NMDARs in neurological diseases: a potential therapeutic target.

Abstract: N-methyl-D-aspartate ionotropic glutamate receptor (NMDARs) is a ligand-gated ion channel that plays a critical role in excitatory neurotransmission, brain development, synaptic plasticity associated with memory formation, central sensitization during persistent pain, excitotoxicity and neurodegenerative diseases in the central nervous system (CNS). Within iGluRs, NMDA receptors have been the most actively investigated for their role in neurological diseases, especially neurodegenerative pathologies such as Alzheimer's and Parkinson's diseases. It has been demonstrated that excessive activation of NMDA receptors (NMDARs) plays a key role in mediating some aspects of synaptic dysfunction in several CNS disorders, so extensive research has been directed on the discovery of compounds that are able to reduce NMDARs activity. This review discusses the role of NMDARs on neurological pathologies and the possible therapeutic use of agents that target this receptor. Additionally, we delve into the role of NMDARs in Alzheimer's and Parkinson's diseases and the receptor antagonists that have been tested on in vivo models of these pathologies. Finally, we put into consideration the importance of antioxidants to counteract oxidative capacity of the signaling cascade in which NMDARs are involved.

Gonzalez|Janneth|J|
Jurado-Coronel|Juan Camilo|JC|
Ávila|Marcos Fidel|MF|
Sabogal|Angélica|A|
Capani|Francisco|F|
Barreto|George E|GE|

NMDARs
neurological diseases
Parkinson's disease
antagonist
antioxidants
Alzheimer's disease


Improved sanitation is associated with reduced child stunting amongst Indonesian children under 3 years of age.

Abstract: Growing evidence suggests that household sanitation is associated with child nutritional status in low- and middle-income countries. This paper examined whether household access to improved sanitation facilities and sources of drinking water was associated with stunting and anaemia amongst children aged 6-35 months of age in Indonesia. The sample for the analysis comprised 1,450 children aged 6-35 months who participated in the end-line survey of the maternal and young child nutrition security project in Asia, conducted in three selected districts in Indonesia. Logistic regression models were used to determine the association between household sanitation and water source, and stunting and anaemia. Approximately 26% and 56% of children 6-35 months of age were stunted and anaemic, respectively. Children living in a household with improved sanitation facilities had 29% reduced odds of being stunted compared with those in a household with unimproved sanitation facilities, after adjusting for potential confounders including child's age and gender, maternal education, and iron-folic acid supplementation, as well as household wealth status and source of drinking water (OR = 0.68, 95% CI:0.48-0.96). No association between household sanitation and childhood anaemia was observed. Source of drinking water was not associated with stunting or anaemia amongst children. There were no synergistic effects of household sanitation and water supply on stunting and anaemia. This suggests that efforts to improve household sanitation condition may need to be considered an essential, integral part of the programmatic responses by governments and development partners for the prevention of childhood nutritional status. Further randomised research is necessary to determine the causal link.

Rah|Jee H|JH|0000-0002-2524-4891
Sukotjo|Sri|S|
Badgaiyan|Nina|N|
Cronin|Aidan A|AA|
Torlesse|Harriet|H|

sanitation stunting Anaemia Indonesia WASH


Observing Tacting Increases Uninstructed Tacts in Children with Autism.

Abstract: The effects of observing an adult emitting tacts on children's rate of uninstructed (i.e., "spontaneous") tacts were examined in three children diagnosed with autism. Each participant was exposed to two conditions in four settings each: in condition 1, participants received 20 trials of teacher-initiated interactions in which the child was asked to tact 20 objects during 5 min. Condition 2 was identical to condition 1 except that the teacher also tacted 20 objects interspersed with the 20 tact trials. The number of uninstructed tacts was recorded in both conditions. Children emitted between 1.58 and 2.68 times more uninstructed tacts in condition 2 than in condition 1. These results indicate that teachers' emission of tacts increases the emission of uninstructed tacts in children with autism.

Pérez-González|Luis Antonio|LA|
Pastor|Ana|A|
Carnerero|José Julio|JJ|

Tacts
Uninstructed tacts
Autism
Induction
Language observing
Modeling
Spontaneous speech


Measurement of γ-H2AX foci, miRNA-101, and gene expression as a means to quantify radiation-absorbed dose in cancer patients who had undergone radiotherapy.

Abstract: Radiological accidents and nuclear terrorism pose an increased threat to members of the public who, following such an event, would need to be assessed for medical care by fast triage. Assay methods such as chromosome aberrations (CA), cytokinesis-block micronucleus (CBMN) and fluorescence in situ hybridization (FISH) techniques have been well established for dose estimation and their potential for handling more samples has also been proved with automation. However, culturing of lymphocytes is an inevitable step, which limits the potential of these markers for triage. In vitro analysis of gamma-H2AX (γ-H2AX), gene and microRNA (miRNA) markers do not require culturing of lymphocytes, and as such have been suggested as attractive tools for triage. Despite studies reporting in vitro dose-response curves, limited evidence is available evaluating the suitability of these assays in real situations. In this study, we have measured the absorbed dose using γ-H2AX, gene (GADD45A, FDXR, and CDKN1A) and miRNA-101 expression in blood samples of cancer patients (n = 20) who had undergone partial-body radiotherapy and compared with the derived equivalent whole-body doses (EWBD). The obtained results from all patients showed a significant (p < 0.05) increase of γ-H2AX foci in post-irradiated as compared to pre-irradiated samples. Moreover, estimated doses using γ-H2AX foci showed a correlation with the derived EWBD (r2 = 0.60, p = 0.0003) and was also shown to be dependent on the irradiated body volume. Consistent with γ-H2AX foci frequency, an increase in fold change expression of genes and miRNA-101 was observed. However, the estimated dose significantly varied among the subjects and showed poor correlation (r2 = 0.09, 0.04, 0.01 and 0.03 for GADD45A, FDXR, CDKN1A and miRNA-101, respectively) with EWBD. The overall results suggest that the established in vitro γ-H2AX assay is suitable for the detection of radiation exposure and can also provide an estimate of the dose in in vivo irradiated samples. The genes and miRNA-101 markers showed increased expression; nevertheless, there is a need for further improvements to measure doses accurately using these markers.

D050759:Cyclin-Dependent Kinase Inhibitor p21

D015972:Gene Expression Regulation, Neoplastic

γ-H2AX foci
Gene expression
Radiotherapy
MicroRNA
Biomarkers


Pulmonary safety of ophthalmic beta-blockers: a nationwide registry-based cohort study.

Abstract:
PURPOSE
Ophthalmic beta-blockers, used in the treatment of increased intraocular pressure, are known to cause pulmonary adverse effects. Few, if any, studies have quantified the extent of the problem in a real-life population. In this nationwide study, we assess the pulmonary safety of patients initiating treatment with ophthalmic beta-blockers.

METHODS
Using the Danish Nationwide Registries from 1995 to 2012, we identified all individuals aged 20-90 years who initiated monotherapy with an intraocular pressure-lowering drug, with or without concomitant obstructive pulmonary disease. Risks of (i) switching to another drug and (ii) new onset of obstructive pulmonary disease during a 90-day follow-up were examined by cumulative risk and logistic regression models adjusted for available covariates.

RESULTS
The cohort consisted of 97 463 individuals. Odds ratios for drug switch in individuals without concomitant obstructive pulmonary disease (n = 86 568) were as follows: 1.47 for beta-blockers (95% confidence interval (CI): 1.35-1.61; p < 0.001), 2.68 for parasympathomimetics (95% CI: 2.32-3.10; p < 0.001) and 4.80 for alfa-2-agonists (95% CI: 4.17-5.53; p < 0.001). Odds ratios in individuals with concomitant obstructive pulmonary disease (n = 10 895) were as follows: 2.61 for parasympathomimetics (95% CI: 1.83-3.72; p < 0.001), 2.96 for beta-blockers (95% CI: 2.31-3.78; p < 0.001) and 3.54 for alfa-2-agonists (95% CI: 2.56-4.88; p < 0.001). There was no significant association between treatment class and new onset of obstructive pulmonary disease (p = 0.30).

CONCLUSION
Ophthalmic beta-blockers were associated with an increased risk of drug switch. However, the absolute risk was very small. No increased risk of new onset of obstructive pulmonary disease was found. Our data suggest that more patients might be eligible for ophthalmic beta-blockers.

D029424:Pulmonary Disease, Chronic Obstructive

beta-blockers
intraocular pressure
adverse effects
obstructive pulmonary disease
glaucoma
timolol


Paediatric non-alcoholic Fatty liver disease: impact on patients and mothers' quality of life.

Abstract:
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is one of the causes of fatty liver in adults and is currently the primary form of chronic liver disease in children and adolescents. However, the psychological outcome (i.e. the behavioural problems that can in turn be related to psychiatric conditions, like anxiety and mood disorders, or lower quality of life) in children and adolescents suffering of NAFLD has not been extensively explored in the literature.

OBJECTIVES
The present study aims at evaluating the emotional and behavioural profile in children suffering from NAFLD and the quality of life in their mothers.

PATIENTS AND METHODS
A total of 57 children (18 females/39 males) with NAFLD were compared to 39 age-matched control children (25 females/14 males). All participants were submitted to the following psychological tools to assess behavior, mood, and anxiety: the Multidimensional Anxiety Scale for Children (MASC), the Child Behavior Checklist (CBCL), and the Children's Depression Inventory (CDI). Moreover, the mothers of 40 NAFLD and 39 control children completed the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire.

RESULTS
NAFLD children scored significantly higher as compared to control children in MASC (P = 0.001) and CDI total (P < 0.001) scales. The CBCL also revealed significantly higher scores for NAFLD children in total problems (P = 0.046), internalizing symptoms (P = 0.000) and somatic complaints (P < 0.001). The WHOQOL-BREF revealed significantly lower scores for the mothers of NAFLD children in the overall perception of the quality of life (P < 0.001), and in the "relationships" domain (P = 0.023).

CONCLUSIONS
Increased emotional and behavioural problems were detected in children with NAFLD as compared to healthy control children, together with an overall decrease in their mothers' quality of life. These results support the idea that these patients may benefit from a psychological intervention, ideally involving both children and parents, whose quality of life is likely negatively affected by this disease.

Mazzone|Luigi|L|
Postorino|Valentina|V|
De Peppo|Lavinia|L|
Della Corte|Claudia|C|
Lofino|Giuseppe|G|
Vassena|Lia|L|
Fatta|Laura|L|
Armando|Marco|M|
Bedogni|Giorgio|G|
Vicari|Stefano|S|
Nobili|Valerio|V|

Children
Adolescence
Anxiety
Depression
Chronic Disease


A pilot randomized controlled trial of a depression and disease management program delivered by phone.

Abstract:
BACKGROUND
Depression in medically ill patients occurs at twice the rate found in the general population. Though pharmacologic and psychotherapeutic interventions for depression are effective, response to treatment and access to care are barriers for this population. A multidimensional telehealth intervention was designed to focus on these barriers by delivering a phone based intervention that addressed managing one's illness and coping emotionally.

METHODS
Veterans with diabetes, hypertension, or chronic pain and depressive symptoms were randomized to one of three conditions: Usual Care (n=23), Illness Management Only (n=31), or Combined Psychotherapy and Illness Management (n=29). Those randomized to the Combined or Illness Management Only intervention group received 10 phone visits. Veterans in the Combined group received all aspects of the illness management program plus a manualized depression intervention. Subjects completed assessments at baseline, week 5, and 10 to test the main hypothesis that veterans in the Combined condition would have a greater decline in depressive symptoms.

