from Australia. A seven-year-old with thalassemia major demonstrated conductive impairment during surveillance for Deferasirox ototoxicity. Otitis media was assumed, however, CT scan of the petrous temporal bone revealed extramedullary haematopoiesis causing bilateral ossicular expansions and fixed conductive deficit. Reports of hearing loss in the thalassemia population focus on sensorineural impairment from iron chelation therapies. Clinicians should suspect ossicular deformation where treatment has been delayed, poorly controlled or conductive deficit persists without effusion.

Sirisena|Melisha|M|
Birman|Catherine S|CS|
McKibbin|Amy J|AJ|
O'Brien|Katie J|KJ|

Paediatric
Ototoxicity
Extramedullary haematopoiesis
Iron chelation therapy
Blood transfusion
Conductive hearing loss


Quantitative assessment of paraoxon adsorption to amphiphilic β-sheet peptides presenting the catalytic triad of esterases.

Abstract: Organophosphate compounds that are used as pesticides affect the nervous system by binding irreversibly to the active site of the enzyme acetylcholine esterase (AChE) and disrupting neuro-signaling nerve cells. In this study we characterized adsorption of paraoxon to a set of designed peptides that present different arrangements of the three amino acids of the AChE catalytic site: histidine, glutamic-acid and serine. The peptides set included two β-strands with no net charge and three β-hairpins that differ in their net charge. Circular dichroism, Thioflavin T assays and TEM images provided only qualitative insights on paraoxon binding to the different peptides. Paraoxon binding to the different peptides was measured with dialysis membrane tubes filled with the peptide solutions and suspended in a reservoir of paraoxon solution. Among all the tested peptides, the single strand peptide, denoted ssESH exhibited at 100 μM in random conformation prefibrillar state, the maximum paraoxon adsorption, with a binding mol ratio of one paraoxon per two peptides and an estimated equilibrium binding constant 5 ∗ 104 M-1. The three β-hairpin peptides demonstrated that a net negative charge is unfavorable for paraoxon adsorption. Surface enhanced Raman spectroscopy measurements with ssESH enabled the detection of nanomolar adsorbed concentrations of paraoxon.

Baruch Leshem|Avigail|A|
Isaacs|Sivan|S|
Srivastava|Sachin K|SK|
Abdulhalim|Ibrahim|I|
Kushmaro|Ariel|A|
Rapaport|Hanna|H|

β-sheet
Catalytic triad
Organophosphates
β-hairpin
Circular dichroism
Thioflavin T
Surface enhanced Raman spectroscopy


OTX015 Epi-Drug Exerts Antitumor Effects in Ovarian Cancer Cells by Blocking GNL3-Mediated Radioresistance Mechanisms: Cellular, Molecular and Computational Evidence.

Abstract: Ovarian cancer (OC) is the most aggressive gynecological tumor worldwide and, notwithstanding the increment in conventional treatments, many resistance mechanisms arise, this leading to cure failure and patient death. So, the use of novel adjuvant drugs able to counteract these pathways is urgently needed to improve patient overall survival. A growing interest is focused on epigenetic drugs for cancer therapy, such as Bromodomain and Extra-Terminal motif inhibitors (BETi). Here, we investigate the antitumor effects of OTX015, a novel BETi, as a single agent or in combination with ionizing radiation (IR) in OC cellular models. OTX015 treatment significantly reduced tumor cell proliferation by triggering cell cycle arrest and apoptosis that were linked to nucleolar stress and DNA damage. OTX015 impaired migration capacity and potentiated IR effects by reducing the expression of different drivers of cancer resistance mechanisms, including GNL3 gene, whose expression was found to be significantly higher in OC biopsies than in normal ovarian tissues. Gene specific knocking down and computational network analysis confirmed the centrality of GNL3 in OTX015-mediated OC antitumor effects. Altogether, our findings suggest OTX015 as an effective option to improve therapeutic strategies and overcome the development of resistant cancer cells in patients with OC.

OTX015
ovarian cancer
radioresistance
BET inhibitors
GNL3 (nucleostemin)


Cymbopogon citratus industrial waste as a potential source of bioactive compounds.

Abstract:
BACKGROUND
Cymbopogon citratus (Cc), commonly known as lemongrass, is a very important crop worldwide, being grown in tropical countries. It is widely used in the food, pharmaceutical, cosmetic and perfumery industries for its essential oil. Cc aqueous extracts are also used in traditional medicine. They contain high levels of polyphenols, which are known for their antioxidant and anti-inflammatory properties. Hydrodistillation of lemongrass essential oil produces an aqueous waste (CcHD) which is discarded. Therefore a comparative study between CcHD and Cc infusion (CcI) was performed to characterize its phytochemical profile and to research its antioxidant and anti-inflammatory potential.

