A Decaheme Cytochrome as a Molecular Electron Conduit in Dye-Sensitized Photoanodes.

Abstract: In nature, charge recombination in light-harvesting reaction centers is minimized by efficient charge separation. Here, it is aimed to mimic this by coupling dye-sensitized TiO2 nanocrystals to a decaheme protein, MtrC from Shewanella oneidensis MR-1, where the 10 hemes of MtrC form a ≈7-nm-long molecular wire between the TiO2 and the underlying electrode. The system is assembled by forming a densely packed MtrC film on an ultra-flat gold electrode, followed by the adsorption of approximately 7 nm TiO2 nanocrystals that are modified with a phosphonated bipyridine Ru(II) dye (RuP). The step-by-step construction of the MtrC/TiO2 system is monitored with (photo)electrochemistry, quartz-crystal microbalance with dissipation (QCM-D), and atomic force microscopy (AFM). Photocurrents are dependent on the redox state of the MtrC, confirming that electrons are transferred from the TiO2 nanocrystals to the surface via the MtrC conduit. In other words, in these TiO2/MtrC hybrid photodiodes, MtrC traps the conduction-band electrons from TiO2 before transferring them to the electrode, creating a photobioelectrochemical system in which a redox protein is used to mimic the efficient charge separation found in biological photosystems.

Hwang|Ee Taek|ET|
Sheikh|Khizar|K|
Orchard|Katherine L|KL|
Hojo|Daisuke|D|
Radu|Valentin|V|
Lee|Chong-Yong|CY|
Ainsworth|Emma|E|
Lockwood|Colin|C|
Gross|Manuela A|MA|
Adschiri|Tadafumi|T|
Reisner|Erwin|E|
Butt|Julea N|JN|
Jeuken|Lars J C|LJ|

dye-sensitized nanoparticles
electron transfer
metalloprotein
photoelectrochemistry
protein-film electrochemistry


The differential organogenesis and functionality of two liver-draining lymph nodes in mice.

Abstract: The liver is an immunological organ. However, fundamental knowledge concerning liver-draining lymph nodes (LNs), which have been newly identified in mice as the portal and celiac LNs, is still lacking. Here, we revealed that the portal LN and celiac LN drain liver lymph through different lymphatic vessels. Although both the portal LN and celiac LN possess typical structures, they have different cell compositions. Interestingly, these two LNs form at different times during fetal development. Moreover, the organogenesis of the celiac LN, but not the portal LN, is controlled by the transcription factor NFIL3. Furthermore, the portal LN and celiac LN also perform different functions. The celiac LN is the predominant site of liver antiviral immune responses, whereas the portal LN functions in the in situ induction of dietary antigen-specific regulatory T cells. In conclusion, the portal LN and celiac LN are two independent liver-draining LNs with different organogenesis histories and separate functions in maintaining immune homeostasis in the liver.

Yu|Jiali|J| Chen|Yongyan|Y| Wu|Yuzhang|Y| Ye|Lilin|L| Lian|Zhexiong|Z| Wei|Haiming|H| Sun|Rui|R| Tian|Zhigang|Z|

D050976:Basic-Leucine Zipper Transcription Factors

D053631:Interleukin Receptor Common gamma Subunit

Organogenesis
Celiac lymph node
Immunotolerance
Portal lymph node
Viral infection


Survivorship and Complications of Revision Total Hip Arthroplasty with a Mid-Modular Femoral Stem.

Abstract: We retrospectively reviewed 161 revision THAs with diaphyseal fitting, mid-modular femoral components performed by ten surgeons at two academic medical centers. The average follow-up was 6.1 years. At final follow-up, 4 patients required re-revision for failure of the femoral component; 3 (2%) for aseptic loosening and 1 for mechanical failure of stem in setting of periprosthetic fracture. There were a total of 24 (14.9%) revisions for any reason, with the most common reason being septic failure (10 of 24). To our knowledge, this is the largest reported series of mid-term survivorship and complications of revision THA with mid-modular femoral components. Our results show that these stems have a low rate of aseptic loosening, subsidence, and mechanical failure.

Riesgo|Aldo M|AM|
Hochfelder|Jason P|JP|
Adler|Edward M|EM|
Slover|James D|JD|
Specht|Lawrence M|LM|
Iorio|Richard|R|

mid-modular femoral stem
loosening
subsidence
Restoration Modular
revision hip arthroplasty


Aortopathy in a Mouse Model of Marfan Syndrome Is Not Mediated by Altered Transforming Growth Factor β Signaling.

Abstract:
BACKGROUND
Marfan syndrome (MFS) is caused by mutations in the gene encoding fibrillin-1 (FBN1); however, the mechanisms through which fibrillin-1 deficiency causes MFS-associated aortopathy are uncertain. Recently, attention was focused on the hypothesis that MFS-associated aortopathy is caused by increased transforming growth factor-β (TGF-β) signaling in aortic medial smooth muscle cells (SMC). However, there are many reasons to doubt that TGF-β signaling drives MFS-associated aortopathy. We used a mouse model to test whether SMC TGF-β signaling is perturbed by a fibrillin-1 variant that causes MFS and whether blockade of SMC TGF-β signaling prevents MFS-associated aortopathy.

METHODS AND RESULTS
MFS mice (Fbn1C1039G/+ genotype) were genetically modified to allow postnatal SMC-specific deletion of the type II TGF-β receptor (TBRII; essential for physiologic TGF-β signaling). In young MFS mice with and without superimposed deletion of SMC-TBRII, we measured aortic dimensions, histopathology, activation of aortic SMC TGF-β signaling pathways, and changes in aortic SMC gene expression. Young Fbn1C1039G/+ mice had ascending aortic dilation and significant disruption of aortic medial architecture. Both aortic dilation and disrupted medial architecture were exacerbated by superimposed deletion of TBRII. TGF-β signaling was unaltered in aortic SMC of young MFS mice; however, SMC-specific deletion of TBRII in Fbn1C1039G/+ mice significantly decreased activation of SMC TGF-β signaling pathways.

CONCLUSIONS
In young Fbn1C1039G/+ mice, aortopathy develops in the absence of detectable alterations in SMC TGF-β signaling. Loss of physiologic SMC TGF-β signaling exacerbates MFS-associated aortopathy. Our data support a protective role for SMC TGF-β signaling during early development of MFS-associated aortopathy.

Wei|Hao|H|
Hu|Jie Hong|JH|
Angelov|Stoyan N|SN|
Fox|Kate|K|
Yan|James|J|
Enstrom|Rachel|R|
Smith|Alexandra|A|
Dichek|David A|DA|

D000077294:Receptor, Transforming Growth Factor-beta Type II

D018125:Receptors, Transforming Growth Factor beta

transforming growth factor‐β pathway aneurysm


Continuous glucose monitoring in the ICU: clinical considerations and consensus.

Abstract: Glucose management in intensive care unit (ICU) patients has been a matter of debate for almost two decades. Compared to intermittent monitoring systems, continuous glucose monitoring (CGM) can offer benefit in the prevention of severe hyperglycemia and hypoglycemia by enabling insulin infusions to be adjusted more rapidly and potentially more accurately because trends in glucose concentrations can be more readily identified. Increasingly, it is apparent that a single glucose target/range may not be optimal for all patients at all times and, as with many other aspects of critical care patient management, a personalized approach to glucose control may be more appropriate. Here we consider some of the evidence supporting different glucose targets in various groups of patients, focusing on those with and without diabetes and neurological ICU patients. We also discuss some of the reasons why, despite evidence of benefit, CGM devices are still not widely employed in the ICU and propose areas of research needed to help move CGM from the research arena to routine clinical use.

Krinsley|James S|JS|
Chase|J Geoffrey|JG|
Gunst|Jan|J|
Martensson|Johan|J|
Schultz|Marcus J|MJ|
Taccone|Fabio S|FS|
Wernerman|Jan|J|
Bohe|Julien|J|
De Block|Christophe|C|
Desaive|Thomas|T|
Kalfon|Pierre|P|
Preiser|Jean-Charles|JC|

Glucose
Monitoring
Insulin
Diabetes
Neurointensive care


Audiovisual plasticity following early abnormal visual experience: Reduced McGurk effect in people with one eye.

Abstract: Previously, we have shown that people who have had one eye surgically removed early in life during visual development have enhanced sound localization [1] and lack visual dominance, commonly observed in binocular and monocular (eye-patched) viewing controls [2]. Despite these changes, people with one eye integrate auditory and visual components of multisensory events optimally [3]. The current study investigates how people with one eye perceive the McGurk effect, an audiovisual illusion where a new syllable is perceived when visual lip movements do not match the corresponding sound [4]. We compared individuals with one eye to binocular and monocular viewing controls and found that they have a significantly smaller McGurk effect compared to binocular controls. Additionally, monocular controls tended to perceive the McGurk effect less often than binocular controls suggesting a small transient modulation of the McGurk effect. These results suggest altered weighting of the auditory and visual modalities with both short and long-term monocular viewing. These results indicate the presence of permanent adaptive perceptual accommodations in people who have lost one eye early in life that may serve to mitigate the loss of binocularity during early brain development.

Moro|Stefania S|SS|
Steeves|Jennifer K E|JKE|

McGurk effect
Multisensory
Audiovisual processing
Face processing
Monocular enucleation
Voice processing


Curvature Blindness Illusion.

Abstract: We report a novel illusion--curvature blindness illusion: a wavy line is perceived as a zigzag line. The following are required for this illusion to occur. First, the luminance contrast polarity of the wavy line against the background is reversed at the turning points. Second, the curvature of the wavy line is somewhat low; the right angle is too steep to be perceived as an illusion. This illusion implies that, in order to perceive a gentle curve, it is necessary to satisfy more conditions--constant contrast polarity--than perceiving an obtuse corner. It is notable that observers exactly "see" an illusory zigzag line against a physically wavy line, rather than have an impaired perception. We propose that the underlying mechanisms for the gentle curve perception and those of obtuse corner perception are competing with each other in an imbalanced way and the percepts of corner might be dominant in the visual system.

illusion
perception
contours or surfaces
curvature perception


Mitochondrial quality control: from molecule to organelle.

Abstract: Mitochondria are organelles central to myriad cellular processes. To maintain mitochondrial health, various processes co-operate at both the molecular and organelle level. At the molecular level, mitochondria can sense imbalances in their homeostasis and adapt to these by signaling to the nucleus. This mito-nuclear communication leads to the expression of nuclear stress response genes. Upon external stimuli, mitochondria can also alter their morphology accordingly, by inducing fission or fusion. In an extreme situation, mitochondria are degraded by mitophagy. Adequate function and regulation of these mitochondrial quality control pathways are crucial for cellular homeostasis. As we discuss, alterations in these processes have been linked to several pathologies including neurodegenerative diseases and cancer.

Roca-Portoles|Alba|A|
Tait|Stephen W G|SWG|

Mitophagy
ISR
Mitochondrial diseases
Mitochondrial dysfunction
Mitochondrial fission
Mitochondrial fusion
PINK1
Parkin
UPRmt


The challenge of cultural gerontology.

