Dipeptidyl peptidase-4 levels are increased and partially related to body fat distribution in patients with familial partial lipodystrophy type 2.

Abstract:
BACKGROUND
Dipeptidyl peptidase-4 (DDP4) is an enzyme responsible for glucagon-like peptide-1 inactivation and plays an important role in glucose metabolism.

OBJECTIVE
The aim of this study was to evaluate DPP4 levels in patients with familial partial lipodystrophy type 2 (FPLD2) and correlate it with body fat distribution.

METHODS
Fourteen patients with FPLD2 were selected to participate in this study and matched to a healthy control group (n = 8). All participants had anthropometrical data registered. Body adiposity index (BAI) was used to evaluate fat distribution in this population. Body fat content and distribution were analyzed by dual X-ray absorptiometry (DXA). Biochemical exams, including DPP4 levels, were performed in all individuals.

RESULTS
Despite the same body mass index, lipodystrophic patients had a significant lower hip (median 92.0 vs 94.5; p = 0.028), HDL cholesterol (42.6 ± 10.4 vs 66.1 ± 16.0; p < 0.01) and BAI (24.1 ± 2.8 vs 29.0 ± 3.7; p = 0.02), suggesting that BAI was able to catch differences in fat distribution between groups. On the other hand, patients with FPLD2 presented significant higher levels of insulin (median 11.2 vs 5.3; p = 0.015), triglycerides (184.9 ± 75.4 vs 89.1 ± 51.0; p < 0.01) and DPP4 (4.89 ± 0.92 vs 3.93 ± 1.08; p = 0.04). A trend toward an inverse statistical significance was observed between DPP4 levels and BAI (r = -0.38; p = 0.072). In the lipodistrophic group, a significant correlation was found between DPP4 levels and percentage of total body fat (r = 0.86; p = 0.0025) and android fat (r = 0.78; p = 0.014).

CONCLUSIONS
Patients with FPLD2 exhibit an increase in DDP4 levels in comparison to a healthy control group. The increase in the levels of this enzyme does not seem to be related to the diagnosis of diabetes and might be associated with an increase in central fat (estimated using BAI and measured using DXA). These results might be used to reinforce the concept that DDP4 is an adipokine related to central fat distribution.

Valerio|Cynthia Melissa|CM|
de Almeida|Juliana Severo|JS|
Moreira|Rodrigo Oliveira|RO|
Aguiar|Luiza Barreto S|LBS|
Siciliano|Priscila O|PO|
Carvalho|Denise P|DP|
Godoy-Matos|Amelio F|AF|

Dipeptidyl peptidase-4
Lipodystrophy
Adipokines


Plumbagin and Its Role in Chronic Diseases.

Abstract: Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a plant-derived naphthoquinones obtained mainly from three families, including Plumbaginaceae, Droseraceae, and Ebenaceae. Plumbagin has exhibited its potential therapeutic benefits on numerous chronic diseases, i.e., breast cancer, non-small cell lung cancer, melanoma, ovarian, squamous cell carcinomas, pancreatic cancer, and prostate cancer. In addition, its anti-inflammatory and antimicrobial activities as well as control of diabetes and cardiovascular diseases have been reported. Thus, plumbagin is a promising agent for development as a new drug for the treatment or control of chronic diseases. Studies on controlled drug release or drug delivery systems have been involved for improvement of its therapeutic efficacy as well as for the reduction of its toxicity. However, most of the recent research information is from in vitro and in vivo studies. Further clinical studies are therefore required for its developments and applications as a novel drug used to treat chronic diseases.

Plumbagin
Chronic diseases
Antimicrobial
Cardiovascular
Toxicity
Anti-inflammation
Anticancer
Antidiabetic


Impact of living alone on the care and outcomes of patients with ST-elevation myocardial infarction.

Abstract:
BACKGROUND
This study aimed to investigate the association between living alone at home and the care and outcomes of patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (pPCI).

METHODS
In total, 557 patients with STEMI underwent pPCI between January 2008 and September 2017. Among them, we included 208 patients who were transferred directly by emergency medical services from their home to the hospital.

RESULTS
Patients were classified into two groups, namely living alone (n = 45) and living with others (n = 163). There were no significant differences in age, sex, and cardiovascular risk factors between the two groups. The onset-to-door (OTD) and onset-to-balloon times were significantly shorter in patients living with others than in those living alone (106.4 vs. 190.8 min, p < 0.01 and 152.3 vs. 236.9 min; p < 0.01, respectively). The left ventricular ejection fraction after pPCI was significantly lower in patients living alone than in those living with others (48.7 % vs. 54.9 %, p < 0.01). Multivariate logistic regression analysis indicated that living alone and the incidence of congestive heart failure were independent predictors of a longer OTD time.

CONCLUSIONS
Patients living alone were less likely to arrive early at the hospital than those living with others. A greater understanding of the inter-relationships among living alone, access to acute cardiac care, and outcomes is essential.

Ohama|Ayumi|A| Mizuguchi|Yukio|Y| Hashimoto|Sho|S| Yamada|Takeshi|T| Taniguchi|Norimasa|N| Nakajima|Shunsuke|S| Hata|Tetsuya|T| Takahashi|Akihiko|A|

D000072657:ST Elevation Myocardial Infarction

Primary percutaneous coronary intervention


Chemotaxis signaling systems in model beneficial plant-bacteria associations.

Abstract: Beneficial plant-microbe associations play critical roles in plant health. Bacterial chemotaxis provides a competitive advantage to motile flagellated bacteria in colonization of plant root surfaces, which is a prerequisite for the establishment of beneficial associations. Chemotaxis signaling enables motile soil bacteria to sense and respond to gradients of chemical compounds released by plant roots. This process allows bacteria to actively swim towards plant roots and is thus critical for competitive root surface colonization. The complete genome sequences of several plant-associated bacterial species indicate the presence of multiple chemotaxis systems and a large number of chemoreceptors. Further, most soil bacteria are motile and capable of chemotaxis, and chemotaxis-encoding genes are enriched in the bacteria found in the rhizosphere compared to the bulk soil. This review compares the architecture and diversity of chemotaxis signaling systems in model beneficial plant-associated bacteria and discusses their relevance to the rhizosphere lifestyle. While it is unclear how controlling chemotaxis via multiple parallel chemotaxis systems provides a competitive advantage to certain bacterial species, the presence of a larger number of chemoreceptors is likely to contribute to the ability of motile bacteria to survive in the soil and to compete for root surface colonization.

Scharf|Birgit E|BE|
Hynes|Michael F|MF|
Alexandre|Gladys M|GM|

D015964:Gene Expression Regulation, Bacterial

Motility
Rhizosphere
Flagella
Nitrogen fixation
Signal transduction
Symbiosis


Developments in purification methods for obtaining and evaluation of collagen derived endogenous angioinhibitors.

Abstract: Collagen constitutes one of the vital components of the basement membrane scaffolds. Non-collagenous domains (NC1) derived from collagens exhibit potent anti-angiogenic properties, thus attaining significance in regulation of angiogenesis promoted diseases. Individual NC1 domains essential for anti-angiogenic evaluations are generally obtained through purification of individual non-collagenous domains, which have undergone steady developments for enhancing the yields, purpose of biological evaluations and solubility based on the nature of different NC1 domains. This review focuses on the method developments in obtaining biologically active NC1 domains and for specific evaluations in different scenarios.

Gunda|Venugopal|V|
Verma|Raj K|RK|
Pawar|Smita C|SC|
Sudhakar|Yakkanti A|YA|

D020533:Angiogenesis Inhibitors
D001485:Basement Membrane
D024141:Collagen Type IV
D005109:Extracellular Matrix
D005786:Gene Expression Regulation
D006801:Humans
D017434:Protein Structure, Tertiary

Non-collagenous domains (NC1)
Anti-angiogenesis
Different expression systems
Different purification methods
Extra cellular matrix (ECM)
Type IV collagen


Oligosaccharide biotechnology: an approach of prebiotic revolution on the industry.

Abstract: Oligosaccharides are polymers with two to ten monosaccharide residues which have sweetener functions and sensory characteristics, in addition to exerting physiological effects on human health. The ones called nondigestible exhibit a prebiotic behavior being fermented by colonic microflora or stimulating the growth of beneficial bacteria, playing roles in the immune system, protecting against cancer, and preventing cardiovascular and metabolic issues. The global prebiotics market is expected to grow around 12.7% in the next 8 years, so manufacturers are developing new alternatives to obtain sustainable and efficient processes for application on a large scale. Most studied examples of biotechnological processes involve the development of new strategies for fructooligosaccharide, galactooligosaccharide, xylooligosaccharide, and mannanooligosaccharide synthesis. Among these, the use of whole cells in fermentation, synthesis of microbial enzymes (β-fructofuranosidases, β-galactosidases, xylanases, and β-mannanases), and enzymatic process development (permeabilization, immobilization, gene expression) can be highlighted, especially if the production costs are reduced by the use of agro-industrial residues or by-products such as molasses, milk whey, cotton stalks, corncobs, wheat straw, poplar wood, sugarcane bagasse, and copra meal. This review comprises recent studies to demonstrate the potential for biotechnological production of oligosaccharides, and also aspects that need more investigation for future applications in a large scale.

Mano|Mario Cezar Rodrigues|MCR|
Neri-Numa|Iramaia Angélica|IA|
da Silva|Juliana Bueno|JB|
Paulino|Bruno Nicolau|BN|
Pessoa|Marina Gabriel|MG|
Pastore|Gláucia Maria|GM|

Oligosaccharides Biotechnology Prebiotics Enzyme By-products


New Measurement for Correlation of Co-evolution Relationship of Subsequences in Protein.

Abstract: Many computational tools have been developed to measure the protein residues co-evolution. Most of them only focus on co-evolution for pairwise residues in a protein sequence. However, number of residues participate in co-evolution might be multiple. And some co-evolved residues are clustered in several distinct regions in primary structure. Therefore, the co-evolution among the adjacent residues and the correlation between the distinct regions offer insights into function and evolution of the protein and residues. Subsequence is used to represent the adjacent multiple residues in one distinct region. In the paper, co-evolution relationship in each subsequence is represented by mutual information matrix (MIM). Then, Pearson's correlation coefficient: R value is developed to measure the similarity correlation of two MIMs. MSAs from Catalytic Data Base (Catalytic Site Atlas, CSA) are used for testing. R value characterizes a specific class of residues. In contrast to individual pairwise co-evolved residues, adjacent residues without high individual MI values are found since the co-evolved relationship among them is similar to that among another set of adjacent residues. These subsequences possess some flexibility in the composition of side chains, such as the catalyzed environment.

Gao|Hongyun|H| Yu|Xiaoqing|X| Dou|Yongchao|Y| Wang|Jun|J|

D000595:Amino Acid Sequence
D019295:Computational Biology
D019143:Evolution, Molecular
D011487:Protein Conformation
D011506:Proteins

Correlation
Subsequence
Adjacent
Mutual information
Pearson’s correlation coefficient


Plasmonic laser treatment for Morpholino oligomer delivery in antisense applications.

Abstract: Several cell transfection techniques have been developed in the last decades for specific applications and for various types of molecules. In this context, laser based approaches are of great interest due to their minimal invasiveness and spatial selectivity. In particular, laser induced plasmon based delivery of exogenous molecules into cells can have great impact on future applications. This approach allows high-throughput laser transfection by excitation of plasmon resonances at gold nanoparticles non-specifically attached to the cell membrane. In this study, we demonstrate specific gene-knockdown by transfection of Morpholino oligos using this technique with optimized particle size. Furthermore, we evaluated the cytotoxicity of plasmonic laser treatment by various assays, including LDH activity and ROS formation. In summary, this study gives important insights into this new approach and clearly demonstrates its relevance for possible biological applications.

