Advancements in Cancer Stem Cell Isolation and Characterization.

Abstract: Occurrence of stem cells (CSCs) in cancer is well established in last two decades. These rare cells share several properties including presence of common surface markers, stem cell markers, chemo- and radio- resistance and are highly metastatic in nature; thus, considered as valuable prognostic and therapeutic targets in cancer. However, the studies related to CSCs pave number of issues due to rare cell population and difficulties in their isolation ascribed to common stem cell marker. Various techniques including flow cytometry, laser micro-dissection, fluorescent nanodiamonds and microfluidics are used for the isolation of these rare cells. In this review, we have included the advance strategies adopted for the isolation of CSCs using above mentioned techniques. Furthermore, CSCs are primarily found in the core of the solid tumors and their microenvironment plays an important role in maintenance, self-renewal, division and tumor development. Therefore, in vivo tracking and model development become obligatory for functional studies of CSCs. Fluorescence and bioluminescence tagging has been widely used for transplantation assay and lineage tracking experiments to improve our understanding towards CSCs behaviour in their niche. Techniques such as Magnetic resonance imaging (MRI) and Positron emission tomography (PET) have proved useful for tracking of endogenous CSCs which could be helpful in their identification in clinical settings.

Jariyal|Heena|H|
Gupta|Chanchal|C|
Bhat|Vedika Sandeep|VS|
Wagh|Jayant Ramakant|JR|
Srivastava|Akshay|A|0000-0001-5048-9420

Cancer stem cells
Flow cytometry
Fluorescent nanodiamonds
Microfluidics
MRI
Positron emission tomography


Severe calcified stylohyoid complex in twins: a case report.

Abstract: The styloid process is a cylindrical, long cartilaginous bone located on the temporal bone. The calcified stylohyoid ligament and elongated styloid process can be identified radiographically, and they are associated with a number of syndromes and symptoms. The exact cause of the styloid process elongation due to calcification and subsequent ossification of ligament is unclear. This report presents a case of severely calcified stylohyoid ligament complex occurred in twins who have the same pattern of calcification.

Kim|Jo-Eun|JE| Min|Jung-Hyun|JH| Park|Hae-Rang|HR| Choi|Bo-Ram|BR| Choi|Jin-Woo|JW| Huh|Kyung-Hoe|KH|

Twins
Elongated Styloid Process Syndrome
Radiography, Panoramic


Impact of death education courses on emergency nurses' perception of effective behavioral responses in dealing with sudden death in China: A quasi-experimental study.

Abstract:
BACKGROUND
Nurses in emergency departments have to provide rescue care and life support for moribund patients, but also emotional support to patients' relatives. On the other hand, emergency nurses are also the most vulnerable to the sudden death of patients. Nurses working in the emergency department were invited to participate in a death education course.

OBJECTIVE
To explore the impact of a death education course on the emergency nurses' perception of effective behavioral responses in dealing with sudden death.

DESIGN
A quasi-experimental study.

SETTINGS
A level A tertiary general hospital in China.

PARTICIPANTS
A total number of 34 emergency nurses who met the inclusion criteria were randomly selected from the emergency department.

METHODS
Participants received a death education course of 20 credit hours based on dealing with a sudden-death model. The general data questionnaire and the Chinese version of the list proposed by Fraser & Atkins were completed before the intervention and six weeks post-intervention. The scores of each item in the effective behavioral response to the sudden death questionnaire of the emergency nurses before and after the intervention were compared.

RESULTS
After the intervention, the nurses considered that 10 items were relatively helpful (above 4 points) and 2 items relatively less helpful (<3 points). The post-intervention average scores of all items were higher than the pre-intervention ones, and there were significant differences in the scores of the 13 items pre- and post-intervention.

CONCLUSION
The death education course enhanced emergency nurses' perceptions of effective behavioral responses in dealing with sudden death, which contributes to the improvement of the quality of their work.

Zhang|Huilin|H| Hu|Muli|M| Zeng|Liyun|L| Ma|Mingdan|M| Li|Lezhi|L|

Death education
Emergency nurse
Dealing with sudden death model
Effective behavioral responses to death


A comparison of 4- and 24-hour urine samples for the diagnosis of proteinuria in pregnancy.

Abstract:
BACKGROUND
Preeclampsia is a serious complication of pregnancy, and it is vital to diagnosis the condition as early as possible. Proteinuria is an important symptom of preeclampsia, and repeated urine analysis to screen for the condition is part of the standard antenatal care. The purpose of this study was to determine the correlation between 4- and 24-hour urine total protein values to examine whether the 4-hour urine samples could be used for the diagnosis of proteinuria in hypertensive disorders of pregnancy.

METHODS
A cross-sectional study was performed on 110 pregnant (after gestational week 20 of pregnancy) patients who were hypertensive (blood pressure ≥140/90 mmHg) and had proteinuria as defined by positive urinary protein of at least 1+ in dipstick. Patients' urine samples were collected over 24 hours; the first 4 hours were collected separately from the next 20-hours. Patients, who did not collect the 24-hour urine, were excluded from the study. One hundred patients met the criteria, and were included in the study. The urine volume, total protein and creatinine levels of 4- and 24-hours samples were measured. The correlation between 4-hour and 24-hour samples was examined using Pearson correlation test.

RESULTS
Of the 100 patients, 42 had no proteinuria, 44 had mild proteinuria, and 14 had severe proteinuria. The urine protein values of 4-hour samples correlated with those of the 24-hours samples for patients with mild and severe forms of the disease (P<0.001, r=0.86).

CONCLUSION
This study showed there was a correlation between 4-hour and 24-hour urine proteins. The finding indicates that a random 4-hour sample might be used for the initial assessment of proteinuria.

proteinuria
Preeclampsia
hypertension in pregnancy


The vibrational signals that male fiddler crabs (Uca lactea) use to attract females into their burrows.

Abstract: In some fiddler crab species, males emit vibrations from their burrows to mate-searching females after they have attracted a female to the burrow entrance using a waving display. Although the vibrations are considered acoustic signals to induce mating, it has not been demonstrated whether the vibrations attract the females into the burrow and, consequently, influence females' mating decisions. We investigated the structures and patterns of the vibrations using a dummy female and demonstrated experimentally a female preference for male vibrations in Uca lactea in the field. The acoustic signals consisted of repetitions of pulses. The dominant frequency of the pulses decreased with male carapace width. The pulse length decreased slightly with an increasing number of vibrational repetitions, and the pulse interval increased with increasing repetitions. These factors imply that the vibrations convey information on male characteristics, such as body size and stamina. In the experiment on female mate choice, the females significantly preferred males with higher pulse repetition rates when they were positioned at the entrance of the burrow, indicating that the females use the male vibrational signals to decide whether to enter the burrow. However, females showed no preference for the vibrations once they were inside a burrow, i.e., whether they decided to copulate, suggesting that the vibrations do not independently affect a female's final decision of mate choice. The vibrations inside the burrow might influence a female's decision by interaction with other male traits such as the burrow structure.

Uca lactea
Acoustic signal
Female mate choice
Communication
Courtship


Genetic variation in EYA4 on the risk of noise-induced hearing loss in Chinese steelworks firm sample.

Abstract:
OBJECTIVES
Noise-induced hearing loss is one of the most serious occupational diseases worldwide. It is caused by interactions between environmental and genetic factors. The purpose of this study was to examine the association between the genetic susceptibility of the eye absent homolog 4 (EYA4) gene and the risk of developing noise-induced hearing loss in China.

METHODS
A case-control association study was carried out with 326 hearing loss cases and 326 controls matched with age and duration of noise exposure, drawn from a cohort of steel workers. Five single nucleotide polymorphisms (SNPs) in the EYA4 were selected and genotyped. Logistic regression was performed to analyse the main effect of genotypes and interactions between genotypes and individual/environmental factors adjusted for confounding factors. Moreover, generalised multiple dimensionality reduction was applied to further detect interaction among the 5 selected SNPs.

RESULTS
Analysis revealed that locus polymorphism of rs3813346 was associated with the risk of developing noise-induced hearing loss in the dominance model, the codominance model and the addictive model (p=0.004, 0.009 and 0.003, respectively). A significant interaction between rs9321402 and cumulative noise exposure was found (p=0.002). A significant main effect p value (p=0.006) was obtained in the high-level exposure group (cumulative noise exposure ≥98 dB(A)). Generalised multiple dimensionality reduction indicated that the combined interaction of the 2 loci-rs3813346 and rs9493627-significantly affected the incidence of noise-induced hearing loss.

CONCLUSIONS
The research suggests that EYA4 genetic variant and its interaction with noise levels may modify the susceptibility to develop noise-induced hearing loss in Chinese population.

Yang|Qiuyue|Q| Xu|Xiangrong|X| Jiao|Jie|J| Zheng|Yuxin|Y| He|Lihua|L| Yu|Shanfa|S| Gu|Guizhen|G| Chen|Guoshun|G| Zhou|Wenhui|W| Wu|Hui|H| Li|Yanhong|Y| Zhang|Huanling|H| Zhang|Zengrui|Z|

D020022:Genetic Predisposition to Disease

D000072499:Manufacturing and Industrial Facilities

Noise-Induced Hearing Loss
EYA4 gene
Genetic Variability


"Musical co-creation"? Exploring health-promoting potentials on the use of musical and interactive tangibles for families with children with disabilities.

Abstract: The point of departure in this text is the ongoing qualitative interdisciplinary research project RHYME (www.RHYME.no), which addresses the lack of health-promoting interactive and musical Information and Communications Technology (ICT) for families with children with severe disabilities. The project explores a new treatment paradigm based on collaborative, tangible, interactive net-based musical "smart things" with multimedia capabilities. The goal in RHYME is twofold: (1) to reduce isolation and passivity, and (2) to promote health and well-being. Co-creation is suggested as a possible path to achieving these goals, by evoking feelings, for example, or accommodating the needs to act and to create social relations; co-creation also motivates users to communicate and collaborate within (new) social relations. This article engages co-creation by incorporating aspects connected to interaction design and the field of music and health. Empirical observations will be referred to. The research question is as follows: What might co-creation imply for families of children with disabilities when musical and interactive tangibles are used as health-promoting implements?


Afatinib helped overcome subsequent resistance to osimertinib in a patient with NSCLC having leptomeningeal metastasis baring acquired EGFR L718Q mutation: a case report.

Abstract:
BACKGROUND
The epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer has been successfully treated with tyrosine kinase inhibitors (TKIs). Acquired resistance becomes a tough issue when patients fail to respond to the third-generation TKI osimertinib. This study aimed to report a case baring acquired EGFR L858R/L718Q mutation in the central nervous system induced by osimertinib, which was successfully overcome using afatinib.

CASE PRESENTATION
A 65-year-old female patient was diagnosed with stage IV non-small-cell lung adenocarcinoma with synchronic brain metastasis in February 2015. Before and during treatment, 416 tumor-related genes were monitored dynamically by liquid biopsies using next-generation sequencing, and the treatment strategy was decided according to the gene status. At baseline, an EGFR L858R mutation in exon 21 was detected, so treatment with icotinib was started. After 8 months, she experienced disease progression with leptomeningeal metastasis and switched to osimertinib based on an acquired EGFR T790 M mutation. After 9 months, her disease progressed and an EGFR L718Q mutation was found in the cerebrospinal fluid. The patient was then challenged with afatinib, and her disease was under control for 4 months. In January 2017, the patient passed away, with an overall survival time of 23 months, 15 months after leptomeningeal metastasis.