Abstract: Over the last decade, Cultural Gerontology has emerged as one of the most vibrant elements of writing about age (Twigg, J., & Martin, W. (Eds.) (2015). The Routledge handbook of cultural gerontology. London: Routledge). Reflecting the wider Cultural Turn, it has expanded the field of gerontology beyond all recognition. No longer confined to frailty, or the dominance of medical and social welfare perspectives, cultural gerontology addresses the nature and experience of later years in the widest sense. In this review, we will explore how the Cultural Turn, which occurred across the social sciences and humanities in the late 20th century, came to influence age studies. We will analyze the impulses that led to the emergence of the field and the forces that have inhibited or delayed its development. We will explore how cultural gerontology has recast aging studies, widening its theoretical and substantive scope, taking it into new territory intellectually and politically, presenting this in terms of 4 broad themes that characterize the work: subjectivity and identity; the body and embodiment; representation and the visual; and time and space. Finally, we will briefly address whether there are problems in the approach.

Identity
Body
Representation
Time
Space
Arts and humanities
Postmodernism
Poststructuralism


Bilateral thoracoscopic sympathectomy for cardiac denervation in pediatric population: Does Kuntz nerve cauterization have an impact on success?

Abstract:
INTRODUCTION
Cardiac sympathetic denervation (CSD) is an effective procedure for the treatment of inherited channelopathies. Left CSD has traditionally been recommended as neuromodulation to prevent arrhythmia episodes; however, it is thought that bilateral sympathectomy in combination with Kuntz ablation may have additional effects effective due to the anatomical variability of preganglionic sympathetic fibers. The aim of the study was to share our single-center clinical experience with bilateral thoracoscopic sympathectomy for cardiac denervation in different groups of pediatric patients with malignant arrhythmias.

METHODS
Fourteen patients (seven with CPVT, five with LQTS, one with resistant ventricular tachycardia as a sequela of myocarditis, and one with cardiomyopathy and atrial tachycardia) underwent bilateral thoracoscopic sympathectomy for cardiac denervation.

RESULTS
In all patients, arrhythmia episodes persisted despite medical therapy, and patients with implantable cardioverter-defibrillator received appropriate therapies. The rate of appropriate therapies was 3.25 per year (1-5 per year) in the year before sympathectomy. No major complications related to the procedure were observed in any of the patients. The QTc interval of LQTS patients decreased from 506.2 ± 16.9 ms before the procedure to 476 ± 28.8 ms after the procedure. The mean duration of follow-up after the procedure was 23.3 months (11-47 months). Only two patients received single episodes of therapy 12 and 22 months after CSD, and one patient had arrhythmic events due to noncompliance to medical therapy.

CONCLUSION
Due to the anatomical variability of preganglionic fibers bilateral CSD with Kuntz nerve ablation effective treatment and is a safe option.

catecholaminergic polymorphic ventricular tachycardia


Contribution of the immune system to follicle differentiation, ovulation and early corpus luteum formation.

Abstract: Much of what we know about the involvement of the immune system in periovulatory follicle differentiation, ovulation and subsequent formation of the corpus luteum in cattle is drawn from the findings of studies in several mammalian livestock species. By integrating published histological data from cattle, sheep and pigs and referring back to the more comprehensive knowledge bank that exists for mouse and humans we can sketch out the key cells of the immune system and the cytokines and growth factors that they produce that are involved in follicle differentiation and luteinization, ovulation and early follicle development. These contributions are reviewed and the key findings, discussed.


Prognostic Impact of the Number of Metastatic Lymph Nodes on the Eighth Edition of the TNM Classification of NSCLC.

Abstract:
INTRODUCTION
Current nodal staging of NSCLC is defined only by anatomical location of lymph nodes (LNs). The aim of this study is to investigate prognostic impacts of the number of metastatic LNs by stratifying the present N classification.

METHODS
We analyzed 1989 patients with NSCLC who underwent complete resection by lobectomy or pneumonectomy involving dissection of the hilar and mediastinal LNs from 2003 to 2012. We classified patients according to the number of metastatic nodes and stations and their current category of metastatic LNs. We analyzed the overall survival in each group and assessed the survival impact of the combination of them.

RESULTS
In the multivariate analyses of all patients, pathological N1 (pN1) (reference [ref.] pN2) and single-node metastasis (ref. multiple-node) were independent prognostic factors whereas single-station metastasis (ref. multiple-station) was not. In the respective multivariate analyses of pN1 and pN2 disease, multiple-node metastasis (ref. single-node) was an independent prognostic factor in pN1 disease (hazard ratio: 1.41, p = 0.04), but not in pN2 disease. Investigation for other boundaries of a number of metastatic LNs of three or more (ref. one to two), four or more (ref. one to three), and five or more (ref. one to four) found that all of them were independent prognostic factors in both pN1 and pN2 diseases.

CONCLUSIONS
The number of metastatic LNs had a strong impact on survival in addition to the current pN classification. To clarify its prognostic impact, further study is needed in other datasets including patients treated by nonsurgical modalities.

Katsumata|Shinya|S| Aokage|Keiju|K| Ishii|Genichiro|G| Nakasone|Shoko|S| Sakai|Takashi|T| Okada|Satoshi|S| Miyoshi|Tomohiro|T| Tane|Kenta|K| Tsuboi|Masahiro|M|

Number of metastatic lymph nodes
TNM
NSCLC
Lymph node metastasis
Number of metastatic station


Oral Intake of Carboxymethyl-Glucan (CM-G) from Yeast (Saccharomyces uvarum) Reduces Malondialdehyde Levels in Healthy Men.

Abstract: Carboxymethyl-glucan (CM-G) is a water-soluble derivative of β(1 → 3)(1 → 6) glucan, a well-known immunostimulant and antioxidant compound. In this experimental, randomized and placebo-controlled study, the effects of oral CM-G intake over a 60-day period on the peripheral blood, cholesterol, glycemic index and malondialdehyde (MDA) levels of healthy men was assessed. The CM-G was obtained from spent brewer's yeast (S. uvarum) with DS 0.8 and molecular weight of 2.2 × 10(5) Da. Following CM-G administration, no changes were observed in red and white blood cell, hematocrit, hemoglobin and platelet counts, or in cholesterol and glycemic indices. After 30 days of CM-G administration, the MDA levels decreased significantly (p ≤ 0.05) in men receiving CM-G. The results showed for the first time that CM-G may act as an adjuvant in preventing oxidative damage in healthy humans.

Araújo|Vilma Barbosa da Silva|VB|
de Melo|Adma Nadja Ferreira|AN|
de Souza|Neyrijane Targino|NT|
da Silva|Vânia Maria Barboza|VM|
Castro-Gomez|Raul H|RH|
Silva|Alexandre Sérgio|AS|
de Souza|Evandro Leite|EL|
Magnani|Marciane|M|

carboxymethyl-glucan
malondialdehyde
blood cells
glucan-derivatives


Kinetics and model development of iohexol degradation during UV/H2O2 and UV/S2O82- oxidation.

Abstract: The degradation rates and kinetics of one commonly used iodinated contrast medium, iohexol, were investigated and compared during ultraviolet (UV) photolysis, UV/H2O2 and UV/S2O82- advanced oxidation processes (AOPs). Results indicate that the iohexol degradation rate increased in the order of UV/H2O2 < UV irradiation < UV/S2O82- and followed pseudo-first-order kinetics. Increasing persulfate concentration significantly increased iohexol degradation rate, whereas increasing H2O2 concentration caused reverse effect. Radical scavenging test results show that UV photolysis, OH and radicals all contributed to iohexol degradation during UV/S2O82-, but OH was the main contributor during UV/H2O2 and was consumed by excess H2O2. The kinetic models of iohexol degradation by both AOPs were developed, and the reaction rate constants with OH and were calculated as 5.73 (±0.02) × 108 and 3.91 (±0.01) × 1010 M-1 s-1, respectively. Iohexol degradation rate remained stable at pH 5-9 during UV irradiation and UV/H2O2, but gradually decreased at pH 5-7 and remained stable at pH 7-9 during UV/S2O82-. The presence of anions displayed inhibitory effects on iohexol degradation during UV/S2O82- in the order of Cl- >HCO3- ≫ SO42-. UV/S2O82- AOP exhibited high degradation efficiency and stability on the basis of UV irradiation, which can be applied as a promising degradation method for iohexol. UV/S2O82- AOP can effectively mineralize iohexol to CO2 but promoted the generation of toxic iodoform (CHI3), and the subsequent chlorination had the potential to reduce the content of disinfection by-products; therefore, further evaluation of possible environmental hazards is warranted.

Hu|Chen-Yan|CY| Hou|Yuan-Zhang|YZ| Lin|Yi-Li|YL| Deng|Yan-Guo|YG| Hua|Shuang-Jing|SJ| Du|Yi-Fan|YF| Chen|Chiu-Wen|CW| Wu|Chung-Hsin|CH|

Kinetics
Hydroxyl and sulfate radicals
Iodinated X-ray contrast media (ICM)
UV/
UV/H(2)O(2)


Electrochemical determination of bentazone using simple screen-printed carbon electrodes.

Abstract: Bentazone is one of the most problematic pesticides polluting groundwater resources. It is on the list of pesticides that are mandatory to analyze at water work controls. The current pesticide measuring approach includes manual water sampling and time-consuming chromatographical quantification of the bentazone content at centralized laboratories. Here, we report the use of an electrochemical approach for analytical determination of bentazone that takes 10 s. The electrochemical electrodes were manually screen printed, resulting in the low-cost fabrication of the sensors. The current response was linearly proportional to the bentazone concentration with a R2 ~ 0.999. We demonstrated a sensitivity of 0.0987 μA/μM and a limit of detection of 0.034 μM, which is below the U.S. Health Advisory level. Furthermore, the sensors have proved to be reusable and stable with a drop of only 2% after 15 times reuse. The sensors have been applied to successfully quantify bentazone spiked in real groundwater and lake water. The sensing method presented here is a step towards on-site application of electrochemical detection of pesticides in water sources.

Geto|Alemnew|A|
Noori|Jafar Safaa|JS|
Mortensen|John|J|
Svendsen|Winnie E|WE|
Dimaki|Maria|M|

Bentazone Pesticide Groundwater Sensor Contamination Electrochemistry


What is the Best Revascularization Strategy for Acute Occlusive Arterial Mesenteric Ischemia: Systematic Review and Meta-analysis.

Abstract:
PURPOSE
Acute mesenteric ischemia (AMI) is a life-threatening disease that leads to bowel infarction and death. The optimal management of AMI remains controversial. The present meta-analysis aimed to estimate the prognostic impact of surgical (SG) versus endovascular or hybrid intervention (EV) as the first-line treatment for acute arterial occlusive mesenteric ischemia and to assess whether endovascular strategy was actually effective in reducing bowel resection.

METHODS
MEDLINE, Scopus and the Cochrane Library databases were searched. There have been no randomized controlled trials comparing SG versus EV for the treatment of AMI. We undertook this systematic review and meta-analysis according to MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines, assessing the included study quality with the Newcastle-Ottawa scale.

RESULTS
Seven studies comparing EV versus SG as first strategy for the treatment of AMI were selected for the analyses, reporting of 3020 patients. EV was associated with a reduced risk of in-hospital mortality (RR 0.68; 95% CI 0.59-0.79; fixed-effects analysis; p < 0.0001; I 2 = 4.9%; τ 2 = 0.025). Pooled prevalence of mortality was 19% for EV and 34% for SG. EV also showed a benefit impact on risk of bowel resection and second-look laparotomy.

CONCLUSIONS
The present meta-analysis outlines that endovascular revascularization strategy seems to offer advantages in terms of in-hospital mortality and morbidity in case of arterial occlusive AMI. A multidisciplinary team consisting of radiologists, interventional radiologists, cardiovascular and general surgeons comes out to be essential to tailor the right procedure to the patient and improve the outcomes associated with AMI.