RESULTS
HPLC-PDA/ESI-MS(n) analysis showed that CcI and CcHD have similar phenolic profiles, with CcHD presenting a higher amount of polyphenols. Additionally, both CcI and CcHD showed antioxidant activity against DPPH (EC50 of 41.72 ± 0.05 and 42.29 ± 0.05 µg mL(-1) respectively) and strong anti-inflammatory properties, by reducing NO production and iNOS expression in macrophages and through their NO-scavenging activity, in a dose-dependent manner. Furthermore, no cytotoxicity was observed.

CONCLUSION
The data of this study encourage considering the aqueous solution from Cc leaf hydrodistillation as a source of bioactive compounds, which may add great industrial value to this crop.

Tavares|Filipa|F|
Costa|Gustavo|G|
Francisco|Vera|V|
Liberal|Joana|J|
Figueirinha|Artur|A|
Lopes|Maria Celeste|MC|
Cruz|Maria Teresa|MT|
Batista|Maria Teresa|MT|

Cymbopogon citratus
industrial waste
lemongrass
polyphenols
antioxidant
anti-inflammatory


TGF-β1 functional polymorphisms: a review.

Abstract: Transforming Growth Factor β (TGF-β) is a multifunctional cytokine that plays a role in several biological processes. TGF-β1 is the most abundantly expressed isoform, associated with susceptibility to various diseases, and several polymorphisms have been described in the TGF-β1 gene structure, and some of them have been associated with functional implications. To date, eight single-nucleotide polymorphisms (SNPs) and one deletion/insertion polymorphism have been shown to affect TGF-β1 expression (rs2317130, rs11466313, rs1800468, rs1800469, rs11466314, rs1800471, rs1800470, and rs11466316); some of these interfere with transcriptional regulation by affecting the binding of transcription factors binding, while others interfere with protein production. These polymorphisms have been associated with different types of diseases (i.e., cancers, cardiac diseases, inflammatory diseases, and others) and could therefore be used as susceptibility biomarkers. Since polymorphism clusters are likely to be more reliable than single polymorphisms in this respect, it is hoped that haplotype analysis of TGF-β1 may reveal the genetic basis of disease susceptibility associated with the TGF-β1 gene.

D053773:Transforming Growth Factor beta1

haplotype
EMSA
TGF-β1 polymorphisms
clinical implications
luciferase


Agonistic reciprocity is associated with reduced male reproductive success within haremic social networks.

Abstract: While individual variation in social behaviour is ubiquitous and causes social groups to differ in structure, how these structural differences affect fitness remains largely unknown. We used social network analysis of replicate bluebanded goby (Lythrypnus dalli) harems to identify the reproductive correlates of social network structure. In stable groups, we quantified agonistic behaviour, reproduction and steroid hormones, which can both affect and respond to social/reproductive cues. We identified distinct, optimal social structures associated with different reproductive measures. Male hatching success (HS) was negatively associated with agonistic reciprocity, a network structure that describes whether subordinates 'reciprocated' agonism received from dominants. Egg laying was associated with the individual network positions of the male and dominant female. Thus, males face a trade-off between promoting structures that facilitate egg laying versus HS. Whether this reproductive conflict is avoidable remains to be determined. We also identified different social and/or reproductive roles for 11-ketotestosterone, 17β-oestradiol and cortisol, suggesting that specific neuroendocrine mechanisms may underlie connections between network structure and fitness. This is one of the first investigations of the reproductive and neuroendocrine correlates of social behaviour and network structure in replicate, naturalistic social groups and supports network structure as an important target for natural selection.

reciprocity
reproductive success
social network
agonistic behaviour
reproductive conflict


Zearalenone causes embryotoxicity and induces oxidative stress and apoptosis in differentiated human embryonic stem cells.