Kalies|Stefan|S|
Heinemann|Dag|D|
Schomaker|Markus|M|
Murua Escobar|Hugo|H|
Heisterkamp|Alexander|A|
Ripken|Tammo|T|
Meyer|Heiko|H|

D000818:Animals
D015153:Blotting, Western
D045744:Cell Line, Tumor
D002462:Cell Membrane
D002470:Cell Survival
D003911:Dextrans
D004285:Dogs
D005110:Extracellular Space
D055785:Gene Knockdown Techniques
D017612:Gold Compounds
D049452:Green Fluorescent Proteins
D006861:Hydrogen Peroxide
D007770:L-Lactate Dehydrogenase
D007834:Lasers
D053768:Metal Nanoparticles
D060172:Morpholinos
D010316:Particle Size
D017382:Reactive Oxygen Species
D014162:Transfection

plasmon
Morpholino
laser transfection
gold nanoparticle
knockdown


Alcohol's Role in Social Reactions to Sexual Assault Disclosures: A Qualitative Study of Informal Support Dyads.

Abstract: Studies of informal support dyads are lacking to understand the disclosure of sexual assaults and social reactions informal supporters make to survivors. This study of 19 informal support dyads using interview data examined how three relationship types-significant others (i.e., romantic partners), family, and friends-differ in social reactions to sexual assaults in the context of drinking or alcohol problems. It was expected that alcohol's role in responses to such disclosures would differ depending on relationship type as well as role alcohol played in the assault and/or in the survivor's life or those in her social network, including the perpetrator. Results show that alcohol has mixed effects and that alcohol-related assaults as well as contexts where survivors, perpetrators, and/or their support networks have alcohol problems need further study to understand how such disclosures and social reactions occur and the impact they have on survivors, their relationships, and recovery.

Ullman|Sarah E|SE|
Lorenz|Katherine|K|
Kirkner|Anne|A|

alcohol
social reactions
sexual assault
qualitative
dyad


A novel dynamic robotic moving phantom system for patient-specific quality assurance in real-time tumor-tracking radiotherapy.

Abstract: In this study, we assess a developed novel dynamic moving phantom system that can reproduce patient three-dimensional (3D) tumor motion and patient anatomy, and perform patient-specific quality assurance (QA) of respiratory-gated radiotherapy using SyncTraX. Three patients with lung cancer were enrolled in a study. 3D printing technology was adopted to obtain individualized lung phantoms using CT images. A water-equivalent phantom (WEP) with the 3D-printed plate lung phantom was set at the tip of the robotic arm. The log file that recorded the 3D positions of the lung tumor was used as the input to the dynamic robotic moving phantom. The WEP was driven to track 3D respiratory motion. Respiratory-gated radiotherapy was performed for driving the WEP. The tracking accuracy was calculated as the differences between the actual and measured positions. For the absolute dose and dose distribution, the differences between the planned and measured doses were calculated. The differences between the planned and measured absolute doses were <1.0% at the isocenter and <4.0% for the lung region. The gamma pass ratios of γ3 mm/3% and γ2 mm/2% under the conditions of gating and no-gating were 99.9 ± 0.1% and 90.1 ± 8.5%, and 97.5 ± 0.9% and 68.6 ± 17.8%, respectively, for all the patients. Furthermore, for all the patients, the mean ± SD of the root mean square values of the positional error were 0.11 ± 0.04 mm, 0.33 ± 0.04 mm, and 0.20 ± 0.04 mm in the LR, AP, and SI directions, respectively. Finally, we showed that patient-specific QA of respiratory-gated radiotherapy using SyncTraX can be performed under realistic conditions using the moving phantom.

Shiinoki|Takehiro|T| Fujii|Fumitake|F| Fujimoto|Koya|K| Yuasa|Yuki|Y| Sera|Tatsuhiro|T|

quality assurance
real-time tumor-tracking radiotherapy
3D printing technology
dynamic robotic phantom


The tipping point: Value differences and parallel dorsal-ventral frontal circuits gating human approach-avoidance behavior.

Abstract: Excessive avoidance and diminished approach behavior are both prominent features of anxiety, trauma and stress related disorders. Despite this, little is known about the neuronal mechanisms supporting gating of human approach-avoidance behavior. Here, we used functional magnetic resonance imaging (fMRI) to track dorsal anterior cingulate and medial prefrontal (dACC/dmPFC) activation along an approach-avoidance continuum to assess sensitivity to competing appetitive and aversive contingencies and correspondence with behavior change. Behavioral and fMRI experiments were conducted using a novel approach-avoidance task where a monetary reward appeared in the presence of a conditioned stimulus (CS), or threat, that signaled increasing probability of unconditioned stimulus (US) delivery. Approach produced the reward or probabilistic US, while avoidance prevented US delivery, and across trials, reward remained fixed while the CS threat level varied unpredictably. Increasing the CS threat level (i.e., US probability) produced the desired approach-avoidance transition and inverted U-shaped changes in decision times, electrodermal activity and activation in pregenual ACC, dACC/dmPFC, striatum, anterior insula and inferior frontal regions. Conversely, U-shaped changes in activation were observed in dorsolateral and ventromedial prefrontal cortex and bimodal changes in the orbitofrontal and ventral hippocampus. These new results show parallel dorsal-ventral frontal circuits support gating of human approach-avoidance behavior where dACC/dmPFC signals inversely correlate with value differences between approach and avoidance contingencies while ventral frontal signals correlate with the value of predictable outcomes. Our findings provide an important bridge between basic research on brain mechanisms of value-guided decision-making and value-focused clinical theories of anxiety and related interventions.

Schlund|Michael W|MW|
Brewer|Adam T|AT|
Magee|Sandy K|SK|
Richman|David M|DM|
Solomon|Scott|S|
Ludlum|MaDonna|M|
Dymond|Simon|S|

Anxiety
Anterior cingulate
Threat
Approach–avoidance
Conflict
Decision making


A flexible data-driven comorbidity feature extraction framework.

Abstract: Disease and symptom diagnostic codes are a valuable resource for classifying and predicting patient outcomes. In this paper, we propose a novel methodology for utilizing disease diagnostic information in a predictive machine learning framework. Our methodology relies on a novel, clustering-based feature extraction framework using disease diagnostic information. To reduce the data dimensionality, we identify disease clusters using co-occurrence statistics. We optimize the number of generated clusters in the training set and then utilize these clusters as features to predict patient severity of condition and patient readmission risk. We build our clustering and feature extraction algorithm using the 2012 National Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP) which contains 7 million hospital discharge records and ICD-9-CM codes. The proposed framework is tested on Ronald Reagan UCLA Medical Center Electronic Health Records (EHR) from 3041 Congestive Heart Failure (CHF) patients and the UCI 130-US diabetes dataset that includes admissions from 69,980 diabetic patients. We compare our cluster-based feature set with the commonly used comorbidity frameworks including Charlson's index, Elixhauser's comorbidities and their variations. The proposed approach was shown to have significant gains between 10.7-22.1% in predictive accuracy for CHF severity of condition prediction and 4.65-5.75% in diabetes readmission prediction.

Sideris|Costas|C| Pourhomayoun|Mohammad|M| Kalantarian|Haik|H| Sarrafzadeh|Majid|M|

Comorbidity
Prediction
Clustering
Knowledge discovery


Attitudes of pregnant women and healthcare professionals to labour induction and obtaining consent for labour induction.

Abstract: Induction of labour is experienced by up to one third of women and can be a negative experience, in relation to both the decision about whether to have an induction of labour (IoL) and the experience of the process of IoL. This paper reviews the limited evidence of women's views on and experiences of: information provision; shared decision-making; preferences for method and location of IoL; indications for IoL; pain management; and effective communication and support. Healthcare professionals' views are reviewed, but are underrepresented, and further research is needed to understand experiences of gaining consent for IoL. Systematic review evidence is drawn on where possible, but reviews often found small numbers of papers for inclusion, and provide insights rather than conclusive evidence. Future research would benefit from using validated measures to assess the experience of IoL.

Shared decision-making
Cervical ripening
Healthcare experience
Labour-induced
Maternal health services
Satisfaction


Understanding memory B cell selection.

Abstract: The mammalian adaptive immune system has evolved over millions of years to become an incredibly effective defense against foreign antigens. The adaptive immune system's humoral response creates plasma B cells and memory B cells, each with their own immunological objectives. The affinity maturation process is widely viewed as a heuristic to solve the global optimization problem of finding B cells with high affinity to the antigen. However, memory B cells appear to be purposely selected earlier in the affinity maturation process and have lower affinity. We propose that this memory B cell selection process may be an approximate solution to two optimization problems: optimizing for affinity to similar antigens in the future despite mutations or other minor differences, and optimizing to warm start the generation of plasma B cells in the future. We use simulations to provide evidence for our hypotheses, taking into account data showing that certain B cell mutations are more likely than others. Our findings are consistent with memory B cells having high-affinity to mutated antigens, but do not provide strong evidence that memory B cells will be more useful than selected naive B cells for seeding the secondary germinal centers.

Lindsly|Stephen|S| Gupta|Maya|M| Stansbury|Cooper|C| Rajapakse|Indika|I|

Memory B cell
Plasma B cell
Warm start
Germinal center
Adversarial mutation


Pectin methylesterase31 positively regulates salt stress tolerance in Arabidopsis.

Abstract: The alteration of cell wall component and structure is an important adaption to saline environment. Pectins, a major cell wall component, are often present in a highly methylesterified form. The level of methyl esterification determined by pectin methylesterases (PMEs) influences many important wall properties that are believed to relate to the adaption to saline stress. However, little is known about the function of PMEs in response to salt stress. Here, we established a link between pectin methylesterase31 (PME31) and salt stress tolerance. Salt stress significantly increases PME31 expression. PME31 is located in the plasma membrane and the expression level of PME31 was high in dry seeds. Knock-down mutants in PME31 conferred hypersensitive phenotypes to salt stress in seed germination and post-germination growth. Real-time PCR analysis revealed that the transcript levels of several stress genes (DREB2A, RD29A and RD29B) are lower in pme31-2 mutant than that in the wild type in response to salt stress. These results suggested that PME31 could positively modulate salt stress tolerance.

Yan|Jingwei|J| He|Huan|H| Fang|Lin|L| Zhang|Aying|A|

D057773:Cold Shock Proteins and Peptides

D018506:Gene Expression Regulation, Plant


Assessment of Subcellular ROS and NO Metabolism in Higher Plants: Multifunctional Signaling Molecules.

Abstract: Reactive oxygen species (ROS) and nitric oxide (NO) are produced in all aerobic life forms under both physiological and adverse conditions. Unregulated ROS/NO generation causes nitro-oxidative damage, which has a detrimental impact on the function of essential macromolecules. ROS/NO production is also involved in signaling processes as secondary messengers in plant cells under physiological conditions. ROS/NO generation takes place in different subcellular compartments including chloroplasts, mitochondria, peroxisomes, vacuoles, and a diverse range of plant membranes. This compartmentalization has been identified as an additional cellular strategy for regulating these molecules. This assessment of subcellular ROS/NO metabolisms includes the following processes: ROS/NO generation in different plant cell sites; ROS interactions with other signaling molecules, such as mitogen-activated protein kinases (MAPKs), phosphatase, calcium (Ca2+), and activator proteins; redox-sensitive genes regulated by the iron-responsive element/iron regulatory protein (IRE-IRP) system and iron regulatory transporter 1(IRT1); and ROS/NO crosstalk during signal transduction. All these processes highlight the complex relationship between ROS and NO metabolism which needs to be evaluated from a broad perspective.