Salsano|Giancarlo|G| Salsano|Antonio|A| Sportelli|Elena|E| Petrocelli|Francesco|F| Dahmane|M'ahmed|M| Spinella|Giovanni|G| Pane|Bianca|B| Mambrini|Simone|S| Palombo|Domenico|D| Santini|Francesco|F|

D000208:Acute Disease
D057510:Endovascular Procedures
D017052:Hospital Mortality
D006801:Humans
D065666:Mesenteric Ischemia
D016896:Treatment Outcome
D014656:Vascular Surgical Procedures

Meta-analysis
Acute mesenteric ischemia
First-line treatment


Evaluation of Beta-Cyfluthrin Resistance of Cigarette Beetle (Coleoptera: Anobiidae) from Cigarette Manufacturing Factories of China and Underlying Metabolic Mechanisms Responsible for Resistance.

Abstract: Beta-cyfluthrin, as a synthetic pyrethroid, has been widely used in cigarette manufacturing factories in China to control Lasioderma serricorne (F.) (Coleoptera: Anobiidae). In this study, spray toxicity bioassays and filter paper residual contact toxicity bioassays were conducted to investigate the beta-cyfluthrin sensitivity level of five field strains of L. serricorne collected from cigarette manufacturing factories in China. Bioassay results indicated that five field strains had developed different levels of resistance to beta-cyfluthrin with RR50 of 3.51-10.20 at 2 hr after application and 4.05-49.50 at 24 hr after application in spray toxicity bioassays, and RR50 of 4.74-14.47 at 2 hr exposure in filter paper residual contact bioassays. In addition, we examined CarE, GST, and CYP450 enzyme activity and content of L. serricorne adults and larvae. Enzyme-linked immunosorbent assay results suggested that there was no significant difference in GST, CYP450, and CarE content of L. serricorne adults between field strains and reference sensitive strain. Biochemical assay results indicated that CYP450 activity of L. serricorne adults and larvae of five field strains was significantly higher than that of reference sensitive strain, with increased CYP450 activity of 1.08-1.82-fold in adults and 1.08-2.12-fold in larvae. The results implied that elevated CYP450 activity may contribute to metabolic resistance of L. serricorne to pyrethroid. Our study indicated that there was no clear evidence that the enhanced CarE and GST activity was associated with pyrethroid resistance of L. serricorne.

Sun|Qian|Q| Chen|Xiang|X| Lin|Tao|T| Cheng|Xinsheng|X|0000-0003-4013-6992

D000072499:Manufacturing and Industrial Facilities


Herbal extracts in oral health care - A review of the current scenario and its future needs.

Abstract:
BACKGROUND
Oral diseases are among the major public health problems and the commonest of chronic diseases that affect mankind. The application of natural products for the control of oral diseases is considered as an interesting alternative to synthetic antimicrobials due to their lower negative impact, and for the effort to overcome primary or secondary resistance to the drug during therapy.

OBJECTIVE
To review the current evidence on the antimicrobial efficacy of 10 plant extracts on dental caries and plaque microorganisms.

MATERIALS AND METHODS
A comprehensive literature search was made by one of the authors for 2 months in PubMed, PubMed Central, MEDLINE, LILACS/BBO, Cochrane database of systematic reviews, SCIENCE DIRECT, and Google scholar databases. The results from the relevant published literatures are discussed.

SUMMARY AND CONCLUSION
The extracts of Azadirachta Indica, Ocimum sanctum, Murraya koenigii L., Acacia nilotica, Eucalyptus camaldulensis, Hibiscus sabdariffa, Mangifera indica, Psidium guajava, Rosa indica, and Aloe barbadensis Miller have all been found to inhibit certain dental caries and periodontal pathogens. The current evidence is on individual plant extracts against bacteria involved in either caries or periodontitis. "Herbal shotgun" or "synergistic multitarget effects" are the terms used for the strategy of combining different extracts. The research assessing the antimicrobial efficacy of a combination of these plant extracts against dental caries and periodontal pathogens is the need of the hour, and such research will aid in the development of a novel, innovative method that can simultaneously inhibit two of the most common dental diseases of mankind, besides slowing the development of drug resistance.

Chandra Shekar|Byalakere Rudraiah|BR|
Nagarajappa|Ramesh|R|
Suma|Shankarappa|S|
Thakur|Rupesh|R|

herbal extracts
Antimicrobial efficacy
dental caries
periodontitis
Lactobacillus acidophilus
Streptococcus mutans


Effect of different drying technologies on drying characteristics and quality of red pepper (Capsicum frutescens L.): a comparative study.

Abstract:
BACKGROUND
Hot air drying and sun drying are traditional drying technologies widely used in the drying of agricultural products for a long time, but usually recognized as time-consuming or producing lower-quality products. Infrared drying is a rather effective drying technology that has advantages over traditional drying technologies. Thus, in order to investigate the application of infrared drying in the dehydration of red pepper, the drying characteristics and quality of infrared-dried red pepper were compared with those of sun-dried and hot air-dried red pepper.

RESULTS
The infrared drying technology significantly enhanced the drying rate when compared with hot air drying and sun drying. Temperature was the most important factor affecting the moisture transfer during the process of infrared drying as well as hot air drying. Effective moisture diffusivity (Deff ) values of infrared drying ranged from 1.58 × 10(-9) to 3.78 × 10(-9) m(2) s(-1) . The Ea values of infrared drying and hot air drying were 42.67 and 44.48 kJ mol(-1) respectively. Infrared drying and hot air drying produced color loss to a similar extent. Relatively higher crispness values were observed for infrared-dried samples.

CONCLUSION
Sun drying produced dried red pepper with the best color when compared with hot air drying and infrared drying. Meanwhile, infrared drying markedly improved the drying rate at the same drying temperature level of hot air drying, and the products obtained had relatively better quality with higher crispness values. © 2015 Society of Chemical Industry.

Cao|Zhen-Zhen|ZZ| Zhou|Lin-Yan|LY| Bi|Jin-Feng|JF| Yi|Jian-Yong|JY| Chen|Qin-Qin|QQ| Wu|Xin-Ye|XY| Zheng|Jin-Kai|JK| Li|Shu-Rong|SR|

drying characteristics
infrared drying
effective moisture diffusivity
color
texture


The Relationship of Anxiety and Depression to Subjective Well-Being in a Mainland Chinese Sample.

Abstract: This pilot study examines anxiety, depression, and well-being in a mainland Chinese sample and discusses the implications for mental health care. The Hospital Anxiety and Depression Scale, Functional Assessment of Chronic Illness Therapy-Spiritual Well-being, and the Body Mind Spirit Well-Being Inventory were administered to 60 mainland China residents. Correlational analyses revealed significant relationships among depression, anxiety, and every domain of well-being except the faith domain. Levels of depression and anxiety are inversely related to levels of well-being in a mainland Chinese sample. Chinese culture was expected to moderate this relationship; however, this was not confirmed by the results.

D011569:Psychiatric Status Rating Scales

Anxiety
Depression
Well-being
Mainland Chinese
Mental health


Lp-PLA2 activity and mass for prediction of incident abdominal aortic aneurysms: A prospective longitudinal cohort study.

Abstract:
BACKGROUND AND AIMS
The pathogenesis of abdominal aortic aneurysm (AAA) shares several common pathways with atherosclerosis. Prospective clinical plasma biomarker studies in AAA have been hampered by the need for very large cohorts and long follow-up time.

METHODS
We analyzed a prospective longitudinal cohort of middle-aged individuals from the cardiovascular cohort of the Malmö Diet and Cancer study (n = 5551; 1991-94). The plasma biomarkers lipoprotein-associated phospholipase A2 (Lp-PLA2 activity and mass), proneurotensin and C-reactive protein, and conventional risk factors at baseline were measured in patients with incident AAA during follow-up, and compared to individuals without a diagnosis of AAA. Subjects were followed until December 31st, 2013. Multivariable analyses were expressed in terms of hazard ratios (HR) per 1 standard deviation increment of each respective log-transformed plasma biomarker in the Cox proportional hazard models.

RESULTS
Cumulative incidence of AAA was 1.5% (men 2.9%, women 0.5%) during a median follow-up period of 20.7 years. Overall, 84 individuals had an incident AAA, of whom 22 (26.2%) were operated on and 16 (19.0%) had ruptured. Mean age of individuals with incident AAA was 59.7 years at study entry and AAA was diagnosed on average 14 years later. When adjusting for age, gender, smoking, body mass index, hypertension, and diabetes mellitus, Lp-PLA2 activity (HR 1.40; 95% CI 1.15-1.72) and Lp-PLA2 mass (HR 1.23; 95% CI 1.00-1.51) were independently associated with incident AAA.

CONCLUSIONS
The plasma biomarkers Lp-PLA2 activity and mass were markers of AAA risk and this implies that AAA is an athero-thrombotic related disease.

Acosta|Stefan|S|
Taimour|Soumia|S|
Gottsäter|Anders|A|
Persson|Margaretha|M|
Engström|Gunnar|G|
Melander|Olle|O|
Zarrouk|Moncef|M|
Nilsson|Peter M|PM|
Smith|J Gustav|JG|

Abdominal aortic aneurysm
Plasma biomarker
Lipoprotein-associated phospholipase
Incident AAA
Epidemiology


Hyperthermia and Temperature-Sensitive Nanomaterials for Spatiotemporal Drug Delivery to Solid Tumors.

Abstract: Nanotechnology has great capability in formulation, reduction of side effects, and enhancing pharmacokinetics of chemotherapeutics by designing stable or long circulating nano-carriers. However, effective drug delivery at the cellular level by means of such carriers is still unsatisfactory. One promising approach is using spatiotemporal drug release by means of nanoparticles with the capacity for content release triggered by internal or external stimuli. Among different stimuli, interests for application of external heat, hyperthermia, is growing. Advanced technology, ease of application and most importantly high level of control over applied heat, and as a result triggered release, and the adjuvant effect of hyperthermia in enhancing therapeutic response of chemotherapeutics, i.e., thermochemotherapy, make hyperthermia a great stimulus for triggered drug release. Therefore, a variety of temperature sensitive nano-carriers, lipid or/and polymeric based, have been fabricated and studied. Importantly, in order to achieve an efficient therapeutic outcome, and taking the advantages of thermochemotherapy into consideration, release characteristics from nano-carriers should fit with applicable clinical thermal setting. Here we introduce and discuss the application of the three most studied temperature sensitive nanoparticles with emphasis on release behavior and its importance regarding applicability and therapeutic potentials.

Amin|Mohamadreza|M|
Huang|Wenqiu|W|
Seynhaeve|Ann L B|ALB|
Ten Hagen|Timo L M|TLM|

hyperthermia
triggered drug release
temperature sensitive nanoparticles
liposomes
polymeric nanoparticles


Bi-Temporal Anodal Transcranial Direct Current Stimulation during Slow-Wave Sleep Boosts Slow-Wave Density but Not Memory Consolidation.