CONCLUSION
The acquired EGFR L718Q mutation in the cerebrospinal fluid resulted in subsequent resistance to osimertinib and could be partly overcome using afatinib, indicating a promising treatment option in the clinic.

Afatinib
NSCLC
Leptomeningeal metastasis
EGFR
L718Q


Extraction Techniques, Biological Activities and Health Benefits of Marine Algae Enteromorpha prolifera Polysaccharide.

Abstract: There is increasing interest in the use of marine algae as functional food additives for improving human health. Enteromorpha (Ulva) prolifera (E. prolifera) is a seaweed green alga (Chlorophyta) that contains many bioactive compounds, of which polysaccharide is the main component. With the advancement of technology in the methods of extraction and analysis, recent studies in in vitro and animals model showed that polysaccharides derived from E. prolifera exert various biological activities, such as gut microbiota modulation, immunomodulation, antioxidant, antidiabetic, antimicrobial, and hypolipidemic. Research evidence has shown that methods of extraction and molecular modification, such as degradation, carboxymethylation, and sulfonation could alter the biological activities of polysaccharides. Therefore, in this review, we discussed the different extraction techniques, structural-activity relationship, and health benefits of sulfated polysaccharides derived from E. prolifera, and suggested future research avenues. This review helps to advance the extraction techniques and promote the application of marine algae polysaccharides as functional food and therapeutic agent.

Wassie|Teketay|T| Niu|Kaimin|K| Xie|Chunyan|C| Wang|Haihua|H| Xin|Wu|W|

extraction technique
biological activity
health benefit
enteromorpha prolifera
microbiota
sulfated polysaccharide


Trait anxiety and bystander motivation to defend victims of school bullying.

Abstract:
INTRODUCTION
School-based bullying is an omnipresent problem, but is less frequent when bystanders are inclined to defend victims. This makes it important to focus on motivation to intervene in bullying.

METHODS
202 students (Mage = 16.44 years, 52% boys) from public Swedish high schools participated in a vignette experiment. Students were randomized to one of two vignettes (victim belonging to/not belonging to ingroup). Self-report measures of motivation to defend and trait anxiety were used.

RESULTS
Participants reported more autonomous motivation when the victim belonged to the ingroup and more extrinsic motivation when the victim did not belong to the ingroup. Trait anxiety interacted with the manipulation: bystanders high in anxiety reported low levels of autonomous motivation when the victim did not belong to the ingroup and low levels of extrinsic motivation when the victim belonged to the ingroup.

CONCLUSIONS
Findings suggest that anti-bullying-programs should focus on how defender motivation is influenced by the way in which victim ingroup status is perceived and address the bystander's level of anxiety as this interacts with such perceptions.

Trait anxiety
Bystanders
School bullying
Ingroup
Prosocial motivation


Enhancer cooperativity as a novel mechanism underlying the transcriptional regulation of E-cadherin during mesenchymal to epithelial transition.

Abstract: Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) highlight crucial steps during embryogenesis and tumorigenesis. Induction of dramatic changes in gene expression and cell features is reflected by modulation of Cdh1 (E-cadherin) expression. We show that Cdh1 activity during MET is governed by two enhancers at +7.8 kb and at +11.5 kb within intron 2 that are activated by binding of Grhl3 and Hnf4α, respectively. Recruitment of Grhl3 and Hnf4α to the enhancers is crucial for activating Cdh1 and accomplishing MET in non-tumorigenic mouse mammary gland cells (NMuMG). Moreover, the two enhancers cooperate via Grhl3 and Hnf4α binding, induction of DNA-looping and clustering at the promoter to orchestrate E-cadherin re-expression. Our results provide novel insights into the cellular mechanisms whereby cells respond to MET signals and re-establish an epithelial phenotype by enhancer cooperativity. A general importance of our findings including MET-mediated colonization of metastasizing tumor cells is suggested.

Alotaibi|Hani|H|
Basilicata|M Felicia|MF|
Shehwana|Huma|H|
Kosowan|Tyler|T|
Schreck|Ilona|I|
Braeutigam|Christien|C|
Konu|Ozlen|O|
Brabletz|Thomas|T|
Stemmler|Marc P|MP|

D015972:Gene Expression Regulation, Neoplastic

Grhl3
Hnf4α
Cadherins
Cancer
Development
Transforming growth factor beta


Biogas production from lignocelluloses by N-methylmorpholine-N-oxide (NMMO) pretreatment: effects of recovery and reuse of NMMO.

Abstract: The effects of N-methylmorpholine-N-oxide (NMMO) pretreatment on barley straw and forest residues were investigated for biogas production. The pretreatments were performed at 90°C with 85% NMMO for 3-30h. The best pretreatment conditions resulted in 100% improvement in methane yield during the subsequent digestion compared to that of the untreated lignocelluloses. Methane yields of 0.23 and 0.15Nm(3) CH4/kg VS were obtained from barley straw and forest residues, respectively, corresponding to 88% and 83% of the theoretical yields. In addition, the effects of the pretreatment with recovered and reused NMMO was also studied over the course of five cycles. Pretreatment with recycled NMMO showed the same performance as the fresh NMMO on barley straw. However, pretreatment of forest residues with recycled NMMO resulted in 55% reduction in methane yield.

Kabir|Maryam M|MM|
Niklasson|Claes|C|
Taherzadeh|Mohammad J|MJ|
Horváth|Ilona Sárvári|IS|

Biogas
Lignocellulose
N-methylmorpholine-N-oxide (NMMO)
Pretreatment
Anaerobic digestion


Sirtuin 3 attenuates neuroinflammation-induced apoptosis in BV-2 microglia.

Abstract: In this study, we explored the upstream regulatory mechanisms underlying inflammation-induced mitochondrial dysfunction in microglial BV-2 cells. Our results demonstrate that Sirtuin 3 (Sirt3) expression was downregulated in response to LPS-induced neuroinflammation. In addition, overexpression of Sirt3 attenuated LPS-induced BV-2 cell death. Functional studies illustrated that Sirt3 overexpression promoted normal mitochondrial function and inhibited mitochondria-dependent apoptosis in LPS-treated BV-2 cells. At the molecular level, suppressor of ras val-2 (SRV2) promoted LPS-mediated mitochondrial damage by inducing mitochondrial fission. Sirt3 overexpression, which suppressed the transcription of SRV2 and thus suppressed mitochondrial fission, played an anti-apoptotic role in LPS-treated BV-2 cells. Furthermore, Sirt3 inhibited SRV2 expression via the Mst1-JNK pathway, and re-activation of this pathway abolished the protective effects of Sirt3 on mitochondrial damage and apoptosis. Taken together, our results indicate that Sirt3-induced, Mst1-JNK-SRV2 signaling pathway-dependent inhibition of mitochondrial fission protected against neuroinflammation-mediated cell damage in BV-2 microglia. Sirt3 might therefore be an effective treatment for neuroinflammation.

apoptosis
microglial BV-2 cells
Sirt3
neuroinflammation
Mst1-JNK pathway


Therapeutic Targeting of the Soluble Guanylate Cyclase.

Abstract: The soluble guanylate cyclase (sGC) is the physiological sensor for nitric oxide and alterations of its function are actively implicated in a wide variety of pathophysiological conditions. Intense research efforts over the past 20 years have provided significant information on its regulation, culminating in the rational development of approved drugs or investigational lead molecules, which target and interact with sGC through novel mechanisms. However, there are numerous questions that remain unanswered. Ongoing investigations, with the critical aid of structural chemistry studies, try to further elucidate the enzyme's structural characteristics that define the association of "stimulators" or "activators" of sGC in the presence or absence of the heme moiety, respectively, as well as the precise conformational attributes that will allow the design of more innovative and effective drugs. This review relates the progress achieved, particularly in the past 10 years, in understanding the function of this enzyme, and focusses on a) the rationale and results of its therapeutic targeting in disease situations, depending on the state of enzyme (oxidized or not, heme-carrying or not) and b) the most recent structural studies, which should permit improved design of future therapeutic molecules that aim to directly upregulate the activity of sGC.

Makrynitsa|Garyfallia I|GI|
Zompra|Aikaterini A|AA|
Argyriou|Aikaterini I|AI|
Spyroulias|Georgios A|GA|
Topouzis|Stavros|S|

D000818:Animals
D002318:Cardiovascular Diseases
D006152:Cyclic GMP
D020536:Enzyme Activators
D006801:Humans
D007674:Kidney Diseases
D009569:Nitric Oxide
D000072417:Protein Domains
D015398:Signal Transduction
D000071756:Soluble Guanylyl Cyclase


Impact of Physician Race on Patient Decision-Making and Ratings of Physicians: a Randomized Experiment Using Video Vignettes.

Abstract:
BACKGROUND
Studies suggest that black patients have better interactions, on average, with physicians of their own race. Whether this reflects greater "cultural competence" in race-concordant relationships, or other effects of race unrelated to physician behavior, is unclear. It is also unclear if physician race influences patient decision-making.

OBJECTIVE
To determine whether physician race affects patients' ratings of physicians and decision-making, independent of physician behavior.

DESIGN
Randomized study using standardized video vignettes.

PARTICIPANTS
Primary care patients with coronary risk factors or disease.

INTERVENTIONS
Each participant viewed one of 16 vignettes depicting a physician reviewing cardiac catheterization results and recommending coronary artery bypass graft (CABG) surgery. Vignettes varied only in terms of physicians' race, gender, age, and communication style (high vs. low patient-centeredness).

MAIN MEASURES
Participants rated the video physician's communication, interpersonal style, competence, trustworthiness, likability, and overall performance (0-4 Likert scales). They also rated the necessity of CABG (0-5 scale) and whether they would undergo CABG or obtain a second opinion if they were the video patient (0-3 scales).

KEY RESULTS
Participants included 107 black and 131 white patients (72% participation rate). Black participants viewing a black (vs. white) video physician gave higher ratings on all physician attributes (e.g., overall rating 3.22 vs. 2.34, p < 0.001) and were more likely to perceive CABG as necessary (4.05 vs. 3.72, p = 0.03) and say they would undergo CABG if they were the video patient (2.43 vs. 2.09, p = 0.004). Patient-centered communication style reduced, but did not eliminate, the impact of race concordance. Physician race was not associated with any outcomes among white patients.

CONCLUSIONS
Black patients viewed the doctor in a scripted vignette more positively, and were more receptive to the same recommendation, communicated in the same way, with a black vs. white physician. Patient-centered communication reduced but did not eliminate the effect of physician race.

patient decision-making
Black Americans
health care disparities
physician-patient relations


Simultaneous Detection of Lactate Enantiomers Based on Diffusion-controlled Bioelectrocatalysis.

Abstract: Amperometric biosensors were constructed for the simultaneous detection of lactate enantiomers. The enantioselectivity of the sensor is based on NAD-dependent l- and d-lactate dehydrogenases that, respectively, oxidize l- and d-lactates into pyruvate. The NADH formed during the enzymatic reduction was catalytically oxidized at Meldola's blue-adsorbed mesoporous electrodes. Stable amperometric measurements were performed in a two-electrode system using Ag|AgCl|sat. KCl as a counter electrode via a salt bridge. The response of the sensor reached a pseudo-steady state within 60 s. The agreement of the sensitivities for l- and d-lactates and the pseudo-steady-state characteristics of the sensors demonstrate that the current is strongly influenced by the diffusion of lactates at the edge of the electrode, enabling reproducible measurements. The pseudo steady-state characteristics are also realized at the chip-type electrode. The sensor was successfully applied for the detection of d- and l-lactates in horse serum.