Abstract: In this study, murine embryonic stem cell test (mEST) and human embryonic stem cell test (hEST) models were developed to evaluate the embryonic toxicity of Zearalenone (ZEN) according to the methods established in our laboratory. The embryotoxicity of ZEN was described by comparing the three functions calculated based on three endpoints, that is, 50% inhibitory proliferation concentration (IC50) of embryonic stem cells (ESCs) and 3T3 cells and 50% inhibition of cardiomyocyte differentiation (ID50) of ESCs determined in the EST model. Moreover, differentiation of human embryonic stem cell (hESC) was initiated by embryoid bodies (EBs) formation; EBs were exposed to different concentrations of ZEN for 24 h to detect cellular reactive oxygen species (ROS) generation, the mitochondrial transmembrane potential (MMP), apoptosis, cell cycle, and the related protein expression. Based on the results of the three endpoints and functions of ZEN in mEST and hEST, ZEN was evaluated to have strong embryonic toxicity both by two models. The increases in cellular ROS and loss of MMP were observed at 2 and 4 μg/ml concentrations. Flow cytometry showed that ZEN induced cell cycle arrest and apoptosis. The upregulation of p53, caspase-9, caspase-3, and the ratio of Bax/Bcl-2 were observed at 2 and 4 μg/ml concentrations. Collectively these results demonstrate that ZEN has strong embryonic toxicity and induces oxidative stress and apoptosis in differentiated human ESCs.

Cao|Hanwen|H| Zhi|Yuan|Y| Xu|Haibin|H| Fang|Haiqin|H| Jia|Xudong|X|

Embryotoxicity
Oxidative stress
Apoptosis
Murine embryonic stem cell test (mEST)
Human embryonic stem cell test (hEST)
Zearalenone (ZEN)
Embryonic stem cell (ESC)
Reactive oxygen species (ROS)


Novel per-oral endoscopic myotomy method preserving oblique muscle using two penetrating vessels as anatomic landmarks reduces postoperative gastroesophageal reflux.

Abstract:
BACKGROUND AND AIM
One of the main concerns related to peroral endoscopic myotomy (POEM) is postoperative gastroesophageal reflux (GER). The two penetrating vessels (TPVs) that are found at the boundary between the circular and oblique muscles in the posterior cardia wall have been suggested to be a good indicator of the optimal distal extent of POEM. However, the effect of performing myotomy using the TPVs as an anatomical reference on the frequency of post-POEM GER has not been studied.

METHODS
This study involved consecutive patients who underwent POEM for the treatment of achalasia between April 2015 and June 2017. All enrolled patients underwent POEM in the 5 o'clock position and were divided into two groups: the conventional line group (CL group, n = 31), in which the TPVs were not exposed during submucosal tunnel dissection in the cardia, and the TPVs line group (TPVs group, n = 83), in which the TPVs were exposed and gastric myotomy was performed along the right side of the TPVs to preserve the oblique muscle. Examinations for post-POEM GER were conducted 3 months after the POEM.

RESULTS
The frequency of grade B or higher reflex esophagitis was 26/83 (31.3%) in the TPVs group and 18/31 (58.1%) in the CL group (P = 0.017). Nine of 83 patients (10.8%) had GER symptoms in the TPVs group, and six of 31 (19.4%) had GER symptoms in the CL group (P = 0.23).

CONCLUSIONS
The novel myotomy method preserving oblique muscle using TPVs as anatomical landmarks significantly reduced the frequency of post-POEM GER.

Myotomy
Oblique muscle
Gastroesophageal reflux
Peroral endoscopic myotomy
Achalasia


Protoporphyrin IX-mediated sonodynamic therapy promotes autophagy in vascular smooth muscle cells.

Abstract: Sonodynamic therapy (SDT) is effective in treating intimal hyperplasia and promoting plaque stability in animal models. The present study aimed to evaluate the effects of SDT with the sonosensitizer protoporphyrin IX (PpIX) on vascular smooth muscle cell (VSMC) viability and autophagy. Cultured VSMCs cells were divided into the following groups: i) Control, ii) ultrasound, iii) PpIX and iv) SDT. Flow cytometry and laser confocal detection were used to measure Annexin V stained VSMCs following different treatments. Alterations in mitochondrial membrane potential (MMP) were evaluated via JC-1 staining. Autophagosome formation was observed using electron and fluorescence microscopy. Western blotting was used to analyze the expression levels of the autophagy markers light chain 3 (LC3-I) and LC3-II. The results demonstrated that SDT did not trigger apoptosis nor induce a significant decline in MMP of VSMCs. However, SDT significantly increased autophagasome formation and increased the LC3-II/LC3-I ratio. The findings demonstrated that PpIX-SDT increased autophagy without inducing mitochondrial-dependent apoptosis in VSMCs.