RESULTS
The Combined intervention yielded a significant decline in depressive symptoms when compared with Usual Care. However, the there was no significant difference between the Combined and Illness Management Only groups.

LIMITATIONS
This is a pilot study with a small sample size relative to a standard randomized controlled trial in psychotherapy.

CONCLUSIONS
This telephone-based intervention succeeded in reducing depressive symptoms in veterans with chronic illness. It adds to the building evidence base for providing phone-delivered mental health services.

Aburizik|Arwa|A| Dindo|Lilian|L| Kaboli|Peter|P| Charlton|Mary|M| Dawn|Klein|K| Turvey|Carolyn|C|

Depression
Telehealth
Diabetes
Hypertension
Chronic pain
Chronic illness


[(18)F]FET-PET Imaging for Treatment and Response Monitoring of Radiation Therapy in Malignant Glioma Patients - A Review.

Abstract: In the treatment of patients suffering from malignant glioma, it is a paramount importance to deliver a high radiation dose to the tumor on the one hand and to spare organs at risk at one the other in order to achieve a sufficient tumor control and to avoid severe side effects. New radiation therapy techniques have emerged like intensity modulated radiotherapy and image guided radiotherapy that help facilitate this aim. In addition, there are advanced imaging techniques like Positron emission tomography (PET) and PET/CT which can help localize the tumor with higher sensitivity, and thus contribute to therapy planning, tumor control, and follow-up. During follow-up care, it is crucial to differentiate between recurrence and treatment-associated, unspecific lesions, like radiation necrosis. Here, too, PET/CT can facilitate in differentiating tumor relapse from unspecific changes. This review article will discuss therapy response criteria according to the current imaging methods like Magnet resonance imaging, CT, and PET/CT. It will focus on the significance of PET in the clinical management for treatment and follow-up.

monitoring
radiation therapy
MRI imaging
PET-CT
glioblastoma multiforme


Reported experiences of bereavement support in Western Australia: a pilot study.

Abstract:
OBJECTIVE
This article describes the pilot testing of a community survey to ascertain the experiences and needs of people who were bereaved 6-24 months before the survey. The pilot study aimed to assess the feasibility and acceptability of the survey and test the theoretical public health model for bereavement support.

METHODS
A postal survey was used to collect information from clients of three funeral providers in Western Australia in 2012.

RESULTS
The findings confirmed the feasibility and acceptability of the survey questions. The analysis of the demographic characteristics, experience of bereavement and satisfaction with support revealed differential needs that align with the expectation of low, moderate and high risk, as articulated in the public health model.

CONCLUSIONS
The data provided tentative empirical support for the public health model of bereavement support. This is the first empirical test of this model nationally and internationally.

IMPLICATIONS
Considering the lack of evidence to guide development and allocation of bereavement programs in Australia, a larger survey will enable us to determine how the support needs of each of the three groups of bereaved people should be serviced. This is important for cost-effective and equitable resource allocation.

Aoun|Samar M|SM|
Breen|Lauren J|LJ|
Rumbold|Bruce|B|
Howting|Denise|D|

public health
bereavement care
family carers
health services
palliative care


Solid/liquid extraction equilibria of phenolic compounds with trioctylphosphine oxide impregnated in polymeric membranes.

Abstract: Trioctylphosphine oxide based extractant impregnated membranes (EIM) were used for extraction of phenol and its methyl, hydroxyl and chloride substituted derivatives. The distribution coefficients of the phenols varied from 2 to 234, in the order of 1-napthol > p-chlorophenol > m-cresol > p-cresol > o-cresol > phenol > catechol > pyrogallol > hydroquinone, when initial phenols loadings was varied in 100-2000 mg/L. An extraction model, based on the law of mass action, was formulated to predict the equilibrium distribution of the phenols. The model was in excellent agreement (R(2) > 0.97) with the experimental results at low phenols concentrations (<800 mg/L). At higher phenols loadings though, Langmuir isotherm was better suited for equilibrium prediction (R(2) > 0.95), which signified high mass transfer resistance in the EIMs. Examination of the effects of ring substitution on equilibrium, and bivariate statistical analysis between the amounts of phenols extracted into the EIMs and factors affecting phenols interaction with TOPO, indicated the dominant role of hydrophobicity in equilibrium determination. These results improve understanding of the solid/liquid equilibrium process between phenols and the EIMs, and these will be useful in designing phenol recovery process from wastewater.

D059625:Liquid-Liquid Extraction
D008567:Membranes, Artificial
D009943:Organophosphorus Compounds
D010636:Phenols
D011108:Polymers
D052616:Solid Phase Extraction
D014865:Waste Disposal, Fluid
D014874:Water Pollutants, Chemical

Extraction
Phenol
Trioctylphosphine oxide
Adsorption
Hollow fiber membrane


Design, synthesis, and evaluation of water-soluble morpholino-decorated paclitaxel prodrugs with remarkably decreased toxicity.

Abstract: Novel water-soluble paclitaxel prodrugs were designed and synthesized by introducing morpholino groups through different linkers. These derivatives showed 400-20,000-times greater water solubility than paclitaxel as well as comparable activity in MCF-7 and HeLa cell lines. The prodrug PM4 was tested in the S-180 tumor mouse model, with paclitaxel as the positive control. The results showed that PM4 had comparable antitumor activity as paclitaxel, with tumor inhibition of 54% versus 56%, and remarkably decreased toxicity. The survival rate of treated mice was 8/8 in the PM4 group, compared to 3/8 in the paclitaxel group.

Feng|Siliang|S| Chen|Kuncheng|K| Wang|Chenhong|C| Jiang|Xifeng|X| Dong|Huajin|H| Gong|Zehui|Z| Liu|Keliang|K|

D004354:Drug Screening Assays, Antitumor

Paclitaxel prodrugs
Morpholino group
Anticancer
Water-soluble derivatives


Search for Partner Proteins of A. thaliana Immunophilins Involved in the Control of Plant Immunity.

Abstract: The involvement of plant immunophilins in multiple essential processes such as development, various ways of adapting to biotic and abiotic stresses, and photosynthesis has already been established. Previously, research has demonstrated the involvement of three immunophilin genes (AtCYP19-1/ROC3, AtFKBP65/ROF2, and AtCYP57) in the control of plant response to invasion by various pathogens. Current research attempts to identify host target proteins for each of the selected immunophilins. As a result, candidate interactors have been determined and confirmed using a yeast 2-hybrid (Y2H) system for protein⁻protein interaction assays. The generation of mutant isoforms of ROC3 and AtCYP57 harboring substituted amino acids in the in silico-predicted active sites became essential to achieving significant binding to its target partners. This data shows that ROF2 targets calcium-dependent lipid-binding domain-containing protein (At1g70790; AT1) and putative protein phosphatase (At2g30020; АТ2), whereas ROC3 interacts with GTP-binding protein (At1g30580; ENGD-1) and RmlC-like cupin (At5g39120). The immunophilin AtCYP57 binds to putative pyruvate decarboxylase-1 (Pdc1) and clathrin adaptor complex-related protein (At5g05010). Identified interactors confirm our previous findings that immunophilins ROC3, ROF2, and AtCYP57 are directly involved with stress response control. Further, these findings extend our understanding of the molecular functional pathways of these immunophilins.

Abdeeva|Inna A|IA|0000-0003-2175-834X
Pogorelko|Gennady V|GV|
Maloshenok|Liliya G|LG|
Mokrykova|Maria V|MV|
Fursova|Oksana V|OV|
Bruskin|Sergey A|SA|

D017360:Arabidopsis
D029681:Arabidopsis Proteins
D020104:Immunophilins
D019696:Peptidylprolyl Isomerase
D057865:Plant Immunity
D010940:Plant Proteins

A. thaliana
plant immunophilins
yeast 2-hybrid
molecular partners of PPIases
plant immunite


Indications for Inpatient Magnetoencephalography in Children - An Institution's Experience.

Abstract: Magnetoencephalography (MEG) is recognized as a valuable non-invasive clinical method for localization of the epileptogenic zone and critical functional areas, as part of a pre-surgical evaluation for patients with pharmaco-resistant epilepsy. MEG is also useful in localizing functional areas as part of pre-surgical planning for tumor resection. MEG is usually performed in an outpatient setting, as one part of an evaluation that can include a variety of other testing modalities including 3-Tesla MRI and inpatient video-electroencephalography monitoring. In some clinical circumstances, however, completion of the MEG as an inpatient can provide crucial ictal or interictal localization data during an ongoing inpatient evaluation, in order to expedite medical or surgical planning. Despite well-established clinical indications for performing MEG in general, there are no current reports that discuss indications or considerations for completion of MEG on an inpatient basis. We conducted a retrospective institutional review of all pediatric MEGs performed between January 2012 and December 2020, and identified 34 cases where MEG was completed as an inpatient. We then reviewed all relevant medical records to determine clinical history, all associated diagnostic procedures, and subsequent treatment plans including epilepsy surgery and post-surgical outcomes. In doing so, we were able to identify five indications for completing the MEG on an inpatient basis: (1) super-refractory status epilepticus (SRSE), (2) intractable epilepsy with frequent electroclinical seizures, and/or frequent or repeated episodes of status epilepticus, (3) intractable epilepsy with infrequent epileptiform discharges on EEG or outpatient MEG, or other special circumstances necessitating inpatient monitoring for successful and safe MEG data acquisition, (4) MEG mapping of eloquent cortex or interictal spike localization in the setting of tumor resection or other urgent neurosurgical intervention, and (5) international or long-distance patients, where outpatient MEG is not possible or practical. MEG contributed to surgical decision-making in the majority of our cases (32 of 34). Our clinical experience suggests that MEG should be considered on an inpatient basis in certain clinical circumstances, where MEG data can provide essential information regarding the localization of epileptogenic activity or eloquent cortex, and be used to develop a treatment plan for surgical management of children with complicated or intractable epilepsy.

Watkins|Michael W|MW|
Shah|Ekta G|EG|
Funke|Michael E|ME|
Garcia-Tarodo|Stephanie|S|
Shah|Manish N|MN|
Tandon|Nitin|N|
Maestu|Fernando|F|
Laohathai|Christopher|C|
Sandberg|David I|DI|
Lankford|Jeremy|J|
Thompson|Stephen|S|
Mosher|John|J|
Von Allmen|Gretchen|G|

magnetoencephalography
epilepsy surgery
SRSE
intractable epilepsy
inpatient MEG
pediatric epilepsy
presurgical epilepsy evaluation


Antagonistic Activity of Antimicrobial Metabolites Produced from Seaweed-Associated Bacillus amyloliquefaciens MTCC 10456 Against Malassezia spp.

Abstract: Members of the genus Malassezia are known to be opportunistic pathogens responsible for causing skin disorders such as seborrheic dermatitis or dandruff, pityriasis versicolor, folliculitis, atopic dermatitis, and psoriasis. Due to the side effects caused by prolonged use of current topical antifungal agents, development of an alternative treatment is necessary. Fermentative production of antimicrobial metabolites from Bacillus amyloliquefaciens MTCC 10456 was carried out, and their antagonistic activity against Malassezia furfur and Malassezia globosa was evaluated. The antifungal metabolites were isolated by acid precipitation, and bioassay-guided simultaneous separation of the antimicrobial compounds was done by reversed-phase high-performance liquid chromatography (RP-HPLC). The fraction which demonstrated antifungal activity consisted of bacilysin, homologues of bacillomycin D, and members of the macrolactin family. The presence of bacilysin was detected using specific inhibitor assays and homologues of bacillomycin D, and macrolactins were identified using liquid chromatography/high-resolution electrospray ionization-mass spectrometry (LC/HRESI-MS/MS) analysis. Synergism among the identified compounds was observed which enhanced the antagonistic activity against Malassezia spp. To our knowledge, this is the first study to report the co-production and separation of members of macrolactin antibiotics, lipopeptides such as bacillomycin D and dipeptide antibiotic bacilysin, by any Bacillus strain from marine environment. Activity of individual compounds against Malassezia has been reported which may facilitate their application in the field of dermatology and in cosmetic products.