Abstract: Slow-wave sleep (SWS) has been shown to promote long-term consolidation of episodic memories in hippocampo-neocortical networks. Previous research has aimed to modulate cortical sleep slow-waves and spindles to facilitate episodic memory consolidation. Here, we instead aimed to modulate hippocampal activity during slow-wave sleep using transcranial direct current stimulation in 18 healthy humans. A pair-associate episodic memory task was used to evaluate sleep-dependent memory consolidation with face-occupation stimuli. Pre- and post-nap retrieval was assessed as a measure of memory performance. Anodal stimulation with 2 mA was applied bilaterally over the lateral temporal cortex, motivated by its particularly extensive connections to the hippocampus. The participants slept in a magnetic resonance (MR)-simulator during the recordings to test the feasibility for a future MR-study. We used a sham-controlled, double-blind, counterbalanced randomized, within-subject crossover design. We show that stimulation vs. sham significantly increased slow-wave density and the temporal coupling of fast spindles and slow-waves. While retention of episodic memories across sleep was not affected across the entire sample of participants, it was impaired in participants with below-average pre-sleep memory performance. Hence, bi-temporal anodal direct current stimulation applied during sleep enhanced sleep parameters that are typically involved in memory consolidation, but it failed to improve memory consolidation and even tended to impair consolidation in poor learners. These findings suggest that artificially enhancing memory-related sleep parameters to improve memory consolidation can actually backfire in those participants who are in most need of memory improvement.

Ruch|Simon|S|
Fehér|Kristoffer|K|
Homan|Stephanie|S|
Morishima|Yosuke|Y|
Mueller|Sarah Maria|SM|
Mueller|Stefanie Verena|SV|
Dierks|Thomas|T|
Grieder|Matthias|M|0000-0002-5124-5302

transcranial direct current stimulation
sleep
memory consolidation
hippocampus
slow wave
temporal lobe


A Noninvasive Method for Quantifying Cerebral Blood Flow by Hybrid PET/MRI.

Abstract: Although PET with 15O-water is the gold standard for imaging cerebral blood flow (CBF), quantification requires measuring the arterial input function (AIF), which is an invasive and noisy procedure. To circumvent this problem, we propose a noninvasive PET/MRI approach that eliminates the need to measure AIF by using global CBF determined by phase-contrast (PC) MRI as a reference region. This approach not only is noninvasive but also involves no additional imaging time, because PC MRI and 15O-water PET are acquired simultaneously. The purpose of this study was to test the accuracy of this hybrid method in an animal model in which AIF was measured directly and CBF was varied by changing the arterial CO2 tension. Methods: PET and MRI data were simultaneously acquired in juvenile pigs at hypocapnia (n = 5), normocapnia (n = 5), and hypercapnia (n = 4). CBF was measured by the MRI reference method and by PET alone using an MRI-compatible blood sampling system to measure AIF. Results: Global CBF estimates from PC MRI and 15O-water PET agreed well, with a correlation coefficient of 0.9 and a slope of 0.88. Strong positive correlations (R2 > 0.96) were also found between regional CBF generated by the PET-only and the MRI-reference methods. Conclusion: These findings demonstrate the accuracy of this hybrid PET/MRI approach, which might prove useful in patients for whom obtaining accurate CBF measurements is challenging.

Ssali|Tracy|T|
Anazodo|Udunna C|UC|
Thiessen|Jonathan D|JD|
Prato|Frank S|FS|
St Lawrence|Keith|K|

cerebral blood flow
PET
15O-water
CBF
noninvasive PET
phase-contrast MRI


Urological fistulas after fetal cystoscopic laser ablation of posterior urethral valves: surgical technical aspects.

Abstract:
OBJECTIVE
To describe the surgical technical aspects associated with the development of urological fistulas after fetal antegrade cystoscopic laser fulguration of the posterior urethral valves (PUV).

METHODS
The perioperative data for all fetal cystoscopies performed between January 2004 and August 2013 at three institutions in the USA, France and Brazil were reviewed, with particular emphasis on surgical technical aspects of the procedure and the complications encountered.

RESULTS
A total of 40 fetal cystoscopies were performed at the three institutions. Laser fulguration of the PUV was performed in 23 of these cases, with a survival rate of 60.9% (14/23) and normal renal function in 85.7% (12/14) of these infants. Urological fistulas were diagnosed postnatally in four (10%) newborns. The presence of fistulas was associated with a higher gestational age at diagnosis of PUV (P < 0.01) and with the use of semi-curved rather than curved sheaths (P < 0.01), the use of a diode laser (P < 0.01) and the use of higher laser power and energy (P < 0.01 and P < 0.01, respectively), as well as with less operator experience (P < 0.01) and with absence of fetal anesthesia/immobilization (P = 0.02).

CONCLUSION
Urological fistulas are a severe complication of fetal cystoscopic laser fulguration of PUV and are associated with type, energy and power settings of the laser and instrumentation. The use of appropriate technique and proper training of the operator are necessary to perform this fetal intervention safely.

Sananes|N|N|
Favre|R|R|
Koh|C J|CJ|
Zaloszyc|A|A|
Braun|M C|MC|
Roth|D R|DR|
Moog|R|R|
Becmeur|F|F|
Belfort|M A|MA|
Ruano|R|R|

fistula
urethral valves
fetal cystoscopy
fetal surgery
lower urinary tract obstruction


Enhancing the Furosemide Permeability by Papain Minitablets Through a Triple Co-culture In Vitro Intestinal Cell Model.

Abstract: The administration of medicines by the oral route is the most used approach for being very convenient. Although it is the most popular, this route also has absorption, and consequently, bioavailability limitations. In this sense, several pharmacotechnical strategies have been used to improve drug absorption, one of which is the use of permeation promoters. Papain is a very versatile plant enzyme that can be used as a permeation promoter of various active compounds. This study aimed to evaluate the safety of papain and the formulation of native papain minitablets to promote in vitro permeation of furosemide through an innovative biomimetic triple co-culture model of Caco-2, HT29-MTX, and Raji cells. Regarding permeation, furosemide and metaprolol concentrations are determined with HPLC; those are used to calculate Papp. Monolayer integrity was evaluated using TEER and Lucifer Yellow. In the presence of papain, TEER decreased two-fold and the Papp of furosemide increased six-fold. The results suggest that native papain minitablets can be used as therapeutic adjuvants to enhance the permeation of drugs significantly improving bioavailability.

papain
TEER
in vitro safety
mucus
oral permeation enhancer


New light on ancient enzymes - in vitro CO2 Fixation by Pyruvate Synthase of Desulfovibrio africanus and Sulfolobus acidocaldarius.

Abstract: Two variants of the enzyme family pyruvate:ferredoxin oxidoreductase (PFOR), derived from the anaerobic sulfate-reducing bacterium Desulfovibrio africanus and the extremophilic crenarchaeon Sulfolobus acidocaldarius, respectively, were evaluated for their capacity to fixate CO2 in vitro. PFOR reversibly catalyzes the conversion of acetyl-CoA and CO2 to pyruvate using ferredoxin as redox partner. The oxidative decarboxylation of pyruvate is thermodynamically strongly favored, and most previous studies only considered the oxidative direction of the enzyme. To assay the pyruvate synthase function of PFOR during reductive carboxylation of acetyl-CoA is more challenging and requires to maintain the reaction far from equilibrium. For this purpose, a biochemical assay was established where low-potential electrons were introduced by photochemical reduction of EDTA/deazaflavin and the generated pyruvate was trapped by chemical derivatization with semicarbazide. The product of CO2 fixation could be detected as pyruvate semicarbazone by HPLC-MS. In a combinatorial approach, both PFORs were tested with ferredoxins from different sources. The pyruvate semicarbazone product could be detected with low-potential ferredoxins of the green sulfur bacterium Chlorobium tepidum and of S. acidocaldarius whereas CO2 fixation was not supported by the native ferredoxin of D. africanus. Methylviologen as an artificial electron carrier also allowed CO2 fixation. For both enzymes, the results are the first demonstration of CO2 fixation in vitro. Both enzymes exhibited high stability in the presence of oxygen during purification and storage. In conclusion, the employed PFOR enzymes in combination with non-native ferredoxin cofactors might be promising candidates for further incorporation in biocatalytic CO2 conversion. ENZYMES: EC1.2.7.1. Pyruvate:Ferredoxin Oxidoreductase.

Witt|Andreas|A| Pozzi|Roberta|R| Diesch|Stephan|S| Hädicke|Oliver|O| Grammel|Hartmut|H|

CO2 fixation
Desulfovibrio
Sulfolobus
pyruvate:ferredoxin oxidoreductase
anaerobic sulfate reducing bacteria
autotrophic pathways
extremophilic archaea


Development of open-cell polyurethane-based bone surrogates for biomechanical testing of pedicle screws.

Abstract: Artificial bones made of polyurethane are frequently used as an alternative to human bone for biomechanical testing. However, the biomechanical characteristics of these materials are often not validated against those of human bones. Thus, synthetic bone surrogates reflecting procedure-specific biomechanical properties of human bones are necessary for reliable implant design and testing. The aim of this study was to evaluate novel custom made open- and close-cell bone surrogates through morphometry assessment and pedicle screw pullout tests as an alternative to human bone for biomechanical testing. Bone surrogates created from polyurethane resin, mineral fillers and varying amounts of blowing agent were customized to various densities. Pedicle screws were manually inserted and pullout tests with a feed rate of 1 mm/min were conducted until failure. Load and displacement curves were recorded and analyzed in terms of maximum pullout forces. The resulting pullout forces of open- (1437 ± 665 N) and close-cell surrogates (951 ± 578 N) showed comparable results to human bone (1417 ± 812N) used as a reference. Furthermore, structural morphometric parameters were in accordance with human vertebral cancellous bone. In conclusion, the customized bone surrogates provide a new opportunity to design and test pedicle screws and further study the relationship between biomechanical properties and apparent density of artificial spongy bone.

Hollensteiner|Marianne|M| Esterer|Benjamin|B| Fürst|David|D| Schrempf|Andreas|A| Augat|Peter|P|

Biomechanics
Morphology
Open-cell cancellous bone
Synthetic vertebral bone
Vertebra


Intestinal Epithelial Expression of MHCII Determines Severity of Chemical, T-Cell-Induced, and Infectious Colitis in Mice.

Abstract:
BACKGROUND & AIMS
Intestinal epithelial cells (IECs) provide a barrier that separates the mucosal immune system from the luminal microbiota. IECs constitutively express low levels of major histocompatibility complex (MHC) class II proteins, which are upregulated upon exposure to interferon gamma. We investigated the effects of deleting MHCII proteins specifically in mice with infectious, dextran sodium sulfate (DSS)-, and T-cell-induced colitis.

METHODS
We disrupted the histocompatibility 2, class II antigen A, beta 1 gene (H2-Ab1) in IECs of C57BL/6 mice (I-AbΔIEC) or Rag1-/- mice (Rag1-/-I-AbΔIEC); we used I-AbWT mice as controls. Colitis was induced by administration of DSS, transfer of CD4+CD45RBhi T cells, or infection with Citrobacter rodentium. Colon tissues were collected and analyzed by histology, immunofluorescence, xMAP, and reverse-transcription polymerase chain reaction and organoids were generated. Microbiota (total and immunoglobulin [Ig]A-coated) in intestinal samples were analyzed by16S amplicon profiling. IgA+CD138+ plasma cells from Peyer's patches and lamina propria were analyzed by flow cytometry and IgA repertoire was determined by next-generation sequencing.

