Time point to perform lung function tests evaluating the effects of an airway clearance therapy session in cystic fibrosis.

Abstract:
BACKGROUND
Lung function parameters are used as end points in most clinical and therapeutic trials in cystic fibrosis (CF) and to evaluate the effects of airway clearance techniques. The aim of the study was to identify at what time point after a physiotherapy session spirometry (FEV1 and FVC) should be performed to obtain the highest result compared to baseline and to determine whether there are inter-individual and intra-individual differences in children and adults with CF.

METHODS
This was a prospective study. Twenty-four subjects with CF and mean FVC 70 ± 30% and FEV1 61 ± 30% of predicted were included. Each subject performed spirometry before their airway clearance session and then immediately after, 30 min after, and 1, 2, and 3 h after their physiotherapy session for 2 consecutive days.

RESULTS
In adult subjects, mean FEV1 improved 30 min (P < .001), 1 h (P < .002), and 2 h (P < .006) after physiotherapy compared to baseline. In pediatric subjects, it improved immediately after the session but was not statistically significant for recommendation. There were no intra-individual variations, but there were inter-individual variations (not statistically significant).

CONCLUSIONS
Performing spirometry 30 min (adults) and immediately (children) after a session might be optimal if individual peak time values cannot be used.

Rodriguez Hortal|Maria Cecilia|MC|
Hjelte|Lena|L|

time point
cystic fibrosis
spirometry
chest physiotherapy


Design, Synthesis, and Structure-Property Relationships of Er3+-Doped TiO₂ Luminescent Particles Synthesized by Sol-Gel.

Abstract: Titania particles doped with various concentrations of Erbium were synthesized by the sol-gel method followed by different heat treatments. The shape and the grain growth of the particles were noticeably affected by the concentration of Erbium and the heat treatment conditions. An infrared emission at 1530 nm, as well as green and red up-conversion emissions at 550 and 670 nm, were observed under excitation at 976 nm from all of the synthesized particles. The emission spectra and lifetime values appeared to be strongly influenced by the presence of the different crystalline phases. This work presents important guidelines for the synthesis of functional Er3+-doped titania particles with controlled and tailored spectroscopic properties for photonic applications.

erbium-doped titania
photoluminescence
sol-gel synthesis


Expression of pY397 FAK promotes the development of non-small cell lung cancer.

Abstract: Focal adhesion kinase (FAK) expression has been identified as associated with cancer development and metastasis. Autophosphorylation of FAK at tyrosine (Y) 397 (pY397) performs a critical role in tumor cell signaling. However, few studies have evaluated the expression of pY397 FAK in non-small cell lung cancer (NSCLC). In the present study, pY397 FAK expression in NSCLC was investigated using immunohistochemistry. pY397 FAK staining scores were compared between various groups of specimens and the associations between clinical and pathological characteristics were investigated. A Kaplan-Meier survival curve was used to determine the association between pY397 FAK expression and the prognosis of NSCLC patients. The results of the present study revealed that pY397 FAK expression was localized to the cytoplasm of lung cells, and that pY397 FAK was overexpressed in NSCLC tissues, as well as associated metastatic tissues, when compared with the corresponding non-tumor tissues. However, no significant difference was identified between the pY397 FAK expression in primary lesions and lymph node metastases. Furthermore, pY397 FAK staining scores were not found to be associated with the tumor size, gender, degree of differentiation, histotypes, presence of lymph node metastases or survival rate of NSCLC patients. These results indicate that pY397 FAK is involved with the development of NSCLC, but is not a prognostic marker for the disease.

Wang|Baichun|B| Qi|Xiuying|X| Li|Danyang|D| Feng|Meiyan|M| Meng|Xiangning|X| Fu|Songbin|S|

non-small cell lung cancer
immunohistochemistry
prognosis
pY397 focal adhesion kinase


Effects of a national economic crisis on dental habits and checkup behaviors - a prospective cohort study.

Abstract:
OBJECTIVES
The effects of economic recessions on dental health behaviors and care utilization are vastly unexamined. Thus, we aimed to ascertain changes in dental health behaviors and checkup frequency from before to after the start of the 2008 Icelandic economic collapse using a nationally representative, prospective cohort - the Health and Wellbeing in Iceland cohort.

METHODS
Participants in the cohort (n = 4100) were contacted first from October to December of 2007 and again from November to December of 2009. The questionnaires assessed respondent's demographics, dental behaviors (brushing, flossing), and dental checkup frequency. We present odds ratios derived from multivariate logistic regression of visiting a dentist annually after the collapse compared with before, as well as odds ratios of daily brushing and flossing habits.

RESULTS
Overall, there was no strong evidence for drastic changes in dental health behaviors as from 2007 to 2009. However, employed men (odds ratio 1.29; 95% confidence interval 1.07-1.54) - as well as unemployed women (1.98; 1.00-3.92) - experienced increased odds of visiting a dentist at least annually. Additionally, men were more likely to brush (1.42; 1.05-1.93) and floss daily (1.20; 1.03-1.42) after the collapse compared with before.

CONCLUSIONS
Overall, it seems as if the collapse did not have drastic negative effects on dental health behaviors of the population in Iceland. Our findings suggest that men may have opted for healthier dental health behaviors following the national economic collapse in 2008.

McClure|Christopher Bruce|CB|
Saemundsson|Sigurður Rúnar|SR|

economics
dental health
dental services research
health services research
public health


Rapid analysis of barley straw before and after dilute sulfuric acid pretreatment by photoluminescence.

Abstract: The fluorescence intensities (FIs) of raw and pretreated barley straws were measured by fluorescence microscopy, and the difference in the fluorescence intensity of barley straw before and after dilute acid pretreatment was analyzed by investigation of the major compounds of barley straw. The difference in fluorescence intensity was due to the difference in xylan content. Barley straw was pretreated using dilute sulfuric acid at various conditions and the correlation between the fluorescence intensity and glucose yield of barley straw was investigated. The coefficient of determination (R(2)) of the correlation was found to be 72.28%. Also the calibration of fluorescence intensity with the xylan content was performed. In addition, the absorption and emission spectra of the raw and the pretreated barley straw were examined to verify the proposed method. The absorption and emission wave lengths were 550 nm and 665 nm, respectively.

Kim|Sung Bong|SB|
Cui|Chunzhi|C|
Lee|Ja Hyun|JH|
Lee|Sang Jun|SJ|
Ahn|Dong June|DJ|
Park|Chulhwan|C|
Kim|Jun Seok|JS|
Kim|Seung Wook|SW|

Photoluminescence
Fluorescence
Dilute acid pretreatment
Xylan
Biomass analysis


Why care about linear hair growth rates (LHGR)? a study using in vivo imaging and computer assisted image analysis after manual processing (CAIAMP) in unaffected male controls and men with male pattern hair loss (MPHL).

Abstract:
BACKGROUND
The words "hair growth" frequently encompass many aspects other than just growth.

OBJECTIVES
Report on a validation method for precise non-invasive measurement of thickness together with linear hair growth rates of individual hair fibres. To verify the possible correlation between thickness and linear growth rate of scalp hair in male pattern hair loss as compared with healthy male controls.

MATERIALS AND METHODS
To document the process of validation of hair growth measurement from in vivo image capturing and manual processing, followed by computer assisted image analysis. We analysed 179 paired images obtained with the contrast-enhanced-phototrichogram method with exogen collection (CE-PTG-EC) in 13 healthy male controls and in 87 men with male pattern hair loss (MPHL).

RESULTS
There was a global positive correlation between thickness and growth rate (ANOVA; p<0.0001) and a statistically significantly (ANOVA; p<0.0005) slower growth rate in MPHL as compared with equally thick hairs from controls. Finally, the growth rate recorded in the more severe patterns was significantly (ANOVA; P ≤ 0.001) reduced compared with equally thick hair from less severely affected MPHL or controls subjects.

CONCLUSION
Reduced growth rate, together with thinning and shortening of the anagen phase duration in MPHL might contribute together to the global impression of decreased hair volume on the top of the head. Amongst other structural and functional parameters characterizing hair follicle regression, linear hair growth rate warrants further investigation, as it may be relevant in terms of self-perception of hair coverage, quantitative diagnosis and prognostic factor of the therapeutic response.

imaging
male pattern hair loss
scalp hair
androgenetic alopecia
clinical trial
phototrichogram


The novel function of JADE1S in cytokinesis of epithelial cells.

Abstract: JADE1 belongs to a small family of PHD zinc finger proteins that interacts with histone acetyl transferase (HAT) HBO1 and is associated with chromatin. We recently reported JADE1 chromatin shuttling and phosphorylation during G2/M to G1 transition, which was sensitive to Aurora A inhibition. In the current study we examined mechanisms of the cell cycle regulation by the small isoform of JADE1 protein, JADE1S, and report data showing that JADE1S has a novel function in the regulation of cytokinesis. Using FACS assays, we show that, JADE1S depletion facilitated rates of G1-cells accumulation in synchronously dividing HeLa cell cultures. Depletion of JADE1S protein in asynchronously dividing cells decreased the proportion of cytokinetic cells, and increased the proportion of multi-nuclear cells, indicative of premature and failed cytokinesis. In contrast, moderate overexpression of JADE1S increased the number of cytokinetic cells in time- and dose- dependent manner, indicating cytokinetic delay. Pharmacological inhibition of Aurora B kinase resulted in the release of JADE1S-mediated cytokinetic delay and allowed progression of abscission in cells over-expressing JADE1S. Finally, we show that JADE1S protein localized to centrosomes in interphase and mitotic cells, while during cytokinesis JADE1S localized to the midbody. Neither JADE1L nor partner of JADE1, HAT HBO1 was localized to the centrosomes or midbodies. Our study identifies the novel role for JADE1S in regulation of cytokinesis and suggests function in Aurora B kinase-mediated cytokinesis checkpoint.

Siriwardana|Nirodhini S|NS|
Meyer|Rosana D|RD|
Panchenko|Maria V|MV|

D048749:Cytokinesis
D004847:Epithelial Cells
D057809:HEK293 Cells
D006367:HeLa Cells
D018398:Homeodomain Proteins
D006801:Humans
D061986:MCF-7 Cells
D025521:Tumor Suppressor Proteins

cytokinesis
chromatin shuttling
Aurora B kinase
MYST2
PHF17
epithelial cell cycle
final abscission


The importance of coagulation factors binding to adenovirus: historical perspectives and implications for gene delivery.

Abstract:
INTRODUCTION
The interaction of human adenovirus (HAdV) serotype 5 (HAdV-5) with the blood coagulation factor X (FX) results in a high liver transduction after AdV intravascular administration, causing toxicity and limiting AdV delivery to the target tissue. However, FX also protects adenoviral vectors from neutralization by the complement system and natural antibodies, potentially benefiting adenoviral gene delivery, as neutralization results in the reduction of HAdV-5 binding to host cells.

AREAS COVERED
This review gives an overview on the use of adenoviruses as gene transfer vehicles and their impact in gene therapy. The structure of coagulation factors and their interactions with HAdV are described, highlighting their influence on the AdV biodistribution profile. The implications of this interaction in immunity and its potential influence on the use of adenoviral vectors in gene therapy applications are discussed.