Bacillus amyloliquefaciens
Malassezia
Macrolactins
Lipopeptides
Antifungal peptides
Polyketides


A global survey of adverse event following immunization surveillance systems for pregnant women and their infants.

Abstract: Strengthening antenatal care as a platform for maternal immunization is a priority of the World Health Organization (WHO). Systematic surveillance for adverse events following immunization (AEFI) in pregnancy is needed to identify vaccine safety events. We sought to identify active and passive AEFI surveillance systems for pregnant women and infants. Representatives from all National Pharmacovigilance Centers and a convenience sample of vaccine safety experts were invited to complete a 14-item online survey in English, French or Spanish. The survey captured maternal immunization policies, and active and passive AEFI surveillance systems for pregnant women and infants in respondents' countries. The analysis was descriptive. We received responses from 51/185 (28%) invited persons from 47/148 (32%) countries representing all WHO regions, and low, middle and high-income countries. Thirty countries had national immunization policies targeting pregnant women. Eleven countries had active surveillance systems to detect serious AEFI in pregnant women and/or their infants, including six low and middle-income countries (LMIC). Thirty-nine countries had passive surveillance systems, including 23 LMIC. These active and passive surveillance programs cover approximately 8% and 56% of the worldwide annual birth cohort, respectively. Data from one active and four passive systems have been published. We identified 50 active and passive AEFI surveillance systems for pregnant women and infants, but few have published their findings. AEFI surveillance appears to be feasible in low and high resource settings. Further expansion of AEFI surveillance for pregnant women and sharing of vaccine safety information will provide additional evidence in support of maternal immunization policies.

Cassidy|Christine|C|
MacDonald|Noni E|NE|
Steenbeek|Audrey|A|
Ortiz|Justin R|JR|
Zuber|Patrick L F|PL|
Top|Karina A|KA|

D016907:Adverse Drug Reaction Reporting Systems

D064420:Drug-Related Side Effects and Adverse Reactions

adverse event following immunization
surveillance
pregnancy
vaccination
neonate


High-resolution melting combines with Bayes discriminant analysis: a novel hepatitis C virus genotyping method.

Abstract: Current hepatitis C virus (HCV) genotyping techniques are often highly technical, costly, or need improvements in sensitivity and specificity. These limitations indicate the need of novel methods for HCV genotyping. The present study aimed to develop a novel genotyping method combining high-resolution melting (HRM) analysis with Bayes discriminant analysis (BDA). Target gene fragment including 5'-untranslated and core region was selected. Four or five inner amplicons for every serum were amplified using nested PCR, HRM was used to determine the melting temperature of the amplicons, and HCV genotypes were then analyzed utilizing BDA. In initial genotyping (HCV genotypes were classified into 1b, 2a, 3a, 3b, and 6a), both the overall accuracy rate and the cross-validation accuracy rate were 92.6 %, external validation accuracy rate was 95.0 %. To enhance the accuracy rate of genotyping, HCV genotypes were firstly classified into 1b, 3a, 3b, and 2a-6a, followed by a supplementary genotyping for 2a-6a. Both the overall accuracy rate and the cross-validation accuracy rate reached 97.5 %, and external validation accuracy rate was 100 %. Comparing adjusted HRM genotyping with type-specific probe technique, the difference in accuracy rates was not significant. However, the limit of detection and cost were lower for HRM. Comparing with sequencing, the limit detection of HRM was the same as the former, but the cost of HRM was lower. Hence, HRM combined with BDA was a novel method that equipped with superior accuracy, high sensitivity, and lower cost and therefore could be a better technique for HCV genotyping.

Wu|Daxian|D| Fu|Xiaoyu|X| Wen|Ya|Y| Liu|Bingjie|B| Deng|Zhongping|Z| Dai|Lizhong|L| Tan|Deming|D|

D003365:Costs and Cost Analysis
D004279:DNA, Viral
D016002:Discriminant Analysis
D060005:Genotyping Techniques
D016174:Hepacivirus
D006526:Hepatitis C
D006801:Humans
D016133:Polymerase Chain Reaction
D012367:RNA, Viral
D012680:Sensitivity and Specificity
D044366:Transition Temperature

Bayes discriminant analysis
Hepatitis C virus
Genotyping
Type-specific probe
Sequencing
High-resolution melting analysis


Eating behaviors in obese children with pseudohypoparathyroidism type 1a: a cross-sectional study.

Abstract:
BACKGROUND
Children with pseudohypoparathyroidism type 1a (PHP-1a) develop early-onset obesity. These children have decreased resting energy expenditure but it is unknown if hyperphagia contributes to their obesity.

METHODS
We conducted a survey assessment of patients 2 to 12 years old with PHP-1a and matched controls using the Hyperphagia Questionnaire (HQ) and Children's Eating Behavior Questionnaire (CEBQ). Results of the PHP-1a group were also compared with an obese control group and normal weight sibling group.

RESULTS
We enrolled 10 patients with PHP-1a and 9 matched controls. There was not a significant difference between the PHP-1a group and matched controls for total HQ score (p = 0.72), Behavior (p = 0.91), Drive (p = 0.48) or Severity (p = 0.73) subset scores. There was also no difference between the PHP-1a group and matched controls on the CEBQ. In a secondary analysis, the PHP-1a group was compared with obese controls (n = 30) and normal weight siblings (n = 6). Caregivers reported an increased interest in food before age 2 years in 6 of 10 PHP-1a patients (60%), 9 of 30 obese controls (30%) and none of the siblings (p = 0.04). The sibling group had a significantly lower Positive Eating Behavior score than the PHP-1a group (2.6 [2.4, 2.9] vs. 3.5 [3.1, 4.0], p < 0.01) and obese controls (2.6 [2.4, 2.9] vs. 3.4 [2.6, 3.8], p = 0.04), but there was not a significant difference between the PHP-1a and obese controls (p = 0.35). The sibling group had a lower Desire to Drink score than both the PHP-1a group (1.8 [1.6, 2.7] vs. 4.3 [3.3, 5.0], p < 0.01) and obese controls (1.8 [1.6, 2.7] vs. 3.3 [3.0, 4.0], p < 0.01) but there was not a significant difference between the PHP-1a and obese control Desire to Drink scores (p = 0.11).

CONCLUSIONS
Patients with PHP-1a demonstrate hyperphagic symptoms similar to matched obese controls.

Eating behaviors
Obesity
Pseudohypoparathyroidism


What do families want to improve in the management of paediatric febrile neutropenia during anti-cancer treatment? Report of a patient/public involvement group.

Abstract:
Background
This study reports how parents and young people who had an experience offebrile neutropenia (FN) improved the design of a trial to inform the management of this condition. Five parents, a young person who had completed treatment and three clinician-researchers contributed.

Methods
The group was formed after an invitation on social media and met via video conference. Many participants were from an existing childhood-cancer parent-involvement group. The initial questions asked during discussion were about the importance of the topic, the views on the need for a trial, which important outcomes should be measured and the practical aspects which would make it easier or more difficult for people to take part in it. The conversation occurred for an entire afternoon, was audio and video recorded, transcribed, analysed and checked by those involved. The fifth parent added to this via email.

Results
The group altered the trial structure by proposing randomising of each child to one of the two management methods through the whole of their anti-cancer treatment, rather than randomising the study sites or the child at each visit. They felt that even if people declined taking part in the study in the first weeks of diagnosis, their views might change and they should be allowed to consent later. They also proposed methods of collecting important patient and family data, enriching the medical information gained in the study. Active follow-up, negotiated for each individual family, was also suggested.

Conclusion
Trials for improving the management of FN in children and young people who are undergoing anti-cancer treatments should consider individual-patient randomisation, collection of 'quality of life' and 'experience of care' aspects using digital and paper-based methods, engage families in shared decision-making about management options and ensure adequate supportive information is available and accessible to all patients regardless of background, geographical location or age.

data collection
infectious diseases
oncology
patient perspective


Aminopeptidase-N-independent entry of porcine epidemic diarrhea virus into Vero or porcine small intestine epithelial cells.

Abstract: A monkey cell line Vero (ATCC CCL-81) is commonly used for porcine epidemic diarrhea virus (PEDV) propagation in vitro. However, it is still controversial whether the porcine aminopeptidase N (pAPN) counterpart on Vero cells (Vero-APN) confers PEDV entry. We found that endogenous expression of Vero-APN was undetectable in the mRNA and the protein levels in Vero cells. We cloned the partial Vero-APN gene (3340-bp) containing exons 1 to 9 from cellular DNA and subsequently generated two APN-knockout Vero cell lines by CRISPR/Cas9 approach. PEDV infection of two APN-knockout Vero cells had the same efficiency as the Vero cells with or without neuraminidase treatment. A Vero cells stably expressing pAPN did not increase PEDV production. SiRNA-knockdown of pAPN in porcine jejunum epithelial cells had no effects on PEDV infection. The results suggest that there exists an additional cellular receptor on Vero or porcine jejunal cells independent of APN for PEDV entry.

Ji|Chun-Miao|CM| Wang|Bin|B| Zhou|Jiyong|J| Huang|Yao-Wei|YW|

D000818:Animals
D000914:Antibodies, Viral
D018826:CD13 Antigens
D002522:Chlorocebus aethiops
D004847:Epithelial Cells
D017353:Gene Deletion
D007421:Intestine, Small
D053485:Porcine epidemic diarrhea virus
D064370:Spike Glycoprotein, Coronavirus
D013552:Swine
D014709:Vero Cells
D053586:Virus Internalization

Porcine epidemic diarrhea virus (PEDV)
Vero cells
CRISPR/Cas9
Receptor
Aminopeptidase N (APN)
IPEC-J2 cells


Invisible burden of COVID-19: enzyme replacement therapy disruptions.

Abstract:
OBJECTIVES
Lysosomal storage diseases (LSD) constitute an important group of metabolic diseases, consisting of approximately 60 disorders. In some types of lysosomal diseases, enzyme replacement therapy (ERT) is administered intravenously in weekly or biweekly doses. Unfortunately, scheduled ERT during COVID-19 was disrupted. We considered the possibility of adverse outcomes caused by the disruption in the treatment of patients with lysosomal storage disorders.

METHODS
During the COVID-19 pandemic, we conducted a questionnaire that was delivered via Internet to assess how this vulnerable patient group was affected by the pandemic in terms of their access to treatment and their disease-related symptoms.

RESULTS
The questionnaire was filled out by 75 patients. There were 35 patients whose treatment dose was missed because of COVID-19. The most common reason for skipping treatment was not wanting to go to the hospital for fear of contracting COVID-19. These 35 patients missed a median of four doses of ERT (range: 1-16 dosages). Twenty-one patients (60%) claimed that they were affected physically by not taking ERT (20 mucopolysaccaridoses, 1 Fabry disease), whereas 14 (40%) did not.

CONCLUSIONS
Interruption of ERT during the COVID-19 pandemic may have significant consequences. It may be beneficial to switch to home treatment or reserve dedicated facilities. With proper planning and management, the treatment disruptions of this particular group can be avoided.