Li|Qingsong|Q| Kang|Jian|J| Xiong|Xiaojing|X| Liu|Yan|Y| Cao|Wenwu|W| Liu|Ying|Y| Li|Yongning|Y|

sonodynamic therapy
autophagy
vascular smooth muscle cells
protoporphyrin IX
apoptosis


Direct Intra-arterial thrombectomy in order to Revascularize AIS patients with large vessel occlusion Efficiently in Chinese Tertiary hospitals: A Multicenter randomized clinical Trial (DIRECT-MT)-Protocol.

Abstract:
RATIONALE
Intravenous thrombolysis combined with mechanical thrombectomy (MT) has been proven safe and clinical effective in patients with acute ischemic stroke of anterior circulation large vessel occlusion. However, despite reperfusion, a considerable proportion of patients do not recover. Incidence of symptomatic intracerebral hemorrhage was similar between patients treated with the combination of intravenous thrombolysis and MT, as compared to intravenous thrombolysis alone, suggesting that this complication should be attributed to pre-treatment with intravenous thrombolysis. Conversely, intravenous thrombolysis may be beneficial in patients with small clots occluding intracranial arteries with underlying intracranial atherosclerotic disease, not accessible for MT.

AIM
To assess whether direct MT is non-inferior compared to combined intravenous thrombolysis plus MT in patients with AIS due to an anterior circulation large vessel occlusion, and to assess treatment effect modification by presence of intracranial atherosclerotic disease.

SAMPLE SIZE
Aim to randomize 636 patients 1:1 to receive direct MT (intervention) or combined intravenous thrombolysis plus MT (control).

DESIGN
This is a multicenter, prospective, open label parallel group trial with blinded outcome assessment (PROBE design) assessing non-inferiority of direct MT compared to combined intravenous thrombolysis plus MT.

OUTCOMES
The primary outcome is the score on the modified Rankin Scale assessed blindly at 90 (±14) days. An common odds ratio, adjusted for the prognostic factors (age, NIHSS, collateral score), representing the shift on the 6-category mRS scale measured at three months, estimated with ordinal logistic regression, will be the primary effect parameter. Non-inferiority is established if the lower boundary of the 95% confidence interval does not cross 0.8.

DISCUSSION
DIRECT-MT could result in improved therapeutic efficiency and cost reduction in treatment of anterior circulation large vessel occlusion stroke.

Yang|Pengfei|P|
Treurniet|Kilian M|KM|
Zhang|Lei|L|0000-0001-5559-6292
Zhang|Yongwei|Y|
Li|Zifu|Z|
Xing|Pengfei|P|0000-0002-2663-1092
Zhang|Yongxin|Y|
Zhang|Ping|P|
Wang|Hao|H|
Hong|Bo|B|
Dippel|Diederik Wj|DW|
Roos|Yvo Bwem|YB|
Majoie|Charles Blm|CB|
Deng|Benqiang|B|
Liu|Jianmin|J|
|||

D016032:Randomized Controlled Trials as Topic

thrombectomy
Thrombolysis
ischemic stroke
alteplase


A qualitative investigation into the patient-centered goal-setting practices of allied health clinicians working in rehabilitation.

Abstract:
OBJECTIVE
To explore the ways clinicians engage rehabilitation patients in patient-centered goal setting and identify factors influencing the goal-setting process.

DESIGN
Ethnographic study utilizing observed practice-thematic analysis.

SETTING
Four rehabilitation wards of a large metropolitan hospital in Melbourne, Australia.

SUBJECTS
Participants included 17 rehabilitation patients, 18 allied health clinicians and one family member. Disciplines represented were speech pathology, occupational therapy, social work and physiotherapy.

METHOD
Multiple qualitative methods were used. A total of 18 routine goal-setting interviews between clinicians and patients were audio recorded and transcribed. Together with associated entries in the patient medical record, transcripts were coded and developed into themes using thematic analysis. Finally, focus groups with clinicians were conducted to validate themes identified.

RESULTS
Three themes were identified describing factors which influence patient centeredness: "a goal-setting collaboration"-the interpersonal exchange between client and clinician; "the environment"-physical, temporal and structural; and "clinician self-awareness"-clinicians' insight into the ways they influence goal setting. The practice of patient-centered goal setting varied considerably between clinicians. Goals developed were strongly influenced by the clinician's views, although strategies of respect for the patient and reflective listening skills increased patient participation and the patient centeredness of goals developed.

CONCLUSION
Goals developed with rehabilitation patients are more likely to be patient-centered when the interaction encourages the patient to express their needs and preferences, and these are heard by the clinician. For this to influence treatment, it must occur in an environment structured to support and value patient-centered goals.