Kohli|Sukhmeen Kaur|SK|
Khanna|Kanika|K|
Bhardwaj|Renu|R|
Abd Allah|Elsayed Fathi|EF|
Ahmad|Parvaiz|P|
Corpas|Francisco J|FJ|

signaling
reactive oxygen species
nitric oxide
antioxidants
organelles
stress


Phenolic-rich smoothie consumption ameliorates non-alcoholic fatty liver disease in obesity mice by increasing antioxidant response.

Abstract: Consumption of foods rich in phenolic compounds can be beneficial for health. This study aimed to examine whether the consumption of a phenolic-rich smoothie, based on juçara, strawberry and banana, ameliorates metabolic status and liver damage of diet-induced obese mice. Forty male C57BL/6J mice were assigned into four groups (n = 10) and fed control diet with free access to water (C) or phenolic-rich smoothie (C-S), or fed high-fat diet with free access to water (HF) or phenolic-rich smoothie (HF-S) for five weeks. HF and HF-S groups had higher body weight gains than the C group, however the HF had a greater adipose index, higher plasma levels of glucose, insulin and leptin, as well as higher plasma and hepatic steatosis than C, C-S and HF-S groups. The liver oxidative stress markers were reduced in C-S and HF-S groups and the activity of catalase and glutathione peroxidase were higher compared with their counterparts. The present study suggests that regular consumption of a phenolic-rich smoothie improves the liver antioxidant status, prevents metabolic disorders and ameliorates non-alcoholic fatty liver disease caused by high-fat diet consumption.

Quitete|Fernanda Torres|FT|
Almeida Santos|Giulia Medeiros|GM|
de Oliveira Ribeiro|Leilson|L|
Aguiar da Costa|Cristiane|C|
Freitas|Suely Pereira|SP|
Martins da Matta|Virgínia|V|
Daleprane|Julio Beltrame|JB|

D065626:Non-alcoholic Fatty Liver Disease

Obesity
Phenolic compounds
Adipose tissue
Antioxidant capacity
Liver steatosis
Tropical fruit


Clinical Reproducibility of the Epworth Sleepiness Scale for Patients With Suspected Sleep Apnea.

Abstract:
STUDY OBJECTIVES
To determine the reproducibility of the Epworth Sleepiness Scale (ESS) score in a clinical population referred for diagnostic testing with suspected obstructive sleep apnea.

METHODS
A retrospective audit of patients referred for a diagnostic sleep study with suspected sleep apnea was undertaken. Data collection was two 3-month time periods from January to March in 2012 and 2014. To evaluate reproducibility, the ESS score at primary care referral was compared to the ESS score at first specialist assessment/sleep assessment. The proportion of scores changing by more than 2, 3, 5, or 7 points was determined. Data were analyzed using Bland-Altman plots and paired t tests.

RESULTS
A total of 154 patients (68% male) with a mean ± standard deviation age of 51 ± 13 years, body mass index 36 ± 10 kg/m2, and apnea-hypopnea index 43 ± 40 events/h were included. The average ESS score change was -0.2 with a standard deviation of 3.9 reflecting a wide scatter. A difference between the sequential ESS scores of 5 or more was seen in 21% of subjects.

CONCLUSIONS
In a clinical obstructive sleep apnea referral population, the ESS score was variable when administered sequentially. Given this variability the ESS should not be used as the sole tool to prioritize patients for obstructive sleep apnea assessment.

COMMENTARY
A commentary on this article appears in this issue on page 711.

Campbell|Angela J|AJ|
Neill|Alister M|AM|
Scott|Daniel A R|DAR|

sleep
primary health care
referral and consultation
sleep apnea syndromes


Assessing the psychosocial factors associated with adherence to exercise referral schemes: A systematic review.

Abstract: This paper aimed to systematically review the evidence base to uncover the key psychosocial factors that underpin adherence to an exercise referral scheme (ERS). Databases PsycINFO, MEDLINE, SPORTDiscus, Web of Science, PubMed, PsycARTICLES, Open Grey, and PsycEXTRA were systematically searched. A parallel results-based convergent synthesis was performed by identifying key themes from quantitative and qualitative studies separately. After applying inclusion and exclusion criteria, the review included 24 eligible studies. Key findings showed intrinsic motivation, psychological need satisfaction, social support, and self-efficacy to be the prominent psychosocial factors associated with ERS adherence. In addition, lower expectations for change when entering the scheme was associated with ERS adherence. This review should serve as a catalyst to provide evidence-based ERS and as such ERS providers should seek to place an emphasis on participants' expectations and beliefs when entering the scheme. Moreover, targeting the key factors of intrinsic motivation, psychological need satisfaction, social support, and self-efficacy throughout the duration of an ERS should serve to facilitate adherence.

GP referral
correlates
exercise maintenance
exercise prescription
physical activity


Survey of Physical Therapists' Attitudes, Knowledge, and Behaviors Regarding Diagnostic Imaging.

Abstract:
OBJECTIVE
The purpose of this study was to describe physical therapists' attitudes, knowledge, and behaviors regarding the use of diagnostic imaging.

METHODS
Physical therapists in the United States were recruited from July 2018 through May 2019 to complete a web-based, cross-sectional survey. Participants were asked about demographics, their perceived knowledge base and skills for recommending or ordering different imaging modalities, and their behaviors regarding diagnostic imaging. Descriptive statistics were used to characterize the participants' demographics and responses to all questions. Chi-square tests were performed to compare responses by characteristics of survey participants and Wilcoxon signed-rank tests to compare levels of agreement.

RESULTS
The mean age was 43 years, and of the 739 respondents, 58% (n = 417) were female. Ninety-two percent of respondents (n = 595) reported having recommended diagnostic imaging to another provider at least once. Only 11.6% (n = 75) reported having ever directly ordered diagnostic imaging. Participants' attitudes about their knowledge base and skills for recommending or ordering plain radiographs were stronger compared with any other imaging modalities followed by magnetic resonance imaging (MRI) over other imaging techniques. Participants' attitudes on recommending plain radiographs or MRI differed by professional education level, board-certification status, fellowship completion, and years since graduation.

CONCLUSION
It is common for physical therapists to recommend imaging, but few have directly ordered imaging. Most survey participants believed that they have an adequate knowledge base and skills for recommending and ordering plain radiographs and MRI.

IMPACT
These results can serve as a benchmark for future comparison as policies and educations evolve. Understanding physical therapists' attitudes, knowledge, and use of diagnostic imaging is important to inform research, policy, and education.

Rundell|Sean D|SD|
Maitland|Murray E|ME|
Manske|Robert C|RC|
Beneck|George J|GJ|

D007722:Health Knowledge, Attitudes, Practice

Physical Therapists
Imaging
Diagnosis
Health Care Surveys


Bioapplications of Cell-SELEX-Generated Aptamers in Cancer Diagnostics, Therapeutics, Theranostics and Biomarker Discovery: A Comprehensive Review.

Abstract: Currently, functional single-stranded oligonucleotide probes, termed aptamers, generated by an iterative technology, Systematic Evolution of Ligands by Exponential Enrichment (SELEX), are utilized to selectively target molecules or cells with high affinity. Aptamers hold considerable promise as multifunctional molecules or conjugates for challenging nanotechnologies or bioapplications now and in the future. In this review, we first describe recent endeavors to select aptamers towards live cancer cells via cell-SELEX. We then introduce several characteristic applications of selected aptamers, especially in imaging, drug delivery and therapy. In part, these advances have been made possible via synthesis of aptamer-based nanomaterials, which, by their sizes, shapes, and physicochemical properties, allow such aptamer-nanomaterial complexes to function as signal reporters or drug carriers. We also describe how these aptamer-based molecular tools contribute to cancer biomarker discovery through high-affinity recognition of membrane protein receptors.

Pang|Xuehui|X| Cui|Cheng|C| Wan|Shuo|S| Jiang|Ying|Y| Zhang|Liangliang|L| Xia|Lian|L| Li|Long|L| Li|Xiaowei|X| Tan|Weihong|W|

aptamer
cancer
biomarker
cell-SELEX
imaging
drug delivery
therapy


Sonodynamic Therapy for the Treatment of Intracranial Gliomas.

Abstract: High-grade gliomas are the most common and aggressive malignant primary brain tumors. Current therapeutic schemes include a combination of surgical resection, radiotherapy and chemotherapy; even if major advances have been achieved in Progression Free Survival and Overall Survival for patients harboring high-grade gliomas, prognosis still remains poor; hence, new therapeutic options for malignant gliomas are currently researched. Sonodynamic Therapy (SDT) has proven to be a promising treatment combining the effects of low-intensity ultrasound waves with various sound-sensitive compounds, whose activation leads to increased immunogenicity of tumor cells, increased apoptotic rates and decreased angiogenetic potential. In addition, this therapeutic technique only exerts its cytotoxic effects on tumor cells, while both ultrasound waves and sensitizing compound are non-toxic per se. This review summarizes the present knowledge regarding mechanisms of action of SDT and currently available sonosensitizers and focuses on the preclinical and clinical studies that have investigated its efficacy on malignant gliomas. To date, preclinical studies implying various sonosensitizers and different treatment protocols all seem to confirm the anti-tumoral properties of SDT, while first clinical trials will soon start recruiting patients. Accordingly, it is crucial to conduct further investigations regarding the clinical applications of SDT as a therapeutic option in the management of intracranial gliomas.

D'Ammando|Antonio|A|
Raspagliesi|Luca|L|
Gionso|Matteo|M|0000-0002-1749-7418
Franzini|Andrea|A|
Porto|Edoardo|E|
Di Meco|Francesco|F|0000-0001-6213-5793
Durando|Giovanni|G|0000-0001-6324-0827
Pellegatta|Serena|S|0000-0001-7804-9486
Prada|Francesco|F|

sonodynamic therapy
gliomas
5-aminolevulinic acid
cavitation
fluorescein


Non-functioning pituitary macroadenomas: factors affecting postoperative recurrence, and pre- and post-surgical endocrine and visual function.

Abstract:
BACKGROUND
Non-functioning pituitary macroadenomas (NFPAs) with visual field defects are ideally managed by transsphenoidal tumour resection to improve vision, and long-term postsurgical follow up is necessary to monitor for tumour recurrence. Regular updates from global data are necessary for developing optimal management strategies of these tumours.

METHODS
Pre- and postoperative visual and endocrine profile, imaging characteristics and details of surgical interventions among patients with NFPAs managed between 2008 and 2019 in a UK regional centre were assessed. The radiological and surgical outcomes including postoperative complications, recurrence risk and the factors influencing outcomes also were assessed.