Matsui|Yukina|Y| Kitazumi|Yuki|Y| Shirai|Osamu|O| Kano|Kenji|K|

Simultaneous detection
bioelectrocatalysis
amperometric biosensor
two-electrode system
lactate dehydrogenase


Mortality Risk Factors for Individuals Experiencing Homelessness in Catalonia (Spain): A 10-Year Retrospective Cohort Study.

Abstract: (1) Background: Current evidence suggests that mortality is considerably higher in individuals experiencing homelessness. The aim of this study was to analyze the mortality rate and the mortality risk factors in a sample of individuals experiencing homelessness in the city of Girona over a ten-year period. (2) Methods: We retrospectively examined the outcomes of 475 people experiencing homelessness with the available clinical and social data. Our sample was comprised of 84.4% men and 51.8% foreign-born people. Cox's proportional hazard models were used to identify mortality risk factors between origin groups. (3) Results: 60 people died during the ten-year period. The average age of death was 49.1 years. After adjusting for demographic characteristics and the duration of homelessness, the risk factors for mortality were origin (people born in Spain) (HR = 4.34; 95% CI = 1.89-10.0), type 2 diabetes (HR = 2.9; 95% CI = 1.62-5.30), alcohol use disorder (HR = 1.9; 95% CI = 1.12-3.29), and infectious diseases (HR = 1.6; 95% CI = 1.09-2.39). Our results show a high prevalence of infectious and chronic diseases. Type 2 diabetes emerges as an important risk factor in homelessness. The average age of death of individuals experiencing homelessness was significantly lower than the average age of death in the general population (which is greater than 80 years). (4) Conclusions: Foreign-born homeless people were generally younger and healthier than Spanish-born homeless people. Chronic diseases were controlled better in Spanish-born people, but this group showed an increased risk of mortality.

mortality
homelessness
type 2 diabetes
alcohol use disorder
infectious disease
drug use disorder
immigration
mental health


Cytomegalovirus in pregnancy and the neonate.

Abstract: Congenital cytomegalovirus (CMV) remains a leading cause of disability in children. Understanding the pathogenesis of infection from the mother via the placenta to the neonate is crucial if we are to produce new interventions and provide supportive mechanisms to improve the outcome of congenitally infected children. In recent years, some major goals have been achieved, including the diagnosis of primary maternal CMV infection in pregnant women by using the anti-CMV IgG avidity test and the diagnosis and prognosis of foetal CMV infection by using polymerase chain reaction real-time tests to detect and quantify the virus in amniotic fluid. This review summarises recent advances in our understanding and highlights where challenges remain, especially in vaccine development and anti-viral therapy of the pregnant woman and the neonate. Currently, no therapeutic options during pregnancy are available except those undergoing clinical trials, whereas valganciclovir treatment is recommended for congenitally infected neonates with moderately to severely symptomatic disease.

cytomegalovirus
pregnancy
pathogenesis
antiviral therapy


Permanent alveolar collapse is the predominant mechanism in idiopathic pulmonary fibrosis.

Abstract: Alveolar epithelial cell loss and impaired epithelial cell regeneration are currently accepted as central initiating events in idiopathic pulmonary fibrosis (IPF), but subsequent downstream effects remain uncertain. The most accepted downstream effect is aberrant and dysregulated mesenchymal cell proliferation and excess extracellular matrix (ECM) accumulation. However, biochemical and imaging studies have perhaps somewhat surprisingly indicated little increase in total lung collagen and lung tissue, and have rather shown a substantial decrease in lung aeration and lung air volume. Loss of tissue aeration is a consequence of alveolar collapse, which occurs in IPF as a result of apposition and septal incorporation of denuded basal lamina. Permanent alveolar collapse is well-documented following epithelial injury, has the ability to mimic interstitial fibrosis radiologically and histologically, and is a better supported explanation than dysregulated fibroblast proliferation and excess ECM accumulation for the constellation of findings in patients with IPF.

Todd|Nevins W|NW|
Atamas|Sergei P|SP|
Luzina|Irina G|IG|
Galvin|Jeffrey R|JR|

alveolar collapse
idiopathic pulmonary fibrosis
extracellular matrix
collagen
collapse induration
epithelial cell injury


Robotic Laparoendoscopic Single Site: Pyeloplasty and Nephrectomy Chapter.

Abstract: Robotic laparoendoscopic single site (RLESS) for upper tract procedures is safe and feasible in the correctly selected patient. An ideal candidate is young, has a low body mass index, and is undergoing surgery for benign indications. For RLESS procedures, we utilize a GelPOINT® access platform for "single-port" placement and ports are configured in a diamond shape. Five millimeter EndoWrist® robotic instruments are placed under direct vision. Range of motion is increased by utilizing the chopstick technique. The surgeon must always be aware of the orientation of each instrument to prevent counter-springing associated with their crossing at the level of the abdominal wall. The robotic camera lens and instruments must be moved synchronously, given their coaxial orientation relative to each other. In this chapter, we describe our technique for two of the most common RLESS upper tract procedures: pyeloplasty and nephrectomy.

laparoendoscopic single site
pyeloplasty
nephrectomy
RLESS


Production of Human IFNγ Protein in Nicotiana benthamiana Plant through an Enhanced Expression System Based on Bamboo mosaic Virus.

Abstract: Plant-based systems are safe alternatives to the current platforms for the production of biologically active therapeutic proteins. However, plant-based expression systems face certain major challenges, including the relatively low productivity and the generation of target proteins in biologically active forms. The use of plant virus-based expression systems has been shown to enhance yields, but further improvement is still required to lower the production cost. In this study, various strategies were employed to increase the yields of an important therapeutic protein, human interferon gamma (IFNγ), in Nicotiana benthamiana through modifications of expression vectors based on potexviruses. Among these, the vector based on a coat protein (CP)-deficient Bamboo mosaic virus (BaMV), pKB△CHis, was shown to exhibit the highest expression level for the unmodified IFNγ. Truncation of the N-terminal signal peptide of IFN (designated mIFNγ) resulted in a nearly seven-fold increase in yield. Co-expression of a silencing suppressor protein by replacing the coding sequence of BaMV movement protein with that of P19 led to a 40% increase in mIFNγ accumulation. The fusion of endoplasmic reticulum (ER) retention signal with mIFNγ significantly enhanced the accumulation ratio of biologically active dimeric mIFNγ to 87% relative to the non-active monomeric form. The construct pKB19mIFNγER, employing the combination of all the above enhancement strategies, gave the highest level of protein accumulation, up to 119 ± 0.8 μg/g fresh weight, accounting for 2.5% of total soluble protein (TSP) content. These findings advocate the application of the modified BaMV-based vector as a platform for high-level expression of therapeutic protein in N. benthamiana.

Jiang|Min-Chao|MC| Hu|Chung-Chi|CC| Lin|Na-Sheng|NS| Hsu|Yau-Heiu|YH|

bamboo mosaic virus
therapeutic protein
interferon gamma
ER retention
potexvirus


Mismatch between bird species sensitivity and the protection of intact habitats across the Americas.

Abstract: Protected areas are highly heterogeneous in their effectiveness at buffering human pressure, which may hamper their ability to conserve species highly sensitive to human activities. Here, we use 60 million bird observations from eBird to estimate the sensitivity to human pressure of each bird species breeding in the Americas. Concerningly, we find that ecoregions hosting large proportions of high-sensitivity species, concentrated in tropical biomes, do not have more intact protected habitat. Moreover, 266 high-sensitivity species have little or no intact protected habitat within their distributions. Finally, we show that protected area intactness is decreasing faster where high-sensitivity species concentrate. Our results highlight a major mismatch between species conservation needs and the coverage of intact protected habitats, which likely hampers the long-term effectiveness of protected areas at retaining species. We highlight ecoregions where protection and management of intact habitats, complemented by restoration, is urgently needed.

D003247:Conservation of Natural Resources

protected areas
conservation
human footprint
threatened species
wilderness


Bisphenol A--sources, toxicity and biotransformation.

Abstract: Bisphenol A (BPA) is a chemical compound used in massive amounts in the production of synthetic polymers and thermal paper. In this review, the sources of BPA, which influence its occurrence in the environment and human surrounding will be presented. Data concerning BPA occurrence in food, water and indoor environments as well as its appearance in tissues and body fluids of human body will be shown. The results of in vitro and in vivo studies and the results of epidemiological surveys showing toxic, endocrine, mutagenic and cancerogenic action of BPA will also be discussed. Moreover, data suggesting that exposure of human to BPA may elevate risk of obesity, diabetes and coronary heart diseases will be presented. Finally, biotransformation of BPA in animals, plants and microorganisms (bacteria, fungi, algae), resulting in the formation of various metabolites that exhibit different from BPA toxicity will be described.

Toxicity
Biotransformation
Bisphenol A
Carcinogenicity
Estrogenicity
Metabolic disorders


Obliterative sinusitis: An underreported clinical entity.

Abstract: Obliterative paranasal sinusitis is a rare sequela and end stage of chronic rhinosinusitis, which is often overlooked on imaging. It is an exuberant form of neo-osteogenesis characterized by complete or partial obliteration of the sinus cavity by new bone formation. This article presents a series of cases of obliterative sinusitis involving the sphenoid and maxillary sinuses. It is important to comment on the presence of obliterative sinusitis in the radiology report and not confuse it for native bone, fibro-osseous lesion, or arrested pneumatization, as this may have clinical implications for patients being considered for surgery. Given its potential implications for severity of sinusitis as well as prognostic significance for outcomes following endoscopic sinus surgery, awareness and timely identification of this entity is important to guide referring clinicians.

Desai|Amit B|AB|
Vibhute|Prasanna|P|
Bhatt|Alok A|AA|

Obliterative sinusitis
Chronic rhinosinusitis
Neo-osteogenesis
Paranasal sinus


Causes of stiffness after total knee arthroplasty: a systematic review.

Abstract:
BACKGROUND
Knee stiffness after total knee arthroplasty (TKA) often leads to pain and discomfort, failing to meet patients' expectations on the surgical procedure. Despite the growing debate on the topic, a comprehensive literature analysis of stiffness causes has never been conducted. Thus, the purpose of the present study was to systematically review the literature regarding the main causes of stiffness after TKA.

METHODS
Pubmed Central, Scopus, and EMBASE databases were systematically reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines for studies on stiffness and pain or discomfort after TKA through November 2020. Overall, 25 articles matched the selection criteria and were included in the study. Clinical relevance and strength of evidence of the included studies were graded using the risk of bias and the methodological index for non-randomized studies quality assessment tools.

RESULTS
The main causes of pain and discomfort due to stiffness were surgery-related issues, i.e., component malpositioning and over-voluming, implant loosening, psychological distress, and obesity, which could be considered "modifiable" factors, and expression of profibrotic markers, high material hypersensitivity-related cytokines level, male gender, previous contralateral TKA, and high pre-operative pain, which could be considered "non-modifiable" factors.