EXPERT OPINION
The protective role of FX brings under discussion how beneficial abolishment of FX binding would be for HAdV-5 liver detargeting. The dispensability of FX for liver transduction in immunocompromised mice suggests the involvement of other blood factors or receptors in enhancing HAdV-5 liver transduction. Better understanding of the interactions that take place in the bloodstream is essential to generate safe and efficient adenoviral vectors.

Lopez-Gordo|Estrella|E|
Denby|Laura|L|
Nicklin|Stuart A|SA|
Baker|Andrew H|AH|

D000260:Adenoviruses, Human
D000818:Animals
D005170:Factor X
D018014:Gene Transfer Techniques
D015316:Genetic Therapy
D005822:Genetic Vectors
D006801:Humans
D008099:Liver
D011485:Protein Binding

adenovirus
serotype
coagulation factor X
liver
toxicity
gene therapy


High expression of COL5A2, a member of COL5 family, indicates the poor survival and facilitates cell migration in gastric cancer.

Abstract:
BACKGROUND
Gastric cancer (GC) metastasis determines the prognosis of patients, and exploring the molecular mechanism of GC metastasis is expected to provide a theoretical basis for clinical treatment. Recent studies have shown that extracellular matrix protein is closely related to GC metastasis. The present study aimed to explore the expression profile and role of COL5A2, as an extracellular matrix protein, in GC.

METHODS
The expression, overall survival, and progression-free survival data of COL5 family members were extracted from The Cancer Genome Atlas (TCGA) database, respectively. Weighted gene co-expression network analysis of the GSE62229 database was performed out to identify modules and associated genes.

RESULTS
COL5A2 was selected as our research target in the TCGA database, and was also verified in the GSE62229 and GSE15459 datasets. COL5A2 was up-regulated in GC tissues by paraffin immunohistochemistry and RT-qPCR. The prognosis of patients with low COL5A2 expression was better than that of patients with high COL5A2 expression. Scratch and migration experiments showed that knockdown of COL5A2 decreased the migration ability of gastric cancer cells compared with the control group. In vivo, mice with tail vein injection COL5A2 knockdown had fewer and smaller metastatic nodules in liver. GSEA results showed that the TCGA and GSE62229 samples were significantly enriched in several well-known cancer-related pathways, such as the TGF-β, MAPK, and JAK2 signaling pathways.

CONCLUSION
COL5A2 was most closely related to advanced GC among COL5 family members. High COL5A2 expression is associated with a poor prognosis, and may be a novel therapeutic target for GC.

Tan|Yuen|Y| Chen|Qingchuan|Q| Xing|Yao|Y| Zhang|Chao|C| Pan|Siwei|S| An|Wen|W| Xu|Huimian|H|

COL5A2
COL5 family
TCGA and GEO databases
WGCNA
advanced gastric cancer (AGC)


Glass-Fabric Reinforced Ag Nanowire/Siloxane Composite Heater Substrate: Sub-10 nm Metal@Metal Oxide Nanosheet for Sensitive Flexible Sensing Platform.

Abstract: The development of flexible chemiresistors is imperative for real-time monitoring of air quality and/or human physical conditions without space constraints. However, critical challenges such as poor sensing characteristics, vulnerability under toxic chemicals, and weak reliability hinder their practical use. In this work, for the first time, an ultrasensitive flexible sensing platform is reported by assembling Pt loaded thin-layered (≈10 nm) SnO2 nanosheets (Pt-SnO2 NSs) based 2D sensing layers on Ag nanowires embedded glass-fabric reinforced vinyl-phenyl siloxane hybrid composite substrate (AgNW-GFRVPH film) as a heater. The thermally stable AgNW-GFRVPH film based heater is fabricated by free radical polymerization of vinyl groups in vinyl-phenyl oligosiloxane and phenyltris(dimethylvinylsiloxy)silane with Ag NW and glass-fabric, showing outstanding heat generation (≈200 °C), high dimensional stability (13 ppm °C-1), and good thermal stability (≈350 °C). The Pt-SnO2 NSs, which are synthesized by calcination of Sn precursor coated graphene oxide (GO) sheets and subsequent Pt functionalization, exhibit high mechanical flexibility and superior response (Rair/Rgas = 4.84) to 1 ppm level dimethyl sulfide. Taking these advantages, GO-templated oxide NSs combined with a highly stable AgNW-GFRVPH film heater exhibits the best dimethyl sulfide sensing performance compared to state-of-the-art flexible chemiresistors, enabling them as a superior flexible gas sensing platform.

Ag nanowires
heater
nanosheets
flexible gas sensor
hybrimer


Trends and Predictors of Oral Anticoagulant Use in People with Alzheimer's Disease and the General Population in Australia.

Abstract:
BACKGROUND
People with Alzheimer's disease (AD) are less likely to use oral anticoagulants than people without AD.

OBJECTIVE
We investigated incidence and prevalence of warfarin and direct oral anticoagulant (DOAC) use, and determined predictors of DOAC and warfarin initiation in older people with AD and the general population.

METHODS
Australian Pharmaceutical Benefits Scheme data for 356,000 people aged ≥65 years dispensed warfarin or DOACs during July 2013-June 2017 were analyzed. Changes in annual incidence and prevalence were estimated using Poisson regression. Predictors of DOAC versus warfarin initiation were estimated using multivariable logistic regression separately for people with AD and the general population.

RESULTS
Oral anticoagulant prevalence increased from 8% in people with AD and 9% in the general population to 12% in both groups from 2013/2014 to 2016/2017. DOAC prevalence increased (from 2.4% to 7.8% in people with AD, 3.2% to 7.7% in the general population) while warfarin prevalence declined (6.6% to 4.5%, 7.0% to 4.3%, correspondingly). The incidence of warfarin use decreased by 45-55%. In people with AD, women were less likely to initiate DOACs than men, whereas presence of arrhythmias or pain/inflammation increased likelihood of initiating DOACs. Age ≥85 years, cardiovascular diseases, gastric acid disorder, diabetes, and end-stage renal disease were associated with lower odds of DOAC initiation in the general population.

CONCLUSION
DOAC introduction has coincided with increased anticoagulation rates in people with AD. Rates are now similar in older people with AD and the general population. Compared to previous years, DOACs are now more likely to be initiated, particularly for those aged ≥85 years.

Ilomäki|Jenni|J|
Fanning|Laura|L|
Keen|Claire|C|
Sluggett|Janet K|JK|
Page|Amy T|AT|
Korhonen|Maarit J|MJ|
Meretoja|Atte|A|
Mc Namara|Kevin P|KP|
Bell|J Simon|JS|

trends
anticoagulants
Australia
incidence
prevalence
warfarin
direct oral anticoagulants
Alzheimer’s disease
atrial fibrillation
dementia


Quantitative clinical and radiological recovery in post-operative patients with superficial siderosis by an iron chelator.

Abstract:
BACKGROUND
Superficial siderosis is a rare neurodegenerative disease caused by hemosiderin deposition on the brain surface. Although the efficacy of the iron chelator-deferiprone-in superficial siderosis has recently been documented, a comparative study of patients who underwent surgical ablation of their bleeding source and subsequently received treatment with or without deferiprone has not yet been conducted.

METHODS
Fifteen postoperative patients with superficial siderosis were recruited, and seven patients were administered deferiprone (combination therapy group). Quantitative changes in the hypointense signals on T2*-weighted magnetic resonance images were acquired; additionally, cerebellar ataxia was assessed (International Cooperative Ataxia Rating Scale score and Scale for the Assessment and Rating of Ataxia). Audiometry was performed and the results were compared with those of patients who did not receive deferiprone (surgical treatment group; controls).

RESULTS
Significant improvements in signal contrast ratios were noted in the lateral orbitofrontal gyrus, superior temporal lobe, insular lobe, brainstem, lingual gyrus, and cerebellar lobe in the combination therapy group. The scores of patients in the combination therapy group on the cerebellar ataxia scales significantly improved. The degree of signal improvement in the cerebellar lobe correlated with the improvement of cerebellar ataxia scores. Early deferiprone administration after disease onset and long-term administration were correlated with greater signal improvements on magnetic resonance imaging. No adverse effects were observed in the clinical or laboratory parameters.

CONCLUSIONS
Deferiprone administration significantly improved radiological and clinical outcomes in patients with postoperative superficial siderosis. Earlier and longer courses of deferiprone could result in better patient prognosis.

Superficial siderosis
Iron chelation
Hemosiderin deposition
Deferiprone
T2 hypointensity


Advantages and challenges associated with implementing an ecosystem services approach to ecological risk assessment for chemicals.

Abstract: The ecosystem services (ES) approach is gaining broad interest in regulatory and policy arenas for use in landscape management and ecological risk assessment. It has the potential to bring greater ecological relevance to the setting of environmental protection goals and to the assessment of the ecological risk posed by chemicals. A workshop, organised under the auspices of the Society of Environmental Toxicology and Chemistry Europe, brought together scientific experts from European regulatory authorities, the chemical industry and academia to discuss and evaluate the challenges associated with implementing an ES approach to chemical ecological risk assessment (ERA). Clear advantages of using an ES approach in prospective and retrospective ERA were identified, including: making ERA spatially explicit and of relevance to management decisions (i.e. indicating what ES to protect and where); improving transparency in communicating risks and trade-offs; integrating across multiple stressors, scales, habitats and policies. A number of challenges were also identified including: the potential for increased complexity in assessments; greater data requirements; limitations in linking endpoints derived from current ecotoxicity tests to impacts on ES. In principle, the approach was applicable to all chemical sectors, but the scale of the challenge of applying an ES approach to general chemicals with widespread and dispersive uses leading to broad environmental exposure, was highlighted. There was agreement that ES-based risk assessment should be based on the magnitude of impact rather than on toxicity thresholds. The need for more bioassays/tests with functional endpoints was recognized, as was the role of modelling and the need for ecological production functions to link measurement endpoints to assessment endpoints. Finally, the value of developing environmental scenarios that can be combined with spatial information on exposure, ES delivery and service provider vulnerability was recognized.

Maltby|Lorraine|L|
van den Brink|Paul J|PJ|
Faber|Jack H|JH|
Marshall|Stuart|S|

D003247:Conservation of Natural Resources

Ecotoxicity tests
Ecological indicators
Landscape-scale risk assessment


Investigating the Role of Health Factors and Psychological Well-Being in Gaming Disorder.

Abstract: The recent recognition of Gaming Disorder (GD) as a mental health issue has provided a unique opportunity for researchers to advance our current understanding of the intricate relationships between GD and specific health-related factors and well-being. This study sought to investigate the role of key physical and psychological health and well-being factors in GD. To achieve this, three goals were explored. First, we tested whether GD can be predicted by health and well-being factors such as depression, anxiety, loneliness, attention problems, physical health problems (PHP), and psychological well-being (PWB). Second, we assessed the role of distress tolerance (DT) as a moderator in the relationship between PWB and GD. Third, we examined whether PWB would mediate the relationship between PHP and GD. A sample of 474 participants (Meanage = 28.86 years; SD = 9.23; range: 18-66 years; 47 percent female) were recruited. The results of the multiple linear regression analysis indicated that age, attention problems, and PHP significantly predicted GD (R2 = 0.15). In addition, the mediation findings uncovered an important direct association between PHP and GD despite the lack of mediation effects through PWB and the absence of moderating effects from DT. The present findings signify important health-related implications related to GD that are further discussed here in terms diagnosis, treatment, and prevention efforts.