RESULTS
105 cases with mean (SD) age 60.1 (14.3) years and follow-up duration 60 (37) months were studied. 67 (64%) patients were male. Five-year recurrence-free survival rate was 71.5% (95% confidence interval [CI] 62.7% to 81.6%) with 33 (31%) tumour recurrences of whom 20 (60%) received radiotherapy and 9 (27%) underwent further surgery. Younger age, tumour volume, and bilateral cavernous sinus extension were the predictors of recurrence on univariate analysis, while younger age was the only factor on multivariate analysis (Hazard ratio 0.95; 95% CI: 0.92, 0.97). 72/78 patients (92%) with preoperative visual field defects improved after surgery, of whom 27 (35%) had full recovery. 20 (24%) patients had recovery of an abnormal hormone axis. 15 patients (16%) developed perioperative complications such as cerebrospinal fluid leak (12 cases), meningitis (2 cases), and bleeding (2 cases).

CONCLUSIONS
Five-year recurrence-free survival after transsphenoidal resection for NFPAs was 71.5% with older age at surgery conferring lower risk of recurrence. Visual recovery/ improvement occurred in 92% of cases with preoperative visual defects following surgery.

Non-functioning pituitary macroadenoma (NFPA)


Letrozole in a low-cost in vitro fertilization protocol in intracytoplasmic sperm injection cycles for male factor infertility: A randomized controlled trial.

Abstract:
INTRODUCTION
Letrozole, a selective aromatase inhibitor, reduces the total dose of gonadotrophin required for inducing follicular maturation. We evaluated if incorporation of letrozole could be an effective alternative for low-cost in vitro fertilization (IVF) protocol particularly in intracytoplasmic sperm injection (ICSI) cycles where male factor infertility is the sole indication for IVF.

MATERIALS AND METHODS
It is a randomized controlled single-blind trial. 94 women with history of severe male factor infertility were selected. 42 women (study group) received letrozole, 5 mg daily from day 3-7 and recombinant FSH (rFSH) 75IU/day from day 5 continuously till hCG injection. 52 women (control group) underwent continuous stimulation by rFSH (150-225IU/day) from day 2. GnRH-antagonist (Inj. Orgalutran 0.25 ml sub-cutaneous) was started at maximum follicle size of 14 in both groups. Ovulation was triggered by 10,000IU of hCG followed by IVF-ET. Main outcome measures were total dose of rFSH (IU/cycle), terminal E2 (pg/ml), number of mature follicles, number of oocyte retrieved, transferable embryo, endometrial thickness, pregnancy rate and mean expenditure. Statistical analysis is done by using SPSS11.

RESULTS
As compared to control group (1756 ± 75IU), the study group i.e., Let-rFSH received (625 ± 98IU) significantly lower (P = 0.0001) total dose of rFSH. Terminal E2 was significantly lower (P = 0.0001) in study group than control (830 ± 36 vs. 1076 ± 41 pg/ml) with significant increment in endometrial thickness (P = 0.0008) in study group, (9.1 ± 0.32 vs. 8.7 ± 0.69) which maintained an improved pregnancy rate though nonsignificant. The risk of hyperstimulation had significantly (P = 0.01) reduced in study group than control (0 vs. 7).Treatment outcome in all other aspects including pregnancy rate were statistically comparable. Per cycle mean expenditure was reduced by 34% in study group than control.

CONCLUSION
Adjunctive use of letrozole may be an effective mean of low-cost IVF therapy.

Mukherjee|Shiuli|S|
Sharma|Sunita|S|
Chakravarty|Baldya Nath|BN|

letrozole
male factor infertility
ICSI
low-cost IVF
Antagonist


Protecting Effects of N-acetyl Cysteine Supplementation Against Lead and Cadmium-Induced Brain Toxicity in Rat Models.

Abstract: We aimed to investigate mitigating effects of N-acetylcysteine (NAC) on the oxidative stress, apoptosis and Parkinson's disease (PD)-related genes in the brain tissue of male rats exposed to continuous doses of cadmium and lead. Rats were randomly divided into five groups, including G1 (control), G2 (continuous dose of Cd), G3 (continuous dose of Pb), G4 (continuous dose of Cd + NAC), and G5 (continuous dose of Pb + NAC). Biomarkers of oxidative stress, malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured. Expression of PD- and apoptosis-related genes was considered using RT-PCR. Chronic exposure to these heavy metals was associated with accumulation of Pb and Cd in the brain and blood and caused severe morphological changes in the brain, as well as decreased body and brain weights. Continuous exposure to Cd and Pb significantly decreased TAC content and SOD expression but increased MDA level in the brain tissues (P < 0.001). A significant increase was observed in expression of PD-related genes, Parkin, Pink1, LRRK2, SNCA, and Caspase-3 in the brain tissues following exposure to Cd and Pb. Pb exhibited stronger toxicity on the brain tissue compared to Cd. NAC supplementation not only improved morphological changes, but also compensated antioxidant capacity and expression of apoptosis- and PD-related genes in the brain tissues when compared to rats exposed to Pb and Cd alone. Chronic exposure to Pb and Cd is strongly associated with accumulation of these heavy metals in the brain, morphological changes, antioxidants depletion, oxidative stress, and brain cells apoptosis. Changes in expression of PD-related genes indicate the higher risk of PD among individuals who are chronically exposed to these heavy metals. NAC can protect brain tissue against Pb and Cd toxicity by elevating antioxidants capacity, mitigating oxidative stress, apoptosis, and down-regulating of PD-related genes.

N-acetyl cysteine
Lead
Oxidative stress
Apoptosis
Cadmium
Antioxidants
Parkinson’s disease


Systematic detection of polyvascular disease combined with aggressive secondary prevention in patients presenting with severe coronary artery disease: The randomized AMERICA Study.

Abstract:
BACKGROUND
The prevalence and associated-risk of asymptomatic multisite artery disease (MSAD) in high risk coronary patients are unknown. Whether systematic identification and aggressive management of asymptomatic MSAD is clinically relevant in high risk coronary patients has not been evaluated.

METHODS
We randomly assigned 521 high risk coronary patients defined by the presence of three-vessel coronary disease (n=304) or recent acute coronary syndrome beyond the age of 75years (n=215) to either a strategy of systematic detection of asymptomatic MSAD combined with an aggressive secondary prevention (n=263) or to a more conventional strategy based on treatment of coronary artery disease only with standard of care (n=258). The primary end point was the time to first occurrence of death, any organ failure or ischemic event leading to re-hospitalization through two years of follow-up.

RESULTS
The pro-active strategy identified asymptomatic MSAD in 21.7% of patients with few revascularizations (3.6%); the pro-active pharmacological secondary prevention was obtained in >85% of patients and life-style changes in <60% of patients. At 2-year follow-up, the primary end point occurred in 44.9% of patients in the pro-active group and 43.0% of patients in the conventional group (HR 1.03; 95% confidence interval [CI], 0.80 to 1.34]. The rate of major bleeding did not differ significantly between groups (4.6% vs 5.0%; HR, 0.97; 95% CI, 0.40 to 1.91).

CONCLUSION
In high risk coronary patients, there is no apparent benefit of a systematic detection of asymptomatic extra-coronary atherothrombotic disease and intensified treatment over a 2-year follow-up period. (Funded by the Academic Allies in Cardiovascular Trials Initiatives and Organized Networks and Institut de l'Athérothrombose; AMERICA ClinicalTrials.gov number, NCT00445835).

Collet|Jean-Philippe|JP| Cayla|Guillaume|G| Ennezat|Pierre-Vladimir|PV| Leclercq|Florence|F| Cuisset|Thomas|T| Elhadad|Simon|S| Henry|Patrick|P| Belle|Loic|L| Cohen|Ariel|A| Silvain|Johanne|J| Barthelemy|Olivier|O| Beygui|Farzin|F| Diallo|Abdourahmane|A| Vicaut|Eric|E| Montalescot|Gilles|G| |||

Coronary artery disease
Atherothrombosis
Myocardial infarction


Cyclobuteno[60]fullerenes as Efficient n-Type Organic Semiconductors.

Abstract: Cyclobuteno[3,4:1,2][60]fullerenes have been prepared in a straightforward manner by a simple reaction between [60]fullerene and readily available allenoates or alkynoates as organic reagents under basic and mild conditions. The chemical structure of the new modified fullerenes has been determined by standard spectroscopic techniques and confirmed by X-ray diffraction analysis. Some of these new fullerene derivatives exhibit a remarkable intrinsic electron mobility (determined by using flash-photolysis time-resolved microwave conductivity (FP-TRMC) measurements), which surpasses that of the well-known phenyl-C61-butyric acid methyl ester, thus behaving as promising n-type organic semiconductors.

Reboredo|Silvia|S|
Girón|Rosa M|RM|
Filippone|Salvatore|S|
Mikie|Tsubasa|T|
Sakurai|Tsuneaki|T|
Seki|Shu|S|
Martín|Nazario|N|

allenoates
alkynoates
fullerenes
electron mobility
cyclobutene


Negative density dependence of seed dispersal and seedling recruitment in a neotropical palm.

Abstract: Negative density dependence (NDD) of recruitment is pervasive in tropical tree species. We tested the hypotheses that seed dispersal is NDD, due to intraspecific competition for dispersers, and that this contributes to NDD of recruitment. We compared dispersal in the palm Attalea butyracea across a wide range of population density on Barro Colorado Island in Panama and assessed its consequences for seed distributions. We found that frugivore visitation, seed removal and dispersal distance all declined with population density of A. butyracea, demonstrating NDD of seed dispersal due to competition for dispersers. Furthermore, as population density increased, the distances of seeds from the nearest adult decreased, conspecific seed crowding increased and seedling recruitment success decreased, all patterns expected under poorer dispersal. Unexpectedly, however, our analyses showed that NDD of dispersal did not contribute substantially to these changes in the quality of the seed distribution; patterns with population density were dominated by effects due solely to increasing adult and seed density.

Jansen|Patrick A|PA|
Visser|Marco D|MD|
Joseph Wright|S|S|
Rutten|Gemma|G|
Muller-Landau|Helene C|HC|

intraspecific competition
competition for dispersers
Clumping
Janzen-Connell
escape
population regulation
recruitment limitation
seed limitation
species coexistence
tropical forest


Selective solid phase extraction of JWH synthetic cannabinoids by using computationally designed peptides.

Abstract: The objective of the present work is to demonstrate a rational way to prepare selective sorbents able to extract simultaneously several structural analogs. For this purpose the binding specificity of two hexapeptides computationally designed (VYWLVW and YYIGGF) versus four synthetic cannabinoids Naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH 018), naphthalen-1-yl-(1-butylindol-3-yl)methanone (JWH 073), (R)-(1-((1-methylpiperidin-2-yl)methyl)-1H-indol-3-yl)(naphthalen-1-yl)methanone (AM 1220) and (R)-(+)-[2,3-Dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-napthalenylmethanone (WIN 55) was computationally studied and then experimentally tested by solid-phase extraction (SPE) clean-up and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis. The two peptides were chosen using a semi combinatorial virtual technique by generating 4 cycles of peptide libraries (around 2.3×104 elements). To select the two peptides, the simulated binding scores between synthetic cannabinoids and peptides was used by maximizing the recognition properties of amino acid motif between the two JWH and the other synthetic cannabinoids. In particular, the peptide YYIGGF, having also affinity for AM 120, was selected as control because it was the only one without tryptophan residues within the best peptides obtained from simulation. Experimentally, the two hexapeptides were tested as SPE sorbent using nanomolar solutions of the four drugs. After optimization of best retentions the binding constants were calculated by loading synthetic cannabinoids solutions at different concentrations. The results indicated a strong interaction between hexapeptide VYWLVW and JWH 018 (15.58±2.03×106M-1), 3-fold and 40-fold larger compared to the analog JWH 073 and both AM 1220 and the WIN 55. Similar trend was observed for the hexapeptide YYIGGF but the binding constants were at least three times lower highlighting the key role of the tryptophan. To demonstrate the hexapeptides specific interaction with only synthetic cannabinoids, a cross-reactivity study was carried out using other drugs (cocaine, morphine, phencyclidine and methamphetamine) in the same SPE condition. Finally the practical utility of these peptide modified sorbent materials was further demonstrated by detecting the synthetic cannabinoids in real samples using hair matrix.