CONCLUSION
The use of alternative technologies such as surgical robots, anatomy-based devices, and more inert and less stiff component materials could help in reducing stiffness caused by both modifiable and even some non-modifiable factors. Furthermore, early diagnostic detection of stiffness onset could consistently support surgeons in patient-specific decision-making.

Zaffagnini|Stefano|S|
Di Paolo|Stefano|S|
Meena|Amit|A|
Alesi|Domenico|D|0000-0002-8841-056X
Zinno|Raffaele|R|
Barone|Giuseppe|G|
Pizza|Nicola|N|
Bragonzoni|Laura|L|


Vascular endothelial cell specification in health and disease.

Abstract: There are two vascular networks in mammals that coordinately function as the main supply and drainage systems of the body. The blood vasculature carries oxygen, nutrients, circulating cells, and soluble factors to and from every tissue. The lymphatic vasculature maintains interstitial fluid homeostasis, transports hematopoietic cells for immune surveillance, and absorbs fat from the gastrointestinal tract. These vascular systems consist of highly organized networks of specialized vessels including arteries, veins, capillaries, and lymphatic vessels that exhibit different structures and cellular composition enabling distinct functions. All vessels are composed of an inner layer of endothelial cells that are in direct contact with the circulating fluid; therefore, they are the first responders to circulating factors. However, endothelial cells are not homogenous; rather, they are a heterogenous population of specialized cells perfectly designed for the physiological demands of the vessel they constitute. This review provides an overview of the current knowledge of the specification of arterial, venous, capillary, and lymphatic endothelial cell identities during vascular development. We also discuss how the dysregulation of these processes can lead to vascular malformations, and therapeutic approaches that have been developed for their treatment.

Endothelial cell specification
Arterial-venous malformations
Blood vessel development
Lymphatic malformations
Lymphatic vessel development


Early brainstem [18F]THK5351 uptake is linked to cortical hyperexcitability in healthy aging.

Abstract: BACKGROUNDNeuronal hyperexcitability characterizes the early stages of Alzheimer's disease (AD). In animals, early misfolded tau and amyloid-β (Aβ) protein accumulation - both central to AD neuropathology - promote cortical excitability and neuronal network dysfunction. In healthy humans, misfolded tau and Aβ aggregates are first detected, respectively, in the brainstem and frontomedial and temporobasal cortices, decades prior to the onset of AD cognitive symptoms. Whether cortical excitability is related to early brainstem tau - and its associated neuroinflammation - and cortical Aβ aggregations remains unknown.METHODSWe probed frontal cortex excitability, using transcranial magnetic stimulation combined with electroencephalography, in a sample of 64 healthy late-middle-aged individuals (50-69 years; 45 women and 19 men). We assessed whole-brain [18F]THK5351 PET uptake as a proxy measure of tau/neuroinflammation, and we assessed whole-brain Aβ burden with [18F]Flutemetamol or [18F]Florbetapir radiotracers.RESULTSWe found that higher [18F]THK5351 uptake in a brainstem monoaminergic compartment was associated with increased cortical excitability (r = 0.29, P = 0.02). By contrast, [18F]THK5351 PET signal in the hippocampal formation, although strongly correlated with brainstem signal in whole-brain voxel-based quantification analyses (P value corrected for family-wise error [PFWE-corrected] < 0.001), was not significantly associated with cortical excitability (r = 0.14, P = 0.25). Importantly, no significant association was found between early Aβ cortical deposits and cortical excitability (r = -0.20, P = 0.11).CONCLUSIONThese findings reveal potential brain substrates for increased cortical excitability in preclinical AD and may constitute functional in vivo correlates of early brainstem tau accumulation and neuroinflammation in humans.TRIAL REGISTRATIONEudraCT 2016-001436-35.FUNDINGF.R.S.-FNRS Belgium, Wallonie-Bruxelles International, ULiège, Fondation Simone et Pierre Clerdent, European Regional Development Fund.

Van Egroo|Maxime|M|
Chylinski|Daphne|D|
Narbutas|Justinas|J|
Besson|Gabriel|G|
Muto|Vincenzo|V|
Schmidt|Christina|C|
Marzoli|Davide|D|
Cardone|Paolo|P|
Vandeleene|Nora|N|
Grignard|Martin|M|
Luxen|André|A|
Salmon|Eric|E|
Lambert|Christian|C|
Bastin|Christine|C|
Collette|Fabienne|F|
Phillips|Christophe|C|
Maquet|Pierre|P|
Bahri|Mohamed Ali|MA|
Balteau|Evelyne|E|
Vandewalle|Gilles|G|

Aging
Alzheimer’s disease
Neuroimaging
Neuroscience


Flaviaesturariibacter flavus sp. nov., isolated from soil in Jeju Island.

Abstract: A Gram-stain-negative, non-motile and yellow-colored bacterium, designated 17J68-12T, was isolated from soil in Jeju Island, Korea. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain 17J68-12T formed a distinct lineage within the family Chitinophagaceae and was mostly related to members of Flaviaesturariibacter luteus (97.5%), Flaviaesturariibacter amylovorans (96.8%) and Flaviaesturariibacter terrae (96.8%). Growth was observed at 18-42 °C (optimum 30 °C) in R2A broth at pH 7.0. The major cellular fatty acids of the strain 17J68-12 T were summed feature 3 (C16:1 ω6c and/or C16:1 ω7c), summed feature 1 (C15:1 iso-H and/or C13:0 3-OH), and iso-C15:0. The predominant respiratory quinones are MK-7 and MK-6. The major polar lipid was identified as phosphatidylethanolamine. Based on biochemical, chemotaxonomic and phylogenetic characteristics, the strain 17J68-12T represents a novel bacterial species within the family Chitinophagaceae, for which the name Flaviaesturariibacter flavus sp. nov. is proposed. The type strain of Flaviaesturariibacter flavus is 17J68-12T (= KCTC 62219T = JCM 33179T).

D015373:Bacterial Typing Techniques
D041963:Bacteroidetes
D001482:Base Composition
D004269:DNA, Bacterial
D005227:Fatty Acids
D010802:Phylogeny
D012336:RNA, Ribosomal, 16S
D056910:Republic of Korea
D012988:Soil Microbiology
D013045:Species Specificity

Flaviaesturariibacter
Chitinophagaceae
Novel species
Taxonomy


Intensity-modulated Radiotherapy in Patients With Aggressive Extranodal Non-Hodgkin Lymphoma of the Head and Neck.

Abstract:
BACKGROUND/AIM
Image-guided intensity-modulated radiotherapy (IG-IMRT) is increasingly being used to treat patients with head and neck malignancies. This analysis compared conventional radiotherapy (CRT) and IMRT outcomes for head and neck aggressive extranodal non-Hodgkin lymphomas (EN-NHL).

PATIENTS AND METHODS
Forty-eight patients who underwent irradiation between 2005 and 2019 were identified.

RESULTS
The median follow-up was 42 months. Patients treated with IMRT experienced higher overall responde rate than patients who received 3DCRT (85% vs. 73%, p=0.4). There was non-significant longer survival following IMRT compared with 3DCRT in terms of 5-year OS (p=0.16). Complete responders after primary treatments had a significantly higher 5-year progression-free (p<0.001) and overall survival (p=0.003) in comparison with those without a complete response. Regarding toxicities, IMRT was associated with less acute and chronic adverse events.

CONCLUSION
IG-IMRT following systemic therapy seems to be associated with a favorable survival and toxicity profile in patients with EN-NHL.

Eismann|Jens|J|
Elsayad|Khaled|K|
Rolf|Daniel|D|
Sarif|Iqbal|I|
Wardelmann|Eva|E|
Berssenbrügge|Hendrik|H|
Lenz|Georg|G|
Eich|Hans Theodor|HT|

IMRT
Extranodal lymphoma
image-guided radiotherapy
immunotherapy
local control
prognosis


Can Hypocaloric, High-Protein Nutrition Support Be Used in Complicated Bariatric Patients to Promote Weight Loss?

Abstract: Bariatric surgery, an effective treatment for morbid obesity, may result in complications that require nutrition support. Common goals for nutrition support in post-bariatric surgery patients include nutrition repletion, avoiding overfeeding, preserving lean body mass, and promoting wound healing. It is often questioned if continued weight loss can be part of the nutrition goals and if weight loss is safe for patients who become critically ill following bariatric surgery. Recent clinical practice guidelines from both the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) and Society of Critical Care Medicine (SCCM) have recommended the use of hypocaloric, high-protein nutrition support in both critically and non-critically ill obese patients. Hypocaloric feedings of 50%-70% of estimated energy requirements based on predictive equations or <14 kcal/kg actual body weight, as well as high-protein feedings of 1.2 g/kg actual weight or 2-2.5 g/kg ideal body weight, are suggested by A.S.P.E.N. in the 2013 clinical guidelines for nutrition support of hospitalized adult patients with obesity. Two small studies in complicated post-bariatric surgery patients requiring nutrition support have shown that the strategy of hypocaloric, high-protein feedings can result in positive outcomes, including positive nitrogen balance, wound healing, weight loss, and successful transition to oral diets. Additional research, including large, randomized studies, is still needed to validate these findings. However, based on a review of available clinical practice guidelines, predictive equations, indirect calorimetry, case studies, and systematic reviews, hypocaloric, high-protein nutrition support appears to at least be equal to eucaloric feedings and may be a useful tool for clinicians to achieve continued weight loss in complicated bariatric surgery patients requiring nutrition support.

D000328:Adult
D050110:Bariatric Surgery
D031204:Caloric Restriction
D016638:Critical Illness
D004044:Dietary Proteins
D006801:Humans
D009751:Nutritional Requirements
D018529:Nutritional Support
D009767:Obesity, Morbid
D011183:Postoperative Complications
D016896:Treatment Outcome
D015431:Weight Loss

nutrition
nutritional support
bariatric surgery
obesity
enteral nutrition
energy intake
nutrition assessment
nutrition support practice
parenteral nutrition
research and diseases


Comparison of simple monophasic versus classical biphasic extraction protocols for comprehensive UHPLC-MS/MS lipidomic analysis of Hela cells.

Abstract: In this study, two monophasic isopropanol-water mixtures (IPA:H2O 75:25 v/v and IPA:H2O 90:10 v/v) were compared with traditionally employed biphasic methods of Bligh & Dyer and Matyash et al. as extraction systems for lipidomics analysis in Hela cells. Samples were analyzed by UHPLC-ESI-QTOF-MS/MS in positive and negative mode using sequential window acquisition of all theoretical fragment ion spectra (SWATH) and a relatively new software (MS-DIAL) was employed for the processing of the data which includes detection of peaks, MS/MS spectra deconvolution, identification of detected lipids and alignment of peaks through the analyzed samples. The studied performance parameters such as precision, recoveries of isotopically labeled internal standards and endogenous lipids, number of extracted lipids, and complexity of employed procedure showed that extraction with IPA:H2O 90:10 v/v performs similar to the Matyash protocol and better than Bligh & Dyer as well as IPA:H2O 75:25 v/v. However, less complex monophasic protocol which is simpler to implement and can be executed in plastic rather than glass, make the monophasic IPA:H2O 90:10 v/v protocol an excellent alternative to the classical biphasic protocols for reversed phase LC-MS lipidomics studies.