Moore|Samuel|S|
Satel|Jason|J|
Pontes|Halley M|HM|0000-0001-8020-7623

psychological well-being
gaming disorder
psychological health
physical health


Effects of Lactobacillus acidophilus LA-3 on physicochemical and sensory parameters of açaí and mango based smoothies and its survival following simulated gastrointestinal conditions.

Abstract: The effects of the incorporation of Lactobacillus acidophilus LA3 (inoculated at 9 log CFU/mL) on physicochemical parameters, contents of sugars and organic acids, phenolic profile and sensory aspects of açaí (AS) and mango based smoothies (MS) during 28 days of refrigerate storage were assessed. The survival of L. acidophilus in AS and MS under simulated human gastrointestinal conditions during storage was also monitored. Counts of L. acidophilus LA-3 were approximately 8.5 log CFU/mL in AS and 7.5 log CFU/mL in MS after 1 day of storage and no changes (p ≥ 0.05) were observed in later evaluated storage time periods. Fruit smoothies (AS or MS) with L. acidophilus LA-3 presented lower (p < 0.05) contents of glucose, fructose and maltose and higher (p < 0.05) contents of lactic and succinic acids compared to those without L. acidophilus LA-3. Phenolic contents increased or decreased (p < 0.05) after 1 day of storage in AS and MS with L. acidophilus LA-3 and did not change (p ≥ 0.05) in AS or MS without L. acidophilus LA-3. The incorporation of L. acidophilus LA-3 increased the acidic flavor and fermented aroma in AS and MS. Viable counts of L. acidophilus LA-3 were approximately 7.5 and 8.5 log CFU/mL in AS and MS, respectively, at the end of in vitro digestion just after the incorporation, as well as on days 14 and 28 of storage. These results show the feasibility of incorporating L. acidophilus LA-3 into AS or MS and suggest these fruit smoothies as matrices for formulation of non-dairy beverages containing potentially probiotic lactobacilli.

Luciano|Winnie Alencar|WA|
Matte|Thais Costa|TC|
Portela|Isabella Araújo|IA|
de Medeiros|Lorena Lucena|LL|
Dos Santos Lima|Marcos|M|
Maciel|Janeeyre Ferreira|JF|
de Souza|Evandro Leite|EL|
Garcia|Estefânia Fernandes|EF|
Magnani|Marciane|M|

Probiotics
Lactobacilli
Fruit phenolics
Functional beverages


Artificial Sensory Memory.

Abstract: Sensory memory, formed at the beginning while perceiving and interacting with the environment, is considered a primary source of intelligence. Transferring such biological concepts into electronic implementation aims at achieving perceptual intelligence, which would profoundly advance a broad spectrum of applications, such as prosthetics, robotics, and cyborg systems. Here, the recent developments in the design and fabrication of artificial sensory memory devices are summarized and their applications in recognition, manipulation, and learning are highlighted. The emergence of such devices benefits from recent progress in both bioinspired sensing and neuromorphic engineering technologies and derives from abundant inspiration and benchmarks from an improved understanding of biological sensory processing. Increasing attention to this area would offer unprecedented opportunities toward new hardware architecture of artificial intelligence, which could extend the capabilities of digital systems with emotional/psychological attributes. Pending challenges are also addressed to aspects such as integration level, energy efficiency, and functionality, which would undoubtedly shed light on the future development of translational implementations.

memory
neuromorphic engineering
artificial neurons
bioinspired sensors


Keratinocyte growth factor in focus: A comprehensive review from structural and functional aspects to therapeutic applications of palifermin.

Abstract: Palifermin (Kepivance™) is the first therapeutic approved by the Food and Drug Administration for preventing and managing the oral mucositis provoked by myelotoxic and mucotoxic therapies. Palifermin is a recombinant protein generated from human keratinocyte growth factor (KGF) and imitates the function of endogenous KGF. KGF is an epithelial mitogen involved in various biological processes which belongs to the FGF family. KGF possesses a high level of receptor specificity and plays an important role in tissue repair and maintaining of the mucosal barrier integrity. Based on these unique features, palifermin was developed to enhance the growth of damaged epithelial tissues. Administration of palifermin has shown success in the reduction of toxicities of chemotherapy and radiotherapy, and improvement of the patient's quality of life. Notwithstanding all merits, the clinical application of palifermin is limited owing to its instability and production challenges. Hence, a growing number of ongoing researches are designed to deal with these problems and enhance the physicochemical and pharmaceutical properties of palifermin. In the current review, we discuss KGF structure and function, potential therapeutic applications of palifermin, as well as the latest progress in the production of recombinant human KGF and its challenges ahead.

Sadeghi|Solmaz|S| Kalhor|Hourieh|H| Panahi|Mohammad|M| Abolhasani|Hoda|H| Rahimi|Bahareh|B| Kalhor|Reyhaneh|R| Mehrabi|Amirmehdi|A| Vahdatinia|Mahsa|M| Rahimi|Hamzeh|H|

Oral mucositis
KGF
Fibroblast growth factor
Therapeutic proteins
cancer therapy


Spatial Vertical Directionality and Correlation of Low-Frequency Ambient Noise in Deep Ocean Direct-Arrival Zones.

Abstract: Wind-driven and distant shipping noise sources contribute to the total noise field in the deep ocean direct-arrival zones. Wind-driven and distant shipping noise sources may significantly and simultaneously affect the spatial characteristics of the total noise field to some extent. In this work, a ray approach and parabolic equation solution method were jointly utilized to model the low-frequency ambient noise field in a range-dependent deep ocean environment by considering their calculation accuracy and efficiency in near-field wind-driven and far-field distant shipping noise fields. The reanalysis databases of National Center of Environment Prediction (NCEP) and Volunteer Observation System (VOS) were used to model the ambient noise source intensity and distribution. Spatial vertical directionality and correlation were analyzed in three scenarios that correspond to three wind speed conditions. The noise field was dominated by distant shipping noise sources when the wind speed was less than 3 m/s, and then the spatial vertical directionality and vertical correlation of the total noise field were nearly consistent with those of distant shipping noise field. The total noise field was completely dominated by near field wind generated noise sources when the wind speed was greater than 12 m/s at 150 Hz, and then the spatial vertical correlation coefficient and directionality pattern of the total noise field was approximately consistent with that of the wind-driven noise field. The spatial characteristics of the total noise field for wind speeds between 3 m/s and 12 m/s were the weighted results of wind-driven and distant shipping noise fields. Furthermore, the spatial characteristics of low-frequency ambient noise field were compared with the classical Cron/Sherman deep water noise field coherence function. Simulation results with the described modeling method showed good agreement with the experimental measurement results based on the vertical line array deployed near the bottom in deep ocean direct-arrival zones.

Yang|Qiulong|Q| Yang|Kunde|K| Cao|Ran|R| Duan|Shunli|S|

vertical directionality
correlation
ambient noise
deep ocean
low frequency


Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles.

Abstract: Despite the existence of effective oral therapy, tuberculosis remains a deadly pathology, namely because of bacterial resistance and incompliance with treatments. Establishing alternative therapeutic approaches is urgently needed and inhalable therapy has a great potential in this regard. As pathogenic bacteria are hosted by alveolar macrophages, the co-localisation of antitubercular drugs and pathogens is thus potentiated by this strategy. This work proposes inhalable therapy of pulmonary tuberculosis mediated by a single locust bean gum (LBG) formulation of microparticles associating both isoniazid and rifabutin, complying with requisites of the World Health Organisation of combined therapy. Microparticles were produced by spray-drying, at LBG/INH/RFB mass ratio of 10/1/0.5. The aerodynamic characterisation of microparticles revealed emitted doses of more than 90% and fine particle fraction of 38%, thus indicating the adequacy of the system to reach the respiratory lung area, thus partially the alveolar region. Cytotoxicity results indicate moderate toxicity (cell viability around 60%), with a concentration-dependent effect. Additionally, rat alveolar macrophages evidenced preferential capture of LBG microparticles, possibly due to chemical composition comprising mannose and galactose units that are specifically recognised by macrophage surface receptors.

Rodrigues|Susana|S|
Alves|Ana D|AD|
Cavaco|Joana S|JS|
Pontes|Jorge F|JF|
Guerreiro|Filipa|F|
Rosa da Costa|Ana M|AM|
Buttini|Francesca|F|
Grenha|Ana|A|

Inhalation
Locust bean gum
Microparticles
Spray-drying
Polysaccharides
Tuberculosis therapy


Glucosylation by the Legionella Effector SetA Promotes the Nuclear Localization of the Transcription Factor TFEB.

Abstract: Legionella pneumophila is an intracellular pathogen that requires nutrients from the host for its replication. It has been shown that replicating L. pneumophila prefers amino acids as main sources of carbon and energy. The homeostasis of amino acids in eukaryotic cells is regulated by the transcription factor EB (TFEB), which translocates into the nucleus and activates genes for autophagy and lysosomal biogenesis. Here we show that the Legionella effector SetA causes a robust nuclear translocation of TFEB when exogenously expressed in mammalian cells and that the translocation is dependent on the glucosyltransferase activity of SetA. We further show that SetA directly glucosylates TFEB at multiple sites. Our findings of TFEB glucosylation by SetA may suggest an alternative strategy for exploiting host nutrients in addition to the control of host mTORC1 signaling by L. pneumophila. Our results provide further insight into the molecular mechanism of the delicate TFEB nuclear shuttling.

Beck|Wendy H J|WHJ|
Kim|Dongsung|D|
Das|Jishnu|J|
Yu|Haiyuan|H|
Smolka|Marcus B|MB|
Mao|Yuxin|Y|


Trivalent inactivated influenza vaccine effective against influenza A(H3N2) variant viruses in children during the 2014/15 season, Japan.

Abstract: The 2014/15 influenza season in Japan was characterised by predominant influenza A(H3N2) activity; 99% of influenza A viruses detected were A(H3N2). Subclade 3C.2a viruses were the major epidemic A(H3N2) viruses, and were genetically distinct from A/New York/39/2012(H3N2) of 2014/15 vaccine strain in Japan, which was classified as clade 3C.1. We assessed vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children aged 6 months to 15 years by test-negative case-control design based on influenza rapid diagnostic test. Between November 2014 and March 2015, a total of 3,752 children were enrolled: 1,633 tested positive for influenza A and 42 for influenza B, and 2,077 tested negative. Adjusted VE was 38% (95% confidence intervals (CI): 28 to 46) against influenza virus infection overall, 37% (95% CI: 27 to 45) against influenza A, and 47% (95% CI: -2 to 73) against influenza B. However, IIV was not statistically significantly effective against influenza A in infants aged 6 to 11 months or adolescents aged 13 to 15 years. VE in preventing hospitalisation for influenza A infection was 55% (95% CI: 42 to 64). Trivalent IIV that included A/New York/39/2012(H3N2) was effective against drifted influenza A(H3N2) virus, although vaccine mismatch resulted in low VE.