COVID-19
enzyme replacement therapy
disruptions
lysosomal storage diseases
survey


Cognitive stimulation of executive functions in mild cognitive impairment: specific efficacy and impact in memory.

Abstract: Executive functions play an important role in the maintenance of autonomy in day-to-day activities. Nevertheless, there is little research into specific cognitive training for Mild Cognitive Impairment (MCI). We present the results of a program which aims to teach specific strategies and metacognitive abilities in order for patients to be able to carry out attentional and executive tasks. Two groups (A and B) were compared in a cross-over design. After the first evaluation, Group A (but not B) participated in a six month cognitive stimulation program. After a second assessment, only Group B received treatment and then a final evaluation was carried out on both groups. The results show that: i) both groups improved their performance as an effect of training; ii) improvements generalized to memory and general cognitive tasks; iii) in the interval without training, Group B's performance worsened and iv) Group A partially maintained their results over time.

Moro|V|V|
Condoleo|M T|MT|
Valbusa|V|V|
Broggio|E|E|
Moretto|G|G|
Gambina|G|G|

D000368:Aged
D000369:Aged, 80 and over
D015928:Cognitive Behavioral Therapy
D060825:Cognitive Dysfunction
D018592:Cross-Over Studies
D018450:Disease Progression
D056344:Executive Function
D005260:Female
D006801:Humans
D008297:Male
D008569:Memory Disorders
D016896:Treatment Outcome

cognitive stimulation
executive functions
mild cognitive impairment
mental deterioration
neuropsychological rehabilitation
strategy training


Who Is Who in Adenosine Transport.

Abstract: Extracellular adenosine concentrations are regulated by a panel of membrane transporters which, in most cases, mediate its uptake into cells. Adenosine transporters belong to two gene families encoding Equilibrative and Concentrative Nucleoside Transporter proteins (ENTs and CNTs, respectively). The lack of appropriate pharmacological tools targeting every transporter subtype has introduced some bias on the current knowledge of the role of these transporters in modulating adenosine levels. In this regard, ENT1, for which pharmacology is relatively well-developed, has often been identified as a major player in purinergic signaling. Nevertheless, other transporters such as CNT2 and CNT3 can also contribute to purinergic modulation based on their high affinity for adenosine and concentrative capacity. Moreover, both transporter proteins have also been shown to be under purinergic regulation via P1 receptors in different cell types, which further supports its relevance in purinergic signaling. Thus, several transporter proteins regulate extracellular adenosine levels. Moreover, CNT and ENT proteins are differentially expressed in tissues but also in particular cell types. Accordingly, transporter-mediated fine tuning of adenosine levels is cell and tissue specific. Future developments focusing on CNT pharmacology are needed to unveil transporter subtype-specific events.

adenosine
transporters
ENT
CNT
purinergic signaling


The 3 R's for Platelet-Rich Fibrin: A "Super" Tri-Dimensional Biomaterial for Contemporary Naturally-Guided Oro-Maxillo-Facial Soft and Hard Tissue Repair, Reconstruction and Regeneration.

Abstract: Platelet-Rich fibrin (PRF) is a three-dimensional (3-D) autogenous biomaterial obtained via simple and rapid centrifugation from the patient's whole blood samples, without including anti-coagulants, bovine thrombin, additives, or any gelifying agents. At the moment, it is safe to say that in oral and maxillofacial surgery, PRFs (particularly, the pure platelet-rich fibrin or P-PRF and leukocyte and platelet-rich fibrin or L-PRF sub-families) are receiving the most attention, essentially because of their simplicity, cost-effectiveness, and user-friendliness/malleability; they are a fairly new "revolutionary" step in second-generation therapies based on platelet concentration, indeed. Yet, the clinical effectiveness of such surgical adjuvants or regenerative platelet concentrate-based preparations continues to be highly debatable, primarily as a result of preparation protocol variability, limited evidence-based clinical literature, and/or poor understanding of bio-components and clinico-mechanical properties. To provide a practical update on the application of PRFs during oral surgery procedures, this critical review focuses on evidence obtained from human randomized and controlled clinical trials only. The aim is to serve the reader with current information on the clinical potential, limitations, challenges, and prospects of PRFs. Accordingly, reports often associate autologous PRFs with early bone formation and maturation; accelerated soft-tissue healing; and reduced post-surgical edema, pain, and discomfort. An advanced and original tool in regenerative dentistry, PRFs present a strong alternative and presumably cost-effective biomaterial for oro-maxillo-facial tissue (soft and hard) repair and regeneration. Yet, preparation protocols continue to be a source of confusion, thereby requiring revision and standardization. Moreover, to increase the validity, comprehension, and therapeutic potential of the reported findings or observations, a decent analysis of the mechanico-rheological properties, bio-components, and their bioactive function is eagerly needed and awaited; afterwards, the field can progress toward a brand-new era of "super" oro-dental biomaterials and bioscaffolds for use in oral and maxillofacial tissue repair and regeneration, and beyond.

Zumarán|Consuelo C|CC|
Parra|Marcelo V|MV|
Olate|Sergio A|SA|
Fernández|Eduardo G|EG|
Muñoz|Francisco T|FT|
Haidar|Ziyad S|ZS|0000-0003-0077-2927

fibrin
regeneration
leukocyte
platelet
oral surgery
dentistry
grafts
growth factors
osteogenesis
periodontology
tissue engineering


Assessment of platelet-to-lymphocyte ratio in patients with retinal vein occlusion.

Abstract:
Purpose
To investigate platelet-to-lymphocyte ratio (PLR) in retinal vein occlusion (RVO) patients.

Methods
In this study, we retrospectively reviewed data of 32 patients with RVO (RVO group) and 32 age- and sex-matched participants without RVO (control group) between January 2017 and March 2019. The PLR was determined by dividing the platelet count by the lymphocyte count.

Results
Age and gender were comparable between the groups (p = 0.204 and p = 0.800, respectively). PLR was significantly elevated in the RVO group compared with the control group (137 (113-164) vs 101 (86-129), p = 0.001)). In the receiver operator characteristics curve analysis, the optimal cut-off value of PLR for predicting RVO was 123, with 69% sensitivity and 72% specificity.

Conclusion
We report that PLR are elevated in RVO, suggesting that PLR may be a useful marker for RVO.

platelet-to-lymphocyte ratio
retinal vein occlusion
inflammation
thrombus


Frontotemporal dementia and amyotrophic lateral sclerosis: revisiting one of the first case reports with neuropathology examination.

Abstract: The occurrence of dementia in amyotrophic lateral sclerosis (ALS) was only widely recognized in the late 20th century. Hitherto, it was believed that dementia was a rare event due to the fortuitous association with other diseases. In 1924, Kostantin Nikolaevich Tretiakoff and Moacyr de Freitas Amorim reported a case of dementia with features of frontotemporal dementia (FTD) that preceded the motor signs of ALS. Neuropathological examination confirmed ALS and found no signs of other dementia-causing diseases. The authors hypothesized that dementia was part of ALS and recommended the search for signs of involvement of motor neurons in cases of dementia with an ill-defined clinical picture, a practice currently accepted in the investigation of cases of FTD. This was one of the first descriptions of dementia preceding the motor impairments of ALS and was published in Portuguese and French in Memórias do Hospício de Juquery.

frontotemporal dementia
dementia
amyotrophic lateral sclerosis
neuropathology
motor neuron disease


Diagnosis and treatment of lymph node metastases of a rectal carcinoid tumor using In111-octreotide-scintigraphy and intraoperative gamma probe detection.

Abstract: Carcinoids represent 1-2% of the rectal cancer. We report the case of a woman with a rectal carcinoid and a hypogastric node metastasis. We propose a less invasive treatment of the metastase using In11-octreotide-scintigraphy and intraoperative gamma-probe detector.

Rossetti|A|A| Travaglia|T|T| Rossini|P|P| Odeh|M|M| Arru|L|L| Ragni|F|F|

Node metastases
Rectal
Carcinoids
Gamma-probe
Octreoscan


The modulating role of gender and aggression in emotional reactions of nursing students: A cross-sectional study.

Abstract:
AIMS
To examine whether and to what extent emotion reactions of nursing students are affected by emotional features inherent in nursing care situations, focusing on gender and aggression.

BACKGROUND
How individual characteristics of nurse students interact with emotional demands inherent in nursing practice and modulate the way they are perceived and acted upon may have an impact on quality of patient care.

DESIGN
Cross-sectional study, conducted from May to September 2013.

METHODS
Nursing students (N = 157) of the Nursing Degree Course of School of Medicine, Bologna University, completed self-report questionnaires assessing individual differences (i.e. aggression, personality traits, empathy) and evaluated emotion-inducing pictures of pleasant, unpleasant and neutral content.

RESULTS
Gender and verbal aggression level modulate emotional responses of nursing students: females rated negative picture categories as significantly less pleasant than male students; those with high compared to low verbal aggression levels rated negative stimuli as less arousing and more pleasant. Verbal aggression level is positively related to physical aggression and anger and negatively related to emotional stability and empathy in both males and females.

CONCLUSION
High verbal aggression scores seem to be associated with attenuated arousal in response to emotional stimuli and decreased aversive reaction towards negative content pictures, indicating a potential facilitation of approach and management of adverse events strictly connected to nursing practice. Nonetheless, aggression can represent a risk factor in nursing practice. Negative implications of verbal aggression are highlighted together with the need for tailoring education programs aimed at enhancing emotion regulation and aggression management skills in nursing context.

aggression
emotional reactions
nursing students
personality traits
empathy
gender differences


Randomised trial on treatment of vaginal intraepithelial neoplasia-Imiquimod, laser vaporisation and expectant management.

Abstract: Vaginal intraepithelial neoplasia (VAIN) is associated with human papillomavirus (HPV) infection. The most common treatment modality is laser vaporisation, but recurrences are common. Imiquimod is an immune response modulator which is used for the treatment of external condylomas and other HPV-related genital neoplasias. The aim of the study was to evaluate the efficacy and tolerability of vaginally administered imiquimod in comparison with laser vaporisation and expectant management of high-grade VAIN. This proof of principle pilot study was a prospective 16-week randomised trial. We enrolled 30 patients with histologically confirmed VAIN 2 or 3 into three study arms: vaginally administered imiquimod, laser vaporisation and expectant management. Follow-up colposcopy visits included high-risk human papillomavirus (hrHPV) testing, cytology and punch biopsies. At baseline 77% (n = 20/26) of the patients were hrHPV positive. HPV clearance was significantly higher in the imiquimod arm (63%, n = 5/8) than in the laser arm (11%, n = 1/9) (p = 0.05) or in the expectant management arm (17%, n = 1/6) (p = 0.138). At baseline 25 patients (83%) had VAIN 2 and five (17%) had VAIN 3. None of the lesions progressed during the follow-up. Histological regression (≤VAIN 1) was observed in 80% (n = 8/10) of patients in the imiquimod arm, 100% (n = 10/10) of the laser arm (p = 0.474) and 67% (n = 6/9) of the expectant management arm (p = 0.628). Vaginal imiquimod appears to be as effective as laser treatment in high-grade VAIN.

Tainio|Karoliina|K| Jakobsson|Maija|M| Louvanto|Karolina|K| Kalliala|Ilkka|I| Paavonen|Jorma|J| Nieminen|Pekka|P| Riska|Annika|A|

vaginal high-grade squamous intraepithelial lesion


Association of IL-36γ with tertiary lymphoid structures and inflammatory immune infiltrates in human colorectal cancer.