Calderón|Carlos|C| Sanwald|Corinna|C| Schlotterbeck|Jörg|J| Drotleff|Bernhard|B| Lämmerhofer|Michael|M|

D002851:Chromatography, High Pressure Liquid

Extraction
Lipidomics
Hela cells
Data-independent acquisition
Lipid profiling
Mass spectrometry


Evaluation of biodegradable microspheres containing nomegestrol acetate in a rat model of endometriosis.

Abstract: We assessed the efficacy of biodegradable microspheres (MSs) containing nomegestrol acetate (NOMAC) for treatment of endometriosis in a rat model and investigated its preliminary mechanism of action. Sprague-Dawley rats with surgically implanted endometrial autografts were divided randomly into four groups of thirteen rats each, and subcutaneously injected twice (10d apart) with either empty MSs or MSs containing nomegestrol acetate (NOMAC-MS; 27-800mg per kg of rat body weight). Twenty-one days after the first injection, blood and endometriotic tissues were collected and assayed for changes in endometriotic tissue, serum hormone, liver function parameters, and apoptotic protein. No remarkable irritation was observed at the site of injection. NOMAC-MS treatment significantly reduced the volume of the endometrial autografts, decreased serum levels of estradiol, progesterone, triiodothyronine, and alanine aminotransferase, and decreased levels of estrogen receptor alpha protein. Furthermore, NOMAC-MS at the highest dose significantly reduced serum aspartate aminotransferase and endometrial antibody, reduced the Bcl-2/Bax protein ratio, and increased caspase-3 and caspase-9 proteins. There was no pronounced difference observed in alkaline phosphatase, carbohydrate antigen 125, progesterone receptor, or vascular endometrial growth factor receptor 2 (VEGFR2) in any of the tested groups relative to the control. NOMAC-MS significantly changed the expression of apoptotic protein only at the highest dose. Our findings warrant the further investigation of sustained application of steroid hormone via microspheres for the treatment of endometriosis.

Zhang|Jianfeng|J| Zhu|Yan|Y| Zhou|Xianying|X| Hao|Shufang|S| Xie|Shuwu|S| Zhou|Jieyun|J| Guo|Xiangjie|X| Li|Zhao|Z| Huang|Yunsheng|Y| Chen|Qinghua|Q|

Biodegradable microsphere
Nomegestrol acetate
Endometriosis
Bcl-2
Bax
Caspase


Fingolimod inhibits proliferation and epithelial-mesenchymal transition in sacral chordoma by inactivating IL-6/STAT3 signalling.

Abstract:
PURPOSE
To explore the sensitivity of the immunosuppressive agent fingolimod (FTY720) in chordoma and determine whether it can serve as an appropriate alternate treatment for unresectable tumours in patients after incomplete surgery.

METHODS
Cell viability assays, colony formation assays and EdU assays were performed to evaluate the sensitivity of chordoma cell lines to FTY720. Transwell invasion assays, wound healing assays, flow cytometry, cell cycle analysis, immunofluorescence analysis, Western blotting analysis and enzyme-linked immunosorbent assays (ELISAs) were performed to evaluate cell invasion, epithelial-mesenchymal transition (EMT) and activation of related pathways after treatment with FTY720. The effect of FTY720 was also evaluated in vivo in a xenograft model.

RESULTS
We found that FTY720 inhibited the proliferation, invasion and metastasis of sacral chordoma cells (P < 0.01). FTY720 also inhibited the proliferation of tumour cells in a xenograft model using sacral chordoma cell lines (P < 0.01). The mechanism was related to the EMT and apoptosis of chordoma cells and inactivation of IL-6/STAT3 signalling in vitro and in vivo.

CONCLUSIONS
Our findings indicate that FTY720 may be an effective therapeutic agent against chordoma. These findings suggest that FTY720 is a novel agent that can treat locally advanced and metastatic chordoma.

Wang|Jiaqi|J| Hu|Wenhao|W| Du|Xiaowen|X| Sun|Ying|Y| Han|Shuai|S| Tu|Guanjun|G|

proliferation
epithelial-mesenchymal transition
sacral chordoma
IL-6/STAT3 signaling
FTY720


Pro-Inflammatory and Pro-Fibrogenic Effects of Ionic and Particulate Arsenide and Indium-Containing Semiconductor Materials in the Murine Lung.

Abstract: We have recently shown that the toxicological potential of GaAs and InAs particulates in cells is size- and dissolution-dependent, tending to be more pronounced for nano- vs micron-sized particles. Whether the size-dependent dissolution and shedding of ionic III-V materials also apply to pulmonary exposure is unclear. While it has been demonstrated that micron-sized III-V particles, such as GaAs and InAs, are capable of inducing hazardous pulmonary effects in an occupational setting as well as in animal studies, the effect of submicron particles (e.g., the removal of asperities during processing of semiconductor wafers) is unclear. We used cytokine profiling to compare the pro-inflammatory effects of micron- and nanoscale GaAs and InAs particulates in cells as well as the murine lung 40 h and 21 days after oropharyngeal aspiration. Use of cytokine array technology in macrophage and epithelial cell cultures demonstrated a proportionally higher increase in the levels of matrix metalloproteinase inducer (EMMPRIN), macrophage migration inhibitory factor (MIF), and interleukin 1β (IL-1β) by nanosized (n) GaAs and n-InAs as well as As(III). n-GaAs and n-InAs also triggered higher neutrophil counts in the bronchoalveolar lavage fluid (BALF) of mice than micronscale particles 40 h post-aspiration, along with increased production of EMMPRIN and MIF. In contrast, in animals sacrificed 21 days after exposure, only n-InAs induced fibrotic lung changes as determined by increased lung collagen as well as increased levels of TGF-β1 and PDGF-AA in the BALF. A similar trend was seen for EMMPRIN and matrix metallopeptidase (MMP-9) levels in the BALF. Nano- and micron-GaAs had negligible subacute effects. Importantly, the difference between the 40 h and 21 days data appears to be biopersistence of n-InAs, as demonstrated by ICP-OES analysis of lung tissue. Interestingly, an ionic form of In, InCl3, also showed pro-fibrogenic effects due to the formation of insoluble In(OH)3 nanostructures. All considered, these data indicate that while nanoscale particles exhibit increased pro-inflammatory effects in the lung, most effects are transient, except for n-InAs and insoluble InCl3 species that are biopersistent and trigger pro-fibrotic effects. These results are of potential importance for the understanding the occupational health effects of III-V particulates.

Jiang|Wen|W|0000-0003-2083-2069
Wang|Xiang|X|
Osborne|Olivia J|OJ|
Du|Yingjie|Y|
Chang|Chong Hyun|CH|
Liao|Yu-Pei|YP|
Sun|Bingbing|B|0000-0002-5444-5078
Jiang|Jinhong|J|
Ji|Zhaoxia|Z|
Li|Ruibin|R|0000-0001-6471-7658
Liu|Xiangsheng|X|
Lu|Jianqin|J|
Lin|Sijie|S|0000-0002-6970-8221
Meng|Huan|H|
Xia|Tian|T|
Nel|André E|AE|

III−V materials
lung fibrosis
lung inflammation
occupational disease
pro-inflammatory cytokine
size


Seniors' experiences of living in special housing accommodation.

Abstract: This article presents a hermeneutic phenomenological analysis of interview material in which 12 seniors living in Special Housing Accommodation (SHA) facilities reflect on the experience of living in such facilities. Of particular interest in the analysis is living in a SHA as a phenomenon. The finding shows that the phenomenon of lived experience in a SHA seems to be a state of ambiguity regarding one's existence, which is made up of several constituents (elements of meaning). The analysis contributes to the understanding of how the phenomenon of SHA living is coming into existence as a need, due to an individual's failing health; however, the SHA is not considered to be a true home. Accordingly, this has consequences to the subject position for the seniors in that they have to navigate between existing and not existing. The seniors learn to cope with living in the SHA by lowering their expectations of life and existence while the SHA provides the prerequisites for their existence. An implication for promoting care is to support the seniors to enable a full existence of life within SHA living.

Hellberg|Ingela|I|
Augustsson|Veronica|V|
Hellström Muhli|Ulla|U|

Seniors
lived experience
ambiguity of existence
lifeworld
residential living


The role of NTHi colonization and infection in the pathogenesis of neutrophilic asthma.

Abstract: Asthma is a complex heterogeneous disease. The neutrophilic subtypes of asthma are described as persistent, more severe and corticosteroid-resistant, with higher hospitalization and mortality rates, which seriously affect the lives of asthmatic patients. With the development of high-throughput sequencing technology, an increasing amount of evidence has shown that lower airway microbiome dysbiosis contributes to the exacerbation of asthma, especially neutrophilic asthma. Nontypeable Haemophilus influenzae is normally found in the upper respiratory tract of healthy adults and is one of the most common strains in the lower respiratory tract of neutrophilic asthma patients, in whom its presence is related to the occurrence of corticosteroid resistance. To understand the pathogenic mechanism by which nontypeable Haemophilus influenzae colonization leads to the progression of neutrophilic asthma, we reviewed the previous literature on nontypeable Haemophilus influenzae colonization and subsequent aggravation of neutrophilic asthma and corticosteroid resistance. We discussed nontypeable Haemophilus influenzae as a potential therapeutic target to prevent the progression of neutrophilic asthma.

Nontypeable Haemophilus influenzae (NTHi)


Acute ischemic stroke in a trauma cohort: Incidence and diagnostic challenges.

Abstract:
INTRODUCTION
Diagnosis of acute ischemic stroke is critical for acute intervention. Its diagnosis may be obscured in trauma patients due to confounding injuries. We report its incidence in trauma patients following their presentation at our institution.

METHODS
Electronic charts of all acute trauma patients presenting to a designated level 1 trauma center emergency department between September 2012-November 2015 were screened and included in the study if they had a discharge diagnosis of acute ischemic stroke. Patient data were reviewed to identify the presence of neurologic deficit on initial triage, imaging type obtained (intracranial or extracranial) and time to diagnosis of stroke.

RESULTS
Of 192 trauma patients screened, 11 were found to have acute ischemic stroke (5.7%). Patients were generally young (median age, 49 years) and predominantly males (n = 8). Presentation after vehicular crash was most frequent (n = 8 or 73%). Patients had predominantly skeletal injuries (n = 8 or 73%). Initial workup involved vascular imaging below the neck (n = 9), while only one had intracranial vascular imaging. When patients underwent cervicocranial vascular imaging, 64% (n = 7) had findings explaining the etiology of their stroke. None of the patients was diagnosed with acute ischemic stroke on admission. Its diagnosis was delayed by an average 1.8 days following presentation.

CONCLUSIONS
Acute ischemic stroke in trauma patients was a frequent diagnosis albeit with delay. Routine craniocervical vascular imaging at the time of presentation could potentially facilitate early diagnosis. A prospective study with routine craniocervical vascular imaging in trauma patients will be needed to further explore this hypothesis.

Yeboah|Kevin|K|
Bodhit|Aakash|A|
Al Balushi|Ali|A|
Krause|Erik|E|
Kumar|Abhay|A|


Large Metastatic Cardiac Tumor from Ascending Colon Cancer with Autopsy.