Sugaya|Norio|N| Shinjoh|Masayoshi|M| Kawakami|Chiharu|C| Yamaguchi|Yoshio|Y| Yoshida|Makoto|M| Baba|Hiroaki|H| Ishikawa|Mayumi|M| Kono|Mio|M| Sekiguchi|Shinichiro|S| Kimiya|Takahisa|T| Mitamura|Keiko|K| Fujino|Motoko|M| Komiyama|Osamu|O| Yoshida|Naoko|N| Tsunematsu|Kenichiro|K| Narabayashi|Atsushi|A| Nakata|Yuji|Y| Sato|Akihiro|A| Taguchi|Nobuhiko|N| Fujita|Hisayo|H| Toki|Machiko|M| Myokai|Michiko|M| Ookawara|Ichiro|I| Takahashi|Takao|T|

Influenza
vaccine effectiveness
Influenza Virus
Laboratory surveillance
vaccine and immunization


Physiologic and psychosocial changes of the menopause transition in US Latinas: a narrative review.

Abstract: Latinos comprise the fastest-growing minority group in the USA, with Hispanic women (Latinas) constituting 17% of women aged 45-54 years. The menopause transition (MT) is associated with many physiological, behavioral, and psychosocial changes that can affect disease risk in women. While several epidemiologic investigations have enhanced our understanding of the MT, to date, menopause research has mostly focused on non-Latina White women. As a consequence, there is a dearth of information on strategies for managing menopause-related issues in Latinas and important factors to consider to provide culturally appropriate care and promote lifestyles that may reduce adverse health outcomes. This narrative review summarizes existing evidence of the MT in Latinas, with a focus on hormonal alterations, menopausal symptoms, mental health, cognition, and cardiometabolic health. The clinical and research implications of the current literature will also be discussed.

Cortés|Y I|YI|0000-0003-1520-2775
Marginean|V|V|
Berry|D|D|

menopause
cognition
Hispanic/Latina
cardiovascular
depression
sexual function
sleep
vasomotor symptoms


The Effect of Vitrification on Expression and Histone Marks of Igf2 and Oct4 in Blastocysts Cultured from Two-Cell Mouse Embryos.

Abstract:
OBJECTIVES
Vitrification is increasingly used in assisted reproductive technology (ART) laboratories worldwide. In this study the effect of vitrification on the expression and modifications of H3 histones of Igf2 and Oct4 was investigated in blastocysts cultured from vitrified and non-vitrified two-cell embryos.

MATERIALS AND METHODS
In this experimental study, two-cell embryos were cultured in KSOM medium to reach the blastocyst stage. Expression of Igf2 and Oct4 and modifications of H3 histones in regulatory regions of both genes were compared with in vivo blastocysts, which comprise the control group. To gene expression evaluation, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and the ChIP assay method were carried out to assess expression and histone modifications of the two genes.

RESULTS
The expression level of Igf2 was significantly higher in both experimental groups than the control group. In the regulatory region of Igf2, H3K9 methylation decreased whereas H3K9 acetylation increased in the experimental group compared with the control group. In contrast, the expression level of Oct4 was significantly lower in experimental groups. The Oct4 gene promoter showed a significant increase in H3K9 methylation and decrease in H3K9 acetylation (P<0.05).

CONCLUSIONS
According to our results, both vitrification and cultivation conditions may lead to changes in expression level and modification of histones in Igf2 and Oct4. However, these effects were the same in vitrified and non-vitrified groups. Indeed, the embryo is most affected by culture environment and in vitro culture. Therefore, vitrification may be used as a low-risk technique for embryo cryopreservation in ART.


Origin and Spread of HIV-1 Subtype B Among Heterosexual Individuals in Bulgaria.

Abstract: Human immunodeficiency virus (HIV) was originally introduced in Bulgaria through heterosexual transmission (HET) and later transferred to other vulnerable groups along with numerous more recent introductions from outside Bulgaria. To define the diversity, origins, and dynamics of the HIV-1 subtypes prevalent in HET population in Bulgaria, we applied phylogenetic and phylodynamic analyses using polymerase (pol) sequences from HET individuals to infer the spatiotemporal evolutionary history of the HIV-1 epidemic in this population in Bulgaria. High genetic diversity was found, including 13 different HIV-1 subtypes: 45.7% subtype B, 19.9% CRF01_AE, 7.5% CRF02_AG, 7.5% sub-subtypes A1 and A6, 7.1% subtype C, 5.3% subtype F1, 4.0% URFs, 1.2% CRF05_DF, 0.6% subtype G, 0.3% CRF04_cpx, 0.3% CRF29_BF, 0.3% CRF14_BG, and 0.3% subtype H. The estimated root of the subtype B in the phylogenetic tree dated back to the year 1980 largely due to multiple introductions of subtype B from outside the country. Several significant clades have been identified highlighting six different main epidemic entrances of subtype B dating from 1989 to 2007. The Bayesian skyline plot showed two different exponential growth periods starting in the 1980s to 1990 followed by a constant phase up to about 2008, with another exponential growth period from 2008 to the year 2012. The migration analysis identified dynamic pattern of gene flow and demonstrated that many HET probably acquired the infection abroad (14.6%), while only (6.6%) of non-HET were infected outside country. The phylogenetic analysis showed an intermixing between sequences from Bulgarians with sequences from other countries, suggesting different HIV introduction in this country followed by the internal spread through local transmission networks.

Alexiev|Ivailo|I|
Lo Presti|Alessandra|A|
Dimitrova|Reneta|R|
Foley|Brian|B|
Gancheva|Anna|A|
Kostadinova|Asya|A|
Nikolova|Lora|L|
Angeletti|Silvia|S|
Cella|Eleonora|E|
Elenkov|Ivaylo|I|
Stoycheva|Mariyana|M|
Nikolova|Daniela|D|
Doychinova|Tsetsa|T|
Pekova|Liliya|L|
Ciccozzi|Massimo|M|

D054302:pol Gene Products, Human Immunodeficiency Virus

subtype
heterosexuals
HIV
evolution
molecular epidemiology


Arthrospira platensis transglutaminase derived antioxidant peptide-packed electrospun chitosan/ poly (vinyl alcohol) nanofibrous mat accelerates wound healing, in vitro, via inducing mouse embryonic fibroblast proliferation.

Abstract: In this present study, we have carried out the antioxidant function of transglutaminase (TG) identified from Arthrospira platensis (Ap) transcriptome. The antioxidant peptide ML11 (MLRSIGIPARL) has been predicted from the transglutaminase core domain and the peptide's free radical scavenging potential was evaluated and it shows that it functions on a dose dependent manner. The ML11 peptide cell toxicity was analysed in the human blood leucocytes which resulted no cytotoxic activity in any of the cell population. Moreover, the nanofibre mat encapsulated with antioxidant peptide ML11 was prepared by electrospinning technique. The antioxidant peptide ML11 encapsulated mat showed increase in fibre diameter compared to the chitosan polyvinyl alcohol blended mat. The change in the crystalline behaviour of both chitosan and polyvinyl alcohol polymer to the amorphous nature was determined by X-ray diffraction at the broad band between 20 and 30° (2θ°). FTIR revealed the functional groups which present in the polymer as well as the interaction between their components of chitosan (CS) and polyvinyl alcohol (PVA). The fibre retains the antioxidant activity due to the peptide encapsulated by scavenging the intracellular ROS that was confirmed by flowcytometry and fluorescence microscopy. The ML11 peptide encapsulated mat showed no cytotoxicity in the NIH-3T3 mouse embryonic fibroblast cells. Also, ML11 peptide encapsulated fibre showed potential wound healing activity in NIH-3T3 cells. Taken altogether, the study indicates that the wound healing potential of the ML11 peptide encapsulated nano fibre mat may be used as biopharmaceutical drug.

Sannasimuthu|Anbazahan|A|
Ramani|Madhura|M|
Paray|Bilal Ahamad|BA|
Pasupuleti|Mukesh|M|
Al-Sadoon|Mohammad K|MK|
Alagumuthu|Tamil Selvi|TS|
Al-Mfarij|Abdul Rahman|AR|
Arshad|Aziz|A|
Mala|Kanchana|K|
Arockiaraj|Jesu|J|

Arthrospira platensis
Wound healing
Antioxidant peptide
Electrospinning
Chitosan
Polyvinyl alcohol


Effects of 14-day treatment with the schedule III anorectic phendimetrazine on choice between cocaine and food in rhesus monkeys.

Abstract:
BACKGROUND
The clinical utility of monoamine releasers such as phenmetrazine or d-amphetamine as candidate agonist medications for cocaine dependence is hindered by their high abuse liability. Phendimetrazine is a clinically available schedule III anorectic that functions as a prodrug for phenmetrazine and thus may have lower abuse liability. This study determined the effects of continuous 14-day treatment with phendimetrazine on cocaine vs. food choice in rhesus monkeys (N=4).

METHODS
Responding was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and cocaine injections (0-0.1mg/kg/injection, fixed-ratio 10 schedule). Cocaine choice dose-effect curves were determined daily before and during 14-day periods of continuous intravenous treatment with saline or (+)-phendimetrazine (0.32-1.0mg/kg/h). Effects of 14-day treatment with (+)-phenmetrazine (0.1-0.32 mg/kg/h; N=5) and d-amphetamine (0.032-0.1mg/kg/h; N=6) were also examined for comparison.

RESULTS
During saline treatment, food was primarily chosen during availability of low cocaine doses (0, 0.0032, and 0.01 mg/kg/injection), and cocaine was primarily chosen during availability of higher cocaine doses (0.032 and 0.1mg/kg/injection). Phendimetrazine initially decreased overall responding without significantly altering cocaine choice. Over the course of 14 days, tolerance developed to rate decreasing effects, and phendimetrazine dose-dependently decreased cocaine choice (significant at 0.032 mg/kg/injection cocaine). Phenmetrazine and d-amphetamine produced qualitatively similar effects.

CONCLUSIONS
These results demonstrate that phendimetrazine can produce significant, though modest, reductions in cocaine choice in rhesus monkeys. Phendimetrazine may be especially suitable as a candidate medication for human studies because of its schedule III clinical availability.

Banks|Matthew L|ML|
Blough|Bruce E|BE|
Negus|S Stevens|SS|

D000697:Central Nervous System Stimulants

Phendimetrazine
Choice
Cocaine
Rhesus monkey
Phenmetrazine
Amphetamine


Association between periodontitis and cognitive impairment: Analysis of national health and nutrition examination survey (NHANES) III.

Abstract:
OBJECTIVES
Periodontitis has been hypothesized as being one of the most common potential risk factors for the development of dementia and cognitive impairment. In order to investigate the relationship between periodontitis and cognition impairment, the National Health and Nutrition Examination Survey (NHANES) database was analysed after adjusting for potential confounding factors, including age and other systemic co-morbidities.