Abstract: IL-1 family cytokines play a dual role in the gut, with different family members contributing either protective or pathogenic effects. IL-36γ is an IL-1 family cytokine involved in polarizing type-1 immune responses. However, its function in the gut, including in colorectal cancer pathogenesis, is not well appreciated. In a murine model of colon carcinoma, IL-36γ controls tertiary lymphoid structure formation and promotes a type-1 immune response concurrently with a decrease in expression of immune checkpoint molecules in the tumor microenvironment. Here, we demonstrate that IL-36γ plays a similar role in driving a pro-inflammatory phenotype in human colorectal cancer. We analyzed a cohort of 33 primary colorectal carcinoma tumors using imaging, flow cytometry, and transcriptomics to determine the pattern and role of IL-36γ expression in this disease. In the colorectal tumor microenvironment, we observed IL-36γ to be predominantly expressed by M1 macrophages and cells of the vasculature, including smooth muscle cells and high endothelial venules. This pattern of IL-36γ expression is associated with a CD4+ central memory T cell infiltrate and an increased density of B cells in tertiary lymphoid structures, as well as with markers of fibrosis. Conversely, expression of the antagonist to IL-36 signaling, IL-1F5, was associated with intratumoral expression of checkpoint molecules, including PD-1, PD-L1, and CTLA4, which can suppress the immune response. These data support a role for IL-36γ in the physiologic immune response to colorectal cancer by sustaining inflammation within the tumor microenvironment.

Tertiary lymphoid structure
Colorectal cancer
Memory T cells
Interleukin (IL)-36 g
M1 classically activated macrophages


Localization of alkali-labile sites in donkey (Equus asinus) and stallion (Equus caballus) spermatozoa.

Abstract: The presence of constitutive alkali-labile sites (ALS) has been investigated using a protocol of DNA breakage detection-fluorescence in situ hybridization and comet assay in spermatozoa of donkey (Equus asinus) and stallion (Equus caballus). These results were compared with those obtained using a similar experimental approach using somatic cells. The relative abundance of ALS was of the order of four times more in spermatozoa than in somatic cells. Alkali-labile sites showed a tendency to cluster localized at the equatorial-distal regions of the sperm. The amount of hybridized signal in the ALS in the sperm of donkey (Equus asinus) was 1.3 times greater than in stallion (Equus caballus), and the length of the comet tail obtained in donkey sperm was 1.6 times longer than that observed in stallion (P < 0.05); however, these differences were not appreciated in somatic cells. In conclusion, ALS localization in sperm is not a randomized event and a different pattern of ALS distribution occurs for each species. These results suggest that ALS represents a species-specific issue related to chromatin organization in sperm and somatic cells in mammalian species, and they might diverge even with very short phylogenetic distances.

Cortés-Gutiérrez|Elva I|EI|
Dávila-Rodríguez|Martha I|MI|
López-Fernández|Carmen|C|
Fernández|José Luis|JL|
Crespo|Francisco|F|
Gosálvez|Jaime|J|

D017404:In Situ Hybridization, Fluorescence

Alkali-labile sites
DNA breakage detection-FISH
Sperm DNA structure


What are the priorities for improving cataract surgical outcomes in Africa? Results of a Delphi exercise.

Abstract:
PURPOSE
The quality of cataract surgery delivered in sub-Saharan Africa (SSA) is a significant constraint to achieving the elimination of avoidable blindness. No published reports from routine SSA cataract services attain the WHO benchmarks for visual outcomes; poor outcomes (<6/60) often comprise 20% in published case series. This Delphi exercise aimed to identify and prioritise potential interventions for improving the quality of cataract surgery in SSA to guide research and eye health programme development.

METHODS
An initial email open-question survey created a ranked list of priorities for improving quality of surgical services. A second-round face-to-face discussion facilitated at a Vision 2020 Research Mentorship Workshop in Tanzania created a refined list for repeated ranking.

RESULTS
Seventeen factors were agreed that might form target interventions to promote quality of cataract services. Improved training of surgeons was the top-ranked item, followed by utilisation of biometry, surgical equipment availability, effective monitoring of outcomes of cataract surgery by the surgeon, and well-trained support staff for the cataract pathway (including nurses seeing post-operative cases).

CONCLUSION
Improving the quality of cataract surgery in SSA is a clinical, programmatic and public health priority. In the absence of other evidence, the collective expert opinion of those involved in ophthalmic services regarding the ranking of factors to promote quality improvement, refined through this Delphi exercise, provides us with candidate intervention areas to be evaluated.

D006301:Health Services Needs and Demand

Cataract
Sub-Saharan Africa
Quality improvement
Delphi technique


Celiac disease in children: Increasing prevalence and changing clinical presentations.

Abstract:
BACKGROUND
Celiac disease (CD) is a chronic autoimmune enteropathy. It results from genetic predisposition and exposure to gluten-containing food. The prevalence and presentation of CD vary among populations.

PURPOSE
This study aimed to describe the prevalence and clinical characteristics of CD in children in Bahrain.

METHODS
We retrospectively reviewed the medical records of children diagnosed with CD in the pediatric department, Salmaniya Medical Complex, Bahrain, in 1988-2018. Their clinical, biochemical, serological, and histopathological findings were documented. Adherence to the recommended gluten-free diet (GFD) was assessed.

RESULTS
Of 86 patients with CD, 67 were included. The CD prevalence was 0.02%. A significant increase in prevalence in the last decade was observed (P<0.0001). Thirty-eight patients (56.7%) were males. The median (interquartile range) age at presentation was 4.45 (1.5-7.3) years. A family history of CD was positive in 13 out of 43 patients (30.2%). Pallor and failure to thrive were the most common presentations. The most frequent associated disease was iron-deficiency anemia in 23 patients (69.7%). Positive serology was found in 32 of 45 patients (71.1%). Marsh-Oberhuber type III was found in 16 of 35 patients (45.7%). Seropositive patients were significantly older (P=0.025) and had more severe duodenal histology (P=0.002). Adherence to GFD was poor in 27 patients (64.3%).

CONCLUSION
This study revealed a significant increase in CD prevalence over the last decade. Atypical presentations were frequent. Most patients had poor adherence to GFD.

Isa|Hasan M|HM|
Farid|Eman|E|
Makhlooq|Jaafar J|JJ|
Mohamed|Afaf M|AM|
Al-Arayedh|Jumana G|JG|
Alahmed|Fawzeya A|FA|
Medani|Shima|S|

Celiac disease
Prevalence
Clinical presentation
Bahrain
Child


Altered Coupling of Psychological Relaxation and Regional Volume of Brain Reward Areas in Multiple Sclerosis.

Abstract: Background: Psychological stress can influence the severity of multiple sclerosis (MS), but little is known about neurobiological factors potentially counteracting these effects. Objective: To identify gray matter (GM) brain regions related to relaxation after stress exposure in persons with MS (PwMS). Methods: 36 PwMS and 21 healthy controls (HCs) reported their feeling of relaxation during a mild stress task. These markers were related to regional GM volumes, heart rate, and depressive symptoms. Results: Relaxation was differentially linked to heart rate in both groups (t = 2.20, p = 0.017), i.e., both markers were only related in HCs. Relaxation was positively linked to depressive symptoms across all participants (t = 1.99, p = 0.045) although this link differed weakly between groups (t = 1.62, p = 0.108). Primarily, the volume in medial temporal gyrus was negatively linked to relaxation in PwMS (t = -5.55, pfamily-wise-error(FWE)corrected = 0.018). A group-specific coupling of relaxation and GM volume was found in ventromedial prefrontal cortex (VMPFC) (t = -4.89, pFWE = 0.039). Conclusion: PwMS appear unable to integrate peripheral stress signals into their perception of relaxation. Together with the group-specific coupling of relaxation and VMPFC volume, a key area of the brain reward system for valuation of affectively relevant stimuli, this finding suggests a clinically relevant misinterpretation of stress-related affective stimuli in MS.

Wakonig|Katharina|K|
Eitel|Fabian|F|
Ritter|Kerstin|K|
Hetzer|Stefan|S|
Schmitz-Hübsch|Tanja|T|
Bellmann-Strobl|Judith|J|
Haynes|John-Dylan|JD|
Brandt|Alexander U|AU|
Gold|Stefan M|SM|
Paul|Friedemann|F|
Weygandt|Martin|M|

psychological relaxation
multiple sclerosis
gray matter
ventromedial prefrontal cortex (vmPFC)
brain reward system
autoimmunity
neuroinflammation
psychophysiological stress responses


Predictive Factors and Time to Development of Hepatic Decompensation in Patients with Non-alcoholic Fatty Liver Disease.

Abstract:
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of cirrhosis in the USA.

OBJECTIVES
We aimed to determine the time to develop hepatic events in patients with NAFLD and develop a simple model to identify patients at risk for hepatic decompensation.

DESIGN
Retrospective cohort study.

PATIENTS
Seven hundred patients with NAFLD met inclusion criteria for the study. Patients were divided into model construction (n = 450) and validation (n = 250) cohorts.

MAIN MEASURES
Demographic, clinical, and laboratory variables were gathered at the time of diagnosis of NAFLD. Kaplan-Meier analysis determined the time to development of hepatic events from initial diagnosis. A time-to-event prediction model was established in the model construction cohort using the multivariate Cox proportional hazards model and was then internally validated.

KEY RESULTS
Forty-nine (7%) patients developed hepatic events at a mean duration of 6.2 ± 4.2 years from initial diagnosis. Kaplan-Meier probability of developing a hepatic event at 5-, 10-, and 12-year intervals was 4.8%, 10.6%, and 11.3%, respectively. Age, presence of diabetes, and platelet count were identified as significant variables to predict hepatic events. NAFLD decompensation risk score was developed as "age × 0.06335 + presence of diabetes (yes = 1, no = 0) × 0.92221 - platelet count × 0.01522" to predict the probability of hepatic decompensation. Risk score model had an area under the curve of 0.89 (95% CI = 0.92, 0.86) and it performed well in both the validation (0.91, 0.87-0.94) and the overall cohort (0.89, 0.87-0.91).

CONCLUSIONS
A significant proportion of patients with NAFLD developed hepatic decompensation. We have provided a simple, objective model to help identify "at-risk" patients.

Ahmed|Heidi S|HS|0000-0001-5115-5385
Pedersen|Natalie|N|
Jayanna|Manju Bengaluru|MB|
Ten Eyck|Patrick|P|
Sanchez|Antonio|A|
Murali|Arvind R|AR|

D065626:Non-alcoholic Fatty Liver Disease

fatty liver
liver disease
cirrhosis
metabolic syndrome
prevention


Ionic liquids as precursors for highly luminescent, surface-different nitrogen-doped carbon dots used for label-free detection of Cu2+/Fe3+ and cell imaging.

Abstract: Carbon nanodots (C-Dots) have attracted much attention in recent years due to their low cost, ready scalability, excellent chemical stability, biocompatibility and multicolor luminescence. Here, we report a facile strategy for producing highly luminescent, surface-different nitrogen-doped carbon dots (C-Dots) by using different ionic liquids (ILs). Intriguingly, the surface-different C-Dots show different selectivity for Cu(2+) and Fe(3+). To the best of our knowledge, this is the first example which shows that ILs are excellent precursors for producing luminescent nanomaterial used for detection of different metal ions. The resultant nitrogen-doped C-Dots are highly photoluminescent and can be used for multicolor bioimaging. Most notable, by taking different ILs as precursors, we obtain surface-different C-Dots, which can be directly used for selective detection of Cu(2+) and Fe(3+) without any modification. These C-Dots based sensors exhibit high sensitivity and selectivity and the sensing process can be easily accomplished with one-step rapid operation. More importantly, compared with other method using QDs, organic dyes and organic solvent, this strategy is much more eco-friendly. This work may offer a new approach for developing low cost and sensitive C-Dots-based sensors for biological and environmental applications.