Abstract: A metastatic cardiac tumor from colon cancer is an exceedingly rare clinical feature associated with a poor prognosis without therapeutic intervention; however, such cases may be frequently encountered in clinical practice, especially among the elderly. We report a case of synchronous double cancer of the prostate and ascending colon with metastases to multiple organs, including a large cardiac tumor. A 71-year-old Japanese man had prostate cancer with neck and para-aortic metastasis. He visited our hospital with complaints of fatigue and a positive fecal occult blood test result. Colonoscopy findings revealed the presence of a tumor in the ascending colon, and contrast-enhanced CT revealed a tumor in the heart, which was possibly due to metastasis from the ascending colon. The patient received palliative care and declined anticancer treatment. He died due to respiratory failure 3 months after the first diagnosis but did not show critical arrhythmia until death. Autopsy revealed the presence of a large mass in the right ventricle with tumor embolism of the right coronary artery. The cardiac mass was pathologically consistent with metastasis from the colon. In case of colorectal cancer with cardiac metastasis involving poor prognosis or performance status, best supportive care without any therapeutic intervention could be the optimal treatment for the quality of the remaining time.

Tomiyama|Takashi|T| Shijimaya|Takuya|T| Sano|Yasuki|Y| Kobayashi|Sanshiro|S| Fukui|Toshiro|T| Ishida|Mitsuaki|M| Naganuma|Makoto|M|

Colon cancer
Autopsy
Palliative care
Heart ventricles
Neoplasm metastasis


A Case Report of Severe Corneal Toxicity following 0.5% Topical Moxifloxacin Use.

Abstract: Moxifloxacin is a widely used topical antibiotic in various bacterial infections of the eye. Its safety and efficacy have been proved by many studies. We report a case of a rare adverse effect following its use. A 10-year-old female who had presented with acute bacterial conjunctivitis in both eyes with no corneal involvement was started on preservative-free 0.5% topical moxifloxacin four times a day. The child developed a severe form of corneal toxicity in both eyes with circumcorneal congestion and corneal edema following its use. The child's visual acuity had dropped from 20/20 to 20/400 in both the eyes. Topical moxifloxacin was discontinued, following which the cornea cleared dramatically and the visual acuity became normal. This case indicates that though rare, topical moxifloxacin can cause severe keratitis and that more studies need to be conducted to evaluate its safety.

Vignesh|A P|AP|
Srinivasan|Renuka|R|
Karanth|Swathi|S|

Topical moxifloxacin
Keratitis
Fluoroquinolones


Correlation of concentrations of high-sensitivity troponin T and high-sensitivity C-reactive protein with plaque progression as measured by CT coronary angiography.

Abstract:
BACKGROUND
Elevated levels of inflammatory biomarkers are associated with increased cardiovascular morbidity and mortality.

OBJECTIVE
We sought to determine whether elevated concentrations of high-sensitivity troponin T (hs-TnT) and high-sensitivity C-reactive protein (hs-CRP) predict progression of coronary artery disease (CAD) as determined by coronary CT angiography (coronary CTA).

METHODS
Patients presenting to the emergency department with acute chest pain who initially showed no evidence of an acute coronary syndrome underwent baseline and follow-up coronary CTA (median follow-up, 23.9 months) using identical acquisition and reconstruction parameters. Coronary CTA data of each major coronary artery were co-registered. Cross-sections were assessed for the presence of calcified and noncalcified plaques. Progression of atherosclerotic plaque and change of plaque composition from noncalcified to calcified plaque was evaluated and correlated to levels of hs-TnT and hs-CRP at the time of the baseline CT.

RESULTS
Fifty-four patients (mean age, 54.1 years; 59% male) were included, and 6775 cross-sections were compared. CAD was detected in 12.2 ± 21.2 cross-sections per patient at baseline. Prevalence of calcified plaque increased by 1.5 ± 2.4 slices per patient (P < .0001) over the follow-up period. On average, 1.6 ± 3.6 slices with new noncalcified plaque were found per patient (P < .0001) and 0.7 ± 1.7 slices with pre-existing noncalcified plaque had progressed to calcified plaque (P < .0001). After multivariate adjustment, change of overall CAD burden was predicted by baseline hs-TnT and hs-CRP (r = 0.29; P = .039 and r = 0.40; P = .004). Change of plaque composition was associated with baseline hs-TnT (r = 0.29; P = .03).

CONCLUSION
Concentrations of hs-TnT and hs-CRP are weakly associated with a significant increase in CAD burden and change in plaque composition over 24 months independent of baseline risk factors.

Seifarth|Harald|H|
Schlett|Christopher L|CL|
Lehman|Sam J|SJ|
Bamberg|Fabian|F|
Donnelly|Patrick|P|
Januzzi|James L|JL|
Koenig|Wolfgang|W|
Truong|Quynh A|QA|
Hoffmann|Udo|U|

Plaque progression
Coronary artery disease
Coronary CT angiography
Cardiac biomarker
Coronary atherosclerotic plaque


Removal of aqueous cyanide with strongly basic ion-exchange resin.

Abstract: The removal of cyanide (CN-) from aqueous solutions using a strongly basic ion-exchange resin, Purolite A-250, was investigated. The effects of contact time, initial CN- concentration, pH, temperature, resin dosage, agitation speed, and particle size distribution on the removal of CN- were examined. The adsorption equilibrium data fitted the Langmuir isotherm very well. The maximum CN- adsorption capacity of Purolite A-250 was found to be 44 mg CN- g(-1) resin. More than 90% CN- adsorption was achieved for most CN- solutions (50, 100, and 200 mg CN- L(-1)) with a resin dose of 2 g L(-1). The equilibrium time was ∼20 min, optimum pH was 10.0-10.5, and optimum agitation speed was 150 rpm. An increase in adsorption of CN- with increasing resin dosage was observed. Adsorption of CN- by the resin was marginally affected (maximum 4% variation) within an environmentally relevant temperature range of 20-50 °C. Fixed-bed column (20.5 mm internal diameters) experiments were performed to investigate the effects of resin bed depth and influent flow rate on breakthrough behaviour. Breakthrough occurred in 5 min for 0.60 cm bed depth while it was 340 min for 5.40 cm bed depth. Adsorption capacity was 25.5 mg CN- g(-1) for 5 mL min(-1) flow rate and 3.9 mg CN- g(-1) for 20 mL min(-1) flow rate. The research has established that the resin can be effectively used for CN- removal from aqueous solutions.

Simsek|Halis|H|
Kobya|Mehmet|M|
Khan|Eakalak|E|
Bezbaruah|Achintya N|AN|

cyanide
ion-exchange resin
adsorption
isotherms
industrial pollution control


The Application of the Principles of Responsible AI on Social Media Marketing for Digital Health.

Abstract: Social media enables medical professionals and authorities to share, disseminate, monitor, and manage health-related information digitally through online communities such as Twitter and Facebook. Simultaneously, artificial intelligence (AI) powered social media offers digital capabilities for organizations to select, screen, detect and predict problems with possible solutions through digital health data. Both the patients and healthcare professionals have benefited from such improvements. However, arising ethical concerns related to the use of AI raised by stakeholders need scrutiny which could help organizations obtain trust, minimize privacy invasion, and eventually facilitate the responsible success of AI-enabled social media operations. This paper examines the impact of responsible AI on businesses using insights from analysis of 25 in-depth interviews of health care professionals. The exploratory analysis conducted revealed that abiding by the responsible AI principles can allow healthcare businesses to better take advantage of the improved effectiveness of their social media marketing initiatives with their users. The analysis is further used to offer research propositions and conclusions, and the contributions and limitations of the study have been discussed.

Responsible AI
Social media marketing
Digital health
Consumer trust theory
Information sharing theory
Technology acceptance model


Information fusion and multi-classifier system for miner fatigue recognition in plateau environments based on electrocardiography and electromyography signals.

Abstract:
BACKGROUND AND OBJECTIVE
Human factors are important contributors to accidents, especially human error induced by fatigue. In this study, field tests and analyses were conducted on physiological indexes extracted from electrocardiography (ECG) and electromyography (EMG) signals in miners working under the extreme conditions of a plateau environment. To provide insights into models for fatigue classification and recognition based on machine learning, multi-modal feature information fusion and miner fatigue identification based on ECG and EMG signals as physiological indicators were studied.

METHODS
Fifty-five miners were randomly selected as field test subjects, and characteristic signals were extracted from 110 groups of ECG and EMG signals as the basic signals for fatigue analysis. We conducted principal component analysis (PCA) and grey relational analysis (GRA) on the measurement indicators. Support vector machine (SVM), random forest (RF) and extreme gradient boosting (XG-Boost) machine learning models were used for fatigue classification based on multi-modal information fusion. The area under the receiver operating characteristic (ROC) curve and the confusion matrix were used to evaluate the performance of the recognition models.

RESULTS
The ECG and EMG signals showed obvious changes with fatigue. The results of fatigue model identification showed that PCA feature fusion was superior to GRA feature fusion for all three machine learning approaches, and XG-Boost achieved the best performance, with a recognition accuracy of 89.47%, a sensitivity and specificity of 100%, and an AUC of 0.90. The SVM model also showed good recognition performance (89.47% accuracy, AUC=0.89). The worst performance was that of the RF model, with a recognition accuracy of only 78.95%.

CONCLUSIONS
This study shows that the physiological indexes of ECG and EMG exhibit obvious, regular changes with fatigue and that it is feasible to use SVM, RF and XG-Boost models for miner fatigue identification. The PCA fusion technique can improve the identification accuracy more than the GRA method. XG-Boost classification yields the best accuracy and robustness. This study can serve as a reference for clinical research on the identification of human fatigue at high altitudes and for the clinical study of acute mountain sickness and human acclimatization to high altitudes.

Chen|Shoukun|S| Xu|Kaili|K| Yao|Xiwen|X| Ge|Ji|J| Li|Li|L| Zhu|Siyi|S| Li|Zhengrong|Z|

Fatigue recognition
Electrocardiography (ECG)
Electromyography (EMG)
Machine learning
Multi-modal information fusion
Physiological signals


Active Inference and Cooperative Communication: An Ecological Alternative to the Alignment View.

Abstract: We present and contrast two accounts of cooperative communication, both based on Active Inference, a framework that unifies biological and cognitive processes. The mental alignment account, defended in Vasil et al., takes the function of cooperative communication to be the alignment of the interlocutor's mental states, and cooperative communicative behavior to be driven by an evolutionarily selected adaptive prior belief favoring the selection of action policies that promote such an alignment. We argue that the mental alignment account should be rejected because it neglects the action-oriented nature of cooperative communication, which skews its view of the dynamics of communicative interaction. We introduce our own conception of cooperative communication, inspired by a more radical ecological interpretation of the active inference framework. Cooperative communication, on our ecological conception, serves to guide and constrain the dynamics of the cooperative interaction via the construction and restructuring of shared fields of affordances, in order to reach the local goals of the joint actions in which episodes of cooperative communication are embedded. We argue that our ecological conception provides a better theoretical standpoint to account for the action-oriented nature of cooperative communication in the active inference framework.

active inference
cooperative communication
communication
affordance
ecological psychology
language


μ-Opioid receptor activation modulates CA3-to-CA1 gamma oscillation phase-coupling.