Allied health
rehabilitation
patient care planning
patient-centered care
qualitative study


Rapid recurrence of squamous cell carcinoma at a lymphocele after nephroureterectomy: A rare case report.

Abstract:
Introduction
Lymphoceles are sometimes formed after pelvic lymph node dissection. However, recurrence at lymphoceles has not been reported previously. Here, we report a case of rapid prognosis of the recurrence at a lymphocele after nephroureterectomy.

Case presentation
A 78-year-old man underwent retroperitoneoscopic radical nephroureterectomy with pelvic lymphadenectomy for left ureteral urothelial carcinoma. The histopathological diagnosis was high-grade invasive urothelial carcinoma with squamous differentiation. Follow-up computed tomography at 3 months postoperatively showed a lymphocele with a small solid component, in the left pelvic region. At 7 months postoperatively, he presented with severe fatigue, and computed tomography showed a solid tumor had replaced the lymphocele. Computed tomography-guided biopsy was performed and histopathological diagnosis was squamous cell carcinoma.

Conclusion
This report provides support for possible recurrence at the lymphocele after nephroureterectomy. If lymphocele occurs after surgery for malignant disease, it is recommended to follow up with the possibility of recurrence in the lymphatic cysts in mind.

lymphocele
urothelial carcinoma
squamous differentiation
metastasis
ureteral cancer


The 'known' genetic potential for microbial communities to degrade organic phosphorus is reduced in low-pH soils.

Abstract: In soil, bioavailable inorganic orthophosphate is found at low concentrations and thus limits biological growth. To overcome this phosphorus scarcity, plants and bacteria secrete numerous enzymes, namely acid and alkaline phosphatases, which cleave orthophosphate from various organic phosphorus substrates. Using profile hidden Markov modeling approaches, we investigated the abundance of various non specific phosphatases, both acid and alkaline, in metagenomes retrieved from soils with contrasting pH regimes. This analysis uncovered a marked reduction in the abundance and diversity of various alkaline phosphatases in low-pH soils that was not counterbalanced by an increase in acid phosphatases. Furthermore, it was also discovered that only half of the bacterial strains from different phyla deposited in the Integrated Microbial Genomes database harbor alkaline phosphatases. Taken together, our data suggests that these 'phosphatase lacking' isolates likely increase in low-pH soils and future research should ascertain how these bacteria overcome phosphorus scarcity.

microbial community
soil
alkaline phosphatase
metagenomics
Acid phosphatase
microbial diversity


Targeting JAK/STAT signaling pathways in treatment of inflammatory bowel disease.

Abstract: Janus kinase/signal transduction and transcriptional activator (JAK/STAT) signaling pathway is a transport hub for cytokine secretion and exerts its effects. The activation of JAK/STAT signaling pathway is essential for the regulation of inflammatory responses. Inappropriate activation or deletion of JAK/STAT signaling pathway is the initiator of the inflammatory response. JAK/STAT signaling pathway has been demonstrated to be involved in the process of innate and adaptive immune response to inflammatory bowel disease (IBD). In this review, we discuss the role of the JAK/STAT signaling pathway in the regulation of different cells in IBD, as well as new findings on the involvement of the JAK/STAT signaling pathway in the regulation of the intestinal immune response. The current status of JAK inhibitors in the treatment of IBD is summarized as well. This review highlights natural remedies that can serve as potential JAK inhibitors. These phytochemicals may be useful in the identification of precursor compounds in the process of designing and developing novel JAK inhibitors.

JAK/STAT
Inflammatory bowel disease
Cytokine
JAK inhibitor
Intestinal inflammation
Traditional Chinese medicine


Supramolecular Self-Healing Sensor Fiber Composites for Damage Detection in Piezoresistive Electronic Skin for Soft Robots.