RESULTS
Mice with IEC-specific loss of MHCII (I-AbΔIEC mice) developed less severe DSS- or T-cell transfer-induced colitis than control mice. Intestinal tissues from I-AbΔIEC mice had a lower proportion of IgA-coated bacteria compared with control mice, and a reduced luminal concentration of secretory IgA (SIgA) following infection with C rodentium. There was no significant difference in the mucosal IgA repertoire of I-AbΔIEC vs control mice, but opsonization of cultured C rodentium by SIgA isolated from I-AbΔIEC mice was 50% lower than that of SIgA from mAbWT mice. Fifty percent of I-AbΔIEC mice died after infection with C rodentium, compared with none of the control mice. We observed a transient but significant expansion of the pathogen in the feces of I-AbΔIEC mice compared with I-AbWT mice.

CONCLUSIONS
In mice with DSS or T-cell-induced colitis, loss of MHCII from IECs reduces but does not eliminate mucosal inflammation. However, in mice with C rodentium-induced colitis, loss of MHCII reduces bacterial clearance by decreasing binding of IgA to commensal and pathogenic bacteria.

Jamwal|Deepa R|DR|
Laubitz|Daniel|D|
Harrison|Christy A|CA|
Figliuolo da Paz|Vanessa|V|
Cox|Christopher M|CM|
Wong|Rachel|R|
Midura-Kiela|Monica|M|
Gurney|Michael A|MA|
Besselsen|David G|DG|
Setty|Prashanth|P|
Lybarger|Lonnie|L|
Bhattacharya|Deepta|D|
Wilson|Jean M|JM|
Ghishan|Fayez K|FK|
Kiela|Pawel R|PR|

D000949:Histocompatibility Antigens Class II

Activation
Antibody Production
Antigen Presentation
Immune Regulation


Induction and subcellular redistribution of progesterone receptor A and B by tamoxifen in the hypothalamic ventromedial neurons of young adult female Wistar rats.

Abstract: The ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) is a brain center for estrogen-dependent triggering of female sexual behavior upon progesterone receptor (PR) activation. We examined the agonistic and antagonistic actions of tamoxifen in this nucleus by analyzing its effects on the total number of PR-immunoreactive neurons, PR mRNA and protein levels, and subcellular location of PRs in ovariectomized Wistar rats. The results show that tamoxifen has no agonistic action in the number of PR-immunoreactive neurons, but increases PR expression and labeling in the nucleus and cytoplasm of VMNvl neurons that constitutively express PRs. As an antagonist, tamoxifen partially inhibited the estradiol-dependent increase in the number of PR-immunoreactive neurons and in PR mRNA and protein levels, without interfering with the subcellular location of the protein. We suggest that tamoxifen influence on PR expression in the VMNvl critically depends on the presence or absence of estradiol.

Sá|Susana I|SI|
Fonseca|Bruno M|BM|
Teixeira|Natércia|N|
Madeira|M Dulce|MD|

D060888:Real-Time Polymerase Chain Reaction

Progesterone receptor
Tamoxifen
Hypothalamic ventromedial nucleus
Estrogen receptor
Stereology
Western blot


Low expression of RBMS3 and SFRP1 are associated with poor prognosis in patients with gastric cancer.

Abstract: RNA binding motif, single stranded interacting protein 3 (RBMS3) has been reported as a tumor suppressor gene (TSG) in some squamous carcinoma. However, its expression levels and clinical significance in gastric cancer (GC) remains unclear. Secreted frizzled-related protein 1 (SFRP1) plays a role of tumor suppressor in many cancers by inhibiting Wnt/β-catenin pathway. Nevertheless, its expression levels and clinical significance in GC are in dispute. In this study, quantitative real-time PCR and Western Blot were used to measure the mRNA and protein level of RBMS3 and SFRP1 in 23 fresh GC and corresponding normal tissues. Immunohistochemistry assay was performed to further measure the protein level of RBMS3 and SFRP1 on population-based tissue microarrays consisting of 172 GC cases. We found that 69.57% (16/23) and 73.91% (17/23) GC tissues expressed remarkably lower RBMS3 than the matched normal tissues respectively in mRNA and protein levels. Similarly, 78.26% (18/23) and 65.22% (15/23) GC tissues expressed lower SFRP1 than the matched normal tissues respectively in mRNA and protein levels. Additionally, the low expression of RBMS3 and SFRP1 protein were all significantly related to the poor histological grades and prognosis (all P<0.05). In multivariate analysis, RBMS3 and SFRP1 co-expression status was independent prognostic factor for GC patients. Finally, the positive correlation between expression levels (mRNA and protein) of RBMS3 and SFRP1 was observed. Overall, RBMS3 and SFRP1 are both aberrantly low expressed in GC, and RBMS3 and SFRP1 co-expression is a potential prognosis predictor of GC.

Zhang|Tao|T| Wu|Youliang|Y| Fang|Zheng|Z| Yan|Qiang|Q| Zhang|Shangxin|S| Sun|Ruochuan|R| Khaliq|Junaid|J| Li|Yongxiang|Y|

RBMS3
SFRP1
prognosis
Gastric cancer
co-expression
biomarker


Unveiling the changes in urban atmospheric CO2 in the time of COVID-19 pandemic: A case study of Florence (Italy).

Abstract: The outbreak of COVID-19 pandemic was accompanied by global mobility restrictions and slowdown in manufacturing activities. Accordingly, cities experienced a significant decrease of CO2 emissions. In this study, continuous measurements of CO2 fluxes, atmospheric CO2 concentrations and δ13C-CO2 values were performed in the historical center of Florence (Italy) before, during and after the almost two-month long national lockdown. The temporal trends of the analyzed parameters, combined with the variations in emitting source categories (from inventory data), evidenced a fast response of flux measurements to variations in the strength of the emitting sources. Similarly, the δ13C-CO2 values recorded the change in the prevailing sources contributing to urban atmospheric CO2, confirming the effectiveness of carbon isotopic data as geochemical tracers for identifying and quantifying the relative contributions of emitting sources. Although the direct impact of restriction measurements on CO2 concentrations was less clear due to seasonal trends and background fluctuations, an in-depth analysis of the daily local CO2 enhancement with respect to the background values revealed a progressive decrease throughout the lockdown phase at the end of the heating season (>10 ppm), followed by a net increase (ca. 5 ppm) with the resumption of traffic. Finally, the investigation of the shape of the frequency distribution of the analyzed variables revealed interesting aspects concerning the dynamics of the systems.

Venturi|Stefania|S| Randazzo|Antonio|A| Tassi|Franco|F| Gioli|Beniamino|B| Buccianti|Antonella|A| Gualtieri|Giovanni|G| Capecchiacci|Francesco|F| Cabassi|Jacopo|J| Brilli|Lorenzo|L| Carotenuto|Federico|F| Santi|Riccardo|R| Vagnoli|Carolina|C| Zaldei|Alessandro|A| Vaselli|Orlando|O|

COVID-19 pandemic
CO(2)
Carbon footprint
Greenhouse gas
Urban air


Lipocalin-2 in Stroke.

Abstract: Stroke is a leading cause of adult disability in the United States. However, limited number of molecularly targeted therapy exists for stroke. Recent studies have shown that Li-pocalin-2 (LCN2) is an acute phase protein mediating neuroinflammation after ischemic and hemorrhagic strokes. This review is an attempt to summarize some LCN2-related research findings and discuss its role in stroke.

Chou|Wen-Hai|WH| Wang|Guona|G| Kumar|Varun|V| Weng|Yi-Chinn|YC|

Lipocalin-2
Stroke
24p3
Biomarker
NGAL
Neutrophil
PKC
Phosphorylation
Reperfusion injury


Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment.

Abstract: The spindle assembly checkpoint (SAC) is a conserved signaling pathway that monitors faithful chromosome segregation during mitosis. As a core component of SAC, the evolutionarily conserved kinase monopolar spindle 1 (Mps1) has been implicated in regulating chromosome alignment, but the underlying molecular mechanism remains unclear. Our molecular delineation of Mps1 activity in SAC led to discovery of a previously unidentified structural determinant underlying Mps1 function at the kinetochores. Here, we show that Mps1 contains an internal region for kinetochore localization (IRK) adjacent to the tetratricopeptide repeat domain. Importantly, the IRK region determines the kinetochore localization of inactive Mps1, and an accumulation of inactive Mps1 perturbs accurate chromosome alignment and mitotic progression. Mechanistically, the IRK region binds to the nuclear division cycle 80 complex (Ndc80C), and accumulation of inactive Mps1 at the kinetochores prevents a dynamic interaction between Ndc80C and spindle microtubules (MTs), resulting in an aberrant kinetochore attachment. Thus, our results present a previously undefined mechanism by which Mps1 functions in chromosome alignment by orchestrating Ndc80C-MT interactions and highlight the importance of the precise spatiotemporal regulation of Mps1 kinase activity and kinetochore localization in accurate mitotic progression.

Dou|Zhen|Z|
Liu|Xing|X|
Wang|Wenwen|W|
Zhu|Tongge|T|
Wang|Xinghui|X|
Xu|Leilei|L|
Abrieu|Ariane|A|
Fu|Chuanhai|C|
Hill|Donald L|DL|
Yao|Xuebiao|X|

D015971:Gene Expression Regulation, Enzymologic

Mps1 kinase
spindle assembly checkpoint
chromosome alignment
kinetochore–microtubule attachment
reversine


Understanding the Relationship between Intention and Cat Containment Behaviour: A Case Study of Kitten and Cat Adopters from RSPCA Queensland.

Abstract: In Australia, cat owners are encouraged to keep their pet cats contained on their property at all times. This study explores the relationship between the intentions and behaviours of 72 kitten and cat adopters from a RSPCA Queensland animal shelter, to provide a more in-depth understanding of the factors influencing the adoption of cat containment behaviours. At the time of adoption, 64 participants (89%) indicated they were intending to keep their cat fully contained. Eight weeks after adoption, 63 participants (87%) reported they were doing so (59 who had stated their intention at the time of adoption, and 4 who had not). We found cat owner containment behaviour was moderately correlated with containment intentions. For some of the participants when it came to enacting this behaviour, their intentions and the provided education information was not enough to overcome the more compelling capability, opportunity and motivational factors which presented themselves once they got home. We were able to identify these factors and suggest additional behaviour change strategies that would assist. Although it is important to provide cat adopters with advice about how to contain their cats properly, these results also highlight the importance of focusing attention on other behaviour change strategies that address the particular barriers faced by some cat-owners who are unsuccessful in keeping their cat contained on their property.

McLeod|Lynette J|LJ|0000-0001-9408-3342
Evans|Di|D|
Jones|Bidda|B|
Paterson|Mandy|M|0000-0003-4564-9877
Zito|Sarah|S|

domestic cat management
human behaviour change
intervention development


Study of the spatio-temporal variation of environmental sustainability at national and provincial levels in China.

Abstract: Environmental problems create a significant barrier for China in achieving its Sustainable Development Goals (SDGs). Assessing environmental sustainability is critical for China to meet the SDGs. Few studies, however, have looked into environmental sustainability in China. This research created a systematic and comprehensive environmental sustainability framework in line with the SDGs (SDG 6, SDG 11, SDG 12, SDG 13, SDG 14, SDG 15). From 2010 to 2018, we used a Constant Elasticity of Substitution (CES) model to assess China's spatio-temporal variation in environmental sustainability at the national and provincial levels. We also evaluated the results with changes to the substitution elasticity value, validating the feasibility of the proposed calculation method. Our results show that the scores of SDG 6, SDG 11, SDG 12, SDG 13, and SDG 15 experienced an increasing trend, while SDG 14 experienced a decline. China's Environmental Sustainability Index (ESI) scores indicate that China's overall environmental sustainability has been improved over time. At the provincial level, the ESI scores of all provinces increased at different levels from 2010 to 2018. The results of this paper may facilitate improvements in environmentally-related SDGs in China's provinces, and help realize China's sustainable development.