Abstract: In the intact brain, hippocampal area CA1 alternates between low-frequency gamma oscillations (γ), phase-locked to low-frequency γ in CA3, and high-frequency γ, phase-locked to γ in the medial entorhinal cortex. In hippocampal slices, γ in CA1 is phase-locked to CA3 low-frequency γ. However, when Schaffer collaterals are cut, CA1 can generate its own high-frequency γ. Here we test whether (un)coupling of CA1 γ from CA3 γ can be caused by μ-opioid receptor (MOR) modulation. In CA1 minislices isolated from rat ventral hippocampus slices, MOR activation by DAMGO reduced the dominant frequency of intrinsic fast γ, induced by carbachol. In intact slices, DAMGO strongly reduced the dominant frequency of CA3 slow γ, but did not affect γ power consistently. DAMGO suppressed the phase coupling of CA1 γ to CA3 slow γ and increased the power of CA1 intrinsic fast γ, but not in the presence of the MOR antagonist CTAP. The benzodiazepine zolpidem and local application of DAMGO to CA3 both mimicked the reduction in dominant frequency of CA3 slow γ, but did not reduce the phase coupling. Local application of DAMGO to CA1 reduced phase coupling. These results suggest that MOR-expressing CA1 interneurons, feed-forwardly activated by Schaffer collaterals, are responsible for the phase coupling between CA3 γ and CA1 γ. Modulating their activity may switch the CA1 network between low-frequency γ and high-frequency γ, controlling the information flow between CA1 and CA3 or medial entorhinal cortex respectively.

Zhang|Yujiao|Y| Ahmed|Sanya|S| Neagu|Georgiana|G| Wang|Yali|Y| Li|Zhenyi|Z| Wen|Jianbin|J| Liu|Chunjie|C| Vreugdenhil|Martin|M|

DAMGO, [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin

P P P P P P M M M M M M M M M M M M M M M R M


Circular RNA circUbe2k promotes hepatic fibrosis via sponging miR-149-5p/TGF-β2 axis.

Abstract: Abundant regulatory genes and complex circuits involving non-coding RNAs (ncRNAs) monitor the formation and development of hepatic fibrosis (HF). Circular RNAs (circRNAs) are a class of RNAs generated from protein coding genes by back-splicing, playing crucial roles in various pathological processes, including HF. However, little is known about mechanisms of action of circRNAs, let alone in HF. In this study, we found circUbe2k enhanced in CCl4 -induced HF mice and LX-2 cells stimulated with TGF-β1, regulating the development of HF. Restraining the expression of circUbe2k inhibited α-SMA and Col1α1 expression in CCl4 -induced HF mice and in LX-2 cells stimulated with TGF-β1. Furthermore, inhibiting circUbe2k expression reduced hepatic stellate cells (HSCs) activation and proliferation in vivo and in vitro. Mechanistically, we demonstrated a direct interaction between circUbe2k and miR-149-5p, which results in the modulation of TGF-β2 expressions. Together, circUbe2k may act as a "catalyst" of HSCs activation and HF through the circUbe2k/miR-149-5p/TGF-β2 axis. Our results provide unprecedented evidence for a significant role for circUbe2k to serve as a potential biomarker for HF therapy.

Zhu|Sai|S| Chen|Xin|X| Wang|Jia-Nan|JN| Xu|Jin-Jin|JJ| Wang|Ao|A| Li|Juan-Juan|JJ| Wu|Sha|S| Wu|Yuan-Yuan|YY| Li|Xiao-Feng|XF| Huang|Cheng|C| Li|Jun|J|

D053781:Transforming Growth Factor beta2


Effects of a multifaceted intervention in psychogeriatric patients: one-year prospective study.

Abstract:
OBJECTIVES
The aetiology of behavioural and psychological symptoms (BPSD) could be related to inadequate treatment in patients with dementia. The aim of this study was to determine how a multifaceted intervention based on a medication review and multidisciplinary follow-up could improve treatment and minimise risk in these patients.

METHODS
A prospective interventional study was undertaken between July 2015 and July 2016 of patients with dementia admitted to control BPSD. Patients with previous psychiatric illness or palliative care were excluded. Prescription information was obtained from Aegerus and the Catalonia clinical record HC3. The intervention was conducted by a multidisciplinary team. The Medication Appropriateness Index (MAI) was used to assess the intervention.

RESULTS
65 patients (60% women, mean age 84.9±6.7 years) with mild-moderate cognitive impairment (mean 4.5±1.8), moderate-severe functional dependence (mean 43.8±23.9) and a high prevalence of geriatric syndromes and comorbidity were included in the study. 87.7% of the patients were taking ≥5 drugs (mean 9.0±3.1) and 38.5% were taking ≥10. Patients presented with BPSD values of 1.9±0.8 at admission. Common symptoms prompting admission were agitation (47.7%) and irritability (43.1%). A total of 175 drug-related problems (DRPs) were detected (2.97 per patient). Significant differences (p<0.001) were found between the MAI score at admission (4±4.6) and post-intervention (0.5±2.6). Most prevalent MAI criteria were related to interactions (40%), dosage (38.5%) and duplication (26.2%). 55 patients (84.6%) were taking anticholinergic drugs at admission (2.6±1.2 anticholinergic drugs per patient), and the post-intervention reduction was significant (p<0.016).

CONCLUSIONS
The balance between effective treatment and safety is complex in these patients. Medication review in interdisciplinary teams is an essential component to optimise interventions and assessment of safety.

D064420:Drug-Related Side Effects and Adverse Reactions

clinical pharmacy
drug safety
geriatric medicine
interdisciplinar
phychogeriatry


BRCA1 and BRCA2 pathogenic variant carriers and endometrial cancer risk: A cohort study.

Abstract:
BACKGROUND
An association between BRCA pathogenic variants and an increased endometrial cancer risk, specifically serous-like endometrial cancer, has been postulated but remains unproven, particularly for BRCA2 carriers. Mechanistic evidence is lacking, and any link may be related to tamoxifen exposure or testing bias. Hysterectomy during risk-reducing bilateral salpingo-oophorectomy is, therefore, of uncertain benefit. Data from a large, prospective cohort will be informative.

METHODS
Data on UK BRCA pathogenic variant carriers were interrogated for endometrial cancer diagnoses. Standardised incidence ratios (SIRs) were calculated in four distinct cohorts using national endometrial cancer rates; either from 1/1/1980 or age 20, prospectively from date of personal pathogenic variant report, date of family pathogenic variant report or date of risk-reducing salpingo-oophorectomy. Somatic BRCA sequencing of 15 serous endometrial cancers was performed to detect pathogenic variants.

RESULTS
Fourteen cases of endometrial cancer were identified in 2609 women (1350 BRCA1 and 1259 BRCA2), of which two were prospectively diagnosed. No significant increase in either overall or serous-like endometrial cancer risk was identified in any of the cohorts examined (SIR = 1.70, 95% confidence interval = 0.74-3.33; no cases of serous endometrial cancer diagnosed). Results were unaffected by the BRCA gene affected, previous breast cancer or tamoxifen use. No BRCA pathogenic variants were detected in any of the serous endometrial cancers tested.

CONCLUSIONS
Women with a BRCA pathogenic variant do not appear to have a significant increased risk of all-type or serous-like endometrial cancer compared with the general population. These data provide some reassurance that hysterectomy is unlikely to be of significant benefit if performed solely as a preventive measure.

Kitson|Sarah J|SJ|
Bafligil|Cemsel|C|
Ryan|Neil A J|NAJ|
Lalloo|Fiona|F|
Woodward|Emma R|ER|
Clayton|Richard D|RD|
Edmondson|Richard J|RJ|
Bolton|James|J|
Crosbie|Emma J|EJ|
Evans|D Gareth|DG|


Direct inversion of the iterative subspace with contracted planewave basis functions.

Abstract: Ways to reduce the computational cost of periodic electronic structure calculations by using basis functions corresponding to linear combinations of planewaves have been examined recently. These contracted planewave (CPW) basis functions correspond to Fourier series representations of atom-centered basis functions, and thus provide access to some beneficial properties of planewave (PW) and localized basis functions. This study reports the development and assessment of a direct inversion of the iterative subspace (DIIS) method that employs unique properties of CPW basis functions to efficiently converge electronic wavefunctions. This method relies on access to a PW-based representation of the electronic structure to provide a means of efficiently evaluating matrix-vector products involving the application of the Fock matrix to the occupied molecular orbitals. These matrix-vector products are transformed into a form permitting the use of direct diagonalization techniques and DIIS methods typically employed with atom-centered basis sets. The abilities of this method are assessed through periodic Hartree-Fock calculations of a range of molecules and solid-state systems. The results show that the method reported in this study is approximately five times faster than CPW-based calculations in which the entire Fock matrix is calculated. This method is also found to be weakly dependent upon the size of the basis set, thus permitting the use of larger CPW basis sets to increase variational flexibility with a minor impact on computational performance. © 2018 Wiley Periodicals, Inc.


Structural insight into the XTACC3/XMAP215 interaction from CD and NMR studies on model peptides.

Abstract: TACC3 is a centrosomal adaptor protein that plays important roles during mitotic spindle assembly. It interacts with chTOG/XMAP215, which catalyzes the addition of tubulin dimers during microtubule growth. A 3D coiled-coil model for this interaction is available but the structural details are not well described. To characterize this interaction at atomic resolution, we have designed a simplified version of the system based on small peptides. Four different peptides have been studied by circular dichroism and nuclear magnetic resonance both singly and in all possible combinations; namely, five peptide pairs and two trios. In cosolvents, all single peptides tend to adopt helical conformations resembling those of the full-length protein. However, neither the single peptides nor pairs of peptides form coiled coils. We show that the simultaneous presence of all preformed helices is a prerequisite for binding. The simplest 3D model for the interaction, based on the NMR results, is proposed. Interestingly, the peptide's structure remains unaffected by mutations at essential positions for TACC3 activity. This suggests that the lack of interaction of this TACC3 mutant with XMAP does not correlate with changes in the protein structure and that specific interactions are likely responsible for the interaction and stability of the complex.

D019906:Nuclear Magnetic Resonance, Biomolecular

D054730:Protein Interaction Domains and Motifs

XTACC3 XMAP215 interactions CD NMR peptides


Public exposure due to external gamma background radiation in boundary areas of Iran.

Abstract: A monitoring program in boundary areas of a country is an appropriate way to indicate the level of public exposure. In this research, gamma background radiation was measured using TL dosimeters at 12 boundary areas as well as in the capital city of Iran during the period 2010 to 2011. The measurements were carried out in semi-annual time intervals from January to June and July to December in each year. The maximum average dose equivalent value measured was approximately 70 μSv/month for Tehran city. Also, the average dose values obtained were less than 40 μSv/month for all the cities located at the sea level except that of high level natural radiation area of Ramsar, and more than 55 μSv/month for the higher elevation cities. The public exposure due to ambient gamma dose equivalent in Iran is within the levels reported by UNSCEAR.

Pooya|S M Hosseini|SM|
Dashtipour|M R|MR|
Enferadi|A|A|
Orouji|T|T|

D001417:Background Radiation
D005720:Gamma Rays
D006801:Humans
D007492:Iran
D011829:Radiation Dosage
D000069079:Radiation Exposure
D011834:Radiation Monitoring
D013819:Thermoluminescent Dosimetry

Public exposure
Gamma
Background
Radiation
Cosmic ray
TLD


Dental pulp stem cells immobilized in alginate microspheres for applications in bone tissue engineering.