Abstract: Self-healing materials can prolong the lifetime of structures and products by enabling the repairing of damage. However, detecting the damage and the progress of the healing process remains an important issue. In this study, self-healing, piezoresistive strain sensor fibers (ShSFs) are used for detecting strain deformation and damage in a self-healing elastomeric matrix. The ShSFs were embedded in the self-healing matrix for the development of self-healing sensor fiber composites (ShSFC) with elongation at break values of up to 100%. A quadruple hydrogen-bonded supramolecular elastomer was used as a matrix material. The ShSFCs exhibited a reproducible and monotonic response. The ShSFCs were investigated for use as sensorized electronic skin on 3D-printed soft robotic modules, such as bending actuators. Depending on the bending actuator module, the electronic skin was loaded under either compression (pneumatic-based module) or tension (tendon-based module). In both configurations, the ShSFs could be successfully used as deformation sensors, and in addition, detect the presence of damage based on the sensor signal drift. The sensor under tension showed better recovery of the signal after healing, and smaller signal relaxation. Even with the complete severing of the fiber, the piezoresistive properties returned after the healing, but in that case, thermal heat treatment was required. With their resilient response and self-healing properties, the supramolecular fiber composites can be used for the next generation of soft robotic modules.

self-healing sensors
electronic skin
soft robotics
strain sensor
self-healing thermoplastic elastomers


Contrasting association of Leptin receptor polymorphisms and haplotypes with polycystic ovary syndrome in Bahraini and Tunisian women: a case-control study.

Abstract:
BACKGROUND
The present study examined the contribution of ethnicity to the association of leptin receptor gene (LEPR) gene variants with polycystic ovary syndrome (PCOS) in Tunisian and Bahraini Arabic-speaking women.

METHODS
Subjects consisted of 320 women with PCOS, and 446 eumenorrhic women from Tunisia, and 242 women with PCOS and 238 controls from Bahrain. Genotyping of (exonic) rs1137100 and rs1137101 and (intronic) rs2025804 LEPR variants was done by allelic exclusion.

RESULTS
The minor allele frequencies (MAFs) of rs1137100 and rs1137101 were significantly different between PCOS cases and control women from Bahrain but not Tunisia, and LEPR rs1137101 was associated with increased PCOS susceptibility only in Bahraini subjects. Furthermore, rs1137100 was associated with decreased PCOS risk among Bahrainis under codominant and recessive models; rs1137100 was negatively associated with PCOS in Tunisians after controlling for testosterone. In addition, rs2025804 was associated with increased PCOS risk among Tunisian but not Bahraini women, after adjusting for key covariates. Negative correlation was seen between rs1137101 and triglycerides in Tunisians, while homeostasis model assessment of insulin resistance (HOMA-IR) and insulin correlated with rs2025804 and rs1137101 among Bahraini subjects, and rs1137101 correlated with estradiol and prolactin. Taking TAG haplotype as common, positive association of TAA and negative association of TGG haplotype with PCOS was seen among Bahraini women; no three-locus PCOS-associated haplotypes were found in Tunisians.

CONCLUSIONS
The present study is the first to demonstrate the contribution of ethnicity to the association of LEPR gene variants with PCOS, thereby highlighting the significance of controlling for ethnicity in gene association investigations.

Dallel|Meriem|M|
Douma|Zeineb|Z|
Finan|Ramzi R|RR|
Hachani|Feten|F|
Letaifa|Dhafer B|DB|
Mahjoub|Touhami|T|
Almawi|Wassim Y|WY|

Leptin receptor
Polycystic ovary syndrome
Genotyping
Gene association


Measurement of thyroglobulin level in lateral neck lymph node fine needle aspiration washout fluid in papillary thyroid cancer.

Abstract:
Background
Thyroglobulin (Tg) level of fine needle aspiration (FNA) washout fluid (FNA-Tg) is useful to detect cervical lymph node (LN) metastasis in patients with papillary thyroid cancer (PTC). The objective of this study was to determine appropriate cutoff values of serum Tg (S-Tg) and FNA-Tg levels for diagnosis of lateral neck LN metastasis and investigate their diagnostic performance.

Methods
A total of 169 patients with PTC who underwent modified radical neck dissection (mRND) were retrospectively reviewed at Seoul St. Mary's Hospital (Seoul, Korea) from December 2011 to September 2019. Diagnostic performance of FNA-Tg, Tg ratio (FNA-Tg level/S-Tg level), and FNA-Tg combined with Tg ratio was evaluated by correlation with FNA cytology results.

Results
FNA-Tg level ≥20 ng/mL exhibited 86.6% sensitivity, 66.7% specificity, and 81.7% accuracy. Tg ratio ≥3 exhibited lower sensitivity but higher specificity (82.7% and 73.8%, respectively) than FNA-Tg level ≥20 ng/mL. FNA-Tg level ≥20 ng/mL combined with Tg ratio ≥3 had 81.9% sensitivity, 80.5% accuracy, and an integrated area under the curve (iAUC) of 0.790.