Mascini|Marcello|M| Montesano|Camilla|C| Perez|German|G| Wang|Joseph|J| Compagnone|Dario|D| Sergi|Manuel|M|

D000595:Amino Acid Sequence
D002186:Cannabinoids
D015195:Drug Design
D008958:Models, Molecular
D009842:Oligopeptides
D011487:Protein Conformation
D052616:Solid Phase Extraction

Solid phase extraction
Synthetic cannabinoids
Peptides
Liquid chromatography–mass spectrometry
Molecular docking
Virtual screening


Electron Microscopic Detection of Proteins and Protein Complexes in Mammalian Cells Using APEX-tagged, Conditionally Stable Nanobodies.

Abstract: The recent development of 3D electron microscopic techniques for cells and tissues has necessitated the development of new methods for the detection of proteins and protein-complexes in situ. The development of new genetic tags, such as the ascorbate peroxidase, APEX, for electron microscopic detection of tagged proteins has expanded the available toolbox and ushered in a new era in biological electron microscopy. Here, we describe methods for combining conditionally-stable nanobodies to fluorescent protein tags with APEX-based detection. These methods are compatible with detection of low levels of expression of fluorescently-tagged proteins and with detection of protein complexes using split GFP-based complementation methods. We describe a simple protocol for applying these methods to the electron microscopic detection of proteins and protein complexes in cultured cells.

Hall|Thomas E|TE|
Rae|James|J|
Ariotti|Nicholas|N|
G Parton|Robert|R|

Nanobodies
Peroxidase
APEX
Electron microscopy
GFP
Localization


Symptomatic and presumed symptomatic focal epilepsies in childhood: An observational, prospective multicentre study.

Abstract:
OBJECTIVE
To describe the clinical, neuropsychological, and psychopathologic features of a cohort of children with a new diagnosis of symptomatic or presumed symptomatic focal epilepsy at time of recruitment and through the first month. The selected population will be followed for 2-5 years after enrollment to investigate the epilepsy course and identify early predictors of drug resistance.

METHODS
In this observational, multicenter, nationwide study, children (age 1 month-12.9 years) with a new diagnosis of symptomatic or presumed symptomatic focal epilepsy were consecutively enrolled in 15 Italian tertiary childhood epilepsy centers. Inclusion criteria were as follows: (1) diagnosis of symptomatic focal epilepsy due to acquired and developmental etiologies, and presumed symptomatic focal epilepsy; (2) age at diagnosis older than 1 month and <13 years; and (3) written informed consent. Children were subdivided into three groups: ≤3 years, >3 to 6 years, and >6 years. Clinical, electroencephalography (EEG), neuroimaging, and neuropsychological variables were identified for statistical analyses.

RESULTS
Two hundred fifty-nine children were enrolled (116 female and 143 male). Median age: 4.4 years (range 1 month-12.9 years); 46.0% (n = 119) of children were younger than 3 years, 24% (61) from 3 to 6 years of age, and 30% (79) older than 6 years. Neurologic examination findings were normal in 71.8%. Brain magnetic resonance imaging (MRI) was abnormal in 59.9%. Children age ≤3 years experienced the highest seizure frequency in the first month after recruitment (p < 0.0001). Monotherapy in the first month was used in 67.2%. Cognitive tests at baseline revealed abnormal scores in 30%; behavioral problems were present in 21%. At multivariate analysis, higher chances to exhibit more than five seizures in the first month after epilepsy onset was confirmed for younger children and those with temporal lobe epilepsy.

SIGNIFICANCE
In this prospective cohort study, an extensive characterization of epilepsy onset in children with symptomatic or presumed symptomatic focal epilepsies is reported in relation to the age group and the localization of the epileptogenic zone.

Vecchi|Marilena|M|
Barba|Carmen|C|0000-0001-5445-5842
De Carlo|Debora|D|
Stivala|Micol|M|
Guerrini|Renzo|R|
Albamonte|Emilio|E|
Ranalli|Domiziana|D|
Battaglia|Domenica|D|
Lunardi|Giada|G|
Boniver|Clementina|C|
Piccolo|Benedetta|B|
Pisani|Francesco|F|
Cantalupo|Gaetano|G|
Nieddu|Giuliana|G|
Casellato|Susanna|S|
Cappanera|Silvia|S|
Cesaroni|Elisabetta|E|
Zamponi|Nelia|N|
Serino|Domenico|D|
Fusco|Lucia|L|
Iodice|Alessandro|A|
Palestra|Filippo|F|
Giordano|Lucio|L|
Freri|Elena|E|
De Giorgi|Ilaria|I|
Ragona|Francesca|F|
Granata|Tiziana|T|
Fiocchi|Isabella|I|
Bova|Stefania Maria|SM|
Mastrangelo|Massimo|M|
Verrotti|Alberto|A|
Matricardi|Sara|S|
Fontana|Elena|E|
Caputo|Davide|D|
Darra|Francesca|F|
Dalla Bernardina|Bernardo|B|
Beccaria|Francesca|F|
Capovilla|Giuseppe|G|
Baglietto|Maria Pia|MP|
Gagliardi|Alessandra|A|
Vignoli|Aglaia|A|
Canevini|Maria Paola|MP|
Perissinotto|Egle|E|
Francione|Stefano|S|

Childhood epilepsy
Behavior impairment
Cognitive function
Focal symptomatic seizures
Intractable epilepsy


Zinc in Preventing the Progression of pre-Diabetes (ZIPPeD Study) - study protocol for a randomised placebo-controlled trial in Australia.

Abstract:
BACKGROUND
Diabetes is increasing in incidence, morbidity and treatment costs globally, hence prevention strategies need to be explored. Animal studies and some human data have shown that zinc can improve glycaemic control, but the impact of this effect in a pre-diabetic population remains uncertain. This study is designed to investigate whether zinc gluconate and lifestyle coaching can improve glucose handling and ultimately reduce diabetes incidence in an at-risk pre-diabetic population in Australia.

METHODS/DESIGN
The study will be a randomised, placebo-controlled, double-blind clinical trial. The study will be conducted at the Hunter New England Local Health District New South Wales (NSW), Australia. Pre-diabetic (haemoglobin A1c [HbA1c] 5.7-6.4) male and female participants (n = 410) aged 40-70 years will be recruited through the Diabetes Alliance Network, a collaboration of diabetes specialists and general practitioner practices. All participants will be given routine care to encourage healthy lifestyle changes using a telephone coaching service (Get Healthy Information and Coaching Service, NSW Health) and then randomised to receive a supplement, either zinc gluconate (equivalent to 30 mg of elemental zinc) or placebo of identical appearance for 12 months. The identity of the supplements will be blinded to both research personnel and the participants. Participants will be asked to complete medical, lifestyle and dietary surveys and will have baseline and final visits at their general practitioner practice. Primary outcomes will be HbA1c and insulin sensitivity collected at baseline and at 1, 6 and 12 months; secondary outcomes will include fasting blood glucose, fasting cholesterol, blood pressure and body mass index. The primary efficacy endpoint will be judged at 6 months.

DISCUSSION
This study will generate new evidence about the potential for health coaching, with or without zinc supplementation, to improve glucose handling and ultimately to reduce progression from pre-diabetes to diabetes.

TRIAL REGISTRATION
Australian and New Zealand Clinical Trials Registry, ACTRN12618001120268 . Registered on 6 July 2018.

D016032:Randomized Controlled Trials as Topic

Pre-diabetes
Australia
Healthy lifestyle
Zinc supplementation
Adults


The relationship between self-esteem and sexual self-concept in people with physical-motor disabilities.

Abstract:
BACKGROUND
Self-esteem is the value that the individuals give themselves, and sexual self-concept is also a part of individuality or sexual-self. Impairment or disability exists not only in the physical body of disabled people but also in their attitudes. Negative attitudes affect the mental health of disabled people, causing them to have lower self-esteem.

OBJECTIVES
This study aimed to examine the relationship between self-esteem and sexual self-concept in people with physical-motor disabilities.

PATIENTS AND METHODS
This cross-sectional study was conducted on 200 random samples with physical-motor disabilities covered by Isfahan Welfare Organization in 2013. Data collection instruments were the Persian Eysenck self-esteem questionnaire, and five domains (sexual anxiety, sexual self-efficacy, sexual self-esteem, sexual fear and sexual depression) of the Persian multidimensional sexual self-concept questionnaire. Because of incomplete filling of the questionnaires, the data of 183 people were analyzed by the SPSS 16.0 software. Data were analyzed using the t-test, Man-Whitney and Kruskal-Wallis tests and Spearman correlation coefficient.

RESULTS
The mean age was 36.88 ± 8.94 years for women and 37.80 ± 10.13 for men. The mean scores of self-esteem among women and men were 15.80 ± 3.08 and 16.2 ± 2.90, respectively and there was no statistically significance difference. Comparison of the mean scores of sexual anxiety, sexual self-efficacy, sexual self-esteem, sexual fear and sexual depression among men and women showed that women scored higher than men in all domains. This difference was statistically significant in other domains except the sexual self-esteem (14.92 ± 3.61 vs. 13.56 ± 4.52) (P < 0.05). The Kruskal-Wallis test showed that except for sexual anxiety and sexual self-esteem, there was a statistical difference between other domains of people's sexual self-concept and degree of disability (P < 0.05). Moreover, Spearman coefficient showed that there was only a correlation between men's sexual anxiety, sexual self-esteem and sexual self-efficacy with their self-esteem. This correlation was positive in sexual anxiety and negative in two other domains.

CONCLUSIONS
Lack of difference in self-esteem of disabled people in different degrees of disability and in both men and women suggests that disabled people should not be presumed to have low self-esteem, and their different aspects of life should be attended to, just like others. Furthermore, studies should be designed and implemented based on psychological, social and environmental factors that can help disabled people to promote their positive sexual self-concept through marriage, and reduce their negative self-concept.

Salehi|Mehrdad|M|
Kharaz Tavakol|Hooman|H|
Shabani|Maede|M|
Ziaei|Tayebe|T|

Self-Esteem
Sexual Self-Concept
Physically Disabled


An Inflammation-Centric View of Neurological Disease: Beyond the Neuron.

Abstract: Inflammation is a complex biological response fundamental to how the body deals with injury and infection to eliminate the initial cause of cell injury and effect repair. Unlike a normally beneficial acute inflammatory response, chronic inflammation can lead to tissue damage and ultimately its destruction, and often results from an inappropriate immune response. Inflammation in the nervous system ("neuroinflammation"), especially when prolonged, can be particularly injurious. While inflammation per se may not cause disease, it contributes importantly to disease pathogenesis across both the peripheral (neuropathic pain, fibromyalgia) and central [e.g., Alzheimer disease, Parkinson disease, multiple sclerosis, motor neuron disease, ischemia and traumatic brain injury, depression, and autism spectrum disorder] nervous systems. The existence of extensive lines of communication between the nervous system and immune system represents a fundamental principle underlying neuroinflammation. Immune cell-derived inflammatory molecules are critical for regulation of host responses to inflammation. Although these mediators can originate from various non-neuronal cells, important sources in the above neuropathologies appear to be microglia and mast cells, together with astrocytes and possibly also oligodendrocytes. Understanding neuroinflammation also requires an appreciation that non-neuronal cell-cell interactions, between both glia and mast cells and glia themselves, are an integral part of the inflammation process. Within this context the mast cell occupies a key niche in orchestrating the inflammatory process, from initiation to prolongation. This review will describe the current state of knowledge concerning the biology of neuroinflammation, emphasizing mast cell-glia and glia-glia interactions, then conclude with a consideration of how a cell's endogenous mechanisms might be leveraged to provide a therapeutic strategy to target neuroinflammation.