Zhao|Andong|A| Zhao|Chuanqi|C| Li|Meng|M| Ren|Jinsong|J| Qu|Xiaogang|X|

Ionic liquids
Carbon dots
Detection
Cell imaging


Effects of six weeks of resistance-endurance training on microRNA-29 expression in the heart of ovariectomised rats.

Abstract:
Introduction
Heart disease risk rises with age. However, women's symptoms become more pronounced following the onset of menopause. The aim of the present study was to evaluate the effects of six weeks of combined resistance-endurance (RE) training on microRNA-29 expression in the heart of ovariectomised rats.

Material and methods
Thirty female Wistar rats were divided into three groups: 1) sham (SHAM); 2) ovariectomy (OVX); and 3) OVX with RE training (OVX + RE). The effects of these treatments on cardiac microRNA-29 expression were measured using real-time PCR. Data were analysed using a 2 × 3 ANOVA and Tukey post-hoc comparisons and presented as mean ±SEM.

Results
Ovariectomy resulted in a significant down-regulation in the heart microRNA-29 gene expression of OVX (0.265 ±0.031 fold changes), OVX + RE (0.699 ±0.038 fold changes) in animals vs. sham animals (1 ±0 fold changes; all, p < 0.05) following six weeks of treatment. However, microRNA-29 expression in the OVX + RE group was significantly greater than in the OVX group (p < 0.05).

Conclusions
Our findings suggest that the six weeks of regular RE training attenuate the reduction in heart muscle microRNA-29 expression observed in ovariectomised rates. If our findings carry over to humans, such an exercise regimen could be beneficial to the cardiovascular disease risk in women during menopause.

Jourkesh|Morteza|M|
Soori|Rahman|R|
Earnest|Conrad P|CP|
Mirheidari|Lamia|L|
Ravasi|Ali Asghar|AA|
Stannard|Stephen R|SR|
Monsalves-Alvarez|Matias|M|

microRNA-29
ovariectomy
cardiac
exercise training


"More than a diet": A qualitative investigation of young vegan Women's relationship to food.

Abstract: One's relationship to food is an important factor that can contribute to wellbeing but can also lead to eating disturbances. Research in this area has linked vegetarianism and veganism to disordered eating. However, through social media, many young women have recently started to share their vegan experiences with many highlighting the role that veganism may have on promoting a 'healthier' psychosocial relationship to food. The current study aims to qualitatively explore the role that veganism plays in young women's wellbeing and relationship to food. Participants were ten young vegan women aged 18 to 25. Semi-structured interviews were analysed using Interpretative Phenomenological Analysis (IPA). These women were found to passionately engage in a vegan lifestyle, as opposed to just a vegan diet, which appeared to have a number of positive effects such as a healthier lifestyle, a stronger sense of control and agency, more meaningful social relationships, and a sense of connection to a vegan sub-culture. Through veganism, many of the women transitioned from social disconnection and a focus on body image, to a stronger emotional (empathic), cognitive (knowledge of animal cruelty and healthy eating), and behavioural (diet and consumption choices, connections with others) investment in their social worlds. We suggest that the healing potential of veganism, is derived from this passionate investment of the self that redefines young women's ways of being in the world. The healing benefits of engaging in a vegan lifestyle may have clinical significance for working with young women who are socially disengaged or who are at risk of disordered eating.

Costa|Isabel|I|
Gill|Peter Richard|PR|
Morda|Romana|R|
Ali|Lutfiye|L|

Diet
Vegan
Women
Vegetarian
Animal ethics
Eating disorders
Identity


18F-Fluoride PET/CT tumor burden quantification predicts survival in breast cancer.

Abstract:
PURPOSE
In bone-metastatic breast cancer patients, there are no current imaging biomarkers to identify which patients have worst prognosis. The purpose of our study was to investigate if skeletal tumor burden determined by 18F-Fluoride PET/CT correlates with clinical outcomes and may help define prognosis throughout the course of the disease.

RESULTS
Bone metastases were present in 49 patients. On multivariable analysis, skeletal tumor burden was significantly and independently associated with overall survival (p < 0.0001) and progression free-survival (p < 0.0001). The simple presence of bone metastases was associated with time to bone event (p = 0.0448).

MATERIALS AND METHODS
We quantified the skeletal tumor burden on 18F-Fluoride PET/CT images of 107 female breast cancer patients (40 for primary staging and the remainder for restaging after therapy). Clinical parameters, primary tumor characteristics and skeletal tumor burden were correlated to overall survival, progression free-survival and time to bone event. The median follow-up time was 19.5 months.

CONCLUSIONS
18F-Fluoride PET/CT skeletal tumor burden is a strong independent prognostic imaging biomarker in breast cancer patients.

Brito|Ana E|AE|
Santos|Allan|A|
Sasse|André Deeke|AD|
Cabello|Cesar|C|
Oliveira|Paulo|P|
Mosci|Camila|C|
Souza|Tiago|T|
Amorim|Barbara|B|
Lima|Mariana|M|
Ramos|Celso D|CD|
Etchebehere|Elba|E|

D000072078:Positron Emission Tomography Computed Tomography

breast cancer
skeletal tumor burden
bone metastases
NaF PET/CT
fluoride-PET/CT


Significance of the hydrophobic residues 225-230 of apoA-I for the biogenesis of HDL.

Abstract: We studied the significance of four hydrophobic residues within the 225-230 region of apoA-I on its structure and functions and their contribution to the biogenesis of HDL. Adenovirus-mediated gene transfer of an apoA-I[F225A/V227A/F229A/L230A] mutant in apoA-I⁻/⁻ mice decreased plasma cholesterol, HDL cholesterol, and apoA-I levels. When expressed in apoA-I⁻/⁻ × apoE⁻/⁻ mice, approximately 40% of the mutant apoA-I as well as mouse apoA-IV and apoB-48 appeared in the VLDL/IDL/LDL. In both mouse models, the apoA-I mutant generated small spherical particles of pre-β- and α4-HDL mobility. Coexpression of the apoA-I mutant and LCAT increased and shifted the-HDL cholesterol peak toward lower densities, created normal αHDL subpopulations, and generated spherical-HDL particles. Biophysical analyses suggested that the apoA-I[225-230] mutations led to a more compact folding that may limit the conformational flexibility of the protein. The mutations also reduced the ability of apoA-I to promote ABCA1-mediated cholesterol efflux and to activate LCAT to 31% and 66%, respectively, of the WT control. Overall, the apoA-I[225-230] mutations inhibited the biogenesis of-HDL and led to the accumulation of immature pre-β- and α4-HDL particles, a phenotype that could be corrected by administration of LCAT.

Fotakis|Panagiotis|P|
Tiniakou|Ioanna|I|
Kateifides|Andreas K|AK|
Gkolfinopoulou|Christina|C|
Chroni|Angeliki|A|
Stratikos|Efstratios|E|
Zannis|Vassilis I|VI|
Kardassis|Dimitris|D|

D057927:Hydrophobic and Hydrophilic Interactions

apolipoprotein A-I mutations
dyslipidemia
high density lipoprotein biogenesis
pre-β- and α-HDL particles


Decolorization pathways of anthraquinone dye Disperse Blue 2BLN by Aspergillus sp. XJ-2 CGMCC12963.

Abstract: Anthraquinone dye represents an important group of recalcitrant pollutants in dye wastewater. Aspergillus sp XJ-2 CGMCC12963 showed broad-spectrum decolorization ability, which could efficiently decolorize and degrade various anthraquinone dyes (50 mg L-1) under microaerophilic condition. And the decolorization rate of 93.3% was achieved at 120 h with Disperse Blue 2BLN (the target dye). Intermediates of degradation were detected by FTIR and GC-MS, which revealed the cleavage of anthraquinone chromophoric group and partial mineralization of target dye. In addition, extracellular manganese peroxidase showed the most closely related to the increasing of decolorization rate and biomass among intracellular and extracellular ligninolytic enzymes. Given these results, 2 possible degraded pathways of target dye by Aspergillus sp XJ-2 CGMCC12963 were proposed first in this work. The degradation of Disperse Blue 2BLN and broad spectrum decolorization ability provided the potential for Aspergillus sp XJ-2 CGMCC12963 in the treatment of wastewater containing anthraquinone dyes.

Pan|Huiran|H| Xu|Xiaolin|X| Wen|Zhu|Z| Kang|Yanshun|Y| Wang|Xinhao|X| Ren|Youshan|Y| Huang|Danqi|D|

anthraquinone dyes
Aspergillus
ligninolytic enzymes
degradation pathway
textile effluents


Identification and Genome Analysis of Vibrio coralliilyticus Causing Mortality of Pacific Oyster (Crassostrea gigas) Larvae.

Abstract: Vibrio coralliilyticus is known as a coral pathogen that also infects marine bivalve larvae worldwide. It is considered to be one of the major constraints in artificial marine bivalve seed production as it causes mortality. In this study, we first isolated and characterized a high virulent of V. coralliilyticus designated as SNUTY-1 that was the cause of Pacific oyster larvae mortality in Korea. In the pathogenicity test, exposure to 2.14 × 105 CFU/mL for 24 h caused mortality to 88.65 ± 2.4% of the tested healthy Pacific oyster larvae. SNUTY-1 showed anti-microbial resistance to β-lactams, such as penicillins, cephalosporins, and carbapenems. We sequenced and assembled the complete genome of SNUTY-1 (5,842,676 bp), consisting of two chromosomes (Chr I and Chr II) and two plasmids (pSNUTY1 and pSNUTY2). The COG functional analysis confirmed that Chr I had more genes associated with basic cellular functions in comparison to Chr II. The results of the phylogenetic trees based on OrthoANI values indicated that the SNUTY-1 was closely related to V. coralliilyticus strains. SNUTY-1 had a unique plasmid (pSNUTY2), which could mean that the Korean isolate is different from other sequenced V. coralliilyticus strains from different geographical origins. Toxic proteins such as cytolysin/hemolysin and extracellular metalloprotease genes were encoded on Chr I and Chr II of SNUTY-1. These data facilitate the control of V. coralliilyticus infections in aquaculture by providing valuable insights into the biodiversity of this organism and valuable information for the study of virulence factors.

Kim|Hyoun Joong|HJ|
Jun|Jin Woo|JW|
Giri|Sib Sankar|SS|0000-0002-2383-1937
Chi|Cheng|C|
Yun|Saekil|S|
Kim|Sang Guen|SG|
Kim|Sang Wha|SW|
Han|Se Jin|SJ|
Kwon|Jun|J|
Oh|Woo Taek|WT|
Lee|Sung Bin|SB|
Kim|Ji Hyung|JH|0000-0002-7921-2625
Park|Se Chang|SC|

Pacific oyster (Crassostrea gigas) larvae


Overexpression of PDX-II gene in potato (Solanum tuberosum L.) leads to the enhanced accumulation of vitamin B6 in tuber tissues and tolerance to abiotic stresses.