MATERIALS AND METHODS
In total, 4,663 participants aged 20-59 years who had received full-mouth periodontal examination and undergone the cognitive functional test were enrolled. The grade of periodontal disease was categorized into severe, moderate, and mild. Cognitive function examinations, including the simple reaction time test (SRTT), symbol digit substitution test (SDST), and serial digit learning test (SDLT), were adopted for the evaluation of cognitive impairment.

RESULTS
The subjects with mild and moderate to severe periodontitis had higher SDLT and SDST scores, which indicated decreased cognitive function, compared with the healthy group. After adjusting for demographic factors, education, smoking, cardiovascular diseases, and laboratory data, periodontitis was significantly correlated with elevated SDST and SDLT scores (p values for trend = 0.014 and 0.038, respectively) by generalized linear regression models.

CONCLUSION
Our study highlighted that periodontal status was associated with cognitive impairment in a nationally representative sample of US adults.

periodontitis
cognitive impairment
dementia
computerized cognitive tests
oral health


Inactivation of norovirus by atmospheric pressure plasma jet on salmon sashimi.

Abstract: This study investigated atmospheric pressure plasma (APP) jet, an emerging novel non-thermal technology, for the inactivation of human norovirus (NoV) on salmon sashimi. The influences of the non-thermal plasma on quality attributes of sashimi were also evaluated. Air, O2, and N2 (15 L/min) were used to produce the plasma jets. N2 plasma treatment for 12 min reduced NoV viral load (VL) (initial inoculums of 2.7 × 104 copies/g) by 2.17 × 104 copies/g, while air-based or O2-based plasma treatment for 9-12 min could reduce the VL to undetectable levels (below 100 copies/g). Under the same operating condition, the air-based or O2-based plasma treatment might increase slightly TBARS values in sashimi, yet the values (far below 1.0 mg MDA/kg) were within acceptable level for sashimi made with salmon fishes. The APP jets (APPJ) treatments could also retain the pH of sashimi at normal levels (6.29 ~ 6.02) to maintain the quality of salmon sashimi, the color quality of which was not affected evidently. The plasma-induced hardness and springiness changes in salmon sashimi were substantially low. These results suggested APPJ could be implemented as technology for inactivation of food-borne viruses and exhibited a high potential for application in fish sashimi processing, retaining product quality as well.

Norovirus
Salmon sashimi
Non-thermal atmospheric plasma jet
Quality evaluation


Evaluation of feature extraction techniques and classifiers for finger movement recognition using surface electromyography signal.

Abstract: Electromyography (EMG) in a bio-driven system is used as a control signal, for driving a hand prosthesis or other wearable assistive devices. Processing to get informative drive signals involves three main modules: preprocessing, dimensionality reduction, and classification. This paper proposes a system for classifying a six-channel EMG signal from 14 finger movements. A feature vector of 66 elements was determined from the six-channel EMG signal for each finger movement. Subsequently, various feature extraction techniques and classifiers were tested and evaluated. We compared the performance of six feature extraction techniques, namely principal component analysis (PCA), linear discriminant analysis (LDA), uncorrelated linear discriminant analysis (ULDA), orthogonal fuzzy neighborhood discriminant analysis (OFNDA), spectral regression linear discriminant analysis (SRLDA), and spectral regression extreme learning machine (SRELM). In addition, we also evaluated the performance of seven classifiers consisting of support vector machine (SVM), linear classifier (LC), naive Bayes (NB), k-nearest neighbors (KNN), radial basis function extreme learning machine (RBF-ELM), adaptive wavelet extreme learning machine (AW-ELM), and neural network (NN). The results showed that the combination of SRELM as the feature extraction technique and NN as the classifier yielded the best classification accuracy of 99%, which was significantly higher than those from the other combinations tested. Graphical abstract Mean of classification accuracies for 14 finger movements obtained with various pairs of SRELM and classifier.

Feature extraction
Electromyography (EMG)
Dimensionality reduction
EMG pattern recognition
Finger movement classification


Patient satisfaction and treatment outcomes of primary care practice in Ghana.

Abstract:
Background
General evidence suggests a strong association between patient satisfaction and treatment outcomes, but data specific to the general Ghanaian population is lacking.

Purpose
To use nationally representative data to examine the effects of primary care practices on patient satisfaction and how satisfaction influences treatment outcomes.

Methods
The study utilized WAVE 1 data from a nationally representative survey (n = 2,967) of patients who received outpatient medical care in Ghana. The data were collected by the World Health Organization between 2007 and 2010 and were analyzed using Kruskal Wallis test, binomial logistic regression, and correlations. Predictors for patients' experiences were waiting time, respectfulness, clear communication, privacy, decision-making, choice, and cleanliness.

Results
Overall, the patients reported positive experiences with all aspects of their primary care services. Thirty-three percent were very satisfied and 57% were satisfied with their last outpatient visit. Adjusted for sociodemographic and other variables, patient satisfaction with primary care was predominantly determined through privacy, decision-making, communication, and respectfulness. The model explained 54.6% (Nagelkerke R 2) of the variance in satisfaction and correctly classified 85.2% of cases. Patient satisfaction and treatment outcomes were significantly related, r(2959) = .54, p < .001.

Conclusion
In a nationally representative sample, quality of patient experiences was associated with high satisfaction, which in turn was positively associated with improved treatment outcomes.

Funding
None.

Patient satisfaction
treatment outcomes
primary care


Cosolvent, ions, and temperature effects on the structural properties of Cecropin A-Magainin 2 hybrid peptide in solutions.

Abstract: Antimicrobial peptides are promising alternative to traditional antibiotics and antitumor drugs for the battle against new antibiotic resistant bacteria strains and cancer maladies. The study of their structural and dynamics properties at physiological conditions can help to understand their stability, delivery mechanisms, and activity in the human body. In this article, we have used molecular dynamics simulations to study the effects of solvent environment, temperature, ions concentration, and peptide concentration on the structural properties of the antimicrobial hybrid peptide Cecropin A-Magainin 2. In TFE/water mixtures, the structure of the peptide retained α-helix contents and an average hinge angle in close agreement with the experimental NMR and CD measurements reported in literature. Compared to the TFE/water mixture, the peptide simulated at the same ionic concentration lost most of its α-helix structure. The increase of peptide concentration at both 300 and 310 K resulted in the peptide aggregation. The peptides in the complex retained the initial N-ter α-helix segment during all the simulation. The α-helix stabilization is further enhanced in the high salt concentration simulations. The peptide aggregation was not observed in TFE/water mixture simulations and, the peptide aggregate, obtained from the water simulation, simulated in the same conditions did dissolve within few tens of nanoseconds. The results of this study provide insights at molecular level on the structural and dynamics properties of the CA-MA peptide at physiological and membrane mimic conditions that can help to better understand its delivery and interaction with biological interfaces.

antimicrobial peptide
molecular dynamics simulations
peptide aggregation
2,2,2-trifluoroethanol
peptide conformation


Effect of increased enteral protein intake on plasma and urinary urea concentrations in preterm infants born at < 32 weeks gestation and < 1500 g birth weight enrolled in a randomized controlled trial - a secondary analysis.

Abstract:
BACKGROUND
Feeding breast milk is associated with reduced morbidity and mortality, as well as improved neurodevelopmental outcome but does not meet the high nutritional requirements of preterm infants. Both plasma and urinary urea concentrations represent amino acid oxidation and low concentrations may indicate insufficient protein supply. This study assesses the effect of different levels of enteral protein on plasma and urinary urea concentrations and determines if the urinary urea-creatinine ratio provides reliable information about the protein status of preterm infants.

METHODS
Sixty preterm infants (birthweight < 1500 g; gestational age < 32 weeks) were enrolled in a randomized controlled trial and assigned to either a lower-protein group (median protein intake 3.7 g/kg/d) or a higher-protein group (median protein intake 4,3 g/kg/d). Half the patients in the higher-protein group received standardized supplementation with a supplement adding 1.8 g protein/100 ml milk, the other half received individual supplementation depending on the respective mother's milk macronutrient content. Plasma urea concentration was determined in two scheduled blood samples (BS1; BS2); urinary urea and creatinine concentrations in weekly spot urine samples.

RESULTS
The higher-protein group showed higher plasma urea concentrations in both BS1 and BS2 and a higher urinary urea-creatinine-ratio in week 3 and 5-7 compared to the lower-protein group. In addition, a highly positive correlation between plasma urea concentrations and the urinary urea-creatinine-ratio (p < 0.0001) and between actual protein intake and plasma urea concentrations and the urinary urea-creatinine-ratio (both p < 0.0001) was shown.

CONCLUSIONS
The urinary urea-creatinine-ratio, just like plasma urea concentrations, may help to estimate actual protein supply, absorption and oxidation in preterm infants and, additionally, can be determined non-invasively. Further investigations are needed to determine reliable cut-off values of urinary urea concentrations to ensure appropriate protein intake.

TRIAL REGISTRATION
Clinicaltrials.gov; NCT01773902 registered 15 January 2013, retrospectively registered.

Mathes|Michaela|M|0000-0001-8737-1821
Maas|Christoph|C|
Bleeker|Christine|C|
Vek|Julia|J|
Bernhard|Wolfgang|W|
Peter|Andreas|A|
Poets|Christian F|CF|
Franz|Axel R|AR|

D001903:Bottle Feeding
D003404:Creatinine
D004044:Dietary Proteins
D005260:Female
D005527:Food, Fortified
D005865:Gestational Age
D006801:Humans
D007231:Infant, Newborn
D007234:Infant, Premature
D019102:Infant, Very Low Birth Weight
D008297:Male
D008895:Milk, Human

Urea concentration
Nutrition
Protein supply
Supplementation
Enteral feeding
Infant, newborn
Infant, premature
Milk, human
Targeted fortification
Very low birth weight infant


Preferences of people with type 2 diabetes for telemedical lifestyle programmes in Germany: protocol of a discrete choice experiment.

Abstract:
INTRODUCTION
Telemedical lifestyle programmes for people with type 2 diabetes mellitus (T2DM) provide an opportunity to develop a healthier lifestyle and consequently to improve health outcomes. When implementing new programmes into standard care, considering patients' preferences may increase the success of the participants. This study aims to examine the preferences of people with T2DM with respect to telemedical lifestyle programmes, to analyse whether these preferences predict programme success and to explore the changes that may occur during a telemedical lifestyle intervention.

METHODS AND ANALYSIS
We outline the protocol of the development and assessment of a discrete choice experiment (DCE) to examine patient preferences in a telemedical lifestyle programme with regard to the functions of the online portal, communication, responsibilities, group activities and time requirements. To develop the design of the DCE, we conducted pilot work involving healthcare experts and in particular people with T2DM using cognitive pretesting. The final DCE is being implemented within a randomised controlled trial for investigating whether participation in a telemedical lifestyle intervention programme sustainably improves the HbA1c values in 850 members of a large German statutory health insurance with T2DM. Preferences are being assessed before and after participants complete the programme. The DCE data will be analysed using regression and latent class analyses.

ETHICS AND DISSEMINATION
The DCE study has been approved by the ethics committee of the medical faculty of the Heinrich Heine University Duesseldorf, registration number 2018-242-ProspDEuA, registered on 6 December 2018. The TeLIPro trial is registered at the US National Library of Medicine, registration number NCT03675919, registered on 15 September 2018. We aim to disseminate our results in peer-reviewed journals, at national and international conferences and among interested patient groups and the public.