Skaper|Stephen D|SD|
Facci|Laura|L|
Zusso|Morena|M|
Giusti|Pietro|P|

inflammation
microglia
mast cells
astrocytes
oligodendrocytes
crosstalk
neuro-immune
palmitoylethanolamide


Preclinical trial of a new dual mTOR inhibitor, MLN0128, using renal cell carcinoma tumorgrafts.

Abstract: mTOR is a rational target in renal cell carcinoma (RCC) because of its role in disease progression. However, the effects of temsirolimus, the only first-generation mTOR inhibitor approved by the FDA for first-line treatment of metastatic RCC, on tumor reduction and progression-free survival are minimal. Second-generation mTOR inhibitors have not been evaluated on RCC. We compared the effects of temsirolimus and MLN0128, a potent second-generation mTOR inhibitor, on RCC growth and metastasis using a realistic patient-derived tissue slice graft (TSG) model. TSGs were derived from three fresh primary RCC specimens by subrenal implantation of precision-cut tissue slices into immunodeficient mice that were randomized and treated with MLN0128, temsirolimus, or placebo. MLN0128 consistently suppressed primary RCC growth, monitored by magnetic resonance imaging (MRI), in three TSG cohorts for up to 2 months. Temsirolimus, in contrast, only transiently inhibited the growth of TSGs in one of two cohorts before resistance developed. In addition, MLN0128 reduced liver metastases, determined by human-specific quantitative polymerase chain reaction, in two TSG cohorts, whereas temsirolimus failed to have any significant impact. Moreover, MLN0128 decreased levels of key components of the two mTOR subpathways including TORC1 targets 4EBP1, p-S6K1, HIF1α and MTA1 and the TORC2 target c-Myc, consistent with dual inhibition. Our results demonstrated that MLN0128 is superior to temsirolimus in inhibiting primary RCC growth as well as metastases, lending strong support for further clinical development of dual mTOR inhibitors for RCC treatment.

Ingels|Alexandre|A|
Zhao|Hongjuan|H|
Thong|Alan E|AE|
Saar|Matthias|M|
Valta|Maija P|MP|
Nolley|Rosalie|R|
Santos|Jennifer|J|
Peehl|Donna M|DM|

D004354:Drug Screening Assays, Antitumor

D051795:Hypoxia-Inducible Factor 1, alpha Subunit

D000076222:Mechanistic Target of Rapamycin Complex 1

D000076225:Mechanistic Target of Rapamycin Complex 2

D023041:Xenograft Model Antitumor Assays

mTOR inhibitor
renal cell carcinoma
tumorgrafts


Virulence factors, antibiotic resistance phenotypes and O-serogroups of Escherichia coli strains isolated from community-acquired urinary tract infection patients in Mexico.

Abstract:
BACKGROUND/PURPOSE
Uropathogenic Escherichia coli (UPEC) strains isolated from patients with community-acquired urinary tract infections (UTIs) were assessed to determine the prevalence of virulence genes, antibiotic resistance, and the O-serogroup of the strains.

METHODS
Consenting patients with community-acquired UTI were enrolled at Unidad Médica Familiar Number 64 (Instituto Mexicano del Seguro Social, Estado de Mexico, Mexico) and 321 urine samples were collected. Polymerase chain reaction (PCR) was used to assess 24 virulence genes and 14 O-serogroups. The Kirby-Bauer method was used to evaluate the antibiotic susceptibility of the isolated strains to 12 commonly used antibiotics.

RESULTS
A total of 194 strains were identified as E. coli using standard biochemical tests, followed by PCR amplification of 16S ribosomal RNA gene. Only 58.2% of the strains belonged to the assessed 14 O-serogroups. The serogroups O25, O15, O8, and O75 were present in 20.6%, 17%, 6.1%, and 4.6% of strains, respectively. The most frequently occurring virulence genes among UPEC strains included kpsMT (92.2% strains), usp (87.1%), irp2 (79.3%), iha (64.9%), fim (61.3%), set (36%), astA (33.5%), pap (24.7%), and papGII (21.1%). In addition, 97% of the strains were multi-drug resistant (coresistance to 3-11 antibiotics).

CONCLUSION
The isolated UPEC strains predominantly belonged to three serogroups (O25, O15, and O8), harboured numerous virulence genes, and are multiresistant to antibiotics. The findings of this study could be used to orient UTI treatment strategies and in epidemiological studies in Mexico.

Paniagua-Contreras|Gloria Luz|GL|
Monroy-Pérez|Eric|E|
Rodríguez-Moctezuma|José Raymundo|JR|
Domínguez-Trejo|Pablo|P|
Vaca-Paniagua|Felipe|F|
Vaca|Sergio|S|

D052978:Disk Diffusion Antimicrobial Tests

virulence factors
O-serogroup
UPEC
multidrug-resistance


Cocaine-seeking is associated with PKC-dependent reduction of excitatory signaling in accumbens shell D2 dopamine receptor-expressing neurons.

Abstract: Stimulation of D1-like dopamine receptors (D1DRs) or D2-like dopamine receptors (D2DRs) in the nucleus accumbens (NAc) shell reinstates cocaine seeking in rats, an animal model of relapse. D2DRs and D1DRs activate protein kinase C (PKC) and recent studies indicate that activation of PKC in the NAc plays an important role in the reinstatement of drug seeking induced by a systemic cocaine priming injection. In the present study, pharmacological inhibition of PKC in the NAc shell attenuated cocaine seeking induced by intra-accumbens shell microinjection of a D2DR agonist, but not a D1DR agonist. D1DRs and D2DRs are primarily expressed on different accumbens medium spiny (MSN) neurons. Neuronal signaling and activity were assessed in these two populations of NAc neurons with transgenic mice expressing fluorescent labels under the control of D1DR and D2DR promoters. Following the extinction of cocaine self-administration, bath application of a PKC inhibitor produced similar effects on single evoked excitatory and inhibitory post-synaptic currents in D1DR- and D2DR-positive MSNs in the NAc shell. However, inhibition of PKC preferentially improved the ability of excitatory, but not inhibitory, synapses to sustain responding to brief train of stimuli specifically in D2DR-positive MSNs. This effect did not appear to involve modulation of presynaptic release mechanisms. Taken together, these findings indicate that the reinstatement of cocaine seeking is at least partially due to D2DR-dependent increases in PKC signaling in the NAc shell, which reduce excitatory synaptic efficacy in D2DR-expressing MSNs.

Ortinski|Pavel I|PI|
Briand|Lisa A|LA|
Pierce|R Christopher|RC|
Schmidt|Heath D|HD|

Dopamine Relapse Self-administration Addiction EPSCs Electrophysiology IPSCs Striatum


Focal segmental glomerular sclerosis: do not overlook the role of immune response.

Abstract: Focal and segmental glomerular sclerosis (FSGS) is a histological pattern characterized by the partial sclerosis of some, but not all, glomeruli. It may be secondary to diverse etiologies such as mutations of podocyte key genes, loss of nephrons, drugs, and virus infection. However, in most cases of FSGS, the etiology is unknown and these forms are called idiopathic (primary) FSGS. A number of different pathogenic hypotheses have been proposed. The frequent recurrence of nephrotic proteinuria after renal transplantation has attracted the attention to search for plasma factors eventually implicated in the pathogenesis. However a decisive and unifying hypothesis is still lacking. On the other hand, recent findings indicate the involvement of cellular immunity and possibly autoantibodies in the pathogenesis of some forms of FSGS. In this paper we report on the recent advances in the pathophysiology of idiopathic FSGS and suggest the possibility that at least some forms of idiopathic FSGS may be caused by autoimmune reactivity.

Focal segmental glomerular sclerosis
Plasma factors
Cellular immunity
Autoimmune reactivity


Real-Time Reaction Monitoring of an Organic Multistep Reaction by Electrospray Ionization-Ion Mobility Spectrometry.

Abstract: The capability of electrospray ionization (ESI)-ion mobility (IM) spectrometry for reaction monitoring is assessed both as a stand-alone real-time technique and in combination with HPLC. A three-step chemical reaction, consisting of a Williamson ether synthesis followed by a hydrogenation and an N-alkylation step, is chosen for demonstration. Intermediates and products are determined with a drift time to mass-per-charge correlation. Addition of an HPLC column to the setup increases the separation power and allows the determination of further species. Monitoring of the intensities of the various species over the reaction time allows the detection of the end of reaction, determination of the rate-limiting step, observation of the system response in discontinuous processes, and optimization of the mass ratios of the starting materials. However, charge competition in ESI influences the quantitative detection of substances in the reaction mixture. Therefore, two different methods are investigated, which allow the quantification and investigation of reaction kinetics. The first method is based on the pre-separation of the compounds on an HPLC column and their subsequent individual detection in the ESI-IM spectrometer. The second method involves an extended calibration procedure, which considers charge competition effects and facilitates nearly real-time quantification.

Zühlke|Martin|M| Sass|Stephan|S| Riebe|Daniel|D| Beitz|Toralf|T| Löhmannsröben|Hans-Gerd|HG|

reaction monitoring
electrospray ionization
HPLC
ion mobility spectrometry
reaction mechanisms


Aberrant NEAT1 expression is associated with clinical outcome in high grade glioma patients.

Abstract: Long noncoding RNA (lncRNA) NEAT1 has been reported to play critical roles in various human tumor entities and related to the survival of patients with malignancies. However, little is known about the role of lncRNA NEAT1 in glioma patients. The aim of this study was to investigate the expression of NEAT1 in human glioma and its correlation with clinicopathological features and prognosis in human glioma; we analyzed the relationship of lncRNA NEAT1 expression with clinicopathological characteristics and prognosis in glioma patients. In our results, the relative level of NEAT1 expression was higher in cancer tissues compared with adjacent noncancerous tissues (p < 0.001). High NEAT1 expression was observed to be closely correlated with larger tumor size (p = 0.023), higher WHO grade (p = 0.005), and recurrence (p = 0.011). Kaplan-Meier curves showed that patients with high NEAT1 expression showed unfavorable overall survival (OS) than the low NEAT1 expression group (p = 0.002). Multivariate analysis results revealed that NEAT1 overexpression was an independent prognostic factor for OS in addition to postoperative chemoradiotherapy and WHO grade. Moreover, high NEAT1 expression in patients with stage III~IV disease and postoperative chemoradiotherapy conferred unfavorable OS (stage III~IV p = 0.002, postoperative chemoradiotherapy p = 0.000). This study supports NEAT1 as a potential prognostic predictor with its high expression in cancer tissues and its association with carcinogenesis and progression in glioma.

He|Chengbiao|C| Jiang|Bing|B| Ma|Jianrong|J| Li|Qiaoyu|Q|

D015972:Gene Expression Regulation, Neoplastic

NEAT1
glioma
Long noncoding RNA
prognosis
qRT-PCR


Accounting for body mass effects in the estimation of field metabolic rates from body acceleration.