Wang|Qi|Q| Liu|Chao|C| Hou|Yuting|Y| Xin|Fei|F| Mao|Zhu|Z| Xue|Xiongzhi|X|

Spatio-temporal variation
Environmental sustainability
SDGs
ESI scores
CES model


Synthesis, characterization and anti-cancer activity of a peptide nucleolipid bioconjugate.

Abstract: The synthesis, characterization and anti-cancer activity of a novel peptide nucleolipid bioconjugate is reported in this study. The prerequisite 5'-carboxy derived nucleolipid was synthesized following a five-step solution-phase approach and then coupled to the cytotoxic D-(KLAKLAK)2 sequence by solid-phase bioconjugation. The biophysical and structural properties of the peptide-nucleolipid bioconjugate were evaluated and compared to the peptide controls. These characterization studies revealed that the amphiphilic peptides favored helical-type secondary structures and well-defined nanoparticle formulations that were found to be contributive towards their biological activity. The peptide-nucleolipid bioconjugate displayed greater lethality in comparison to the native D-(KLAKLAK)2AK sequence when treated within the human A549 non-small cell lung carcinoma cell line. Thus, the amphiphilic peptide-nucleolipid forms a new class of anti-cancer peptides that may be developed into promising leads in the fight against cancer.

Rana|Niki|N| Huang|Suiying|S| Patel|Pradeepkumar|P| Samuni|Uri|U| Sabatino|David|D|

D004354:Drug Screening Assays, Antitumor

Anti-cancer activity
Nucleolipid
Amphiphilic peptides
Peptide bioconjugate


Analysis of the impact of EEA stapler size on risk of anastomotic complications in colorectal anastomosis: does size matter?

Abstract:
BACKGROUND
Colorectal anastomotic complications are dreaded and dramatically affect outcomes. Causes are multifactorial, with the size of the end-to-end anastomosis (EEA) stapler a modifiable factor and potential target for risk reduction. Our goal was to examine the impact of the EEA stapler size on the risk of anastomotic complications in left-sided colorectal resections.

METHODS
A prospective divisional database was reviewed for consecutive elective left-sided resections with a colorectal anastomosis using an EEA stapler from January 2013 May 2018 inclusive. Patients were stratified into 25-29 mm or 30-33 mm cohorts. Patient and disease demographics, operative variables, and postoperative outcomes were evaluated. The main outcome measures were the rate and factors associated with anastomotic complications.

RESULTS
Four hundred seventy-three cases were evaluated, 185 ( 39.1%) were in the 25-29 mm group and 288 (60.9%) in the 30-33 mm group. Patients were comparable in demographics and operative variables. More males were anastomosed with the 30-33 mm than with the 25-29 mm stapler (57.6% vs 28.6%, p < 0.01). Significantly more patients developed an anastomotic stricture with the 25-29 mm than with the 30-33 mm staplers (7.1% vs. 2.1%; p = 0.007). There was no significant difference in leak rates or reoperation/interventions between groups. On logistic regression, neither gender, operative indication nor approach were associated with anastomotic leak, readmission, or reoperation/intervention. Stapler size remained significantly associated with stricture (p = 0.032).

CONCLUSIONS
The 25-29 mm EEA staplers were associated with an increased rate of anastomotic stricture compared to 30-33 mm staplers in left-sided colorectal anastomoses. As stapler size is a simple process measure that is easily modifyable, this is a potential target for improving anastomotic complication rates. Further controlled trials may help assess the impact of stapler size on improving patient and quality outcomes.

Reif de Paula|T|T|
Simon|H|H|
Shah|M|M|
Lee-Kong|S|S|
Kiely|J M|JM|
Kiran|R P|RP|
Keller|D S|DS|0000-0002-8645-6206

Anastomosis
Anastomotic leak
Colorectal neoplasms
Constriction
Elective surgical procedures
Outcome assessment
Surgical stapler
health care
pathologic
surgical


What can be done to reduce the damages, costs and fees paid out by the NHS for claims for clinical negligence?

Abstract: This article considers different approaches with a view to reducing NHS legal costs and damages for clinical failures on the basis that these are out of control and reducing resources for the treatment of current and future patients.

cash for patient care diminished by claims

should claiming against the NHS be made more difficult?

soaring legal costs defending claims for clinical negligence


Anatomic and Functional Connectivity Relationship in Autistic Children During Three Different Experimental Conditions.

Abstract: A group of 21 autistic children were studied for determining the relationship between the anatomic (AC) versus functional (FC) connectivity, considering short-range and long-range brain networks. AC was assessed by the DW-MRI technique and FC by EEG coherence calculation, in three experimental conditions: basal, watching a popular cartoon with audio (V-A), and with muted audio track (VwA). For short-range connections, basal records, statistical significant correlations were found for all EEG bands in the left hemisphere, but no significant correlations were found for fast EEG frequencies in the right hemisphere. For the V-A condition, significant correlations were mainly diminished for the left hemisphere; for the right hemisphere, no significant correlations were found for the fast EEG frequency bands. For the VwA condition, significant correlations for the rapid EEG frequencies mainly disappeared for the right hemisphere. For long-range connections, basal records showed similar correlations for both hemispheres. For the right hemisphere, significant correlations incremented to all EEG bands for the V-A condition, but these significant correlations disappeared for the fast EEG frequencies in the VwA condition. It appears that in a resting-state condition, AC is better associated with functional connectivity for short-range connections in the left hemisphere. The V-A experimental condition enriches the AC and FC association for long-range connections in the right hemisphere. This might be related to an effective connectivity improvement due to full video stimulation (visual and auditory). An impaired audiovisual interaction in the right hemisphere might explain why significant correlations disappeared for the fast EEG frequencies in the VwA experimental condition.

Machado|Calixto|C| Rodríguez|Rafael|R| Estévez|Mario|M| Leisman|Gerry|G| Melillo|Robert|R| Chinchilla|Mauricio|M| Portela|Liana|L|

D038524:Diffusion Magnetic Resonance Imaging

functional connectivity
EEG
coherence
MRI
anatomic connectivity
autism
autism spectrum disorder


Response of bacterial communities in rubber plantations to different fertilizer treatments.

Abstract: In the present study, the effects of chemical fertilizer (CF) and organic fertilizer plus chemical fertilizer application (OF-CF) on natural rubber yield, soil properties, and soil bacterial community were systematically investigated in rubber plantations. The rubber dry yield was 26.3% more in the OF treatment group than in the CF treatment group. The contents of total nitrogen (TN), available nitrogen (AN), available phosphorus (AP), and available potassium (AK) as well as soil organic matter (SOM) and pH value were higher following OF-CF treatment. Using Illumina sequencing, a total of 927 operational taxonomic units (OTUs) were obtained following CF treatment, while 955 OTUs were obtained after OF-CF treatment. Relative abundance analysis showed the relative abundances of four phyla (Acidobacteria, Proteobacteria, Actinobacteria, Gemmatimonadetes) were different between the two treatment groups. Correlation analysis revealed Acidobacteria, Bacteroidetes, Thaumarchaeota, Elusimicrobia, Verrucomicrobia were the key taxa that determined the soil properties. Additionally, five OTUs (OTU_506, OTU_391, OTU_189, OTU_278, OTU_1057) were thought to be related to the biodegradation of natural rubber. Taken together, these results improve our understanding of the OF-mediated improvement in soil fertility and contribute to the identification of rubber-degrading bacteria in rubber plantations.

Zhang|Zhiyang|Z| Zhang|Peisong|P| Lin|Qinghuo|Q| Cha|Zhengzao|Z| Luo|Wei|W|

Bacterial communities
Chemical fertilizer
Organic fertilizer
Natural rubber yield
Hevea brasiliensis Muell. Arg.


A Software Deep Packet Inspection System for Network Traffic Analysis and Anomaly Detection.

Abstract: In this paper, to solve the problem of detecting network anomalies, a method of forming a set of informative features formalizing the normal and anomalous behavior of the system on the basis of evaluating the Hurst (H) parameter of the network traffic has been proposed. Criteria to detect and prevent various types of network anomalies using the Three Sigma Rule and Hurst parameter have been defined. A rescaled range (RS) method to evaluate the Hurst parameter has been chosen. The practical value of the proposed method is conditioned by a set of the following factors: low time spent on calculations, short time required for monitoring, the possibility of self-training, as well as the possibility of observing a wide range of traffic types. For new DPI (Deep Packet Inspection) system implementation, algorithms for analyzing and captured traffic with protocol detection and determining statistical load parameters have been developed. In addition, algorithms that are responsible for flow regulation to ensure the QoS (Quality of Services) based on the conducted static analysis of flows and the proposed method of detection of anomalies using the parameter Hurst have been developed. We compared the proposed software DPI system with the existing SolarWinds Deep Packet Inspection for the possibility of network traffic anomaly detection and prevention. The created software components of the proposed DPI system increase the efficiency of using standard intrusion detection and prevention systems by identifying and taking into account new non-standard factors and dependencies. The use of the developed system in the IoT communication infrastructure will increase the level of information security and significantly reduce the risks of its loss.

network anomaly
Hurst parameter
DPI
intrusion detection
IoT
WSN


Photo-Controlled Macroscopic Self-Assembly Based on Photo-Switchable Hetero-Complementary Quadruple Hydrogen Bonds.

Abstract: A photo-switchable hetero-complementary quadruple H-bonding array, which consists of an azobenzene-derived ureidopyrimidinone (UPy) module (Azo-UPy) and a nonphotoactive diamidonaphthyridine (DAN) derivative (Napy-1), is constructed based on a reversible photo-locking approach. Upon UV (390 nm)/Vis (460 nm) light irradiations, photo-switchable quadruple H-bonded dimerization between Azo-UPy and Napy-1 can be achieved with exhibiting 4.8×104 -fold differences in binding strength (ON/OFF ratios). Furthermore, smart polymeric gels with unique photo-controlled macroscopic self-assembly behavior can be fabricated by introducing such quadruple H-bonding array as photo-regulable noncovalent interfacial connections.

hetero-complementary multiple hydrogen bonds


Novel investigational vascular endothelial growth factor (VEGF) receptor antagonists for psoriasis.

Abstract:
INTRODUCTION
Affecting 1 million people in the UK, psoriasis is a commonly diagnosed inflammatory disease arising from autoimmune processes that are triggered by environmental factors in genetically susceptible individuals. The pathophysiology of psoriasis has been widely studied and there is evidence that angiogenesis is a key component.

AREAS COVERED
In this review the role of vascular endothelial growth factor-A (VEGF), as a key angiogenic mediator in psoriasis pathogenesis is discussed. VEGF is found in higher levels in plaques, normal skin and plasma of patients with psoriasis. The level of VEGF also fluctuates in accordance with disease activity and in response to conventional treatments. There are several VEGF inhibitors currently licenced for use; primarily in the fields of oncology and there are case reports of patients being treated with these therapies for metastatic cancer who have demonstrated significant improvement in their psoriasis. VEGF inhibitory agents have suggested promising utility for the treatment of psoriasis following animal studies.

EXPERT OPINION
VEGF may represent a novel treatment target in psoriasis. However, VEGF inhibitors can cause significant side effects such as hypertension and left ventricular dysfunction. The risks of treatment must be carefully evaluated before VEGF inhibitors are trialled or advocated for psoriasis.