Abstract: Vitamin B6 is a vital metabolite required for living organisms as a cofactor in several metabolic biochemical reactions and recognized as a potent antioxidant molecule which modulates the expression of the proteins responsible for the scavenging of cellular reactive oxygen species. It is well established that the microorganisms and plants can synthesize the B6 de novo, therefore, all the animals including humans must acquire it from the plant dietary resources. However, the bioavailability of the vitamin in the edible portions of the commonly consumed plants is insufﬁcient to meet the daily recommended doses. Genetic engineering techniques have proven successful in increasing the vitamin B6 content in the model plants. Present study describe the development of transgenic potato (Solanum tuberosum L. cv. Kufri chipsona) overexpressing key vitamin B6 pathway gene, the PDXII (NCBI database Ref. ID- NM_125447.2) isolated from Arabidopsis thaliana under the control of CaMV 35S constitutive promoter. The stable integration and expression of transgene in the transgenic lines were confirmed by PCR, Southern blot and RT-PCR analysis. Transgenic tubers exhibited considerably improved vitamin B6 accumulation (up to 107-150%) in comparison to the untransformed controls potato. This increase in vitamin B6 was also correlated with the increased mRNA expression of PDXII gene. The prominent increase in the B6 content of transgenic potato was also associated with the capability to survive under abiotic stresses, therefore, the transgenic lines were able to withstand various abiotic stresses imposed by salinity (NaCl) or methyl viologen (MV). We thus demonstrated that overexpression of PDXII gene under the control of a constitutive promoter enhanced the accumulation of the vitamin B6 which also augmented the tolerance under various abiotic stresses in potato (Solanum tuberosum L.).

Bagri|Deepak Singh|DS|
Upadhyaya|Devanshi Chandel|DC|
Kumar|Ashwani|A|
Upadhyaya|Chandrama Prakash|CP|

Vitamin B6
Abiotic stress tolerance
Bio-fortification
Crop biotechnology
Oxidative stress
PDX II gene


Employing exogenous melatonin applying confers chilling tolerance in tomato fruits by upregulating ZAT2/6/12 giving rise to promoting endogenous polyamines, proline, and nitric oxide accumulation by triggering arginine pathway activity.

Abstract: In the present study, the mechanisms employed by exogenous melatonin applying for conferring chilling tolerance in tomato fruits during storage at 4 °C for 28 days were investigated. Conferring chilling tolerance in tomato fruits in response to exogenous melatonin applying at 100 µM may arise from upregulating SlZAT2/6/12 giving rise to triggering CBF1 gene expression. Employing higher arginine pathway activity in tomato fruits by exogenous melatonin applying demonstrating by higher endogenous polyamines accumulation arising from higher ornithine decarboxylase (ODC) and arginine decarboxylase (ADC) genes expression and enzymes activity, higher endogenous proline accumulation arising from higher pyroline 5-carboxylate synthetase (P5CS) and ornithine aminotransferase (OAT) genes expression and enzymes activity accompanying by lower proline dehydrogenase (PDH) gene expression and enzyme activity and higher endogenous nitric oxide (NO) accumulation arising from higher nitric oxide synthase (NOS) gene expression and enzyme activity may be responsible for keeping safe membrane integrity.

Aghdam|Morteza Soleimani|MS|
Luo|Zisheng|Z|
Jannatizadeh|Abbasali|A|
Sheikh-Assadi|Morteza|M|
Sharafi|Yavar|Y|
Farmani|Boukaga|B|
Fard|Javad Rezapour|JR|
Razavi|Farhang|F|

Melatonin
Polyamines
Arginine pathway
Chilling injury
Postharvest


Investigate the correlation between clinical sign and symptoms and the presence of P. gingivalis, T. denticola, and T. forsythia individually or as a "Red complex" by a multiplex PCR method.

Abstract:
AIM
The aim of this study was to investigate the correlation between endodontic clinical signs and symptoms and the presence of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia or their association by Multiplex polymerase chain reaction assay.

MATERIALS AND METHODS
Microbial samples were taken from 30 cases with necrotic pulp tissues in primary infections. DNA was extracted from the samples, which were analyzed for the presence of three endodontic pathogens by using species-specific primers.

RESULTS
P. gingivalis, T. denticola, T. forsythia, and Red Complex were present in 11, 17, 4, and 2 canals, respectively. Clinical and statistically significant relationships were found between T. forsythia and mobility and between T. denticola and swelling. (P < 0.05). Presence of other Red complex bacteria shows clinical association with presence of signs and symptoms but no statistically significant relationship.

CONCLUSION
The high prevalence of P. gingivalis, T. denticola, and T. forsythia in the examined samples suggests that these bacteria are related to the etiology of symptomatic periradicular diseases.

Sanghavi|Tulsi Hasmukhrai|TH|
Shah|Nimisha|N|
Shah|Ruchi Rani|RR|
Sanghavi|Akta|A|


Everolimus (EVE) and exemestane (EXE) in patients with advanced breast cancer aged ≥ 65 years: new lessons for clinical practice from the EVA study.

Abstract:
BACKGROUND
The present analysis focuses on real-world data of Everolimus-Exemestane in advanced HR+ve, HER2-ve elderly breast cancer patients (aged 65 years) included in the EVA study, with unique findings in those aged 70 years.

METHODS
Data are collected from clinical records and analysed according to age cut-off (< 65 years; 65 - 69 years and {greater than or equal to} 70 years). Relationship of analyzed variables with response were tested by mean of a Mantel-Haenszel chi square test. Time to event analysis was described by Kaplan Meier approach and association with baseline characteristics was analysed by stratified log-rank test and proportional hazard model.

RESULTS
From July 2013 to December 2015, the EVA study enrolled overall 404 pts. 154 patients out of 404 (38,1%) were aged {greater than or equal to} 65 years, of whom 87 were {greater than or equal to} 70 years. Median duration of EVE treatment was 28.5 weeks (95% CI 19.0 - 33.8) in patients aged 65-69 years and 24,4 weeks (95% CI 19,2 - 33,2) in those aged {greater than or equal to} 70 years. Fewer patients aged 65 years received the highest EVE Dose-Intensity (>7.5 mg/day) in comparison to younger patients (49,6% vs. 66,8%). Grade 3-4 toxicities occurred to 55 patients (35,7%), mainly stomatitis (10,9%), rash (5,8%) and non-infectious pneumonitis (NIP) (3,6%). Some toxicities, such as weight loss and anaemia were peculiarly observed in patients aged {greater than or equal to} 70 years. Five treatment-related deaths were collected (3,2%).

CONCLUSIONS
EVE-EXE combination remains one of the potential treatments in HR+ patients also for elderly ones.

Torri On Behalf Of The Eva Study Group|Valter|V|

everolimus
exemestane
advanced breast cancer
elderly
hormone-receptor positive


Two-step optimization process for grass hydrolysate application as biodiesel feedstock with novel quality characteristics.

Abstract: A major obstacle to biodiesel commercialization is supplying feedback which increases production costs. The potential of some oleaginous yeast for conversion of waste materials to biodiesel feedstock can overcome this problem. In this study, a potential oleaginous yeast strain was used for single-cell oil (SCO) production. Two sets of experiments were designed for the optimization process. According to the results obtained from the first experiment, lipid production and lipid content of this strain increased from 1.96 g/L and 22.6% to 3.85 g/L and 35.18% by optimization of grass hydrolysis, respectively. The results of the second experiment indicate an increase in SCO production and lipid content to 7.28 g/L and 56.39%, respectively. These results were obtained when HNO3 was used for substrate pre-treatment. Lipid analysis by gas chromatography-mass spectrometry showed a suitable and high potential of fatty acid profile for biodiesel production, which was then confirmed by evaluating the physicochemical properties of the biodiesel obtained in compliance with the US and EU standards. Consumption of microbial oil and low-cost substrate can compensate the high costs of feedstock in biodiesel production.

Oleaginous yeast
Waste materials
Grass hydrolysis
Gas chromatography-mass spectrometry
Microbial oil
Single cell oil production


Urethane-Acrylate/Aramid Nanocomposites Based on Graphenic Materials. A Comparative Study of Their Mechanical Properties.

Abstract: Urethane-acrylate thermoset resins (UATR) are a new type of polymeric matrix that have recently made a strong breakthrough in the composites sector. This is because of their properties, which make them an advantageous alternative to epoxy resins, especially if they are reinforced with high-performance fibers such as aramids. Graphene-based nanocomposites are one of the most dynamic research fields in nanotechnology, because graphenic materials greatly improve the properties of traditional composites. This work represents a comparative study of the effect of adding three types of graphenic materials on the mechanical properties of UATR/aramid composites. Several UATR polymeric matrices were doped at 2% w/w with graphene nanoplatelets (GNPs), reduced graphene oxide (rGO) and pristine few-layer graphene (FLG), and reinforced with Twaron CT709 para-aramid fibers. The obtained laminates showed low density (1.38 g·cm-3), a high volumetric fiber-resin ratio (80:20), homogeneous dispersion of the nanoreinforcement, high reproducibility, and easy scalability. The tensile, flexural and impact strength properties of the undoped composite and the graphene-doped nanocomposites were determined. FLG-doped nanocomposites showed the highest increase in all the mentioned mechanical properties and attained a very significant relative improvement over the undoped laminate (up to 134.4% in aCU).

Gago|Israel|I|
Del Río|Manuel|M|
León|Gerardo|G|
Miguel|Beatriz|B|0000-0002-5089-9259

urethane-acrylate/aramid
graphenic materials
mechanical properties
graphene nanocomposites


Photolysis of atorvastatin in aquatic environment: Influencing factors, products, and pathways.

Abstract: Atorvastatin (ATV), a second generation cholesterol-lowering drug, is detected frequently in natural water because of its extensive use and incomplete removal from wastewater. In this study, the photochemical behavior of ATV under simulated solar irradiation was systematically investigated in order to assess the potential of photolysis as its transformation pathway in aquatic environment. The quantum yield of ATV direct photolysis was determined to be 0.0041. Among various water components investigated, including pH, Suwannee River Fulvic Acid (SRFA), Fe3+, HCO3-, SO42- and NO3-, the major factors contributing to the indirect photolysis of ATV were SRFA and NO3-, and the co-existence of SRFA and NO3- showed no interaction in synthetic water containing the above water components. The results were further verified in natural water samples. Singlet oxygen (1O2) played dominant role in the indirect photolysis of ATV, and the contributions of 1O2 and ·OH to the photolysis of ATV in the solution with optimum combination of water components were calculated to be 67.14% and 0.66%, respectively. Nine phototransformation intermediates were identified by liquid chromatography - time-of-flight - mass spectrometry (LC-TOF-MS), and the degradation pathways were speculated as hydroxyl addition, pyrrole-ring open and debenzamide reactions. In addition, the evolution of products in the degradation process showed that the ring-opened product P416 and hydroxylation product P575 still remained at a certain level after two days of photodegradation, which may accumulate and cause additional ecological risks. This study provides significant information for understanding the risk and fate of ATV in aquatic environment.

Wang|Mengjie|M| Li|Jianhua|J| Shi|Huanhuan|H| Miao|Dong|D| Yang|Yun|Y| Qian|Li|L| Gao|Shixiang|S|

Atorvastatin
Degradation pathways
Photodegradation
Orthogonal experiment


BTA-MM: Burst traffic awareness-based adaptive mobility model with mobile sinks for heterogeneous wireless sensor networks.