Abstract:
AIM
To immobilize dental pulp stem cells (DPSC) in alginate microspheres and to determine cell viability, proliferation, stem cell characteristics and osteogenic potential of the immobilized DPSCs.

METHODOLOGY
Human DPSCs isolated from the dental pulp were immobilized in 1% w/v alginate microspheres. Viability and proliferation of immobilized DPSCs were determined by trypan blue and MTT assay, respectively. Stem cell characteristics of DPSCs post immobilization were verified by labelling the cells with CD73 and CD90. Osteogenic potential of immobilized DPSCs was assessed by the presence of osteocalcin. Alizarin red staining and O-cresolphthalein complexone method confirmed and quantified calcium deposition. A final reverse transcriptase PCR evaluated the expression of osteogenic markers - ALP, Runx-2 and OCN.

RESULTS
More than 80% of immobilized DPSCs were viable throughout the 3-week study. Proliferation appeared controlled and consistent unlike DPSCs in the control group. Presence of CD73 and CD90 markers confirmed the stem cell nature of immobilized DPSCs. The presence of osteocalcin, an osteoblastic marker, was confirmed in the microspheres on day 21. Mineralization assays showed high calcium deposition indicating elevated osteogenic potential of immobilized DPSCs. Osteogenic genes- ALP, Runx-2 and OCN were also upregulated in immobilized DPSCs. Surprisingly, immobilized DPSCs in the control group cultured in conventional stem cell media showed upregulation of osteogenic genes and expressed osteocalcin.

CONCLUSION
Dental pulp stem cells immobilized in alginate hydrogels exhibit enhanced osteogenic potential while maintaining high cell viability both of which are fundamental for bone tissue regeneration.

Kanafi|M M|MM|
Ramesh|A|A|
Gupta|P K|PK|
Bhonde|R R|RR|

D020133:Reverse Transcriptase Polymerase Chain Reaction

dental pulp stem cells
immobilization
microspheres
bone tissue engineering
alginate hydrogels


"Property Phase Diagrams" for Compound Semiconductors through Data Mining.

Abstract: This paper highlights the capability of materials informatics to recreate "property phase diagrams" from an elemental level using electronic and crystal structure properties. A judicious selection of existing data mining techniques, such as Principal Component Analysis, Partial Least Squares Regression, and Correlated Function Expansion, are linked synergistically to predict bandgap and lattice parameters for different stoichiometries of GaIn1-AsSb1-, starting from fundamental elemental descriptors. In particular, five such elemental descriptors, extracted from within a database of highly correlated descriptors, are shown to collectively capture the widely studied "bowing" of energy bandgaps seen in compound semiconductors. This is the first such demonstration, to our knowledge, of establishing relationship between discrete elemental descriptors and bandgap bowing, whose underpinning lies in the fundamentals of solid solution thermodyanamics.

phase diagrams
data mining
materials informatics
III–V materials
bandgap engineering
crystal stoichiometry
high dimensional data
semiconductor compounds
structure-property relationships


Prescreening clinical trial volunteers using an online personality questionnaire.

Abstract:
Background
The cost of a clinical trial is affected by the efficiency of participant recruitment. It would be desirable to create a prescreening method that identifies appropriate candidates for full screening, in order to prevent inconvenience for both trial and volunteers. This study presents an online prescreening tool for this purpose.

Methods
In order to facilitate recruitment of 24 individuals meeting the criteria for generalized anxiety disorder to a pharmacological functional magnetic resonance imaging trial, we created an online personality questionnaire that generated a personality profile for each respondent and screened for the trial's basic criteria.

Results
Our online platform screened 6,293 people for anxious personality traits in 1 year. A total of 862 eligible individuals were identified through this route, each of whom automatically received an email invitation to contact the study team for further telephone screening, if interested. Of those, 266 individuals contacted the team and 173 were telephone screened, with 53 attending the study site for medical checks. Twenty-eight individuals were fully eligible, and 24 completed the trial. This permitted completion on time and on budget.

Conclusion
Our online prescreening personality questionnaire platform did not remove the need for telephone screening or onsite medical checks, but increased the efficiency of recruitment through noninvasive identification of those meeting key requirements. Thus, our platform is a useful recruitment technique for clinical trials and is time-saving for both the trial and potential participants.

Patrick|Fiona|F|
Young|Allan H|AH|
Williams|Steven Cr|SC|
Perkins|Adam M|AM|

prescreening
clinical trials
personality
recruitment
mental health


Assessment of dual-probe Her-2 fluorescent in situ hybridization in breast cancer by the 2013 ASCO/CAP guidelines produces more equivocal results than that by the 2007 ASCO/CAP guidelines.

Abstract: Dual-probe fluorescence in situ hybridization (D-FISH) is a widely accepted method to determine the gene amplification status of human epidermal growth factor receptor 2 (Her-2). In 2013, the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) updated the guidelines on the Her-2 testing for invasive breast cancer (BCa). The interpretation criteria for D-FISH changed accordingly. In this study, we compared the Her-2 FISH statuses based on the 2013 and 2007 ASCO/CAP guidelines in 1931 cases of BCa with Her-2 D-FISH testing at our hospital. We analyzed the clinicopathologic features of cases with equivocal results by the 2013 ASCO/CAP guidelines. Although the guideline update significantly improved the detection rate of Her-2 amplification, it also significantly increased the rate of equivocal results, posing a dilemma for clinical management. The equivocal results had a good reproducibility. The distribution of D-FISH-equivocal cases did not correlate with Her-2 status by immunohistochemistry, suggesting that Her-2 D-FISH equivocality may not reflect Her-2 overexpression. Compared with Her-2-negative cases by D-FISH, Her-2 D-FISH-equivocal cases had higher Ki67 expression, higher histological grade, more frequent lymph node metastasis, and lower estrogen receptor α expression, indicating a group of BCa with worse prognosis. The clinical significance of Her-2-equivocal results by D-FISH warrants further investigation.

Qian|Xiao-Long|XL|
Wen|Hannah Y|HY|
Yang|Yi-Ling|YL|
Gu|Feng|F|
Guo|Xiao-Jing|XJ|
Liu|Fang-Fang|FF|
Zhang|Lanjing|L|
Zhang|Xin-Min|XM|
Fu|Li|L|

D017404:In Situ Hybridization, Fluorescence


Critical role of c-jun N-terminal protein kinase in promoting mitochondrial dysfunction and acute liver injury.

Abstract: The mechanism by which c-Jun N-terminal protein kinase (JNK) promotes tissue injury is poorly understood. Thus we aimed at studying the roles of JNK and its phospho-target proteins in mouse models of acute liver injury. Young male mice were exposed to a single dose of CCl4 (50mg/kg, IP) and euthanized at different time points. Liver histology, blood alanine aminotransferase, and other enzyme activities were measured in CCl4-exposed mice without or with the highly-specific JNK inhibitors. Phosphoproteins were purified from control or CCl4-exposed mice and analyzed by differential mass-spectrometry followed by further characterizations of immunoprecipitation and activity measurements. JNK was activated within 1h while liver damage was maximal at 24h post-CCl4 injection. Markedly increased phosphorylation of many mitochondrial proteins was observed between 1 and 8h following CCl4 exposure. Pretreatment with the selective JNK inhibitor SU3327 or the mitochondria-targeted antioxidant mito-TEMPO markedly reduced the levels of p-JNK, mitochondrial phosphoproteins and liver damage in CCl4-exposed mice. Differential proteomic analysis identified many phosphorylated mitochondrial proteins involved in anti-oxidant defense, electron transfer, energy supply, fatty acid oxidation, etc. Aldehyde dehydrogenase, NADH-ubiquinone oxidoreductase, and α-ketoglutarate dehydrogenase were phosphorylated in CCl4-exposed mice but dephosphorylated after SU3327 pretreatment. Consistently, the suppressed activities of these enzymes were restored by SU3327 pretreatment in CCl4-exposed mice. These data provide a novel mechanism by which JNK, rapidly activated by CCl4, promotes mitochondrial dysfunction and acute hepatotoxicity through robust phosphorylation of numerous mitochondrial proteins.

Jang|Sehwan|S|
Yu|Li-Rong|LR|
Abdelmegeed|Mohamed A|MA|
Gao|Yuan|Y|
Banerjee|Atrayee|A|
Song|Byoung-Joon|BJ|

D048031:JNK Mitogen-Activated Protein Kinases

Acute liver injury
JNK
Differential proteomics
Carbon tetrachloride
Mitochondria
Protein phosphorylation


Preventive psychiatry: Concept appraisal and future directions.

Abstract: Preventive psychiatry is a branch of psychiatry that aims at health promotion, protection from specific mental illnesses, early diagnosis, effective treatment, disability limitation and rehabilitation. Prevention of neuropsychiatric illnesses as compared to other illnesses is particularly important as they run a chronic course and cause substantial disability. Preventive measures have been found to be effective in reducing incidence and disability in a wide range of mental illnesses such as depression, psychosis, anxiety and conduct disorders. The need of the hour is to translate advances in our understanding of mental illness into effective intervention programmes for the prevention of mental illness and the promotion of positive mental health.

Trivedi|Jitendra K|JK|
Tripathi|Adarsh|A|
Dhanasekaran|Saranya|S|
Moussaoui|Driss|D|

Preventive psychiatry
concepts
future directions
evidence-based interventions


A Preliminary Study of the Action of Virtosomes from Non-dividing Cells on Tumour Cell Replication in vitro and in vivo.

Abstract:
BACKGROUND
A DNA-RNA-lipoprotein complex, termed as virtosome, is released spontaneously from healthy human, other mammalian, avian, amphibian and plant cells in a regulated and energy-dependent manner. Studies on human and mouse lymphocytes, hepatocytes, NIH 3T3 cells and mouse tumour cell lines have shown that virtosomes may be acting as inter-cellular messengers. In particular, virtosomes from non-dividing cells blocked 3H-thymidine incorporation into DNA in tumour cell lines.

OBJECTIVE
Study of the effect of virtosomes on tumors "in vivo" and "in vitro".

METHODS AND RESULTS
The present study shows in vitro effects of virtosomes isolated from rat liver, essentially nondividing cell populations, on cultures of healthy smooth muscle cells (SMC), human umbilical vein endothelial cells (HUVEC), human fibroblasts (h-fibroblasts) and mouse embryonic fibroblasts (NIH-3T3) together with two tumour cell lines, human Duke's type B colorectal adenocarcinoma cells (SW480) and human connective tissue fibrosarcoma cells (HT1080). Multiplication of all cell lines was inhibited by the liver virtosomal preparation even with various dilutions of the extract (100 - 0.5%). In an in vivo study, tumours were initiated by subcutaneous injection of 1.0 x 106 DHD/K12-PROb cells in 6 weeks old male BIDX rats. Visible tumours (<1cm) appeared after 3 weeks and lung metastases after 8 weeks (80%). Virtosomes introduced via a tail vein on tumour initiation resulted in a reduction in tumour size and number.

CONCLUSION
Virtosomal preparation from a non-dividing cell population inhibited cell division, reduced tumour size and partially blocked metastasis.

Garcia-Arranz|Mariano|M| Garcia-Olmo|Damian|D| Vega-Clemente|Luz|L| Stroun|Maurice|M|

tumour cell replication
tumours
metastasis
Non-dividing cell virtosomes
mitotic count