D040262:Receptors, Vascular Endothelial Growth Factor

vascular endothelial growth factor
VEGF
Psoriasis
angiogenesis
treatment


Users of retail medications for opioid use disorders faced high out-of-pocket prescription spending in 2011-2017.

Abstract:
INTRODUCTION
High out-of-pocket spending has been a barrier to treatment for the estimated 2.0 million Americans suffering from opioid use disorders (OUD). This paper provides national estimates of financial costs faced by the population receiving retail medications for OUD (MOUD).

METHODS
We used pooled annual data from the 2011-2017 Medical Expenditure Panel Survey (MEPS), a nationally representative sample of the civilian noninstitutionalized population in the United States. The sample includes individuals who reported filling a retail prescription for buprenorphine or naltrexone, the two most common medications available from retail pharmacies to treat OUD. The main outcome is out-of-pocket spending of retail MOUD prescriptions per fill and per person.

RESULTS
Patients with retail MOUD prescriptions spent 3.4 times more out-of-pocket for prescriptions on average than the rest of the U.S. population, with 18.8% of this population paying entirely out-of-pocket for their MOUD prescriptions. Insurance coverage is associated with reduced annual out-of-pocket MOUD expenditures between $316 and $328 per year.

CONCLUSIONS
Future policies that expand insurance and address out-of-pocket spending on MOUD could increase access to medications among individuals with OUD.

Medications for opioid use disorders (MOUD)


Diaporthe Seed Decay of Soybean [Glycine max (L.) Merr.] Is Endemic in the United States, But New Fungi Are Involved.

Abstract: Diaporthe seed decay can compromise seed quality in soybean [Glycine max (L.) Merr.] in the warm and humid production areas of the United States during crop maturation. In the current study, 45 isolates of Diaporthe were recovered from seed sampled from soybean fields affected by Diaporthe-associated diseases in eight U.S. states in 2017. The isolates obtained belonged to 10 species of Diaporthe based on morphology and phylogenetic analyses of the internal transcribed spacer, partial translation elongation factor 1-α, and β-tubulin gene sequences. The associated species included D. aspalathi, D. caulivora, D. kongii, D. longicolla, D. sojae, D. ueckerae, D. unshiuensis, and three novel fungi, D. bacilloides, D. flavescens, and D. insulistroma. One isolate each of the 10 species was examined for pathogenicity on seed of cultivar Sava under controlled conditions. Seven days postinoculation, significant differences in the percentages of decayed seeds and seedling necrosis were observed among the isolates and the noninoculated control (P < 0.0001). While the isolates of D. bacilloides, D. longicolla, and D. ueckerae caused a significantly greater percentage of decayed seeds (P < 0.0001), the isolate of D. aspalathi caused the greatest seedling necrosis (P < 0.0001). The observation of new fungi causing Diaporthe seed decay suggests the need for a more comprehensive survey in U.S. soybean producing areas since members of the genus Diaporthe appear to form a complex that causes seed decay.

Diaporthe
soybean
fungi
Phomopsis seed decay
field crops
new taxa
oilseeds and legumes
pathogen diversity
taxonomy


World Market Development and Consumer Acceptance of Irradiation Technology.

Abstract: Food irradiation is an efficient technology that can be used to ensure food safety by eliminating insects and pathogens to prolong the shelf life. The process could be applied to fresh or frozen products without affecting the nutritional value. Presently more than 60 countries have adopted the technology. However, the technology adaptation differs from one country to another and, in some cases, consumers' misunderstanding and lack of acceptance may hinder the technology adaptation process. This review summarizes the development of irradiation treatment worldwide and consumer attitudes towards the introduction of this technology. Also, the wholesomeness, beneficial effects, and regulation of irradiation are assessed.

Maherani|Behnoush|B| Hossain|Farah|F| Criado|Paula|P| Ben-Fadhel|Yosra|Y| Salmieri|Stephane|S| Lacroix|Monique|M|

consumer acceptance
nutritional value
bacterial radiosensitivity
consumer communication
consumer response
food quality
global perception
irradiated foods


Out-of-pocket costs and HIV pre-exposure prophylaxis persistence in a US multicity demonstration project.

Abstract:
OBJECTIVE
To evaluate whether out-of-pocket (OOP) costs reduced HIV pre-exposure prophylaxis (PrEP) persistence.

DATA SOURCE
Participants from five urban community health centers (CHCs) in four US cities enrolled in a PrEP demonstration project from September 2014 to August 2017.

STUDY DESIGN
Patients initiating PrEP were followed quarterly until they withdrew from PrEP care or the study ended. Self-reported OOP medication and clinic visit costs were assessed by semiannual questionnaires. Persistence was defined as the time from study enrollment to the last visit after which two subsequent 3-month visits were missed. Multivariable Cox proportional hazard regression was used to assess the effect of demographics, insurance, and OOP costs on PrEP persistence.

PRINCIPAL FINDINGS
Among 918 participants with OOP cost data, the average quarterly OOP cost was $34 (median: $5, IQR: $0-$25). Participants who were men, White, employed, completed college, and had commercial insurance had higher OOP costs. Higher OOP costs were not associated with lower PrEP persistence by Cox proportional hazards regression (adjusted hazard ratio = 1.00 per $50 increase, 95% CI = 0.97, 1.02).

CONCLUSION
Among patients receiving care from these urban CHCs, OOP costs were low and did not undermine PrEP persistence.

out-of-pocket costs
pre-exposure prophylaxis
persistence
HIV prevention
community health clinic


Regulation of histone deacetylase activities and functions by phosphorylation and its physiological relevance.

Abstract: Histone deacetylases (HDACs) are conserved enzymes that regulate many cellular processes by catalyzing the removal of acetyl groups from lysine residues on histones and non-histone proteins. As appropriate for proteins that occupy such an essential biological role, HDAC activities and functions are in turn highly regulated. Overwhelming evidence suggests that the dysregulation of HDACs plays a major role in many human diseases. The regulation of HDACs is achieved by multiple different mechanisms, including posttranslational modifications. One of the most common posttranslational modifications on HDACs is reversible phosphorylation. Many HDAC phosphorylations are context-dependent, occurring in specific tissues or as a consequence of certain stimuli. Additionally, whereas phosphorylation can regulate some HDACs in a non-specific manner, many HDAC phosphorylations result in specific consequences. Although some of these modifications support normal HDAC function, aberrations can contribute to disease development. Here we review and critically evaluate how reversible phosphorylation activates or deactivates HDACs and, thereby, regulates their many functions under various cellular and physiological contexts.

Histone deacetylase
Phosphorylation
Cell signaling
Epigenetics


Holding our breath: The emerging and anticipated roles of microRNA in pulmonary hypertension.

Abstract: Over the past decade, the importance of non-coding RNA such as microRNA has been established in numerous processes that drive human pathogenesis. These crucial molecular regulators modulate networks of target gene transcripts that, in turn, orchestrate cellular phenotypes such as cell survival, differentiation, proliferation, and metabolism among others and thus affect cardiopulmonary vascular disease conditions. Many of these same pathophenotypes figure prominently in the complex pathogenesis of pulmonary hypertension, an enigmatic vascular disorder characterized by a histological panvasculopathy and driven by disparate upstream triggers such as hypoxia, inflammation, and bone morphogenetic protein signaling. Yet, the importance of just a few microRNAs in pulmonary hypertension has been recognized, and we are only beginning to understand the integrative functions of these molecules in this disease. By combining systems biology with traditional experimental approaches, more direct insight into the pleiotropy of microRNA should not only further reveal the spectrum of molecular pathways that cause pulmonary hypertension, but also offer novel and much needed diagnostic and therapeutic strategies.

White|Kevin|K|
Loscalzo|Joseph|J|
Chan|Stephen Y|SY|

microRNA
pulmonary hypertension
hypoxia
network biology


Moving toward consensus on diagnosis and management of severe asthma in children.

Abstract: Children with severe asthma continue to experience symptoms despite long-term treatment with high doses of corticosteroids. Moreover, the heterogeneous nature of asthma and the presence of several phenotypes have limited our ability to develop an optimized management strategy for these patients. Adequate management of severe asthma in children necessitates a detailed understanding of what makes asthma difficult to control, knowledge of the causal factors, review of diagnosis for accurate identification of pediatric patients with severe asthma and a precise definition of the phenotypes to be able to better target the therapy. Advancement in all these aspects is likely to improve childhood asthma treatment in the future. Although our understanding of severe pediatric asthma has grown in recent years, there remains a lack of consensus and clarity around critical aspects of this condition. This review attempts to present a harmonized view on the definition of severe asthma in the pediatric age group, identification of phenotypes and diagnosis, the inflammatory cascade, pharmacological and non-pharmacological treatment strategies, considerations for follow-up and referral to specialists, and disease prevention strategies.

Larenas-Linnemann|Désirée|D|
Nieto|Antonio|A|
Palomares|Oscar|O|
Pitrez|Paulo Márcio|PM|
Cukier|Gherson|G|

consensus
diagnosis
Severe childhood asthma
disease management


Comparing subjective and objective response to medications in Parkinson's disease patients using the Personal KinetiGraph™.

Abstract:
BACKGROUND
Management of motor symptoms in Parkinson's Disease(PD) relies on subjective information provided by patients, the quality of which can be affected by many factors.

RATIONALE
Objective data collected during daily life could complement this information and improve management of motor symptoms.

OBJECTIVES
To assess the usefulness of the Personal KinetiGraph (PKG) in characterizing the intensity and timing of motor symptoms in PD patients.

METHODS
Retrospective study of all PD patients followed at a tertiary academic movement disorders center assessed by PKG between December 1, 2016 and October 30, 2018. PKG was worn for 7 days prior to the clinical visit. We compared the information obtained from the interview and the clinical visit, and assessed the impact of the PKG on treatment decision making.

RESULTS
170 PKG results were reviewed. PKG complemented patient input in 82.9%(141/170) and led to medication changes in 71%(100/141) of the complemented inputs. PKG contributed the least to correcting or complementing patients' input when patients self-reported as undertreated (22%) and the most when patient were unable to answer all questions regarding motor response to individual doses (100%) (Fisher, p < 0.0001). The majority of patient undergoing 3 or 4 PKG encounters did not reach a controlled state as defined by PKG until the 3rd or 4th encounter, suggesting that repeated use of the PKG might be needed to help optimize motor control as therapy changes done after one encounter might not be enough.

CONCLUSIONS
PKG might be useful in supplementing patient-provided information for accurate assessment and treatment plan.

Parkinson's disease
Personal kinetigraph
Objective assessment
Wearable technology


Implementation Science Strategies Promote Fidelity in The Food, Feeding, and Your Family Study.

Abstract:
OBJECTIVE
Use of implementation science strategies to promote fidelity in the Food, Feeding, and Your Family study.

DESIGN
Cluster randomized controlled trial with 3 conditions: control, in-class, or online, delivered in English or Spanish. Observations of 20% of classes.

SETTING
Expanded Food and Nutrition Education Program (EFNEP) in 2 states.

PARTICIPANTS
EFNEP peer educators (n = 11).

INTERVENTION
Parental feeding content incorporated into EFNEP lessons (in-class) or through text with links to videos/activities (online). Extensive educator training, scripted curriculum, frequent feedback.

ANALYSIS
Assessment of fidelity compliance. Qualitative analysis of verbatim educator interviews and classroom observer comments.