Abstract: Dynamic body acceleration (DBA), measured through animal-attached tags, has emerged as a powerful method for estimating field metabolic rates of free-ranging individuals. Following respirometry to calibrate oxygen consumption rate (ṀO2) with DBA under controlled conditions, predictive models can be applied to DBA data collected from free-ranging individuals. However, laboratory calibrations are generally performed on a relatively narrow size range of animals, which may introduce biases if predictive models are applied to differently sized individuals in the field. Here, we tested the mass dependence of the ṀO2-DBA relationship to develop an experimental framework for the estimation of field metabolic rates when organisms differ in size. We performed respirometry experiments with individuals spanning one order of magnitude in body mass (1.74-17.15 kg) and used a two-stage modelling process to assess the intraspecific scale dependence of the ṀO2-DBA relationship and incorporate such dependencies into the coefficients of ṀO2 predictive models. The final predictive model showed scale dependence; the slope of the ṀO2-DBA relationship was strongly allometric (M1.55), whereas the intercept term scaled closer to isometry (M1.08). Using bootstrapping and simulations, we evaluated the performance of this coefficient-corrected model against commonly used methods of accounting for mass effects on the ṀO2-DBA relationship and found the lowest error and bias in the coefficient-corrected approach. The strong scale dependence of the ṀO2-DBA relationship indicates that caution must be exercised when models developed using one size class are applied to individuals of different sizes.

Byrnes|Evan E|EE|
Lear|Karissa O|KO|
Brewster|Lauran R|LR|
Whitney|Nicholas M|NM|
Smukall|Matthew J|MJ|
Armstrong|Nicola J|NJ|
Gleiss|Adrian C|AC|

Respirometry
Oxygen consumption rate
Negaprion brevirostris
Biologging
Ecophysiology
Elasmobranch
Lemon shark


Effects of Pulsed Electric Field Processing and Sous Vide Cooking on Muscle Structure and In Vitro Protein Digestibility of Beef Brisket.

Abstract: Pulsed electric fields (PEF) in conjunction with sous vide (SV) cooking has been explored for meat tenderisation. The aim of this experiment was to study the effect of PEF-SV treatment on the muscle structure and in vitro protein digestibility of beef brisket. Pulsed electric field treatment (specific energy of 99 ± 5 kJ/kg) was applied to bovine Deep and Superficial pectoral muscles in combination with sous vide (SV) cooking (60 °C for 24 h). A similar micro- and ultrastructure was detected between the control SV-cooked and PEF-treated SV-cooked pectoral muscles. The combined PEF-SV treatment increased the in vitro protein digestibility of the pectoral muscles by approximately 29%, in terms of ninhydrin-reactive free amino nitrogen released at the end of simulated digestion. An increment in proteolysis of the PEF-treated SV-cooked meat proteins (e.g., myosin heavy chains and C-protein) during simulated digestion was also observed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. More damaged muscle micro- and ultrastructure was detected in PEF-treated SV-cooked muscles at the end of in vitro digestion, showing its enhanced digestive proteolysis compared to the control cooked meat.

pulsed electric field
sous vide cooking
in vitro protein digestion
meat structure


Effect of fluctuation of oxygenation and time spent in the target range on retinopathy of prematurity in extremely low birth weight infants.

Abstract:
BACKGROUND
The association between saturation of peripheral oxygenation (SpO2) fluctuation and severity of retinopathy of prematurity (ROP) is well elucidated in extremely low birth weight (ELBW) infants. Time spent in the Target range of SpO2 is also associated with the severity of ROP.

METHODS
In a prospective observational study, the SpO2 of all ELBW infants admitted to our unit were monitored for the first four weeks of life, and averaged every minute for analysis. The percent time spent at SpO2 <90%, 90-95%, and >95% and weekly SpO2 fluctuations [as SpO2 coefficient of variation (CoV)] were calculated.

RESULTS
During the study period 21 infants had moderate to severe ROP and 35 infants served as controls. Infants with moderate to severe ROP were smaller and younger than their controls [676±124 grams vs. 796±148 grams (p < 0.001); and 24.0±1.0 weeks vs. 25.0±1.7 weeks (p < 0.001) respectively]. There were no significant differences in time spent in the 90-95% range between groups (p = 0.66). However there was a significant increase in weekly SpO2 CoV in infants with moderate to severe ROP vs. controls (p = 0.007).

CONCLUSION
In ELBW infants, there was an association between SpO2 fluctuation during the first four weeks of life and severity of ROP, although, no association was established with time spent in the target range of SpO2.

Das|A|A|
Mhanna|M|M|
Sears|J|J|
Houdek|J W|JW|
Kumar|N|N|
Gunzler|D|D|
Einstadter|D|D|
Collin|M|M|

D052577:Infant, Extremely Low Birth Weight

fluctuation
Retinopathy of prematurity
prematurity
saturation of peripheral oxygen
target oxygen saturation


Evaluation of community eye outreach programs for early glaucoma detection in Nigeria.

Abstract:
PURPOSE
To evaluate the relevance of community eye outreach programs in the early detection of glaucoma patients in southwest Nigeria.

METHODS
This was a retrospective, cross-sectional study that was conducted among glaucoma patients referred to the eye clinic of the University College Hospital (UCH), Ibadan, Nigeria, between January 2009 and December 2010 from different sources, including community eye outreach programs. The source of referral, stage of glaucoma, and visual field were recorded.

RESULTS
Six hundred and fifty-three patients were studied during this period. The mean age was 56.3 years ± 16.6 years, with a median age of 60 years. Patients referred from eye outreach programs were more likely to have mild to moderate disease than patients referred from other sources, who were more likely to have severe disease according to both the optic nerve head assessment (P < 0.01, Pearson's Chi-square = 10.67, odds ratio = 1.7 [confidence interval = 1.23-2.31]) and visual field assessment (24-2) (P < 0.01, Pearson's Chi-square = 6.07, odds ratio = 1.5 [confidence interval = 1.08-2.03]).

CONCLUSION
Community eye outreach programs appear highly useful in the earlier detection of glaucoma in sub-Saharan Africa.

Olawoye|Olusola|O|
Fawole|Olufunmilayo I|OI|
Teng|Christopher C|CC|
Ritch|Robert|R|

community eye outreach
early glaucoma detection
sub-Saharan Africa
Nigeria glaucoma detection
glaucoma awareness


CeF3-Doped Porous Carbon Nanofibers as Sulfur Immobilizers in Cathode Material for High-Performance Lithium-Sulfur Batteries.

Abstract: In this study, the CeF3-doped porous carbon nanofibers (PCNFs), prepared via electroblown spinning technique and carbonization process, are used as sulfur immobilizers in cathodes for lithium-sulfur (Li-S) batteries for the first time. The cathode composed of CeF3-doped PCNFs, carbon nanotubes (CNTs), and S is successfully prepared through the ball-milling and heating method. The formed porous structure in the PCNFs and CNTs facilitates the construction of highly electrically conductive pathways and effectively alleviates volume changes, which can maintain the stability of the cathode structure and make them in close contact between the electrodes. Meanwhile, the intermediate polysulfide dissolved and lost in the electrolyte can also be suppressed because of the hierarchical porous carbon nanofibers and CeF3. The Li-S battery using the cathode can display excellent electrochemical properties and stable capacity retention, presenting an initial discharge capacity of 1395.0 mAh g-1 and retaining a capacity of 901.2 mAh g-1 after 500 cycles at 0.5C. During the rate capability tests of battery, the discharge capacity of Li-S battery with the electrode slowed down from the discharge capacity of 1284.6 mAh g-1 at 0.5C to 1038.6 mAh g-1 at 1C and 819.3 mAh g-1 at 2C, respectively. It is noteworthy that the battery can still endow an outstanding discharge capacity of 1269.73 mAh g-1 with a high retention of 99.2% when the current density returns to 0.5C.

CeF3-doped
hierarchical porous carbon nanofibers
stable capacity retention
high initial discharge capacity
lithium−sulfur battery


Parental knowledge on infant crying and abusive head trauma and relevant shaking behaviors in China.

Abstract:
BACKGROUND
This study aims to characterize the knowledge about infant crying and abusive head trauma (AHT), and shaking behaviors in parents of children in China, which are lacking currently.

METHODS
A cross-sectional survey was conducted in 2020. We collected information about the knowledge of the typical patterns of infant crying and AHT, and asked about beliefs of the effects of violent shaking on children's health, and shaking behavior among parents.

RESULTS
A total of 568 parents completed the questionnaire, and only 1.6 % of them answered all nine knowledge questions related to infant crying correctly. Overall, 42.6 % of participants reported they had heard about AHT, but only 17.1 % of the parents reported they knew enough about the dangers of infant shaking. About 45 % of the parents acknowledged that they had shaken their infants at least once. Parents who were from western region of China (OR = 3.860; 95 % CI = 1.871, 7.966; p < 0.001) and have felt very frustrated because of the baby's crying over half of the time (OR = 3.401; 95 % CI = 1.862, 6.211; p < 0.001) had the highest risk of shaking. Majority of the parents reported that they needed further information about infant soothing techniques, knowledge of prevention and treatment about AHT.

CONCLUSIONS
Majority of Chinese parents do not have enough knowledge about normal infant crying, nevertheless, most of them expressing needs in learning more. Community-wide advocating efforts aiming to educate parents on awareness and knowledge about AHT should be a health priority in China.

Gao|Qi|Q| Tong|Linhang|L| Tang|Lixia|L| Zhong|Weiqiang|W| Zhu|Huiping|H|

Infant crying
Abusive head trauma
Behavior
Chinese
Shaken baby syndrome


Homo- and Heterotypic Association Regulates Signaling by the SgK269/PEAK1 and SgK223 Pseudokinases.

Abstract: SgK269/PEAK1 is a pseudokinase and scaffolding protein that plays a critical role in regulating growth factor receptor signal output and is implicated in the progression of several cancers, including those of the breast, colon, and pancreas. SgK269 is structurally related to SgK223, a human pseudokinase that also functions as a scaffold but recruits a distinct repertoire of signaling proteins compared with SgK269. Structural similarities between SgK269 and SgK223 include a predicted α-helical region (designated CH) immediately preceding the conserved C-terminal pseudokinase (PK) domain. Structure-function analyses of SgK269 in MCF-10A mammary epithelial cells demonstrated a critical role for the CH and PK regions in promoting cell migration and Stat3 activation. Characterization of the SgK269 "interactome" by mass spectrometry-based proteomics identified SgK223 as a novel binding partner, and association of SgK269 with SgK223 in cells was dependent on the presence of the CH and PK domains of both pseudokinases. Homotypic association of SgK269 and SgK223 was also demonstrated and exhibited the same structural requirements. Further analysis using pulldowns and size-exclusion chromatography underscored the critical role of the CH region in SgK269/SgK223 association. Importantly, although SgK269 bridged SgK223 to Grb2, it was unable to activate Stat3 or efficiently enhance migration in SgK223 knock-out cells generated by CRISPR/Cas9. These results reveal previously unrecognized interplay between two oncogenic scaffolds and demonstrate a novel signaling mechanism for pseudokinases whereby homotypic and heterotypic association is used to assemble scaffolding complexes with distinct binding properties and hence qualitatively regulate signal output.