Conclusions
Measurement of FNA-Tg level increases preoperative diagnostic accuracy for the detection of metastatic LNs in patients with PTC. Diagnostic accuracy is higher using a 20 ng/mL FNA-Tg cutoff level. Tg ratio is also valuable and FNA-Tg combined with Tg ratio shows promise.

Kim|Kwangsoon|K|
Bae|Ja Seong|JS|
Kim|Jeong Soo|JS|

fine needle aspiration (FNA)
papillary thyroid cancer (PTC)
modified radical neck dissection (mRND)
Thyroglobulin washout
lymph node metastasis


An Investigation on Spray-Granulated, Macroporous, Bioactive Glass Microspheres for a Controlled Drug Delivery System.

Abstract: Bioactive glass (BG) has been regarded as an excellent candidate for biomedical applications due to its superior properties of bioactivity, biocompatibility, osteoconductivity and biodegradability. Thus, in this study, we aimed to fabricate drug carriers that were capable of loading therapeutic antibiotics while promoting bone regeneration using macroporous BG microspheres, prepared by a spray drying method. Characterizations of particle morphology and specific surface area were carried out via scanning electron microscopy and nitrogen adsorption/desorption isotherm. Evaluations of in vitro bioactivity were performed based on Kokubo's simulated body fluid to confirm the formation of the hydroxyapatite (HA) layer after immersion. In addition, the in vitro drug release behaviors were examined, using tetracycline as the therapeutic antibiotic in pH 7.4 and 5.0 environments. Finally, the results showed that BG microspheres of up to 33 μm could be mass-produced, targeting various therapeutic situations and their resulting bioactivities and drug release behaviors, and related properties were discussed.

bioactive glass
controlled drug delivery
electron microscopy
spray granulation


Lectin-like transcript 1 is a marker of germinal center-derived B-cell non-Hodgkin's lymphomas dampening natural killer cell functions.

Abstract: Non-Hodgkin's lymphomas (NHLs) are malignant neoplasms which are clinically and biologically diverse. Their incidence is constantly increasing and despite treatment advances, there is a need for novel targeted therapies. Here, we identified Lectin-like transcript 1 (LLT1) as a biomarker of germinal center (GC)-derived B-cell NHLs. LLT1 identifies GC B cells in reactive tonsils and lymph nodes and its expression is maintained in B-cell NHLs which derive from GC, including Burkitt lymphoma (BL), follicular lymphoma (FL), and GC-derived diffuse large B-cell lymphoma (DLBCL). We further show that LLT1 expression by tumors dampens natural killer (NK) cell functions following interaction with its receptor CD161, uncovering a potential immune escape mechanism. Our results pinpoint LLT1 as a novel biomarker of GC-derived B-cell NHLs and as a candidate target for innovative immunotherapies.

Germain|Claire|C|
Guillaudeux|Thierry|T|
Galsgaard|Elisabeth D|ED|
Hervouet|Catherine|C|
Tekaya|Nedra|N|
Gallouet|Anne-Sophie|AS|
Fassy|Julien|J|
Bihl|Franck|F|
Poupon|Gwenola|G|
Lazzari|Anne|A|
Spee|Pieter|P|
Anjuère|Fabienne|F|
Pangault|Céline|C|
Tarte|Karin|K|
Tas|Patrick|P|
Xerri|Luc|L|
Braud|Veronique M|VM|


Loss of anti-hepatitis C virus antibodies following therapeutic sustained virological response in a HIV co-infected patient.

Abstract: No data are available for the kinetics of anti-Hepatitis C Virus (HCV) antibodies in HIV/HCV co-infected patients after sustained virological response (SVR). We present a case of a HIV/HCV co-infected patient, showing a significant anti-HCV antibodies decrease during therapy, who achieved a HCV seroreversion 3 years after SVR. Among them, antibodies to core protein, the most strongly antigenic protein showed significant decrease. Our results indicate an absence of antigenic stimulation suggesting a total clearance of HCV.

Maylin|Sarah|S|
de Verdière|Nathalie Colin|NC|
Salmona|Maud|M|
Simon|François|F|
Delaugerre|Constance|C|

D000328:Adult
D000998:Antiviral Agents
D015658:HIV Infections
D006526:Hepatitis C
D018937:Hepatitis C Antibodies
D006801:Humans
D008297:Male
D016896:Treatment Outcome
D019562:Viral Load

HIV
HCV
SVR
anti-HCV antibodies
Clearance


The role of the intestinal microbiota in uremic solute accumulation: a focus on sulfur compounds.