Sommer|Jana|J|0000-0001-7262-5657 Dyczmons|Jan|J| Grobosch|Sandra|S| Gontscharuk|Veronika|V| Vomhof|Markus|M| Roden|Michael|M| Icks|Andrea|A|

D016032:Randomized Controlled Trials as Topic

general diabetes
health economics
protocols & guidelines
qualitative research
statistics & research methods
telemedicine


Radial glia in the zebrafish brain: Functional, structural, and physiological comparison with the mammalian glia.

Abstract: The neuroscience community has witnessed a tremendous expansion of glia research. Glial cells are now on center stage with leading roles in the development, maturation, and physiology of brain circuits. Over the course of evolution, glia have highly diversified and include the radial glia, astroglia or astrocytes, microglia, oligodendrocytes, and ependymal cells, each having dedicated functions in the brain. The zebrafish, a small teleost fish, is no exception to this and recent evidences point to evolutionarily conserved roles for glia in the development and physiology of its nervous system. Due to its small size, transparency, and genetic amenability, the zebrafish has become an increasingly prominent animal model for brain research. It has enabled the study of neural circuits from individual cells to entire brains, with a precision unmatched in other vertebrate models. Moreover, its high neurogenic and regenerative potential has attracted a lot of attention from the research community focusing on neural stem cells and neurodegenerative diseases. Hence, studies using zebrafish have the potential to provide fundamental insights about brain development and function, and also elucidate neural and molecular mechanisms of neurological diseases. We will discuss here recent discoveries on the diverse roles of radial glia and astroglia in neurogenesis, in modulating neuronal activity and in regulating brain homeostasis at the brain barriers. By comparing insights made in various animal models, particularly mammals and zebrafish, our goal is to highlight the similarities and differences in glia biology among species, which could set new paradigms relevant to humans.

glia
zebrafish
astroglia
astrocytes
neurogenesis
blood-brain barrier
ependyma


Concurrent and Predictive Validity of Arm Kinematics With and Without a Trunk Restraint During a Reaching Task in Individuals With Stroke.

Abstract:
OBJECTIVE
To examine the concurrent and predictive validity of measurements of kinematic variables during reaching tasks with and without a trunk constraint in individuals with stroke.

DESIGN
Randomized controlled trials.

SETTINGS
Hospitals and a laboratory.

PARTICIPANTS
Individuals with stroke (N=95) enrolled in previous and ongoing clinical trials.

INTERVENTIONS
Upper limb training protocols were 90 to 120 minutes of intervention every weekday for 3 to 4 weeks.

MAIN OUTCOME MEASURES
Functional capacity was assessed using the Action Research Arm Test and motor impairment using the Fugl-Meyer Assessment for the Upper Extremity. Movement kinematics were measured during a reaching task with and without a trunk constraint. We derived 5 endpoint control variables and 3 joint recruitment variables for estimating concurrent and predictive validity.

RESULTS
The adjusted R(2) values for the constraint tasks ranged from .24 to .38 and for the unconstraint tasks from .29 to .40. Movement time was the most prominent kinematic variable for the Fugl-Meyer Assessment for the Upper Extremity before and after the intervention (P<.05). For the Action Research Arm Test, movement time and endpoint displacement were the most significant variables before and after the intervention, respectively (P<.05).

CONCLUSIONS
Measuring kinematic performance during an unconstrained task is appropriate and possibly sufficient to represent motor impairment and functional capacity of individuals with stroke. Movement time is the dominant variable associated with motor impairment and functional capacity, and endpoint displacement is unique in reflecting functional capacity of individuals with stroke.

Li|Kuan-yi|KY| Lin|Keh-chung|KC| Chen|Chih-kuang|CK| Liing|Rong-jiuan|RJ| Wu|Ching-yi|CY| Chang|Wan-ying|WY|

Validity
Kinematics
Motor
Functional residual capacity
Rehabilitation


A modified natural cycle results in higher live birth rate in vitrified-thawed embryo transfer for women with regular menstruation.

Abstract: There is no consensus regimen for the optimal endometrial preparation for cryopreservation and vitrified-thawed embryo transfer cycles. This is largely caused by the lack of sufficient investigation and analyses on the respective pregnancy and perinatal outcomes by different regimens. This study aimed to compare both pregnancy and perinatal outcomes between the modified natural and artificial cycles in vitrified-thawed day three embryo transfer for women with regular menstruation. A total of 1,482 vitrified-thawed day three embryo transfer cycles were reviewed including 427 modified natural cycles (NC), 132 ovulation induction cycles (OC), 794 artificial cycles (AC), and 129 GnRH agonist artificial cycles (GAC). The primary outcome that was evaluated was live birth rate. The NC regimen demonstrated a higher rate of ongoing pregnancy (43.8% vs. 30.2%, P = 0.002) and a lower rate of late abortion (2.8% vs. 14.0%, P = 0.003) than the GAC regimen as well as a higher implantation rate (31.9% vs. 27.1%, P = 0.008) and live birth rate (43.1% vs. 34.1%, P = 0.002) than the AC regimen. A significantly higher peak endometrial thickness before transfer was observed in patients using the NC and GAC regimens (10.0 ± 1.7, 9.9 ± 2.4) compared to the AC regimens (9.2 ± 1.5, P = 0.000). Multivariate logistic regression showed that the NC protocol was associated with a higher live birth rate. There were no significant differences in rates of pregnancy complications, neonatal mortality, birth defects, mean birth weight, and other perinatal outcomes among the regimens. Modified natural cycle endometrial preparation regimen for vitrified-thawed day three embryo transfer is associated with superior live birth pregnancy outcomes compared to artificial cycles. Future studies are warranted to investigate the underlying biologic mechanisms of these findings. Abbreviations ART: assisted reproductive technology; BMI: body mass index; FET: frozen-thawed embryo transfer; HCG: human chorionic gonadotropin; IVF: in-vitro fertilization; IVF-ET: in-vitro fertilization and embryo transfer; OHSS: ovarian hyperstimulation syndrome; RCTs: randomized controlled trials.

Guan|Yichun|Y|
Fan|Hongfang|H|
Styer|Aaron K|AK|
Xiao|Zhiying|Z|
Li|Zhen|Z|
Zhang|Jianrui|J|
Sun|Lijun|L|
Wang|Xingling|X|
Zhang|Zhan|Z|

live birth rate
Day three embryo transfer
endometrial preparation regimens
vitrification


Rat peri-implant soft tissue specifically expressed CXCL2 on titanium implant during wound healing.

Abstract: Many of genes specifically expressed in peri-implant soft tissue (PIST) selected by microarray analysis are involved in the inflammatory response. This study investigated the gene expression and localization of PIST-specific inflammatory markers in PIST during wound healing. Pure titanium implants were implanted into the rat upper mandibular socket to create PIST. Samples were harvested from PIST as an experimental group, and tooth extracted area of oral mucosa tissue (OMT) and healthy periodontal tissue (PT) as control groups. The gene expressions of four standard inflammatory markers and nine PIST-specific inflammatory markers including chemokine (C-X-C motif) ligand 2 (CXCL2) during wound healing were examined. Immunoreactions of CXCL2 and immune cells in PIST and control tissues were compared. During wound healing, gene expression of PIST-specific inflammatory markers was higher in PIST than in OMT (p < .05), but there were no significant differences in the expression of standard inflammatory markers. The molecule CXCL2 was expressed locally at the implant-connective tissue interface, and localization of immune cells closely matched the CXCL2 expression pattern. In PIST, seven of PIST-specific inflammatory markers were expressed specifically and strongly during wound healing and their expression was maintained until the end of healing. Furthermore, CXCL2 expression was due to the creation of the implant-connective tissue interface, and it established a unique defense mechanism in PIST that was not apparent in OMT or PT.

peri-implant soft tissue
CXCL2
wound healing
chemokine
dental implant


Molecular analysis of sugar transporters and glycolysis pathways in Ettlia sp. under heterotrophy using fructose and glucose.

Abstract: Fructophilic behavior in microalgae is a rare trait that could benefit biorefineries by enabling substitution of carbon source with fructose, and our previous study identified that Ettlia sp. prefers fructose relative to glucose. In this study, by analyzing the transcription levels of genes related to sugar transport and the glycolysis pathway, the fructose utilization of Ettlia sp. was investigated. In a fructose-containing medium, the expression levels of fructokinase (EttFRK3) and glucokinase (EttGCK1 and EttGCK2) genes were significantly upregulated in heterotrophic cultivation of Ettlia sp. under fructose supplementation conditions. Further, a sugar transporter (EttSTF11) was significantly upregulated by 3.2-fold in 1 day, and this increase was analogous to the specific growth rate exhibited by the species. Subsequent cultivation tests with multi-sugar sources also showed a significant upregulation of EttSTF11 relative to other treatments without fructose. A phylogenetic tree derived from the analysis of different transporters of interest identified that EttSTF11 was adjacent to reference fructose transporters with a high bootstrap value of 71. Given that the transmembrane domains of EttSTF11 were analogous to those of reference fructose transporter genes, EttSTF11 appeared to play a critical role in fructose consumption and metabolism in Ettlia sp.

sugar transporter
glycolysis pathway
Ettlia sp
fructose
glucose
RNA expression


Ocular delivery of proteins and peptides: Challenges and novel formulation approaches.

Abstract: The impact of proteins and peptides on the treatment of various conditions including ocular diseases over the past few decades has been advanced by substantial breakthroughs in structural biochemistry, genetic engineering, formulation and delivery approaches. Formulation and delivery of proteins and peptides, such as monoclonal antibodies, aptamers, recombinant proteins and peptides to ocular tissues poses significant challenges owing to their large size, poor permeation and susceptibility to degradation. A wide range of advanced drug delivery systems including polymeric controlled release systems, cell-based delivery and nanowafers are being exploited to overcome the challenges of frequent administration to ocular tissues. The next generation systems integrated with new delivery technologies are anticipated to generate improved efficacy and safety through the expansion of the therapeutic target space. This review will highlight recent advances in formulation and delivery strategies of protein and peptide based biopharmaceuticals. We will also describe the current state of proteins and peptides based ocular therapy and future therapeutic opportunities.

Mandal|Abhirup|A|
Pal|Dhananjay|D|
Agrahari|Vibhuti|V|
Trinh|Hoang My|HM|
Joseph|Mary|M|
Mitra|Ashim K|AK|

Drug delivery
Controlled release
Targeting
Biopharmaceuticals
AMD
Barriers
Biologics
Eye
Macromolecules


Exosomes from Melatonin Treated Hepatocellularcarcinoma Cells Alter the Immunosupression Status through STAT3 Pathway in Macrophages.