Liu|Ling|L|
Phua|Yu Wei|YW|
Lee|Rachel S|RS|
Ma|Xiuquan|X|
Jenkins|Yiping|Y|
Novy|Karel|K|
Humphrey|Emily S|ES|
Chan|Howard|H|
Shearer|Robert|R|
Ong|Poh Chee|PC|
Dai|Weiwen|W|
Saunders|Darren N|DN|
Lucet|Isabelle S|IS|
Daly|Roger J|RJ|

D047908:Intracellular Signaling Peptides and Proteins

scaffold protein
oncogene
breast cancer
protein kinase
signal transduction


Bixasteroid, a new compound from the fruits of Bixa orellana and its anti-inflammatory activity.

Abstract: Bixasteroid (1), one new steroid together with five known compounds (2-6), were isolated from the ethyl acetate fraction of ethanol extract of Bixa orellana fruits. All of these known compounds were isolated from the plant for the first time. Their structures were elucidated on the basis of spectroscopic analysis, and the absolute configuration of compound 1 was determined by X-ray crystallographic data analysis as well as by the quantum chemical ECD calculations. All the isolated compounds were tested for their anti-inflammatory activities. Compounds 1 and 2 showed inhibiting NO release activities in LPS-induced RAW 264.7 macrophages with the IC50 values of 4.72 ± 0.28 and 5.48 ± 1.48 μM, respectively.

Chen|Yi-Min|YM| Xu|Tian-Qi|TQ| Zhang|Xiao-Qi|XQ| Fan|Chun-Lin|CL| Ye|Wen-Cai|WC| Xu|Wei|W| Zhou|Guang-Xiong|GX|

bixasteroid
Bixa orellana
anti-inflammatory activity
ECD calculations
X-ray diffraction


Survival of advanced melanoma patients treated with immunotherapy and targeted therapy: A real-world study.

Abstract:
INTRODUCTION
We aimed to examine the survival outcomes plus patient and treatment characteristics of advanced melanoma patients treated with first-line immunotherapy (IT), targeted therapy (TT), and chemotherapy (CTH) and compare findings with information from pivotal trials for each therapy.

MATERIALS AND METHODS
We retrospectively reviewed the use of systematic IT, TT and CTH therapies in melanoma patients in four Queensland public hospitals. We estimated median duration of overall survival (OS) and survival rates (6 months, 1, and 2 years) using Kaplan-Meier methods. We compared our findings to those of clinical trials.

RESULTS
Five hundred three patients who met the inclusion criteria were divided into three groups based on the first-line treatment: IT 232; TT 157; and CTH 114. OS was 18 months with IT (95% CI 13, 22); 12 months with TT (95% CI 8, 15); and 5 months with CTH (95% CI 5, 6). The demographic characteristics, treatment protocols, and durations for IT and TT were generally consistent with trials but fewer patients in our study had subsequent therapy than in the trials. The OS in our study was slightly lower than the OS reported in trials.

CONCLUSION
The OS of novel cancer therapy in the real world was lower than seen in trials but is expected given these are patients who have a poorer prognosis. A future study could investigate the impact of prognostic factors on survival in the longer term. This study provides evidence that we can use routinely collected real-world data to evaluate the effectiveness of checkpoint and kinase inhibitors in patients with advanced melanoma.

melanoma
immunotherapy
targeted therapy
effectiveness
pharmacoepidemiology
retrospective study


Genetic variants of CHEK1, PRIM2 and CDK6 in the mitotic phase-related pathway are associated with nonsmall cell lung cancer survival.

Abstract: The mitotic phase is a vital step in cell division and may be involved in cancer progression, but it remains unclear whether genetic variants in mitotic phase-related pathways genes impact the survival of these patients. Here, we investigated associations between 31 032 single nucleotide polymorphisms (SNPs) in 368 mitotic phase-related pathway genes and overall survival (OS) of patients with nonsmall cell lung cancer (NSCLC). We assessed the associations in a discovery data set of 1185 NSCLC patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and validated the findings in another data set of 984 patients from the Harvard Lung Cancer Susceptibility Study. As a result, we identified three independent SNPs (ie, CHEK1 rs76744140 T>C, PRIM2 rs6939623 G>T and CDK6 rs113181986 G>C) to be significantly associated with NSCLC OS with an adjusted hazard ratio of 1.29 (95% confidence interval = 1.11-1.49, P = 8.26 × 10-4 ), 1.26 (1.12-1.42, 1.10 × 10-4 ) and 0.73 (0.63-0.86, 1.63 × 10-4 ), respectively. Moreover, the number of combined unfavorable genotypes of these three SNPs was significantly associated with NSCLC OS and disease-specific survival in the PLCO data set (Ptrend  < .0001 and .0003, respectively). Further expression quantitative trait loci analysis showed that the rs76744140C allele predicted CHEK1 mRNA expression levels in normal lung tissues and that rs113181986C allele predicted CDK6 mRNA expression levels in whole blood tissues. Additional analyses indicated CHEK1, PRIM2 and CDK6 may impact NSCLC survival. Taken together, these findings suggested that these genetic variants may be prognostic biomarkers of patients with NSCLC.

Mu|Rui|R|
Liu|Hongliang|H|
Luo|Sheng|S|0000-0003-4214-5809
Patz|Edward F|EF|
Glass|Carolyn|C|
Su|Li|L|
Du|Mulong|M|
Christiani|David C|DC|
Jin|Lei|L|
Wei|Qingyi|Q|0000-0002-3845-9445

nonsmall cell lung cancer
survival
mitotic phase
single-nucleotide polymorphism


Sexual and reproductive health and rights and mHealth in policy and practice in South Africa.

Abstract: Information and Communications Technology (ICT) offers enormous opportunity and innovation to improve public health and health systems.This paper explores the intersections between mHealth and sexual and reproductive health and rights in both policy and practice. It is a qualitative study, informed by policy review and key informant interviews. Three case studies provide evidence of what is happening on the ground in relation to ICTs and reproductive health and rights. We argue that in terms of policy, there is little overlap between health rights and communication technology. In the area of practice, however, significant interventions address aspects of reproductive health. At present, the extent to which mHealth addresses the full range of reproductive justice and sexual and reproductive health and rights is limited, particularly in terms of government initiatives. The paper argues that mHealth projects tend to avoid contentious aspects of sexual health, while addressing favourable topics such as pregnancy and motherhood. The ways in which information is framed in mHealth mirrors current gaps within sexual and reproductive health and rights, where a limited and conservative lens predominates, and which may result in narrow programming and implementation of services.

reproductive health policy and programmes


Demographics and frequency of the intermittently upturned omentum at CT.

Abstract:
OBJECTIVES
To describe the demographics and frequency of the intermittently upturned omentum at CT.

METHODS
We retrospectively reviewed abdominal CT scans of 336 consecutive patients (189 men and 147 women) who were imaged between June 1 and June 17, 2010 and who had prior comparison scans. Readers recorded the presence or absence of an intermittently upturned omentum, defined as a thick rind of fat interposed between the liver and the anterior abdominal wall seen on one but not the other scan. At chart review, we recorded patient demographics and other clinical characteristics (prior surgical history, presence of cirrhosis).

RESULTS
An intermittently upturned omentum was found in 10 of 336 (3.0%) patients. An intermittently upturned omentum was seen more commonly in men than in women (9 of 189 men, or 4.8% versus 1 of 147 women, or 0.7%, p=0.047) and in cirrhotics (4 of 37 cirrhotics, or 10.8% versus 6 of 299 non-cirrhotics, or 2.0%, p=0.023). In a sub-analysis of patients without prior abdominal surgery, this finding was again seen more commonly in men than women (7 of 163 men, or 4.3% versus 0 of 134 women, or 0%, p=0.018) and in cirrhotics (3 of 33 cirrhotics, or 9.1% versus 4 of 264 non-cirrhotics, or 1.5%, p=0.032).

CONCLUSIONS
An intermittently upturned omentum is not uncommon and is more frequently seen in men and in patients with cirrhosis who may have a larger anterior hepatic space.

Penn|Alex|A|
Wang|Wilbur|W|
Wang|Zhen Jane|ZJ|
Yee|Judy|J|
Webb|Emily M|EM|
Yeh|Benjamin M|BM|

Upturned omentum
CT
Cirrhosis
Greater omentum
Omental torsion


Determination of five Alternaria toxins in wolfberry using modified QuEChERS and ultra-high performance liquid chromatography-tandem mass spectrometry.

Abstract: A modified quick, easy, cheap, effective, rugged, and safe method coupled with ultra-high performance liquid chromatography-tandem mass spectrometry was established for the simultaneous detection of five Alternaria toxins (tenuazonic acid, alternariol, alternariol monomethyl ether, altenuene, and tentoxin) in wolfberry. The sample pretreatment conditions including the dilution solvent, the extraction solvent and the QuEChERS purification parameters were optimized. Detection of the five Alternaria toxins was performed in MRM mode under ESI + conditions. The results showed that the five Alternaria toxins exhibitedgood linearity (1-200 μg/L, with correlation coefficients > 0.999). The limits of detection were 0.07-0.24 μg/kg, and the limits of quantification were 0.32-0.77 μg/kg. The trueness was between 73.8% and 111.5%, and the precision was lower than 10%. The established method was effectively used for the determination of five Alternaria toxins in 155 wolfberry samples from Northwest China.

Xing|Lijie|L| Zou|Liangjun|L| Luo|Ruifeng|R| Wang|Yuan|Y|

D002851:Chromatography, High Pressure Liquid

Ultra-high performance liquid chromatography-tandem mass spectrometry


Intra-Abdominal Hematoma Following Enoxaparin Injection.

Abstract: An elderly patient, who was being treated for therapeutic enoxaparin for a couple of days due to suspected deep vein thrombosis, was admitted to hospital following a collapse and severe abdominal pain. She was in hypovolemic shock and was fluid resuscitated. Ultrasound scan and computed tomography (CT) scan showed a large pelvic hematoma. Radiologists also suspected a possibility of bleeding from inferior epigastric artery following a CT angiogram. The patient was stabilized and transferred to intensive care unit (ICU) for further hemodynamic supports and close monitoring. The patient was then transferred back to the general ward when she was stable. She was managed conservatively as there were no more signs of active bleeding. Unfortunately, she died of recurrent bleeding three days after ICU discharge.

enoxaparin
deep vein thrombosis
intra-abdominal bleeding


A computer simulation study of soft tissue characterization using low-frequency ultrasonic tomography.

Abstract: We investigate the potential of using ultrasonic diffraction tomography technique for characterization of biological tissues. Unlike most of other studies where ultrasonic tomography operates at frequencies higher than 1 MHz, low-frequency tomography uses lower frequencies on the order of 0.3-0.5 MHz. Such a choice is due to low attenuation at these frequencies, resulting in higher precision of input data. In this paper we explore transmission and reflection schemes for both 2D (layer-by-layer) and 3D tomography. We treat inverse tomography problems as coefficient inverse problems for the wave equation. The time-domain algorithms employed for solving the inverse problem of low-frequency tomography focus on the use of GPU clusters. The results obtained show that a spatial resolution of about 2-3mm can be achieved when operating at the wavelength of about 5mm even using a stationary 3D scheme with a few fixed sources and no rotating elements. The study primarily focuses on determining the performance limits of ultrasonic tomography devices currently designed for breast cancer diagnosis.

Goncharsky|A V|AV|
Romanov|S Y|SY|
Seryozhnikov|S Y|SY|

Ultrasonic tomography
Wave equation
GPU clusters
3D coefficient inverse problems
Reflection and transmission tomography