Abstract: The gut microbiota is considered to be a novel important factor to take into account in the pathogenesis of chronic kidney disease and uremia. Much attention has been paid to specific uremic retention solutes of microbial origin, such as indoxyl sulfate, p-cresyl sulfate, and trimethylamine-N-oxide. However, other novel less well studied compounds, such as hydrogen sulfide and related sulfur metabolites (sulfane sulfur, lanthionine, etc.), should be included in a more comprehensive appraisal of this topic, in light of the potential therapeutic opportunities for the future.

Microbiota
Chronic kidney disease
Uremia
Hydrogen sulfide
Sulfane sulfur
Lanthionine
Dialysis
Homocysteine
Uremic toxins


Cytotoxic phenylpropanoid glycosides from Fagopyrum tataricum (L.) Gaertn.

Abstract: Fagopyrum tataricum (L.) Gaertn (tartary buckwheat) is an ancient dicotyledonous crop belonging to Polygonaceae family. Besides its benefits for human consumption, tartary buckwheat is also an important folk medicine in China for its antioxidant, antitumour, hypotensive, hypoglycaemic and hypolipidaemic activities. Phytochemical investigation of the ethyl acetate fraction of tartary buckwheat roots led to the isolation of seven new phenylpropanoid glycosides, tatarisides A-G (1-7), together with a known phenylpropanoid glycoside, diboside A (8). Their structures were elucidated by means of spectroscopic methods. All compounds (1-8) were evaluated for their cytotoxic activity against four human cancer cell lines (A-549, HCT116, ZR-75-30 and HL-60). Tatariside C (3) was the most active compound with IC50 values of 6.44-7.49μg/ml against the four tested cell lines.

Zheng|Chengjian|C| Hu|Changling|C| Ma|Xueqin|X| Peng|Cheng|C| Zhang|Hong|H| Qin|Luping|L|

Phenylpropanoid glycosides
Fagopyrum tataricum (L.) Gaertn
Cytotoxic activity
Tatarisides A–G


Targeted Reminder Phone Calls to Patients at High Risk of No-Show for Primary Care Appointment: A Randomized Trial.

Abstract:
BACKGROUND
No-shows, or missed appointments, are a problem for many medical practices. They result in fragmented care and reduce access for all patients.

OBJECTIVE
To determine whether telephone reminder calls targeted to patients at high risk of no-show can reduce no-show rates.

DESIGN
Single-center randomized controlled trial.

PARTICIPANTS
A total of 2247 primary care patients in a hospital-based primary care clinic at high risk of no-show (>15 % risk) for their appointment in 7 days.

INTERVENTION
Seven days prior to their appointment, intervention arm patients were placed in a calling queue to receive a reminder phone call from a patient service coordinator. Coordinators were trained to engage patients in concrete planning. All patients received an automated phone call (usual care).

MAIN MEASURES
Primary outcome was no-show rate. Secondary outcomes included arrival rate, cancellation rate, reschedule rate, time to cancellation, and change in revenue.

KEY RESULTS
The no-show rate in the intervention arm (22.8 %) was significantly lower (absolute risk difference -6.4 %, p < 0.01, 95 % CI [-9.8 to -3.0 %]) than that in the control arm (29.2 %). Arrival, cancellation, and reschedule rates did not differ significantly. In the intervention arm, rescheduling and cancellations occurred further in advance of the appointment (mean difference, 0.35 days; 95 % CI [0.07-0.64]; p = 0.01). Reimbursement did not differ significantly.

CONCLUSIONS
A phone call 7 days prior to an appointment led to a significant reduction in no-shows and increased reimbursement among patients at high risk of no-show. The use of targeted interventions may be of interest to practices taking on increased accountability for population health.

Shah|Sachin J|SJ|
Cronin|Patrick|P|
Hong|Clemens S|CS|
Hwang|Andrew S|AS|
Ashburner|Jeffrey M|JM|
Bearnot|Benjamin I|BI|
Richardson|Calvin A|CA|
Fosburgh|Blair W|BW|
Kimball|Alexandra B|AB|

D000046:Academic Medical Centers
D000328:Adult
D000368:Aged
D001071:Appointments and Schedules
D040421:Cell Phone
D005260:Female
D006801:Humans
D008297:Male
D008875:Middle Aged
D000067455:No-Show Patients
D010044:Outpatient Clinics, Hospital
D010349:Patient Compliance
D011320:Primary Health Care
D017010:Reminder Systems
D012307:Risk Factors
D060145:Text Messaging

population health
access to care
applied informatics
behavior change
primary care redesign