Abstract: Immunosuppression is a significant factor in the progression of tumor invasion and metastasis. Melatonin, a well-known hormone, has certain cytotoxic and immune regulatory effects to inhibit tumor function. Exosomes are small membrane vesicles released by many kinds of cells, which contain different macromolecules, such as mRNAs and microRNAs (miRNAs), and proteins that can mediate communications between cells. Tumor-derived exosomes may cause immunosuppression, however, it is unknown whether melatonin can attenuate an immunosuppressive status by altering the function of tumor-derived exosomes. In the present study, we evaluated the effects of hepatocellularcarcinoma-derived exosomes (Exo-con) and exosomes derived from hepatocellularcarcinoma cells treated with 0.1 mM melatonin (Exo-MT), on the expression of inflammatory factors and programmed death ligand 1(PD-L1) by co-culturing Exo-con and Exo-MT, respectively, with macrophages differentiated from THP-1 cells or RAW264.7 cells. Our in vitro results indicate that Exo-MT can downregulate the expression of PD-L1 on macrophages while Exo-con can upregulate the expression of PD-L1 through flow cytometry and immunofluorescence analysis. In addition, Exo-con upregulates the secretion of cytokines, such as IL-6, IL-10, IL-1β, and TNF-α in macrophages. Accordingly, Exo-MT could attenuate the high expression of these inflammatory cytokines. Furthermore, in vivo experiments confirmed the results found in vitro. PD-L1 expression and cytokine secretion were lower in the Exo-MT group compared with those in the Exo-con group. Working to identify a specific mechanism, our research shows that Exo-MT decreases STAT3 activation compared to the Exo-con group. In summary, we found exosomes from melatonin treated hepatocellularcarcinoma cells alters the immunosupression status through STAT3 pathway in macrophages. Our study may provide a new avenue to investigate the mechanisms of melatonin in regulating an immunosuppressive status.

Cheng|Liang|L| Liu|Jiatao|J| Liu|Qingqing|Q| Liu|Yu|Y| Fan|Lulu|L| Wang|Fang|F| Yu|Hanqing|H| Li|Yuhuan|Y| Bu|Lijia|L| Li|Xiaoqiu|X| Wei|Wei|W| Wang|Hua|H| Sun|Guoping|G|

D015972:Gene Expression Regulation, Neoplastic

exosomes
melatonin
PD-L1
cytokines
macrophages.
Hepatoma cell


l-Scoulerine attenuates behavioural changes induced by methamphetamine in zebrafish and mice.

Abstract: Methamphetamine (METH), a substance with a high potential for abuse and addiction, is a serious worldwide public health problem. METH addicts often show extreme paranoia, anxiety, and depression. Thus, there is no effective medication for the treatment of METH-induced abnormalities. In the present study, we investigated the effects of l-Scoulerine (l-SLR), a tetrahydroprotoberberine (THPBS) alkaloid, on METH-induced anxiety-like behaviour in zebrafish and METH-induced addictive behavior in mice. In the novel tank test, acute administration of METH (2 mg/L) induced a significant decrease in the number of total vertical transitions and time spent in the upper zone. Moreover, METH produced significant avoidance behaviour showing increased swimming time in the central area and high speed movement in the mirror area in the mirror stimulation test; these anxiety-like changes were attenuated by l-SLR. Chronic administration of METH (2 mg/kg) produced a steady increase in locomotor activity and conditioned place preference in mice. l-SLR (5 mg/kg) failed to reduce acute METH-induced hyperlocomotion, but attenuated chronic METH-induced behavioural sensitization and significantly blocked the expression of conditioned place preference induced by METH in mice. The present study suggests that l-SLR may be a promising agent for the treatment of addiction and anxiety induced by METH.

Mi|Guiyun|G| Gao|Yunyun|Y| Yan|Hui|H| Jin|Xiao|X| Ye|Enmao|E| Liu|Shuai|S| Gong|Zehui|Z| Yang|Hongju|H| Yang|Zheng|Z|

Methamphetamine
Zebrafish
Conditioned place preference
Sensitization


Antibiotic decision making in surgical intensive care: a qualitative analysis.

Abstract:
BACKGROUND
Antibiotic use in hospitals is high, particularly in surgical specialty and intensive care units. Antimicrobial stewardship programmes (ASPs) are increasingly intervening in antibiotic use by surgeons and intensivists. However, there is limited information on the features which characterize antibiotic decision making in the surgical intensive care unit (SICU), an area in hospital practice where critically ill surgery patients can be kept under close observation.

AIM
To explore the features which characterize antibiotic decision making in the SICU.

METHODS
A total of 160 h of ethnographic observation and 10 semi-structured interviews were conducted at two teaching hospitals in the USA. Data were analysed using thematic coding.

FINDINGS
Three key characteristics of SICU practice with regard to antibiotic use were identified: (1) physical proximity makes SICU clinicians acutely aware of changes in patient status; (2) communication of patient status relies on active involvement by SICU clinicians; (3) SICU clinicians have contested and variable autonomy over antibiotic decisions.

CONCLUSIONS
Antibiotic decision making in the SICU is a complex process involving multiple clinician teams with varying levels of physical proximity to and autonomy over patient cases. This study found that the SICU clinician team has increased physical proximity to patient cases but little autonomy over antibiotic decisions. If these characteristics are not considered, antimicrobial stewardship (AMS) interventions may have diminished success in addressing high levels of the antibiotic use in the SICU.

Rynkiewich|K|K| Schwartz|D|D| Won|S|S| Stoner|B|B|

D000900:Anti-Bacterial Agents
D000073602:Antimicrobial Stewardship
D001291:Attitude of Health Personnel
D003422:Critical Care
D003657:Decision Making
D006784:Hospitals, Teaching
D006801:Humans
D007407:Interviews as Topic
D015146:Midwestern United States
D010820:Physicians
D017009:Professional Autonomy
D036301:Qualitative Research

Antibiotic decision making
Antimicrobial stewardship
SICU
Clinician autonomy


Phytochemical and pharmacological investigation of Spiraea chamaedryfolia: a contribution to the chemotaxonomy of Spiraea genus.

Abstract:
OBJECTIVE
Diterpene alkaloids are secondary plant metabolites and chemotaxonomical markers with a strong biological activity. These compounds are characteristic for the Ranunculaceae family, while their occurrence in other taxa is rare. Several species of the Spiraea genus (Rosaceae) are examples of this rarity. Screening Spiraea species for alkaloid content is a chemotaxonomical approach to clarify the classification and phylogeny of the genus. Novel pharmacological findings make further investigations of Spiraea diterpene alkaloids promising.

RESULTS
Seven Spiraea species were screened for diterpene alkaloids. Phytochemical and pharmacological investigations were performed on Spiraea chamaedryfolia, the species found to contain diterpene alkaloids. Its alkaloid-rich fractions were found to exert a remarkable xanthine-oxidase inhibitory activity and a moderate antibacterial activity. The alkaloid distribution within the root was clarified by microscopic techniques.

D052978:Disk Diffusion Antimicrobial Tests

Spiraea Chemotaxonomy Alkaloids Xanthine-oxidase Antibacterial Phytochemistry


Mass Spectrometry Imaging with Isomeric Resolution Enabled by Ozone-Induced Dissociation.

Abstract: Mass spectrometry imaging (MSI) enables the spatial distributions of molecules possessing different mass-to-charge ratios to be mapped within complex environments revealing regional changes at the molecular level. Even at high mass resolving power, however, these images often reflect the summed distribution of multiple isomeric molecules, each potentially possessing a unique distribution coinciding with distinct biological function(s) and metabolic origin. Herein, this chemical ambiguity is addressed through an innovative combination of ozone-induced dissociation reactions with MSI, enabling the differential imaging of isomeric lipid molecules directly from biological tissues. For the first time, we demonstrate both double bond- and sn-positional isomeric lipids exhibit distinct spatial locations within tissue. This MSI approach enables researchers to unravel local lipid molecular complexity based on both exact elemental composition and isomeric structure directly from tissues.

D021241:Spectrometry, Mass, Electrospray Ionization

mass spectrometry imaging
biochemistry
brain
isomers
phospholipids


Progressive, Long-Term Hearing Loss in Congenital CMV Disease After Ganciclovir Therapy.

Abstract:
BACKGROUND
Long-term hearing outcomes among children with symptomatic congenital cytomegalovirus (CMV) disease who received 6-week ganciclovir therapy early in life are unknown.

METHODS
Longitudinal study of 76 children with symptomatic congenital CMV disease, born 1983-2005, who were categorized into three groups: group A treated with ganciclovir; group B untreated who had microcephaly, chorioretinitis, or sensorineural hearing loss (SNHL; ≥25 dB) diagnosed in the first month of life (congenital); and group C untreated who did not meet criteria for group B.

RESULTS
Patients in groups A (n = 17), B (n = 27), and C (n = 32) were followed to median age of 13, 11, and 13 years, respectively. In group A, patients received ganciclovir for median of 40 (range, 11-63) days; 7 (41%) had grade 3 or 4 neutropenia. Congenital SNHL was diagnosed in 11 (65%) patients in group A, 15 (56%) in group B, and none in group C. Early-onset SNHL was diagnosed between ages ≥1-12 months in an additional 4 (24%), 6 (22%), and 8 (25%) patients in groups A, B, and C, respectively. By the end of follow-up, 12 (71%), 16 (59%), and 7 (22%) of patients in groups A, B, and C, respectively, had severe (>70 dB) SNHL in the better-hearing ear.

CONCLUSIONS
In this study, most patients with symptomatic congenital CMV disease and congenital or early-onset SNHL eventually developed hearing loss severe enough to have been potential candidates for cochlear implantation, with or without 6-week ganciclovir therapy. Understanding long-term hearing outcomes of patients treated with 6-month oral valganciclovir (current standard of care) is needed.

Lanzieri|Tatiana M|TM|
Caviness|Alison Chantal|AC|
Blum|Peggy|P|
Demmler-Harrison|Gail|G|
|||

ganciclovir
congenital cytomegalovirus
sensorineural hearing loss


Electrochemical immunoassay for the detection of IgM antibodies using polydopamine particles loaded with PbS quantum dots as labels.

Abstract: Here, we report for the first time, an electrochemical immunoassay to detect IgM antibodies using lead sulfide quantum dots (PbS QDs) as electrochemical labels. In this sense, dendritic-like polydopamine particles loaded with PbS QDs were synthesized by the self-polymerization of dopamine in basic media in the presence of QDs (PbS@PDA) and further tagged with anti-IgM antibodies, dengue specific antigens, and streptavidin moieties. The analytical features of the sandwich immunoassay on ELISA microplate were carried out with the PbS@PDA-labeled anti-IgM as secondary antibody. The system was interrogated by acid dissolution of PbS@PDA, followed by differential pulse anodic stripping voltammetry in the presence of Bi(III) ions using carbon screen-printed electrodes. The results indicate that the voltammetric current increased with the increasing of the concentration of target IgM within a range of 0-0.5 mg mL-1. The limit of detection of this electrochemical immunoassay was evaluated to 130 ng. The measures of satisfactory recoveries from 88.5% to 114% of spiked samples indicate that such a method has good specificity and is applicable to the quantification of IgM antibodies in complex biological samples. No significant differences at the 0.05 significance level were encountered in the analysis of IgM samples between the electrochemical immunoassay and a Bradford assay.