Abstract: Using mobile sink increases the coverage time and energy expenditure when there is a burst traffic condition in wireless sensor networks (WSNs). Hence, it is essential to handle burst traffic using mobile sinks in an energy-efficient mobility manner. In most studies, mechanisms of the clustering and routing have not taken into account burst traffic. In fact, the number of studies with integrated mobile sink nodes, burst traffic awareness, multi-criteria cluster head (CH) selection, and mobile sink routing is negligible. For this purpose, a novel burst traffic awareness adaptive mobility scheme is proposed based on heterogeneous clustered WSNs, namely Burst Traffic Awareness-Mobility Model (BTA-MM). In the proposed scheme, the network area is first divided into two cluster groups. The CH selection is performed for each round by the average residual energy an d node load, taking into account the network coverage. An adaptive Gauss-Markov-burst traffic combination model is proposed in the study. In the proposed model, the mobile sinks collect all data in a single-hop communication as soon as they join the coverage intersection points (CIPs) of the CHs. The mobility model utilizes the adaptive minimum-weighted cost of the nodes. Once the burst packets are perceived in a CH, the data packets are backed up on the nearest and highest energy node in the cluster. Then, the mobile sink suddenly updates its trajectory towards the node, including the burst data traffic. Performance analysis of the proposed scheme was performed in NS-2 simulation environment. The most notable of the performance results is that the proposed method increased the network lifetime 42.5% more than any other method and also reduced the control overhead and average mobile path length by 72.5% and 35.9%, respectively. Also, the simulation results showed that the proposed method significantly reduced the average energy consumption 34.2% more than any other method, and increased the packet delivery rate 4.5% more than any other method, even in burst traffic.

Burst traffic
Wireless sensor networks
Data collecting
Energy efficiency
Mobile routing


Frontline Science: CXCR7 mediates CD14+CD16+ monocyte transmigration across the blood brain barrier: a potential therapeutic target for NeuroAIDS.

Abstract: CD14+CD16+ monocytes transmigrate into the CNS of HIV-positive people in response to chemokines elevated in the brains of infected individuals, including CXCL12. Entry of these cells leads to viral reservoirs, neuroinflammation, and neuronal damage. These may eventually lead to HIV-associated neurocognitive disorders. Although antiretroviral therapy (ART) has significantly improved the lives of HIV-infected people, the prevalence of cognitive deficits remains unchanged despite ART, still affecting >50% of infected individuals. There are no therapies to reduce these deficits or to prevent CNS entry of CD14+CD16+ monocytes. The goal of this study was to determine whether CXCR7, a receptor for CXCL12, is expressed on CD14+CD16+ monocytes and whether a small molecule CXCR7 antagonist (CCX771) can prevent CD14+CD16+ monocyte transmigration into the CNS. We showed for the first time that CXCR7 is on CD14+CD16+ monocytes and that it may be a therapeutic target to reduce their entry into the brain. We demonstrated that CD14+CD16+ monocytes and not the more abundant CD14+CD16- monocytes or T cells transmigrate to low homeostatic levels of CXCL12. This may be a result of increased CXCR7 on CD14+CD16+ monocytes. We showed that CCX771 reduced transmigration of CD14+CD16+ monocytes but not of CD14+CD16- monocytes from uninfected and HIV-infected individuals and that it reduced CXCL12-mediated chemotaxis of CD14+CD16+ monocytes. We propose that CXCR7 is a therapeutic target on CD14+CD16+ monocytes to limit their CNS entry, thereby reducing neuroinflammation, neuronal damage, and HIV-associated neurocognitive disorders. Our data also suggest that CCX771 may reduce CD14+CD16+ monocyte-mediated inflammation in other disorders.

Veenstra|Mike|M|
Williams|Dionna W|DW|
Calderon|Tina M|TM|
Anastos|Kathryn|K|
Morgello|Susan|S|
Berman|Joan W|JW|

D023241:Antiretroviral Therapy, Highly Active

D057705:Transendothelial and Transepithelial Migration


Hospital-based inpatient resource utilization associated with autosomal dominant polycystic kidney disease in the US.

Abstract:
OBJECTIVE
Polycystic kidney disease (PKD) is a clinically and genetically heterogeneous class of genetic disorders characterized by development of renal cysts leading to renal failure and end stage renal disease (ESRD). Autosomal dominant polycystic kidney disease (ADPKD) accounts for the majority of PKD cases and is the predominant monogenic cause of ESRD. Limited information on patient characteristics and healthcare resource utilization is available in this population. This study assessed hospital-based inpatient utilization of patients with ADPKD in the US to help further understand the disease, which may lead to treatments that delay progression and reduce healthcare resource utilization.

METHODS
A cross-sectional analysis was conducted using MedAssets Health System Data to investigate inpatient resource utilization for a total of 1876 patients hospitalized with ADPKD or chronic kidney disease (CKD). Patient characteristics and inpatient resource utilization were compared between hospitalized patients with ADPKD and CKD, including demographic and clinical characteristics, overall health, rates of complications and surgical interventions, and average length of hospital and intensive care unit stay.

RESULTS
Compared with patients with CKD, patients with ADPKD were more likely to have commercial insurance as their primary payer (36.1 vs 17.8%) and were significantly younger (mean age 57.9 vs 69.5 years) and generally healthier (Charlson Comorbidity Score of 2.0 vs 3.3). Patients with ADPKD also had a substantially shorter average length of hospital stay (6.3 vs 10.3 days). However, patients with ADPKD experienced more kidney-related complications and a higher surgical procedure rate (mainly for transplant and complete nephrectomy).

CONCLUSIONS
Although patients with ADPKD were generally healthier than patients with CKD, specific kidney function complications were more frequent. Patients with ADPKD had a higher rate of major kidney procedures, which may contribute to the high burden of ADPKD-related hospital-based inpatient resource utilization.

Blanchette|Christopher M|CM|
Craver|Christopher|C|
Belk|Kathy W|KW|
Lubeck|Deborah P|DP|
Rossetti|Sandro|S|
Gutierrez|Benjamin|B|

D016891:Polycystic Kidney, Autosomal Dominant


Activated ezrin controls MISP levels to ensure correct NuMA polarization and spindle orientation.

Abstract: Correct spindle orientation is achieved through signaling pathways that provide a molecular link between the cell cortex and spindle microtubules in an F-actin-dependent manner. A conserved cortical protein complex, composed of LGN (also known as GPSM2), NuMA (also known as NUMA1) and dynein-dynactin, plays a key role in establishing proper spindle orientation. It has also been shown that the actin-binding protein MISP and the ERM family, which are activated by lymphocyte-oriented kinase (LOK, also known as STK10) and Ste20-like kinase (SLK) (hereafter, SLK/LOK) in mitosis, regulate spindle orientation. Here, we report that MISP functions downstream of the ERM family member ezrin and upstream of NuMA to allow optimal spindle positioning. We show that MISP directly interacts with ezrin and that SLK/LOK-activated ezrin ensures appropriate cortical MISP levels in mitosis by competing with MISP for actin-binding sites at the cell cortex. Furthermore, we found that regulation of the correct cortical MISP levels, by preventing its excessive accumulation, is essential for crescent-like polarized NuMA localization at the cortex and, as a consequence, leads to highly dynamic astral microtubules. Our results uncover how appropriate MISP levels at the cortex are required for proper NuMA polarization and, therefore, an optimal placement of the mitotic spindle within the cell.This article has an associated First Person interview with the first author of the paper.

MISP
NuMA
Spindle orientation
ERM
Astral microtubule


Sleep quality and insomnia in nurses with different circadian chronotypes: morningness and eveningness orientation.

Abstract:
BACKGROUND
Morningness and eveningness preference (chronotype), an endogenous component of the circadian clock could play a key role in a worker's ability for adjusting to shift work. Morning types are those individuals who prefer going to bed and waking up early, whereas Evening types tend to sleep at later hours and find it difficult to get up in the morning.

OBJECTIVE
The objective of this study was to survey, the relationship between morningness-eveningness type, sleep quality and insomnia in shift worker nurses.

PARTICIPANTS
The participants comprised 160 nurses working in three different wards in two university hospitals in Iran.

METHODS
Nurses completed the Horne and Ostberg questionnaire to assess the distribution of morningness or eveningness preference, the Pittsburg Sleep Quality Index and Insomnia Severity Index questionnaire to measure self reported sleep quality and insomnia. Demographic information was also collected in order to explore the relationship between circadian rhythms, sleep quality and prevalence of insomnia in shift workers.

RESULTS
The results showed that the prevalence of poor sleep quality was high. More than half of the participants had poor sleep. Evening type nurses had worse sleep quality in our study (P < 0.05). There is not any significant association between the shift type and age of the nurses with their quality of sleep (P > 0.05).

CONCLUSIONS
The results suggested that nurses who had a morning sleep preference had better sleep quality. A survey of chronotype of nurses could be useful, so that individuals may be assigned to different shifts according to their sleep preference.

Yazdi|Zohreh|Z|
Sadeghniiat-Haghighi|Khosro|K|
Javadi|Ali Reza Haj Seid|AR|
Rikhtegar|Ghasem|G|

D007319:Sleep Initiation and Maintenance Disorders

Chronotype
morningness-eveningness
circadian rhythms
nurse management
sleep disturbance


Validity and reliability of the Thai version of the Spine Oncology Study Group Outcomes Questionnaire version 2.0 to assess Quality of Life in Patients with Spinal Metastasis.

Abstract:
BACKGROUND CONTEXT
The Spine Oncology Study Group Outcomes Questionnaire version 2.0 (SOSGOQ2.0) is a spinal metastasis (SM)-specific quality of life (QoL) questionnaire that was previously reported to have good reliability and validity. There is currently no Thai version of the SOSGOQ 2.0. (TH-SOSGOQ2.0).

PURPOSE
To assess the psychometric properties of the TH-SOSGOQ 2.0.

STUDY DESIGN/SETTING
Cross-sectional study. Faculty of Medicine Siriraj Hospital, Mahidol University.

PATIENT SAMPLE
Patients who were confirmed diagnosis of metastatic spinal disease, age 18 to 75 years, and having already undergone surgery and/or radiotherapy for the treatment of spinal metastasis.

OUTCOME MEASURES
Validity and reliability of the TH-SOSGOQ 2.0 to assess QoL in Patients with SM.

METHODS
Using the forward-backward translation technique, the SOSGOQ2.0 was translated into Thai language to create the TH-SOSGOQ2.0. SM patients were prospectively enrolled and evaluated for patient QoL using both the TH-SOSGOQ2.0 and the EQ-5D-5L (Thai version) at baseline and 3 months after treatment. Construct validity was assessed using multi-trait scaling analysis, confirmatory factor analysis, and correlation with EQ-5D-5L. Test-retest reliability was assessed in a subgroup of patients who took the TH-SOSGOQ2.0 two times one week apart.

RESULTS
Sixty-eight patients (mean age: 57 years; 30 males, 38 females) were included. The Cronbach's alpha values for the total score, physical function, neurological function, pain, mental health, social function, and post-therapy domains were 0.87, 0.89, 0.91, 0.84, 0.82, 0.75, and 0.85, respectively. Good reliability was demonstrated (interclass correlation coefficient range: 0.70-0.84), except for the social function domain (0.60). Regarding concurrent validity, the TH-SOSGOQ2.0 domains demonstrated moderate to good correlation with the corresponding EQ-5D-5L 9 (Thai version) domains (range: -0.32 to -0.78). Physical function was the most well-correlated domain with the EQ-5D-5L (Thai version) (-0.77).

CONCLUSIONS
TH-SOSGOQ2.0 demonstrated good reliability and validity for assessing QoL in Thai SM patients.

Luksanapruksa|Panya|P| Phikunsri|Pariwat|P| Trathitephun|Warayos|W| Santipas|Borriwat|B| Suvithayasiri|Siravich|S| Wattanapaiboon|Komkrich|K| Wilartratsami|Sirichai|S|