RESULTS
During 128 class observations (40-45 per condition), peer educators followed scripted lesson plan 78% to 89% of the time. There was no evidence of cross-contamination of parental feeding content in control and only minor sharing in online conditions. Variations with fidelity were primarily tied to the EFNEP curriculum, not the parent feeding content. Educators (n = 7) expressed favorable opinions about the Food, Feeding, and Your Family study, thought it provided valuable information, and appreciated support from EFNEP leadership.

CONCLUSIONS AND IMPLICATIONS
Incorporating implementation science strategies can help ensure successful adherence to research protocols. With proper training and support, EFNEP peer educators can deliver an evidence-based curriculum as part of a complex research study.

Aragón|M Catalina|MC|
Auld|Garry|G|
Baker|Susan S|SS|
Barale|Karen V|KV|
Garcia|Karina Silva|KS|
Micheli|Nilda|N|
Parker|Louise|L|
Lanigan|Jane D|JD|
Power|Thomas G|TG|
Hughes|Sheryl O|SO|

implementation science
fidelity
EFNEP
peer educators
parental feeding


Absence of the BRAF V600E mutation in pheochromocytoma.

Abstract:
PURPOSE
Pheochromocytomas (PCCs) are rare endocrine tumors originating from the adrenal medulla. These tumors display a highly heterogeneous mutation profile, and a substantial part of the causative genetic events remains to be explained. Recent studies have reported presence of the activating BRAF V600E mutation in PCC, suggesting a role for BRAF activation in tumor development. This study sought to further investigate the occurrence of the BRAF V600E mutation in these tumors.

METHODS
A cohort of 110 PCCs was screened for the BRAF V600E mutation using direct Sanger sequencing.

RESULTS
All cases investigated displayed wild-type sequences at nucleotide 1799 in the BRAF gene.

CONCLUSIONS
Taken together with all previously screened tumors up to date, only 1 BRAF V600E mutation has been found among 361 PCCs. These findings imply that the BRAF V600E mutation is a rare event in pheochromocytoma.

Paulsson|Johan O|JO|
Svahn|F|F|
Welander|J|J|
Brunaud|L|L|
Söderkvist|P|P|
Gimm|O|O|
Stenman|A|A|
Juhlin|C C|CC|

BRAF Mutation Pheochromocytoma Adrenal Sequencing


Supported Gold Nanoparticles for Efficient α-Oxygenation of Secondary and Tertiary Amines into Amides.

Abstract: Although the α-oxygenation of amines is a highly attractive method for the synthesis of amides, efficient catalysts suited to a wide range of secondary and tertiary alkyl amines using O2 as the terminal oxidant have no precedent. This report describes a novel, green α-oxygenation of a wide range of linear and cyclic secondary and tertiary amines mediated by gold nanoparticles supported on alumina (Au/Al2 O3 ). The observed catalysis was truly heterogeneous, and the catalyst could be reused. The present α-oxygenation utilizes O2 as the terminal oxidant and water as the oxygen atom source of amides. The method generates water as the only theoretical by-product, which highlights the environmentally benign nature of the present reaction. Additionally, the present α-oxygenation provides a convenient method for the synthesis of (18) O-labeled amides using H2 (18) O as the oxygen source.

Jin|Xiongjie|X| Kataoka|Kengo|K| Yatabe|Takafumi|T| Yamaguchi|Kazuya|K| Mizuno|Noritaka|N|

gold
α-oxygenation
amines
amides
heterogeneous catalysis


Network analysis of hyphae forming proteins in Candida albicans identifies important proteins responsible for pathovirulence in the organism.

Abstract: Candida albicans causes two types of major infections in humans: superficial infections, such as skin and mucosal infection, and life-threatening systemic infections, like airway and catheter-related blood stream infections. It is a polymorphic fungus with two distinct forms (yeast and hyphal) and the morphological plasticity is strongly associated with many disease causing proteins. In this study, 137 hyphae associated proteins from Candida albicans (C. albicans) were collected from different sources to create a Protein-Protein Interaction (PPI) network. Out of these, we identified 18 hub proteins (Hog1, Hsp90, Cyr1, Cdc28, Pkc1, Cla4, Cdc42, Tpk1, Act1, Pbs2, Bem1, Tpk2, Ras1, Cdc24, Rim101, Cdc11, Cdc10 and Cln3) that were the most important ones in hyphae development. Ontology and functional enrichment analysis of these proteins could categorize these hyphae associated proteins into groups like signal transduction, kinase activity, biofilm formation, filamentous growth, MAPK signaling etc. Functional annotation analysis of these proteins showed that the protein kinase activity to be essential for hyphae formation in Candida. Additionally, most of the proteins from the network were predicted to be localized on cell surface or periphery, suggesting them as the main protagonists in inducing infections within the host. The complex hyphae formation phenomenon of C. albicans is an attractive target for exploitation to develop new antifungals and anti-virulence strategies to combat C. albicans infections. We further tried to characterize few of the most crucial proteins, especially the kinases by their sequence and structural prospects. Therefore, through this article an attempt to understand the hyphae forming protein network analysis has been made to unravel and elucidate the complex pathogenesis processes with the principal aim of systems biological research involving novel Bioinformatics strategies to combat fungal infections.

Das|Sanjib|S| Bhuyan|Rajabrata|R| Bagchi|Angshuman|A| Saha|Tanima|T|


The minimal that kills: Why defining and targeting measurable residual disease is the "Sine Qua Non" for further progress in management of acute myeloid leukemia.

Abstract: Patients with acute myeloid leukemia (AML) who achieve morphologic remission in the bone marrow after initial treatment often continue to harbor residual leukemic cells that can give rise to disease relapse. Achievement of a deeper remission has been associated with a reduced risk of relapse and improved event-free and overall survival in several studies. However, standardization of diagnostic techniques, sample acquisition and test timing are needed before minimal, also known as measurable, residual disease (MRD) quantification can be used to guide treatment decision making. Furthermore, clinical trial evidence that preemptive intervention at MRD level can alter the natural history of AML is required. Herein, we outline the current landscape of MRD assessment in AML, summarize the available evidence and challenges, and highlight the potential for MRD status to serve as a surrogate endpoint for hard clinical outcomes and as an approvable endpoint in clinical trials for regulatory purposes.

Bewersdorf|Jan Philipp|JP|
Shallis|Rory M|RM|
Boddu|Prajwal C|PC|
Wood|Brent|B|
Radich|Jerald|J|
Halene|Stephanie|S|
Zeidan|Amer M|AM|

Acute myeloid leukemia
MRD
Immune checkpoint
Minimal residual disease
Next generation sequencing


Gut microbiome and microbial metabolites: a new system affecting metabolic disorders.

Abstract:
INTRODUCTION
The gut microbiome is emerging as an important player in the field of metabolic disorders.

MATERIALS AND METHODS
Currently, several studies are ongoing to determine whether the effect of gut microbiome on obesity, type 2 diabetes, non-alcoholic fatty liver disease, and other metabolic diseases is determined by singular species or rather by a functional role of bacterial metabolism at higher taxonomical level. Deciphering if a single or more species are responsible for metabolic traits or rather microbial metabolic pathways are responsible for effects on host metabolism may help to identify appropriate dietary interventions to support microbial functions according to the prevalent host disease. Furthermore, the combination of metagenomics and metabolomics-based signature might be applied in the future to improve the risk prediction in healthy subjects.

CONCLUSION
In this review, I will summarize the current findings regarding the role of gut microbiome and metabolites in metabolic disorders to argue whether the current achievements may be translated into clinical practice.

Gut microbiome
Obesity
Diabetes
Metagenomics
Metabolomics


Schistosome and liver fluke derived catechol-estrogens and helminth associated cancers.

Abstract: Infection with helminth parasites remains a persistent public health problem in developing countries. Three of these pathogens, the liver flukes Clonorchis sinensis, Opisthorchis viverrini and the blood fluke Schistosoma haematobium, are of particular concern due to their classification as Group 1 carcinogens: infection with these worms is carcinogenic. Using liquid chromatography-mass spectrometry (LC-MS/MS) approaches, we identified steroid hormone like (e.g., oxysterol-like, catechol estrogen quinone-like, etc.) metabolites and related DNA-adducts, apparently of parasite origin, in developmental stages including eggs of S. haematobium, in urine of people with urogenital schistosomiasis, and in the adult stage of O. viverrini. Since these kinds of sterol derivatives are metabolized to active quinones that can modify DNA, which in other contexts can lead to breast and other cancers, helminth parasite associated sterols might induce tumor-like phenotypes in the target cells susceptible to helminth parasite associated cancers, i.e., urothelial cells of the bladder in the case of urogenital schistosomiasis and the bile duct epithelia or cholangiocytes, in the case of O. viverrini and C. sinensis. Indeed we postulate that helminth induced cancers originate from parasite estrogen-host epithelial/urothelial cell chromosomal DNA adducts, and here we review recent findings that support this conjecture.

Correia da Costa|José M|JM|
Vale|Nuno|N|
Gouveia|Maria J|MJ|
Botelho|Mónica C|MC|
Sripa|Banchob|B|
Santos|Lúcio L|LL|
Santos|Júlio H|JH|
Rinaldi|Gabriel|G|
Brindley|Paul J|PJ|


Cultural and Linguistic Practice with Children with Developmental Language Disorder: Findings from an International Practitioner Survey.

Abstract:
BACKGROUND
The cultural and language diversity across many European countries presents a range of challenges and opportunities for speech and language therapists and other practitioners working with children with developmental language disorders (DLD) and their families.

OBJECTIVE
The aim of this study was to explore practitioners' perceptions of cultural and linguistic differences in response to children with DLD across different countries.

METHODS
A survey was developed by practitioners and researchers working with children with DLD across Europe and beyond as part of the work of Cost Action IS1406. Data from 1,358 practitioners from 8 European countries - Ireland, UK, Bulgaria, Poland, Croatia, Spain, Norway and Sweden - and 2 neighbour countries - Turkey and Lebanon - were included in the present analyses, which address two groups of questions. The first focuses on practitioners' perceptions of the way that parents think about cultural differences and their relationship to language development in their children. The second concerns the extent to which practitioners consider themselves to have the skills to work with children from other cultures and using different languages.

RESULTS/CONCLUSIONS
Most countries present a similar profile with intermediate results about their perception of cultural issues, but Lebanon and Turkey are the group with the most positive responses. In terms of bilingual issues most practitioners indicated that they only worked in their country's primary language. The only country where this was not the case was Lebanon. Professionals from Spain and Lebanon form a subgroup in terms of their confidence to work with different cultural/language groups. The paper highlights both the universal importance of cultural and linguistic competence in managing young children's needs and indicates that in most cases professionals do not think they have the necessary expertise to work with cultural and linguistic diversity.

Stankova|Margarita|M|
Rodríguez-Ortiz|Isabel R|IR|
Matić|Ana|A|
Levickis|Penny|P|
Lyons|Rena|R|
Messarra|Camille|C|
Kouba Hreich|Edith|E|
Vulchanova|Mila|M|
Vulchanov|Valentin|V|
Czaplewska|Ewa|E|
Ringblom|Natalia|N|
Hansson|Kristina|K|
Håkansson|Gisela|G|
Jalali-Moghadam|Niloufar|N|
Dionissieva|Katya|K|
Günhan Senol|N Evra|NE|
Law|James|J|

Developmental language disorder
Cultural and linguistic differences
Language development
Cultural and linguistic competence