Ortega|Greter A|GA|
Zuaznabar-Gardona|Julio C|JC|
Reguera|Edilso|E|

IgM
Polydopamine
Quantum dots
Stripping voltammetry


Interactions between poly-(phthalazinone ether sulfone ketone) (PPESK) and TNT or TATB in polymer bonded explosives: a molecular dynamic simulation study.

Abstract: The glass transition temperature (T g) and density of poly-(phthalazinone ether sulfone ketone) (PPESK A) were estimated by molecular dynamic (MD) simulation. A novel poly-(phthalazinone ether sulfone ketone) (PPESK B) was constructed by introducing nitrol and amini energetic groups into PPESK A, and T g and density were also simulated for PPESK B. The estimated T g values of PPESK A were very close to experimental results, while for PPESK B three estimated values differed by < 5 K. The interactions between explosives and polymer binders of polymer bonded explosives (PBXs) were simulated by MD. Comparison of the cohesive energy densities (CED) and solubility parameter (δ) values of PBXs, polymer binders, and mono-explosives indicate that, upon introducing polymer binders, the CED and δ values of PBXs decreased compared with those of corresponding mono-explosives. The binding energies (E bind) imply that 2,4,6-trinitrotoluene-based PBXs are more stable than 1,3,5-triamino-2,4,6-trinitrobenzene (TATB)-based PBXs. The mechanical properties, Young's modulus E, shear modulus G, bulk modulus K, Poisson's ratio γ and Cauchy pressure (C 12 -C 44) of the PBXs were assessed. The rigidity of the PBXs was found to be lower than that of mono-explosives. All K/G values were positive, indicating that PBXs are flexible. Based on these mechanical properties results, PBXs using PPESK B as a binder are superior to those using PPESK A as a binder. Due to the low C 12 -C 44 values of the PBXs, the ductility of the materials of the fracture surface is poorer, especially for TATB-based PBXs.

Poly-(phthalazinone ether sulfone ketone) (PPESK)


Defect-Induced Tunable Permittivity of Epsilon-Near-Zero in Indium Tin Oxide Thin Films.

Abstract: Defect-induced tunable permittivity of Epsilon-Near-Zero (ENZ) in indium tin oxide (ITO) thin films via annealing at different temperatures with mixed gases (98% Ar, 2% O₂) was reported. Red-shift of λENZ (Epsilon-Near-Zero wavelength) from 1422 nm to 1995 nm in wavelength was observed. The modulation of permittivity is dominated by the transformation of plasma oscillation frequency and carrier concentration depending on Drude model, which was produced by the formation of structural defects and the reduction of oxygen vacancy defects during annealing. The evolution of defects can be inferred by means of X-ray diffraction (XRD), atomic force microscopy (AFM), and Raman spectroscopy. The optical bandgaps (Eg) were investigated to explain the existence of defect states. And the formation of structure defects and the electric field enhancement were further verified by finite-difference time domain (FDTD) simulation.

Lian|Jiqing|J|0000-0002-8595-7914 Zhang|Dawei|D| Hong|Ruijin|R| Qiu|Peizhen|P| Lv|Taiguo|T| Zhang|Daohua|D|

Epsilon-Near-Zero
defect
ITO thin films
optical modulation


Simultaneous bilateral total knee arthroplasty in severe hemophilia: a retrospective cost-effectiveness analysis.

Abstract:
INTRODUCTION
Simultaneous bilateral total knee arthroplasty (TKA) is proposed in the general population as an alternative to staged bilateral TKA and has the advantage of reducing costs with equivalent complication rates. The aim of this study was to evaluate the cost-effectiveness of this alternative in a population of patients with severe hemophilia.

HYPOTHESIS
Simultaneous bilateral TKA is less expensive than staged bilateral TKA.

MATERIALS AND METHODS
We performed a retrospective case control study in patients with severe hemophilia A to compare the direct costs of coagulation factors, the length of hospital stay and sick leave as well as the clinical outcome (KKS) of simultaneous bilateral TKA (group 1; G1: 5 patients) and staged bilateral TKA (group 2; G2: 12 patients).

RESULTS
The mean cost of coagulation factors was 65,880 € in G1 and 139,000 € in G2 (P<0.001). The length of the hospital stay (24 days vs 44 cumulative days, respectively) and sick leave (105 days vs 183 cumulative days, respectively) was significantly reduced in G1. There was no significant difference in clinical outcome at the final follow-up. One patient in G2 had a late knee infection.

DISCUSSION
Simultaneous bilateral TKA in severe hemophilia is associated with lower costs than staged bilateral TKA with equivalent clinical results.

LEVEL OF EVIDENCE
Level 3, case control study.

D000328:Adult
D019645:Arthroplasty, Replacement, Knee
D003362:Cost-Benefit Analysis
D005260:Female
D006467:Hemophilia A
D006801:Humans
D007902:Length of Stay
D008297:Male
D008875:Middle Aged
D020370:Osteoarthritis, Knee
D012189:Retrospective Studies
D055815:Young Adult

Hemophilia A
Bilateral knee replacement
Cost-benefit analysis
Simultaneous total knee arthroplasty


Analysis of the mitigation strategies for COVID-19: From mathematical modelling perspective.

Abstract: In this article, a mathematical model for the transmission of COVID-19 disease is formulated and analysed. It is shown that the model exhibits a backward bifurcation at   when recovered individuals do not develop a permanent immunity for the disease. In the absence of reinfection, it is proved that the model is without backward bifurcation and the disease free equilibrium is globally asymptotically stable for   . By using available data, the model is validated and parameter values are estimated. The sensitivity of the value of  to changes in any of the parameter values involved in its formula is analysed. Moreover, various mitigation strategies are investigated using the proposed model and it is observed that the asymptomatic infectious group of individuals may play the major role in the re-emergence of the disease in the future. Therefore, it is recommended that in the absence of vaccination, countries need to develop capacities to detect and isolate at least 30% of the asymptomatic infectious group of individuals while treating in isolation at least 50% of symptomatic patients to control the disease.

Kassa|Semu M|SM|
Njagarah|John B H|JBH|
Terefe|Yibeltal A|YA|

Mitigation strategy
COVID-19
Backward bifurcation
Disease threshold
Epidemiological model
Self-protection
Sensitivity analysis


Differing Contributions of Classical Risk Factors to Type 2 Diabetes in Multi-Ethnic Malaysian Populations.

Abstract: The prevalence of type 2 diabetes is escalating rapidly in Asian countries, with the rapid increase likely attributable to a combination of genetic and lifestyle factors. Recent research suggests that common genetic risk variants contribute minimally to the rapidly rising prevalence. Rather, recent changes in dietary patterns and physical activity may be more important. This nested case-control study assessed the association and predictive utility of type 2 diabetes lifestyle risk factors in participants from Malaysia, an understudied Asian population with comparatively high disease prevalence. The study sample comprised 4077 participants from The Malaysian Cohort project and included sub-samples from the three major ancestral groups: Malay (n = 1323), Chinese (n = 1344) and Indian (n = 1410). Association of lifestyle factors with type 2 diabetes was assessed within and across ancestral groups using logistic regression. Predictive utility was quantified and compared between groups using the Area Under the Receiver-Operating Characteristic Curve (AUC). In predictive models including age, gender, waist-to-hip ratio, physical activity, location, family history of diabetes and average sleep duration, the AUC ranged from 0.76 to 0.85 across groups and was significantly higher in Chinese than Malays or Indians, likely reflecting anthropometric differences. This study suggests that obesity, advancing age, a family history of diabetes and living in a rural area are important drivers of the escalating prevalence of type 2 diabetes in Malaysia.

risk factor
type 2 diabetes
genetic
Malaysia
Asian populations
rural


Trace derivatives of kynurenine potently activate the aryl hydrocarbon receptor (AHR).

Abstract: Cellular metabolites act as important signaling cues, but are subject to complex unknown chemistry. Kynurenine is a tryptophan metabolite that plays a crucial role in cancer and the immune system. Despite its atypical, non-ligand-like, highly polar structure, kynurenine activates the aryl hydrocarbon receptor (AHR), a PER, ARNT, SIM (PAS) family transcription factor that responds to diverse environmental and cellular ligands. The activity of kynurenine is increased 100-1000-fold by incubation or long-term storage and relies on the hydrophobic ligand-binding pocket of AHR, with identical structural signatures for AHR induction before and after activation. We purified trace-active derivatives of kynurenine and identified two novel, closely related condensation products, named trace-extended aromatic condensation products (TEACOPs), which are active at low picomolar levels. The synthesized compound for one of the predicted structures matched the purified compound in both chemical structure and AHR pharmacology. Our study provides evidence that kynurenine acts as an AHR pro-ligand, which requires novel chemical conversions to act as a receptor agonist.

Seok|Seung-Hyeon|SH|
Ma|Zhi-Xiong|ZX|
Feltenberger|John B|JB|
Chen|Hongbo|H|
Chen|Hui|H|
Scarlett|Cameron|C|
Lin|Ziqing|Z|
Satyshur|Kenneth A|KA|
Cortopassi|Marissa|M|
Jefcoate|Colin R|CR|
Ge|Ying|Y|
Tang|Weiping|W|
Bradfield|Christopher A|CA|
Xing|Yongna|Y|

kynurenine
pro-ligand
Ah receptor
aryl hydrocarbon receptor (AhR) (AHR)
chemical biology
dioxin
ligand-binding protein
structural determinants
structure-function


Palliative Care Interventions for Patients with Heart Failure: A Systematic Review and Meta-Analysis.

Abstract:
OBJECTIVE
To systematically characterize interventions and effectiveness of palliative care for advanced heart failure (HF) patients.

BACKGROUND
Patients with advanced heart failure experience a high burden of distressing symptoms and diminished quality of life. Palliative care expertise with symptom management and healthcare decision-making benefits HF patients.

METHODS
A systematic PubMed search was conducted from inception to June 2016 for studies of palliative care interventions for HF patients. Studies of humans with a HF diagnosis who underwent a palliative care intervention were included. Data were extracted on study design, participant characteristics, intervention components, and in three groups of outcomes: patient-centered outcomes, quality-of-death outcomes, and resource utilization. Study characteristics were examined to determine if meta-analysis was possible.

RESULTS
The fifteen identified studies varied in design (prospective, n = 10; retrospective, n = 5). Studies enrolled older patients, but greater variability was found for race, sex, and marital status. A majority of studies measuring patient-centered outcomes demonstrated improvements including quality of life and satisfaction. Quality-of-death outcomes were mixed with a majority of studies reporting clarification of care preferences, but less improvement in death at home and hospice enrollment. A meta-analysis in three studies found that home-based palliative care consults in HF patients lower the risk of rehospitalization by 42% (RR = 0.58; 95% Confidence Interval 0.44, 0.77).

DISCUSSION
Available evidence suggests that home and team-based palliative interventions for HF patients improve patient-centered outcomes, documentation of preferences, and utilization. Increased high quality studies will aid the determination of the most effective palliative care approaches for the HF population.

Diop|Michelle S|MS|
Rudolph|James L|JL|
Zimmerman|Kristin M|KM|
Richter|Mary A|MA|
Skarf|L Michal|LM|

palliative care
heart failure
symptoms
quality of life
utilization
cultural care